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Hua Liu,1,&ast; Wenxi Wu,1,&ast; Min Xu,2 Xiaoyang Ling,2 Wei Lu,2 Feng Cheng,1 Jian Wang2 1Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China; 2Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Cheng, Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China, Email chengf1215@163.com Jian Wang, Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China, Email wj458381670@126.comBackground and Aim: Traumatic brain injury (TBI) is a severe public health problem in elderly patients, and frailty is associated with higher mortality rates in older patients. This study aims to assess the prognostic value of frailty in patients with TBI.Methods: Clinical data from 348 TBI patients treated at Affiliated Kunshan Hospital of Jiangsu University and Kunshan Hospital of Traditional Chinese Medicine between December 2018 and December 2020 were retrospectively collected. Univariate and multivariate logistic regression analyses were used to determine risk factors affecting in-hospital mortality, and receiver operating characteristic (ROC) curves were plotted to assess the discriminatory power of the frailty index. Frailty was assessed using the FRAIL scale, where FRAIL stands for Fatigue, Resistance, Ambulation, Illness, and Loss of weight, with each item scored as 0 or 1.Results: Using the FRIAL questionnaire, 122 patients had low frailty and 226 had high frailty. Multivariate logistic regression analysis showed that high frailty was a risk factor for in-hospital mortality in TBI patients (P< 0.001, OR=2.012 [1.788– 2.412]). The proportion of infections occurring in the two groups was statistically different (P=0.015), with severely infected TBI patients being more likely to develop complications. The ROC curve showed an area under the curve for the FRAIL score of 0.845 [0.752– 0.938].Conclusion: Frailty is an important risk factor for in-hospital mortality in elderly TBI patients, and more attention should be paid to patients with high levels of frailty. Clinicians should consider the degree of frailty when assessing TBI and making treatment decisions.Keywords: frailty, traumatic brain injury, in-hospital mortality, prognosis

Hao Huang,1 Zhiping Long,2 Ying Deng,3 Zhicong Huang,3 Zhonghua Lv,4 Qian Sun,4 Hui Liu,4 Hongsheng Liang,5 Fulan Hu6 1Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Epidemiology, Public Health School of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 6Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Fulan Hu, Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of China, Email hufu1525@163.com Hao Huang, Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China, Email hhxiaowo@163.comPurpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes. Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity. However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear.Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNA-seq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas.Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas. Our findings revealed that the TGFβ signaling pathway exhibited a higher relative strength in astrocyte subpopulations. Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction. Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (Ptraining set < 0.001; Ptest set = 0.037).Conclusion: Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma. We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas. Keywords: scRNA-seq, gliomas, astrocyte, cuproptosis, prognosis

Meixin Yu,1,&ast; Ling Pei,1,&ast; Han Liu,1 Jiaxin Wang,1 Yun Wen,1 Xian Yang,1 Caixia Ma,1 Xiaofang Zhang,2,3 Liangyan Wu,1 Lihong Wang1,2 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2The Academician Cooperative Laboratory of Basic and Translational Research on Chronic Diseases, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3The Guangzhou Key Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihong Wang, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, No. 613, Huang Pu Avenue West, Guangzhou, Guangdong, People’s Republic of China, Email nd6688@163.comPurpose: To explore the relationship between Red cell distribution width/albumin ratio (RAR) and vascular complications, including atherosclerosis of the lower limbs, diabetic nephropathy(DN), and diabetic retinopathy(DR), in patients with type 2 diabetes mellitus(T2DM).Patients and Methods: The study included 427 patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Jinan University (Guangzhou, China) between April 1, 2022 and May 31, 2023. Baseline characteristics were displayed according to the quartiles of the RAR. Logistic regression analysis and receiver operating characteristic curves (ROC) were used to analyze the data.Results: After adjusting for confounders, a higher RAR quartile(the fourth quartile) was associated with an increased risk of atherosclerosis of the lower limbs(OR: 2.973, 95% CI 1.281– 6.906, p = 0.011), and diabetic nephropathy(OR: 2.876, 95% CI 1.315– 6.287, p = 0.008) compared to the lowest RAR quartile. The patients were further divided into two groups according to urinary albumin to creatinine ratio (UACR≥ 30mg/g and UACR < 30mg/g) and Glomerular Filtration Rate (eGFR< 60 mL·min⁻¹ (1.73 m²) ⁻¹ and eGFR≥ 60 mL·min⁻¹ (1.73 m²) ⁻¹). Similar results were observed. However, We found that RAR quartile did not significantly increase the likelihood of developing diabetic retinopathy(OR: 1.183, 95% CI 0.633– 2.211, p = 0.598).Conclusion: The RAR ratio is associated with an increased risk of atherosclerosis of the lower limbs and diabetic nephropathy in patients with T2DM. The RAR ratio may be an important clinical marker of vascular complications in T2DM.Keywords: Type 2 diabetes mellitus, red blood cell distribution width, albumin, complications, inflammation

Qingqing Shen,1– 3,&ast; Qing Zhang,2,3,&ast; Yunxiao Liu,1– 3,&ast; Yingao Cui,1– 3 Jingwen Shang,1– 3 Xiaoping Yuan,2,3 Feng Geng,4 Liang Sun,5 Zhiwei Liu,5 Rongchun Yang,5 Kai Zhang,2,3 Huanzhong Liu2,3,6 1Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Psychiatry, Fuyang Third People’s Hospital, Fuyang, Anhui, People’s Republic of China; 6Brain Bank Construction and Resource Utilization, Anhui Provincial Key Laboratory, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zhang; Huanzhong Liu, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zhangkai@ahmu.edu.cn; huanzhongliu@ahmu.edu.cnPurpose: The purpose of this study was to further explore the association of pain intensity and sensitivity with suicidal ideation in adolescents with depressive disorder by comparing the differences in pain intensity and sensitivity between adolescent patients with depressive disorders and healthy controls.Patients and Methods: A consecutive enrollment method was used to select 158 adolescent patients with depressive disorders from three hospitals in Anhui Province as the MDD group, and 47 healthy adolescents were recruited as the Control group. The subjects’ suicidal ideation was assessed using the Positive and Negative Suicide Ideation scale (PANSI), and the intensity of somatic pain was assessed using the Numerical Rating Scale-11 (NRS-11). Subjects were assessed for forearm and tibial pain sensitivity using a hand-held pressure pain instrument, and experimental pain sensitivity measures included pressure pain threshold (PPT) and pressure pain tolerance (PTO). Differences in pain intensity and sensitivity between the MDD group and the Control group were compared, and the association of pain intensity and sensitivity with suicidal ideation was analyzed.Results: The incidence of physical pain in adolescent depressive disorder was higher at 88.6%, which was significantly higher than the Control group (P< 0.001), and the pain intensity in the MDD group (3.77± 2.48) was significantly higher than the Control group (0.617± 0.99) (P < 0.001).The Pain tolerance was significantly higher in the MDD group (forearm 105.37 ± 41.46; tibia 121.29 ± 41.60) than in the Control group (forearm 91.92 ± 37.62; tibia 105.47 ± 35.52) (P < 0.05).Linear regression analysis showed that the greater the pain intensity and pain tolerance, the higher the total PANSI score.Binary logistic regression showed that pain intensity was an influencing factor for suicidal ideation.Conclusion: Adolescents with depressive disorders have higher pain intensity and lower pain sensitivity than healthy adolescents. Increased pain intensity and pain tolerance were positively correlated with suicidal ideation.Keywords: adolescents, depressive disorder, pain intensity, pain sensitivity, suicidal ideation

Ying Pan,1 Mengjie Zhao,1 Tiantian Song,2 Jia Tang,2 Ming Kuang,2 Hongying Liu,2,&ast; Shao Zhong3,&ast; 1Department of General Practice, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, People’s Republic of China; 2Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.com Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, 310000, People’s Republic of China, Tel +86 02164045531, Email hongyingliu@91jkys.comAbstract: Insulin resistance (IR) is the major mechanism in the pathogenesis of type 2 diabetes mellitus (T2DM). Early identification of IR is of great significance for preventing the onset of T2DM and delaying the progression of the disease. Previous studies have shown that triglyceride-glucose (TyG) index can be used as an effective surrogate marker for IR. There is a significant correlation between TyG index and T2DM and its common complications. In addition, the predictive efficacy of TyG index is better than that of other IR surrogate indicators. TyG index may not only become an important marker to identify people at high risk of T2DM and its complications, but is also expected to become a strong predictor of the prognosis of these diseases. However, there are still some challenges in the widespread application of TyG index in clinical practice. In the future, more high-quality studies are needed to clarify the assessment methods of TyG index for the prognosis of T2DM and its complications. Further investigations of the relationship between TyG index and T2DM and its complications will be expected to provide new ideas and methods for the prevention and treatment of T2DM and its complications.Keywords: triglyceride-glucose index, type 2 diabetes mellitus, complication, insulin resistance

Yang Gou,1,2 Ping Wang,1,2 Wucheng Yang,1,2 Yimei Feng,1,2 Xiangui Peng,1,2 Hong Liu,1,2 Shuiqing Liu,1,2 Xi Zhang1,2 1Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 2Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Hong Liu; Shuiqing Liu, Email 1241580141@qq.com; liushuiqing062@tmmu.edu.cnAbstract: Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 μmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned.Keywords: hereditary spherocytosis, Gilbert syndrome, SPTB, UGT1A1

Ting Liu,1,2 Luxu Wang,1– 3 Tuo Shi,4 Hongrui Liu,1,2 Bo Liu,5 Jie Guo,1,2 Minqi Li1,2,5 1Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 2Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, People’s Republic of China; 3School of Stomatology, Jinzhou Medical University, Jinzhou, People’s Republic of China; 4School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5School of Clinical Medicine, Jining Medical University, Jining, People’s Republic of ChinaCorrespondence: Bo Liu, School of Clinical Medicine, Jining Medical University, Jining, 272067, People’s Republic of China, Tel +86-0537-6051782, Email liubo7230@mail.jnmc.edu.cn Jie Guo, Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-0531-88382923, Email kqgj@sdu.edu.cnPurpose: Bone loss is a common complication of type 2 diabetes mellitus (T2DM). Circadian rhythms play a significant role in T2DM and bone remodeling. Eldecalcitol (ED-71), a novel active vitamin D analog, has shown promise in ameliorating T2DM. We aimed to investigate whether the circadian rhythm coregulator BMAL1 mediates the anti-osteoporotic effect of ED-71 in T2DM and its associated mechanisms.Methods: A T2DM mouse model was established using high-fat diet (HDF) and streptozotocin (STZ) injection, and blood glucose levels were monitored weekly. HE staining, Masson staining, and Micro-CT were performed to assess the changes in bone mass. IHC staining and IF staining were used to detect osteoblast status and BMAL1 expression and RT-qPCR was applied to detect the change of oxidative stress factors. In vitro, high glucose (HG) stimulation was used to simulate the cell environment in T2DM. RT-qPCR, Western blot, IF, ALP staining and AR staining were used to detect osteogenic differentiation and SIRT1/GSK3β signaling pathway. DCFH-DA staining was used to detect reactive oxygen species (ROS) levels.Results: ED-71 increased bone mass and promoted osteogenesis in T2DM mice. Moreover, ED-71 inhibited oxidative stress and promoted BMAL1 expression in osteoblasts The addition of STL1267, an agonist of the BMAL1 transcriptional repressor protein REV-ERB, reversed the inhibitory effect of ED-71 on oxidative stress and the promotional effect on osteogenic differentiation. In addition, ED-71 facilitated SIRT1 expression and reduced GSK3β activity. The inhibition of SIRT1 with EX527 partially attenuated ED-71’s effects, whereas the GSK3β inhibitor LiCl further enhanced ED-71’s positive effects on BMAL1 expression.Conclusion: ED-71 ameliorates bone loss in T2DM by upregulating the circadian rhythm coregulator BMAL1 and promoting osteogenesis through inhibition of oxidative stress. The SIRT1/GSK3β signaling pathway is involved in the regulation of BMAL1.Keywords: eldecalcitol, type 2 diabetic mellitus, osteoblast, BMAL1, SIRT1/GSK3β signaling pathway

Yong Liu,1 Hui Liu,2 Queqiao Bian,1 Shuhuan Zhang,1 Yanmin Guan3 1Department of Dermatology & STD, The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center; Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 2Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 3Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yong Liu, Department of Dermatology & STD, The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center; Tianjin Institute of Hepatobiliary Disease, No. 83, Jintang Road, Hedong District, Tianjin, 300170, People’s Republic of China, Email liuyongtj@163.comBackground: Herpes zoster (HZ) and postherpetic neuralgia (PHN) significantly affect patients’ quality of life (QoL). Cultural differences may lead to different patient-reported outcomes across countries. The current study aims to evaluate the detrimental impact of HZ and PHN on QoL in China.Methods: This prospective study was conducted from January 2020 to April 2023. We used the Zoster Brief Pain Inventory (ZBPI) and 5-level EuroQol-5 Dimension (EQ-5D-5L) questionnaire to assess the QoL of HZ and PHN patients. Patients were required to complete the questionnaires at 15, 30, 60, and 90 days after the onset of the HZ rash. Additional questionnaires were administered at 120, 150, and 180 days for those who developed PHN within three months of the rash’s onset.Results: A cohort of 633 patients with a median age of 63 years were included in the study. The mean delay from the appearance of the initial HZ rash to the first medical consultation was 5.1 ± 2.8 days. Approximately 30% of the HZ patients (189/633) went on to develop PHN. For patients with HZ who did not progress to PHN, the ZBPI worst pain score and impaired QoL had nearly resolved by day 90 post-rash onset. Conversely, there was no significant improvement in the ZBPI worst pain score and QoL for those with PHN, even by day 180 post-rash onset.Conclusion: Both HZ and PHN significantly impaired patients’ QoL. However, the impairment caused by PHN was more severe in both intensity and duration.Keywords: herpes zoster, pain, post-herpetic neuralgia, quality of life

Hongtao Liu,1 Zhaoyu Li,2 Su Yan,2 Shaopeng Ming2 1Clinical Medical School, Guangxi Health Science College, Nanning, People’s Republic of China; 2Anesthesiology Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Shaopeng Ming, Anesthesiology Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530011, People’s Republic of China, Email mingshaopeng@stu.gxmu.edu.cnObjective: The goal of this study is to explore the research advancements on Post-COVID-19 syndrome, through bibliometric analysis, thus summarizing our current comprehension of the subject and suggesting directions for future research strategies.Methods: We acquired literature data from the Web of Science Core Collection (WoSCC) and conducted keyword and country analyses utilizing CiteSpace and R-project tools.Results: Until November 2, 2022, a total of 3633 publications were cataloged from WoSCC. The key terms commonly associated with Post-COVID-19 syndrome symptoms included: immune response, posttraumatic stress disorder, depression, acute lung injury, mental health, and quality of life. The United States emerged as leading in both producing the most research and fostering international cooperation. It was observed that the output of publications from a country is directly proportional to the cumulative number of COVID-19 cases and deaths therein.Conclusion: Utilizing bibliometric analysis, the study highlights the detrimental impact of mental health issues on Post-COVID-19 patients’ quality of life, emphasizing the urgency for further research and treatment. The sheer scale of COVID-19 cases underscores this need, while international collaboration emerges as a pivotal tool for advancing our understanding and addressing this challenge.Keywords: bibliometrics, Post-COVID-19 Syndrome, mental health

Jun Yan,1 Rongrong Zheng,1 Zhongdong Zhang,1 Jinchuan Shi,1 Tingbo Yan,2 Hong Liu,3 Feng Li1 1The Second Infectious Disease Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 2Radiology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 3Pathology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Feng Li, The Second Infectious Disease Department, Xixi Hospital of Hangzhou, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, 310023, People’s Republic of China, Email lfnice@foxmail.comBackground: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging.Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient’s uncomfortable symptoms had resolved, and he is currently undergoing further review.Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.Keywords: non-tuberculous mycobacteria, Mycobacterium paracondontium, lymph nodes, case report

Nan Tang,1 Mengyue Pei,2 Huihui Liu,3 Jingru Chen,1 Youting Wang,1 Lei Xie,4 Junping Hu,3,5 Jing Wang,6 Yuan Gao1 1Department of Nursing, 1st Medical Centre of PLA General Hospital, Beijing, People’s Republic of China; 2School of Medicine, Henan Kaifeng College of Science Technology and Communication, Kaifei, Henan Province, People’s Republic of China; 3School of Nursing, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 4Renji Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Department of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 6Department of Gynecology, 1th Medical Centre of PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang; Yuan Gao, Email wangjing353535@163.com; gaoyuanzd@163.comBackground: The purpose of this study was to explore the relationship between infertility-related stress and dyadic coping with quality of life (QoL) in couples with infertility issues, and verify gender differences and dyadic interactions in the associations between them.Methods: This cross-sectional study included 340 couples who were recruited from the First Affiliated Hospital of Lanzhou University between March 2022 and November 2022. The Fertility Problem Inventory, Dyadic Coping Inventory and FertiQoL were used to measure infertility-related stress, dyadic coping and QoL. The Actor-Partner Interdependence Model was used to analyze the effects of infertility-related stress and dyadic coping on the couple’s own QoL (actor effect) as well as on their partner’s QoL (partner effect).Results: Female patients perceived significantly lower levels of QoL and dyadic coping than those of husbands. There was no statistically significant difference in the infertility-related stress between wives and husbands. Husbands’ infertility-related stress had actor and partner effects on their own and their wives’ QoL, while wives’ infertility-related stress only had an actor effect on their own QoL. Husbands’ dyadic coping had both actor effect and partner effects on their own and their wives’ QoL, meanwhile wives’ dyadic coping had both actor effect and partner effects on their own and their husbands’ QoL.Conclusion: Husbands’ QoL was impacted by their own infertility-related stress, dyadic coping and their wives’ dyadic coping. Whereas wives’ QoL was influenced by infertility-related stress and dyadic coping from both their own and their spouses. Therefore, elevating the level of dyadic coping may contribute to improving QoL for both husbands and wives. Moreover, enhancing the ability to cope with infertility-related stress might be useful for husbands and indirectly contribute to wives’ QoL.Keywords: infertility, couple, infertility-related stress, dyadic coping, QoL

Wei Zhang, Haiqing Liu, Tuantuan Li, Ying Jiang, Xiaoyu Cao, Li Chen, Lili Zhou The Second People’s Hospital of Fuyang City, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Lili Zhou, The Second People’s Hospital of Fuyang City, No. 1088, West Yinghe Road, Fuyang, Anhui, People’s Republic of China, Email zw2314160@163.comObjective: Investigate the differences in clinical manifestations, imaging features, and associated inflammatory markers between Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) and Pulmonary Tuberculosis (PTB), identify potential risk factors for NTM-PD, and establish a logistic regression model to evaluate its diagnostic value.Methods: Baseline data were collected from 145 patients with NTM-PD and 206 patients with PTB. Propensity score matching (PSM) was utilized to achieve a 1:1 match between the two groups, resulting in 103 matched pairs. The differences in comorbidities, imaging features, and inflammatory markers were compared between the two groups. Multivariate binary logistic regression analysis was conducted to identify independent influencing factors, and the diagnostic value of the established model was evaluated.Results: After matching, significant differences were observed between the NTM-PD group and the PTB group in terms of diabetes, bronchiectasis, chronic obstructive pulmonary disease(COPD), cystic and columnar changes, lung cavity presentation, and monocyte percentage (MONO%), lymphocyte count (LYMPH&num;), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) (P

Shengfeng Wang,1,&ast; Ruxue Fang,1,&ast; Lei Huang,1,&ast; Liping Zhou,1,2 Haibo Liu,3 Meiling Cai,4 Abubakar Sha’aban,5 Chunxiang Yu,1 Mohammed Ahmed Akkaif3 1Rehabilitation Department of Chinese Medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China; 2Department of Community Health, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Pulau Pinang, Malaysia; 3Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Obstetrics and Gynecology, Qingpu Branch, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Health and Care Research Wales Evidence Centre, Cardiff University, Heath Park, Cardiff, UK&ast;These authors contributed equally to this workCorrespondence: Mohammed Ahmed Akkaif, Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email akkaif@fudan.edu.cn Chunxiang Yu, Rehabilitation Department of Chinese medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China, Email yuchunxiang868@gmail.comAbstract: Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people’s living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients’ well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.Keywords: cardiovascular diseases, traditional Chinese medicine, acupuncture, clinical treatment

Lingling Wang,1 Huiguo Liu,1 Ling Zhou,1 Pengdou Zheng,1 Hai Li,2,3 Huojun Zhang,4,&ast; Wei Liu2,3,&ast; 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huojun Zhang, Email hjzhang@whu.edu.cn; Wei Liu, Email 404793938@tjh.tjmu.edu.cnAbstract: Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.Keywords: intermittent hypoxia, hypoxia-inducible factor 1 alpha, nonalcoholic fatty liver disease, oxidative stress, dyslipidemia, leptin resistance

Hongtao Liu, Xiao Huang, Hongji Wei, Yanchang Nong Clinical Medical School, Guangxi Health Science College, Nanning, People’s Republic of ChinaCorrespondence: Yanchang Nong, Clinical Medical School, Guangxi Health Science College, Nanning, People’s Republic of China, Email nongyanchang@live.cnBackground: Non-scarring hair loss (NSHL) is a global health concern with increasing prevalence due to lifestyle changes and an aging population. It can cause psychological distress and affect quality of life.Objective: This study aimed to identify the associations between NSHL and immune cell phenotypes using a two-sample Mendelian randomization (MR) analysis, offering insights for future immune-based therapies for NSHL.Methods: We obtained immunocyte data from the IEU Open GWAS Project and NSHL data from the same database and used MR analysis to evaluate the causal association between each immunophenotype and NSHL. Three statistical methods were employed: the MR-Egger regression, weighted median estimation, and inverse variance weighting (IVW).Results: The MR resonance imaging identified 31 immunocyte phenotypes associated with NSHL. Among these, 19 immunocyte phenotypes were negatively associated with NSHL, indicating their protective effects. The remaining 12 immunocyte phenotypes were positive association. Sensitivity analyses suggested the robustness of all MR findings.Conclusion: These findings highlight a clear correlation between NSHL and immunity, demonstrating the significant role of certain immune cell phenotypes. This study offers a new direction for immune-based therapies in the treatment of NSHL.Keywords: non-scarring hair loss, immune cell, Mendelian randomization, immunotherapy

Yuan Gao,1– 3,&ast; Ce Zong,1,&ast; Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Meng Zhang,1,2 Qi Yuan,1 Peiwen Wang,1 Fan Zhang,1 Dan Wu,1 He Bai,1 Jieting Liu,1 Haifeng Liu,1 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2The First Hospital of Qiqihar, Qiqihar, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang, 157011, People’s Republic of China, Tel/Fax +86-453-6984401, Email yuanxiaohuan@mdjmu.edu.cnPurpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D).Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting.Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK.Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.Keywords: bone mesenchymal stem cell, nanovesicles, curcumin analogue H8, type 2 diabetes

Hang Jin,1,2,&ast; Zhongqiang Yan,3,&ast; Xin Ge,4,&ast; Qi Wang,2 Hui Wang,2 Xinying Du,2 Hongbo Liu,2 Chaojie Yang,2 Ying Xiang,2 Sai Tian,2 Shaofu Qiu,1,2 Yu Zhou5 1School of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Infectious Disease Control and Prevention, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China; 3Department of Disease Prevention and Control, The Second Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaofu Qiu, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China, Email qiushf0613@hotmail.com Yu Zhou, Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhouy427@163.comPurpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission.Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the blaKPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location.Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly β-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including blaKPC-2, blaCTX-M-65, blaTEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0– 13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital.Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of blaKPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.Keywords: Klebsiella aerogenes, carbapenem resistance, blaKPC-2, clonal transmission

Meng Cai,&ast; Jing Yin,&ast; YongFen Zeng, HongJun Liu, Yi Jin Department of Pain Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Jin, Department of Pain Medicine, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305&num; Zhongshan East Road, Nanjing, Jiangsu Province, 210002, People’s Republic of China, Email kimye@vip.163.comObjective: To determine the risk of postherpetic neuralgia (PHN) in patients with acute herpes zoster (HZ), this study developed and validated a novel clinical prediction model by incorporating a relevant peripheral blood inflammation indicator.Methods: Between January 2019 and June 2023, 209 patients with acute HZ were categorized into the PHN group (n = 62) and the non-PHN group (n = 147). Univariate and multivariate logistic regression analyses were conducted to identify risk factors serving as independent predictors of PHN development. Subsequently, a nomogram prediction model was established, and the discriminative ability and calibration were evaluated using the receiver operating characteristic curve, calibration plots, and decision curve analysis (DCA). The nomogram model was internally verified through the bootstrap test method.Results: According to univariate logistic regression analyses, five variables, namely age, hypertension, acute phase Numeric Rating Scale (NRS-11) score, platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index, were significantly associated with PHN development. Multifactorial analysis further unveiled that age (odds ratio (OR) [95% confidence interval (CI)]: 2.309 [1.163– 4.660]), acute phase NRS-11 score (OR [95% CI]: 2.837 [1.294– 6.275]), and PLR (OR [95% CI]: 1.015 [1.010– 1.022]) were independent risk factors for PHN. These three predictors were integrated to establish the prediction model and construct the nomogram. The area under the receiver operating characteristic curve (AUC) for predicting the PHN risk was 0.787, and the AUC of internal validation determined using the bootstrap method was 0.776. The DCA and calibration curve also indicated that the predictive performance of the nomogram model was commendable.Conclusion: In this study, a risk prediction model was developed and validated to accurately forecast the probability of PHN after HZ, thereby demonstrating favorable discrimination, calibration, and clinical applicability.Keywords: postherpetic neuralgia, platelet-to-lymphocyte ratio, nomogram, risk factors

Song Wang,1,&ast; Xiang Zhang,1,&ast; Bo Qu,2,&ast; Kunhai Yang,1 Yongrong Hu,1 Hao Liu,2 Juntao Hong,2 Hao Niu,3 Hongsheng Yang2 1School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Niu, Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Email 13438368112@139.com Hongsheng Yang, Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China, Email hongsheng228@163.comPurpose: This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality.Methods: PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores’ effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF.Results: In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718).Conclusion: The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.Keywords: muscle quality, osteoporosis, magnetic resonance imaging, dual-energy X-ray absorptiometry, vertebral bone quality score, osteosarcopenia

Zheng Zhang,1,2,&ast; Binbin Shao,3,&ast; Hongzhou Liu,2,4 Ben Huang,2,5 Xuechen Gao,1 Jun Qiu,1 Chen Wang1,2 1Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2Center for Gene Diagnosis, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 3Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, Jiangsu Province, People’s Republic of China; 4School of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuang Province, People’s Republic of China; 5Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Wang; Jun Qiu, Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou, Jiangsu Province, 215006, People’s Republic of China, Email 1617657224@qq.com; 13606136542@126.comPurpose: Early recognition of coronary artery disease (CAD) could delay its progress and significantly reduce mortality. Sensitive, specific, cost-efficient and non-invasive indicators for assessing individual CAD risk in community population screening are urgently needed.Patients and Methods: 3112 patients with CAD and 3182 controls were recruited from three clinical centers in China, and differences in baseline and clinical characteristics were compared. For the discovery cohort, the least absolute shrinkage and selection operator (LASSO) regression was used to identify significant features and four machine learning algorithms (logistic regression, support vector machine (SVM), random forest (RF) and extreme gradient boosting (XGBoost)) were applied to construct models for CAD risk assessment, the receiver operating characteristics (ROC) curve and precision-recall (PR) curve were conducted to evaluate their predictive accuracy. The optimal model was interpreted by Shapley additive explanations (SHAP) analysis and assessed by the ROC curve, calibration curve, and decision curve analysis (DCA) and validated by two external cohorts.Results: Using LASSO filtration, all included variables were considered to be statistically significant. Four machine learning models were constructed based on these features and the results of ROC and PR curve implied that the XGBoost model exhibited the highest predictive performance, which yielded a high area of ROC curve (AUC) of 0.988 (95% CI: 0.986– 0.991) to distinguish CAD patients from controls with a sensitivity of 94.6% and a specificity of 94.6%. The calibration curve showed that the predicted results were in good agreement with actual observations, and DCA exhibited a better net benefit across a wide range of threshold probabilities. External validation of the model also exhibited favorable discriminatory performance, with an AUC, sensitivity, and specificity of 0.953 (95% CI: 0.945– 0.960), 89.9%, and 87.1% in the validation cohort, and 0.935 (95% CI: 0.915– 0.955), 82.0%, and 90.3% in the replication cohort.Conclusion: Our model is highly informative for clinical practice and will be conducive to primary prevention and tailoring the precise management for CAD patients. Keywords: coronary artery disease, predictive model, machine learning, XGBoost, primary prevention

Hui Liu,1,2 Xuan Xu,3 Ji Li,3 Zheyu Liu,1 Yuwen Xiong,1 Mengli Yue,4 Pi Liu1 1Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Gastroenterology Institute of Jiangxi Province, Nanchang, People’s Republic of China; 3Department of Gastroenterology, The People’s Hospital of Longhua, Shenzhen, People’s Republic of China; 4Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Pi Liu, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China, Tel +86-13507913736, Email liupi126@sina.comPurpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present.Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways.Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, β-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, β-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, β-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1.Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP. Keywords: severe acute pancreatitis, plakophilin2, capillary leak syndrome, tight junction, p38/MAPK signaling pathway

Yong Liu,1 Hui Liu,2 Queqiao Bian,1 Shuhuan Zhang,1 Yanmin Guan3 1Department of Dermatology & STD, the Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 2Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 3Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yong Liu, Department of Dermatology & STD, the Third Central Hospital of Tianjin, No. 83, Jintang Road, Hedong District, Tianjin, 300170, People’s Republic of China, Tel +8602284112488, Email liuyongtj@163.comBackground: Herpes zoster (HZ) typically manifests in the acute phase with distinct blisters and severe neuropathic pain. Remarkably, a subset of patients initially presents with only a mild skin rash and moderate pain that gradually intensifies, following a parabolic pattern. Despite being frequently observed in clinical settings, the underlying causes of this trajectory and its potential connection with post-herpetic neuralgia (PHN) remain unclear.Methods: To investigate this phenomenon in-depth, we conducted a meticulous retrospective study involving 529 eligible HZ patients. All these patients sought medical care at the Third Central Hospital of Tianjin, China, between January 2020 and December 2023.Results: The research identified that 14.6% of the sample (77 patients) experienced pain scores aligning with a parabolic curve. This trend was significantly more prevalent in patients aged 60 and above, accounting for 90.9% of this group, and demonstrated a positive correlation with age. Moreover, 87.0% of these patients had pre-existing medical conditions, highlighting the potential role of comorbidities in influencing the pain trajectory. A concerning 45.5% of patients sought medical attention more than seven days after the onset of symptoms, a delay that could exacerbate neurological damage. Notably, among those following a parabolic pain pattern, 66.2% eventually developed PHN, a considerably higher rate compared to the broader patient population.Conclusion: We emphasize that healthcare practitioners meticulously assess patients who initially report lower pain scores for high-risk factors potentially leading to parabolic pain increases, including being over 60 years old, having comorbid conditions, and delaying medical consultation beyond seven days from symptom onset. Early implementation of supplementary pain management therapies may mitigate the risk of PHN development and enhance the quality of life for patients. This study furnishes clinicians with a deeper understanding of the variations in HZ-related pain trajectories, promising to improve treatment approaches and prognoses for HZ patients while paving the way for enriched clinical practice in the future.Keywords: parabolic pain trajectory, herpes zoster, post-herpetic neuralgia, delayed-onset pain, adjunctive analgesics, early intervention strategies

Siyu Fan,1,&ast; Yu Zhao,1,&ast; Shiyu Wang,1,&ast; Na Zhang,1,&ast; Zhi Li,1,&ast; Hongyuan Liu,1 Yaodi Wei,1 Yunhui Yu,1 Yifeng Gu,2 Qun Wei,3 Weijuan Ye,4 Ninghan Feng,5 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Surgical Oncology, Institute of Clinical Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Lishui Maternal and Child Health center, Lishui, Zhejiang, People’s Republic of China; 5Department of Urology, Jiangnan University Medical Center, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ninghan Feng, Department of Urology, Jiangnan University Medical Center, Wuxi, Jiangsu, 214002, People’s Republic of China, Email n.feng@njmu.edu.cn Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnAim: This study aims to explore the psychological reactions of medical students during the pandemic.Design: A qualitative study.Methods: A purposive sampling technique was employed, and a qualitative approach was adopted. Semi-structured questionnaires were utilized, and online interviews were conducted. Forty medical students were selected as participants for the interviews. The interview data were analyzed using Colaizzi’s seven-step analysis method.Results: The study identified five themes related to the psychological reactions of medical students during the pandemic. Firstly, COVID-19’s influence on medical careers was characterized by increased interest and determination in pursuing medical professions, heightened admiration for frontline workers, reinforced commitment to a medical career due to the pandemic, and recognition of the significance of medical education. Secondly, challenges and concerns in medical career pursuit were identified, including negative sentiments towards medical careers during COVID-19 and hesitations and concerns about entering the medical field amidst the pandemic. Thirdly, the impact on mental well-being encompassed diverse anxieties expressed by participants regarding control, transmission, treatment, and intentional spreading of the virus. Participants experienced an emotional progression from calmness to fear and anxiety, with heightened anxiety when relatives or acquaintances contracted COVID-19. Academic delays also contributed to anxiety among medical students. Fourthly, changes in behaviors and mindset were observed, including altered behaviors and mindset in response to the pandemic, as well as increased attention to personal hygiene and disease prevention measures. Lastly, expectations of medical students from government, public, and parents were explored.Conclusion: Understanding the psychological reactions of medical students during public health emergencies is crucial for their well-being and professional development. The findings have implications for medical education and the development of strategies to enhance the psychological well-being of medical students during similar crises.Keywords: COVID-19, medical students, psychological reactions, pandemic, mental health

Changxiu Ma,1 Ying Zhang,1 Tingchao Tian,2 Ling Zheng,1 Jing Ye,1 Hui Liu,1 Dahai Zhao1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huoqiu First People’s Hospital, Huoqiu, 237400, People’s Republic of ChinaCorrespondence: Dahai Zhao, Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Tel +86-13721027959, Email zhaodahai@ahmu.edu.cnPurpose: To explore the role of the mean apnea–hypopnea duration (MAD) and apnea–hypopnea duration per hour (HAD) in hypoxemia and evaluate whether they can effectively predict the occurrence of hypoxemia among adults with OSA.Patients and Methods: A total of 144 participants underwent basic information gathering and polysomnography (PSG). Logistic regression models were conducted to evaluate the best index in terms of hypoxemia. To construct the prediction model for hypoxemia, we randomly divided the participants into the training set (70%) and the validation set (30%).Results: The participants with hypoxemia tend to have higher levels of obesity, diabetes, AHI, MAD, and HAD compared with non-hypoxemia. The most relevant indicator of blood oxygen concentration is HAD (r = 0.73) among HAD, MAD, and apnea–hypopnea index (AHI). The fitness of HAD on hypoxemia showed the best. In the stage of establishing the prediction model, the area under the curve (AUC) values of both the training set and the validation set are 0.95. The increased HAD would elevate the risk of hypoxemia [odds ratio (OR): 1.30, 95% confidence interval (CI): 1.13– 1.49].Conclusion: The potential role of HAD in predicting hypoxemia underscores the significance of leveraging comprehensive measures of respiratory disturbances during sleep to enhance the clinical management and prognostication of individuals with sleep-related breathing disorders.Keywords: mean apnea–hypopnea duration, obstructive sleep apnea, apnea–hypopnea duration per hour, polysomnography, apnea–hypopnea index

Hongyuan Liu,1,&ast; Yaodi Wei,1,&ast; Zhenyi Xu,2,&ast; Hao Lin,2,&ast; Yu Zhao,1 Shiyu Wang,1 Fengbao Gao,1 Ninghan Feng,2 Alan J Wolfe,3 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Urology, Affiliated Wuxi No. 2 Hospital, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA&ast;These authors contributed equally to this workCorrespondence: Alan J Wolfe, Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA, Email awolfe@luc.edu Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnPurpose: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.Patients and Methods: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.Results: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients’ decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients’ decisions to pursue fecal microbiota transplantation; (3) the patients’ perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.Conclusion: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.Registration: CHiCTR2100048970.Keywords: barriers, decision making, facilitators, fecal microbiota transplantation, qualitative study, recurrent urinary tract infections

Hua Liu,1,2,&ast; Yang-Min Hao,1,2,&ast; Sheng Jiang,1,2,&ast; Maiheliya Baihetiyaer,1,2 Cheng Li,3 Guo-Yao Sang,4 Zhiming Li,5 Guo-Li Du1,2,6 1State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Data Statistics and Analysis Center of Operation Management Department, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 4Laboratory Medicine Diagnostic Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 5Department of Ultrasound, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 6Bazhou People’s Hospital, Korla, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Li Du, Email genemagic@126.comPurpose: This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs).Methods: A case–control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated.Results: The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P< 0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index.Conclusion: SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.Keywords: MASLD, type 2 diabetes mellitus, sodium-glucose co-transporter-2 inhibitors, MACCEs, FIB-4 index

Nan Du,1 Xiaolei Wang,1 Zhaohui Wang,2 Hongwei Liu,1 Hui Liu,1 Hongfang Duan,1 Shaozhi Zhao,1 Santasree Banerjee,3 Xinwen Zhang1 1Department of Medical Genetics, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, Shaanxi, 710004, People’s Republic of China; 2Center for Children Health Care, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, Shaanxi, 710004, People’s Republic of China; 3Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, 130021, People’s Republic of ChinaCorrespondence: Xinwen Zhang, Department of Medical Genetics, Xi’an People’s Hospital (Xi’an Fourth Hospital), 21 Jiefang Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Tel +86- 13992809311, Email xianxinwen@163.com Santasree Banerjee, Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, Jilin, 130021, People’s Republic of China, Tel +86-13823715105, Email santasree.banerjee@yahoo.comBackground: Charcot–Marie–Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot–Marie–Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance. Patients with CMT4B1 usually manifested with dysfunction of the motor and sensory systems which leads to gradual and progressive muscular weakness and atrophy, starting from the peroneal muscles and finally affecting the distal muscles. Germline mutations in MTMR2 gene causes CMT4B1.Material and Methods: In this study, we investigated a 4-year-old Chinese boy with gradual and progressive weakness and atrophy of both proximal and distal muscles. The proband’s parents did not show any abnormalities. Whole-exome sequencing and Sanger sequencing were performed.Results: Whole-exome sequencing identified a novel homozygous nonsense mutation (c.118A>T; p.Lys40&ast;) in exon 2 of MTMR2 gene in the proband. This novel mutation leads to the formation of a truncated MTMR2 protein of 39 amino acids instead of the wild- type MTMR2 protein of 643 amino acids. This mutation is predicted to cause the complete loss of the PH-GRAM domain, phosphatase domain, coiled-coil domain, and PDZ-binding motif of the MTMR2 protein. Sanger sequencing revealed that the proband’s parents carried the mutation in a heterozygous state. This mutation was absent in 100 healthy control individuals.Conclusion: This study reports the first mutation in MTMR2 associated with CMT4B1 in a Chinese population. Our study also showed the importance of whole-exome sequencing in identifying candidate genes and disease-causing variants in patients with CMT4B1.Keywords: Charcot–Marie–Tooth disease, MTMR2 gene, novel mutation, homozygous, whole-exome sequencing

Guo-Wang Yang,1,2 Hao Cheng,1,2 Xiao-Yang Song,3 Yu-Fan Yang,1,2 Hong Liu,4 Fu-Hai Ji,1,2 Ke Peng1,2 1Department of Anaesthesiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anaesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Anaesthesiology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of China; 4Department of Anaesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USACorrespondence: Ke Peng, Department of Anaesthesiology, the First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-15962155989, Email pengke0422@163.comPurpose: Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery.Methods: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0– 24 h postoperatively, assessed using the numerical rating scale (0– 10) with a minimal clinically important difference of 1.Results: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=− 0.60, 95% CI, − 1.16 to − 0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=− 0.98, 95% CI, − 1.66 to − 0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18– 65 years or > 65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups.Conclusion: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100052085).Keywords: laparoscopic gastrointestinal surgery, oxycodone, patient-controlled analgesia, visceral pain

Qingxiang Liu,1,&ast; Haitao Liu,2,&ast; Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Sepsis is a life-threatening clinical syndrome caused by dysregulated host response to infection. The mechanism underlying sepsis-induced immune dysfunction remains poorly understood. Natural killer T (NKT) cells are cytotoxic lymphocytes that bridge the innate and adaptive immune systems, the role of NKT cells in sepsis is not entirely understood, and NKT cell cluster differences in sepsis remain unexplored.Methods: Mendelian randomization (MR) analyses were first conducted to investigate the causal relationship between side scatter area (SSC-A) on NKT cells and 28-day mortality of septic patients. A prospective and observational study was conducted to validate the relationship between the percentage of NKT cells and 28-day mortality of sepsis. Then, the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from healthy controls and septic patients were profiled.Results: MR analyses first revealed the protective roles of NKT cells in the 28-day mortality of sepsis. Then, 115 septic patients were enrolled. NKT percentage was significantly higher in survivors (n = 84) compared to non-survivors (n = 31) (%, 5.00 ± 3.46 vs 2.18 ± 1.93, P < 0.0001). Patients with lower levels of NKT cells exhibited a significantly increased risk of 28-day mortality. According to scRNA-seq analysis, NKT cell clusters exhibited multiple distinctive characteristics, including a distinguishing cluster defined as FOS+NKT cells, which showed a significant decrease in sepsis. Pseudo-time analysis showed that FOS+NKT cells were characterized by upregulated expression of crucial functional genes such as GZMA and CCL4. CellChat revealed that interactions between FOS+NKT cells and adaptive immune cells including B cells and T cells were decreased in sepsis compared to healthy controls.Conclusion: Our findings indicate that NKT cells may protect against sepsis, and their percentage can predict 28-day mortality. Additionally, we discovered a unique FOS+NKT subtype crucial in sepsis immune response, offering novel insights into its immunopathogenesis.Keywords: natural killer T cells, sepsis, outcome, Mendelian randomization

Lisheng Chen,1,2 Tingting He,3 Ruilin Wang,3 Honghong Liu,4 Xin Wang,1,2 Haotian Li,2 Manyi Jing,2 Xuelin Zhou,5 Shizhang Wei,6 Wenjun Zou,1 Yanling Zhao1,2 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Division of Integrative Medicine, The Fifth Medical Center of General Hospital of PLA, Beijing, People’s Republic of China; 4Integrated TCM & Western Medicine Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China; 6Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Yanling Zhao, Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhaoyl2855@126.com Wenjun Zou, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email zouwenjun@163.comBackground: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated.Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism.Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins.Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin.Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.Keywords: Zuojin Pill, chronic atrophic gastritis, network pharmacology, molecular docking, PI3K/Akt signaling pathway

Qingxiang Liu,1,&ast; Fei Peng,1,&ast; Haitao Liu,2,&ast; Qin Sun,1 Hui Chen,1 Xinyi Xu,1 Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Jianfeng Xie,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood.Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration.Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46± 4.40 vs 11.65± 6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand–receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS.Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.Keywords: ARDS, inflammation, natural killer cells, sepsis

Bingcong Zhao,1,2 Zhigang Li,3 Chuan Shi,4 Yan Liu,5 Yang Sun,3 Bin Li,1,2 Jie Zhang,6 Zhizhong Gong,7 Yuanzheng Wang,8 Xuehong Ma,9 Xinjing Yang,10 Huili Jiang,3 Yuanbo Fu,1,2 Xin Wang,1,2 Yang Li,6 Hengchia Liu,6 Tuya Bao,3 Yutong Fei11– 13 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Psychological Assessment Center, Peking University Sixth Hospital, Beijing, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Psychosomatic Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7Division of Medical Affairs, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Department of Integrative TCM and Western Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 9Department of Acupuncture & Moxibustion, Dongfang Hospital, the Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Department of Traditional Chinese Medicine, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 11Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 12Institute of Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 13Beijing GRADE Centre, Beijing, People’s Republic of ChinaCorrespondence: Tuya Bao, 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 tuyab@263.net Yutong Fei, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email feiyt@bucm.edu.cnPurpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.Clinical Trials Registration: ChiCTR-TRC-08000297.Keywords: anxious depression, non-anxious depression, acupuncture, SSRIs, subgroup analysis

Jinrui Ji,1,2,&ast; Xiaoyun Wei,1,2,&ast; Dongyun Wan,1,2,&ast; Lei Wu,1,2,&ast; Guangyao Chen,1,3,&ast; Hengliang Liu1,2,&ast; 1Clinical Medical Department, Faculty of Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 2Department of Cardiology, People’s Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 3Zhengzhou Institute of Gastroenterology, People’s Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengliang Liu, Henan University of Traditional Chinese Medicine, No. 33, Huanghe Road, Jinshui District, Zhengzhou, Henan Province, 450000, People’s Republic of China, Tel/Fax +86 0371-67077158, Email hnzzjjr@163.comPurpose: This study investigated the influence of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) levels on the degree of atherosclerosis and major adverse cardiovascular and cerebrovascular events (MACCE) in older adults with non-alcoholic fatty liver disease.Methods: The degree of atherosclerosis severity was assessed by the standard Gensini score quartile method. According to the degree of atherosclerosis, patients were divided into mild (0– 24 points; n=84), moderate (25– 53 points; n=86), and severe groups (≥ 54 points; n=84) and then categorized as MACCE (n=30) or non-MACCE (n=224) according to 6-month follow-up data. The patients’ age, sex, smoking history, medical history, and early morning fasting venous blood, for measuring biochemical indexes, were collected. Clinical data were compared between groups and the relationship between Gensini scores and PCSK9 was evaluated.Results: Compared with the mild group, the moderate and severe groups had higher high-sensitivity C-reactive protein(hs-CRP), PCSK9, triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)[Lp(a)] levels and lower high-density lipoprotein cholesterol(HDL-C) levels (all P< 0.05). Moreover, PCSK9 positively correlated with Gensini scores (r=0.657, P< 0.01). The MACCE and non-MACCE groups had significantly different ages, statin use, Gensini scores, PCSK9, and LDL-C (all P< 0.05). Multi-factorial Cox risk regression analysis showed the Gensini score (HR=1.018, 95% CI: 1.006~1.029) and PCSK9 (HR=1.147, 95% CI: 1.038~1.287) were independent risk factors for MACCE.Conclusion: The Gensini score and PCSK9 levels can be used as predictive indicators for the degree of illness and occurrence of MACCE in older NAFLD patients.Keywords: older adults, non-alcoholic fatty liver disease, proprotein convertase subtilisin/kexin 9, atherosclerosis, major adverse cardiovascular and cerebrovascular events

Rongge Jiang,1 Haibai Liu,2 Xue Jiang,2 Ding Wang,2 Xiaoyu Li,2 Yi Shang3 1Neurosurgery Department 1, Baoding No.1 Central Hospital, Baoding, 071000, People’s Republic of China; 2Department of Nursing, Shijiazhuang Medical College, Shijiazhuang, 050599, People’s Republic of China; 3Department of Mammary, Shijiazhuang Fourth Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Xiaoyu Li, Shijiazhuang Medical College, No. 1 Tongxin Road, Lingshou County, Shijiazhuang, Hebei, 050599, People’s Republic of China, Tel + 8613603117321, Email lixiaoyu_li03@126.comObjective: This study explores the impact of a nursing intervention grounded in empowerment theory, focusing on behavioral change, on brain metastasis patients post-breast cancer surgery.Methods: Between June 2021 and June 2023, 102 patients diagnosed with brain metastasis after breast cancer surgery at Bao Ding No.1 Central Hospital were randomized into two groups. The control group (51 patients) received standard nursing care, while the observation group (51 patients) participated in a behavioral change nursing intervention influenced by empowerment theory. The evaluation metrics included measures of negative emotions, compliance with treatment protocols, overall quality of life, and nursing satisfaction, assessed at multiple time points during the study period.Results: The intervention led to significant reductions in negative emotions for all patients when compared to their pre-intervention statuses, with the observation group exhibiting notably lower depression and anxiety scores at one and three months post-intervention (P < 0.05). Additionally, this group achieved higher compliance scores and demonstrated greater improvements in quality of life than the control group (P < 0.05). Nursing satisfaction was also significantly higher in the observation group, with 96.08% reporting high satisfaction compared to 80.39% in the control group (P < 0.05).Conclusion: Implementing a nursing intervention that emphasizes behavioral changes and leverages empowerment theory significantly enhances the quality of life, reduces negative emotions, boosts compliance with treatment, and increases nursing satisfaction among patients with brain metastasis following breast cancer surgery. This suggests that such interventions could be a valuable component of postoperative care for this patient population.Keywords: behavioral change, empowerment theory, negative emotions, nursing intervention, brain metastasis, breast cancer, quality of life

XiaoLiang Wang,1,&ast; XiaoDong Ni,1,&ast; YanYan Wei,1 LiHua Xu,1 XiaoChen Tang,1 HaiChun Liu,2 ZiXuan Wang,3 Tao Chen,4,5 JiJun Wang,1 Qing Zhang,1 TianHong Zhang1 1Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Engineering Research Center of Intelligent Psychological Evaluation and Intervention, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 2Department of Automation, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Psychology, Shanghai Xinlianxin Psychological Counseling Center, Shanghai, People’s Republic of China; 4Big Data Research Lab, University of Waterloo, Waterloo, Ontario, Canada; 5Labor and Worklife Program, Harvard University, Cambridge, MA, USA&ast;These authors contributed equally to this workCorrespondence: TianHong Zhang; Qing Zhang, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Road, Shanghai, 200030, People’s Republic of China, Tel +86-21-34773065, Fax +86-21-64387986, Email zhang_tianhong@126.com; qing.zhang@smhc.org.cnIntroduction: Despite numerous studies investigating personality disorder (PD) and childhood maltreatment (CM) characteristics in individuals with schizophrenia (SZ), there remains a scarcity of research focusing on sex differences in PD and CM within large samples of SZ patients.Methods: A total of 592 participants (257 males, 335 females) were consecutively sampled from patients diagnosed with SZ at the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. PDs were assessed using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were evaluated using the Chinese version of the Child Trauma Questionnaire Short Form.Results: Male patients exhibited a prominent self-reported trait of antisocial PD (t=1.972, p=0.049), while female patients demonstrated a notable emphasis on histrionic PD traits (t=− 2.057, p=0.040). Structured interviews for PD diagnoses further indicated a higher comorbidity of schizotypal (χ2=4.805, p=0.028) and schizoid (χ2=6.957, p=0.008) PDs among male patients compared to female patients. Additionally, male patients reported a higher degree (t=2.957, p=0.003) and proportion (χ2=5.277, p=0.022) of experiences of physical abuse in their self-reported CM. Logistic regression analyses highlight distinct factors: higher antisocial PD traits and physical abuse are associated with male patients, while histrionic PD traits and emotional abuse are associated with female patients.Discussion: These findings underscore the importance of recognizing and addressing sex-specific manifestations of personality pathology and the nuanced impact of CM in the clinical management of individuals with SZ. The study advocates for tailored interventions that consider the distinct needs associated with sex differences in both personality traits and CM experiences among SZ patients.Keywords: personality disorder, psychosis, abuse, neglect, schizophrenia

Fangmin Gong,1 Zhuliu Gong,1 Haimeng Liu,2 Pei Yi,1 Yuhan Jia,3 Jingwen Zhuang,1 Jilin Shu,1 Xincheng Huang,4 Yibo Wu5 1College of Literature and Journalism Communication, Jishou University, Jishou, People’s Republic of China; 2College of Minority Preparatory Education, Jishou University, Zhangjiajie, People’s Republic of China; 3Office of the Party and Administration, Hebei Academy of Fine Arts, Shijiazhuang, People’s Republic of China; 4School of Economics and Management, Beijing Institute of Graphic Communication, Beijing, People’s Republic of China; 5School of Public Health, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Haimeng Liu, Zhangjiajie Campus, Jishou University, Dayongqiao Street, Ziwu Road, Yongding District, Zhangjiajie, Hunan Province, 427000, People’s Republic of China, Tel +86 15074328922, Email Liu.Haimeng@outlook.com Yibo Wu, Peking University School of Public Health, No.38 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 18810169630, Email bjmuwuyibo@outlook.comPurpose: To explore the relationship between adolescents’ problematic Internet use and loneliness and the mediating roles of social support and family communication.Methods: A questionnaire survey of 2483 adolescents aged 12– 17 years in 148 cities in China was conducted using the Problematic Internet Use Scale, the Collaborative Social Support Scale, the Family Communication Scale, and the Loneliness Scale. The data were statistically analyzed by SPSS 26.0 and validated by AMOS 28.0. Structural equation modelling (SEM) was conducted to test the effects of problematic Internet use on adolescents’ loneliness and the mediating effects of perceptions of social support and family communication.Results: There was a significant positive effect of adolescents’ problematic Internet use on loneliness (B-0.471, P< 0.001), and the mediating effects of perceptual social support (0.003, 0.012) and family communication (0.008, 0.019) were found to play a chain effect between adolescents’ problematic Internet use and loneliness, respectively. Use and feelings of loneliness played a chain mediating role (0.002, 0.006).Conclusion: This study identified the effects of adolescent problematic Internet use on loneliness and its mechanism of action, emphasized the importance of social support and family communication, and provided practical insights for improving family parenting styles and preventing and intervening in adolescent loneliness problems.Keywords: problematic internet use, adolescents, loneliness, perceived social support, family communication

Ke Wang,1,2,3 Yuying Kou,4 Xing Rong,1,2 Lingling Wei,5 Jingyuan Li,6 Hongrui Liu,1,2 Minqi Li,1,2 Hui Song31Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 2Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, People’s Republic of China; 3Department of Health Care (Department of General Dentistry II), School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 4School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Department of Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 6Department of Oral Mucosal Disease, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of ChinaCorrespondence: Hui Song, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration No.44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +0086-531-88382912, Email songhui@sdu.edu.cnPurpose: Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71.Methods: In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H2O2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot.Results: ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts.Conclusion: ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.Keywords: osteoporosis, eldecalcitol, osteoclasts, EphrinB2-EphB4, osteoblasts, RANKL/RANK/OPG

Aguo Cheng,1,2 Suohui Zhang,1,3 Fanda Meng,4 Mengzhen Xing,5 Han Liu,3 Guozhong Yang,3 Yunhua Gao1– 3 1Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry of Chinese Academy of Sciences, Beijing, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Beijing CAS Microneedle Technology Ltd, Beijing, People’s Republic of China; 4School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China; 5Key Laboratory of New Material Research Institute, Department of Pharmaceutical Research Institute, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Yunhua Gao, Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry of Chinese Academy of Sciences, Beijing, People’s Republic of China, Tel +86 (10)82543581, Email yhgao@mail.ipc.ac.cnPurpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum’s barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility.Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance.Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action’s duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1β compared with the methotrexate subcutaneous injection method.Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration. Keywords: nanosuspension, highly lipophilic drugs, dissolving microneedle, cannabidiol, knee synovitis

Mengyang Li,1,&ast; Yuting Wang,2,&ast; He Liu,2 Xiaonan Huang,2 Huagang Peng,2 Yi Yang,2 Zhen Hu,2 Jianxiong Dou,2 Chuan Xiao,2 Juan Chen,3 Weilong Shang,2 Xiancai Rao1,2 1Department of Microbiology, School of Medicine, Chongqing University, Chongqing, 400044, People’s Republic of China; 2Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Chongqing, 400038, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiancai Rao; Weilong Shang, Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing, Chongqing, 400038, People’s Republic of China, Email raoxiancai@126.com; shangwl0414@163.comIntroduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated.Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2–MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor.Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2–MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10− 3 μg. Antares2–MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2–MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo.Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment. Keywords: Staphylococcus aureus, membrane vesicles, Antares2, cancer therapy, pyroptosis, caspase-1, GSDMD

Luxia Xiao, Meilin Yao, Hongrui Liu Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Hongrui Liu, Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China, Email hrliu@bnu.edu.cnPurpose: Drawing upon the cognitive-behavioral model of pathological Internet use (PIU) and tunnel effect, this study aimed to construct a moderated mediation model from the perspective of social ecology. Specifically, the model investigated the relationship between perceived social mobility and smartphone dependence, with a focus on the mediating role of hope and the moderating effect of family socioeconomic status (SES) underlying this relationship.Methods: A cross-sectional study was conducted with 718 Chinese university students (Mage = 19.19, 70.2% female) from Beijing, Henan, and Tianjin, who anonymously filled out the Perceptions of Socioeconomic Mobility Scale, Mobile Phone Addiction Index Scale, Openness to the Future Scale, and family socioeconomic status questionnaire. Preliminary data analysis was executed using SPSS 22.0, and the moderated mediation effect was tested using the latent moderated structural equations approach in Mplus 8.3.Results: The results showed that (a) less perceived social mobility was linked with greater smartphone dependence; (b) hope mediated the aforementioned relationship; and (c) family SES moderated the first-stage path of the indirect effect through hope. For university students with low (rather than high) family SES, their level of hope increased with the improvement of perceived social mobility, and in turn, that of smartphone dependence decreased.Conclusion: These findings suggest that positive perceptions of upward social class mobility and hopeful attitudes toward future opportunities and personal development among disadvantaged university students may alleviate their reliance on smartphones. Researchers and policymakers should pay attention to the role of individuals’ perceptions of the macro environment in motivating specific risky behaviors among university students. Future interventions are essential to mitigate pessimistic environmental perceptions and foster a sense of hope among university students.Keywords: family socioeconomic status, hope, moderated mediation, perceived social mobility, smartphone dependence

Yu Gao,1 Haiyan Liu,2 Yuechi Sun2 1School of Psychology, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2School of Economics and Management, China University of Geosciences (Beijing), Beijing, People’s Republic of ChinaCorrespondence: Haiyan Liu, School of Economics and Management, China University of Geosciences (Beijing), 29 Xueyuan Road, Haidian District, Beijing, 100083, People’s Republic of China, Email liuhy@cugb.edu.cnBackground: In the digital age, people’s attitudes and psychological security towards public health emergencies will be shared. Similar or identical psychological security states are prone to clustering and differentiation, while differentiated group psychological security is more prone to polarization, leading to group psychological security risks and then posing a threat to social stability and national security. However, existing studies mostly use qualitative analysis methods to study group emotional risks. There are still limitations in the study of dynamics of group psychological security risks through mining real data of social media.Purpose: The study aims to use intelligent analysis methods to understand how group psychological security risks dynamically change.Methods: The study draws on text sentiment analysis, Markov chains and time series analysis to construct a framework for the evolution of group psychological security risks. Based on this framework, text data was crawled on Sina Weibo platform, mainly consisting of posts during public health emergencies (March 1st to June 30th, 2022) in Shanghai, and a psychological security lexicon in the field of public health emergencies was constructed. This laid the foundation for identifying the tendencies, intensity, and transitions of individual text psychological security, and then exploring the evolution trend of group psychological security risks.Results: Compared with the generation and reduction periods, group psychological security risks are more likely to occur during the outbreak and recovery periods, and the intensity level is also higher. The overall intensity of group psychological security risks shows an evolution trend of first increasing, then decreasing, and then increasing again.Conclusion: The paper provides an opportunity to explore the dynamics of psychological security in the digital space. Meanwhile, we call on the government and relevant management departments to pay more attention to the group psychological security risks formed during the outbreak and recovery periods of public health emergencies, and take corresponding measures in a timely manner to guide the public to transform the extreme psychological security state into the normal psychological security state, in order to prevent and resolve group psychological security risks, promote social stability and national security.Keywords: group psychological security risks, psychological security lexicon, machine learning, evolution trend

Chen Yang,1,2,&ast; Wangjun Dong,2,&ast; Jianbo Luo,2 Mengzhao Ma,2 Yeyue Gao,2 Lijie Ni,2 Huixing Liu,2 Chengjun Cha,2 Yangli Xiao,2 Shaoqiang Huang1 1Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesia, Yongping County People’s Hospital, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqiang Huang, Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, 128&num; Shenyang Road, Shanghai, 200090, People’s Republic of China, Email Drhuangsq@163.comObjective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude.Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded.Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52– 9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48– 9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed.Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.Keywords: bupivacaine, high altitude, spinal anesthesia, ED50 dose

Jing Wang,1,2,&ast; Yi Duan,2,&ast; Liangrong Geng,2 Xiaoyu Li,3 Shujin Yue,2 Hongxia Liu2 1Department of Nursing, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Nursing, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Center for Treatment of Undiagnosed Diseases, the First Affiliated Hospital of Nanchang University, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shujin Yue, Beijing University of Chinese Medicine, No. 11 North 3rd Ring East Road, Chao-Yang District, Beijing, 100029, People’s Republic of China, Email yueliang874@126.comPurpose: To (1) investigate the changes in 5 domains (lack of family support, impact on finance, impact on daily schedule, impact on health, and self-esteem) of family caregiver (FC) burden and overall burden for first diagnosed colorectal cancer; (2) exploring changes in FC burden for colorectal cancer patients over time and analyze the trajectory and sub-trajectories of FC burden; and (3) identify the FC‐related and patient‐related factors most associated with the overall FC burden and each of its sub-trajectories.Patients and methods: This study is a descriptive longitudinal study. A convenience sampling method was used to recruit patients with colorectal cancer and their primary FCs from seven hospitals.Results: A total of 185 pairs of first diagnosed colorectal cancer patient and their FC were investigated for 4 times. The results reveal the overall burden and 5 domains of burden showed a trend of increasing first and then decreasing, and the burden was the heaviest at the time in the middle of chemotherapy. In the course of time, the aspect that caused the greatest amount of burden on average transitioned from the “effect on daily schedule” (range= 3.3 and 3.9) to the “effect on finances” (range= 3.1 to 3.4).Conclusion: Almost 88% of FCs have a either a moderate or a high level of burden. The quality of life of patients and the self-efficacy, social support and care ability of FCs have a great impact on the overall FC burden and each sub-trajectory.Keywords: care burden, colorectal cancer, family caregiver, longitudinal study, trajectories

Sifen Jiang,1,2,&ast; Tingyu Luo,2,&ast; Zhuoqi Zhu,3,&ast; Yanling Huang,2 Haopeng Liu,4 Bing Li,2 Suibin Feng,5 Kun Zeng1 1Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China; 2School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Guangxi, People’s Republic of China; 4School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Surgery Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suibin Feng, Surgery Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), No. 68 South West Lake 3 Road, Shilong Town, Dongguan City, Guangdong Province, 523321, People’s Republic of China, Tel +86 13430293807, Email 19526620667@163.com Kun Zeng, Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), No. 68 South West Lake 3 Road, Shilong Town, Dongguan City, Guangdong Province, 523321, People’s Republic of China, Tel +86 13790300213, Email Zengkun660524@163.comBackground: The treatment of Type 2 Diabetes Mellitus (T2DM) is a protracted and arduous process. Medication, being a universally crucial therapeutic measure, underscores the significance of medication adherence in managing the disease effectively. Medication beliefs have emerged as a significant predictor of adherence, attracting considerable scholarly attention in recent years. However, there remains a paucity of research utilizing individual-centered approaches to explore medication beliefs among the T2DM population during the hospital-home transition, leaving the relationship between these beliefs and medication adherence unclear.Purpose: To investigate latent categories of medication beliefs among patients with T2DM during the transition from hospital to home, and to analyze variations in medication adherence across these categories of patients.Patients and methods: Between August 2022 and September 2023, this study selected 304 patients with a pre-discharge diagnosis of T2DM as study subjects from a tertiary hospital in Dongguan City. The patients’ profiles were assessed comprehensively via the Sociodemographic and Clinical Characteristics Questionnaire, alongside the Chinese version of Beliefs about Medicines Questionnaire-Specific and Morisky Medication Adherence Scale-8. The present study conducted latent profile analysis using Mplus 7.4 software and analyzed the influencing factors of different medication belief categories and their differences in medication adherence using SPSS 26.0 software.Results: The medication beliefs of 304 patients were rated at 3.36± 5.24 points, while medication adherence scored 6.23± 1.56 points. The medication beliefs were classified into four categories: moderate necessity - low to moderate concern group (40.13%), high necessity - low concern group (9.54%), moderate necessity - moderate to high concern group (19.08%), and moderate necessity - high concern group (31.25%). Age, monthly per capita household income, and place of residence emerged as influential factors for the four categories. Moreover, the disparity in medication adherence among these categories demonstrated statistical significance (P < 0.001).Conclusion: The medication beliefs of patients were classified into four distinct categories, and variations in medication adherence were evident across these categories. The high necessity - low concern group demonstrated the highest medication adherence scores, while the moderate necessity - high concern group exhibited the lowest scores. Healthcare providers are advised to tailor personalized medication belief enhancement programs based on patients’ homogeneous beliefs, addressing specific issues encountered by each category. This approach aims to ensure optimal medication adherence across diverse medical and social environments, effectively improving patient prognosis and enhancing quality of life.Keywords: diabetes mellitus, T2DM, medication beliefs, medication adherence, latent profile analysis, influencing factors

Canhao Lai,1,&ast; Ruichen Li,1,&ast; Weili Tang,1 Jinyu Liu,1 Xinfang DXF Duan,1 Dingsu Bao,1,2 Huan Liu,1 Shijie Fu1 1Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 2Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijie Fu; Huan Liu, Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 13882759783, Email fushijieggj@126.com; 20016040@163.comAbstract: Metabolic syndrome (MS) is a multifaceted pathological condition characterized by the atypical accumulation of various metabolic components such as central obesity or excess weight, hyperlipidemia, low-density lipoprotein (LDL), hypertension, and insulin resistance. Recently, MS has been recognized as a notable contributor to heart and circulatory diseases. In addition, with increasing research, the impact of MS on tendon repair and disease has gradually emerged. Recent studies have investigated the relationship between tendon healing and diseases such as diabetes, dyslipidemia, obesity, and other metabolic disorders. However, diabetes mellitus (DM), hypercholesterolemia, obesity, and various metabolic disorders often coexist and together constitute MS. At present, insulin resistance is considered the major pathological mechanism underlying MS, central obesity is regarded as the predominant factor responsible for it, and dyslipidemia and other metabolic diseases are known as secondary contributors to MS. This review aims to evaluate the current literature regarding the impact of various pathological conditions in MS on tendon recovery and illness, and to present a comprehensive overview of the effects of MS on tendon recovery and diseases, along with the accompanying molecular mechanisms.Keywords: metabolic syndrome, tendon, diabetes mellitus, hyperlipidemia, obesity, hypertension

Tao Jiang,1,2 Weijian Chen,3 Chao Lu,1,2 Jiyong Yang,3 Ziquan Zeng,1,2 Wenqiang Li,4 Hongsheng Liu,5 Nana Huang,5 Yuhui Chen,6 Wengang Liu1,2 1Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 2Department of Orthopedics, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 3The Fifth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 4Engineering Technology Research Center for Sports Assistive Devices of Guangdong, School of Sport and Health, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 5Guangdong Huayan Biomedical Science and Technology Center, Guangzhou, 511441, People’s Republic of China; 6Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of ChinaCorrespondence: Wengang Liu, Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Hengfu Road 60, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email liuwengang74@163.com Yuhui Chen, Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China, Email ah1990726@163.comBackground: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy.Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo.Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe’s remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day.Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.Keywords: Cu-HMCe nanozyme, antioxidation, antibacterial, vascularization, wound healing

Danfei Zhou, Jun Ying, Shanshan Hu, Jiangdong Li, Haijian Liu Department of Respiratory and Critical Care Medicine, Ningbo No.2 Hospital, Ningbo, People’s Republic of ChinaCorrespondence: Haijian Liu, Department of Respiratory and Critical Care Medicine, Ningbo No.2 Hospital, NO. 41, Xibei Street, Ningbo, 315000, People’s Republic of China, Email qixingcao2010@163.comBackground: Anaplastic lymphoma kinase (ALK) rearrangements have been reported as an important oncogenic driver in 5– 7% non-small cell lung cancer (NSCLC) patients. Reports about the intergenic region (IGR) as an ALK fusion partner are rare. In this study, we report a novel IGR (chr2: 30,316,870)-ALK fusion in an advanced lung adenocarcinoma patient that responded effectively to crizotinib combined with pemetrexed.Case Presentation: A 68-year-old Chinese female was diagnosed with stage IV right lung adenocarcinoma (cT3N3M1c). The targeted next-generation sequencing (NGS) of 14 cancer-related genes identified an IGR (chr2: 30,316,870)-ALK fusion. Her lung lesions have been successfully converted from a partial response to a complete response after administrating crizotinib for 1 year combined with 6 cycles of chemotherapy with pemetrexed. So far, her progression-free-survival has reached 21 months.Conclusion: In this case, we firstly report a novel IGR (chr2: 30,316,870)-ALK fusion by using targeted NGS, and highlight the efficacy of crizotinib combined with pemetrexed to reduce unbearable gastrointestinal adverse reactions. It provides valuable clinical guidance for the treatment of similar cases in the future.Keywords: NSCLC, IGR-ALK, NGS, crizotinib, pemetrexed

Jie Zhang,1 Yuhuan Zheng,1 Hongjuan Liu,2 Bo Liu3 1Department of Blood Transfusion, Ankang Central Hospital, Ankang, Shannxi, 725000, People’s Republic of China; 2Operating Room, Ankang Central Hospital, Ankang, Shannxi, 725000, People’s Republic of China; 3Department of Blood Transfusion, Ankang Hospital of Traditional Chinese Medicine, Ankang, Shannxi, 725000, People’s Republic of ChinaCorrespondence: Bo Liu, Ankang Hospital of Traditional Chinese Medicine, Ankang Municipality of Bashan East Road No. 47, Ankang, Shannxi, 725000, People’s Republic of China, Email 541906839@qq.comBackground: Acute myeloid leukemia (AML) is a hematological malignancy with poor patient prognosis. Cuprotosis is a newly discovered cell death that regulates the proliferation and progression of tumor cells. Long non-coding RNAs (lncRNAs) are key molecules and potential biomarkers for the diagnosis and treatment of various diseases. However, the effect of cuprotosis-associated lncRNAs on AML remains unclear.Objective: The aim of this study was to investigate the relationship between the expression of cuprotosis-related gene and the prognosis of AML.Methods: Consensus cluster analysis was performed on AML patients according to the cuprotosis-related gene expression matrix, and survival analysis and differential gene analysis were performed. Then lncRNA and miRNA related to AML tumor progression were screened according to univariate COX regression analysis. After that, Kaplan-Meier analysis, correlation analysis, and AUC curve were used to determine the ceRNA network that might regulate AML. The regulatory relationship of ceRNA was verified in AML cell lines by RT-qPCR and Western blotting.Results: The AC024896.1/miR-363-3p axis drives MYO1B to promote the malignant progression of AML. First, a change in the expression of AC024896.1 and miR-363-3p can affect the proliferation of AML by regulating MYO1B. Mechanistically, AC024896.1 regulates the expression of MYO1B as the ceRNA of miR-363-3p. Moreover, the regulation of AC024896.1 in the malignant progression of AML depends partly on miR-363-3p.Conclusion: In summary, our study reveals AC024896.1/miR-363-3p/MYO1B Axis in AML, which can be regarded as a new potential target for the diagnosis and treatment of AML.Keywords: acute myeloid leukemia, cuprotosis, ceRNA network, bioinformatics analysis

Yan Fang,1,2 Huali Liu,1,2 Yuan Li,1,2 Ji Cheng,1 Xia Wang,1 Bing Shen,3 Hongbo Chen,1,2 Qunhua Wang4 1Department of Obstetrics and Gynaecology, Maternal and Child Health Hospital Affiliated to Anhui Medical University, Hefei, People’s Republic of China; 2The Fifth Clinical College of Anhui Medical University, Hefei, People’s Republic of China; 3School of Basic Medicine, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Obstetrics and Gynaecology, the First Affiliated Hospital of USTC, Hefei, People’s Republic of ChinaCorrespondence: Hongbo Chen, Maternal and Child Health Hospital Affiliated to Anhui Medical University, No. 15 Yimin Street, Luyang District, Hefei City, Anhui Province, People’s Republic of China, Email chenhongbo@ahmu.edu.cn Qunhua Wang, Department of Obstetrics and Gynaecology, the First Affiliated Hospital of USTC, Hefei, People’s Republic of China, Email wqh971234@163.comPurpose: To investigate the risk factors associated with preeclampsia in hyperglycemic pregnancies and develop a predictive model based on routine pregnancy care.Patients and Methods: The retrospective collection of clinical data was performed on 951 pregnant women with hyperglycemia, including those diagnosed with diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM), who delivered after 34 weeks of gestation at the Maternal and Child Health Hospital Affiliated to Anhui Medical University between January 2017 and December 2019. Observation indicators included liver and kidney function factors testing at 24– 29+6 weeks gestation, maternal age, and basal blood pressure. The indicators were screened univariately, and the “rms” package in R language was applied to explore the factors associated with PE in HIP pregnancy by stepwise regression. Multivariable logistic regression analysis was used to develop the prediction model. Based on the above results, a nomogram was constructed to predict the risk of PE occurrence in pregnant women with HIP. Then, the model was evaluated from three aspects: discrimination, calibration, and clinical utility. The internal validation was performed using the bootstrap procedure.Results: Multivariate logistic regression analysis showed that cystatin C, uric acid, glutamyl aminotransferase, blood urea nitrogen, and basal systolic blood pressure as predictors of PE in pregnancy with HIP. The predictive model yielded an area under curve (AUC) value of 0.8031 (95% CI: 0.7383– 0.8679), with an optimal threshold of 0.0805, at which point the sensitivity was 0.8307 and specificity of 0.6604. Hosmer–Lemeshow test values were P = 0.3736, Brier score value was 0.0461. After 1000 Bootstrap re-samplings for internal validation, the AUC was 0.7886, the Brier score was 0.0478 and the predicted probability of the calibration curve was similar to the actual probability. A nomogram was constructed based on the above to visualize the model.Conclusion: This study developed a model for predicting PE in pregnant women with HIP, achieving high predictive performance of PE risk through the information of routine pregnancy care.Keywords: hyperglycemia in pregnancy, preeclampsia, prediction model, nomogram, internal validation