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Shaoxia Wang,1– 3 Xiang Zhang,1 Yanru Ding,1 Yanrong Wang,2,4 Chujun Wu,2,4 Shihao Lu,1,2 Jianqun Fang2,4 1School of First Clinical, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Ningxia Civil Affairs Department Minkang Hospital, Yinchuan, Ningxia, 750001, People’s Republic of China; 4Mental Health Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of ChinaCorrespondence: Jianqun Fang, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email fjq7887215@163.comObjective: Vitamin B12 is crucial for neurological functions and linked to various psychiatric disorders. Given its importance, this study explores the impact of vitamin B12 deficiency on sleep quality in Obsessive-Compulsive Disorder (OCD) patients, while also examining folate and homocysteine levels to explore their potential interactions with OCD symptoms and sleep quality.Methods: This cross-sectional study included 52 patients with OCD and 42 healthy controls. Serum levels of vitamin B12, homocysteine, and folate were measured. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of OCD symptoms and the quality of sleep, respectively. Correlations and mediating effects between these variables were also assessed.Results: Vitamin B12 levels were significantly lower in OCD patients compared to healthy controls, and scores for sleep disturbances were significantly higher in the OCD group. No significant differences were observed in the levels of folate and homocysteine between the groups. Correlation analysis indicated that lower levels of vitamin B12 were significantly associated with more severe OCD symptoms and poorer sleep quality. Further mediation analysis suggested that low levels of vitamin B12 partially mediated the relationship between OCD symptoms and sleep disturbances.Conclusion: Lower levels of vitamin B12 not only affect sleep quality but also partially mediate the impact of OCD symptoms on sleep disturbances. Future clinical attention to vitamin B12 deficiency is crucial for further assessing the relationship between OCD symptoms and sleep disorders.Keywords: obsessive-compulsive disorder, sleep disturbances, vitamin b12, mediating effects

Shu Wang,1,* Chengzhong Liu,2,* Ruipei Ding,2 Shumei Wang,2 Yousheng Ye,1 Maozhang He2 1Department of Geriatrics, The First People’s Hospital of Hefei, Hefei, 230061, People’s Republic of China; 2Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maozhang He; Yousheng Ye, Email jnzd_hemaozhang@hotmail.com; ye.ys@qq.comBackground: Over the past years, there has been a significant increase in the incidence of Mycoplasma pneumoniae (MP) infections, particularly among pediatric patients, nationwide. An emerging body of research has established a link between dysbiosis of the host microbiome and the metabolic functioning of the host, which contributes to the development of respiratory diseases.Methods: A total of 25 children were included in the study, comprising 15 pneumonia patients and 10 healthy children. Stool samples were collected from all participants to analyze the 16S ribosomal RNA (16S rRNA) gene, while serum samples were prepared for untargeted metabolomics to qualitatively and quantitatively assess short-chain fatty acids.Results: The gut microbial composition of individuals with Mycoplasma pneumoniae pneumonia (MPP) exhibited significant differences compared to healthy children. Notably, diseased children demonstrated higher microbial diversity and an enrichment of opportunistic pathogens, such as Erysipelatoclostridium and Eggerthella. Analysis revealed elevated levels of two specific short-chain fatty acids, namely acetic acid and isobutyric acid, in the MPP group, suggesting their potential as biomarkers for predicting MP infection. Metabolomic signature analysis identified a significant increase in major classes of glycerophospholipids in the MPP group. Moreover, we identified a total of 750 significant correlations between gut microbiota and circulating serum metabolites. MPP enriched genera Erysipelatoclostridium and Eggerthella, exhibited negative associations with indole-3-butyric acid. Additionally, Eggerthella showed a positive correlation with inflammatory metabolites LPC (18:0).Discussion: Collectively, these findings provide novel insights into the selection of potential biomarkers and the pathogenesis of MPP in children based on the gut microbiota and systemic circulating metabolites.Keywords: Mycoplasma pneumoniae, gut microbiota, serum metabolomics, short-chain fatty acids, inflammation

Pilong Shi,1,* Yuetong Sha,1,* Xinran Wang,1,* Tao Yang,1 Jiawei Wu,1 Jiajun Zhou,1 Kai Liu,1 Xue Guan,2 Song Wang,1 Yongsheng Liu,1 Jingquan Gao,3 Hongli Sun,1 Tao Ban,1 Yonggang Cao1 1Department of Pharmacology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Morphological Experiment Center, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Nursing, School of Medicine, Lishui University, Lishui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonggang Cao; Hongli Sun, Email 437343482@qq.com; sunhongli@hmudq.edu.cnPurpose: Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods: In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results: Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion: Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2. Keywords: myocardial ischemia-reperfusion injury, lutein, ROS, MDM2, NDUFS1, ferroptosis

Sheng Wang,1,* Demeng Xia,2,3,* Wenxue Dou,4,* Aimin Chen,1 Shuogui Xu2 1Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Traumatic Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Clinical Medicine, Hainan Health Vocational College, Haikou, 570100, People’s Republic of China; 4Department of Stomatology, Shanghai East Hospital, Tongji University, Shanghai, 200120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuogui Xu, Department of Emergency, Changhai Hospital, Naval Medical University, Xiangyin Road, Shanghai, 200433, People’s Republic of China, Email 18516116672@163.com Aimin Chen, Department of traumatic orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China, Email chenaimin2023@163.comBackground: Delayed healing and non-healing of bone defects pose significant challenges in clinical practice, with metal materials increasingly recognized for their significance in addressing these issues. Among these materials, Strontium (Sr) and Zinc (Zn) have emerged as promising agents for promoting bone repair. Building upon this insight, this research evaluates the impact of a porous Sr@Zn@SiO2 nanocomposite implant on bone regeneration, aiming to advance the field of bone repair.Methods: The preparation of the Sr@Zn@SiO2 composite implant involves various techniques such as roasting, centrifugation, and washing. The material’s composition is examined, and its microstructure and element distribution are analyzed using TEM and elemental scanning technology. In vitro experiments entail the isolation and characterization of BMSCs followed by safety assessments of the implant material, evaluation of cell migration capabilities, and relevant proliferation markers. Mechanistically, this study delves into key targets associated with significant changes in the osteogenic process. In vivo experiments involve establishing a rat femur bone defect model, followed by assessment of the osteogenic potential of Sr@Zn@SiO2 using Micro-CT imaging and tissue section staining.Results: Through in vivo and in vitro investigations, we validate the osteogenic efficacy of the Sr@Zn@SiO2 composite implant. In vitro analyses demonstrate that porous Sr@Zn@SiO2 nanocomposite materials upregulate BMP-2 expression, leading to the activation of Smad1/5/9 phosphorylation and subsequent activation of downstream osteogenic genes, culminating in BMSCs osteogenic differentiation and bone proliferation. And the migration of BMSCs is closely related to the high expression of CXCL12/CXCR4, which will also provide the conditions for osteogenesis. In vivo, the osteogenic ability of Sr@Zn@SiO2 was also confirmed in rats.Conclusion: In our research, the porous Sr@Zn@SiO2 composite implant displays prominent osteogenic effect and promotes the migration and differentiation of BMSCs to promote bone defect healing. This bioactive implant has surgical application potential in the future. Keywords: bioactive porous composite, differentiation and migration, bone reconstruction, smad1/5/9

Xiao Wang,1,* Ying Cao,2,* Jing Hu,3 Lian-Cheng Jia,4 Bo Li,3 Baoli Liu,5 Wei-Hai Yao,2 Xiao-Lu Pei,6 Wei Peng,2 Shuang Wang,2 Cun-Zhi Liu,1,7 Jian-Feng Tu,1,7 Zhi-Cheng Qu2 1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Evidence Based Medicine Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Urinary Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 5Nephrology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 6Nursing Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Cheng Qu, Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email qzhch0824@163.com Jian-Feng Tu, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tujianfeng1@126.comIntroduction: Analgesia is often delayed for suspected acute renal colic due to urinary calculi (ARCUC) even in emergency department. Acupuncture has a rapid onset and is effective for analgesia, however, evidence about early-acupuncture for suspected ARCUC is limited. This trial aims to evaluate the efficacy of early-intervention acupuncture compared with sham acupuncture on pain relief among emergency department suspected ARCUC patients.Methods and Analysis: A total of 84 eligible patients who are suspected diagnosed with ARCUC will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture before diagnostic imaging. The primary outcome will be the response rate at 10 min after needle manipulation, defined as the proportion of patients whose Numeric Rating Scale (NRS) score decrease by at least 50% from baseline. Secondary outcomes will include pain intensity assessed by NRS, further analgesia requirement, revisit rate, surgical intervention rate, satisfaction evaluation, and adverse events. The final diagnosis rate determined by radiography will be recorded and reported. All patients who receive randomization will be included in the intention-to-treat analysis.Conclusion: This study’s findings are anticipated to evaluate the analgesic effect of early-intervention acupuncture for acute renal colic in emergency department, which could be useful for moving the timing of analgesia forward and aligning pain management for acute renal colic more with the guidelines.Trial Registration Number: ChiCTR2100049069 (https://www.chictr.org.cn/showproj.html?proj=125338).Keywords: acupuncture, complementary medicine, pain management, emergency medicine, renal colic

Wei Song,1,2,&ast; Yaoyang Li,1,&ast; Yifan Jia,1 Lingling Xu,3 Lin Kang,4 Yunshuang Yang,5 Shuyu Wang,1 Qian Zhang,1 Qunli Wu1 1Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Institute of Clinical Medicine, National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 4Department of Geriatric, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 5Department of Preventive Medicine, Beijing Longfu Hospital, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Zhang; Qunli Wu, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email zhangqian1@pumch.cn; chinlie@163.comPurpose: The axon guidance factors and Rho/ROCK pathway play crucial roles in axon protection and nerve repair and has been implicated in the development of diabetic peripheral neuropathy (DPN). This study investigates the protective effects of quercetin against DPN, focusing on axon guidance factors and Rho/ROCK pathway.Methods: DPN was induced by intraperitoneal injection of streptozotocin (STZ) to Sprague-Dawley rats. The DPN model rats were allocated into three groups and administered quercetin at two different doses (30 mg/kg/day and 60 mg/kg/day) or a placebo. Concurrently, healthy rats were divided into two groups and administered either a placebo or quercetin (60 mg/kg/day). Administration was initiated 8 weeks post-STZ injection and continued for a duration of six weeks. To assess quercetin’s neuroprotective effects, biochemical analyses, neurological function tests (mechanical threshold, thermal response latency, motor nerve conduction velocity), and morphological assessments via transmission electron microscopy were conducted. Immunofluorescence and immunohistochemical assays were performed on sciatic nerve tissue and high glucose-induced RSC96 rat Schwann cells to explore quercetin’s pharmacological effects on DPN.Results: Quercetin exhibited neuroprotective effects on both DPN rats and RSC96 cells exposed to high-glucose. A six-week administration of quercetin at both doses significantly improved the peripheral neurological functions and alleviated the pathological changes in sciatic nerve of DPN rats (P< 0.05). Mechanistically, quercetin markedly upregulated the expressions of axonal growth factors, Slit-2 and Netrin-1 in vivo and in vitro (P< 0.05), while inhibiting the aberrant activation of Rho/ROCK signaling pathway in the sciatic nerve of DPN rats.Conclusion: Our findings suggest that quercetin improves DPN through a novel mechanism, indicating its potential as a therapeutic agent for DPN therapy. Keywords: quercetin, diabetic peripheral neuropathy, Rho/ROCK pathway, axon guidance factor, Netrin-1, Slit-2

Xuexue Bai,1 Hao Xing,1 Ming Feng,1 Wenbin Ma,1 Shiyong Wang2 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Ming Feng; Shiyong Wang, Email pumchfming@126.com; Washiyong@126.comPurpose: We retrospectively analyzed the effect of Bevacizumab (BEV) on recurrent high-grade glioma (rHGG) and examined the relationship between dose and efficacy.Methods: A total of 182 patients with rHGG were included in this study. Patients were divided into a non-BEV group and a BEV group according to the treatment they received, and the BEV group was further divided into a low-dose group and a high-dose group based on the dose. Depending on the number of groups and the characteristics of numerical variables, t-test, ANOVA, or rank-sum test were selected. Categorical variables were compared using the chi-squared test.Results: Progression-free survival (PFS) was lower in the non-BEV group compared to the BEV group, while overall survival (OS) was not different between the two groups. There was no difference in PFS and OS between low-dose group and high-dose group. Notably, we found that patients with longer PFS and OS were more likely to be from the BEV group. In addition, differences in Karnofsky Performance Score (KPS), steroid dose, and brain edema were observed in the non-BEV, low-dose, and high-dose groups from 3 to 12 months after treatment.Conclusion: BEV can improve PFS in patients with rHGG, although its impact on OS is limited. There was no difference in the efficacy of different doses of BEV on rHGG. Interestingly, patients with longer PFS and OS were more likely to be from the BEV group. Based on these findings, long-term low-dose BEV appears to be an effective treatment option for rHGG.Keywords: bevacizumab, temozolomide, recurrent high-grade glioma, progression free survival, overall survival

Lijuan Shi,1 Jieyu Xiao,1 Juanjuan Guo,1 Saijun Zeng,2 Suhong Wang,3 Jingbo Gong4 1School of Education, Hunan University of Science and Technology, Xiangtan, Hunan, People’s Republic of China; 2Yiyang Special Education School, Yiyang, Hunan, People’s Republic of China; 3Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China; 4Shanghai Changning Mental Health Centre, Affiliated Mental Health Center of East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Jingbo Gong, Shanghai Changning Mental Health Center, Affiliated Mental Health Center of East China Normal University, Shanghai, 200335, People’s Republic of China, Email yefenhua@126.com Suhong Wang, Department of Clinical Psychology, the Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China, Email yarmine@gmail.comBackground: Non-suicidal self-injury (NSSI) is a serious mental health problem among adolescents and young adults. Childhood trauma is a distal factor for NSSI and can also lead to cognitive abnormalities and maladaptive emotion regulation during the growth and development of individuals. However, it is unclear how childhood trauma and cognitive-emotional factors interact with NSSI.Objective: This study investigated the roles of childhood trauma and cognitive-emotional factors in NSSI among Chinese college students using network analysis.Methods: A total of 999 students from a university in central China were included in this study. Network analysis was used to examine the interrelationships between the frequency of NSSI thoughts and behaviors, childhood trauma subtypes (measured using the Childhood Trauma Questionnaire-Short Form), and cognitive-emotional factors such as early maladaptive schemas (EMSs) (measured using the Young Schema Questionnaire-Short Form), core self-evaluation (measured using the Core Self-Evaluations Scale), and emotion regulation (ER) strategies (measured using the Emotion Regulation Questionnaire). Structural equation modeling was used to further explore the role of the nodes most closely related to NSSI in the network analysis.Results: Emotional abuse and disconnection/rejection EMS are found to be directly related to NSSI thoughts (edge weight = 0.16 and 0.08, respectively). Disconnection/rejection EMS partially mediated (28.64%) the relationship between emotional abuse and NSSI thoughts, with a higher level of expression suppression corresponding to a greater positive relationship between emotional abuse and the disconnection/rejection EMS (p < 0.01).Conclusion: Our findings were in line with the cognitive-emotional model of NSSI, highlighting the importance of NSSI prevention in identifying risk groups who experienced emotional abuse in childhood and tended to use expressive suppression as an ER strategy.Keywords: childhood trauma, early maladaptive schema, emotion regulation strategy, non-suicidal self-injury, network analysis

Si Wang,1,2,&ast; Lin Zhang,1,2,&ast; Yigao Wu,3 Jun Ma1,2 1Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 2Department of Psychiatry, Wuhan Hospital for Psychotherapy, Wuhan, People’s Republic of China; 3Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Ma, Department of Psychiatry, Wuhan Mental Health Center, No.89, Gongnongbing Road, Wuhan, Hubei, People’s Republic of China, Email majun0313@wo.cn Yigao Wu, Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu, People’s Republic of China, Email wuyigao2000@126.com.Background: Major depressive disorder (MDD) and metabolic syndrome (MetS) are both major health threats nowadays, and the relationship between them is complex and close. The purpose of this paper is to compare differences in the prevalence and risk factors of MetS in first hospitalized patients with MDD with and without antidepressant exposure.Methods: A total of 636 first hospitalized MDD patients (study group) with antidepressant exposure and 345 drug-naïve patients (control group) were included in this study. Their socio-demographic data, routine biochemical indices, and psychological symptom assessment were collected.Results: There was no difference in the prevalence of MetS between the study group and the control group (F = 2.49, p = 0.115). Factors affecting MetS and its severity differed between the two groups, in the study group, the identified risk factors for MetS were onset age (B = 0.05, p < 0.001, OR = 1.05, 95% CI = 1.02– 1.08), TSH level (B = 0.42, p < 0.001, OR = 1.53, 95% CI = 1.39– 1.68). Meanwhile, in the control group, the identified risk factors for MetS were more extensive and they were, onset age (B = 0.11, p < 0.001, OR = 1.12, 95% CI = 1.07– 1.16), suicidal behavior (B = 1.54, p = 0.007, OR = 4.65, 95% CI = 1.51– 14.33), HAMD scores (B = 0.23, p = 0.008, OR = 1.26, 95% CI = 1.06– 1.49) and TSH levels (B = 0.33, p < 0.001, OR = 1.39, 95% CI = 1.17– 1.65). The number of risk factors identified was lower in the study group.Conclusion: Antidepressant use was associated with greater MetS severity but did not affect overall prevalence. Antidepressants appear to modify MetS risk factors, highlighting the need to differentiate these effects from those in drug-naïve patients when developing MetS interventions for the MDD population.Keywords: major depressive disorder, metabolic syndrome, antidepressant-exposed, drug-naïve, risk factor

Yue Fang,1,2,&ast; Yi Yue,3,&ast; Sensen Hao,1 Ying Zhang,4 Nan Liu,1 Shengling Wang,1 Yan Li,1 Hongzhi Wang1 1Galactophore Oncology Center, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei City, Anhui Province, People’s Republic of China; 2Science Island Branch, Graduate School of University of Science and Technology of China, Hefei City, Anhui Province, People’s Republic of China; 3The Second Clinical College, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhi Wang, Email wanghz@hfcas.ac.cnBackground: Serpin B9 is highly expressed in breast cancer, melanoma, and various malignant cells and inhibits NK cell killing through the Serpin B9-GrB axle. However, the current studies have only validated the role of Serpin B9 in vivo and vitro, and lack of systematic studies on the expression of Serpin B9 in patients’ tumor tissues and its prognostic implications. In this study, we propose to further validate the role of Serpin B9 by comparing its expression level in tissues of lung adenocarcinoma patients and its correlation with the efficacy of immunotherapy.Methods: This study included 200 patients with LUAD between Feb 2022 and Feb 2023. IHC scoring assessed Serpin B9 expression in the tumor and adjacent tissues, with an H-score of 2 as the cutoff value. Patients were divided into high- and low-expression groups. T-tests were used to compare Serpin B9 expression and treatment efficacy between the tumor and adjacent tissues in both groups. Baseline characteristics were compared using X2 tests. Prognostic risk factors were identified using Cox regression and Kaplan-Meier survival curves.Results: The expression level of Serpin B9 in LUAD tumor tissues are higher than adjacent tissues and positively correlated with the TNM stage and negative correlated with PFS in patients with LUAD. Additionally, immunotherapy efficacy was inversely correlated with Serpin B9 expression.Conclusion: The increased expression of Serpin B9 in LUAD tumor tissues is negatively linked to prognosis and immunotherapy efficacy. This underscores their potential as prognostic and therapeutic targets.Keywords: serine proteinase inhibitor B9, lung adenocarcinoma, progression free survival, PD-1/PD-L1

Shuang Wang,1– 4,&ast; Xuexia Liu,5 Xinhua Lin,1– 4,&ast; Xiaojing Lv,2– 4 Hua Zhang2– 4 1School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 5Shandong Stem Cell Engineering Technology Research Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuexia Liu; Hua Zhang, Department of Otorhinolaryngology & Head and Neck Surgery, Yuhuangding Hospital Affiliated to Qingdao University, No. 20 East, Yuhuangding Road, Yantai, Shandong, 264000, People’s Republic of China, Tel +86-15154502782, Email xue6er6@163.com; zhang0hua@163.comAbstract: Allergic rhinitis (AR), which presents symptoms like sneezing and a runny nose, is categorized as an upper respiratory condition of type 2. Recent progress in comprehending AR has revealed the significant role played by type 2 cytokines, specifically interleukin (IL)-13, IL-4, and IL-5. These cytokines are released by helper T cells 2 (Th2) and innate lymphoid cells (ILC2s). ILC2s have the ability to interact with various immune cells and are essential in promoting both type 2 immune response and tissue repair, contributing to normal homeostatic functions within the body. This article presents a summary of the latest advancements in comprehending the activity of ILC2s, with particular emphasis on their potential role involvement in AR. It explores how they collaborate with Th2 cells to exacerbate nasal inflammation and interact with regulatory T cells (Tregs) to counteract the suppressive role mediated by Tregs during allergic inflammation. The significance of ILC2s in allergen-specific therapy is highlighted. A comprehensive understanding of ILC2s biology establishes a robust foundation for unraveling the pathogenesis of AR and devising innovative therapeutic approaches for its management.Keywords: allergic rhinitis, group 2 innate lymphoid cells, cytokines, Treg cells, Th2 cells

Jiyang Li,1,&ast; Xinxing Fei,2,&ast; Shiqi Wang,3,4,&ast; Zhangyu Xu,5,6 Fangyuan Xu,5,6 Jianxiong Wang,5,6 Yaqian Gao,7 Yue Hu5,6 1Department of Rehabilitation Medicine, Sichuan Tianfu New Area People’s Hospital, Chengdu, People’s Republic of China; 2Department of Psychiatry, Chengdu Eighth People’s Hospital (Geriatric Hospital of Chengdu Medical College), Chengdu, People’s Republic of China; 3Department of Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, Sichuan, People’s Republic of China; 5Department of Rehabilitation Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 6Rehabilitation Medicine and Engineering Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 7Department of Rehabilitation Medicine, the First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqian Gao; Yue Hu, Email 673509366@qq.com; huyue@swmu.edu.cnBackground: Many studies have been conducted on the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression. However, the overall trends in research publications in this field remain elusive. There is still little quantitative analysis of the literature in this field. Therefore, we conducted a bibliometric analysis to explore the research patterns surrounding SSRIs for depression, aiming to gain a deeper understanding of their development and impact.Methods: Publications about the use of SSRIs for the treatment of depression were identified in the Web of Science Core Collection. Visualization analysis was performed with Bibliometrix, VOSviewer, and CiteSpace.Results: A total of 1149 publications published from 1990 to 2024 were included in the bibliometric analysis. Since 1990, the annual number of published papers has increased annually, reaching the maximum value of output in 2004. Fitted curve showed that after 2004, the number of publications per year was essentially stable The United States dominates the field. Among these institutions, University of Pittsburgh excels in this field. Fava M has the highest scientific productivity and extensive academic influence. European Neuropsychopharmacology is the most active journal in this field. The three most relevant keywords were “fluoxetine”, “double-blind”, and “major depression”. The trend topics in recent years were “connectivity”, “c-reactive protein”, and “anhedonia”.Conclusion: Research on the use of SSRIs for the treatment of depression continues to receive increased attention but still requiraes further exploration and innovation. We further analyze the current research hotspots and frontiers in this field.Keywords: selective serotonin reuptake inhibitors, depression, bibliometrics, double-blind, fluoxetine, major depression

Guanghui Zheng,1– 3 Yijun Shi,1– 3 Jialu Sun,1 Siqi Wang,1 Lingye Qian,4 Hong Lv,1– 3 Guojun Zhang,1– 3 Kelin Chen1– 3 1Clinical Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2NMPA Key Laboratory for Quality Control of in vitro Diagnostics, Beijing, People’s Republic of China; 3Beijing Engineering Research Center of Immunological Reagents Clinical Research, Beijing, People’s Republic of China; 4Clinical Laboratory of Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Guojun Zhang; Kelin Chen, Clinical Laboratory of Beijing Tiantan Hospital, Capital Medical University, NO. 119 Nansihuan West Road, Fengtai District, Beijing, People’s Republic of China, Tel +86 15811219411 ; +86 13810876107, Email zgjlunwen@163.com; chenkelin214316@163.comAim: To express the clinical characteristics of patients with post-neurosurgical meningitis (PNM) and launch a survival analysis to screen mortality predictors.Methods: A cohort analysis containing more than 70000 patients was evaluated, and all of them received neurosurgical procedure. Clinical and microbial epidemiology, therapy and mortality of PNM patients were reviewed. Multi-variable Cox proportional hazard models were applied to achieve survival analysis.Results: About 900 PNM patients from 3244 cases were selected for characteristics and survival analysis, the mean age of them was 41 (27– 54) years, 516 (57.3%) were men and 384 (42.7%) were women. The 28-day mortality was 12.4% (112 of 900) in patients with PNM. Hypertension, external ventricular drainage (EVD), and lumbar drainage (LD) are mortality predictors for PNM, with a hazard ratio (HR) of 2.641 (95% C.I. 1.563– 4.464, P< 0.001), 2.196 (95% C.I. 1.317– 3.662, P=0.003), and 1.818 (95% C.I. 1.126– 2.936, P=0.014). In treatment, the outcome of patients receiving three or more antibiotic combinations is better than that of patients receiving dual-drug combinations.Conclusion: The mortality of patients with PNM was relatively high, and the risk factors related to 28-days mortality were hypertension, EVD and LD and treatment with three or more antibiotics are much better.Keywords: Post-neurosurgical meningitis, survival analysis, mortality, characteristics, treatment

Tielong Chen,1,&ast; Jianwu Zheng,1,&ast; Cheng Bao,1 Yu Wang,1 Shiwang Wang,1 Lu Liang,1 Li Zhang,2 Hui Zhang,2 Chaoxia Ji,2 Jian Wang,2 Xudong Zhang,1 Guangli Zhu,1 Houyong Zhu1 1Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tielong Chen; Houyong Zhu, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, Zhejiang, 310007, People’s Republic of China, Email ctlppp@foxmail.com, ctlppp@163.com; houyongzhu@foxmail.comBackground: Despite statins and other medications central to atherosclerotic cardiovascular disease (ASCVD) secondary prevention, stable coronary artery disease (SCAD) patients remain at significant cardiovascular risk, partly due to residual inflammation risk (RIR). This study aims to assess if adding Guanxinning to standard ASCVD therapy further mitigates RIR in SCAD patients.Methods: In a prospective, randomized, single-blind endpoint design, 50 patients with SCAD who received ASCVD standardized treatment strategy were randomly assigned to either take Guanxinning tablets (4 tablets, thrice daily) or no Guanxinning tablets and were followed up for an average of 12 weeks. The primary outcomes were changes in inflammation-related indicators, including interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP).Results: Compared with the control group, the intervention group showed significantly greater decreases in the levels of IL-2, IL-6, TNF-α, and hs-CRP (all P < 0.05). However, there was no significant difference in the IL-4 level between the two groups (P > 0.05). Compared with the control group, there were also significant improvements in endothelial function-related indicators (vascular endothelial growth factor (VEGF), nitric oxide (NO), and peroxisome proliferator-activated receptor-γ (PPAR-γ)), blood lipid profile (total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C)), and chest pain related scores (angina and Traditional Chinese medicine syndrome scores) in the intervention group (all P< 0.05). There was no significant difference in the triglyceride (TG) and carotid intima-media thickness between the two groups (P< 0.05). Compared to the control group, there was no significant difference in the white blood cell line, liver and kidney function, anemia, and bleeding in the intervention group (all P< 0.05).Conclusion: The addition of Guanxinning tablets (4 tablets, thrice daily) to the standard treatment strategy for ASCVD was associated with a reduction in the RIR in patients with SCAD and demonstrated good safety.Plain Language Summary: In the quest for a heart-healthy life, even with statins at our side, some folks with stable heart troubles still face a sneaky foe: lingering inflammation. Our study explored whether adding Guanxinning, a traditional Chinese medicine, to the standard treatment might help. Over 12 weeks, patients who took Guanxinning along with their usual heart meds showed promising signs of reduced inflammation and improved heart health markers. These preliminary positive signs hint at the potential benefits of Guanxinning, which, however, need further studies to confirm. Fortunately, it appears to be safe to use Guanxinning alongside conventional treatments for now. As we delve deeper into the mysteries of heart health, every promising discovery brings us one step closer to developing better therapeutic strategies.Keywords: Guanxinning, stable coronary artery disease, risk of residual inflammation, secondary prevention

Xinqing Zhu,1,&ast; Abdullah Al-danakh,1,&ast; Yuli Jian,2,&ast; Mohammed Safi,3,&ast; Sijie Luo,1,&ast; Qiwei Chen,1 Shujing Wang,2 Deyong Yang1,4 1Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, Liaoning People’s Republic of China; 3Thoracic/Head and Neck Medical Oncology Department, MD Anderson Cancer Center, Houston, TX, USA; 4Department of Surgery, Healinghands Clinic, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyong Yang; Shujing Wang, Email yangdeyong@dmu.edu.cn; wangshujing@dmu.edu.cnBackground: Clear cell renal cell carcinoma (ccRCC), the predominant subtype of RCC, is distinguished by unique biological characteristics and heterogeneity, including eosinophilic and clear subtypes. Notwithstanding progress in therapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs), the prognosis for individuals with metastatic ccRCC remains poor, presumably owing to metabolic alterations leading to mitochondrial dysfunction, which affects treatment response variability.Methods: We analyzed histological and immunohistochemical data from a cohort at Dalian Medical University’s First Affiliated Hospital alongside RNA-sequencing transcriptome data from the TCGA database. Histologically, eosinophilic and clear ccRCC subtypes were evaluated using Kaplan-Meier and Cox proportional hazards models for survival analysis and prognosis. Differential gene expression (DEG) analysis and Gene Set Enrichment Analysis were performed to explore transcriptomic differences and relevant pathways.Results: The study discovered substantial histological and molecular differences between the eosinophilic and clear cell subtypes of ccRCC. The eosinophilic subtype linked with frequent high-grade tumors (69.05% eosinophil vs 35.35% clear) and a poorer prognosis (HR=2.659, 95% CI:1.437– 4.919, P=0.002). DEG analysis revealed distinct expression patterns among subtypes and identified a risk score signature that remained significant even after adjusting for clinical variables (HR=3.967, 95% CI: 1.665– 9.449, P=0.002), showing less favorable survival in the high-risk group (P < 0.0001). RRM2 emerged as the most prognostic gene from this risk score, particularly in the eosinophilic subtype, alongside other clinical variables. By IHC, RRM2 shows high IHC score in eosinophilic compared to clear subtype (P=0.019). In addition, highly expressed RRM2 correlates with poor outcomes and is linked to mitochondrial genes, immunological pathways, and ICIs treatment.Conclusion: These findings show significant differences in prognosis between subtypes. RRM2 was the most prognostic gene from the discovered novel risk score signature associated with subtypes. Future research is essential to validate these insights and their therapeutic implications for ccRCC management.Keywords: clear cell renal cell carcinoma subtypes, metabolic reprogramming. mitochondria, tumor microenvironment, RRM2, immune checkpoint inhibitors

Wenhao Chen,1 Yuanliang Liu,2 Xunwei Deng,3 Bin Li,1 Hao Wang,1 Guoliang Wei,1 Kehui Chen,1 Shen Wang1 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Computer Tomography, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Research Experimental Center, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Wenhao Chen, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 18319255493@163.comObjective: Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the CYP2C19 gene represents downregulation of CYP2C19 enzyme indication limited or no enzymatic function, which may be, in turn, associated with some disease susceptibility. The relationship between CYP2C19 polymorphisms and susceptibility to premature coronary artery disease (PCAD) is not fully understood. This study aimed to assess this relationship.Methods: This study included 635 PCAD patients, and 548 age-matched non-CAD individuals as controls, from November 2019 to August 2023. The CYP2C19 rs4244285 (681G > A, &ast;2) and rs4986893 (636G > A, &ast;3) were genotyped, and the distribution of CYP2C19 polymorphisms between patients and controls and the relationship between CYP2C19 polymorphisms and PCAD risk were analyzed.Results: A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had CYP2C19 extensive metabolizer (EM) (&ast;1/&ast;1), intermediate metabolizer (IM) (&ast;1/&ast;2 and &ast;1/&ast;3), and poor metabolizer (PM) (&ast;2/&ast;2, &ast;2/&ast;3, and &ast;3/&ast;3) phenotypes, respectively. CYP2C19 &ast;2/&ast;2 genotype frequency was higher, &ast;1/&ast;1 genotype was lower in PCAD patients than controls. Individuals with CYP2C19 PM phenotype had higher triglyceride (TG) levels than those with CYP2C19 EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041– 1.688, p = 0.022), smoking (OR: 1.974, 95% CI: 1.283– 3.306, p = 0.002), hypertension (OR: 1.327, 95% CI: 1.044– 1.687, p = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054– 1.834, p = 0.020), CYP2C19 PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200– 2.411, p = 0.003), and CYP2C19 IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077– 1.740, p = 0.010) were associated with PCAD.Conclusion: CYP2C19 PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.Keywords: premature coronary artery disease, cytochrome P450, CYP2C19, loss-of-function

Henan Li,&ast; Didaer Talanaite,&ast; Zitong Pan,&ast; Zhiren Wang, Shuyi Wang, Hui Wang Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Henan Li; Hui Wang, Department of Clinical Laboratory, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China, Email lihenan@pkuph.edu.cn; whuibj@163.comBackground: Patients with hematological malignancies are more susceptible to infections, leading to a poor prognosis. Acinetobacter colonization is a risk factor for secondary bacteremia.Methods: Antibiotic susceptibility phenotypes and genomic characteristics of 48 oral Acinetobacter spp. and one bloodstream Acinetobacter baumannii from patients with hematological malignancies were analyzed by antimicrobial susceptibility tests and whole-genome sequencing. We conducted comparative genomic analysis of oral and blood isolates from the same patient.Results: A. baumannii was the most common (72.92%, 35/48) Acinetobacter species in oral Acinetobacter spp. isolates. Seventeen different A. baumannii sequence types were identified using the Pasteur MLST scheme; however, the dominant global clones GC1 and GC2 were not present. Among the isolates, 46 (95.8%) were carbapenem-susceptible Acinetobacter spp. One patient treated with meropenem for 15 days developed A. baumannii bacteremia 46 days after the isolation of oral A. baumannii AOR07. Oral and bloodstream isolates from the same patient were closely related to only four non-synonymous mutations on the chromosome. The blaOXA-58 gene was transferred between plasmids through XerCD-mediated recombination, leading to an elevated copy number, causing carbapenem resistance in bloodstream isolates.Conclusion: Oral Acinetobacter spp. may cause secondary bacteremia. The amplification and transfer of blaOXA-58 in the plasmids explained the increased carbapenem resistance in the bloodstream isolate.Keywords: Acinetobacter, within-host evolution, oral colonization, bloodstream infection, hematological malignancies

Runing Fu,1,&ast; Wenping Lian,1,&ast; Bohao Zhang,2,&ast; Gang Liu,3 Xinyu Feng,1 Yingjie Zhu,1 Jiuan Zhou,1 Xinyu Zhang,4 Shukai Wang,1 Huijuan Huo,1 Daxin Wang,1 Cui Liu,1 Saisai Gao,1 Yajie Ma,4 Mengle Peng1,&ast; 1Department of Clinical Laboratory, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 3The Center of Meige Syndrome, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 4Department of Medical Affair, the Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengle Peng; Yajie Ma, Email pengmengle1990@126.com; szsyywk@sina.comPurpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People’s Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model’s performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.Keywords: Meige syndrome, inflammatory marker, nomogram, LMR, SII

Yu Yang,1,2 Shuqi Wang,1,3 Boying Jia,1,3 Shuchun Chen1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuc2014@163.comPurpose: To investigate the relationship between the triglyceride-glucose (TyG) index and pulmonary function metrics among the general population undergoing health examinations.Materials and Methods: The enrollment totaled 696 participants. Fasting triglycerides and glucose levels were used to calculate the TyG index. Participants were divided into two categories according to their median TyG: one with high TyG and the other with low TyG. A portable spirometer was used to assess lung function. Fundamental clinical features and lung function indicators were compared between the two groups, and the relationship between the TyG index and lung function parameters was explored.Results: Compared with the low TyG group, the high TyG group exhibited significantly reduced levels of FEV1/FVC, FVC% pred, FEV1% pred, FEV3% pred, FEV3/FVC, FEF75, FEF75% pred, FEF25-75% pred, and MVV% pred, suggesting poor pulmonary function. The TyG index was significantly inversely correlated with multiple pulmonary function metrics, including FVC% pred, FEV1% pred, FEV3% pred, FEV1/FVC, FEV3/FVC, FEF75, FEF75% pred and FEF25-75% pred, which persisted even after accounting for confounding variables.Conclusion: In summary, the present study establishes a correlation between the TyG index and some lung function indicators, offering a new indicator of metabolic abnormalities related to lung functionality.Keywords: triglyceride-glucose index, lung function, insulin resistance, FEV1, FVC

Shiyang Wang, Binhe Tian, Hanping Wang Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Hanping Wang, Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86010-69158760, Email wanghanping78@163.comObjective: This study aimed to investigate the risk factors for immune checkpoint inhibitor (ICI)-related colitis and its impact on prognosis in the treatment of lung cancer.Methods: This retrospective, single-center, observational study included lung cancer patients who received ICIs treatment between January 2016 and January 2022. The correlation between immune-related colitis and prognosis was evaluated. Kaplan-Meier analysis was used to compare the median overall survival (OS).Results: Among the lung cancer patients treated with ICIs, the incidence of colitis was 5.88% (35/595). The severity of colitis was graded as follows: grade 1 (8 cases), grade 2 (15 cases), grade 3 (9 cases), and grade 4 (3 cases). Except for the 1 case that resulted in death due to grade 4 adverse events, the remaining patients showed significant improvement after corticosteroid intervention. Among the 35 patients with ICI-related colitis, complete remission was not achieved. Partial remission was observed in 11 cases, disease stability in 16 cases, disease progression in 7 cases, and death in 1 case. Among the included patients, 19 chose to continue ICI treatment after symptom relief. The overall survival for all participants was 34 months (IQR: 24– 36), while the overall survival for those who received ICI treatment again was 36 months (IQR: 32-NA), and for those who did not receive ICI treatment again was 32 months (IQR: 21– 35). Kaplan-Meier survival curve analysis showed that patients who received ICI treatment again had significantly better overall survival compared to other patients.Conclusion: Immune-related colitis remains a significant concern in lung cancer patients treated with ICIs and requires close monitoring and timely intervention. Restarting treatment after symptom relief can provide additional benefits for patients.Keywords: lung cancer, immune checkpoint inhibitors, colitis, risk factors, prognosis

Jinqi Ding,1,&ast; Yue Wu,1,&ast; Hanxiaoran Li,1 Shengsheng Wang,1 Jia Cai,2 Hong Cheng,3 Sugai Liang1 1Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Hangzhou City University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sugai Liang, Email liangsugai@zju.edu.cnPurpose: Network modeling has been suggested as an effective method to explore intricate relationships among antecedents, mediators, and symptoms. In this study, we aimed to investigate whether the severity of depressive symptoms in college students affects the multivariate relationships among anhedonia, smartphone addiction, and mediating factors.Methods: A survey was conducted among 1347 Chinese college students (587 female) to assess depressive symptoms, anhedonia, addictive behaviors, anxiety, and insomnia. The participants were categorized the non-depressive symptom (NDS) and depressive symptom (DS) groups based on a cut-off score of 5 on the 9-item Patient Health Questionnaire-9. Network analysis was performed to investigate the symptom-to-symptom influences of symptoms in these two groups.Results: The network of the DS group was more densely connected than that of the NDS group. Social anticipatory anhedonia was a central factor for DS, while withdraw/escape (one factor of smartphone addiction) was a central factor for NDS. The DS group exhibited greater strength between the PHQ9 score and social anticipatory anhedonia, as well as between the PHQ9 score and alcohol misuse score, compared to the NDS group. On the other hand, the NDS group had higher strength between anxiety and feeling lost, as well as between anxiety and withdraw/escape, compared to the DS group.Conclusion: The findings suggest that there is a close relationship between social anhedonia, smartphone addiction, and alcohol consumption in the DS group. Addressing on ameliorating social anhedonia and smartphone addiction may be effective in preventing and managing depression in college students.Keywords: depressive symptoms, anhedonia, smartphone addiction, network analysis, college students

Tongzuo Liu,1,2,&ast; Jingyi Zhang,1,2,&ast; Zhiqiang Zhao,1 Yingfei Bi,1 Ying Zheng,1 Shuai Wang,1 Xiaohua Dai,3 Jun Li,4 Qian Lin,5 Daimei Ni,6 Chenglong Wang,7 Jianguang Wu,8 Yitao Xue,9 Mingjun Zhu,10 Xianliang Wang,1,&ast; Jingyuan Mao1,&ast; 1Cardiovascular Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 2Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Cardiovascular Department, The First Affiliated Hospital of Anhui University of Chinese Medicine, Anhui, People’s Republic of China; 4Cardiovascular Department, Guang’anmen Hospital of China Academy of Chinese Medicine Science, Beijing, People’s Republic of China; 5Cardiovascular Department, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Cardiovascular Department, Taihe Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Chinese Medicine, Anhui, People’s Republic of China; 7Cardiovascular Department, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 8Cardiovascular Department, Affiliated Hospital of Jiangxi University of Chinese Medicine, Jiangxi, People’s Republic of China; 9Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong, People’s Republic of China; 10Cardiovascular Department, The First Affiliated Hospital of He’nan University of Traditional Chinese Medicine, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyuan Mao; Xianliang Wang, Cardiovascular Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China, Tel +86-13820498886 ; +86-13920007825, Email jymao@126.com; xlwang1981@126.comBackground: Stable angina pectoris (SAP), as a common type of coronary heart disease (CHD), is characterized by transient retrosternal squeezing pain or suffocation induced by exercise, mood swings, or other stress. Most patients with stable angina pectoris do not benefit from interventional therapy and medication, so optimizing treatment plans has important clinical significance. Jiuxin pill is a Chinese patent medicine developed by Huatuo Chinese Medicine Co. Ltd. (Bozhou, China) to relieve the symptoms of stable angina pectoris (SAP). However, there is a lack of evidence support from high-quality clinical studies.Methods: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 170 patients with SAP were recruited from 11 centers in China. The patients were randomized to either the treatment group (Jiuxin pill, 2 pills, bid) or the control group (Jiuxin pill simulant, 2 pills, bid) without changing the original conventional western medicine. The trial was set up with a run-in period of 7 days, a treatment period of 28 ± 2 days, and a follow-up period of 28 ± 2 days. Total exercise time (TED) in the treadmill test and Seattle Angina Questionnaire (SAQ) scores were set as the main efficacy outcomes, and the 1-minute heart rate recovery (HRR1), metabolic equivalents (METs), maximum ST segment depression, Borg perceived exertion after exercise, the average number of angina attacks per week, usage of nitroglycerin, drug withdrawal and reduction rate, information scoring of four diagnostic methods in traditional Chinese medicine and incidence of major adverse cardiovascular events were set as the secondary efficacy outcomes. Adverse events were monitored throughout the trial.Discussion: In China, the use of Chinese patent medicine in the treatment of stable angina pectoris is more common. This trial evaluated the efficacy and safety of the Jiuxin pill in the treatment of patients with SAP, and the trial results provide high-quality research evidence for its clinical application.Trial Registration: This trial has been registered in the China Clinical Trial Registry on 11 June 2022 (Registration No.: ChiCTR2200060780, https://www.chictr.org.cn/showproj.html?proj=172352).Keywords: traditional Chinese medicine, Jiuxin pill, stable angina pectoris, protocol, randomized controlled trial

Sicong Wang, Yan Li, Fang Chen, Hua-Cheng Liu, Lezhou Pan, Wangning Shangguan Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Key Laboratory of Pediatric Anesthesiology of Ministry of Education, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Wangning Shangguan, Email sgwning@163.comPurpose: This study aimed to estimate the effect of different doses of fentanyl on the median effective dose (ED50) of ciprofol for attenuating the airway and motor response to laryngeal mask airway (LMA) insertion response in healthy children.Patients and Methods: 90 healthy preschool patients undergoing inguinal hernia repair surgery were randomly assigned to one of three groups: C0 (ciprofol+saline), C1 (ciprofol + fentanyl 1μg/kg), C2 (ciprofol + fentanyl 2μg/kg). Anesthesia was induced with either prepared fentanyl or saline, followed by ciprofol. The dose of ciprofol for each patient was determined using the up-and-down sequential study design. The primary outcome was the ED50 of ciprofol required for smooth LMA insertion in the three groups. Additionally, the time to loss of consciousness and any perioperative adverse events were recorded.Results: Compared with the C0 group, the ED50 (95% confidence interval) of ciprofol in the C1 and C2 groups were significantly lower (1.81 [1.73– 1.90]mg/kg versus 0.67 [0.64– 0.71]mg/kg and 0.48 [0.42– 0.54] mg/kg, respectively; P< 0.05). Additionally, the ED50 of ciprofol in the C2 group was lower than that in the C1 group (0.42 [0.42– 0.54] mg/kg vs 0.67 [0.64– 0.71]mg/kg; P< 0.05). Furthermore, the time to loss of consciousness in the C1 and C2 groups decreased by 60% and 53%, respectively, compared to the C0 group. There were no significant differences in the incidence of drug-related hypotension after anesthesia induction among the three groups. No adverse events of hypoxia, bradycardia, or injection pain were observed in any groups.Conclusion: In healthy, non-obese Chinese children undergoing elective inguinal hernia repair surgery, fentanyl 1 μg/kg and 2 μg/kg before ciprofol injection significantly reduced the ED50 of ciprofol for attenuating LMA response, with minimal occurrence of severe side effects.Keywords: ciprofol, laryngeal mask airway, pediatric anesthesia, 50% effective dose

Shangtao Wang,1 Chenghao Zhu,1 Shurui Zhang,1 Siyu Ma,1 Baoshan Li,1 Shengbo Zhao,2 Wei Zhang,3 Zhirong Sun1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Ningqiang Tianma Research Institution Limited Liability Company, Hanzhong, Shaanxi, People’s Republic of China; 3Ningqiang County Traditional Chinese Medicinal Industry Development Center, Hanzhong, Shaanxi, People’s Republic of ChinaCorrespondence: Zhirong Sun, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Northeast Corner of the Intersection of Yangguang South Street and Baiyang East Road, Fangshan District, Beijing, 102401, People’s Republic of China, Email szrbucm67@163.comBackground: Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear.Objective: This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms.Methods: The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting.Results: In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways.Conclusion: Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN. Keywords: gastrodin, gallic acid, synergistic effects, inflammation, apoptosis, sphingolipid pathways

Abdullah Al Mamun,1,2 Peiwu Geng,1 Shuanghu Wang,1 Chuxiao Shao1 1Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Chuxiao Shao; Shuanghu Wang, Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, the Lishui Hospital of Wenzhou Medical University, the First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Email scx1818@126.com; wangshuanghu@lsu.edu.cnAbstract: Pyroptosis is an inflammatory cell death induced by inflammasomes that release several pro-inflammatory mediators such as interleukin-18 (IL-18) and interleukin-1β (IL-1β). Pyroptosis, a type of programmed cell death, has recently received increased interest both as a therapeutic and immunological mechanism. Numerous studies have provided substantial evidence supporting the involvement of inflammasomes and pyroptosis in a variety of pathological conditions including cancers, nerve damage, inflammatory diseases and metabolic conditions. Researchers have demonstrated that dysregulation of pyroptosis and inflammasomes contribute to the progression of endometriosis and gynecological malignancies. Current research also indicates that inflammasome and pyroptosis-dependent signaling pathways may further induce the progression of endometrial cancer (EC). More specifically, dysregulation of NLR family pyrin domain 3 (NLRP3) and caspase-1-dependent pyroptosis play a contributory role in the pathogenesis and development of EC. Therefore, pyroptosis-regulated protein gasdermin D (GSDMD) may be an independent prognostic biomarker for the detection of EC. This review presents the molecular mechanisms of pyroptosis-dependent signaling pathways and their contributory role and function in advancing EC. Moreover, this review offers new insights into potential future applications and innovative approaches in utilizing pyroptosis to develop effective anti-cancer therapies. Keywords: endometrial cancer, pyroptosis, NLRP3, caspase-1, GSDMD, IL-1β, IL-18

Hongmei Xu,1 Ningning Wu,2 Hui Yu,3 Chuanqing Wang,4 Jikui Deng,5 Hongmei Wang,5 Chunzhen Hua,6 Yinghu Chen,6 Xuejun Chen,7 Ting Zhang,8 Hong Zhang,9 Yiping Chen,10 Shifu Wang,11 Qing Cao,12 Huiling Deng,13 Sancheng Cao,14 Jianhua Hao,15 Wei Gao,16 Chunmei Jing2 1Infectious Disease Department, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, People’s Republic of China; 3Infectious Disease Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Clinical Microbiology Laboratory, Nosocomial Infection Control Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 5Infectious Disease Department, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 6Infectious Disease Department, Children’s Hospital of Zhejiang University, Zhejiang, People’s Republic of China; 7Department of Medical Laboratory, Children’s Hospital of Zhejiang University, Zhenjiang, People’s Republic of China; 8Digestive and Infectious Disease Department, Children’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 9Department of Medical Laboratory, Children’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 10Pediatric Infectious Disease Department, Second Affiliated Hospital, and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 11Department of Medical Laboratory, Qilu Children’s Hospital, Shandong University, Shandong, People’s Republic of China; 12Infectious Disease Department, Shanghai Children’s Medical Center, Shanghai, People’s Republic of China; 13Infectious Disease Department, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 14Department of Medical Laboratory, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 15Infectious Disease Department, Children’s Hospital of Kaifeng City, Kaifeng, People’s Republic of China; 16Department of Medical Laboratory, Children’s Hospital of Kaifeng City, Kaifeng, People’s Republic of ChinaCorrespondence: Chunmei Jing, Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing Medical University, No. 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014, People’s Republic of China, Email jcm791203@163.comObjective: Aim to investigate the pathogens distribution and drug resistance of gram-negative bacteria causing bloodstream infection (BSIs) in Infectious Disease Surveillance of Pediatric from 2016 to 2022. The prevalence of four important drug resistance phenotypes was studied: difficult-to-treat resistance, fluoroquinolone resistance, carbapenem resistance, and extended-spectrum cephalosporin resistance, and to provide reference basis for preventing and treating BSIs diseases in children.Methods: Strain identification and antimicrobial susceptibility tests were independently performed at each hospital. Data were analyzed using Whonet 5.6 and GraphPad Prism 8 software. The Mann–Whitney U-test was used to examine and compare temporal changes.Results: A total of 39977 BSIs strains were isolated, with 27.1% of the negative bacteria causing BSIs (10824 strains). The highest bacteria detected were E. coli and S. maltophilia in the neonatal and pediatric groups. The detection rate of carbapenem-resistant-K. pneumoniae (CRKPN) in neonate group was 31.4%, significantly increased compared with pediatric group, whose detection rate was 24.7%. The rates of resistance to levofloxacin and trimethoprim/sulfamethoxazole were significantly lower in neonatal groups than pediatric groups in BSIs caused by K. pneumoniae. To imipenem and meropenem were 3.6% and 3.9% among neonatal isolates, which was lower than 4.7% and 5.8 among pediatric BSIs caused by E. coli. Isolated from neonatal BSIs caused by A. baumannii showed lower resistance ratios to all the agents tested than those from pediatric. However, only the prevalence of piperacillin/tazobactam resistance was statistically lower than that in pediatric BSIs caused by P. aeruginosa. The average detection rates of carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance for K. pneumoniae and E. coli were 28.1%,41.4%,11.6% and 4.0%,24.3%,31.1%, respectively.Conclusion: The detection rate of gram-negative pathogens showed an increasing trend among the bloodstream infection. The detection rate of CRKPN assumed a downward trend in 2018. There are differences types of pathogens between the neonatal group and the pediatric group, The detection rate of CRKPN in the neonate group was significantly higher than pediatric group. The first average detection rates for carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance were obtained for A. baumannii, K. pneumoniae, and Escherichia coli, respectively. Those data showed a high level of antimicrobial resistance, which has posed an urgent threat to Children’s health, suggested that effective monitoring of antimicrobial resistance and antimicrobial stewardship among children in China are required.Keywords: bloodstream infection, pathogenic bacterium, difficult-to-treat resistance, carbapenem resistance, extended-spectrum cephalosporin resistance, fluoroquinolone resistance

Peiyu Xing,1,&ast; Yucheng Zhang,2,&ast; Yong Zhang,1 Shaowei Wang,2 Xiaojia Hu,1 Meihua Wang,1 Fan Xia,1 Yang Zhao,1 Wei Qu,2 Bo Meng2 1Department of Ophthalmology, China Medical University the Fourth People’s Hospital of Shenyang, Shenyang, People’s Republic of China; 2Department of Ophthalmology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Meng, Department of Ophthalmology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email m18204507737@163.comPurpose: The objective of this research was to assess the effectiveness and safety of using Conbercept injection and dexamethasone implant (DEX I) in sequence for treating refractory macular edema (ME) caused by central retinal vein occlusion (CRVO) in patients.Methods: A study was conducted on 34 patients with persistent macular edema caused by central retinal vein occlusion, reviewing their medical history and interventions performed. Sequential implantation of DEX I was performed 1 week after the Conbercept injection. OCTA images were used to measure central retinal thickness (CRT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and pre- and post-treatment vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), with a 1-year follow-up period.Results: At the 12-month follow-up, participants demonstrated notable improvements in central retinal thickness and intraocular pressure (p < 0.05). Throughout the monitoring period, no significant differences were found in BCVA improvement or vessel density reduction (p > 0.05). Two patients required topical treatment to lower their intraocular pressure during the study period.Conclusion: In conclusion, patients experiencing persistent ME due to secondary CRVO may benefit from transitioning to a treatment regimen involving Conbercept and DEX I, potentially resulting in a reduction in CRT. However, no significant improvement was observed in BCVA or deep and superficial capillary plexus vessel density.Keywords: macular edema, sequential, central retinal thickness, best corrected visual acuity

Yongkun Du, Shuai Wang, Ting Zhou, Zhongyan Zhao Department of Critical Care Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of ChinaCorrespondence: Zhongyan Zhao, Email zhongyan@jlu.edu.cnBackground: Recent evidence suggests that the gut microbiome and metabolites are intricately involved in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis, yet the precise causal relationships remain unclear due to confounding factors and reverse causation. This study employs bidirectional two-sample Mendelian Randomization (MR) to clarify these connections.Methods: Summary data from publicly available Genome-Wide Association Studies (GWAS) concerning the gut microbiome, metabolites, and COPD were compiled. The selection of genetic instrumental variables (Single Nucleotide Polymorphisms, or SNPs) for MR analysis was conducted meticulously, primarily utilizing the Inverse Variance Weighting (IVW) method, supplemented by MR-Egger regression and the Weighted Median (WM) approach. The evaluation of heterogeneity and horizontal pleiotropy was performed using Cochran’s Q test, the MR-Egger intercept test, and the MR-PRESSO global test. Sensitivity analyses, including leave-one-out tests, were conducted to verify the robustness of our results. And the mediation effect of gut microbiota-mediated changes in metabolites on the causal relationship with COPD was analyzed.Results: Our study identified nine significant gut microbiota taxa and thirteen known metabolites implicated in COPD pathogenesis. Moreover, associations between the onset of COPD and the abundance of five bacterial taxa, as well as the concentration of three known metabolites, were established. These findings consistently withstood sensitivity analyses, reinforcing their credibility. Additionally, our results revealed that gut microbiota contribute to the development of COPD by mediating changes in metabolites.Conclusion: Our bidirectional Two-Sample Mendelian Randomization analysis has revealed reciprocal causal relationships between the abundance of gut microbiota and metabolite concentrations in the context of COPD. This research holds promise for identifying biomarkers for early COPD diagnosis and monitoring disease progression, thereby opening new pathways for prevention and treatment. Further investigation into the underlying mechanisms is essential to improve our understanding of COPD onset.Keywords: chronic obstructive pulmonary disease, gut microbiota, metabolites, Mendelian randomization, causal effect

Liang Wang,1,2,&ast; Shuo Wang,3,&ast; Chujiao Tian,3 Tao Zou,3 Yunshan Zhao,2 Shaodan Li,3 Minghui Yang,3 Ningli Chai1 1Department of Gastroenterology, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Health Medicine Department, the 955th Hospital of the Army, Changdu, Tibet, 854000, People’s Republic of China; 3Department of TCM, Sixth Medical Center, Chinese PLA General Hospital, Beijing, 100048, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaodan Li, Department of TCM, Sixth Medical Center, Chinese PLA General Hospital, Beijing, 100048, People’s Republic of China, Email lsd301@126.com Ningli Chai, Department of Gastroenterology, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email chainingli@vip.163.comPurpose: Sleep deprivation (SD), a common sleep disease in clinic, has certain risks, and its pathogenesis is still unclear. This study aimed to identify ferroptosis-cuproptosis-related genes (FCRGs) associated with SD through bioinformatics and machine learning, thus elucidating their biological significance and clinical value.Methods: SD-DEGs were obtained from GEO. We intersected key WGCNA module genes of DE-FCRGs with SD-DEGs to obtain SD-DE-FCRGs. GO and KEGG analyses were performed. Machine learning was used to screen SD-DE-FCRGs, and filtered genes were intersected to obtain SD characteristic genes. ROC curves were used to evaluate the accuracy of SD characteristic genes. CIBERSORT was used to analyze the correlation between SD-DE-FCRGs and immune cells. We constructed a ceRNA network of SD-DE-FCRGs and used DGIbd to predict gene drug targets.Results: The 156 DEGs were identified from GSE98566. Five SD-DE-FCRGs from DE- FCRGs and SD-DEGs were analyzed via WGCNA, and enrichment analysis involved mainly ribosome regulation, mitochondrial pathways, and neurodegenerative diseases. Machine learning was used to obtain Four SD-DE-FCRGs (IKZF1, JCHAIN, MGST3, and UQCR11), and these gene analyses accurately evaluated the distribution model (AUC=0.793). Immune infiltration revealed that SD hub genes were correlated with most immune cells. Unsupervised cluster analysis revealed significant differential expression of immune-related genes between two subtypes. GSVA and GSEA revealed that enriched biological functions included oxidative phosphorylation, ribonucleic acid, metabolic diseases, activation of oxidative phosphorylation, and other pathways. Four SD-DE-FCRGs associated with 29 miRNAs were identified via the construction of a ceRNA network. The important target lenalidomide of IKZF1 was predicted.Conclusion: We first used bioinformatics and machine learning to screen four SD-DE-FCRGs. These genes may affect the involvement of infiltrating immune cells in pathogenesis of SD by regulating FCRGs. We predicted that lenalidomide may target IKZF1 from SD-DE-FCRGs. Keywords: sleep deprivation, ferroptosis, cuproptosis, bioinformatics, machine learning, immune infiltration

Haoyang Xin,1,&ast; Man Wang,2,&ast; Shuo Wang,3 Haiyan Han,3 Nan Jiang1 1Department of Nephrology and Rheumatology, Second Affiliated Hospital of Tianjin University of TCM, Tianjin, People’s Republic of China; 2Department of Pharmacy, Tianjin Forth Central Hospital, Tianjin, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Jiang, Department of Nephrology and Rheumatology, Second Affiliated Hospital of Tianjin University of TCM, No. 69, Zengchan Street, Hebei District, Tianjin, 300250, People’s Republic of China, Tel +86 18622997255, Email jingnan_jn@126.comObjective: This study aimed to explore the potential active components and therapeutic targets of Shentong Zhuyu Decoction (SZD) in the treatment of ankylosing spondylitis (AS) through network pharmacology and animal experiments.Methods: Targets for AS and related pathways were obtained by network pharmacology, and the pathways with the best binding affinity in molecular docking were verified by animal experiments.Results: The network pharmacology analysis found 248 chemical components, 1068 drug targets and 803 AS-related targets in SZD. After intersection targets analysis, 116 common drug–disease targets were obtained, and matrix metalloproteinase-9, nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) and cytochrome P450 2D6 were identified as the key targets of SZD for the treatment of AS. A total of 2152 biological processes, 38 cellular component expressions and 150 molecular function terms were obtained in gene ontology enrichment analysis, and 153 Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathways were obtained in KEGG enrichment analysis. Molecular docking analysis showed that the absolute binding energies of glypallichalcone and NLRP3, quercetin and NLRP3 and kaempferol and NLRP3 were > 7. Animal experiments showed that the expressions of NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 were significantly increased in the model group and the treatment group compared with those in the blank group, and the expression levels in the treatment group were significantly decreased compared with those in the model group (p < 0.05).Conclusion: The active components in SZD, such as baicalin, quercetin, kaempferol and glypallichalcone, may reduce the expression of IL-1β and IL-18 via the NLRP3/Caspase-1 signalling pathway to inhibit the development and progression of inflammation and play a role in the treatment of AS.Keywords: Shentong Zhuyu Decoction, ankylosing spondylitis, network pharmacology, mechanism of action

Haoming Luo,1,2,&ast; Miao Guo,3,4,&ast; Mingxing Li,1 Yueshui Zhao,1 Jing Shen,1 Fukuan Du,1 Yu Chen,1 Shuai Deng,1 Yuhong Sun,1 Li Gu,1 Wanping Li,1 Xiaobing Li,1 Meijuan Chen,1 Zhangang Xiao,1,5,6 Shengpeng Wang,3,4 Xu Wu1,7 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2Department of Pharmacy, Three Gorges University Hospital of Traditional Chinese Medicine & Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443003, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 4Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 5Department of Pharmacy, Gulin County Hospital of Traditional Chinese Medicine, Luzhou, Sichuan, 646500, People’s Republic of China; 6School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan, 621000, People’s Republic of China; 7Department of Paediatric Care, Luzhou People’s Hospital, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengpeng Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China, Email swang@um.edu.mo Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@swmu.edu.cnIntroduction: Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms.Methods: The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids.Results: Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier.Discussion: Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy. Keywords: rosavin, colitis, inflammatory bowel disease, organoid, intestinal stem cell

Juan Li,1,&ast; Shu Wang,2,&ast; Chaoping Ma,1,&ast; Ning Ning,3,&ast; Yingying Huang,1,4,&ast; Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Sheng Wang,1– 3,&ast; Wufei Ye,1,3,&ast; Kui Yang,1,3 Xiongwen Lv,2 Jiajie Luan1,3 1Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, 241001, People’s Republic of China; 2The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3School of Pharmacy, Wannan Medical College, Wuhu, Anhui, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiongwen Lv, The Key Laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China, Email xiongwen_lv2019@163.com Jiajie Luan, Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, 241001, People’s Republic of China, Email luanjiajie775@163.comObjective: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer. Hypoxia can be involved in HCC tumor growth, invasion and metastasis through inducing angiogenesis. Nevertheless, the assessment of the impact of hypoxia and angiogenesis on the prognosis of HCC remains inadequate.Methods: According to hypoxia-angiogenesis-related genes (HARGs) expression information and clinical data from patients within the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a prognostic model (HARG-score) using bioinformatic tools. In addition to assessing the predictive ability of this prognostic model in both Liver Cancer-Riken-Japan (LIRI-JP) and GSE14520 cohorts, we analyzed the correlation between HARG-score and clinical characteristics, immune infiltration and immunotherapy efficacy. Moreover, we investigated the exact role and underlying mechanism of key HARGs through molecular experiments.Results: We constructed a 5-gene prognostic model HARG-score consisting of hypoxia-inducible lipid droplet-associated (HILPDA), erythropoietin (EPO), solute carrier family 2 member 1 (SLC2A1), proteasome subunit alpha type 7 (PSMA7) and cAMP responsive element-binding protein 1 (CREB1) through differentially expressed HARGs. The findings demonstrated that HARG-score was a good predictor of the prognosis of HCC patients from distinct cohorts and was correlated with clinical characteristics and immune infiltration. Furthermore, the HARG-score was identified as an independent prognostic factor. Lower HARG-score implied greater immunotherapy efficacy and better response. The expression and prognostic significance of these 5 genes were additionally validated in clinical data. In addition, experimental data revealed that the key gene HILPDA contributes to the progression of HCC through facilitating angiogenesis and affecting the expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA4).Conclusion: HARG-score has promising applications in prognosis prediction of HCC patients, in which HILPDA may be a latent prognostic biomarker and therapeutic target, providing a foundation for further research and treatment of HCC.Keywords: hepatocellular carcinoma, hypoxia-angiogenesis, HILPDA, prognosis, immunotherapy efficacy

Xueen Liu,1 Fang Pan,1 Qingmei Wang,1 Shuai Wang,1 Jiale Zhang2 1Department of Nursing, Beijing Hepingli Hospital, Beijing, People’s Republic of China; 2Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jiale Zhang, Email zhang_tcm@163.comAbstract: Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.Keywords: traditional Chinese rehabilitation exercise, pain, myofascial chain, rehabilitation

Yapu Liu, Yuanyuan Su, Zhonghao Luan, Xiuwei Hou, Guangliang Wu, Yonghui Xu, Songmao Wang, Lifeng Gao, Xiaochen Zheng Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, Luohe, People’s Republic of ChinaCorrespondence: Yapu Liu, Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, 463 Haihe Avenue, Luohe, 462300, People’s Republic of China, Tel/Fax +86-0395-6162312, Email 460547380@qq.comPurpose: To introduce the surgical methods and clinical results of percutaneous vertebroplasty (PVP) combined with hollow screw placement as a treatment for patients with Kummell’s disease and pedicle rupture.Methods: From January 2020 to January 2023, a total of 10 patients with Kummell’s disease and pedicle rupture confirmed via imaging underwent three-column intensive therapy using hollow screws combined with PVP. There were two males and eight females with an average age 75.7± 6.11 years old. The time of operation, bone cement injection amount, bone cement leakage during operation were recorded. X-ray and CT were reexamined after operation. The improvement in quality of life was assessed using the Oswestry Disability Index (ODI), and the improvement in low back pain was assessed using the visual analogue scale (VAS).Results: Hollow screw placement combined with PVP was successfully performed in all patients. The average operation time was 39.2± 5.1 min, and the average volume of bone cement injected was 5.85± 0.83mL. No leakage of bone cement into spinal canal occurred.The mean preoperative ODI score was 75.70± 4.39, but this decreased significantly postoperatively(P< 0.05), being 37.70± 6.95 at 1 day and 26.40± 4.90, 23.70± 4.87, 21.70± 5.46, and 20.50± 4.21 at 1, 3, 6, and 12 months after the operation, respectively. The mean VAS pain score before the operation was 8.35± 0.63, but the symptoms of back pain were significantly relieved after operation(P< 0.05). The mean VAS scores 1 day and 1, 3, 6, and 12 months after the operation were 3.45± 0.47, 2.55± 0.60, 1.89± 0.48, 1.50± 0.27, and 1.12± 0.20, respectively.Conclusion: Hollow screw placement combined with percutaneous vertebroplasty serves as a valuable three-column intensive treatment for patients with Kummell’s disease and pedicle rupture. This procedure has the advantages of minimal trauma, less pain and quick recovery. The strong anchoring of bone cement and hollow screws provides stable and firm healing conditions for vertebral and pedicle fractures.Keywords: three-column enhancement, PVP, hollow screw, Kummell’s disease, pedicle rupture

Pair Ahmed Jiko,1 Mahathir Mohammad,1 Fahmida Tasnim Richi,2 Md. Anisul Islam,3 Safaet Alam,2,4 Mohammad Abdullah Taher,2,5 Chuxiao Shao,6 Shuanghu Wang,6 Peiwu Geng,6 Abdullah Al Mamun6 1Department of Chemistry, Chittagong University of Engineering & Technology, Chittagong, 4349, Bangladesh; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh; 3Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4202, Bangladesh; 4Chemical Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, 1205, Bangladesh; 5Bangladesh Reference Institute for Chemical Measurements (BRiCM), Laboratory Road, Dhaka, 1205, Bangladesh; 6Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Abdullah Al Mamun, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Tel +86-19715780050, Email pharmaalmamun@yahoo.comBackground: Shirakiopsis indica (Willd)., commonly known as Sa-Mor-Ta-Lay in Thailand, is a mangrove plant belonging to the Euphorbiaceae family. As mangrove plants’ medicinal potentials are less explored, this study sought to qualitatively and quantitatively verify the bioactive components of Shirakiopsis indica fruits methanolic extract (SIF-ME) at the side of its analgesic, anti-inflammatory and anti-oxidant effects followed by in-silico studies.Methods: The in-vivo assessments of analgesic activity involved the hot plate test, acetic acid-induced writhing test, and formalin-induced licking test. The anti-inflammatory efficacy was assessed through the human RBC membrane stabilization assay (HRBC), protein denaturation assay, and xylene-induced ear edema methods. Antioxidant potential was implemented by the DPPH scavenging method.Results: The SIF-ME consistently displayed significant anti-nociceptive activity in a dose-dependent pattern (p < 0.05). The maximum analgesic activity was found in the highest dose (200 mg/kg; p < 0.001) in a hot plate, acetic acid-induced writhing test 43.47%, and in formalin-induced licking test in both early phase (43.3%; p < 0.01) and late phase (61.84%; p < 0.001%). The extract provided optimal protection against hemolysis (83.41% decrease) at 1000 μg/mL and significantly inhibited protein denaturation (67.34– 26.05%) at doses of 1000– 62.5 μg/mL. At 200 mg/kg, the extract showed dose-dependent and substantial inhibition (54.07%; p < 0.01) of xylene-induced ear edema. The in-vitro DPPH (IC50 = 469.5 μg/mL) results showed remarkable scavenging activity and concentration-dependent reducing power. The extract demonstrates no acute oral toxicity, as indicated by an LD50 value exceeding 1000 mg/kg body weight. Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS) analysis was performed which yielded sixty bioactive compounds. In-silico and molecular docking studies revealed favorable pharmacological properties, including good binding affinities and ADME/T profiles.Conclusion: These results support the medicinal use of the plant, which makes it a potential source of analgesic, anti-inflammatory, and antioxidant candidates.Keywords: natural products, medicinal plants, shirakiopsis indica, acute oral toxicity, analgesic, anti-inflammatory, antioxidant, GC-MS/MS, molecular docking

Junyi Li,1,2,&ast; Zugui Wu,3,&ast; Bin Lu,2,&ast; Congcong Li,1 Shuai Wang,1 Jiahao Zhang,1 Xingxing Shen,1 Ruian Xiang,1 Jiahao Chen,1 Tao Jiang,1 Chuanxi Zhao,1 Wengang Liu,1 Xuemeng Xu1 1Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Osteoarthropathy II, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang, People’s Republic of China; 3Department of Orthopedics and Traumatology, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemeng Xu; Wengang Liu, Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, No. 60 Hengfu Road, Guangzhou, 510030, People’s Republic of China, Email xuxuemeng@163.com; 914194079@qq.comPurpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults.Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed.Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030).Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.Keywords: knee osteoarthritis, quadriceps femoris, ultrasound, muscle tone, stiffness

Qiujing Li,1 Mingwu Li,2 Shuxian Wang,2 Alan F Geater,3 Jingyi Dai1 1Department of Public Laboratory, The Third People’s Hospital of Kunming City, Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 2Department of Tuberculosis, The Third People’s Hospital of Kunming City, Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 3Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, HatYai, Songkhla, ThailandCorrespondence: Jingyi Dai, Department of Public Laboratory, The Third People’s Hospital of Kunming City, Kunming, People’s Republic of China, Email daijingyidjy@163.comAbstract: This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.Keywords: Talaromyces marneffei, HIV-negative patient, tuberculosis, misdiagnose, Next-generation sequencing

Dan Li,1 Fang Lv,2 Chenyuan Ding,3 Zhaohan Zhuang,3 Shijun Wang1 1Department of Obstetrics & Gynecology, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 2Department of Medical Record Statistics, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 3Education Section, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Shijun Wang, Department of Obstetrics & Gynaecology, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13601222289, Email wangshijun20158866@126.comPurpose: This case report aimed to summarize the risk factors, clinical characteristics, imaging changes, and maternal and fetal prognosis associated with Moyamoya disease in pregnant women and to explore effective management strategies and a comprehensive delivery plan.Case Presentation: The clinical data of four pregnant women who were diagnosed with Moyamoya disease and admitted to our hospital between January 2010 and January 2019 were retrospectively analyzed. Their diagnosis, treatment, delivery, and postpartum management during the pregnancy were analyzed. Among the four pregnant women, three were primipara and one was multipara. The age ranged from 27 to 41 years old. The gestational week of termination of pregnancy ranged between 8 and 39 weeks. During pregnancy, one case died in utero; one case was complicated with postpartum hemorrhage; one case was complicated with chronic hypertension, multiple cerebral artery stenosis and occlusion, bilateral middle cerebral artery occlusion, bilateral internal carotid artery occlusion, and Hashimoto’s thyroiditis. Under epidural anesthesia, two cases underwent a lower segment cesarean section; one case underwent artificial abortion; and one case underwent induced labor during late pregnancy. Two newborns survived.Conclusion: Moyamoya disease is a rare and serious complication of pregnancy. Pregnancy and childbirth may exacerbate the progression of this disease or induce cerebrovascular accidents, with a high mortality and disability rate, which seriously threatens the safety of mother and infant lives; however, with the close collaboration of a multidisciplinary team, it is possible to maximize a good pregnancy outcome.Keywords: pregnancy, cerebrovascular lesions, moyamoya disease

Xuebing Zhang,1 Lianjie Wang,1 Ge Wang,1 Jiayue Li,1 Yiming Mu,2 Shidong Wang,1 Xiaoran Li1 1Department of Endocrinology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Endocrinology, First Medical Centre of Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Shidong Wang; Xiaoran Li, Email A2082@bucm.edu.cn; 466187309@qq.comBackground: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China.Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression.Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345– 1.957) and 1.990 (95%CI: 1.709– 2.316) in women with NAFLD, compared with the subjects without NAFLD.Conclusions: NAFLD is independently associated with increased risk of CVD development.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, cardiovascular disease, middle-aged and elderly, Chinese

Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Liu Yang,1 Kaijie Gao,1 Weihua Gong,1 Ci Li,1 Nan Chen,1 Tiewei Li,1 Shan Wang,1 Jiajia Ni,2,3 Junmei Yang1 1Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, Henan, People’s Republic of China; 2Research and Development Center, Guangdong Meilikang Bio-Science Ltd, Foshan, Guangdong People’s Republic of China; 3Department of Detection and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Junmei Yang, Email yangjunmei7683@163.comPurpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies.Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system.Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p< 0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0– 3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p< 0.05).Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.Keywords: allergen, childhood allergies, IgE antibodies, source of food allergens, allergy prevention

Jing Ren,1,&ast; Jiahua Zhou,2,&ast; Qinhui Wang,1,&ast; Linna Liu,1 Wei Liu,3 Shan Wang,4 Yao Zheng,1 Li Luo,1 Qi Yang1 1Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Orthopedics, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Pharmacy, New York University Langone Hospital – Long Island, Mineola, NY, USA&ast;These authors contributed equally to this workCorrespondence: Qi Yang; Li Luo, Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China, Tel +86 15829673096, Fax +86 029-84777154, Email 376230719@qq.com; luolixueshu@163.comAbstract: Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient’s left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.Keywords: aseptic abscess, inflammatory bowel disease, ulcerative colitis, extra-intestinal manifestation

Shanshan Wu,1,2,&ast; Shuren Wang,3,&ast; Yonghong Ding,2 Zongwang Zhang1,2 1Department of Anesthesiology, Liaocheng People’s Hospital, Shandong University, Liaocheng, People’s Republic of China; 2Department of Anesthesiology, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 3Department of Anesthesiology, Dongchangfu District Maternal and Child Health Hospital, Liaocheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongwang Zhang, Department of Anesthesiology, Liaocheng People’s Hospital, Shandong University, Liaocheng, People’s Republic of China, Tel +86-13346256809, Email zwzhang68@sina.comObjective: Postoperative pain is a common complication in endoscopic submucosal dissection (ESD) patients. This study aimed to develop and validate predictive models for postoperative pain associated ESD.Methods: We retrospectively constructed a development cohort comprising 2162 patients who underwent ESD at our hospital between January 2015 and April 2022. The dataset was randomly divided into a training set (n = 1541) and a validation set (n = 621) in a 7:3 ratio. The bidirectional stepwise regression with Akaike’s information criterion (AIC) and multivariate logistic regression analysis were used to screen the predictors of post-ESD pain and construct three nomograms. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, Hosmer–Lemeshow (HL) goodness-of-fit test and decision curve analysis (DCA) in internal validation.Results: The proportion of patients developing postoperative pain in the training and testing data set was 25.6% and 28.5%, respectively. Three nomograms were constructed according to the final logistic regression models. The clinical prediction models for preoperative risks, preoperative and intraoperative risks, and perioperative risks consisted of seven, nine and six independent predictors, respectively, after bidirectional stepwise elimination. The models demonstrated the AUC of 0.794 (95% CI 0.768– 0.820), 0.823 (95% CI 0.799– 0.847) and 0.817 (95% CI 0.792– 0.842) in the training cohort and 0.702 (95% CI 0.655– 0.748), 0.705 (95% CI 0.659– 0.752) and 0.747 (95% CI 0.703– 0.790) in the validation cohort. The calibration plot, HL and DCA demonstrated the model’s favorable clinical applicability.Conclusion: We developed and validated three robust nomogram models, which might identify patients at risk of post-ESD pain and promising for clinical applications.Keywords: endoscopic submucosal dissection, postoperative pain, nomograms

Ming Wei,1 Xi Chen,1 Jun Liu,1 Tianmeng Li,1 Peng Wang,1 Shuai Wang,1 Jing Wang,2,3 Li Gu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang, Beijing Anding Hospital, Capital Medical University, 5 Ankang Hutong Road, Xicheng District, Beijing, 100088, People’s Republic of China, Email kycwangjing@mail.ccmu.edu.cn Li Gu, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Email didcm2006@mail.ccmu.edu.cnPurpose: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods.Methods: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay.Results: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2× 102 copies/mL to 8× 102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing.Conclusion: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.Keywords: carbapenem-resistant Enterobacterales, carbapenemases detection, multiplex real-time PCR assay, mCIM/eCIM, combined disk test, immunochromatographic test

Senlan Wang,1,2,&ast; Jifan Tan,1,2,&ast; Can Wang,1,2 Jia Huang,1,2 Canquan Zhou1,2 1Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Canquan Zhou; Jia Huang, Email zhoucanquan@mail.sysu.edu.cn; hjia@mail.sysu.edu.cnPurpose: It is well known that androgen excess impairs oocyte quality, endometrial receptivity and even embryo invasion to some extent. Free androgen index (FAI) is strongly recommended to evaluate active androgen. Previous studies have showed conflicting conclusions on the effect of hyperandrogenism on the pregnancy outcomes in patients with polycystic ovary syndrome (PCOS). This study aims to analyze the influence of hyperandrogenemia based on FAI on frozen embryo transfer (FET) outcomes in patients with PCOS.Patients and Methods: Patients diagnosed with PCOS who underwent their first FET between January 2017 and April 2022 were stratified into two cohorts using FAI, a highly recommended parameter: PCOS with hyperandrogenemia (n=73) and PCOS without hyperandrogenemia (n=255). Basic and infertility characteristics were analyzed using Student’s t-test or chi-square (χ 2) statistics. Logistic regression analysis was performed to verify whether FAI was helpful in predicting pregnancy outcomes in women with PCOS.Results: Body mass index (BMI), total gonadotropin (Gn), basal serum follicle-stimulating hormone (bFSH), basal serum testosterone (bT), sex hormone binding globulin (SHBG), and FAI were significantly different between the two groups. (P=0.005, P< 0.001, P< 0.001, P< 0.001, and P< 0.001, respectively). However, clinical pregnancies, abortions, and live births did not differ significantly. Further regression analyses showed that FAI was not related to clinical pregnancy, abortion, or live birth rates (adjusted odds ratio (OR)=0.978, 95% confidence interval (CI)=0.911– 1.050, P=0.539; adjusted OR=1.033, 95% CI=0.914– 1.168, P=0.604; and adjusted OR=0.976, 95% CI=0.911– 1.047, P=0.499, respectively).Conclusion: FAI was not associated with pregnancy outcomes in patients with PCOS; that is, it did not reflect any negative effects of hyperandrogenemia on pregnancy outcomes in patients with PCOS and was not an informative clinical parameter. Therefore, more attention should be paid to the factors that influence the accuracy of FAI in reflecting androgen levels in vivo, and further discussion is needed.Keywords: FAI, Hyperandrogenemia, PCOS, Pregnancy, FET

Yishan Duan,1,&ast; Jing Ren,2,&ast; Jing Wang,3,&ast; Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Zhuoran Li,1,&ast; Yirui Zhai,1,&ast; Fan Wu,2,&ast; Dayong Cao,2,&ast; Feng Ye,3,&ast; Yan Song,4 Shulian Wang,1 Yueping Liu,1 Yongwen Song,1 Yuan Tang,1 Hao Jing,1 Hui Fang,1 Shunan Qi,1 Ningning Lu,1 Ye-Xiong Li,1 Jianxiong Wu,2 Bo Chen1 1State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 3Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 4Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Chen, State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87788280, Email chenboo@outlook.com Jianxiong Wu, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87781700, Email Dr_wujx@163.comPurpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30– 65 Gy for planning target volume and 40– 65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level > 1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588– 20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027– 0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.Keywords: liver cancer, immunotherapy, systemic therapy, radiation therapy

Demeng Xia,1,2,&ast; Qingqing Qian,1,&ast; Sheng Wang,3,&ast; Xiao Dong,4 Ying Liu5 1Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, People’s Republic of China; 2Department of Pharmacy, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, People’s Republic of China; 3Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4School of Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 5Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu; Xiao Dong, Email liuchanger1984@163.com; dong-xiao@shu.edu.cnIntroduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.Results: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.Conclusion: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.Keywords: bone targeting, alendronate functionalized liposome, pomolic acid, osteoporosis therapy

Chao Meng,1 Ping Yang,2 Yanan Wang,3 Siyan Liu,3 Xueyan Wu,3 Shaolian Wang3 1Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Integrated Chinese and Western Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Shaolian Wang, Email 15318816221@sina.cnBackground: To investigate the prevalence of thyroid nodules among medical staff and health check-up population in a Level-A hospital (Primary-level hospital) in Jinan City and analyze its influencing factors.Methods: A total of 5812 cases from the two groups were screened. t-test and χ2 tests were used to analyze the differences in the prevalence of thyroid nodules. Multivariate Logistic regression analysis was used to explore the influencing factors.Results: The average age of medical staff was (36.20± 9.11) years old, and the total prevalence was 48.5%. The average age of the healthcare population was (57.89± 12.51) years old, and the total prevalence rate was 63.9%, with statistical significance between the two groups (P