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Ciyi Hua,1 Feifei Li,1 Youyang Shi,2 Yuan Xu,1 Mengdie Zhu,1 Yang Wang,1 Xiqiu Zhou,2 Sheng Liu1,3 1Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Breast Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Sheng Liu, Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Tel +86 18917763005, Fax +86-64385700, Email shengliu@shutcm.edu.cnBackground: Patients with clinically cured granulomatous lobular mastitis (GLM) still face a high probability of recurrence and new occurrence.Purpose: To evaluate the long-term efficacy of traditional Chinese medicine (TCM) in treating GLM and to hypothesize potential risk factors for recurrence or new occurrence.Patients and Methods: A retrospective analysis was conducted on GLM patients treated with TCM at Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine from January 2016 to July 2021. We analyzed general data, two-year recurrence and new occurrence rates, and 12 risk factors associated with recurrence or new occurrence.Results: This cross-sectional study included 261 GLM patients with an average age at onset of 31.95 years (primarily aged 31– 40). The two-year recurrence rate for GLM was 1.53%, and the new occurrence rate was 4.21%. Univariate and multivariate conditional logistic regression analyses revealed that a history of inverted nipples was associated with the risk of both recurrence and new occurrence of GLM (HR = 8.672, 5.375, P < 0.05), and menstrual irregularity was related to a higher risk of recurrence (HR = 13.172, P < 0.001).Conclusion: A history of inverted nipples is identified as a potential risk factor associated with the long-term recurrence and new occurrence of GLM, while menstrual irregularity is associated with recurrence. Despite this, patients with GLM undergoing TCM demonstrate low rates of long-term recurrence and new occurrence after achieving clinical cure, underscoring the effectiveness of TCM. This study lays the groundwork for a long-term effectiveness strategy to guide future GLM treatments.Keywords: granulomatous lobular mastitis, GLM, recurrence, new occurrence, risk factor

Yajie Wang,1,&ast; Bo Yuan,2,&ast; Wei Liu,3,&ast; Jianlin Cui,2 Xueyan Zhou,2 Liyun Yuan,2 Zihao Deng,4 Yuhao Li,5,6 Xiaoyong Yuan1,2 1Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Tianjin Zhonghe Gene Technology Limited Company, Tianjin, People’s Republic of China; 4Cancer Center, Capital Medical University, Beijing, People’s Republic of China; 5Central Laboratory, Xuanwu Hospital Capital Medical University, Beijing Geriatric Medical Research Center, Beijing, People’s Republic of China; 6Optometry Institute, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyong Yuan, Tianjin Eye Hospital, Tianjin key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, People’s Republic of China, Email yuanxy_cn@hotmail.com Yuhao Li, Central Laboratory, Xuanwu Hospital Capital Medical University, Beijing Geriatric Medical Research Center, Beijing, People’s Republic of China, Email liyuhao@xwhosp.orgBackground: Age-related macular degeneration (AMD) is becoming the leading cause of blindness in the aged population. The death of photoreceptors is the principal event which is lack of curative treatment. Xaliproden, a highly selective synthetic 5-OH-tryptamine (5HT) 1A receptor agonist, has the neuroprotective potential. However, its application has been limited by the insoluble formulation, low utilization efficiency and side effects caused by systemic administration.Methods: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was used as a skeleton and loaded with xaliproden (XAL) to prepare a novel kind of nanoparticle, namely, XAL-NPMOF. The human umbilical vein endothelial cells, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of XAL-NPMOF both in vitro and in vivo. A photoreceptor degeneration model was generated by intense light injury in adult zebrafish and XAL-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration, inflammatory response and visual function were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and optomotor response analysis.Results: Following a single XAL-NPMOF intraocular injection, the injured retina underwent the faster photoreceptor regeneration with a recovery of visual function via promoting cell proliferation, suppressing the inflammatory responses and increasing the expression of antioxidases.Conclusion: As an amplifier, NPMOF can enhance the anti-inflammatory efficacy and neuroprotective effect of xaliproden. XAL-NPMOF could be a novel and convenient option for the treatment of AMD.Keywords: nanoscale zirconium-porphyrin metal-organic framework, xaliproden, photoreceptor, anti-inflammatory effect, regeneration

Tiansu Lv,1,2,&ast; Jie Tian,1,3,&ast; Yaohuan Sun,1,3 Yujuan Zhang,1,2 Fang Qi,1,2 Liulan Xiang,1,2 Yutian Cao,1,2 Wenhui Zhang,1,2 Jiaxuan Huai,1,2 Yinfeng Dong,4 Xiqiao Zhou1,2 1Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiqiao Zhou; Yinfeng Dong, Email zhouxiqiao@njucm.edu.cn; dongyf@njucm.edu.cnBackground: Metabolic Associated Fatty Liver Disease (MAFLD) poses a significant threat to human health, as it can result in hepatic fibrosis and potentially progress to cirrhosis, in addition to causing a range of extrahepatic complications. The early detection of MAFLD is crucial, particularly during the initial stages when the condition may be amenable to reversal and the body composition could be vital importance.Methods: Data from participants at the Jiangsu Province Hospital of Traditional Chinese Medicine, covering the period from January 1 to December 31, 2022, were collected and subsequently randomized into training and validation cohorts. Independent risk factors for MAFLD were identified using statistical methodologies in conjunction with clinical relevance, and these factors were ultimately utilized to develop the nomogram.Results: In the training cohort, there were 356 cases of MAFLD out of a total of 513 patients, representing 71.2%, while in the validation cohort, 161 cases of MAFLD were identified out of 220 patients, accounting for 73.2%. In terms of statistical outcomes and clinical relevance, we identified a total of 12 closely related or significant variables. To enhance our understanding of the critical role of body composition parameters in predicting the incidence of MAFLD, we developed two distinct nomograms, one of which included body composition data. Notably, the nomogram that incorporated body composition demonstrated superior predictive performance, as evidenced by a well-fitted calibration curve and a C-index of 0.893 (with a range of 0.8625 to 0.9242). Furthermore, the decision curve analysis indicated that utilizing the nomogram that included body composition would yield greater benefits.Conclusion: The nomogram serves as an effective tool for predicting MAFLD. Its utility in early risk identification of MAFLD is of significant importance, as it facilitates timely intervention and treatment for patients affected by this condition.Keywords: Metabolic Associated Fatty Liver Disease, Body Composition, Nomogram

Mi Tang,1,2,&ast; Liling Xiong,3,&ast; Jianghui Cai,2,4,&ast; Xuejia Gong,2 Li Fan,1 Xiaoyu Zhou,1 Shasha Xing,1 Xiao Yang3 1Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2School of medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Obstetrics Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Pharmacy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shasha Xing; Xiao Yang, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China, Email xingshasha1230@126.com; wcchgcptg@163.comPurpose: Intrahepatic cholestasis of pregnancy (ICP) is a disorder that characterized by maternal pruritus, abnormal liver function, and an elevation in total bile acid concentrations during pregnancy. Immune factors have been recognized as playing a vital role in the mechanism of ICP. However, the underlying mechanisms regulating dysfunctional immune cells and immune genes remain to be fully elucidated.Patients and Methods: Single-cell RNA sequencing and bulk RNA sequencing data of the placenta were downloaded from the SRA database. The AUCell package, Monocle package and SCENIC package were utilized to explored immune cell activity, cell trajectory and transcription factor, respectively. GO, KEGG, and GSEA were employed to explore potential biological mechanisms. Cell-cell communications were further investigated using the CellChat package. RT-PCR, and Western blot were used to verify the gene expression in placenta.Results: In placenta cells, macrophages were found to be significantly increased in ICP. Additionally, macrophages exhibited the highest immune gene score and were divided into four subclusters (MF1-4). Our analysis revealed significant elevations in MF2, associated with LPS response and antigen presentation, and MF4, associated with TNF and cytokine production. MF3 displayed an anti-inflammatory phenotype. MF1, closely related to ribosomes and proteins, exhibited a sharp decrease. Although ICP maintained an anti-inflammatory state, macrophage trajectories showed a gradual progression toward inflammation. Subsequently, we confirmed that cytokine- and chemokine-related signaling pathways were emphasized in macrophages. Within the CXCL signaling pathway, the increased expression of CXCL1 in macrophages can interact with CXCR2 in neutrophils, potentially inducing macrophage infiltration, stimulating neutrophil chemotaxis, and leading to an inflammatory response and cellular damage.Conclusion: In conclusion, we firstly revealed the transcriptional signatures of macrophages in ICP and discovered a tendency toward an inflammatory state. This study also provides new evidence that the CXCL1-CXCR2 axis may play an important role in the pathogenesis of ICP.Keywords: intrahepatic cholestasis of pregnancy, scRNA-Seq, bulk RNA-Seq, immune gene, macrophage

Taoying Lu,1– 3 Mingyue Fan,1 Jianxiong Cai,4 Aolin Liu,1 Qianwen Xie,2,3 Xiaowen Zhou,1 Bei Chang,1 Lingjia Yin,2,3,5 Guli Jiang,6 Bin Sun,7 Wenyi Tang,7 Darong Wu4 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Outcome Assessment Research Team in Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Outcome Assessment Research Team in Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 6Department of Scientific Research, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of China; 7Department of Traditional Chinese Medicine, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of ChinaCorrespondence: Darong Wu, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China, Tel +86 13808869436, Email darongwu@gzucm.edu.cnBackground: Dampness syndrome is a basic syndrome of many major and chronic diseases. Early screening and identification of dampness syndrome are important. The Dampness Syndrome Scale of Chinese Medicine (DSSCM) was developed to measure the occurrence and severity of dampness syndrome. The measurement characteristics of the DSSCM should be further validated. The objective of this study is to evaluate the reliability and validity of the DSSCM based on a cross-sectional survey.Methods: The development of DSSCM was based on the traditional Chinese medicine (TCM) theory, expert consensus and clinical investigations. Participants were recruited from Guangdong Provincial Hospital of Chinese Medicine and Guangzhou Cadre Health Management Center in Guangdong Province, China. All participants completed the baseline questionnaire and DSSCM. The reliability of the DSSCM was evaluated by internal consistency reliability and test–retest reliability. The factor structure was tested with confirmatory factor analysis (CFA), while discriminant validity was evaluated by calculating the difference between the total score of the DSSCM and its four dimensions for participants with or without dampness syndrome. We used a clinician’s diagnosis of dampness syndrome as a criterion to evaluate the criterion validity. Multivariate regression analysis was used to analyze the associations among gender, age, height, and weight and dampness syndrome.Results: A total of 880 participants were enrolled for psychometric validation and 869 participants were included in the final analyses after exclusion. The mean age of the participants was 42.62± 12.86 years. The Cronbach’s alpha coefficients for the four dimensions of the DSSCM were 0.809, 0.891, 0.816 and 0.780. The ICCs for the four dimensions of the DSSCM were 0.806, 0.674, 0.780 and 0.760. For validity, the results showed that the DSSCM had good content validity, discriminant validity and criterion validity. For the CFA, the root mean square error of approximation (RMSEA) was 0.091; the standardized root mean square residual (SRMR) was 0.074; the comparative fit index (CFI) was 0.766; and the Tucker–Lewis index (TLI) was 0.745. Weight was found to be associated with the total scores of the DSSCM and its three dimensions.Conclusion: The DSSCM has good reliability and validity to support its use as a tool for assessing the severity of dampness syndrome. This study provides empirical evidence for future updates to the DSSCM.Keywords: dampness syndrome, dampness syndrome scale of Chinese medicine, reliability, validity

Qizhi Diao,1 Yongpei Long,2 Fangyu Yang,3 Cuihui Nong,1 Huamiao Tang,1 Xiangmin Zhou,1 Guoqiang Zhu,4 Qiang Ding5 1Hainan Branch, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Jianyang City, Sichuan, People’s Republic of China; 3Department of Clinical Laboratory Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chong Qing King Med Center for Clinical Laboratory Co., Ltd, Chongqing, People’s Republic of China; 5The Sixth People’s Hospital of Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Guoqiang Zhu; Qiang Ding, Email Guoqiangzhu01@163.com; yung10167086@126.comBackground and Objective: Inadequate risk assessment and a lack of risk monitoring are common deficiencies in clinical laboratory, and are also the main causes of biosafety incidents. Therefore, we summarized the experience of implementing adequate risk assessment and maintaining risk monitoring, and established a procedure for continuously improving biosafety management.Methods: Learning from our laboratory’s experience in implementing risk assessment, risk response, and risk monitoring before and during the COVID-19 epidemic, we summarized the procedures for fully identifying risks, accurately evaluating risks, maintaining risk monitoring, establishing and regular reviewing safety indicators. On this basis, we established a system for continuously improving biosafety management through risk monitoring and reviewing safety indicator.Results: We identified a total of 30 unacceptable risks prior to the COVID-19 pandemic, and developed and implemented appropriate risk control measures. After risk control, residual risks were acceptable, and no biosafety incidents have occurred. During the COVID-19 pandemic, after multiple risk monitoring, we identified ten new risks, three ineffective risk control measures, and multiple control measures for excessive protection. Then, we timely adjusted risk control measures to avoid laboratory personnel infection and excessive protection. Meanwhile, We established eight safety indicators and identified two improvement opportunities through regular reviews.Conclusion: Adequate risk identification and accurate risk assessment are particularly important for effectively controlling biosafety risks. Biosafety management should be continuously improved to deal with ineffective and excessive protection caused by various changes in experimental activities. Continuous improvement of biosafety management can be achieved through risk monitoring, regular review of safety indicators, and management reviews. This study will help laboratory managers to fully and accurately assess risks, as well as update risks and their control measures through risk monitoring, and the continuous improvement procedure established in the study has certain reference value for laboratories to effectively respond to emerging infectious diseases and avoid excessive protection.Keywords: risk assessment, risk monitoring, management review, continuous improvement, biosafety management

Chunrong Zuo,1,2 Nor Shafrin Ahmad,2 Lyu Zeng,1 Xiaogang Zhou,3 Feifei Li,2,4 Wuman Hong,2 Ping Gao1 1School of Education, Huainan Normal University, Anhui, 232038, People’s Republic of China; 2School of Educational Studies, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia; 3College of Physical Education and Health Science, Zhejiang Normal University, Jinhua, 321000, People’s Republic of China; 4Department of Art, Shandong Agricultural University, Shandong, 271000, People’s Republic of ChinaCorrespondence: Nor Shafrin Ahmad, School of Educational Studies, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia, Tel +60 465 325 69, Email sham@usm.my Xiaogang Zhou, College of Physical Education and Health Science, Zhejiang Normal University, Jinhua, 321000, People’s Republic of China, Tel +86 183 2904 0923, Email brucechou123456@gmail.comBackground and Objective: The mental health of economically disadvantaged college students in China is notably inferior to that of their non-disadvantaged peers. As such, these students necessitate a broader spectrum of psychological support beyond mere financial assistance. Seligman’s PERMA theory has established a compelling association between social support and positive emotions with subjective well-being. However, there is a scarcity of research focusing on character strengths within this framework, particularly the mechanisms that underlie their relationship. Hence, this study aims to examine the relationship between character strengths and subjective well-being among Chinese impoverished college students, while also delving into the chain mediating roles of perceived social support and positive emotions.Methods: A convenience sampling method was employed to collect cross-sectional data from impoverished college students. Participants (N=336, Mean age=20.67) were assessed using four instruments: the Chinese Virtues Questionnaire (CVQ-96), the Perceived Social Support Scale (PSSS), the Positive and Negative Affect Scale (PANAS), and the Satisfaction with Life Scale (SWLS).Results: Character strengths, perceived social support, positive emotions, and subjective well-being were all significantly positively correlated with each other (p< 0.01). In addition, regression analysis indicated that character strengths positively predicted perceived social support (β=0.71, p< 0.001), positive emotions (β=0.44, p< 0.001), and subjective well-being (β=0.52, p< 0.001). Perceived social support positively predicted positive emotions (β=0.34, p< 0.001), and subjective well-being (β=0.44, p< 0.001). Positive emotions positively predicted subjective well-being (β=0.88, p< 0.001). Furthermore, chain mediation analysis revealed that character strengths influenced subjective well-being both directly and indirectly through perceived social support and positive emotions.Conclusion: Perceived social support and positive emotions play a chain mediating role between character strengths and subjective well-being among impoverished college students.Keywords: character strengths, perceived social support, positive emotions, subjective well-being, Chinese, impoverished college students

Jiangping Zhang,&ast; Xinran Liu,&ast; Xiaorong Zhou, Yumei Li, Ke Chen, Tingting Kang, Wenting Du, Rongfei Suo The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Zhou, The Fifth Affiliated Hospital of Sun Yat-sen University, Meihua Road, Xiangzhou District, Zhuhai City, Guangdong Province, People’s Republic of China, Tel +86-756-15916286566, Email joxiaoro@163.comObjective: To explore the relationships among benefit finding (BF), self-management, and quality of life (QOL) among patients with COPD.Methods: A total of 205 patients with COPD were selected via a convenient sampling method. BF refers to the ability to find meaning or benefit from difficult situations. The Benefit Finding Scale (BFS), self-management scale, and 36-item Short-Form Health Survey (MOS SF-36) were used to investigate BF, self-management and QOL (including a physical component summary (PCS) and a psychological component summary (MCS)). Structural equation modeling was used to examine the relationships among BF, self-management and QOL in patients with COPD and to analyze the effects of BF and self-management on QOL.Results: The total QOL score of patients with COPD was 61.38± 21.15, and the PCS and MCS scores were 57.67± 23.60 and 65.09± 21.24, respectively. BF and self-management had positive predictive effects on both the PCS (βBF = 0.519, PBF = 0.012; βself-management = 0.473, Pself-management = 0.012) and MCS (βBF = 0.425, PBF = 0.013; βself-management = 0.535, Pself-management = 0.016) of patients with COPD, and self-management mediated the relationships of BF with the PCS (β = 0.144, P = 0.008) and MCS (β = 0.162, P = 0.007).Conclusion: The QOL of patients with COPD needs to be improved, especially in terms of physical aspects. Helping COPD patients obtain better BF not only helps them improve their PCS and MCS directly but also indirectly through enhancing self-management to improve their PCS and MCS.Keywords: COPD, benefit finding, self-management, quality of life

Huasheng Huang,1– 3 Shayong Peng,1– 3 Yongguang Wei,1– 3 Chenlu Lan,1– 3 Wei Qin,1– 3 Xiwen Liao,1– 3 Cheng-Kun Yang,1– 3 Guangzhi Zhu,1– 3 Xin Zhou,1– 3 Tao Peng1– 3 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, People’s Republic of China; 3Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Tao Peng; Xin Zhou, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6&num;, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86-771-5356528, Fax +86-771-5350031, Email pengtaogmu@163.com; zhouxin_gxmu@163.comBackground: This study aimed to identify dendritic cells (DCs) related genes in hepatocellular carcinoma (HCC) patients, establish DC-related subtypes and signatures, and correlate them with prognosis and treatment response.Methods: DC-related genes were screened using Weighted Gene Co-expression Network Analysis (WGCNA) based on RNA sequencing from the TCGA (374 samples), GSE14520 (242 samples), and GSE76427 datasets (115 samples), following immune infiltration assessment by the TIME method. Two DC-related subtypes in HCC were identified through unsupervised clustering. A DC-related signature (DCRS) predictive of overall survival was constructed using LASSO and Cox regression models, and validated across the three datasets. Additionally, genetic mutation characteristics, immune infiltration levels, and treatment sensitivity were explored in DCRS risk groups. The expression levels of DCRS genes and risk scores were validated in the transcriptome of 13 HCC patients receiving combined targeted therapy and immunotherapy in the Guangxi cohort using Wilcoxon test.Results: A signature consisting of 13 genes related to DCs was constructed, and the superior prognostic consistency of the low DCRS risk group was validated across the TCGA (P=0.003), GSE76427 (P=0.005), and GSE14520 (P=0.047) datasets. Furthermore, in the 147-sample transarterial chemoembolization (TACE) treatment dataset GSE104580, the response group exhibited lower risk scores than the non-response group (P=0.01), whereas in the 140-sample Sorafenib treatment dataset GSE109211 (P=0.041) and the 17-sample anti-PD-1 treatment dataset GSE202069 (P=0.027), the risk scores were higher in the response group. We also validated the gene expression levels of DCRS and the higher risk scores in the response group of the Guangxi cohort (P=0.034).Conclusion: A DCRS consisting of 13 genes was established in HCC, facilitating the prediction of patient prognosis and responsiveness to TACE, targeted therapy, and immunotherapy. Keywords: hepatocellular carcinoma, dendritic cells, prognosis, immunotherapy, targeted therapy

Ranran Lu,1,2,&ast; Xu Zhou,1,2,&ast; Lijie Zhang,3 Mengdie Hao,1,2 Xinling Yang1,4 1Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang, People’s Republic of China; 2Xinjiang Key Laboratory of Neurological Disease Research, Ürümqi, Xinjiang, People’s Republic of China; 3Xinjiang Production and Construction Corps Hospital, Ürümqi, Xinjiang, People’s Republic of China; 4Xingjiang Medical University, Ürümqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinling Yang, Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, No. 38, Nanhu East Road, Shuimogou District, Urumqi, Xinjiang, 830026, People’s Republic of China, Tel +86-13139699251, Email yangxinling2014@163.comBackground: Parkinson’s disease (PD) is a movement disorder characterized by the progressive loss of dopamine neurons. Microglia-mediated neuroinflammation drives disease progression and becomes a critical factor in neuronal degeneration. Recent studies have found that nuclear factor-erythroid 2-related-2 (Nrf2) expression levels are reduced during aging and neurodegenerative diseases, but its regulatory mechanism on microglia-induced neuroinflammation has not been fully elucidated.Methods: In vivo, we used the intraperitoneal injection of the neurotoxic drug neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish an animal model of PD and, at the same time, administered Nrf2 inhibitors ML385 and dimethyl fumarate to regulate Nrf2 protein levels. In vitro, we used si-RNA to knock out the Nrf2 gene to intervene in BV2 cells and used lipopolysaccharide (LPS) to stimulate and induce the cell model.Results: The study found that inhibition of Nrf2 expression aggravated the motor defects of PD mice, accompanied by a significant loss of dopaminergic neurons in the substantia nigra and striatum of the brain. In addition, after inhibition of Nrf2, the malondialdehyde (MDA) level in the substantia nigra of the midbrain of mice increased, and the levels of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) decreased, accompanied by the proliferation of microglia and astrocytes. In addition, the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, the assembly of apoptosis-associated speck-like protein containing a CARD (ASC) protein in microglia, and the release of downstream inflammatory factors caspase-1 and interleukin (IL)-1β, were aggravated. At the cellular level, it was found that knocking out the expression of Nrf2 would aggravate the activation of NLRP3 inflammasomes and the assembly of ASC in LPS-induced BV2 cells.Conclusion: Inhibited Nrf2 activity can reduce the downstream antioxidant enzyme HO-1 and antioxidant levels, induce NLRP3 inflammasome activation and ASC protein assembly in microglia, and ultimately aggravate PD inflammatory response and dopamine neuron degeneration.Keywords: Parkinson’s disease, Nrf2, oxidative stress, NLRP3 inflammasome, microglia

Xia Zhou,1 Wei Feng,1 Xiaolong Wang,2 Zejun Niu,1 Peng Wang,1 Li Yuan,1 Pei Wang1 1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province,People’s Republic of China; 2Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Pei Wang, Email wangpei@qdu.edu.cnPurpose: Anesthesia for metabolic–bariatric surgery is challenging due to the increased risk of opioid-related adverse events. The purpose of the investigation was to assess the feasibility and efficacy of multimodal opioid-free general anesthesia with transversus abdominis plane (TAP) block for laparoscopic sleeve gastrectomy in contrast with conventional opioid-based general anesthesia.Patients and Methods: Eighty patients who underwent laparoscopic sleeve gastrectomy and eventually 71 patients included in the analysis. They were randomly divided into an opioid-based anesthesia group (control group) with sufentanil or opioid-free anesthesia (OFA) group. Esketamine, dexmedetomidine, and TAP were as part of the OFA. Sevoflurane, dexamethasone, and muscle relaxants were administered intraoperatively to all patients. The primary outcome was antiemetic rescue within 24 hours after surgery. The secondary outcomes included pain scores, analgesic needs, extubation time, complications, the hemodynamic changes, and duration of hospital stay.Results: In contrast with the control group, the need for antiemetic rescue was significantly reduced (p= 0.035). Furthermore, the visual Analog Scale (VAS) for postoperative pain was considerably lower in the OFA group (p < 0.01) than it was in the control group. There was no significant difference in the need for analgesic rescue in both groups (p= 0.155). Extubation time and post-anesthesia care unit (PACU) stay duration were equal between the two groups (p =0.328 and p =0.54). At the end of the surgery and after extubation, hemodynamic changes was more pronounced in the OFA group (p =0.027) than the control group. The length of the hospital stay was significantly shorter compared with the control group (p =0.002).Conclusion: OFA with TAP results in a significant decrease in the need for antiemetic rescue, a lower level of pain after the surgery, and a shorter hospital stay in contrast with anesthesia based on opioids.Keywords: opioid-free, nerve block, esketamine, post-operative nausea and vomiting, bariatric surgery

Xinyuan Zhou,1,2,&ast; Fuxiang Zhu3,&ast; 1Department of Nephrology, the First People’s Hospital of Pinghu, Jiaxing, Zhejiang, People’s Republic of China; 2Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuxiang Zhu, Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, People’s Republic of China, Email zfxywh@163.comPurpose: Depression is a major concern in maintenance hemodialysis. However, given the elusive nature of its risk factors and the redundant nature of existing assessment forms for judging depression, further research is necessary. Therefore, this study was devoted to exploring the risk factors for depression in maintenance hemodialysis patients and to developing and validating a predictive model for assessing depression in maintenance hemodialysis patients.Patients and Methods: This cross-sectional study was conducted from May 2022 to December 2022, and we recruited maintenance hemodialysis patients from a multicentre hemodialysis centre. Risk factors were identified by Lasso regression analysis and a Nomogram model was developed to predict depressed patients on maintenance hemodialysis. The predictive accuracy of the model was assessed by ROC curves, area under the ROC (AUC), consistency index (C-index), and calibration curves, and its applicability in clinical practice was evaluated using decision curves (DCA).Results: A total of 175 maintenance hemodialysis patients were included in this study, and cases were randomised into a training set of 148 and a validation set of 27 (split ratio 8.5:1.5), with a depression prevalence of 29.1%. Based on age, employment, albumin, and blood uric acid, a predictive map of depression was created, and in the training set, the nomogram had an AUC of 0.7918, a sensitivity of 61.9%, and a specificity of 89.2%. In the validation set, the nomogram had an AUC of 0.810, a sensitivity of 100%, and a specificity of 61.1%. The bootstrap-based internal validation showed a c-index of 0.792, while the calibration curve showed a strong correlation between actual and predicted depression risk. Decision curve analysis (DCA) results indicated that the predictive model was clinically useful.Conclusion: The nomogram constructed in this study can be used to identify depression conditions in vulnerable groups quickly, practically and reliably.Keywords: nomogram, depression, maintenance hemodialysis, risk factors, prediction

Qian Liu,1,&ast; Jun Zhang,2,&ast; Mingqin Wei,1 Xue Zhou,3 Hao Sun,4 Youhong Dong,1 Dongdong Zhang1 1Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 2Department of Neurology, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 3Department of Pathology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 4Department of Oncology, Baokang County People’s Hospital, Xiangyang, 441000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youhong Dong, Dongdong Zhang, Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Jiefang Road No. 15, Xiangyang, Hubei, 441000, People’s Republic of China, Tel +8615072278600, Email dongyouhong2005@163.com; zhangdongdong@whu.edu.cnBackground: Pulmonary spindle cell carcinoma (PSCC), a highly malignant tumor, often exhibits cell pleomorphism, a histopathological characteristic. Owing to its extremely low incidence, atypical imaging and clinical presentations, and insufficient awareness among clinicians, PSCC is often misdiagnosed, which results in delays in treatment. Herein, we reported a rare case of PSCC that was initially misdiagnosed as granulomatous inflammation.Case Presentation: A 66-year-old male visited a local hospital with symptoms such as cough and hemoptysis. A computed tomography (CT) scan of the chest revealed a mass in his right lung, and no mediastinal lymphadenopathy was observed. Bronchoscopy showed no major abnormalities, and the results of fine needle aspiration biopsy showed granulomatous inflammation. Even though the patient received anti-infection treatment, his symptoms did not improve markedly. After two months, a follow-up CT scan of the lung showed a noticeably enlarged mass accompanied by multiple instances of mediastinal lymphadenopathy in the upper lobe of the right lung. Consequently, he underwent a second CT-guided lung biopsy at our hospital. The pathology report indicated PSCC. Due to financial constraints, genetic testing was not performed. Given his poor overall physical condition, the patient was unable to undergo systemic chemotherapy and instead received palliative radiotherapy. The prescribed radiotherapy dose for the right upper lobe lung cancer and multiple metastatic lymph nodes was 60 Gy, administered in 30 fractions. Unfortunately, he failed to adhere to scheduled follow-ups and succumbed to the disease 6 months later, as confirmed during a telephone follow-up.Conclusion: PSCC is a rare but highly malignant lung cancer. Multiple pathological biopsies are necessary to accurately and promptly diagnose the disease, which is crucial for early treatment intervention as well as improving patient prognosis.Keywords: pulmonary spindle cell carcinoma, granulomatous inflammation, radiotherapy, multiple pathological biopsies

Ying Yang,1– 3,&ast; Bixia Zhou,1,2,&ast; Min Li,4 Yishuai Sun,1,2 Xulei Jiang,1,2 Xinxin Zhou,1,2 Chengjun Hu,1,2 Dou Zhang,3 Hang Luo,3 Wuyuan Tan,1,2 Xinghua Yang,1,2 Shaorong Lei1,2 1Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, People’s Republic of China; 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Oncology, Changsha Central Hospital, University of South China, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaorong Lei, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email leishaorong@csu.edu.cn Xinghua Yang, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email yxhua8805@sina.comPurpose: The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect.Methods: In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential.Results: We found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing.Conclusion: Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios. Keywords: nanomaterials, hybrid hydrogel, bone scaffolds, craniofacial bone defects, bone regeneration

Xun Zhou,1,2,&ast; Jingzhou Liu,2,&ast; Shuang Xiao,2,3,&ast; Xiaoqing Liang,1,2 Yi Li,2 Fengzhen Mo,3 Xin Xin,2 Yang Yang,2 Chunsheng Gao1,2 1School of Pharmacy, Henan University, Kaifeng, People’s Republic of China; 2State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China; 3School of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengzhen Mo; Xin Xin, Email mofzhen@163.com; 13511014091@163.comAbstract: Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.Keywords: AAV engineering, capsid modification, surface tethering, virus load, rational design, directed evolution, machine learning

Xiaoming Zhou,1 Weiwei Shen,1 Jue Zhu,2 Yichen Chen,2 Jing Zhang2 1Department of Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People’s Republic of China; 2Department of Gynecology, Ningbo Women & Children’s Hospital, Ningbo, Zhejiang, 315010, People’s Republic of ChinaCorrespondence: Jing Zhang, Department of Gynecology, Ningbo Women & Children’s Hospital, 339 Liuting Street, Haishu District, Ningbo, 315010, Zhejiang, People’s Republic of China, Tel +86-15867877000, Email jzhang_nbdr@outlook.comPurpose: To investigate the association between the oxidative balance score (OBS) and endometriosis.Methods: This cross-sectional study used four cycles of the National Health and Nutrition Examination Survey (NHANES) (1999– 2000, 2001– 2002, 2003– 2004, and 2005– 2006). OBS involved 16 dietary nutrients and 4 lifestyle factors, including 5 pro-oxidants and 15 anti-oxidants. According to weighted quartiles, the OBS was divided into four categories: < 12.54, 12.54– 18.70, 18.71– 24.68, and > 24.68. Endometriosis was diagnosed based on a question from the reproductive health questionnaire. Weighted multivariate logistic analysis was used to investigate the association between OBS and endometriosis. Subgroup analysis was performed based on menstrual regularity and female hormone use.Results: A total of 5095 women were included, with 1140 (22.37%), 1232 (24.18%), 1224 (24.02%), and 1499 (29.42%) women in the OBS < 12.54, of 12.54– 18.70, of 18.71– 24.68, and > 24.68 categories, respectively. After adjusting age, race, family poverty-to-income ratio (PIR), education level, uterine fibroids, menstrual regularity, oophorectomy, female hormone use, hypertension, dyslipidemia, and steroid drug, a high OBS (> 24.68) was found to be associated with lower odds of endometriosis [odds ratio (OR) = 0.70, 95% confidence interval (CI): 0.50– 0.97, P = 0.033] compared to a low OBS (< 12.54). The similar result was also found in women with irregular menstruation (OR = 0.58, 95% CI: 0.37– 0.91, P = 0.020) and with female hormone use (OR = 0.71, 95% CI: 0.52– 0.98, P = 0.037).Conclusion: A high OBS was associated with lower odds of endometriosis, especially in women with irregular menstruation and female hormone use.Keywords: Oxidative balance score, endometriosis, menstruation, female hormones, NHANES

Xiaowei Zhou, Liyong Zou, Haoyue Deng, Yuanqun Zhou, Yue Wu, Xingnan Ouyang, Liangming Liu, Li Wang,&ast; Tao Li&ast; Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang; Tao Li, Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China, Email wangli8134@163.com; lt200132@tmmu.edu.cnPurpose: Cold seawater immersion aggravates hemorrhagic shock-induced homeostasis imbalance and organ dysfunction, leading to increased mortality. Previous studies have shown that treatments targeting oxidative stress and mitochondrial dysfunction have limited efficacy for cold seawater immersion combined with hemorrhagic shock (SIHS). Thus, the mechanisms responsible for SIHS need further investigation.Methods and Results: Data from the hemorrhagic shock transcriptome and cold seawater immersion targets used for bioinformatics analysis revealed the involvement of endoplasmic reticulum stress (ERS) in SIHS occurrence and progression. Based on these findings, the effects and possible mechanism of inhibiting ERS in SIHS rats were investigated. SIHS causes a lethal triad and impairment of vital organ function, leading to death. Compared to lactated Ringer’s solution, the ERS inhibitor 4-phenylbutyric acid (PBA)significantly ameliorated acidosis and coagulopathy and protected vital organ function while prolonging survival and the golden treatment time. Through target screening and validation, 7 targets were identified for the ERS inhibitor PBA for the treatment of SIHS, among which S1PR1, MMP8 and CFTR may play more important roles.Conclusion: ERS plays a crucial role in the progression of SIHS. Inhibition of ERS caused by SIHS alleviates the lethal triad, protects organ function, and prolongs survival and the golden treatment time. The ERS inhibitor PBA may be an effective therapeutic measure for treating SIHS.Keywords: cold seawater immersion, hemorrhagic shock, lethal triad, organ function, ER stress, 4-phenylbutyric acid

Shuang Du,1,&ast; Ke Lin,2,&ast; Jing Li,3 Xin Zhou,4 Chaolan Wang,2 Jun Liu,3 Na Li,2 Jian Chen2 1Department of Rehabilitation Medicine, The First People’s Hospital of Jin Tang County, Chengdu, Sichuan, 610400, People’s Republic of China; 2Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 4Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Chen, Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China, Tel +86-10-18908176456, Email chenjian792@163.comPurpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD.Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure.Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07– 1.31, p< 0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06– 1.24, p< 0.001). Compared to the medium group (Q2 ≥ 3.15, < 4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08– 2, p=0.013), and 1.31 (95% CI: 1.06– 1.61, p=0.013) for 90-day mortality in the high group (Q3≥ 4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468– 0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141– 1.509, p< 0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102– 1.386, p< 0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results.Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation.Keywords: COPD, serum phosphate, mortality, MIMIC-IV, critically ill

Qiqi Cheng,1 Xiaolin Zhou,1 Peng Wang,2 Rong Liu,3 Qiang Liu1 1Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 2Department of Clinical Laboratory, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 3Department of Ultrasound, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Qiang Liu, Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Tel +86 13720181669, Email liuqiang@ctgu.edu.cnAbstract: We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient’s blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.Keywords: infective endocarditis, Neisseria sicca, aortic valve, bacteremia

Xu Zhang,1,&ast; Xue Zhou,2,&ast; Wenhao Zhai,1,&ast; Jing Cui,1 Ziyi Pan,1 Liuyi Du,1 Linlin Wen,1 Rongrong Ye,1 Boya Zhang,1 Lei Huang,1 Daowei Li,1 Chungang Wang,2 Hongchen Sun1 1Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Chemistry, Northeast Normal University, Changchun, 130024, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daowei Li; Lei Huang, Email jluldw@jlu.edu.cn; huanglei17@mails.jlu.edu.cnBackground: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue.Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP–AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining.Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin.Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis. Keywords: nanocomposite hydrogel, vital pulp therapy, pulpitis, p38 signaling pathway

Xiamin Pu,1 Houqiang Huang,2 Xiaolei Zhao,3 Feng Liu,1 Yebo Leng,4 Ya Deng,5 Lingyi Huang,5 Xingchen Zhou,5 Fen Xu,1 Yongli Huang,6 Shengmin Guo2 1Department of Cardiovascular Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5School of Nursing, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Outpatient, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Shengmin Guo, Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-13980255653, Email 2930773281@qq.comBackground: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients.Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI.Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended.Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P< 0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p< 0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p< 0.05).Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.Keywords: acute myocardial infarction, older, frailty, neuromuscular electrical stimulation, PCI

Jun Zhang,1,&ast; Yinyu Wu,1,&ast; Yuanlin Du,1,&ast; Yunxia Du,1 Daiqin Bao,1 Haibin Lu,2 Xiaoqiong Zhou,1 Rui Li,1 Haoyu Pei,1 Han She,1 Qingxiang Mao1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Intensive Care Unit, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han She; Qingxiang Mao, Email mazuishehan@163.com; qxmao@tmmu.edu.cnBackground: This study aimed to discover diagnostic and prognostic biomarkers for sepsis immunotherapy through analyzing the novel cellular death process, cuproptosis.Methods: We used transcriptome data from sepsis patients to identify key cuproptosis-related genes (CuRGs). We created a predictive model and used the CIBERSORT algorithm to observe the link between these genes and the septic immune microenvironment. We segregated sepsis patients into three subgroups, comparing immune function, immune cell infiltration, and differential analysis. Single-cell sequencing and real-time quantitative PCR were used to view the regulatory effect of CuRGs on the immune microenvironment and compare the mRNA levels of these genes in sepsis patients and healthy controls. We established a sepsis forecast model adapted to heart rate, body temperature, white blood cell count, and cuproptosis key genes. This was followed by a drug sensitivity analysis of cuproptosis key genes.Results: Our results filtered three key genes (LIAS, PDHB, PDHA1) that impact sepsis prognosis. We noticed that the high-risk group had poorer immune cell function and lesser immune cell infiltration. We also discovered a significant connection between CuRGs and immune cell infiltration in sepsis. Through consensus clustering, sepsis patients were classified into three subgroups. The best immune functionality and prognosis was observed in subgroup B. Single-cell sequencing exposed that the key genes manage the immune microenvironment by affecting T cell activation. The qPCR results highlighted substantial mRNA level reduction of the three key genes in the SP compared to the HC. The prediction model, which combines CuRGs and traditional diagnostic indicators, performed better in accuracy than the other markers. The drug sensitivity analysis listed bisphenol A as highly sensitive to all the key genes.Conclusion: Our study suggests these CuRGs may offer substantial potential for sepsis prognosis prediction and personalized immunotherapy.Keywords: sepsis, cuproptosis, prognosis, immune cell infiltration, nomogram

Bo Zhang,1,2 Minmin Guo,2 Ting Dong,2 Huajuan Yang,2 Qiujuan Zhang,2 Quanxin Yang,2 Xiaoqian Zhou,2 Cuiping Mao,2 Ming Zhang1 1Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Department of Medical Imaging, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of ChinaCorrespondence: Ming Zhang, Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email zmmri@163.comPurpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP.Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc.Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton’s Depression Scale (HAMD) scores (r = − 0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC.Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.Keywords: low back pain, nucleus accumbens, resting-state functional connectivity, dynamic causal modelling

Xiaoling Zhou,1,2 Jing Wu,3 Ying Liu,3 Yuzhong Yan,2 Geyao Zhou,1 Ming Li1,4 1School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, People’s Republic of China; 2Research Department, Shanghai University of Medicine&Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 3School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Party Committee office, Tongji University Affiliated Shanghai East Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ming Li; Geyao Zhou, Email liming1070202306@163.com; zhougeyao@163.comBackground: The health status of the occupational population is critical to the development of countries and regions as it is the main force of social and economic development. However, there is a dearth of comprehensive and systematic indicators to evaluate the health of occupational groups. This study aimed to construct a multi-dimensional evaluation index system for the general population.Methods: This study combined a literature review and initially established a multidimensional health system framework for the occupational population based on health ecology theory and then used two rounds of Delphi expert consultation to construct the final multidimensional health index system for the occupational population. Fifteen experts from related fields were selected for two rounds of Delphi expert consultation.Results: The recovery rates of the two rounds of expert questionnaires were 100.00% and 93.33% respectively, the expert authority coefficient were 0.90, and the Kendall’s coordination coefficients of the first and second level indexes were 0.32 and 0.42 (P ≥ 0. 001). The final index system includes four primary indicators (individual characteristics, health knowledge, health behavior, and health skills), 13 second-level indicators, and 41 third-level indicators; the weight coefficients of the four primary health dimensions are relatively close, and the “health knowledge” is slightly higher.Conclusion: The multi-dimensional health index system of the occupational population established in this study is comprehensive and reasonable from the perspective of health ecology, which can provide a solid foundation for the further development of a comprehensive health status prediction model for the occupational population.Keywords: health ecology, delphi method, multidimensional health, index system

Mingming Li,1,2,&ast; Xin Zhou,1,&ast; Doudou Huang,1,&ast; Yingkui Zhao,2 Jiani Chen,2 Zhiying Dong,1 Wansheng Chen,1,2 Feng Zhang,2 Lianna Sun1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianna Sun; Wansheng Chen, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Tel +86-13818946096 ; +86-15901818646, Email sssnmr@163.com; chenwansheng@shutcm.edu.cnBackground: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties.Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS.Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins.Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin’s action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.Keywords: diabetes mellitus, streptozotocin, metformin, davidiin, metabolomics

Di Zhang,1,&ast; Yu Guan,1,&ast; Xiuxiu Zhou,1 Mingzi Zhang,2 Yu Pu,1 Pengchen Gu,2 Yi Xia,1 Yang Lu,2 Jia Chen,2 Wenting Tu,1 Kunyao Huang,2 Jixin Hou,2 Hua Yang,2 Chicheng Fu,2 Qu Fang,2 Chuan He,2 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Scientific Research Department, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan; Shiyuan Liu, Department of Radiology, Second Affiliated Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +13564684699 ; +13761304518, Fax +86 21 63587668, Email czyxfl@smmu.edu.cn; radiology_cz@163.comPurpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.Results: The RSA and RSA% were significantly different among the three groups (p< 0.05) and related to FEV1/FVC (r = − 0.70, p < 0.001; r = − 0.67, p < 0.001), FEV1% predicted (r = − 0.60, p = 0.002; r = − 0.57, p = 0.004), MEF50% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001), MEF75% predicted (r = − 0.71, p < 0.001; r = − 0.60, p = 0.002) and MMEF 75/25% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001).Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.Keywords: COPD, small airway disease, CT, fluid dynamics

Ne Yan,1,2 Ying Long,2 Huiling Yuan,3 Xiaofei Zhou,3,4 Bin Xie,2 Ying Wang1,3 1Department of Psychiatry, Xi’an Honghui Hospital, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Department of Psychology, Xi’an Physical Education University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Psychiatry, Xi’an International Medical Center Hospital, the Affiliated Hospital of Northwest University, Xi’an, Shaanxi, People’s Republic of China; 4The College of Life Sciences and Medicine, Northwest University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Ying Wang, Xi’an Honghui Hospital, 666 Jianyuan 2nd Road, Economic and Technological Development Zone, Xi’an City, Shaanxi Province, 710000, People’s Republic of China, Email fgx995@163.comBackground: The 18– 24 age group has a much higher rate of depression risk than other age groups, and this age group has the highest proportion among users of mobile social media. The relationship between the use of mobile social media and depressive mood is inconsistent and the mechanism of action is controversial.Purpose: This study explored the relationship among the intensity of social media use, upward social comparison, cognitive overload and depressive mood.Methods: In this research, we used the Brief Self-rating Depression Scale (PHQ-9), the Social Media Usage Intensity Questionnaire, the Social Comparison Scale on Social Networking Sites and the Social Networking Site Cognitive Overload Scale to investigate the depressive mood and mobile social media use of 568 college students.Results: The intensity of mobile social media use, social networking site upward social comparison, and social networking site cognitive overload are all positively correlated with depressive mood. The intensity of mobile social media use has a positive predictive effect on depressive mood, with upward social comparison and cognitive overload acting as independent mediators in the relationship between mobile social media use intensity and depressive symptoms, as well as exhibiting a chained mediating effect of upward social comparison-cognitive overload.Conclusion: The upward social comparison and cognitive load that occur during the use of mobile social media are important predictive factors for the occurrence of depressive mood. This study is a supplement to the mechanism of the relationship between mobile social media use and depression, providing more evidence-based evidence and intervention directions for university teachers, mobile social media developers, and psychologists.Keywords: mobile social media, upward social comparison, cognitive overload, depressive mood, chain mediation

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

Yaping Jiang,1,&ast; Yuying Cai,1,&ast; Xin Zhang,1 Li Chen,1 Xingtao Zhou,2 Yihui Chen1 1Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Eye Institute and Department of Ophthalmology, Institute for Medical and Engineering Innovation, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingtao Zhou, Eye Institute and Department of Ophthalmology, Institute for Medical and Engineering Innovation, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, No. 19 Baoqing Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email doctzhouxingtao@163.com Yihui Chen, Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai, 200090, People’s Republic of China, Email 1300089@tongji.edu.cnBackground: Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends.Methods: We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks.Results: From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies.Conclusion: This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.Keywords: laser, bibliometric, research trend, systematic review, CiteSpace

Xiaoyu Zhou,1– 3 Fei Du,1– 3 Wei Peng,4 Li Bai,5 Leyi Peng,1– 3 Xiaorong Hou1– 3 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Medical Data Science Academy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Chongqing Engineering Research Center for Clinical Big Data and Drug Evaluation, Chongqing, 400016, People’s Republic of China; 4The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, People’s Republic of China; 5Hospital of Zigong Mental Health Central, Sichuan, 643021, People’s Republic of ChinaCorrespondence: Xiaorong Hou, Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email xiaoronghou@cqmu.edu.cnPurpose: Long-term care facilities are increasingly challenged with meeting the diverse healthcare needs of the elderly population, particularly concerning medication management. Understanding medication information literacy and behavior among this demographic is imperative. Therefore, this qualitative study aims to explore medication information literacy and develop distinct medication profiles among elderly long-term care residents.Material and Methods: In this study, we conducted in-depth semi-structured interviews with 32 participants aged 65 or older residing in a long-term care facility. The interviews were designed to explore participants’ understanding of medication information, medication management practices, and experiences with healthcare providers. Thematic analysis was employed to analyze the interview data, allowing for the identification of common patterns and themes related to medication-taking behavior among the elderly residents.Results: The thematic analysis revealed four distinct medication behavior profiles among the elderly long-term care residents: (1) Proactive Health Self-Managers, (2) Medication Information Adherents, (3) Experience-Based Medication Users, and (4) Nonadherent Medication Users. These findings provide valuable insights into the diverse approaches to medication management within long-term care facilities and underscore the importance of tailored interventions to support the specific needs of each profile.Conclusion: This study highlights the necessity for tailored medication education and support to optimize medication management for the elderly. With the aging population expansion, addressing the unique medication challenges within long-term care facilities becomes increasingly critical. This research contributes to ongoing endeavors to enhance healthcare services for the elderly, striving for safer and more effective medication-taking behavior.Keywords: medication information literacy, medication profile, long-term care facility, qualitative study, elderly

Yiyang Gong,1,2,&ast; Minqin Zhou,2,&ast; Yanting Zhu,2,&ast; Jingying Pan,2 Xuanrui Zhou,2 Yike Jiang,2 Hong Zeng,2 Hao Zheng,2 Xitong Geng,2 Da Huang1 1Department of Thyroid Surgery; Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Tel +13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma is the most common primary liver cancer, with poor prognosis. Complex immune microenvironment of the liver is linked to the development of HCC. PVALB is a calcium-binding protein which has been described as a cancer suppressor gene in thyroid cancer and glioma. Nevertheless, the role of PVALB in HCC is unknown.Materials and Methods: We obtained data from TCGA and GSE54236 datasets. MCP-counter, WGCNA and LASSO model were applied to identify PVALB. With UALCAN, MethSurv, and other websites, we probed the expression, methylation and survival of PVALB. LinkedOmics and GSEA were adopted for functional analysis, while TIMER, TISIDB, Kaplan-Meier plotter, TIDE databases were utilized to evaluate the relevance of PVALB to the tumor immune microenvironment and predict immunotherapy efficacy. TargetScan, DIANA, LncRNASNP2 databases and relevant experiments were employed to construct ceRNA network. Finally, molecular docking and drug sensitivity of PVALB were characterized by GeneMANIA, CTD, and so on.Results: PVALB was recognized as a gene associated with HCC and NK cell. Its expression was down-regulated in HCC tissue, which lead to adverse prognosis. Besides, the hypomethylation of PVALB was related to its reduced expression. Notably, PVALB was tightly linked to immune, and its reduced expression attenuated the anticancer effect of NK cells via the Fas/FasL pathway, leading to a adverse outcome. The lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB axis may regulate the PVALB expression. Finally, we found immunotherapy might be a viable treatment option.Conclusion: In a word, PVALB is a prognostic indicator, whose low expression facilitates HCC progression by impacting NK cell infiltration.Keywords: PVALB, hepatocellular carcinoma, immune, ceRNA, bioinformatics, prognostic factor

Weiwei Xie,1,&ast; Junqi Luo,1,&ast; Ruowei Tang,2,&ast; Xuan Zhou,3 Xiaohong Wang,4,5 Guojie Wang,1,5 Yaqin Zhang1 1Department of Radiology, the Fifth Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China; 2Department of Radiology, Beijing Friendship Hospital, Beijing, People’s Republic of China; 3Departments of Pathology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, People’s Republic of China; 4Department of Radiology, the Third Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi Prefecture, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqin Zhang; Guojie Wang, Department of Radiology, the Fifth Hospital of Sun Yat-sen University, 52 East Meihua Road, Xiangzhou District, Zhuhai, Guangdong Province, People’s Republic of China, Email zhyaqin@mail.sysu.edu.cn; wanggj5@mail.sysu.edu.cnPurpose: To explore the clinical and imaging features of rare site Kimura’s disease (KD).Methods: Retrospective analysis was conducted on the clinical manifestations, laboratory examinations, and imaging features of five patients with rare site KD. All imaging data, including the location, quantity, size, uniformity, boundary, and enhanced appearance of the lesion were evaluated by two independent radiologists.Results: Of the five patients, four were asymptomatic, and one experienced localized skin itching. Four cases involved subcutaneous nodules in the upper arm, while one was in the inguinal region. The main manifestations were single (three cases) or multiple (two cases) subcutaneous nodules/masses, with three patients accompanied by local lymph node enlargement. Four patients exhibited elevated eosinophil counts in their peripheral blood. Four patients had lesions with vascular flow voids; in three of these, the lesions also showed prominent enhancement. Notably, the lesion in a 5-year-old did not show vascular flow voids but displayed significant enhancement. Additionally, two patients showed edema around the lesions.Conclusion: The presence of solitary or multiple subcutaneous nodules/masses in the upper arm or inguinal area, accompanied by lymph node enlargement, elevated eosinophils in the peripheral blood, and the observation of internal vascular within the lesion, can aid in the diagnosis of KD occurring in uncommon anatomical locations.Keywords: Kimura disease, increased eosinophils, image, uncommon anatomical locations

Qiaoling Wei,1– 3,&ast; Liangliang Niu,1– 3,&ast; Xianjin Zhou,4 Han Chen,1,2 Rui Jiang1– 3 1Department of Ophthalmology, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, People’s Republic of China; 3Ocular Trauma Center, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Jiang; Han Chen, Tel +86-21-64377134, Fax +86-21-6477134, Email 2jiang@163.com; avnus@163.comPurpose: To evaluate the effects of retinal surgery on the ocular surface and corneal subbasal nerve plexus (SNP).Methods: Ninety-eight patients undergoing 23-gauge pars plana vitrectomy for various vitreoretinal disorders were prospectively studied. We collected detailed operative and perioperative data, measuring dry eye syndrome (DED) severity and Ocular Surface Disease Index (OSDI) scores before surgery and at postoperative intervals. In vivo confocal microscopy (IVCM) quantified SNP and dendritic cell (DC) densities.Results: Fifty-three patients were analyzed. Post-surgery, OSDI scores rose from a baseline of 5.5 ± 3.5 to 12.24 ± 6.5 at one month, later reducing to 7.8 ± 4.0 after a year. DED severity increased from 0.6 ± 0.6 initially to 1.6 ± 0.6 at three months, returning to near baseline (0.9 ± 0.6) one year after surgery. DC densities increased notably by the third (58.85 ± 75.6 cells/mm²) and ninth (59.95 ± 86 cells/mm²) postoperative months, especially in patients undergoing combined phacoemulsification, vitrectomy, and C3F8 gas tamponade. SNP parameters, particularly nerve fiber density and length, showed significant declines one month post-surgery, not recovering to baseline levels within a year. Fiber density dropped from 19.06 ± 8.3 fibers/mm² preoperatively to 4.68 ± 4.8 fibers/mm² at one month, partially recovering to 10.64 ± 8.2 fibers/mm² at twelve months. Fiber length decreased from 13.31 ± 3.2 mm/mm² to 6.86 ± 3.4 mm/mm² at one month, later improving to 9.81 ± 4.5 mm/mm² at twelve months, notably in patients with silicone oil (SiO2) tamponade.Conclusion: Retinal surgery, especially when combined with phacoemulsification and C3F8 or SiO2 tamponade, significantly affects ocular surface integrity and SNP density, with these changes lasting up to a year. Expanded studies with more patients and longer follow-up, using finer 25- and 27-gauge vitrectomy tools, are recommended to confirm and extend these findings.Keywords: corneal subbasal nerve plexus, ocular surface, retinal surgical procedures, confocal microscopy, dry eye syndrome after vitrectomy, intraocular surgery

Shaofei Zhang,1– 3,&ast; Xu Ouyang,1– 3,&ast; Kefei Yang,2,3,&ast; Yunyun Shen,2,3 Siyuan Zheng,1– 3 Ruoqi Wang,1– 3 Xuanlian Sheng,1– 3 Menglin Ge,1– 3 Meng Yang,1– 3 Xiaoqin Zhou1,2 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei City, People’s Republic of China; 2Second Affiliated Hospital of Anhui Medical University, Hefei City, People’s Republic of China; 3Chaohu Hospital of Anhui Medical University, Hefei City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqin Zhou, Second Affiliated Hospital of Anhui Medical University, Hefei City, People’s Republic of China, Tel +8613865913378, Email zhouxqlulu@126.comPurpose: In schizophrenia, aggressive conduct is frequent. And depressed mood can also contribute to the occurrence of aggressive behaviors. The aim of this study was to investigate the risk factors for the occurrence of aggression in stable schizophrenia patients in rural China, mainly to investigate the role of depressed mood in the occurrence of aggression in schizophrenia patients.Patients and Methods: This is a cross-sectional study conducted in the townships surrounding Chaohu City, Anhui Province, China. Patients’ depressive mood was evaluated using the PHQ-9 (The 9-item Patient Health Questionnaire). Patients’ aggressiveness was evaluated using the Modified Overt Aggression Scale (MOAS). A score of ≥ 4 was used as a threshold and divided into aggressive and non-aggressive groups.Results: This study comprised a total of 821 schizophrenia patients. Among them, the prevalence of having aggressive behavior was 18.8%. After correcting for confounders, logistic regression analysis showed that low education level (OR=0.470, 95% CI 0.254– 0.870; p=0.016), living with family (OR=0.383, 95% CI 0.174– 0.845; p=0.017) depressed mood (OR=1.147, 95% CI 1.112– 1.184; p< 0.001) was significantly associated with the risk of aggressive behavior in patients with schizophrenia. Multivariate linear regression indicated that higher levels of aggression were linked with lower levels of education and higher depressive mood.Conclusion: This study suggests that aggression is more common in patients with stable schizophrenia, and lower levels of education and higher levels of depression are associated risk factors for its occurrence. Living alone may be helpful in reducing the likelihood of aggression.Keywords: schizophrenia depression aggression Chinese

Yue Chen,1,&ast; Aili Gao,1,&ast; Yanan Ke,1 Xin Zhou,1 Li Lin,2 Sha Lu,2 Yumei Liu1 1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Liu, Director of Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, People’s Republic of China, Tel/Fax +86- 20-83593472, Email liuyumei1109@163.comAbstract: Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid–Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.Keywords: protothecosis, Prototheca wickerhamii, terbinafine

Shipeng Chen,1– 3 Mengna Li,1– 3 Changning Xue,1– 3 Xiangting Zhou,1– 3 Jianxia Wei,1– 3 Lemei Zheng,1– 3 Yumei Duan,1– 3 Hongyu Deng,1 Faqing Tang,1 Wei Xiong,1– 3 Bo Xiang,1– 3 Ming Zhou1– 3 1NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People’s Republic of China; 2Cancer Research Institute, Central South University, Changsha, 410078, People’s Republic of China; 3The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, People’s Republic of ChinaCorrespondence: Ming Zhou; Bo Xiang, Email zhouming2001@163.com; xiangbolin@csu.edu.cnPurpose: Cinobufotalin injection has obvious curative effects on liver cancer patients with less toxicity and fewer side effects than other therapeutic approaches. However, the core ingredients and mechanism underlying these anti-liver cancer effects have not been fully clarified due to its complex composition.Methods: Multidimensional network analysis was used to screen the core ingredients, key targets and pathways underlying the therapeutic effects of cinobufotalin injection on liver cancer, and in vitro and in vivo experiments were performed to confirm the findings.Results: By construction of ingredient networks and integrated analysis, eight core ingredients and ten key targets were finally identified in cinobufotalin injection, and all of the core ingredients are tightly linked with the key targets, and these key targets are highly associated with the cell cycle-related pathways, supporting that both cinobufotalin injection and its core ingredients exert anti-liver cancer roles by blocking cell cycle-related pathways. Moreover, in vitro and in vivo experiments confirmed that either cinobufotalin injection or one of its core ingredients, cinobufagin, significantly inhibited cell proliferation, colony formation, cell cycle progression and xenograft tumor growth, and the key target molecules involved in the cell cycle pathway such as CDK1, CDK4, CCNB1, CHEK1 and CCNE1, exhibit consistent changes in expression after treatment with cinobufotalin injection or cinobufagin. Interestingly, some key targets CDK1, CDK4, PLK1, CHEK1, TTK were predicted to bind with multiple of core ingredients of cinobufotalin injection, and the affinity between one of the critical ingredients cinobufagin and key target CDK1 was further confirmed by SPR assay.Conclusion: Cinobufotalin injection was confirmed to includes eight core ingredients, and they play therapeutic effects in liver cancer by blocking cell cycle-related pathways, which provides important insights for the mechanism of cinobufotalin injection antagonizing liver cancer and the development of novel small molecule anti-cancer drugs. Keywords: cinobufotalin injection, liver cancer, cinobufagin, network pharmacology, cell cycle, core ingredients

Xiaochun Zhou,1– 3,&ast; Kaiying He,1,3,&ast; Jing Zhao,1,3 Guohua Wei,3 Qicai You,1,3 Hongxuan Du,1,3 Wenjiao Gu,1,2 Haiyu Niu,1,4 Qiaoying Jin,1,5 Jianqin Wang,3 Futian Tang1,2 1The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 4Department of Tumor, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 5Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futian Tang, Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, No. 82, Cuiyingmen, Lanzhou, Gansu, People’s Republic of China, Tel +8613321330515, Email Tangfutian2023@126.comPurpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD).Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis.Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p< 0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes.Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.Keywords: diabetic kidney disease (DKD), mixture of astragalus, rhubarb, saffron, transcriptome sequencing, db/db mice

Na Qi,1,&ast; Xiantai Zhou,2,&ast; Ningzhu Ma,2 Jianguo Zhang,2 Zhenlin Wang,2 Xin Zhang,1 Aimin Li1 1Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, People’s Republic of China; 2Department of Pharmacy, Guilin Medical University, Guilin, 541004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aimin Li; Xin Zhang, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, People’s Republic of China, Email liaimin2005@163.com; 252089553@qq.comIntroduction: The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvβ 3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects.Methods: LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice.Results: The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers.Conclusion: The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers. Keywords: modified liposome, LHRHa, RGD, paclitaxel, ovarian cancer

Xingping Zhou,1,&ast; Jinjin Luo,1,&ast; Xi Liang,1,2 Peng Li,1 Keke Ren,1 Dongyan Shi,1,2 Jiaojiao Xin,1,2 Jing Jiang,1,2 Jiaxian Chen,1 Lulu He,1 Hui Yang,1 Shiwen Ma,1 Bingqi Li,1 Jun Li1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel/Fax +86-571-87236425, Email lijun2009@zju.edu.cnBackground and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality. Effective biomarkers are required for its early diagnosis and prognosis. This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF.Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis. The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA).Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710). High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788). Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway. External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796). Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure. Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702). Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥ 8.4 ng/mL.Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.Keywords: thrombomodulin, HBV-ACLF, biomarker, organ failure

Qianyu Bai,1,&ast; Yichi Zhang,1,&ast; Runqiu Cai,1 Haiyan Wu,1 Huiqun Fu,2 Xuemei Zhou,2 Jie Chai,3 Xuepeng Teng,3 Tianlong Liu1 1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agriculture University, Beijing, People’s Republic of China; 2 101 Institute of the Ministry of Civil Affairs, Beijing, People’s Republic of China; 3Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemei Zhou, 101 Institute of the Ministry of Civil Affairs, South Fourth Ring West Road No.188, Beijing, 100070, Email zxmcaur@126.com; Tianlong Liu, College of Veterinary Medicine, China Agriculture University, Yuanmingyuan West Road No. 2, Beijing, 100193, Email liutianlong@cau.edu.cnBackground: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed.Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs.Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 μg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs.Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.Keywords: nanoparticles, otitis media, zinc oxide, mesoporous titanium dioxide, antimicrobial peptide, antimicrobial, hydroxyl radical

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, &num;1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Xu Zhou,1,2,&ast; Aolin Tang,2,3,&ast; Chengjie Xiong,2,&ast; Guoquan Zhang,2 Liangliang Huang,1,2 Feng Xu1,2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, 430070, People’s Republic of China; 3Department of Orthopaedics, Minda Hospital of Hubei Minzu University, Enshi, 445000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangliang Huang; Feng Xu, Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, 430070, People’s Republic of China, Email hll666789@163.com; fengxu1969@163.comBackground: Treating peripheral nerve injuries (PNI) with defects remains challenging in clinical practice. The commercial conduits have shown suboptimal nerve regeneration and functional recovery due to their basic tubular design without electroactive and oriented topographical cues.Purpose: To develop a new scaffold with oriented microstructure and electroactive Graphene oxide (GO) and investigate its’ therapeutic effect on nerve regeneration in vitro and in vivo.Methods: This study employed a straightforward approach to co-spin PCL and GO, yielding an oriented hybrid nanofibrous scaffold known as the O-GO/PCL scaffold. The physical and chemical properties of nanofibrous scaffold were tested by scanning electron microscopy (SEM), transmission electron microscope (TEM), tensile test and so on. Primary Schwann cells (SCs) and dorsal root ganglia (DRG) were used to investigate the impact of the newly developed scaffolds on the biological behavior of neural cells in vitro. Transcriptome sequencing (mRNA-seq) was employed to probe the underlying mechanisms of the synergistic effect of electroactive GO and longitudinal topographic guidance on nerve regeneration. Furthermore, the developed O-GO/PCL scaffold was utilized to bridge a 10-mm sciatic nerve defect in rat, aiming to investigate its therapeutic potential for peripheral nerve regeneration in vivo.Results and discussion: The SEM and TEM revealed that the newly developed O-GO/PCL scaffold showed longitudinally oriented microstructure and GO particles were homogenously and uniformly distributed inside the nanofibers. Primary SCs were utilized to assess the biocompatibility of the GO-based scaffold, revealing that negligible cytotoxicity when GO concentration does not exceed 0.5%. In vitro analysis of nerve regeneration demonstrated that axons in the O-GO/PCL group exhibited an average length of 1054.88 ± 161.32 μm, significant longer than those in the other groups (P < 0.05). Moreover, mRNA sequencing results suggested that the O-GO/PCL scaffold could enhance nerve regeneration by upregulating genes associated with neural regeneration, encompassing ion transport, axon guidance and cell–cell interactions. Most importantly, we employed the O-GO/PCL scaffold to repair a 10-mm sciatic nerve defect in rat, resulting in augmented nerve regeneration, myelination, and functional recovery.Conclusion: The O-GO/PCL scaffold with oriented microstructure and electroactive GO represents a promising heral nerve reconstruction. Keywords: nanofibers, topographical guidance, electroactive, graphene oxide, nerve regeneration

Mi Qi, Yajuan Cheng, Ke Liu, Jingxing Cai, Tianyu Liu, Xiaoying Wu, Huili Tang, He Huang, Qinbiao Chen, Xiaoguang Zhou The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Mi Qi; Xiaoguang Zhou, Tel +86-13510794978 ; +86-18818780760, Email qimi@mail.sysu.edu.cn; gzzhouxg@163.comPurpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms.Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2−) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model.Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity.Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury. Keywords: human heavy chain ferritin, ROS scavenger, ischemic stroke, SOD-mimetic, neuroprotection

Xuqing Zhou,1,2,&ast; Xu Wang,1,2,&ast; Jiaqi Li,3,&ast; Mengxue Zhang,4 Yi Yang,1 Shihui Lei,1 Ying He,3 Hua Yang,3 Desheng Zhou,4 Chun Guo1,2 1Experiment Center of Medical Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 2The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 3College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, 410128, People’s Republic of China; 4Department of Neurology, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Guo, Email chunguosm@163.comBackground: Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating.Aim: To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects.Materials and Methods: The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments.Results: Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3).Conclusion: ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins. Keywords: intracerebral hemorrhage, Annao Pingchong decoction, oxidative stress, network pharmacology, vivo experiments, SIRT1

Simin Liu,1,2 Xiu Zhou,1,2 Huiying Jie,1,2 Zetong Zheng,1,2 Bing Cai,1,2 Qingyun Mai,1– 3 Canquan Zhou1– 3 1Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, People’s Republic of China; 3Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, People’s Republic of ChinaCorrespondence: Canquan Zhou, Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 1 Zhongshan Second Road, Guangzhou, 510080, People’s Republic of China, Fax +86 87330736, Email zhoucanquan@mail.sysu.edu.cnPurpose: To determine the impact of polycystic ovary syndrome on in vitro fertilization/intracytoplasmic sperm injection and embryo transfer outcomes while analyzing the influencing factors.Patients and Methods: A retrospective cohort study comprised 4839 patients who underwent their first cycle of IVF/ICSI treatment from January 2016 to December 2021. Cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared between the PCOS group and control group. Subgroup analysis and binary regression were used to analyze the influence of BMI on clinical outcomes among individuals diagnosed with PCOS.Results: Non-obese PCOS patients exhibited higher cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared to the control group with the normal BMI population (84.7% vs71.2%, P < 0.001; 74.1% vs 61.6%, P < 0.001; 4.1% vs 2.0%, P = 0.002), but there was no significant difference in early miscarriage rates between the two groups.Conclusion: Non-obese PCOS patients demonstrated a notably higher cumulative live birth rate but also a higher risk of late miscarriage compared to non-PCOS females with a normal BMI.Keywords: body mass index, cumulative live birth rate, in vitro fertilization, intracytoplasmic sperm injection, late miscarriage, polycystic ovary syndrome

Xu Zeng,1,2 Xianjie Zhang,2 Wencai Jiang,2,&ast; Xinyu Zhou1,&ast; 1Department of Anaesthesiology, Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Anesthesiology, People’s Hospital of Deyang City, Deyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianjie Zhang, Department of Anesthesiology, People’s Hospital of Deyang City, Deyang, People’s Republic of China, Email zxianjiemazui@163.comPurpose: Investigating the efficacy of intraoperative fractionated intravenous esketamine in the prevention of rebound pain after cessation of thoracic paravertebral nerve blockade.Methods: One hundred and twenty patients who underwent elective thoracoscopic lobectomy were selected for the study and were randomly divided into two groups, the esketamine group was given 0.5 mg/kg and 0.3 mg/kg of esketamine at the induction of anaesthesia and 30 minutes before the end of the operation, respectively, and the control group was given an equal amount of saline. The incidence of rebound pain (RP) 7 days after surgery and postoperative recovery were compared between the two groups.Results: The NRS pain scores at 24 and 48 hours postoperatively in the esketamine group were significantly lower than those in the control group (P < 0.05). The incidence of postoperative rebound pain was significantly lower in the esketamine group than in the control group (P < 0.05). The consumption of sufentanil was less in the esketamine group in the postoperative 48 hours (P < 0.05). Postoperative recovery was compared between the two groups and the difference was not statistically significant.Conclusion: Intravenous esketamine reduces postoperative pain scores, decreases the incidence of rebound pain after cessation of thoracic paravertebral block, and reduces opioid consumption.Keywords: esketamine, rebound pain, paravertebral nerve block, postoperative pain

Jiapei Yao,1,2 Xindie Zhou,1,3 Dongmei Xu,1 Ting Liu,1 Yuanyuan Gui,4 Yong Huang1,3 1Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Hunan Normal University, Changsha, People’s Republic of China; 3Changzhou Medical Center, Nanjing Medical University, Changzhou, People’s Republic of China; 4Department of Psychogeriatric Intensive Care Medicine, Xianlin Campus, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of ChinaCorrespondence: Yuanyuan Gui; Yong Huang, Email Guiyuanyuansltd@163.com; huangyong@njmu.edu.cnObjective: Secondary traumatic stress (STS) is stress caused by helping or wanting to help someone who has suffered a traumatic event. STS has adverse effects on nurses and their work, such as reduced career achievement, an increased staff turnover rate, inability to complete work, avoidance of contact with patients, mental exhaustion, negative emotions which seriously affect the quality of their work and life. The study to investigate secondary traumatic stress in emergency and intensive care nurses and analyze factors that influence it.Material and Methods: The study was a cross-sectional survey. Convenience sampling was used to select hospital emergency and intensive care department nurses (n=434) who met the inclusion and exclusion criteria from August to October 2021 to participate in this study. They provided demographic data and completed measures of secondary traumatic stress, emotional intelligence, anxiety and depression. Data analysis included independent samples t-tests, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis.Results: Almost one-third (30.7%) of participants were at moderate risk for Secondary Traumatic Stress Scale or above, with high average scores on measures of anxiety (GAD-7 average = 6.05 ± 4.13), and depression (PHQ-9 average = 6.35 ± 4.85). The results of multiple linear regression analysis showed that the average daily amount of sleep in the past week, the number of night shifts in the past month, emotional intelligence, anxiety, and depression influenced secondary traumatic stress, explaining 70.8% of the variance.Conclusion: The STS of emergency and intensive care nurses in Changzhou is at a high level. Sleep time, number of night shifts and emotional intelligence are related to secondary traumatic stress and anxiety and depression significantly predicted the degree of secondary traumatic stress. Nurses need to master effective treatment methods for secondary traumatic stress, to improve their work efficiency and nursing quality and ensure nursing safety.Keywords: secondary traumatic stress, emergency and intensive care department nurses, anxiety, depression, emotional intelligence

Xiaolan Zhou,1 Rumeng Chen,2 Yichen Cai,1 Qiu Chen1 1Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qiu Chen, Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shierqiao Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 18981885702, Fax +86 28-87765517, Email chenqiu1005@cdutcm.edu.cnPurpose of Review: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM.Recent Findings: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized.Summary: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.Keywords: fecal microbiota transplantation, type 2 diabetes mellitus, gastrointestinal microbiome, treatment