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Xuerong Jia,1,&ast; Min Peng,2,&ast; Zewen Wang,3,&ast; Xiang Li,4,5 Tao Mou,1 Xiaoke Wang,1 Yaqian Xia,6 Jizi Ma,1 Qing Wang,1 Zefang Li,4 Longjiang Zhang,3 Wusheng Zhu,1 Gelin Xu1,2,4 1Department of Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China; 2Department of Neurology, Inst Translat Med, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, 518000, People’s Republic of China; 3Department of Radiology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210002, People’s Republic of China; 4Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People’s Republic of China; 5Department of Neurology, The Ninth People’s Hospital of Chongqing, Chongqing, 400700, People’s Republic of China; 6Department of Neurology, The People’s Hospital of Rugao, Rugao, Jiangsu, 226500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gelin Xu; Wusheng Zhu, Department of Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305&num; East Zhongshan Road, Nanjing, Jiangsu, 210002, People’s Republic of China, Tel + 86-18951919349, Fax + 86-25-84801861, Email gelinxu@nju.edu.cn; zwsemail@sina.comBackground and Purpose: Diet may influence systemic inflammatory status, vascular calcification, and, therefore, the development of atherosclerosis. The Dietary Inflammatory Index (DII) is a measure of the inflammatory potential of diet. Although previous studies have examined the relationship between DII and cardiovascular diseases, its specific association with carotid artery calcification in ischemic stroke patients remains insufficiently explored. This study aimed to evaluate the relationship between Dietary Inflammatory Index (DII) and carotid artery calcification in patients with ischemic stroke.Methods: This is a retrospective cross-sectional analysis based on a prospective registry database. Patients with ischemic stroke were enrolled via Nanjing Stroke Registry Program. DII was calculated based on 39 food components with the help of a food frequency questionnaire. Carotid artery calcification was quantified as calcification score using the Agatston method based on computed tomography angiography. The data were compared among patients stratified by tertiles of DII. Multiple logistic regression models were used to evaluate the influence of DII on carotid artery calcification. Spearman analysis was used to evaluate the relationship between DII and ln-transformed carotid artery calcification score.Results: Of the 601 enrolled, carotid artery calcification was detected in 368 (61.23%) patients. Compared with patients with the lowest DII, those with higher DII had a higher ratio of stroke subtypes of large artery atherosclerosis (p =0.050), a higher calcification score (p < 0.001), and a higher ratio of calcification (p < 0.001). Other baseline characteristics, including sex and age, showed no significant differences across the DII tertiles. Patients with carotid artery calcification had significantly higher DII scores compared to those without calcification (p = 0.018). Logistic regression analysis showed that patients with the highest DII tertile had a higher risk of carotid artery calcification after adjusting for significant cofounders (OR =1.880, 95% CI, 1.205− 2.932; p =0.005). Spearman correlation analysis indicated that DII was associated with ln-transformed carotid artery calcification score in patients with carotid artery calcification (R =0.110, p =0.035).Conclusion: DII was associated with carotid artery calcification in patients with ischemic stroke. Considering a possible causal relationship, the mechanism of this relationship warrants further investigation.Keywords: dietary inflammatory index, artery calcification, carotid, ischemic stroke

Xudong Wang,1– 3,&ast; Zhiyong Li,1,&ast; Jianhong Xu,1 Jun Wang,1 Ying Li,1 Qiang Li,4 Jianrong Niu,5 Rongya Yang2 1Outpatient Department of Yangfangdian, Southern Medical District of Chinese PLA General Hospital, Beijing, 100843, People’s Republic of China; 2Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4Medical Health Care Dept, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China; 5Department of Dermatology, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongya Yang, Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China, Email yangrya@sina.com Qiang Li, Medical Health Care Department, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China, Email 16585260@qq.comPurpose: Heat shock protein A4 (HSPA4) is associated with a variety of human diseases. However, its function in cutaneous malignant melanoma (CMM) remains uncertain.Patients and Methods: The gene and protein expression level of HSPA4 in CMM was investigated with public databases. Cell Counting Kit-8 (CCK8) assay was performed to assess the effect of HSPA4 on the proliferation of melanoma cells. Then, the diagnostic and prognostic value of HSPA4 in CMM were analyzed. Gene variations and methylation levels, and the correlation between HSPA4 expression and immune cell infiltration were evaluated, followed by the construction of HSPA4 related protein-protein interaction networks and functional enrichment analysis.Results: The mRNA and protein expression level of HSPA4 was significantly higher in CMM. Knocking down HSPA4 in A-375 cell line could inhibit tumor cell growth. The receiver operating characteristic (ROC) curve analysis confirmed the diagnostic value of HSPA4. Survival analysis showed that high expression of HSPA4 was associated with poor prognosis. HSPA4 gene alterations were observed in 3% of CMM patients. Five CpG sites are associated with the prognosis of CMM. HSPA4 is negatively correlated with most immune cells in CMM. The protein interaction network shows that HSPA4 is closely related to proteins such as DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) and DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6), and the expression of DNAJB1 is positively correlated with HSPA4. Functional enrichment analysis indicated that HSPA4 may be associated with immune suppression and immune escape within the tumor microenvironment of CMM.Conclusion: HSPA4 may participate in the regulation of tumor development and microenvironment, which may be a potential diagnostic and prognostic marker of CMM.Keywords: heat shock protein, melanoma, HSPA4, TCGA, bioinformatics

Zhaoyi Li, Yibin Zhao The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 31000, People’s Republic of ChinaCorrespondence: Yibin Zhao, Email 510496772@qq.comAim: Increasing observational studies are revealing a positive correlation between body mass index (BMI) and the risk of Immune-mediated and Inflammatory Skin Diseases (IMID), however the causal relationship is not yet definite.Objective: The aim of the study was to conduct a two-sample Mendelian randomization (TSMR) to explore the potential causality between BMI, and IMID and biomarkers.Methods: The summary statistics for BMI (n = 322,154), at genome-wide significant level, were derived from the Genetic Investigation of Anthropometric Traits consortium (GIANT). The outcome data for IMID (Psoriasis, vitiligo, Atopic dermatitis (AD), acne, Bullous diseases, Dermatitis herpetiformis, Systemic lupus erythematosus (SLE), Alopecia Areata (AA), Hidradenitis suppurativa (HS) and Systemic sclerosis), and biomarkers were obtained from genome-wide association studies (GWAS). The TSMR analyses were performed in four methods, including inverse variance weighted (IVW) method, MR-Egger regression, the weighted median estimator (WME) and simple mode.Results: The IVW analysis showed that the per standard deviation (SD) increase in BMI increased a 57% risk of psoriasis. We also observed the suggestive evidence of a causal relationship between BMI and AD and HS. This analysis did not support causality of Vitiligo, Acne, Bullous pemphigoid, Dermatitis herpetiformis, SLE, AA and Systemic sclerosis. The higher risk of BMI may be explained by higher levels of Triglycerides, C-reactive protein (CRP), Interleukin 6, Erythrocyte sedimentation rate (ESR) and Neutrophil count. The high-density lipoprotein (HDL) has an inverse relationship with BMI. No influences were defined for Total cholesterol, low-density lipoprotein (LDL), Rheumatoid factor (RF), Basophil count and Eosinophil count.Conclusion: Our two-sample MR analysis proved the causal evidence for the associations between BMI and IMID, including psoriasis, AD and HS, which might be related to the elevated expression of biomarkers, including Triglycerides, CRP, Interleukin 6, ESR and neutrophil count.Keywords: Mendelian randomization, BMI, immune-mediated and inflammatory skin diseases, biomarkers, causal association

Zhongyuan Li,1,&ast; Pengfei Xu,2,&ast; Yang Deng,3,&ast; Rui Duan,1 Qiang Peng,1 Shiyao Wang,1 Zhaohan Xu,1 Ye Hong,1 Yingdong Zhang1 1Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 3Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, Nanjing, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Hong; Yingdong Zhang, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, 210000, People’s Republic of China, Email dg1735053@smail.nju.edu.cn; zhangyingdong@aliyun.comBackground: After ischemic stroke (IS), microglia and astrocytes undergo polarization, transforming into a pro-inflammatory phenotype (M1 or A1). According to previous studies, exosomes might play an important role in the interplay between M1 microglia and A1 astrocytes after IS.Methods: We used the microglial oxygen-glucose deprivation/reperfusion (OGD/R) model and ultracentrifugation to extract M1 microglial exosomes (M1-exos). Subsequently, we identified circSTRN3 enriched in exosomes through RNA sequencing and detected the role of circSTRN3 in astrocyte activation based on bioinformatics analysis, immunofluorescence, Western blotting, and polymerase chain reaction analysis. We validated these findings in the middle cerebral artery occlusion/reperfusion (MCAO/R) model of adult male C57BL/6J mice. Finally, we confirmed the correlation among circSTRN3, miR-331-5p, and stroke severity score in exosomes isolated from peripheral blood of IS patients.Results: Our findings revealed that M1-exos promoted A1 astrocyte activation. CircSTRN3 was abundant in M1-exos, which could sponge miR-331-5p to affect mitochondrial antiviral signaling protein (MAVS), activate NF-κB pathway, and participate in A1 astrocyte activation. In addition, overexpressed circSTRN3 augmented the infarct size and neurological dysfunction in MCAO/R models, while miR-331-5p mimics reversed the effect. Furthermore, circSTRN3 in IS patients was positively correlated with stroke severity score (R2 = 0.83, P < 0.001), while miR-331-5p demonstrated a negative correlation with the same score (R2 = 0.81, P < 0.001).Conclusion: Taken together, our research indicated that circSTRN3 from M1-exos could promote A1 astrocyte activation and exacerbate ischemic brain injury via miR331-5p/MAVS/NF-κB axis.Keywords: ischemic stroke, microglia, astrocyte, exosome, circSTRN3, miR-331-5p

Yongfeng Fan, Xiulun Liu, Zhongkui Li, Daokang Xiang Department of Cardiac Surgery, Guizhou Provincial People’s Hospital, Guizhou, 550499, People’s Republic of ChinaCorrespondence: Daokang Xiang, Email dao57115973@163.comObjective: To investigate the impact of surgical intervention on hemodynamic parameters and postoperative delirium in Stanford Type A aortic dissection patients.Methods: A retrospective analysis was conducted on 139 patients who underwent surgery for Stanford Type A aortic dissection from February 2022 to February 2024. Hemodynamic parameters, including maximum ascending aortic diameter (MAAD), left ventricular end-diastolic diameter (LVEDd), and ejection fraction (LVEF), were compared pre- and post-surgery. Patients were divided into two groups based on delirium occurrence postoperatively: Group A (n=49, with delirium) and Group B (n=90, without delirium). Differences in surgical factors and intensive care conditions were analyzed, and risk factors for postoperative delirium were identified. Group sizes differ due to retrospective categorization based on observed outcomes rather than controlled sampling.Results: ① Hemodynamic parameters: Postoperative MAAD and LVEDd were significantly reduced, while LVEF increased compared to preoperative levels (P < 0.05). ② Surgical and postoperative conditions: Group A had longer surgery, cardiopulmonary bypass, and deep hypothermic circulatory arrest times than Group B (P < 0.05). ③ Univariate analysis of baseline data: Group A had higher rates of patients aged ≥ 60, hypertension, history of stroke, and elevated preoperative D-dimer levels (P < 0.05). ④ Multivariate logistic analysis: Independent risk factors for postoperative delirium included age ≥ 60, hypertension, history of stroke, surgery time > 6 hours, cardiopulmonary bypass time > 3 hours, and deep hypothermic circulatory arrest time > 40 minutes (OR > 1, P < 0.05).Conclusion: Surgical treatment of Stanford Type A aortic dissection has a good effect, significantly improving long-term cardiac function. However, the incidence of postoperative delirium is relatively high and is closely related to factors such as age, hypertension, history of stroke, surgery time, cardiopulmonary bypass time, and deep hypothermic circulatory arrest time.Keywords: Stanford Type A aortic dissection, surgical intervention, hemodynamic parameters, postoperative delirium, impact, investigation

Zhile Li, Han Gan, Siyuan Li, Yuchen Xue, Kai Luo, Kai Huang, Yunqian Zhang, Yan Wang, Lai Jiang, Hui Zhang Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Lai Jiang; Hui Zhang, Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of China, Email jianglai@xinhuamed.com.cn; zhanghui22002@xinhuamed.com.cnBackground: Septic lung injury (SLI) is a severe condition with high mortality, and ferroptosis, a form of programmed cell death, is implicated in its pathogenesis. However, the explicit mechanisms underlying this condition remain unclear. This study aimed to elucidate and validate key ferroptosis-related genes involved in the pathogenesis of SLI through bioinformatics analysis and experimental validation.Methods: Microarray data related to SLI from the GSE130936 dataset were downloaded from the Gene Expression Omnibus (GEO) database. These data were then intersected with the FerrDb database to obtain ferroptosis-related differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks and functional enrichment analysis were employed to identify key ferroptosis-related DEGs. The Connectivity Map (c-MAP) tool was used to search for potential compounds or drugs that may inhibit ferroptosis-related DEGs. The transcriptional levels of the key genes and potential therapeutic compounds were verified in an LPS-induced mouse model of lung injury. The expression of these key genes was further verified using the GSE60088 and GSE137342 datasets.Results: 38 ferroptosis-related DEGs were identified between the septic and control mice. PPI network analysis revealed four modules, the most significant of which included eight ferroptosis-related DEGs. Functional enrichment analysis showed that these genes were enriched in the HIF-1 signaling pathway, including IL-6 (Interleukin-6), TIMP1 (Tissue Inhibitor of Metalloproteinase 1), HIF-1α (Hypoxia-Inducible Factor-1α), and HMOX1 (Heme Oxygenase-1). Phloretin, a natural compound, was identified as a potential inhibitor of these genes. Treatment with phloretin significantly reduced the expression of these genes (p < 0.05), mitigated lung injury, improved inflammatory profiles by approximately 50%, and ferroptosis profiles by nearly 30% in the SLI models.Conclusion: This study elucidates the significant role of ferroptosis in SLI and identifies phloretin as a potential therapeutic agent. However, further research, particularly involving human clinical trials, is necessary to validate these findings for clinical use.Keywords: sepsis, SLI, ferroptosis, bioinformatics, HIF-1α, phloretin

Wenjun Chang,1 Zheng Li,2 Qianqian Liang,1 Wei Zhao,1 Fengsen Li2 1Department of Fourth Clinical College, Xinjiang Medical University, Urumqi, 830054, People’s Republic of China; 2Department of Respiratory, Unit Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, 830000, People’s Republic of ChinaCorrespondence: Fengsen Li, Department of Respiratory, Unit Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, No. 119, Huang He Road, Urumqi, 830000, People’s Republic of China, Tel +86-13999980996, Email Fengsen602@163.comObjective: To assess the incidence and risk factors of tuberculosis-associated obstructive pulmonary disease (TOPD) in individuals with treatment-naive pulmonary tuberculosis (PTB) and develop a predictive model to enhance its management.Methods: The incidence of TOPD among patients with treatment-naive PTB in Xinjiang, China, was followed up for one year. Patient characteristics, such as demographics, medical histories, laboratory test results, lung radiological evidence, and pulmonary function, were collected upon hospital admission and throughout follow-up visits. Risk factors associated with TOPD were evaluated by multivariate logistic regression analysis, and then a predictive model was established using LASSO regression.Results: Of the 159 included patients, 69 (43.4%) developed TOPD during the follow-up period. Multivariate regression analysis identified age, body mass index, ESR, and symptom duration as significant risk factors. Subsequently, a model formula was derived from these factors to predict TOPD. Utilizing a cut-off value of 0.435, the model demonstrated a sensitivity of 89% and a specificity of 83%.Conclusion: In Xinjiang, the prevalence of TOPD appears notably high among treatment-naive PTB patients. Our findings, such as the risk factors and predictive model, may facilitate the early detection and improved interventions for TOPD among patients with PTB, potentially leading to better patient outcomes.Keywords: tuberculosis, tuberculosis-associated obstructive pulmonary disease, risk factor, predictive model, diagnosis

Shuai Tang,1– 4 Wenyu Feng,2– 4 Zekun Li,1 Xinjuan Liu,1 Tong Yang,1– 4 Fulan Wei,2– 4 Gang Ding1 1School of Stomatology, Shandong Second Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Shandong Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Gang Ding, School of Stomatology, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, Shandong, 261053, People’s Republic of China, Email dinggang@sdsmu.edu.cn Fulan Wei, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Wenhua West Road No. 44-1, Jinan, Shandong, 250012, People’s Republic of China, Email weifl@sdu.edu.cnIntroduction: Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.Methods: A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.Results: The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.Conclusion: LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway. Keywords: inflammatory bowel disease, periodontal ligament stem cells, extracellular vesicles, gut microbiota, PI3K/AKT signaling pathway

Zheng Li,1,2,&ast; Guang-Xin Duan,3,&ast; Jia-Hui Zhang,3 Yun Xu,3 Yun Luo3 1Department of Rehabilitation, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Rehabilitation, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Xu; Yun Luo, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China, Email xuyun208@163.com; luoyun@njglyy.comBackground: Chronic hypertension is an independent risk factor for ischemic stroke and worsens prognosis. However, the level of blood pressure control in hypertensive patients with severe intracranial stenosis is controversial.Purpose: To investigate the effect of different levels of blood pressure on cerebral perfusion in patients with middle cerebral artery severe stenosis or occlusion.Materials and methods: A total of 105 patients with isolated steno-occlusive middle cerebral artery (MCA) diagnosed by digital subtraction angiography (DSA) were enrolled, and PWI was compulsory. Relative risk factors were obtained by intergroup analysis in both hypertensive and non-hypertensive groups, and multivariable logistic regression was performed to determine whether hypertension was independently associated with PWI values. Next, the effects of different levels of blood pressure levels on cerebral perfusion as a whole and subgroup were further compared.Results: The hypertension (HT) group (Am 1.04± 0.05, Lm 1.07± 0.06, Pm 1.07± 0.05) demonstrated lower cerebral perfusion pressure at a larger rMTT (p=0.0001, 0.004, 0.006) than the nonhypertension (NHT) group (Am 1.01± 0.21, Lm 1.04± 0.04, Pm 1.04± 0.04). After adjustment for age, diabetes, and fibrinogen (FIB), HT was independently associated with the rMTT of Am, Lm, and Pm (P=0.015, 0.001, 0.022). Significant differences were observed with HT+SBP< 140 (p=0.035, 0.048, 0.049) and HT+DBP< 80 (p=0.034, 0.045, 0.055) in rMTT compared with NHT.Conclusion: Chronic hypertension might damage cerebral perfusion. Strictly control of blood pressure (< 140/80mmHg) in hypertensive patients with intracranial artery stenosis will further reduce ipsilateral cerebral perfusion.Keywords: blood pressure control, isolated severe steno-occlusive, PWI, cerebral perfusion

Jun Zhao,1,2,&ast; Xia Li,3,&ast; Xin Wang,4 Xuefei Wang,4 Xin Hao,2 Zhigang Li,2 Lin Zhu1 1Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610044, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 4Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigang Li; Lin Zhu, Email lizhigang620@126.com; 13880262860@163.comBackground: To identify irritable bowel syndrome with diarrhea (IBS-D) combined with anxiety and/or depression through a psychological screening tool and to further explore the relationships between patients with comorbidities and gut microbiota.Methods: The GAD-7, SAS, PHQ-9 and SDS were administered to evaluate anxiety and depression. Faeces were subsequently collected from 44 patients with emotional disorders (IBS-EDs), 22 patients without emotional disorders (IBS-nEDs) and 18 healthy controls (HCs) via 16S rRNA sequencing, depending on the participants’ wishes. The differences in gut microbiota among different groups were analysed. Spearman analysis was conducted at the genus level and was based on psychological assessment scores. Patients with IBS-D were recruited from December 2020 to November 2022.Results: This study included 124 outpatients with IBS-D. According to the GAD-7 and SAS scores, 40.3% and 19.3% of the participants, respectively, had anxiety (P < 0.05). Similarly, a significantly greater percentage of participants had depression according to the PHQ-9 than according to the SDS (61.3% vs 33.1%) (P < 0.05). Overall, approximately 66.1% of the participants had emotional disorders (anxiety and/or depression) according to the GAD-7 and PHQ-9. Correlation analysis revealed that the abundances of Eubacterium_hallii_group, Monoglobus and Lachnoclostridium were closely related to the PHQ-9 scores and that the abundances of Subdoligranulum and Holdemanella were closely related to the GAD-7 scores.Conclusion: In comparison to the SAS and SDS, both the GAD-7 and PHQ-9 identified a greater number of individuals with emotional disorders within the IBS-D population. Furthermore, our findings demonstrated that Lachnoclostridium is not only a biomarker for IBS-ED patients but also that its abundance changes are related to PHQ-9 scores, which may provide insights for further brain gut investigations.Keywords: depression, anxiety, IBS-D, 16S rRNA

Haoran Chen,1 Meng Wang,2,3 Lin Yang,1,4 Jiao Li,1,4,&ast; Zixiao Li2,3,5,&ast; 1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 4Key Laboratory of Medical Information Intelligent Technology, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Li, Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 3 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Email li.jiao@imicams.ac.cn Zixiao Li, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, Southern Fourth Ringroad, Fengtai District, Beijing, 100070, People’s Republic of China, Email lizixiao2008@hotmail.comAim: The interaction between inflammatory biomarkers (high-sensitivity C-reactive protein, hsCRP) and antioxidants (uric acid, UA) regarding prognosis after ischemic stroke or transient ischemic attack (TIA) remains inadequately explored. This study aimed to assess (1) the individual and joint effects of hsCRP and UA, and (2) the neuroprotective role of UA in patients with elevated hsCRP levels concerning poor functional outcomes at 90 days.Methods: A prospective cohort study was conducted involving 2140 consecutive ischemic stroke or TIA patients with hsCRP and UA levels. The primary outcome was defined as a poor functional outcome, indicated by a modified Rankin Scale (mRS) score of 3– 6 at 90 days, with a shift in the mRS score as a secondary outcome. Logistic regression and propensity score (PS) analyses were employed to ensure robustness.Results: Poor functional outcome occurred in 345 (16.1%) patients. Individual effects found that the highest quartiles of hsCRP (adjusted OR = 3.090; 95% CI 2.150– 4.442) and UA (adjusted OR = 0.671; 95% CI 0.551– 0.883) were associated with increased or decreased risk of poor functional outcome, respectively. Joint effects (adjusted OR = 3.994; 95% CI 2.758– 5.640) between hsCRP and UA on the primary outcome were more apparent in patients with high hsCRP levels (hsCRP > 1.60 mg/L) and low UA levels (UA ≤ 291.85 μmol/L). For the patients with high hsCRP levels, patients with low UA levels had a higher risk of primary and secondary outcomes, compared with those with high UA levels, after unadjusted or adjusted for hsCRP. Similar and reliable results were observed in PS-based models.Conclusion: In patients with ischemic stroke or TIA, joint high levels of hsCRP and low UA levels significantly correlate with increased risk of poor functional outcome at 90 days. In addition, high UA levels could reduce the risk of poor functional outcome for patients with high hsCRP levels. Keywords: biomarkers, ischemic stroke, poor functional outcome, joint effects, neuroprotective effects

Wenchao Xie,1,&ast; Wang Liao,1,&ast; Hongming Lin,2 Guanglin He,2 Zhaohai Li,2 Lang Li1 1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Cardiology, The First People Hospital of Yulin & The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, Guangxi, 537000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lang Li, Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email drlilang1968@126.comPurpose: Our study aimed to establish a prediction model for coronary artery disease (CAD) that integrates immune infiltration and a gene expression signature.Methods: 613 differentially expressed genes (DEGs) and 12 hub genes were screened via the GSE113079 dataset. The pathway enrichment analysis indicated that these genes (613 DEGs and 12 hub genes) were closely associated with the inflammatory and immune responses. Based on the differentially expressed miRNA (DEmiRNA)-DEG regulatory network and immune cell infiltration, the Lasso algorithm constructed a CAD risk prediction model containing the risk score and immune score. Then, ROC-AUC and polymerase chain reaction (PCR) were performed for validation.Results: Six hub genes (PTGER1, PIK3R1, ADRA2A, CORT, CXCL12, and S1PR5) had a high distinguishing capability (AUC > 0.90). In addition, the miRNAs targeting 12 hub genes were predicted and intersected with the DEmiRNAs, and the DEmiRNA-DEG regulatory network was then constructed. Two LASSO models and a novel CAD risk prediction model were constructed through LASSO regression analysis, and they both accurately obtained the risk of CAD. The CAD risk prediction model shows good performance (AUC = 0.988). We also constructed a valid nomogram, and PCR results verified three downregulation hub genes and one upregulation gene in the CAD risk model.Conclusion: We demonstrated the molecular mechanism of the hub genes in CAD and provided a valuable tool for predicting the risk of CAD.Keywords: coronary artery disease, DEmiRNA-DEG regulatory network, nomogram, immune score, immune infiltration

Bohong Cen,1,2 Jian Zhang,1 Xinghua Pan,3 Zhongyuan Xu,2 Rong Li,1 Chengcong Chen,1 Baiyao Wang,1 Zhiyong Li,4 Guoqian Zhang,1 Aimin Ji,5 Yawei Yuan1 1Department of Radiation Oncology, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China; 2Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, Guangdong, 510515, People’s Republic of China; 4Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Department of Pharmacy, The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, 528244, People’s Republic of ChinaCorrespondence: Yawei Yuan; Aimin Ji, Email yuanyawei@gzhmu.edu.cn; aiminji_007@163.comPurpose: To develop a novel approach for increasing radiosensitivity in glioblastoma (GBM) by using targeted nanoparticles to deliver siRNA aimed at silencing the EGFR and RELA/P65 genes, which are implicated in radioresistance.Patients and Methods: We engineered biodegradable, tumor-targeted, self-assembled, and stimuli-responsive peptide nanoparticles for efficient siRNA delivery. We evaluated the nanoparticles’ ability to induce gene silencing and enhance DNA damage under radiation in vitro and in vivo. The nanoparticles were designed to exhibit pH-responsive endosomal escape and αvβ 3 integrin targeting, allowing for preferential accumulation at tumor sites and traversal of the blood-brain tumor barrier.Results: The application of these nanoparticles resulted in significant gene silencing, increased apoptosis, and decreased cell viability. The treatment impaired DNA repair mechanisms, thereby enhancing radiosensitivity in GBM cells. In a GBM mouse model, the combination of nanoparticle treatment with radiotherapy notably prolonged survival without apparent toxicity.Conclusion: Our findings suggest that nanoparticle-mediated dual gene silencing can effectively overcome GBM radioresistance. This strategy has the potential to improve clinical outcomes in GBM treatment, proposing a promising therapeutic avenue for this challenging malignancy.Keywords: glioblastoma, siRNA delivery, self-assembly nanoparticles, radiation sensitizer

Yu Sun,1 Zhaoyong Li,1 Jiahao Duan,1 Enxu Liu,1 Fei Sun,1 Lei Yang,2 Long Chen,2 Shaofeng Yang2 1Graduate School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Shaofeng Yang, Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, No. 300 Xue-Shi Road, Yuelu District, Changsha, 410007, Hunan, People’s Republic of China, Tel +86 18391076233, Email a18391076233@163.comAbstract: The gut microbiome (GM), often referred to as the second genome of the human body, plays a crucial role in various metabolic processes and mediates the development of numerous diseases. Intervertebral disc degeneration (IDD) is an age-related degenerative spinal disease characterized by the loss of disc height, hydration, and integrity, leading to pain and reduced mobility. Although the pathogenesis of IDD is not fully understood, recent studies suggest that dysbiosis of the gut microbiome may accelerate the progression of IDD through multiple mechanisms. This article begins by discussing the potential relationship between GM dysbiosis and human diseases, followed by a comprehensive review of the regulatory mechanisms of GM in skeletal diseases within the gut-disc axis framework. Furthermore, it explores three potential pathways through which GM dysbiosis may mediate the development of IDD: immunomodulation, bacterial translocation and colonization, and the decomposition and absorption of intestinal metabolites. These pathways can disrupt disc cell homeostasis and promote degenerative changes. Finally, this paper summarizes for the first time the potential therapeutic approaches for delaying IDD by targeting the gut-disc axis, providing new insights into the pathogenesis and regenerative repair strategies for IDD.Keywords: intervertebral disc degeneration, microbiome, inflammation, immunity, metabolism

Mingyue Shang,&ast; Zhehong Li,&ast; Guangzhong Xu, Dongbo Lian, Zhaohui Liao, Dezhong Wang, Buhe Amin, Zheng Wang, Weijian Chen, Dexiao Du, Nengwei Zhang, Liang Wang Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nengwei Zhang; Liang Wang, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +8613801068802 ; +8619800320171, Email zhangnw@ccmu.edu.cn; 1911110644@pku.edu.cnPurpose: Gastroesophageal reflux disease (GERD) is a common complication after laparoscopic sleeve gastrectomy (LSG); This study aimed to construct a model that can predict the incidence of GERD after LSG by exploring the correlation between the results of high-resolution esophageal manometry (HREM) and the incidence of GERD after LSG.Patients and Methods: We collected the clinical data of patients who had undergone HREM before bariatric surgery from September 2013 to September 2019 at the bariatric center of our hospital. The Gerd-Q scores during the postoperative follow-up were collected to determine the incidence of GERD. A logistic regression analysis was performed to explore the correlation of the HREM results and general clinical data with the incidence of GERD after LSG.Results: The percentage of synchronous contractions, lower esophageal sphincter (LES) resting pressure, and history of smoking were correlated with the development of GERD after LSG, with the history of smoking and percentage of synchronous contractions as risk factors and LES resting pressure as a protective factor. The training set showed an area under the ROC curve (AUC) of the nomogram model of 0.847. The validation set showed an AUC of 0.761. The decision and clinical impact curves showed a high clinical value for the prediction model.Conclusion: The HREM results correlated with the development of GERD after LSG, with the percentage of synchronous contractions and LES resting pressure showing predictive value. Combined with the history of smoking, the predictive model showed a high confidence and clinical value.Keywords: gastroesophageal reflux disease, laparoscopic sleeve gastrectomy, high-resolution esophageal manometry, complications

Shiyao Zhang,1 Xiuying Zhang,2 Chenghao Wei,1 Lai Zhang,1 Zhaoyang Li1 1Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 2The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of ChinaCorrespondence: Xiuying Zhang, Email pcxtcm@163.comObjective: To investigate the causal relationship between 91 circulating inflammatory proteins and Various asthma phenotypes by means of Mendelian randomization.Methods: Genome-wide association Studies (GWAS) of 91 inflammatory proteins were pooled from the Olink Target platform with 14,824 participants. Various asthma phenotypes were derived from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the main method for MR Analysis, supplemented by Mr-Egger, Weighted median, Simple mode, and Weighted mode. The MR-Egger intercept term test and Cochran’s Q test were used to test the polymorphism and heterogeneity of IVs, and visual analysis was carried out to draw scatter plots, funnel plots, and leave-out-one plots. The FDR correction was performed due to the possibility of a type 1 error.Results: Genetically predicted IVW results revealed a total of 30 data sets suggesting a potential causal relationship between circulating inflammatory proteins and asthma phenotypes. Among them, 2 results were still strongly positive after FDR correction. The level of CST5 (OR=1.184; 95% CI: 1.075– 1.305; P=0.0001; P-FDR=0.028) is associated with an increased risk of non-allergic asthma. LIF-R (OR=0.723; 95% CI: 0.620– 0.842; P=0.000; P-FDR=0.003) is associated with a reduced risk of asthma in children. There was no pleiotropy or heterogeneity in the remaining 16 results that suggested a potential causal relationship.Conclusion: Increased CST5 levels are associated with an increased risk of non-allergic asthma. LIF-R is associated with a reduced risk of asthma in children.Keywords: mendelian randomization, inflammatory protein, asthma, childhood asthma, allergic asthma, non-allergic asthma, suggestive for eosinophilic asthma, obesity related asthma

Guiyun Zhang,1 Zhe Liu,1 Zhen Li,2 Yangchun Xu1 1Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Medical Administration, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Yangchun Xu, Department of Dermatology, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun, 130041, People’s Republic of China, Tel +86-431-81136244, Email Xuyc@jlu.edu.cnAbstract: Keloids are pathologic scars that pose a significant functional and cosmetic burden. While the literature on keloid management continues to expand, the absence of standardized guidelines or treatment protocols endorsed by academic governing bodies remains a significant challenge. The pathogenesis of keloid scars is not fully elucidated. This review delves into the intricate pathogenesis of keloids, exploring the molecular and cellular mechanisms underlying their formation. Conventional therapies are analyzed in-depth considering their efficacy and limitations, including surgical excision, pharmacotherapies, radiotherapy, cryotherapy, silicone-based product, pressure therapy, and light-based therapy. The emergence of novel therapeutic approaches is discussed, including pharmacotherapies, physical therapies, and biological therapies, shedding light on their potential in treating keloid scars. We also contemplate future directions in the field, encompassing the application of targeted therapies, gene-editing tools, tissue engineering, and regenerative medicine, together with psychosocial support and patient education. In synthesizing current knowledge, scrutinizing therapeutic modalities, and envisioning future avenues, this review aims to provide a comprehensive reference for clinicians, researchers, and stakeholders engaged in the intricate field of keloid management.Keywords: keloid scars, pathogenesis, therapies

Yi Yu,1 Ricong Xu,1 Zhijian Li,2,3 Qijun Wan1 1Department of Nephrology, The First Affiliated Hospital of Shenzhen University, The Second People’s Hospital of Shenzhen, Shenzhen, 518039, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 3NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Qijun Wan, Department of Nephrology, The First Affiliated Hospital of Shenzhen University, The Second People’s Hospital of Shenzhen, Shenzhen, 518039, People’s Republic of China, Email yiyuan2224@sina.comAbstract: Primary membranous nephropathy (PMN) is one of the prevalent pathological types of adult primary nephrotic syndrome. Pathogenic autoantibodies targeting podocyte antigens such as phospholipase A2 receptor (PLA2R) lead to the disease. Patients frequently experience notable adverse effects when treated with conventional immunosuppressive therapies. Rituximab (RTX), a mouse/human monoclonal antibody, selectively depletes B cells and leads to a decrease in the antibody levels in the circulation, which helps to alleviate membranous nephropathy. Various RTX dosage regimens have been applied globally in the PMN treatment with satisfactory effects. Nevertheless, the optimal dosage of RTX has yet to be determined. This article reviews the application of different doses of RTX in the management of PMN so far.Keywords: membranous nephropathy, nephrotic syndrome, rituximab, dosage

Zhaoxian Li,1 Wei Bao,1 Yao Wang,1 Shangsong Yan,1 Hong Zheng,2 Junlong Luo1,3 1Psychology College, Shanghai Normal University, Shanghai, People’s Republic of China; 2Changning Mental Health Center Affiliated with East China Normal University, Shanghai, People’s Republic of China; 3Lab for Educational Big Data and Policymaking, Ministry of Education, Shanghai Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Hong Zheng; Junlong Luo, Email zhhmm2@163.com; luo831023@vip.163.comIntroduction: The impact of emotions on intuitive and analytical thinking has been widely studied. Most research suggests that negative emotions enhance analytical processing. However, there are studies indicating that the sense of certainty associated with disgust can stimulate intuitive processing. Despite these findings, the neuroelectrophysiological evidence supporting the role of disgust in promoting intuitive processing remains unexplored.Methods: This study aimed to investigate the neuroelectrophysiological mechanisms by which disgust promotes intuitive processing. A total of 54 participants were recruited and randomly assigned to specific emotion groups. Emotional states were induced by exposing participants to disgust and fear videos designed to evoke specific dimensions of certainty and uncertainty. Event-related potentials (ERP) and the Cognitive Reflection Test (CRT) were utilized as experimental materials to measure participants’ responses.Results: The results demonstrated that disgust facilitated intuitive thinking, as evidenced by the lowest accuracy in behavioral outcomes. ERP findings showed that disgust led to smaller N2 and larger P3b amplitudes under conditions of conflict. These results suggest that disgust reduces individuals’ conflict-detection ability, resulting in a stronger sense of certainty in intuitive but incorrect answers.Conclusion: This study provides neuroelectrophysiological evidence that disgust enhances intuitive thinking. The findings offer a new perspective on the influence of emotions on dual-process thinking, highlighting the role of disgust in shaping intuitive and analytical thought processes.Keywords: certain, uncertain, disgust, fear, dual-process theory, N2, P3b

Renjiao Liu,1 Zhouhuiling Li,2 Yanju Zhang,2 Meiyang Du,2 Xincheng Wang,3 Shi Zhang,3 Chunjun Li1,3 1Graduate School, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Chunjun Li, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, No. 190 of Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of China, Tel +86-22-13752090635, Email li_chunjun@126.comBackground: Insulin resistance (IR) is a key feature of type 2 diabetes (T2D) and an independent risk factor for metabolic syndrome. Previous studies have linked elevated serum uric acid (SUA) to an increased risk of T2D.Aim: The purpose of this study was to investigate the relationship between SUA and IR. At the same time, the correlation between New model and SUA compared with other IR alternatives was compared, so as to provide a simple and effective new indicator for early detection and prediction of IR risk and early prevention of T2D.Methods: The first cohort was the Discovery Cohort, which included 318 obese patients. And the second cohort was the Verification Cohort, which included a total of 4333 subjects who underwent a routine health checkup at our hospital. Spearman correlation analysis and binary logistic regression analysis were used to discuss the correlation between SUA and IR.Results: Regardless of sex, fasting insulin (FINS) and IR replacement markers increased with SUA (P< 0.001). In both cohorts, SUA was associated with IR alternatives, especially with New model, and differed between men and women in all correlation analyses. After adjusting for confounding factors, SUA was still associated with IR (P< 0.001).Conclusion: The correlation between SUA and IR was significantly stronger in women than in men. And the correlation between SUA and New model is stronger than other IR replacement models. However, the causal relationship between SUA and IR has not been clearly established.Keywords: insulin resistance, serum uric acid, HDL-c, triglycerides

Xinyang Nie,1– 3,&ast; Jian Liu,1,2,&ast; Daohan Wang,1,2,&ast; Chuan Li,1,2 Yuxin Teng,1,2 Zhufeng Li,1,2 Yangpu Jia,1,2 Peiyao Wang,1,2 Jingyu Deng,2,3 Weidong Li,1,2 Li Lu1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Lu; Weidong Li, Department of General surgery, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Email luli_1989@126.com; tjmughgs_lwd@163.comBackground: Cisplatin (DDP) resistance in gastric cancer (GC) is likely to come from gastric cancer stem cells (GCSC). It is a new idea to study the mechanism of the DDP-resistance in GCSC from miRNA.Materials and Methods: CD44+ GCSCs and CD44- control cells were constructed based on the HGC27 gastric cancer cell line. DDP sensitivities in CD44+ and CD44- cells were detected via CCK-8 assay. The differential expression of miR-21-5p in these cell lines was detected by RT‒qPCR. The expression levels of downstream TGF-β 2, SMAD2 and SMAD3 were determined through RT‒PCR and Western blotting. A luciferase assay was used to detect the relationship between miR-21-5p and TGFB2, and the TCGA database, clinical data from our centre, and vivo experiment were used for validation. Finally, we knocked down miR-21-5p to detect changes in cisplatin resistance in GCSCs and to verify changes in the levels of downstream pathways in GCSCs.Results: CD44+ GCSCs induced cisplatin resistance compared with CD44- cells. miR-21-5p was highly expressed in GCSCs, and the TGF-β 2/SMAD pathway was also highly expressed. TGFB2 was proven to be a downstream target gene of miR-21-5p and had a positive relationship with it in phenotype. After knockdown of miR-21-5p, the TGF-β 2/SMAD pathway was also inhibited, and the resistance of GCSCs to cisplatin was specifically decreased.Conclusion: MiR-21-5p promotes cisplatin resistance in gastric cancer stem cells by regulating the TGF-β 2/SMAD signalling pathway.Keywords: miR-21-5p, cisplatin resistance, GCSCs, TGF-β 2 pathway

Mu Yuan,1,2,&ast; Weijun Wan,1,2,&ast; Wei Xing,1,2 Chengxiu Pu,1,2 Xiaofeng Wu,1,2 Zhikang Liao,3 Xiyan Zhu,3 Xueting Hu,1,2 Zhan Li,1,2 Qing Zhao,1,2 Hui Zhao,3,&ast; Xiang Xu1,2,&ast; 1Department of Stem Cell and Regenerative Medicine, National Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Xu, Stem Cell and Regenerative Medicine Department, Daping Hospital, Army Medical University, Chongqing, No. 10, Changjiang Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email xiangxu@tmmu.edu.cn Hui Zhao, Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China, Email Zhaohui@tmmu.edu.cnPurpose: We aimed to investigate whether peripheral blood biomarkers B2M related to immune response can serve as indicators of HAPE pathophysiological characteristics or disease progression.Patients and Methods: Bioinformatics technology was used to explore the peripheral blood pathophysiological mechanisms and immune hub genes related to the occurrence of HAPE. The hub gene was verified through animal experiments, and its function and correlation between its expression level and the diagnosis, treatment effect and prognosis of HAPE were explored.Results: The GSVA results showed that the occurrence of HAPE was related to the down-regulation of immune response pathways by RUNX3 and STING. WGCNA results showed that the peripheral blood immune gene module related to the development of HAPE was related to the decrease of immune function and the increase of immune checkpoint molecule PD-L1 gene expression, and the expression of immune checkpoint genes LILRB2 and SIGLEC15 increased. Cytoscape software, RT-qPCR and WB confirmed that the hub gene B2M is a specific peripheral blood biomarker of HAPE. ROC, DCA, RT-qPCR, HE and Masson results showed that the expression of peripheral blood B2M has the ability to indicate the diagnosis, treatment effect and prognosis of HAPE. The decreased expression of B2M protein in peripheral blood leukocytes may be a marker of HAPE. Single-gene GSEA confirmed that the reduced expression of B2M in peripheral blood may be involved in the down-regulation of the antigen presentation pathway mediated by MHC class I molecules, was positively correlated with the down-regulation of the TNF signaling pathway, and was negatively correlated with the expression of LILRB2 and SIGLEC15.Conclusion: The occurrence of HAPE may be related to decreased immune function and immune tolerance. Peripheral blood B2M may be involved in the related pathways, its expression level can prompt the diagnosis, treatment and prognosis of HAPE. Keywords: high altitude pulmonary edema, immune tolerance, biomarker, B2M, prognosis

Yongcheng Yao,1,2 Jie Tang,3 Zhenzhen Li,1 Shuyan Chen,1 Haixia Du,1 Lingeng Lu4 1School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, People’s Republic of China; 2WorldPop, School of Geography and Environmental Science, University of Southampton, Southampton, UK; 3Library, Zhengzhou University of Technology, Zhengzhou, Henan, People’s Republic of China; 4Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, USACorrespondence: Yongcheng Yao, School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, 450044, People’s Republic of China, Email 806306944@qq.comObjective: COVID-19-related lockdown can lead to mental health problem, which displays heterogeneous between individuals. The aim of this study was to explore the association between mental health, social support and psychological capital state of professional staff with different personalities during the COVID-19 pandemic in China.Methods: A cross-section study was conducted via online survey using the questionnaires of General Health Questionnaire (GHQ-12), Multidimensional Scale of Perceived Social Support (MSPSS), Psychological Capital Questionnaire (PCQ), Eysenck Personality Questionnaire-Revision Short Scale of China (EPQ-RSC). A total of 626 employees were included. Multiple regression analysis was performed to investigate the association of psychological capital, perceived social support, EPQ-N and EPQ-E and their interactions in general mental health.Results: About 2.7% of professionals had mental health. The married had a higher mental health score than the single (P

Xuanling Chen,1,&ast; Xuewei Qin,1,&ast; Yutong Zhuang,2 Zhengqian Li,3 Zhenhu Liang,4 Hua Zhang,5 Lan Yao,1 Xiaoli Li,6 Jianghong He,7 Xiangyang Guo3 1Department of Anesthesiology, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Institute of Electrical Engineering, Yanshan University, Qinhuangdao, People’s Republic of China; 5Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 6The State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People’s Republic of China; 7Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo, Peking University, Third Hospital, 49 huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn Jianghong He, Beijing Tiantan Hospital, 119 South Fourth Ring Road West, Fengtai District, Beijing, 100069, People’s Republic of China, Email hejianghong@sina.cnObjective: To observe whether maintaining the appropriate depth of anesthesia with Bispectral Index (BIS) can improve the prognosis of Spinal Cord stimulation (SCS) implantation in patients with chronic Disorders of consciousness (DoC).Methods: 103 patients with DoC undergoing SCS implantation were reviewed, and 83 patients with DoC were included according to the standard of inclusion and exclusion Criteria. Patients were divided into a BIS group (n =45) and a non-BIS group (n =38) according to whether BIS monitoring was used during the operation. The depth of anesthesia in the BIS group was maintained between 40– 60. The anesthesiologist adjusted the depth of anesthesia in the non-BIS group according to clinical experience. Relevant information such as disease course, cause, anesthesia time, and operation time were collected. Preoperative CRS-R(preoperative) score, postoperative CRS-R(24h), and postoperative CRS-R(3m) changes were collected.Results: The CRS-R(3m) score in the BIS group was higher than that in the non-BIS group (preoperative), and the difference was statistically significant (P < 0.05). In CRS-R (24h), the BIS group was higher than the non-BIS group, and the difference was statistically significant (X2=8.787, P =0.004). The improvement of consciousness was included in the multivariate Logistic regression analysis model, and it was found that the thalamus was an independent factor affecting the improvement of consciousness (P < 0.05). During follow-up, 1 patient in the BIS group had a decrease in consciousness from MCS− to VS/ UWS and 2 patients in the non-BIS group died during follow-up.Conclusion: Patients can be benefit in hearing in CRS-R (24h). We recommend the use of BIS to monitor the depth of anesthesia in patients with DoC to improve patient outcomes.Keywords: chronic disturbance of consciousness, vegetative state/unresponsive wakefulness syndrome, spinal cord stimulation, general anesthesia, bispectral index, improved coma recovery scale

Anbang Zhao,1,2,&ast; Bin Hao,1,2,&ast; Simin Liu,3,&ast; Xiaoyu Qiu,1,2,&ast; Xiaoping Ming,1,2 Xiuping Yang,1,2 Jie Cai,1,2 Zhen Li,4,5 Xiong Chen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Neurosurgery, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Bariatric and Metabolic Disease Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Chen, Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email zn_chenxiong@whu.edu.com Zhen Li, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email kamel_li@163.comPurpose: The diagnosis of severe OSA still relies on polysomnography, which causes a strong sense of restraint in patients with obesity. However, better prediction tools for severe OSA applicable to patients with obesity have not been developed.Patients and Methods: Relevant clinical data of 1008 patients with OSA who underwent bariatric surgery in our hospital were collected retrospectively. Patients were divided into training and test cohorts by machine learning. Univariate and multivariate logistic regression analysis was used to screen associations, including liver stiff measurement (LSM) and abdominal visceral tissue (aVAT), and to construct a severe OSA risk prediction nomogram. Then, we evaluated the effectiveness of our model and compared our model with the traditional Epworth Sleepiness Scale (ESS) model. Finally, our associations were used to explore the correlation with other indicators of OSA severity.Results: Our study revealed that age, biological sex, BMI, LSM, aVAT, and LDL were independent risk factors for severe OSA in patients with obesity. A severe OSA risk prediction nomogram constructed by six indicators possessed high AUC (0.845), accuracy (77.6%), and relatively balanced specificity and sensitivity (72.4%, 82.8%). The Hosmer-Lemeshow test (P=0.296, 0.785), calibration curves, and DCA of the training and test cohorts suggested better calibration and more net clinical benefit. Compared with the traditional ESS model, our model had higher AUC (0.829 vs 0.545), sensitivity (78.9% vs 12.2%), PPV (77.9% vs 53.3%), and accuracy (75.4% vs 55.2%). In addition, the associations in our model were independently correlated with other indicators reflecting OSA severity.Conclusion: We provided a simple, cheap, and non-invasive nomogram of severe OSA risk prediction for patients with obesity, which would be helpful for preventing further complications associated with severe OSA.Plain Language Summary: Question: Can we predict severe OSA in patients with obesity by their metabolic complications through some non-invasive examinations?Findings: Compared with traditional questionnaires, we developed and validated a new prediction model, including liver stiffness measurement and abdominal visceral adipose tissue, to screen severe OSA in bariatric surgery candidates through non-invasive examinations, which may contribute to perioperative safety and ultimate weight loss outcomes.Meaning: For patients with obesity who are in hospital because of metabolic disorders, it is necessary for them to be screened for possible severe OSA according to our new prediction nomogram, which is helpful for preventing further complications and perioperative risk associated with severe OSA.Keywords: obstructive sleep apnea, obesity, liver stiffness measurement, visceral adipose tissue, nomogram

Mingyue Shang,&ast; Zhehong Li,&ast; Dexiao Du,&ast; Guangzhong Xu, Dongbo Lian, Zhaohui Liao, Dezhong Wang, Buhe Amin, Zheng Wang, Weijian Chen, Nengwei Zhang, Liang Wang Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nengwei Zhang; Liang Wang, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +8613801068802 ; +8619800320171, Email zhangnw@ccmu.edu.cn; 1911110644@pku.edu.cnPurpose: Obesity and related complications are managed by One Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG), both of which are adapted from traditional gastric bypass procedures. However, there are no current comparative studies on the safety and efficacy of these two surgical procedures.Patients and Methods: Preoperative baseline data of patients who had undergone OAGB and SADJB-SG surgeries from June 2019 to June 2021 were retrospectively analyzed at our bariatric facility. Postoperative data, including weight changes, improvement in type 2 diabetes (T2DM), and complication rates were collected over 2 years. This was followed by a comprehensive evaluation of the safety and efficacy of the two surgical procedures.Results: A total of 63 patients completed the follow-up in this study. At the 24-month follow-up, excess weight loss percentage (EWL%) for the OAGB and SADJB-SG was 73.970± 5.005 and 75.652± 7.953, respectively (P-value = 0.310); total weight loss percentage (TWL%) was 24.006± 8.231 and 23.171± 6.600, respectively (P-value = 0.665). The diabetes remission rates for the two groups were 71.429% and 69.048%, respectively (P-value = 0.846). The cost for OAGB was 55088.208± 1508.220 yuan, which was significantly lower than the 57538.195± 1374.994 yuan for SADJB-SG (P-value< 0.001).Conclusion: The two surgical procedures are reliable in terms of safety and efficacy, and each has distinct advantages. While OAGB has reduced operational expenses, SADJB-SG offers a broader range of applicability.Keywords: one anastomosis gastric bypass, single anastomosis duodeno-jejunal bypass with sleeve gastrectomy, safety, efficacy

Xinyong Lu,1,&ast; Zixuan Li,2,&ast; XianFeng Zhu,3 Dong Li,4 Jiahui Wei1 1College of Economy and Trade, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, People’s Republic of China; 2Peking University, School of Psychological and Cognitive Sciences, Beijing, People’s Republic of China; 3University of Macau, Faculty of Education, Macau, People’s Republic of China; 4Department of International Culture Education, Chodang University, Muan, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jiahui Wei, College of Economy and Trade, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, People’s Republic of China, Email weijiahui@zhku.edu.cnPurpose: There is robust evidence indicating the adverse association between childhood abuse and depressive symptoms. However, the ways in which childhood physical abuse is indirectly associated with adulthood depressive symptoms by alexithymia and moral disengagement remain poorly understood, particularly in the context of China. The present study aims to investigate how childhood physical abuse may be associated with depressive symptoms via the serial mediation effects of alexithymia and moral disengagement among college students in China.Methods: A total of 686 college students (female: 53.2%) aged from 17 to 28 years old (M = 21.33; SD = 2.53) were recruited from mainland China to participate in an online survey assessing the variables of interest. Structural equation modeling and multiple group analysis were performed using Mplus 7.0 to investigate the hypothesized model.Results: College students’ experiences with childhood physical abuse was significantly associated with their depressive symptoms. This relationship was partially mediated by alexithymia and then by moral disengagement. Meanwhile, alexithymia and moral disengagement had a chain mediating effect on childhood physical abuse and depressive symptoms. Furthermore, multigroup analysis revealed that the association between alexithymia and depressive symptoms was stronger among rural students compared to urban students. Furthermore, the mediation model involving moral disengagement applies exclusively to rural students.Conclusion: Alexithymia and moral disengagement exerted serial mediating effect on the association between childhood physical abuse and depressive symptoms. This pattern was particularly pronounced among rural students. These findings underscore the importance of addressing both childhood adversity and maladaptive cognitive processes in the prevention and treatment of depression.Keywords: childhood physical abuse, depressive symptoms, alexithymia, moral disengagement, urban-rural areas

Mina Wang,1,2,&ast; Yashuo Ren,1,&ast; Hongli Xiao,1 Anming Liu,1,2 Chunying Ma,2 Zhuohao Li,2 Zixi Wang,2 Qiuyu Xia,2 Pu Dou,1 Bin Li,2 Peng Chen2 1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Chen; Bin Li, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23 Meishuguanhou Street, Beijing, Dongcheng District, 100010, People’s Republic of China, Email chenpenger@126.com; libin@bjzhongyi.comIntroduction: Parkinson’s disease (PD)-related chronic pain is a prevalent non-motor symptom, this study aimed to detect the effect and safety of fire needling therapy (FNT) for PD-related chronic pain relief.Methods: Patients with PD-related chronic pain were randomly allocated to FNT group and control group with a treatment phase of 8 weeks and a follow-up phase of 4 weeks. Primary outcome was the King’s Parkinson’s Pain Scale (KPPS), Secondary outcomes included Visual Analogue Scale (VAS), Unified Parkinson’s Disease Rating Scale-III (UPDRS-III), and the Parkinson’s Disease Questionnaire-39 (PDQ-39). Study was registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2400084951).Results: 60 participants were randomized, with 30 in the FNT group and 30 in the control group. KPPS was significantly influenced by the interaction of treatment and time, with a significant reduction in pain observed in the FNT group compared to the control group at Week 4 (difference [95% CI]: − 20.693[− 27.619,-13.767], P< 0.001), Week 8 (difference [95% CI]: 44.680[− 52.359,-37.000], P< 0.001), and Week 12 (difference [95% CI]: − 44.982[− 52.771,-37.193], P< 0.001). For VAS, UPDRS-III, and PDQ-39, there were significant differences between groups at Week 4, Week 8, and Week 12.Conclusion: FNT could be an effective and safe method for managing PD-related chronic pain. However, large-sample studies conducted in multiple centers are necessary to further verify the findings in the future.Keywords: parkinson’s disease, pain, fire needling therapy, acupuncture, pilot randomized controlled trial

Jiafeng Lu,1,&ast; Zhaoyan Li,2,&ast; Xingjing Liu,2 Bin Xu,1 Weiyu Zhang2 1Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiyu Zhang, Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, People’s Republic of China, Tel +86-021-67888394 ; Tel +86-13818103558, Email zhangweiyu33@163.com Bin Xu, Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, People’s Republic of China, Tel +86-021-67888176 ; Tel +86-18917762607, Email xb40291@rjh.com.cnBackground: The resistance to endocrine therapy can lead to recurrence and metastasis of breast cancer (BC), affecting the survival period. Tiaogan Bushen Xiaoji (TGBSXJ) Formula, a traditional Chinese medicine (TCM) decoction, has been widely used in the treatment of estrogen receptor-positive (ER+) BC. However, the underlying mechanism of TGBSXJ Formula in ER+BC treatment has not been totally elucidated.Methods: Network pharmacology (NP) and RNA sequencing were used to predict the candidate ingredients and explore the potential targets of TGBSXJ Formula. Then, the results of NP and RNA sequencing were investigated by in vitro experiments.Results: Active ingredients of TGBSXJ Formula mainly included Mangiferin, Rutin, Anemarrhena asphodeloides saponin BII, Ganoderic acid A and Acacetin, etc. A protein-protein interaction (PPI) network was created based on the active ingredients of TGBSXJ Formula and target genes of ER+ BC, in which TGF-β, MMP2 and SMAD3 were defined as the hub genes. In vitro experiments showed that TGBSXJ Formula significantly inhibited the viability, colony ability and migration of ER+ BC cells, and significantly increased the sensitivity to TAM. Western blot analysis showed that TGBSXJ Formula significantly downregulated TGF-β, E-cadherin, MMP2, MMP9, N-cadherin, p-Smad2 and p-Smad3 in ER+ BC cells.Conclusion: TGBSXJ Formula increases the sensitivity of ER+ BC cells to TAM by inhibiting the TGF-β/Smad signaling pathway.Keywords: estrogen receptor-positive breast cancer, network pharmacology, traditional Chinese medicine, endocrine resistance

Min He, Huinan Wu, Guanrong Lin, Yongqin Wang, Longling Shi, Chaoling Huang, Qingyun Xu, Zhenxing Li, Shanbo Huang, Yanni Chen, Na Li Department of Endocrinology, Shishi General Hospital, Shishi, Fujian, 362700, People’s Republic of ChinaCorrespondence: Min He, Department of Endocrinology, Shishi General Hospital, No. 2156 Shijin Road, Shishi, Fujian, 362700, People’s Republic of China, Tel +8613506048712, Email heminhem463@163.comObjective: This study proposes a region-wide blood glucose management system to solve the problem of blood glucose management in patients with diabetes.Methods: A professional team of doctors, nurses and dietitians jointly developed a region-wide blood glucose management system. The system operates through a collaborative approach where each team member utilises their specialised role, such as data monitoring, algorithm development or patient support, to contribute to a comprehensive blood glucose management network. This integration ensures accurate glucose tracking, personalised feedback and timely adjustments to treatment plans. The system allows the patient to have a good treatment plan, giving comprehensive medical guidance, and the physician team is responsible for the patient’s health status.Results: The region-wide blood glucose management system increased the overall blood glucose monitoring rate of patients and reduced the hospitalisation time (from 11.27 days to 9.52 days) and hospitalisation costs (from 12,173.8 yuan to 9502.4 yuan). At the same time, the system effectively counted the incidence and occurrence time of hyperglycaemia and hypoglycaemia adverse events, which can provide a reference for clinical prevention of adverse events.Conclusion: A region-wide blood glucose management system can improve medical efficiency, save medical resources and provide a strong guarantee for the health of patients with diabetes. Compared with the traditional diabetes management mode, the region-wide blood glucose management system is more systematic and standardised, meaning it can better meet the needs of patients with diabetes.Keywords: diabetic, glucose management, professional team, guarantee for the health, improve medical efficiency

Jun Guo,1 Jie Yang,2 Jinghua Wang,3 Wei Liu,1 Yingjie Kang,4 Zhi Li,1 Chen Hao,1 Shuai Qi1 1General Surgery, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 2Cadre Ward, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 3Nephrology, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 4General Surgery, Hebei Yiling Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Jie Yang, Cadre Ward, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China, 398 West Zhongshan Road, Shijiazhuang, People’s Republic of China, Tel +8615350539632, Email 270593583@qq.comPurpose: This study examined gender differences in the association of Triglyceride-Glucose (TyG) index with the prevalence of chronic obstructive pulmonary disease (COPD), particularly in a non-diabetic population.Methods: The study leveraged data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2018, with a cohort of 23,456 participants. Logistic regression and restricted cubic spline analyses were employed to explore the relationship between the TyG index and COPD prevalence.Results: Statistical analyses revealed a significant positive association between the TyG index and COPD prevalence among non-diabetic women after adjustment for all covariates (OR=1.50; 95% CI, 1.08– 2.08), supported by a linear relationship (P for non-linearity=0.298). No equivalent significant association was found in non-diabetic men (OR=1.00; 95% CI, 0.67– 1.48). Within the diabetic group, the TyG index did not show a significant association with COPD prevalence, regardless of gender.Conclusion: Our study reveals a significant positive correlation between the TyG index and COPD prevalence in the non-diabetic population, marked by notable gender differences.Keywords: TyG index, insulin resistance, chronic obstructive pulmonary disease, cross-sectional study

Zonglin Li,1,&ast; Xingming Shu,1,&ast; Xin Liu,1 Qiuyun Li,2 Yifu Hu,2 Bingbing Jia,2 Min Song3 1Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Grade 2023, Clinical Medicine College, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Song, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +8615883059785, Email songminlele2007@126.comAbstract: Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract, and chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from chemotherapy in the long term, which ultimately leads to tumor recurrence, metastasis, and patient death. Elucidating the detailed mechanism of chemoresistance in GC and identifying specific therapeutic targets will help to solve the difficult problem of chemoresistance and improve the prognosis of patients with GC. This review summarizes and clarifies the cellular and molecular mechanisms underlying chemoresistance for GC.Keywords: gastric cancer, chemoresistance, cellular mechanisms, molecular mechanisms

Xiaoqin Wei,1,&ast; Fang Wang,2,&ast; Ying Liu,3 Zeyong Li,4 Zhong Xue,2 Mingyue Tang,5 Xiaowen Chen1 1School of Medical Imaging, North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China; 2Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City, Sichuan Province, People’s Republic of China; 4Department of Radiology, Bishan Hospital of Chongqing Medical University, ChongQing, People’s Republic of China; 5Department of Physics, School of Basic Medicine, North Sichuan Medical College, Nanchong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaowen Chen, School of Medical Imaging, North Sichuan Medical College, 234 Fujiang Road, Nanchong City, Sichuan Province, People’s Republic of China, 637001, Email 56833804@qq.comPurpose: To predict the efficacy of patients treated with hepatectomy and transarterial chemoembolization (TACE) based on machine learning models using clinical and radiomics features.Patients and Methods: Patients with HCC whose first treatment was hepatectomy or TACE from June 2016 to July 2021 were collected in the retrospective cohort study. To ensure a causal effect of treatment effect and treatment modality, perfectly matched patients were obtained according to the principle of propensity score matching and used as an independent test cohort. Inverse probability of treatment weighting was used to control bias for unmatched patients, and the weighted results were used as the training cohort. Clinical characteristics were selected by univariate and multivariate analysis of cox proportional hazards regression, and radiomics features were selected using correlation analysis and random survival forest. The machine learning models (Deathhepatectomy and DeathTACE) were constructed to predict the probability of patient death after treatment (hepatectomy and TACE) by combining clinical and radiomics features, and an optimal treatment regimen was recommended. In addition, a prognostic model was constructed to predict the survival time of all patients.Results: A total of 418 patients with HCC who received either hepatectomy (n=267, mean age, 58 years ± 11 [standard deviation]; 228 men) or TACE (n=151, mean age, 59 years ± 13 [standard deviation]; 127 men) were recruited. After constructing the machine learning models Deathhepatectomy and DeathTACE, patients were divided into the hepatectomy-preferred and TACE-preferred groups. In the hepatectomy-preferred group, hepatectomy had a significantly prolonged survival time than TACE (training cohort: P < 0.001; testing cohort: P < 0.001), and vise versa for the TACE-preferred group. In addition, the prognostic model yielded high predictive capability for overall survival.Conclusion: The machine learning models could predict the outcomes difference between hepatectomy and TACE, and prognostic models could predict the overall survival for HCC patients.Keywords: radiomics, hepatocellular carcinoma, prognosis, hepatectomy

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

Yi Fang,1 Yuqi Jiang,2 Linlin Ma,1 Huixian Chen,1 Zhi Li,1 Fen Luo,1 Wen Jiang,1 Shuya Cai,1 Qiaoqiao Guo,3 Zhiqin Yin1,4 1School of Nursing, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2The First Hospital of Jiaxing City, Jiaxing City, Zhejiang Province, People’s Republic of China; 3College of Renji, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 4Wenzhou Health Promotion Research Center, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Zhiqin Yin; Qiaoqiao Guo, Email yzq@wmu.edu.cn; 1574612325@qq.comPurpose: While previous studies have extensively examined the impact of receiving positive social support during social support interactions on depressive symptoms among older adults, adverse effects experienced, such as being rejected or ignored, are often overlooked. Moreover, there has been limited discussion on the effects of giving social support to others. Thus, this study investigates the impacts of social support given by disabled older adults to others on their own depressive symptoms, as well as the mediating role of receiving social support (both positive and negative aspects) and the moderating effect of the activity of daily living (ADL).Patients and Methods: This cross-sectional, community-based study was conducted in Wenzhou and Jiaxing City, China, from September 2021 to September 2022, with a total of 255 disabled older adults meeting the inclusion and exclusion criteria. The data were collected face-to-face using a structured questionnaire. The participants were asked to complete the Barthel Index Scale, the Chinese version of the Positive and Negative Social Exchange Scale, the Giving Social Support questionnaire, and the Short Form Chinese Geriatric Depression Scale to measure disability, receiving positive and negative social support, giving social support, and depressive symptoms, respectively. Descriptive statistical analysis, correlation analysis, mediation effect tests, and moderation effect tests were used to analyse the questionnaire data.Results: The social support provided by disabled older adults to others primarily involved companionship and care. The positive aspect of social support received was largely emotional support, while the negative aspect was mainly characterised by failure to obtain help and unsympathetic behaviour. Providing social support was found to be associated with a potential beneficial effect on depressive symptoms, linked to lower severity, with this effect fully mediated by receiving social support. Specifically, receiving emotional support accounted for 56.63% of the effect size, while failure to obtain help and unsympathetic behaviour contributed 21.55%, and rejection and neglect collectively accounted for 21.83%. Additionally, the effect was partially moderated by ADL, with older adults exhibiting lower ADL scores showing a greater benefit from both giving and receiving social support compared to those with higher ADL scores.Conclusion: It is imperative to recognise and encourage disabled older adults to provide social support to others, especially emotional support, while reducing negative feedback, such as neglect and unnecessary blame. This could alleviate their depressive symptoms and promote psycho-social well-being.Keywords: disabled older adults, social support, social exchange, depressive symptoms, ADL

Zhuajin Bi,1,2 Huajie Gao,1,2 Jing Lin,1,2 Mengcui Gui,1,2 Yue Li,1,2 Zhijun Li,1,2 Bitao Bu1,2 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhijun Li, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, Email lizhijun@tjh.tjmu.edu.cn Bitao Bu, Email bubitao@tjh.tjmu.edu.cnPurpose: To investigate the predictors for poor outcomes (including disease exacerbation, hospitalization and myasthenic crisis) in patients with pre-existing myasthenia gravis (MG) following Coronavirus disease 2019 (COVID-19), and to explore the potential effects of COVID-19 on inflammatory and immune responses in MG patients.Patients and Methods: This retrospective cohort study analyzed medical records of 845 MG patients who were diagnosed with COVID-19 between January 2020 to March 2023 at a single medical center.Results: Generalized MG at onset and comorbidities (chronic kidney disease and malignancy) were independent risk factors of poor outcomes. Patients achieving minimal manifestation or better status before COVID-19 had a significantly reduced risk for poor outcomes. Furthermore, patients with older onset age or anti-acetylcholine receptor antibody had a higher risk of exacerbation and hospitalization than those without. Prednisone or immunosuppressant treatment had the potential to reduce the occurrence of poor outcomes, while the duration of prednisone or immunosuppressant usage was associated with a higher risk of poor outcomes. Of the 376 MG patients with blood results available, patients with COVID-19 tended to have higher levels of leukocyte counts, neutrophil-lymphocyte-ratio, hypersensitive C-reactive protein, and Interleukin-6, as well as lower percentages of lymphocytes and regulatory T cells compared to patients without COVID-19.Conclusion: Disease severity at onset, comorbidities, and unsatisfactory control of myasthenic symptoms predicted the occurrence of poor outcomes in MG patients following COVID-19. The risk of poor outcomes was reduced in patients controlled by short-term immunosuppressive therapy. Novel coronavirus might affect inflammatory and immune responses in MG patients, particularly in altering interleukin-6 and regulatory T cell levels.Keywords: myasthenia gravis, COVID‐19, poor outcomes, immunosuppressive treatment, immune responses

Liyan Sun,1 Jinshuai Lan,1,2 Zhe Li,1,2 Ruifeng Zeng,1,2 Yi Shen,1 Tong Zhang,1,2 Yue Ding1– 3 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3National Innovation Platform for Medical Industry-Education Integration, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Yue Ding; Tong Zhang, Email dingyue-2001@hotmail.com; zhangtongshutcm@hotmail.comAbstract: Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery. Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. Nano-delivery systems increase drug concentration at the tumor site by improving pharmacological activity and tissue distribution, enhancing drug bioavailability. Organic nanocarriers have advantages for berberine delivery including biocompatibility, encapsulation, and controlled release of the drug. While the advantages of inorganic nanocarriers for berberine delivery mainly lie in their efficient loading ability of the drug and their slow release ability of the drug. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery.Keywords: berberine, anti-cancer, nano drug delivery system, combination therapy

Tingting Zhang,1– 3,&ast; Jinglin Mi,1– 3,&ast; Xinling Qin,1– 3,&ast; Zhechen Ouyang,1– 3 Yiru Wang,1– 3 Zhixun Li,1– 3 Siyi He,1– 3 Kai Hu,1– 3 Rensheng Wang,1– 3 Weimei Huang1– 3 1Department of Radiation Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimei Huang; Rensheng Wang, Department of Radiation Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email huangweimei@gxmu.edu.cn; wangrensheng@gxmuhospital.cnBackground: Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved.Methods: m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation.Results: We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF.Conclusion: These findings suggest that RA is a potential therapeutic agent for RIPF.Keywords: rosmarinic acid, exosomes, tRNA, N7-methylguanosine, radiation-induced pulmonary fibrosis

Zheng Wang,1,2,&ast; Yifan Wu,1,2,&ast; Wanrong Yi,1,2 Yifeng Yu,1,2 Xue Fang,1,2 Zonghuan Li,1,2 Aixi Yu1,2 1Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Clinical Medical Research Center of Trauma and Microsurgery, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aixi Yu; Zonghuan Li, Email yuaixi@whu.edu.cn; lizonghuan@whu.edu.cnBackground: Traumatic heterotopic ossification (HO) is a devastating sequela of orthopedic surgeries and traumatic injuries; however, few studies have explored the effects of the estrogen-deficient state on HO formation. In the present study, we investigated the impact of estrogen deficiency on ectopic cartilage and bone formation in tendon after Achilles tenotomy in an ovariectomized mouse model.Methods: A total of 45 female C57BL/6 mice were randomly divided into three groups: sham-operated (control), estrogen depletion by ovariectomy (OVX) and OVX with 17β-estradiol supplementation (OVX + E2), with 15 animals in each group. Three weeks after OVX, all mice were subjected to an Achilles tenotomy using a posterior midpoint approach to induce HO. At 1, 3 and 9 weeks after tenotomy, the left hind limbs were harvested for histology, immunohistochemistry and immunofluorescence evaluations. The volume of ectopic bone was assessed by micro-CT.Results: Mice in the OVX group formed more ectopic cartilage 3 weeks after tenotomy, as well as ectopic bone 9 weeks after tenotomy, compared to the control group. Estrogen deficiency resulted in more severe inflammatory infiltration at the injury sites 1 week after tenotomy, involving the recruitment of more macrophages and mast cells, as well as increasing the expressions of pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α. Moreover, the local TGF-β/SMAD signaling pathway was dysregulated after OVX, which manifested as upregulated expressions of TGF-β and pSMAD2/3. E2 supplementation protected against OVX-induced HO deterioration, inhibited inflammatory infiltration, and downregulated the TGF-β/SMAD signaling pathway.Conclusion: Estrogen deficiency exacerbated HO formation in the Achilles tenotomy model. These findings might be attributable to the disturbance of the inflammatory response and the activation of TGF-β/SMAD signaling at the injury sites during the early stages of HO development.Keywords: heterotopic ossification, estrogen deficiency, inflammation, TGF-β/SMAD signaling

Jiaqin Yu,1,&ast; Ting Shen,2,&ast; Zongshan Li,3 Tian Lv,4 Lisan Zhang3 1School of Medicine, Shaoxing University, Shaoxing, Zhejiang, People’s Republic of China; 2Department of Neurology, Zhuji People’s Hospital of Zhejiang Province, Zhuji, People’s Republic of China; 3Department of Neurology and Center for Sleep Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lisan Zhang, Department of Neurology and Center for Sleep Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email zls09@zju.edu.cnAbstract: Narcolepsy type 1 (NT1) is a unique central sleepiness disorder that affects individuals with excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, and hypnagogic hallucinations. The etiology and pathogenesis of NT1 remains unclear, although some viral infections are thought to be related to NT1. This paper reports an unusual case of late-onset NT1 with human immunodeficiency virus (HIV) infection and antiretroviral therapy for five years. The relationship between HIV infection, immune, Immune reconstitution inflammatory syndrome (IRIS) and NT1 should be further investigated, as excessive daytime sleepiness is more common in HIV-infected patients than in the general population.Keywords: narcolepsy, excessive daytime sleepiness, HIV, immune, Immune reconstitution inflammatory syndrome

Baokun Liu,1,2,&ast; Lujun Shen,3,4,&ast; Wen Liu,5 Zhiyong Zhang,1,2 Jieqiong Lei,1,2 Zhengguo Li,1,2 Qinquan Tan,6 Hengfei Huang,7 Xingdong Wang,1,2 Weijun Fan3,4 1Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center Gansu Hospital, Lanzhou, 730050, People’s Republic of China; 2Department of Minimally Invasive Interventional Therapy, Gansu Provincial Cancer Hospital, Lanzhou, 730050, People’s Republic of China; 3Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 5Department of Radiotherapy, Lanzhou University Second Hospital, Lanzhou, 730030,People’s Republic of China; 6Department of Oncology, Dongguan People’s Hospital, Dongguan, 523000, People’s Republic of China; 7Department of General Surgery, Chongzuo People’s Hospital, Chongzuo, 523000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingdong Wang; Weijun Fan, Email wxd101027@163.com; fanwj@sysucc.org.cnPurpose: The majority of new diagnoses of hepatocellular carcinoma (HCC) still pertain to unresectable cases. Currently, the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors has become the mainstream treatment. According to multiple clinical guidelines, it is strongly advised to consider local therapy as the primary treatment choice for uHCC. This research was conducted to examine the safety and effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with TKIs and PD-1 inhibitors for the treatment of uHCC.Methods: Between 2015 and 2020, 208 HCC patients received HAIC alone or HAIC in combination with TKIs and PD-1 inhibitors. The overall survival(OS), and progression-free survival(PFS) and the best treatment response were compared between the two treatment groups. Propensity score matching (PSM)was used to minimize confounding bias.Results: Among the enrolled patients, 116 patients (55.8%) received combination therapy, while 92 patients (44.2%) received HAIC alone. The baseline characteristics were similar between the two groups. After PSM, 82 pairs of well-matched liver cancer patients were selected; the overall response rate in the combination group trended better than that in the HAIC alone group. The hazard ratios (HRs) for OS and PFS of the combination approach compared to the HAIC-alone approach were 0.47 (95% CI, 0.322– 0.687; p< 0.001) and 0.58 (95% CI, 0.397– 0.848; p=0.005), respectively.Conclusion: For uHCC patients, combination therapy can provide better OS and PFS compared to HAIC alone.Keywords: hepatocellular carcinoma, TKIs, PD-1, HAIC, combination therapy

Wei Zhang,1,&ast; Jiayu Zhang,2,&ast; Dian Jiao,1,&ast; Qisheng Tang,1 Xiaoping Gao,1 Zhenyu Li,1 Fa Yang,3 Zhiguang Zhao,1 Longfei Yang4 1Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 2Department of Urology, Air Force Hospital of Southern Theater Command, Guangzhou, Guangdong, 510062, People’s Republic of China; 3Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 4Department of Transfusion Medicine, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Longfei Yang; Zhiguang Zhao, Email y68lf@163.com; zzg13991809889@163.comPurpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear.Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results.Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell–cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor–ligand pair.Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD. Keywords: lichen sclerosus, urethral stricture disease, single-cell RNA sequencing, heterogeneity, fibroblasts, macrophages

Zhuying Zhang,1,2,&ast; Mai Shi,1,2,&ast; Jinghui Li,3 Dian Chen,1,2 Jie Ren,1,2 Zhenghui Li,1,2 Hsiaohan Tuan,1,2,&ast; Yi Zhao1,2,&ast; 1Department of Dermatology, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 2Photomedicine Laboratory, Institute of Precision Medicine, Tsinghua University, Beijing, People’s Republic of China; 3School of Medicine, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Zhao; Hsiaohan Tuan, Department of Dermatology, Beijing Tsinghua Changgung Hospital, No. 168 Litang Road, Changping District, Beijing, 102218, People’s Republic of China, Tel +86-13718646181 ; +86-18610015166, Email zhaoyimd@tsinghua.edu.cn; dxha00337@btch.edu.cnIntroduction: The aging of the skin, which is affected by both external and internal causes, can reflect the external age and the internal health status. While the aging characteristics differ across ethnic groups, the specific changes in skin aging within the Chinese population have been underexplored. Moreover, investigating the similarity of aging skin characteristics between parent-offspring pairs remains uncharted territory. This study aims to fill these gaps by examining the skin aging features of Chinese women and assessing the similarity in aging skin characteristics between mother-daughter pairs.Methods: A total of 40 mother-daughter pairs were recruited and analyzed. The perceived ages of the participants were evaluated, and their aging skin traits were systematically graded. Statistical methods were employed to discern the trends of the aging skin characteristics. By introducing a novel similarity parameter, we compared whether various skin aging characteristics have similar patterns between mothers and daughters.Results: Our findings indicate that age 50 represents a pivotal point in skin aging. Beyond this age, the increase in rhytides and laxity scores accelerated noticeably, whereas the escalation in dyschromia scores became less marked. By introducing similar parameters between mother-daughter pairs and the radar map, we discovered that the skin aging characteristics are remarkably consistent between mother-daughter pairs.Conclusion: Understanding the main aging skin characteristics of different age groups can allow caregivers to devise treatments for preventing skin aging in women of various ages. The mother’s skin aging trend is also significant for the daughter’s skin aging prevention.Plain Language Summary: Skin aging, a complex process influenced by both internal and external factors, exhibits distinct patterns across ethnic groups. Despite this, the specific aging characteristics within the Chinese population and the hereditary similarities between parents and offspring have not been thoroughly investigated. To address this gap, our study focused on the skin aging features of Chinese women and explored the resemblance in these features between mother-daughter pairs. Eighty-seven women from the same community, including 40 mother-daughter pairs, participated in our study. We assessed how old each participant appeared to be and methodically evaluated their skin aging signs by a modified scale. With the introduction of a new similarity parameter, we further examined the extent to which skin aging traits showed parallel trends between mothers and their daughters.Our findings pinpoint age 50 as a pivotal moment in the skin aging trajectory, where the increase in wrinkles and skin laxity becomes more pronounced, contrasting with a deceleration in skin discoloration. Remarkably, a consistent pattern of aging characteristics was observed between mother-daughter pairs, suggesting a potential genetic influence. This study not only sheds light on the specific skin aging patterns among Chinese women but also underscores the significance of genetic factors in shaping these patterns. The insights gained pave the way for developing targeted interventions for skin aging prevention and treatment, emphasizing the importance of considering familial aging trends.Keywords: Chinese female, skin aging pattern, aging characteristics, intergenerational analysis

Zhongbiao Nie,1 Cuilv Liang,2 Zhihong Li,1 Xinqiang Han,3 Ran Zhang4 1Department of Pharmacy, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 2Department of Pharmacy, Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 3Department of General, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 4Department of Nephrology, Affiliated Hospital of Shanxi University of Chinese Medicine, Taiyuan, 030024, People’s Republic of ChinaCorrespondence: Ran Zhang, Department of Nephrology, Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, Taiyuan, 030024, People’s Republic of China, Tel +86-13633516515, Email 115462888@qq.comPurpose: This study comprehensively describes and evaluates the correlation between gabapentinoids and all types of delirium.Methods: We used AERSMine to select all adverse reaction data from 2004 Q1 to the 2022 Q4 in the FDA Adverse Event Reporting System (FAERS) database, and delirium events reported by gabapentinoids drugs were included in this study. Collected and analyzed the clinical details of these reports. We have developed four models. Among the four models, reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to evaluate the potential association between and delirium. We undertook a subgroup analysis for the age and sex cohorts.Results: A total of 2950 reports of gabapentinoids-related delirium was collected. Excluding cases with a history of delirium (Model 2), opioid drugs (Model 3), and other adverse events related to gabapentinoids drugs (Model 4), pain cases with gabapentin drugs as the main suspected drug were selected. In model 1, the reporting rates of delirium at the delirium and delirium tremens levels were higher in the gabapentinoids group than in the non-gabapentinoids group (ROR 1.09(1.05,1.13); ROR 1.54(1.16,2.04)). In model 2.3 the delira and the delirium level were higher in the gabapentinoids group (ROR 1.42(1.29,1.56), ROR 1.44(1.31,1.59); ROR 1.43(1.30,1.58), ROR 1.46(1.33,1.61)). There is no difference in delirium levels in Model 4. Delirium levels were higher in the gabapentinoids group than in the non-gabapentinoids group in ≥ 65 years old. The delirium and deliria levels were higher in the male group than in the female group.Conclusion: The delirium adverse reactions of the gabapentinoids group were significantly higher than those of non-gabapentinoids group in the first three models. However, with the removal of confounding factors, there was no significant difference in this type of adverse reaction in Model 4. In elderly and male patients, the incidence of delirium with gabapentinoids was significantly increased.Keywords: gabapentinoids, delirium, adverse reactions, FAERS, pharmacovigilance

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

Zhanjie Li,1,&ast; Jian Li,2,&ast; Chuanlong Zhu,3 Shengyuan Jiao1,2 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Disease Prevention and Control, Air Force Hospital of Eastern Theater, Nanjing, People’s Republic of China; 3Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengyuan Jiao, Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8618021136781, Email 17319884906@163.com Chuanlong Zhu, Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +8617714316539, Email zhuchuanlong@jsph.org.cnBackground: To identify risk factors for acquiring HAIs in COVID-19 patients and establish visual prediction model.Methods: Data was extracted from Xinglin Hospital Infection Monitoring System to analyze COVID-19 patients diagnosed between December 1, 2022, and March 1, 2023. Univariate and multivariate analyses were conducted to identify risk factors. Predictive signature was developed by selected variables from lasso, logistic regression, and their intersection and union. Models were compared using DeLong’s t-tests. Likelihood ratio (LR) and Youden’s index was used to evaluate the predictive performance. Nomogram was constructed using optimal variables ensemble, prediction accuracy was evaluated using AUC, DCA and calibration curve.Results: Total of 739 patients met the criteria, of which 53 (7.2%) were HAIs. NSAIDs, surgery, fungi and MDRO detected, hormone drugs and LYMR were independent risk factors. Lasso model screened seven variables, and logistic model identified six risk factors. Union model performed the best with the maximum of the Youden’s index is 0.703, the sensitivity is 95.6%, the specificity is 74.7%, the LR is 3.778. The best AUC of union model is 0.953 (0.928– 0.978), and the accuracy is 87.5%. DCA indicated that the union model provided the best net benefits and calibration curve demonstrated good predictive agreement.Conclusions: HAIs prediction in COVID-19 patients is feasible and beneficial to improve prognosis. Physicians can use this nomogram to identify high-risk COVID-19 populations for HAIs and tailor follow-up strategies.Keywords: risk factors, healthcare-associated infection, COVID-19, nomogram, prediction model

Zhaoyong Li,1,&ast; Yanping Lin,1,&ast; Ting Qiu,2,&ast; Junsheng Liang,1 Yintao Lan,3 Fan Meng,4 Chaohao Liang,4 Yiqing Zhang,4 Qingyun Wang,1 Da Shi,1 Changli Zhang,1 Yanan Shi,1 Liujun Liu,1 Yanlan Yang,1 Jian Zhang4,5 1Department of Radiology, DongGuan Tungwah Hospital, Dongguan Key Laboratory of Radiology and Molecular Imaging, DongGuan, Guangdong, 523000, People’s Republic of China; 2Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, 510030, People’s Republic of China; 4School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 5Department of Oncology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, 511500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Zhaoyong Li, Email jianzhang@gzhmu.edu.cn; lizhaoyong2003@163.comBackground: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC).Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC.Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT.Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.Keywords: nasopharyngeal carcinoma, photoacoustic imaging, photothermal therapy, PATQ-DPP nanoparticles

Zhenyu Li,1 Jimin Liu,2 Haishan Cui,3 Wenlong Qi,4 Yangyang Tong,4 Tan Wang4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 2Department of Respiratory, The Third Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 3Department of Traditional Chinese Medicine, The Third Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 4Department of Respiratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, People’s Republic of ChinaCorrespondence: Tan Wang, Department of Respiratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, People’s Republic of China, Email wangtan0215@163.comAbstract: The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.Keywords: non-small cell lung cancer, Astragalus membranaceus, antitumor activity, immunoregulation, cisplatin

Zhengmei Li,1 Shiai Wang,2 Xunli Yin,2 Dong Tao,2 Xuebing Wang,2 Junli Zhang3 1School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, People’s Republic of China; 2Department of Cardiovascular Medicine, The Seventh People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 3Department of Emergency Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of ChinaCorrespondence: Junli Zhang, Email tyfyzjl@163.comBackground: Myocardial infarction (MI) is a chronic cardiovascular disease. This study aims to discern potentially angiogenesis- and epithelial mesenchymal transition (EMT)-related genes as biomarkers for MI diagnosis through bioinformatics.Methods: All datasets and angiogenesis- and EMT-related genes were collected from the public database. The differentially expressed genes (DEGs) of MI and MI-related genes were acquired. DEGs, MI-related genes, and angiogenesis- and EMT-related genes were intersected to obtain hub genes. Functional enrichment, immune microenvironment, and transcription factors (TFs)-hub genes regulatory network analysis were performed. The diagnostic markers and models were developed and validated. Drug prediction and molecular docking were performed. Finally, diagnostic markers expressions were validated using RT-qPCR.Results: A total of 224 angiogenesis- and EMT-related genes, 2,897 DEGs, 1,217 MI-related genes, and 9 hub genes were acquired. The immune infiltration levels of plasma cells, T cells CD4 memory activated, monocytes, macrophages M0, mast cells resting, and neutrophils were higher in patients with MI. LRPAP1, COLGALT1, QSOX1, THBD, VCAN, PLOD1, and PLAUR as the diagnostic markers were identified and used to construct diagnostic models, which can distinguish MI from controls well. Then, 9 drugs were screened, and the binding energies ranged from − 7.08 to − 5.21 kcal/mol. RT-qPCR results showed that the expression of LRPAP1, PLAUR, and PLOD1 was significantly increased in the MI group.Conclusion: The 7 diagnostic markers may play potential roles in MI and could contribute to improved future diagnostics.Keywords: myocardial infarction, angiogenesis, epithelial mesenchymal transition, diagnostic markers

Jingfang Chen,1,2 Linlin Liu,3 Junxiong Huang,1 Youli Jiang,4 Chengliang Yin,1 Lukun Zhang,5 Zhihuan Li,1 Hongzhou Lu1,5 1Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China; 2Department of Research and Teaching, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, People’s Republic of China; 3Hengyang Medical School, School of Nursing, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Neurology, The People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of China; 5Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, People’s Republic of ChinaCorrespondence: : Zhihuan Li; Hongzhou Lu, Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China, Email baopullon@163.com; luhongzhou@szsy.sustech.edu.cnBackground: Both HIV and TB are chronic infectious diseases requiring long-term treatment and follow-up, resulting in extensive electronic medical records. With the exponential growth of health and medical big data, effectively extracting and analyzing these data has become the research hotspot. As a fundamental aspect of artificial intelligence, machine learning has been extensively applied in medical research, encompassing diagnosis, treatment, patient monitoring, drug development, and epidemiological investigations. This significantly enhances medical information systems and facilitates the interoperability of medical data.Methods: In our study, we analyzed longitudinal data from the electronic health records of 4540 patients, gathered from the National Clinical Research Center for Infectious Diseases in Shenzhen, China, spanning from 2017 to 2021. Initially, we employed the fine-tuned ChatGLM to structure the electronic medical records. Subsequently, we utilized a multi-layer perceptron to classify each patient and determined the presence of tuberculosis in HIV patients. Using machine learning-based natural language processing, we structured these records to build a specialized database for HIV and TB co-infection. We studied the epidemiological characteristics, focusing on incidence patterns, patient characteristics, and influencing factors, to uncover the transmission characteristics of these diseases in Shenzhen. Additionally, we used Long Short-Term Memory to create a predictive model for TB co-infection among HIV patients, based on their medical records. This model predicted the risk of TB co-infection, providing scientific evidence for clinical decision-making and enabling early detection and precise intervention.Results: Based on the refined ChatGLM model tailored for structured electronic health records, the accuracy of symptom extraction consistently surpassed 0.95 precision. Key symptoms such as diarrhea and normal showed precision rates exceeding 0.90. High scores were also achieved in recall and F1 scores. Among 4540 HIV patients, 758 were diagnosed with concurrent tuberculosis, indicating a 16.7% co-infection rate, while syphilis co-infection affected 25.1%, underscoring the prevalence of concurrent infections among HIV patients. Utilizing electronic health records, a Multilayer Perceptron classifier was developed as a benchmark against Long Short-Term Memory to predict high-risk groups for HIV and tuberculosis co-infections. The Multilayer Perceptron classifier demonstrated predictive ability with AUROC values ranging from 0.616 to 0.682 on the test set, suggesting opportunities for further optimization and generalization despite its accuracy in identifying HIV-TB co-infections. In tuberculosis intelligent diagnosis based on laboratory results, the Long Short-Term Memory showed consistent performance across 5-fold cross-validation, with AUROC values ranging from 0.827 to 0.850, indicating reliability and consistency in tuberculosis prediction. Furthermore, by optimizing classification thresholds, the model achieved an overall accuracy of 81.18% in distinguishing HIV co-infected tuberculosis from simple HIV infection.Conclusion: Combining the Multilayer Perceptron classifier with Long Short-Term Memory represented an advanced approach for effectively extracting electronic health records and utilizing it for disease prediction. This underscored the superior performance of deep learning techniques in managing both structured and unstructured medical data. Models leveraging laboratory time-series data demonstrated notably better performance compared to those relying solely on electronic health records for predicting tuberculosis incidence. This emphasized the benefits of deep learning in handling intricate medical data and provided valuable insights for healthcare providers exploring the use of deep learning in disease prediction and management.Keywords: Prediction models, HIV, Tuberculosis, Machine Learning, Artificial Intelligence