Search

Zhihong Liu,1,2,* Xiaofang Liang,1,* Yu Zhang,1 Wenbo Deng,1 Yulin Wang,3 Zhangping Lu,2 Qianqian Liu,2 Lianhua Wei2 1School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lianhua Wei, Email 107306723@qq.comAbstract: The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.Keywords: antimicrobial resistance, multi-drug resistance, niclosamide, a derivative, drug repurposing

Qian Li, Leipeng Ren, Weitong Wu, Dangze Sun, Lin Wei, Chao Ding, Peijia Luo Department of Thoracic Surgery, Xi’an Chest Hospital, Xi’an, Shaanxi, 710100, People’s Republic of ChinaCorrespondence: Peijia Luo, Department of Thoracic Surgery, Xi’an Chest Hospital, Xi’an, Shaanxi, 710100, People’s Republic of China, Email 1171185306@qq.comBackground: To establish and validate a nomogram for predicting the culture results of Mycobacterium tuberculosis in superficial lymph nodes.Methods: The clinical data of patients with superficial lymph node tuberculosis admitted to Xi’an City Chest Hospital from November 23, 2018, to May 30, 2024, were selected and divided into a training set and a validation set according to a ratio of 7:3. Influencing factors were identified through multivariate logistic regression analyses. Using R version 4.3.2, we developed a predictive model and generated a nomogram based on this model. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curve analysis (CCA), and decision curve analysis (DCA).Results: The positive rate of superficial lymph node tuberculosis culture was 23.0% (103/446). Multivariate Logistic regression analysis showed that anti-tuberculosis treatment duration (OR=0.98, 95% CI: 0.97 ~ 0.99), initial treatment or retreatment (OR=0.12, 95% CI: 0.05 ~ 0.28), and adenosine deaminase (OR=1.12, 95% CI: 1.03 ~ 1.22) were independent factors affecting the culture results of Mycobacterium tuberculosis in superficial lymph nodes. The areas under the ROC curves were 0.86 (95% CI: 0.82– 0.91) for the training set and 0.89 (95% CI: 0.84– 0.95) for the validation set. The P values of calibration curves were 1.000 and 0.961, respectively, and the predicted values were in good agreement with the actual values. The threshold probabilities of clinical decision curves were 3%~64% and 1%~68%, respectively.Conclusion: The positive rate of Mycobacterium tuberculosis culture in superficial lymph nodes is low. The increase in retreatment patients and anti-tuberculosis treatment time are obstacle factors for Mycobacterium tuberculosis culture positivity, while an increase in adenosine deaminase is a promoting factor for Mycobacterium tuberculosis culture positivity. The nomogram model established based on these factors can be used to predict the results of Mycobacterium tuberculosis culture in superficial lymph nodes.Keywords: superficial lymph node tuberculosis, mycobacterium culture, predictive model, nomogram

Yuntao Lu,1,2,* Minyan Yin,3,4,* Ye Yang,1,2,* Wenshuo Wang,1,2 Lili Dong,5 Xue Yang,3,4 Chunsheng Wang,1,2 Xiaolin Wang,3,4 Jinmiao Chen,1,2 Lai Wei1,2 1Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Heart Valve, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 4Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lai Wei; Jinmiao Chen, Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 021 64041990, Email wei.lai@zs-hospital.sh.cn; chen.jinmiao@zs-hospital.sh.cnPurpose: Transcatheter aortic valve replacement (TAVR) induced coronary artery obstruction (CAO) is a rare but devastating complication. Current preventive strategies need additional procedures and may be associated with adverse events. This study aimed to evaluate the early safety and efficacy of stand-alone TAVR using the J-Valve (Jianshi JieCheng Medical Technology Co. Ltd, Shanghai, China) in patients at potential high risk for CAO.Patients and Methods: CAO was defined as coronary ostia obstruction requiring intervention. Patients at potential high risk for CAO were identified retrospectively from 673 consecutive patients who underwent TAVR from January 2015 to July 2021 at Zhongshan Hospital, Fudan University. Procedural results and early outcomes were evaluated according to Valve Academic Research Consortium-3 definitions.Results: A total of 20 consecutive patients (age 72 ± 9 years; 85% female;) were included. The Society of Thoracic Surgeons-Predicted Risk of Mortality was 5% (interquartile range, 4 to 10%). All patients (100%) had at least 2 classical risk factors for CAO by pre-procedural computed tomography analysis, and 90% patients had native aortic valve diseases. TAVR was successful in 95% of cases, with only 1 patient requiring second device implantation. Early safety at 30 days was achieved in all cases without death. All patients were free from CAO, stroke or emergency reintervention. Post-procedural mean aortic valve gradient was 7 (interquartile range, 4, 12) mmHg, and none/trace or mild aortic regurgitation was present in all patients.Conclusion: Stand-alone TAVR using the J-Valve may mitigate the risk of TAVR-induced CAO. Keywords: TAVR, coronary artery obstruction, aortic regurgitation, aortic stenosis, structural heart disease

Qiaolin Zhang,1,* Zhu Mei,2,* Lan Wei,1 Dong Liu,1 Chengbing Xie,1 Yongzhu Xu1 1Department of Clinical Laboratory, Chongqing Blood Center, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongzhu Xu, Department of Clinical Laboratory, Chongqing Blood Center, Chongqing, People’s Republic of China, Email xucqbc123@126.comObjective: Hepatitis B virus (HBV) infection is a significant global public health concern, with variable prevalence rates across regions. The prevalence of transfusion-transmitted HBV infection (TT-HBV) via donated blood necessitates an evaluation of blood safety and potential risks to the population. This study assessed the prevalence of HBV infection among blood donors in Southwestern China over 6 years.Methods: We analyzed 903,023 blood donations from a central blood center in Southwestern China between January 2017 and December 2022. The prevalence of HBV in donations was determined for one-time and repeat donors, considering birth cohorts and covariates. Demographic characteristics, donation frequency, and anti-HBV antibody status were analyzed to estimate the incidence of TT-HBV.Results: One-time donors provided 47.78% of the samples, and 52.22% were from repeat donors. The HBV prevalence decreased from 1.0% in 2017 to 0.87% in 2022 in one-time donors and from 0.30% to 0.09%, respectively, in repeat donors. A significantly lower HBV prevalence was identified in the post-1992 birth cohort (0.33%) than in the pre-1992 birth cohort (1.67%). The estimated incidences of TT-HBV occurring from one-time donors, repeat donors, post-1992 birth cohort donors, and pre-1992 birth cohort donors were 20.76, 13.84, 0.82, and 20.98 per 104 person-years, respectively.Conclusion: Our findings indicate a decreasing trend in HBV prevalence among blood donors in Southwestern China over the 6-year study period. This decline may be attributed to the widespread administration of HBV vaccinations and stringent screening measures implemented by blood donation centers. Continuous monitoring for HBV among blood donors is necessary to evaluate the effectiveness of preventive measures and inform future strategies to reduce transmission.Keywords: hepatitis B virus, transfusion-transmitted infections, epidemiology, vaccination

Xiuju Guan,1 Yue Liu,2 Yajuan An,1 Xinshuang Wang,1 Liping Wei,2 Xin Qi2 1School of Graduate Studies, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Department of Cardiology, Tianjin Union Medical Center, Tianjin, People’s Republic of ChinaCorrespondence: Xin Qi, Email qixinx2011@126.comAbstract: Atherosclerosis (AS) is a chronic progressive inflammatory disease of the vascular wall and the primary pathological basis of cardiovascular and cerebrovascular disease. Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), two highly homologous members of the FAK family kinases, play critical roles in integrin signaling. They also serve as scaffolding proteins that contribute to the assembly of cellular signaling complexes that regulate cell survival, cell cycle progression, and cell motility. Research indicates that the FAK family kinases is involved in the gene regulation of vascular cells and that aberrant expression of this family is associated with pathological changes in vascular disease. These findings establish the FAK family kinases as a critical signaling mediator in atherosclerotic lesions and inhibition of its activity has the potential to attenuate the pathological progression of AS. This review highlights the indispensable role of the FAK family kinases in abnormal vascular smooth muscle cell proliferation, endothelial cell dysfunction, inflammation, and lipid metabolism associated with AS. We also summarize therapeutic targets against the FAK family kinases, providing valuable insights into therapeutic strategies for AS.Keywords: FAK family kinases, atherosclerosis, inhibitors, cellular signaling

Haotian Chen, Juan Zhi, Lei Wang, Zibin Jin, Jin Xu, Fei Xing, Chao Wen, Qianyu Wang, Chunmei Chen, Weiou Li, Ermeng Xu, Jie An, Lingxin Wei Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lingxin Wei, Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 010 85557917, Email weilx3934@sina.comPurpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15– 0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction.Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62– 0.79), anxiety level (OR, 0.77; 95% CI, 0.62– 0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56– 0.98) were identified as significant predictors associated with patient satisfaction.Conclusion: A subanesthetic dose of esketamine (0.15– 0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Clinical Trial Registration: ChiCTR2400080363.Keywords: esketamine, sedation, analgesia, satisfaction, liposuction

Haoyang Tian,1,&ast; Hui Chen,2,&ast; Xiaochun Yin,2 Meiyi Lv,3 Lingling Wei,1 Yuna Zhang,4 Shuhan Jia,5 Jingyuan Li,1 Hui Song1 1School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 2Department of Endodontics, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 3Department of Pediatric Dentistry, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 4Department of Stomatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Stomatology, Yancheng NO. 1 People’s Hospital, Yancheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Song; Jingyuan Li, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-531-88382912, Fax +86-531-88382923, Email songhui@sdu.edu.cn; jingyuan_31@163.comIntroduction: Diabetes has been recognized as an independent risk factor for periodontitis. Increasing evidences indicate that hyperglycemia aggravates inflammatory response of human periodontal ligament cells (hPDLCs). Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble compound that can release carbon monoxide (CO) in a controllable manner. CORM-3 has been shown the anti-inflammatory effect in different cell lineages.Methods: We stimulated periodontal ligament cells with LPS and high glucose. The expression of inflammatory cytokine was detected by ELISA. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of TLR2, TLR4, RAGE and the activation of NF-κB pathway. We performed silencing and overexpression treatment of RAGE targeting the role of RAGE. We performed the immunostaining of paraffin sections of the periodontitis model in diabetes rats.Results: The results showed that CORM-3 significantly inhibited the expression of inflammatory cytokine in hPDLCs stimulated with LPS and high glucose. CORM-3 also inhibited LPS and high glucose-induced expression of RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway. Silence of RAGE resulted in significantly decreased expression of proteins above. Overexpression of RAGE significantly enhanced the expression of these factors. CORM-3 abrogated the effect of RAGE partially. In animal model, CORM-3 suppressed the inflammatory response of periodontal tissues in experimental periodontitis of diabetic rats.Discussion: Our research proved CORM-3 reduced the inflammatory response via RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway in the process of high glucose exacerbated periodontitis. These findings demonstrated the role of RAGE in the process of high glucose exacerbated periodontitis and suggested that CORM3 be a potential therapeutic strategy for the treatment of diabetes patients with periodontitis. Keywords: carbon monoxide-releasing molecules, periodontitis, diabetes, receptor for advanced glycation end products, lipopolysaccharide

Keke Li,1,&ast; Yaozhou Wu,1,2,&ast; Meng Liu,1 Junwen Yan,1 Lianhua Wei1 1Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China; 2First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua Wei; Junwen Yan, Department of Clinical Laboratory, Gansu Provincial Hospital, No. 204 Donggang West Road, Chengguan District, Lanzhou, 730000, People’s Republic of China, Email 3752131518@qq.com; 249380017@qq.comPurpose: Accurate detection and identification of pathogens and their associated resistance mechanisms are essential prerequisites for implementing precision medicine in the management of Carbapenem-resistant Enterobacterales (CRE). Among the various resistance mechanisms, the production of KPC carbapenemase is the most prevalent worldwide. Consequently, this study aims to develop a convenient and precise nucleic acid detection platform specifically for the blaKPC gene.Methods: The initial phase of our research methodology involved developing a CRISPR/Cas12a detection framework, which was achieved by designing highly specific single-guide RNAs (sgRNAs) targeting the blaKPC gene. To enhance the sensitivity of this system, we incorporated three distinct amplification techniques—polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA)—into the CRISPR/Cas12a framework. Subsequently, we conducted a comparative analysis of the sensitivity and specificity of these three amplification methods when used in combination with the CRISPR/Cas12a system. Additionally, we assessed the clinical applicability of the methodologies by evaluating fluorescence readouts from 80 different clinical isolates. Furthermore, we employed lateral flow assay technology to provide a visual representation of the results, facilitating point-of-care testing.Results: Following a comparative analysis of the sensitivity and specificity of the three methods, we identified the RPA-Cas12a approach as the optimal detection technique. Our findings demonstrated that the limit of detection (LoD) of the RPA-Cas12a platform was 1 aM (~1 copy/μL) for plasmid DNA and 5 × 10³ fg/μL for genomic DNA. Furthermore, both the sensitivity and specificity of the platform achieved 100% upon validation with 80 clinical isolates.Conclusion: These findings suggest that the developed RPA-Cas12a platform represents a promising tool for the cost-effective, convenient, and accurate detection of the blaKPC gene.Keywords: Klebsiella pneumoniae carbapenemase, CRISPR-Cas12a, isothermal amplification, polymerase chain reaction, loop-mediated isothermal amplification, recombinase polymerase amplification, lateral flow strips

Hang Wang,1,&ast; Bobin Hu,1,&ast; Hengkai Liang,1 Rongming Wang,1 Lu Wei,1 Tumei Su,1 Qingmei Li,1 Qianbing Yin,1 Yanfei Feng,1 Minghua Su,1 Jianning Jiang1,2 1Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianning Jiang; Minghua Su, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Tel +86-0771-5356531, Email gxjjianning@163.com; smh9292@163.comPurpose: Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.Patients and Methods: We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.Results: After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.Conclusion: HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.Keywords: hepatitis B virus, long-term antiviral therapy, hepatocellular carcinoma, integration, gene rearrangement

Lanyi Wei, Jingjing Meng, Danfeng Xiang, Quanjun Yang, Yangyun Zhou, Lingyan Xu, Junjun Chen,&ast; Yonglong Han&ast; Department of Pharmacy, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junjun Chen; Yonglong Han, Department of Pharmacy, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China, Email chenjunjun8812@sina.com; yonglongh@126.comBackground: The specific cytotoxic effects of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy have led to impressive outcomes in individuals previously treated for B-cell malignancies. However, the specific biological role of CD19(+) target cells, which exert antitumor immunity against some solid tumors, remains to be elucidated.Methods: We collected information regarding the level of CD19 mRNA and protein expression from various databases including The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) for both tumor and normal samples. To evaluate the patient’s prognosis according to CD19 expression, a Kaplan-Meier (KM) analysis and univariate Cox regression were performed. Furthermore, using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using the Expression Data (ESTIMATE) algorithm, we estimated the ratio of immune cells infiltrating malignant tumor tissues. Afterward, the GSCALite repository was employed to evaluate the vulnerability of tumors expressing CD19 to drugs used in chemotherapy. To validate the results in clinical samples of certain cancer types, immunohistochemistry was then performed.Results: Most tumor types exhibited CD19 expression differently, apart from colon adenocarcinoma (COAD). The early diagnostic value of CD19 has been demonstrated in 9 different tumor types, and the overexpression of CD19 has the potential to extend the survival duration of patients. Multiple tumors showed a positive correlation between CD19 expression and tumor mutation burden (TMB), microsatellite instability (MSI), and ESTIMATE score. Furthermore, a direct association was discovered between the expression of CD19 and the infiltration of immune cells, particularly in cases of breast invasive carcinoma (BRCA). Moreover, CD19 is highly sensitive to a variety of chemotherapy drugs.Conclusion: The study reveals the potential of CD19 as both a predictive biomarker and a target for different cancer immunotherapies.Keywords: CD19, pan-cancer, prognosis, immune infiltration, biomarker

Linping Wei,1 Jari A Laukkanen,2– 4 Yufeng Li,1 Xinrui Chen,1 Gang Li1 1Division of Cardiology, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Institute of Clinical Medicine, Department of Medicine, University of Eastern Finland, Kuopio, 70211, Finland; 3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, 70211, Finland; 4Wellbeing Services County of Central Finland, Department of Medicine, Jyväskylä, 40620, FinlandCorrespondence: Gang Li, Division of Cardiology, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 23 89011518, Fax +86 23 68811487, Email ganglicqmu@126.com; ganglicqmu@hospital.cqmu.edu.cnBackground: Previous studies have confirmed that high apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio was associated with increased mortality from heart failure (HF). Furthermore, the association of plasma apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling is still limited in chronic HF with mildly reduced ejection fraction (HFmrEF) elderly patients. Therefore, this study investigated the association of apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling in chronic HFmrEF elderly patients.Methods: A total of 587 Chinese elderly (≥ 65 years) with coronary heart disease (CHD), HFmrEF (EF 40– 50%) and related blood biochemical data were collected retrospectively. The cross-sectional data of echocardiographic and blood parameters were compared between binary apoB/apoA1 groups.Results: In the elderly CHD patients with chronic HFmrEF, the univariate correlation analysis showed that apoB/apoA1 was correlated with younger age, increased prevalence of type 2 diabetes, erythrocytes, platelet/lymphocyte ratio (PLR), D-dimer, fibrinogen, high sensitivity C-reactive protein and uric acid, and adverse cardiac remodeling (All P < 0.05). However, multivariate logistic binary regression analysis found that high apoB/apoA1 ratio (≥ 0.62) was independently correlated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling (All P < 0.05).Conclusion: In this retrospective study, the high apoB/apoA1 ratio is found to be associated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling in Chinese CHD elderly with chronic HFmrEF.Keywords: apolipoprotein B, apolipoprotein A1, platelet/lymphocyte ratio, adverse cardiac remodeling, chronic heart failure, elderly

Wen-Bo Wei,1– 3,&ast; Sha-Jie Dang,4,&ast; Hao-Zhe Liu,5 Da-Peng Duan,1,2 Ling Wei6 1Department of Orthopedics, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 2Shaanxi Province Key Laboratory of Basic and Clinical Translation for Bone and Joint Diseases, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 3State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Anesthesia, Shaanxi Provincial Cancer Hospital, Xi’an, Shaanxi, People’s Republic of China; 5Department of Surgery, Hancheng Maternal and Child Health Hospital, Hancheng, Shaanxi, People’s Republic of China; 6Department of Pain, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Wei, Department of Pain, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China, 710005, Email sxweiling@126.comBackground: As the latest endoscopic spine surgery, percutaneous endoscopic interlaminar discectomy (PEID) and unilateral biportal endoscopic (UBE) discectomy have distinct technical characteristics. This study aimed to evaluate the clinical outcomes of PEID and UBE discectomy in the treatment of single-level lumbar disc herniation (LDH).Methods: Between February 2019 and April 2022, 115 patients with single-level LDH at L4-5 or L5-S1 received PEID or UBE discectomy. The patients were separated into two groups based on the surgical method used: Group 1 (the PEID group) (n = 60) and Group 2 (the UBE group) (n = 55). Various parameters, including operative time, hospitalization time, fluoroscopy frequency, total costs, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI), were evaluated and compared between the two groups.Results: There were no significant differences in the VAS and ODI scores in 12 months after the operation between two groups (P > 0.05). However, the VAS of lower back pain on the first day after the operation in Group 2 (2.53± 0.89) was higher than that in Group 1 (2.19± 0.74) (P < 0.05). There were no significant differences in the operation time and incidence of complications between two groups (P > 0.05). But total costs in Group 2 (43,121± 4280) were significantly higher than those in Group 1 (30,069± 3551) (P < 0.05).Conclusion: Both UBE and PEID procedures have similar efficacy in alleviating pain and improving functional ability in patients with LDH. However, UBE surgery results in higher costs than PEID surgery.Keywords: unilateral biportal endoscopic discectomy, percutaneous endoscopic interlaminar discectomy, lumbar disc herniation

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

Pengwei Hou,1,&ast; Yang Yang,2,&ast; Ziqi Li,1,&ast; Dan Ye,2 Li Chen,1 Tianshun Feng,3 Jiateng Zeng,4 Liangfeng Wei,1 Shousen Wang1,5 1Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), Fuzhou, Fujian Province, People’s Republic of China; 2Fuzhou General Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Neurosurgery, Dongfang Affiliated Hospital of Xiamen University School of Medicine, Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 4Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Fujian Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Neurovascular Diseases, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangfeng Wei; Shousen Wang, Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), No. 156, Xierhuanbei Road, Fuzhou, Fujian Province, 350025, People’s Republic of China, Tel +8613960760177 ; +8613950482966, Email wlf74@163.com; wshsen1965@126.comPurpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats.Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1β, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3.Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS.Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.Keywords: NF-κB activator2, CNS infection, CCI, inflammation, TAK-3

Lujie Wei,1,&ast; Pingyang Li,2,&ast; Xiaofeng Liu,1 Yuxia Wang,1 Zhengping Tang,1 Hang Zhao,1 Lu Yu,3 Kaixiu Li,1 Jianping Li,1 Min Du,4 Xinzhu Chen,2 Xin Zheng,2 Yixiong Zheng,5 Yao Luo,2 Jing Chen,5 Xiamin Jiang,6 Xiaobing Chen,7 Huaicong Long1 1Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Medical College, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Nanbu County People’s Hospital, Nanbu, Sichuan, People’s Republic of China; 5College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 6Clinical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaicong Long, Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86 18981838105, Fax +86-28-8779 5585, Email longhc69@163.comBackground: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear.Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year.Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People’s Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC).Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P< 0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663– 0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693– 0.891); sensitivity, 86.3%; specificity, 60.0%).Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.Keywords: chronic obstructive pulmonary disease, frailty, acute exacerbations

Shu-Fen Chu,1 Kuo-Hsing Liao,2– 5 Li Wei2,6 1College of Nursing and Health Management, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 2Division of Neurosurgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Critical Medicine, Department of Emergency and Critical Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Neurotraumatology and Intensive Care, Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan; 5Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, TaiwanCorrespondence: Li Wei, Graduate Institute of Injury Prevention and Control, Taipei Medical University, 250 Wu-Hsing Street, Taipei City, Taiwan 110, Taiwan, Email weili@tmu.edu.twBackground: Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial.Aim: This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period.Methods: This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression.Results: Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a > 3.03 times risk of dementia after correcting for age, sex, and comorbidities.Conclusion: These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.Keywords: neurodegenerative diseases, dementia, epilepsy, traumatic brain injury, data-driven, population-based study

Wenzhen Tang,1 Yuanxi Xie,1 Qingfeng Yan,2 Yanjuan Teng,1 Li Yu,1 Liuying Wei,3 Jinmei Li,4 Yuhui Chen,1 Xiaolin Huang,1 Shaoli Yang,1 Kui Jia1 1The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2The Sanming Second Hospital, Sanming, Fujian Province, 366099, People’s Republic of China; 3Nanning Fourth People’s Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Wanxiu District Chengnan Community Health Service Center, Wuzhou, Guangxi Zhuang Autonomous Region, 543000, People’s Republic of ChinaCorrespondence: Kui Jia, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email 1960728884@qq.comAim: To investigate the current status of experience and support of nurses as second victims and explore its related factors in nurses.Design: A sequential, explanatory, mixed-method study was applied.Methods: A total of 406 nurses from seven tertiary hospitals in China were chosen as participants between September to October 2023. The Chinese version of the Second Victim Experience and Support Questionnaire (SVEST), Somatic Complaints of Sub-health Status Questionnaire (SCSSQ) and Generalized Anxiety Disorder (GAD-7) were applied to collect quantitative data. Eight nurses were selected for a qualitative study through in-depth interviews. Through interpretive phenomenological analysis, the interview data were analysed to explore the experience and support of nurses as second victims.Results: Practice distress (15.74 ± 4.97) and psychological distress (15.48 ± 3.74) were the highest dimensions, indicating Chinese nurses experienced second victim-related practice and psychological distress. Nurses with different gender, age, education, marital status, income, working hours, professional titles, and unit types have different levels of second victim-related experience and support (p

Liu J, Kang Y, Yin S, et al. Int J Nanomedicine. 2017;12:8085–8099. The authors have advised the control images for Figure 4A and B were the same to represent the one and the same control group. To alleviate any potential confusion this may have created, the authors have provided a corrected Figure 4. This correction does not change the scientific conclusions of the article in any way. Figure 4 Confocal microscopy investigation of the cellular distribution of lysosomes and zinc ions in SH-SY5Y cells after the two types of ZnO NP treatments.Abbreviation: NP, nanoparticle.Notes: After the SH-SY5Y cells were untreated (the Control group) or treated with the ZnOa NPs and ZnOb NPs (50 µg/mL) for 1 h, 3 h, or 5 h, the cells were loaded with FluoZin3 (green), LysoTracker (red) and Hoechst 33342 (blue). We observed almost no zinc ion fluorescence in the Control group, but significant zinc ions (green) were observed within 1 h after the ZnO NP treatment, and a slight increase in the zinc fluorescence (green) was observed in a time-dependent manner. Treatment with ZnOb NPs exhibited more potent fluorescence values than treatment with ZnOa NPs at 1 h. Moreover, significant overlaps (yellow) between cellular zinc ions and lysosomes were observed at all timepoints. Scale bar = 50µm. Magnification x600.

ABSTRACT Antibiotic resistance in Mycobacterium tuberculosis exclusively originates from chromosomal mutations, either during normal DNA replication or under stress, when the expression of error-prone DNA polymerases increases to repair damaged DNA. To bypass DNA lesions and catalyze error-prone DNA synthesis, translesion polymerases must be able to access the DNA, temporarily replacing the high-fidelity replicative polymerase. The mechanisms that govern polymerase exchange are not well understood, especially in mycobacteria. Here, using a suite of quantitative fluorescence imaging techniques, we discover that in Mycobacterium smegmatis, as in other bacterial species, the replicative polymerase, DnaE1, exchanges at a timescale much faster than that of DNA replication. Interestingly, this fast exchange rate depends on an actinobacteria-specific nucleoid-associated protein (NAP), Lsr2. In cells missing lsr2, DnaE1 exchanges less frequently, and the chromosome is replicated more faithfully. Additionally, in conditions that damage DNA, cells lacking lsr2 load the complex needed to bypass DNA lesions less effectively and, consistently, replicate with higher fidelity but exhibit growth defects. Together, our results show that Lsr2 promotes dynamic flexibility of the mycobacterial replisome, which is critical for robust cell growth and lesion repair in conditions that damage DNA.IMPORTANCEUnlike many other pathogens, Mycobacterium tuberculosis has limited ability for horizontal gene transfer, a major mechanism for developing antibiotic resistance. Thus, the mechanisms that facilitate chromosomal mutagenesis are of particular importance in mycobacteria. Here, we show that Lsr2, a nucleoid-associated protein, has a novel role in DNA replication and mutagenesis in the model mycobacterium Mycobacterium smegmatis. We find that Lsr2 promotes the fast exchange rate of the replicative DNA polymerase, DnaE1, at the replication fork and is important for the effective loading of the DnaE2-ImuA′-ImuB translesion complex. Without lsr2, M. smegmatis replicates its chromosome more faithfully and acquires resistance to rifampin at a lower rate, but at the cost of impaired survival to DNA damaging agents. Together, our work establishes Lsr2 as a potential factor in the emergence of mycobacterial antibiotic resistance.

Lu Wei,1 Buxin Zhang,2 Li Wang,2 Juntao Xu,2 Aimin Liu1,2 1Department of Dermatology, Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Department of Dermatology, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Aimin Liu, Department of Dermatology, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, No, 6, Dongfeng Road, Jinshui District, Zhengzhou city, Henan Province, 450053, People’s Republic of China, Tel +86 13592603226, Fax +86-371-60973329, Email hnzylam@126.comBackground: Generalised pustular psoriasis (GPP) is a chronic inflammatory skin disease. We aimed to visualize the research hotspots and trends of GPP using bibliometric analysis to enhance our comprehension of the future advancements in both basic science and clinical research.Methods: Relevant publications from July 2003 to July 2023 were obtained from the Web of Science Core Collection on July 12, 2023. The analysis of countries, institutions, authors, references, and keywords associated with this subject was conducted through the utilisation of CiteSpace 6.2.R4, VOSviewer 1.6.18, and Microsoft Excel 2019.Results: A total of 578 papers were analyzed, authored by 2758 researchers from 191 countries/regions and 1868 institutions, published in 174 academic journals. There was an overall upward trajectory in the volume of annual publications, accompanied by a gradual intensification of research interest in GPP. The United States, UDICE-French Research Universities, and Akiyama M of Nagoya University were the most productive and influential country, institution, and author, respectively. The Journal of Dermatology ranked first with the highest publications, and the Journal of the American Academy of Dermatology received the most citations. High-frequency keywords included “generalized pustular psoriasis”, “psoriasis, interleukin-36”, “plaque psoriasis”, “skin-disease”, and “antagonist deficiency”. Recent research focuses have included “safety”, “secukinumab”, “spesolimab”, “ap1s3 mutations”, and “interleukin-36”. Burst detection analysis of keywords showed that “moderate”, “ixekizumab treatment”, “mutations”, “efficacy”, and “safety” are current research frontiers in this field.Conclusion: This bibliometric analysis delineated the landmark publications in GPP that have defined current research hotspots and development trends, notably the applications, efficacy, and safety of biological agents. Future research endeavors are warranted to explore other biological therapeutic options for both acute GPP and the long-term management of chronic GPP.Keywords: generalised pustular psoriasis, psoriasis, interleukin-36, developing trends, bibliometric analysis

Daniel Hsiang-Te Tsai,1,2 J Simon Bell,3 Shahab Abtahi,4 Brenda N Baak,5 Marloes T Bazelier,4 Ruth Brauer,6 Adrienne YL Chan,6– 9 Esther W Chan,9– 12 Haoqian Chen,13 Celine SL Chui,9,14,15 Sharon Cook,16 Stephen Crystal,16 Poonam Gandhi,13 Sirpa Hartikainen,17 Frederick K Ho,18 Shao-Ti Hsu,1 Jenni Ilomäki,3 Ju Hwan Kim,19 Olaf H Klungel,4 Marjaana Koponen,17 Wallis CY Lau,6,8,9 Kui Kai Lau,20,21 Terry YS Lum,22 Hao Luo,22 Kenneth KC Man,6,8,9 Jill P Pell,18 Soko Setoguchi,13,23 Shih-Chieh Shao,1,24 Chin-Yao Shen,1 Ju-Young Shin,19,25,26 Patrick C Souverein,4 Anna-Maija Tolppanen,17 Li Wei,6,9 Ian CK Wong,6,8,9,27 Edward Chia-Cheng Lai1 1School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Centre for Neonatal and Paediatric Infection, St George’s University of London, London, UK; 3Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia; 4Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; 5PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands; 6Research Department of Practice and Policy, UCL School of Pharmacy, London, UK; 7Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, ‐Epidemiology and ‐Economics, University of Groningen, Groningen, the Netherlands; 8Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 9Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, Special Administrative Region, People’s Republic of China; 10Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 11Department of Pharmacy, the University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China; 12The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, People’s Republic of China; 13Center for Pharmacoepidemiology and Treatment Science (PETS), Institute for Health, Rutgers University, New Brunswick, NJ, USA; 14School of Nursing, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 15School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 16Center for Health Services Research, Rutgers University, New Brunswick, NJ, USA; 17Kuopio Research Centre of Geriatric Care and School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 18School of Health and Wellbeing, University of Glasgow, Glasgow, UK; 19School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; 20Division of Neurology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 21State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 22Department of Social Work and Social Administration, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 23Department of Medicine, Rutgers Robert Wood Johnson Medical School and Pharmacoepidemiology and Treatments Science, Institute for Health, Rutgers University, New Brunswick, NJ, USA; 24Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 25Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea; 26Department of Biohealth Regulatory Science, Sungkyunkwan University, Seoul, South Korea; 27Aston Pharmacy School, Aston University, Birmingham, UKCorrespondence: Edward Chia-Cheng Lai, School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Email edward_lai@mail.ncku.edu.twPurpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN).Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives.Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK.Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.Keywords: meta-data, data repository, Neurological and Mental Health Global Epidemiology Network, NeuroGEN

Longlong Wei,1,2 Yan Zhao,2 Siyue Xu,2 Cuilian Zhang1,2 1Department of Reproductive Medicine Center, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Reproductive Medicine Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Cuilian Zhang, Email zclian@zzu.edu.cnBackground: Endometrial polyps (EPs) are one of the most common intrauterine benign tumors, and are an important cause of uterine bleeding and female infertility. Previous studies have suggested that endometritis may contribute to the onset of EPs. This study aims to reveal the causal effect of endometritis on EPs by a two-sample Mendelian randomization (MR) study.Methods: Utilizing summarized statistics from genome-wide association studies (GWAS) in the European population, we conducted a Mendelian randomization study. In order to select suitable instrumental variables (IVs) that were significantly related to the exposures, a number of quality control approaches were used. For endometritis, 2144 cases and 111,858 controls were included, while for EPs, 2252 cases and 460,758 controls. Utilizing the inverse variance weighted (IVW) as the primary analysis, the data were subjected to a two-sample MR analysis, and the weighted median (WM) technique and MR-Egger regression were carried out additionally. The sensitivity analysis revealed neither heterogeneity nor horizontal pleiotropy.Results: Four independent single nucleotide polymorphisms (SNPs) from endometritis GWAS as IVs were selected. The IVW data did not agree to a causal association between endometritis and EPs (β=1.11e-04, standard error [SE] =4.88e-04, P = 0.82). Directional pleiotropy did not affect the outcome, according to the MR-Egger regression (intercept = 0.09, P = 0.10); Additionally, it showed no causation association between endometritis and EPs (β= − 3.28e-03, SE = 3.54e-03, P = 0.45). Similar results were obtained using the weighted-median method (β=8.56e-05, SE=5.97e-04, P = 0.89). No proof of heterogeneity and horizontal pleiotropy between IV estimates was discovered.Conclusion: In conclusion, by large scale genetic data, the results of this MR analysis provided suggestive evidence that the presence of endometritis is not associated with higher EPs risk.Keywords: two-sample Mendelian randomization, GWAS, endometritis, endometrial polyp

Hong-Xia Duan, Xiu-Mei Wang, Yue Guo, Ling Wei, Rui-Xia Hao, Zhen-Shan Guo Department of Surgery, Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences), Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Hong-Xia Duan, Department of Surgery, Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences), No. 99 Longcheng Street, Taiyuan, Shanxi, People’s Republic of China, Tel +86-3518379228, Email Duan_hongxia@yeah.netObjective: To investigate the application of a multidisciplinary collaboration model to optimise the configuration management of orthopaedic external device sets in general hospitals.Methods: A pretest–post-test study design was used. Sixty patients who underwent unilateral total knee arthroplasty and 60 patients who underwent posterior lumbar interbody fusion between March and May 2022 were recruited as the control stage. Additionally, a total of 120 patients, 60 of each, who underwent the two procedures between September and November 2022, were recruited as the experimental stage. For the control stage, conventional external equipment management was used, and for the experimental stage, an external device management programme was implemented based on multidisciplinary collaboration with the control stage. Based on the PDSA cycle, the configuration management of orthopaedic external device sets was optimised, and the differences in collating and counting external devices, nurses’ overtime in the external device stage and orthopaedic surgeon satisfaction were compared between the two stages.Results: Compared with the control stage, the collation count took less time (8.65 ± 0.25 min vs 5.37 ± 0.13 min; 13.55 ± 1.10 min vs 7.85 ± 0.82 min), the number of overtime hours was shorter (175.80 ± 12.19 min vs 96.68 ± 13.66 min) and orthopaedic surgeon satisfaction was improved (4.58 ± 0.62 vs 4.10 ± 0.68; 4.33 ± 0.73 vs 3.87 ± 0.77; 4.20 ± 0.71 vs 3.82 ± 0.71; 4.12 ± 0.69 vs 3.87 ± 0.72; 4.05 ± 0.68 vs 3.79 ± 0.68) in the experimental stage (all P < 0.05).Conclusion: Multidisciplinary collaboration offers various benefits for optimising the configuration of external device sets, such as reducing the time taken for the preoperative sorting and counting of external devices, enhancing nurses’ work efficiency and improving surgeons’ job satisfaction; therefore, it is worthy of reference in clinical practice.Keywords: operating theatre, optimisation configuration, external instruments, item counting, scientific management, work efficiency

Linfei Su,1,2 Zehui Lin,1 Youyuan Li,1 Xiaoyan Wang,3 Zengping Lin,3 Lanjuan Dong,3 Ling Wei1 1Department of Psychology, School of Health, Fujian Medical University, Fuzhou, People’s Republic of China; 2Institute of Psychology, School of Education Science, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Fuzhou Xingyu School, Fuzhou, People’s Republic of ChinaCorrespondence: Ling Wei, Tel +86-15960096260, Email ysyang-78@163.comBackground: The own-age effect is the phenomenon in which individuals perceive and recognize faces of their own age better than others in terms of cognitive processing. Previous eye movement studies on children with autism spectrum disorders (ASD) have reported that children with ASD have an attentional bias toward own-age faces and own-age scenes.Methods: The present study used own-age faces as the intervention material and examined the application of the own-age effect in the emotional recognition of faces in ASD. The length of the intervention was 12 weeks, and 2 sessions were conducted each week.Results: The results revealed that the own-age face intervention group gazed at children’s faces significantly more often than before the intervention, gazed at children’s angry faces significantly longer than before the intervention, and gazed at adults’ happy faces significantly longer and more often than before the intervention; the other-age faces intervention group did not differ significantly from the preintervention in gazing at children’s and adults’ faces after the intervention.Conclusion: The results suggest that own-age faces as teaching materials can better promote the emotion recognition ability of children with ASD than other-age faces.Plain language summary: ASD have difficulties with facial emotion recognition and previous study found that children with ASD correctly identified emotions in own-age faces more often than in other-age faces. Therefore, using pictures of children’s faces to intervene in children with ASD is beneficial to improve their facial emotion recognition ability. Previous studies have mostly used questionnaires to assess the effects of peer-matched interventions, and few have used an eye-movement technique that can effectively monitor changes in eye gaze patterns across different emotions.We found that the own-age face intervention group gazed at children’s faces significantly more often than before the intervention, gazed at children’s angry faces significantly longer than before the intervention, and gazed at adults’ happy faces significantly longer and more often than before the intervention. It indicates that own-age faces as teaching materials can better promote the emotion recognition ability of children with ASD than other-age faces.The own-age effect can be applied to experimental materials, the attribute settings of intervention materials, and the selection of accompanying objects to further expand the own-age effect in the educational intervention and training of social and cognitive abilities in ASD. It is expected to help autism improve its social skills and better integrate into the society.Keywords: children with autism spectrum disorders, own-age faces, intervention, eye tracking

Ling Wei,1,&ast; Qiyan Chen,2,3,&ast; Lu Yang,2,3 Tongzhen Ji,4 Wenjing Peng,5 Bing Shao,2 Hui Li2 1Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 3National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 5College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li; Bing Shao, Email lihui@bjcdc.org; shaobingch@sina.comObjective: The emerging epidemic of extended-spectrum β-lactamase-producing E. coli (ESBL-EC) is a global public health crisis. ESBL-EC infections are increasing worldwide and contribute to morbidity and mortality among newborn infants. However, the antimicrobial resistance characteristics and clonal transmission of maternal and neonatal ESBL-EC isolates need to be further deciphered.Materials and Methods: We performed phenotypic and genotypic characterization of 33 ESBL-EC isolates from pregnant women and newborn during 2019– 2020.Results: Minimum inhibitory concentrations of 17 antimicrobial agents showed that all isolates were multidrug-resistant (MDR) and had a resistance rate of 100% to ampicillin, and mild resistance to florfenicol, gentamicin, ceftazidime, and amoxicillin-clavulanate. Additionally, imipenem, meropenem, polymyxin, and tigecycline exhibited good activity against the tested ESBL-EC isolates with low MIC50 (0.06– 1 μg/mL) and MIC90 (0.06– 1 μg/mL). Whole genome sequencing indicated that ESBL-EC isolates contained diverse antimicrobial resistant genes (blaCTX-M, blaTEM, blaSHV, tetA, etc.) and toxin genes (ompA, csg, fimH, hybtA, etc.). blaCTX-M genes were the main ESBL genotype. ST1193 (18.2%) was the second most abundant ST among the ESBL-EC isolates (ST131 was the most common, with 30.3%), and this is the first report of its mother-to-infant colonization transmission in China.Conclusion: These findings revealed the occurrence of high-risk ST1193 clone among ESBL-EC isolates from pregnant women and newborn colonization in China. Further national or regional multicenter studies are needed to assess the dissemination and evolution of ESBL-EC ST1193 clone as a nosocomial pathogen in China.Keywords: ESBL, E. coli, antibiotic resistance, colonization transmission, ST1193 clone

Xiaofeng Zhang,1,&ast; Jiaqi Zhang,1,&ast; Yongzhi Cai,1 Yue Li,1 Shiyun Qin,1 Jingtao Li,1 Decai Zeng,1 Tongtong Huang,1 Liu Liu Huang,2 Yanfen Zhong,1 Lihui Wei,1 Ji Wu1 1Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Email gxnnwuji@163.comBackground: Rheumatic mitral stenosis(RMS) may leads to left ventricular remodeling (LVR), which can persist even after valve surgery. Identifying markers for early structure and function in patients with rheumatic heart disease who are at risk for adverse LVR after surgery can help determine the optimal timing of intervention. This study aimed to investigate whether preoperative parameters of global left ventricular long-axis strain (LVGLS) and mechanical discretization (MD) could predict postoperative adverse LVR.Methods: A total of 109 adult patients with RMS and 50 healthy controls were enrolled in this study. Baseline clinical features, conventional echocardiography results, LVGLS, and MD were compared between the two groups. Pre- and post-surgery echocardiography measurements were collected, and adverse LVR was defined as a> 15% increase in left ventricular end-diastolic volume or > 10% decrease in left ventricular ejection fraction. Binary regression analysis was used to determine independent predictors of poor left ventricular remodeling.Results: The variables associated with adverse LVR in this study were LVGLS (P< 0.001, odds ratio: 1.996, 95% CI: 1.394– 2.856) and MD (P=0.011, odds ratio: 1.031, 95% CI: 1.007– 1.055). The poorly reconstructed group had lower absolute values of LVGLS and higher MD than the healthy control group and the non-poorly reconstructed group. A LVGLS cutoff of − 15.0% was the best predictor for patients with poorly reconstructed LVR (sensitivity: 75.7%; specificity: 100.0%; AUC: 0.93), and a MD cutoff of 63.8ms was the best predictor (sensitivity: 63.8%; specificity: 98.6%; AUC: 0.88).Conclusion: Speckle tracking echocardiography has potential value for predicting the progression of adverse LVR and for identifying non-responders among patients with RMS undergoing surgery.Keywords: rheumatic mitral stenosis, left ventricular remodeling, left ventricular global longitudinal strain, mechanical dispersion, speckle tracking echocardiography

Abstract Thermal homeostasis is vital for mammals and is controlled by brain neurocircuits. Yet, the neural pathways responsible for cold defense regulation are still unclear. Here, we found that a pathway from the lateral parabrachial nucleus (LPB) to the dorsomedial hypothalamus (DMH), which runs parallel to the canonical LPB to preoptic area (POA) pathway, is also crucial for cold defense. Together, these pathways make an equivalent and cumulative contribution, forming a parallel circuit. Specifically, activation of the LPB → DMH pathway induced strong cold-defense responses, including increases in thermogenesis of brown adipose tissue (BAT), muscle shivering, heart rate, and locomotion. Further, we identified somatostatin neurons in the LPB that target DMH to promote BAT thermogenesis. Therefore, we reveal a parallel circuit governing cold defense in mice, which enables resilience to hypothermia and provides a scalable and robust network in heat production, reshaping our understanding of neural circuit regulation of homeostatic behaviors.

Jihai Chen,1,2 Lijun Wei,2 Xiaoxia Zhu,2 Wenli Xu,2 Yuxin Zou,2 Xinyu Qi,2 Jia Fang,2 Xiaodong Wang,2 Xiaolan Shi,1 Yunlu Sheng,2 Guoxian Ding,2 Xiaojun Ouyang,1 Yu Duan2 1Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Nanjing, 210024, People’s Republic of China; 2Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Yu Duan, Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email duanyujsph@163.com Xiaojun Ouyang, Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Luojia Road 30, Nanjing, 210024, People’s Republic of China, Email xiaojun_ouyang@aliyun.comBackground and Aims: Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population.Subjects and Methods: A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty.Results: Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk.Conclusion: There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.Graphical Abstract: Keywords: sarcopenia, thyroid hormone, elderly, muscle strength

Lu Wei,&ast; Jialin Zhang,&ast; Dake Di, Dongmei Wang, Guangpu Luo Department of Traditional Chinese Medicine Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangpu Luo; Dongmei Wang, Department of Traditional Chinese Medicine Dermatology, Dermatology Hospital of Southern Medical University, No. 2, Lujing Road, Yuexiu District, Guangzhou City, Guangdong Province, 510091, People’s Republic of China, Tel +86 13926166004 ; +86 13431086997, Fax +86-20-87257353, Email 102931@163.com; wongdongmei@163.comAbstract: Cutaneous plasmacytosis (CP) is a rare disorder of uncertain etiology. We report an unusual and rare case of CP in a 57‑year‑old male who presented with popular nodules all over the body, accompanied by head plaques. Pathological biopsy of the skin revealed large infiltration of mature plasma cells within the dermis. Elevated serum IgG4 concentrations were found. Immunohistochemical analysis confirmed the polyclonal nature of the plasma cells. The diagnosis of CP was established. Steroid therapy was administered at a dose of 20 mg/day. After 1 month of treatment, the patient’s eruption showed regression. These findings remind dermatologists to include CP in their clinical differential diagnosis of patients with head plaques. Meanwhile, clinicians should carefully that individuals diagnosed with CP at risk for malignant transformation.Keywords: cutaneous plasmacytosis, IgG4-related disease, plasma cell, IgG4

Donglei Shi,&ast; Li Wei,&ast; Hongsen Liang, Dongqing Yan, Junhang Zhang, Zhaojun Wang Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China, Email wangzhj55@mail.sysu.edu.cnBackground: Malaria remains a substantial concern in the realm of public health on a worldwide level. Using information from the global burden of disease (GBD) 2019 for 204 countries and territories between 1990 and 2019, we assessed the burden of malaria.Methods: Data on malaria were derived from the GBD 2019 study between 1990 and 2019. We evaluated the number of incidence, deaths, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR), examining them across variables such as age, year, gender, country, region, and socio-demographic index (SDI).Results: The burden of malaria decreased globally between 1990 and 2019. There were 2313.57× 105 incident cases and 6.43× 105 deaths in 2019, contributing to 464.38× 105 DALYs. Largest incident cases were observed in Western Sub-Saharan Africa [1151.72 (95% UI: 890.01– 1527.17)] × 105 in 2019. The only region where deaths increased between 1990 and 2019 was Western Sub-Saharan Africa. ASRs of malaria are distributed heterogeneously in different regions. The highest ASIR was observed in Central Sub-Saharan Africa [21,557.65 (95% UI: 16,639.4– 27,491.48)] in 2019. From 1990 to 2019, the ASMR of malaria declined. Compared to other age cohorts, the ASIR, ASMR, and ASDR for children aged between 1 to 4 years were found to be higher. Worst-affected regions by malaria infection were the low-middle SDI region and low SDI region.Conclusion: Malaria threatens global public health, especially in Central Sub-Saharan Africa and Western Sub-Saharan Africa. Children 1– 4 years old continue to bear the most significant burden of malaria. The study’s results will guide efforts to reduce malaria’s impact on the global population.Keywords: malaria, global burden of disease, ASIR, ASMR, ASDR

Shudi Liao,1 Jianpeng Zeng,1 Lihua Wei2 1School of Business, Hubei University, Wuhan, People’s Republic of China; 2School of Business, Zhengzhou University of Aeronautics, Zhengzhou, People’s Republic of ChinaCorrespondence: Lihua Wei, School of Business, Zhengzhou University of Aeronautics (East Campus), Zhengzhou, 45000, Henan Province, People’s Republic of China, Email lhwpaper@sina.comPurpose: Although plenty of studies have examined the antecedents of organizational citizenship behavior, empirical studies exploring the role of individual narcissism in relation to college students’ organizational citizenship behavior are relatively scarce. Drawing on the dual theory of narcissism and the conservation of resources theory, this study aimed to explore the relationship between narcissistic duality traits (narcissistic admiration and narcissistic rivalry) and organizational citizenship behavior of college students, and to further examine the mediating role of impression management motivation (assertive impression management motivation and defensive impression management motivation) and the moderating roles of teamwork, interpersonal relationships, and optimism.Methods: We used the questionnaire method with a sample of undergraduate and graduate students from several universities in Hubei, China. The data sample for analysis consists of 583 college students.Results: (1) Narcissistic admiration had a significant and positive effect on college students’ organizational citizenship behavior, while the effect of narcissistic rivalry was significant and negative; (2) assertive impression management motivation mediated the relationship between narcissistic admiration and college student’s organizational citizenship behavior, and defensive impression management motivation mediated the relationship between narcissistic rivalry and college student’ s organizational citizenship behavior; and (3) teamwork, interpersonal relationships, and optimism positively moderated the relationship between narcissistic admiration and assertive impression management motivation, and these variables positively moderated the indirect effects of assertive narcissism on college student’s organizational citizenship behavior through assertive impression management motivation.Conclusion: We found that college students with narcissistic admiration engaged in more organizational citizenship behaviors than those with narcissistic rivalry. In addition, narcissistic admiration had a positive effect on organizational citizenship behavior through assertive impression management motivation, and narcissistic rivalry had a negative effect on organizational citizenship behavior through defensive impression management motivation. Finally, teamwork, interpersonal relationships, and optimism significantly and positively mediated the relationship between narcissistic admiration and assertive impression management motivation, and the indirect effect of narcissistic admiration on organizational citizenship behavior through assertive impression management motivation. However, the direct effects of teamwork, interpersonal relationships, and optimism on the relationship between narcissistic rivalry and defensive impression management motivation, and the indirect effect of narcissistic rivalry on organizational citizenship behavior through defensive impression management motivation were not significant.Keywords: narcissistic admiration, narcissistic rivalry, impression management motivation, college student, organizational citizenship behavior

Li Zhou,1 Lai Wei,1 Yalin Chu,1 Qinhong Xie2 1Department of Health Management, School of Management, Zunyi Medical University, Zunyi, People’s Republic of China; 2Center for Mental Health Research, School of Management, Zunyi Medical University, Zunyi, People’s Republic of ChinaCorrespondence: Qinhong Xie, Center for Mental Health Research, School of Management, Zunyi Medical University, Zunyi, People’s Republic of China, Email xqinhongzmc@163.comObjective: The current study aimed to explore comprehensively college graduates’ negative life experiences, coping strategies, and enlightenment in a qualitative way.Methods: This was a qualitative study. Purposeful sampling was used to select 31 college graduates majoring in various subjects from a Chinese University. The one-on-one semi-structured interviews were conducted online through Tencent QQ/WeChat and were recorded and transcribed verbatim. A phenomenological approach was used to guide this research in the data collection and analysis. Thematic analysis was used to identify themes across interviews around their negative life experiences, coping strategies, and enlightenment.Results: College graduates’ negative life experiences were mainly focused on three aspects: negative work experience (eg, lack of adaptation, busy schedule, low salary), negative personal life experience (eg, multiple pressure, psychological problems, the hardship of life), and negative social life experience (eg, the incomprehension of those around you, complex interpersonal relationship, social complexity). The coping strategies they used can be classified into two categories: emotion-focused strategies (eg, accepting reality, self-persuasion, keeping a positive attitude), and problem-focused strategies (eg, goal-setting, asking for help to solve the problem, persistence). As for life enlightenment, six themes emerged: accept life, strive to life, love life, cherish life, recognize life, and learn to live.Conclusion: College graduates’ negative experiences came from multiple levels, and they use multiple coping strategies to deal with the challenges. Our results provide important guidance for researchers and policymakers to design effective and targeted intervention programs to improve college graduates’ coping abilities in response to negative life experiences and help them better transition from school to work. Specifically, future research and intervention to promote college graduates’ mental health should target various social-ecological levels, focus on promoting coping from an ecological perspective, as well as facilitate post-traumatic growth to help them grow from negative life experiences and cope positively.Keywords: college graduates, negative life experiences, coping, enlightenment, qualitative research, COVID-19 pandemic

Haoran Lu,1,&ast; Rou Zhao,2,&ast; Qianqian Qin,3 Liyong Tang,1 Guodong Ma,1 Baoyu He,2 Jing Liang,2 Li Wei,2 Xutong Wang,2 Qingli Bie,2 Xuning Wang,4 Bin Zhang2,5 1Department of Hepatobiliary Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 3Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 4Department of General Surgery, The Air Force Hospital of Northern Theater PLA, Liaoning, People’s Republic of China; 5Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Zhang, Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China, Tel +86 186 0647 3594, Fax +86 537 2213030, Email zhb861109@163.comBackground: Hepatocellular carcinoma (HCC) is one of the most common type of cancers, but there is still a lack of known biomarkers for the effective diagnosis or prognosis of HCC. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a substrate of protein kinase C, which was located in the cell plasma membrane. The purpose of our study was to evaluate the role of MARCKS in HCC.Methods: The role of MARCKS in HCC was explored by bioinformatics and experiment.Results: We demonstrated that MARCKS expression was significantly elevated in HCC datasets of TCGA. MARCKS was up-regulated in tumor sample in HCC. Functional enrichment indicated that MARCKS-related differentially expressed genes (DEGs) were mainly enriched in cell junction tissue, response to growth factors and cell population proliferation. Tumor and ECM-receptor interactions related pathways were enriched by the KEGG. MARCKS expression in HCC patients was higher in females, younger individuals, and those at worse clinical stages. Cox regression analysis showed that MARCKS expression was a risk factor for overall survival and disease-specific survival of patients.Conclusion: MARCKS was up-regulated in HCC, may play a crucial role in HCCs, and has prognostic value for clinical outcomes.Keywords: myristoylated alanine-rich C-kinase substrate, HCC, TCGA, prognostic value

Shan Tang,1 Jingxiao Lu,1 Cheng Xu,2 Lu Wei,1 Shenglan Mei,1 Rong Chen,1,2 Qing-Tao Meng1,2 1Department of Anesthesiology, East Hospital, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Qing-Tao Meng, Tel +8615178857650, Email mengqingtao2018@126.comPurpose: This study aimed to evaluate the efficacy and safety of remazolam compared with propofol in patients who underwent laryngeal mask airway (LMA) insertion without the use of muscle relaxant agents during hysteroscopic surgery.Patients and Methods: A total of 72 patients undergoing hysteroscopy with LMA insertion were assigned to two groups. The patients in the remazolam group received 0.3 μg/kg sufentanil, 0.3 mg/kg remazolam and 1.2 mg/kg remifentanil, whereas the patients in the propofol group received 0.3 μg/kg sufentanil, 2.0 mg/kg propofol and 1.2 mg/kg remifentanil for insertion of the LMA. The primary endpoint was the summed score of the insertion conditions. The secondary endpoints included hemodynamics, the duration of induction, the duration of insertion, tidal volume, plateau pressure and adverse events.Results: No difference was identified between the propofol group and remazolam group in the median summed score [18.0 (18.0, 18.0), 18.0 (17.0, 18.0), respectively, P > 0.05]. The induction duration was significantly longer (P < 0.05) in the remazolam group than propofol group. The cost of dopamine (P < 0.05) was significantly lower in the remazolam group compared with the patients in the propofol group, while the plateau pressure (P < 0.05) and the incidence of transient mild laryngospasm (P < 0.05) were significantly higher in the remazolam group. No differences were identified between the two groups in terms of heart rate, tidal volume, injection pain or hiccups (P > 0.05).Conclusion: Remazolam provided similar insertion conditions and better hemodynamic stability than propofol during LMA insertion without the use of muscle relaxant agents. However, a higher incidence of transient mild laryngospasm was found in the remazolam group, which should be considered.Keywords: remazolam, propofol, laryngeal mask airway, muscle relaxants

Xin Su,1,&ast; Haifeng Li,2,&ast; Fajun Li,3 Hongsen Liang,4 Li Wei,4 Donglei Shi,4 Junhang Zhang,4 Zhaojun Wang4 1Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 2Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, People’s Republic of China; 4Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhang Zhang; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628, Zhenyuan Road, Guangming (New) Dist, Shenzhen, 518107, People’s Republic of China, Email zhangjh33@mail.sysu.edu.cn; wangzhj55@mail.sysu.edu.cnObjective: Exposure to ambient particulate matter (PM2.5) is the leading risk factor for developing chronic obstructive pulmonary disease (COPD) in China. The present study aimed to investigate the trends in COPD mortality attributable to ambient PM2.5 exposure in China from 1990 to 2019.Methods: Data on COPD burden attributable to ambient PM2.5 exposure in China were extracted from the Global Burden of Disease (GBD) study 2019. The estimated annual percentage change (EAPC) was used to assess COPD mortality from 1990 to 2019. The APC model was used to analyze the temporal trends in the rate of COPD mortality attributable to ambient PM2.5 exposure according to age, period, and cohort.Results: Exposure to ambient PM2.5 contributed to 192.4 thousand deaths in 1990 and 263.6 thousand deaths in 2019. The age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) due to ambient PM2.5 exposure showed a gradual downward trend, the ASMR and ASDR in 2019 decreased to 16.6 per 100,000 with an EAPC of − 2.82 (95% CI: − 8.61 to 3.34) and 278.6 per 100,000 with an EAPC of − 2.02 (95% CI: − 7.85 to 4.19), compared to those in 1990, respectively. The relative risk (RR) of COPD increased with age in females, while in males, mortality significantly increased from the levels among those in the 60– 64 age group to that among those in the 90– 94 age group. In the period group, the RR of COPD in males remained above 1.0 from the 2000 to 2004 period, but it gradually decreased in females. The cohort effect showed an overall downward trend.Conclusion: Although the ASMR and ASDR are decreasing in Chinese patients with COPD, the number of deaths due to COPD is increasing. Ambient PM2.5 exposure is more harmful in males and older people above 60 years of age.Keywords: chronic obstructive pulmonary disease, PM2.5, age-period-cohort model

Lan Wei,1 Yuanyuan Han,2 Chao Tu1 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, People’s Republic of ChinaCorrespondence: Chao Tu, Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, 213000, People’s Republic of China, Email tcmedical21@czfph.comAbstract: Diabetic kidney disease (DKD) affects an estimated 20– 40% of type 2 diabetes patients and is among the most prevalent microvascular complications in this patient population, contributing to high morbidity and mortality rates. Currently, changes in albuminuria status are thought to be a primary indicator of the onset or progression of DKD, yet progressive nephropathy and renal impairment can occur in certain diabetic individuals who exhibit normal urinary albumin levels, emphasizing the lack of sensitivity and specificity associated with the use of albuminuria as a biomarker for detecting diabetic kidney disease and predicting DKD risk. According to the study, a non-invasive method for early detection or prediction of DKD may involve combining proteomic analytical techniques such second generation sequencing, mass spectrometry, two-dimensional gel electrophoresis, and other advanced system biology algorithms. Another category of proteins of relevance may now be provided by renal tissue biomarkers. The establishment of reliable proteomic biomarkers of DKD represents a novel approach to improving the diagnosis, prognostic evaluation, and treatment of affected patients. In the present review, a series of protein biomarkers that have been characterized to date are discussed, offering a theoretical foundation for future efforts to aid patients suffering from this debilitating microvascular complication.Keywords: diabetic kidney disease, proteomics, diagnostic biomarkers, therapeutic targets

Longlong Wei,1,2 Yan Zhao,2 Chunyu Xu,1,2 Cuilian Zhang1,2 1Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Reproductive Medicine Center, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Cuilian Zhang, Department of Reproductive Medicine Center, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China, Email zclian@zzu.edu.cnBackground: The effect of premature progesterone elevation on assisted reproductive technology has been debated. In different ovarian stimulation protocols, ovarian responses, and embryos transferred, conflicting results reside regarding the impact of elevated progesterone on pregnancy outcomes, according to previous studies. In addition, most studies have focused on significantly elevated progesterone levels, eg, above 1.5ng/mL, 1.75ng/mL, 2ng/mL. However, studies focusing on levels that are just slightly elevated are lacking, and some have concluded that such levels have no adverse effects on pregnancy outcomes.Methods: Clinical data of patients who underwent early follicular phase prolonged protocol cycle in vitro fertilization/intracytoplasmic sperm injection treatment were collected. Patients were divided into two groups according to progesterone level on the trigger day of human chorionic gonadotropin (HCG): Group 1:

Qi Zheng,1,&ast; Le Kuai,2,&ast; Wencheng Jiang,1,&ast; Yan Qiang,3 Lei Wei,2 Siting Chen,2 Bin Li,1 Ruiping Wang3,4 1Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Clinical Research and Innovation Transformation Center, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 4School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li; Ruiping Wang, Email 18930568129@163.com; w19830901@126.comBackground: Gender difference is prevalent in clinical feature, disease severity for noncommunicable diseases (NCD), but studies on gender disparity in clinical feature, disease severity and NCD comorbidity among psoriasis patients are limited. This cross-sectional study explores gender differences in clinical feature, lifestyle behavior and NCD comorbidity among psoriasis patients.Methods: Psoriasis patients were recruited through cluster survey method in two hospitals, and questionnaire interviews were applied to collect the demographic feature, lifestyle habits, clinical feature and NCD among patients.Results: A total of 2102 psoriasis patients included 1332 males (63.4%), 70% were over 35 years old and approximately 50% of them were overweight or obesity. The median value for psoriasis initiation age and disease duration was 33 years old (34 for male and 32 for female) and 9 years (10 for male and 7 for female), respectively. The psoriasis recurrence was mainly in winter (73.4%) and autumn (34.2%) both for patients. The prevalence of tobacco smoking and alcohol drinking was 31.2% and 12.6%. Male patients had higher prevalence of tobacco smoking (odds ratio (OR) = 13.26, 95% confidence interval (CI): 9.54– 18.44) and alcohol drinking (OR = 14.44, 95% CI: 7.90– 26.40). The prevalence of diabetes, hypertension, hyperlipidemia, and metabolic syndrome were 13.2%, 28.5%, 23.4% and 21.5%, respectively. Male patients had higher prevalence of diabetes (OR = 1.53, 95% CI: 1.16– 2.02), hypertension (OR = 1.87, 95% CI: 1.52– 2.30), hyperlipidemia (OR = 2.34, 95% CI: 1.85– 2.95) and metabolic syndrome (OR = 2.06, 95% CI: 1.63– 2.62) than female patients. The proportions for 4 types of NCDs diagnosed after psoriasis onset were over 58%, which were also higher in males than females.Conclusion: Female patients had shorter disease duration and with less NCD, and male patients had more body weight issue, with fewer sleep time and higher prevalence of tobacco smoking and alcohol drinking and NCDs. We recommend that dermatologist should notice the gender disparity in psoriasis patients, which is helpful for the disease diagnosis and treatment.Keywords: psoriasis, gender disparity, tobacco smoking, alcohol drinking, overweight, metabolic diseases, comorbidity

Ge Du, Fangfang Liu, Xiaomin Ma, Shanshan Chen, Min Dai, Li Wei,&ast; Zishuang Liu&ast; Department of Rehabilitation Center for Elderly, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wei; Zishuang Liu, Department of Rehabilitation Center for Elderly, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing, 100144, People’s Republic of China, Tel/Fax + 86-010-56981582, Email weili2014@sina.com; 1774332663@qq.comPurpose: We retrospectively compared the complications, blood biochemical indexes and outcomes in patients with swallowing disturbances receiving nasogastric tube (NGT) feeding and percutaneous endoscopy gastrostomy (PEG).Methods: Among 160 patients, 72 cases received PEG and 88 cases received NGT. All patients were followed up for two years. We collected their clinical data from the medical records. Indicators, such as body mass index (BMI), white blood cell (WBC), hemoglobin (HGB), complications, including recurrent aspiration pneumonia, gastrointestinal bleeding, reflux esophagitis, and outcomes (survival or death) were compared between the two groups semi-annually.Results: SAt both six months and one year after receiving treatment, there was no statistical difference between the two groups in indicators, complications and outcomes, with all P > 0.05. It can be seen that, when the patients were followed up for one and a half years18 months, ALB was lower in the NGT group (33.81± 0.46) compared with the PEG group (36.14± 0.50) (P < 0.05). After two years of follow-up, differences between the NGT and PEG group could be seen in a variety of indicators, including BMI (20.08± 0.27 vs 21.03± 0.25), WBC (9.12± 0.56 vs 7.08± 0.29), ALB (33.11± 0.43 vs 35.75± 0.49), creatinine (55.07± 1.83 vs 63.21± 2.94), and the complications, such as aspiration pneumonia, gastrointestinal bleeding, reflux esophagitis, and electrolyte disorder, in the PEG group were significantly reduced compared to the NGT groupthan that in its counterpart, P < 0.05. In the two-year follow-up period, there were 13 and 22 patients died in the PEG group and NGT group, respectively.Conclusion: Both techniques are safe and effective in the short term. However, on a longer-term basis, PEG is shown to be superior to NGT feeding in improving nutrition and preventing common complications for patients with swallowing disturbances.Keywords: percutaneous endoscopy gastrostomy, nasogastric tube feeding, swallowing disturbances, two-year, follow-up

Yi Jiang,1 Lijie Wei,1 Huiting Zhang,1 Yuting Chen,1 Peng Gao,1 Jingyi Zhang,1 Xuan Zhou,1 Shenglan Zhu,1 Yuanyuan Du,1 Chenyun Fang,1 Jiaqi Li,2 Ling Feng,1 Mengzhou He,1 Shaoshuai Wang,1 Jun Yu1 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 33006, People’s Republic of ChinaCorrespondence: Jun Yu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei Province, People’s Republic of China, Email yjtj2010@163.comIntroduction: Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy and results in poor pregnancy outcomes for both mother and fetus. MiR-17-5p is considered as the strongest predictor of metabolic syndrome status, but the relationship between GDM and miR-17-5p remains unclear. TXNIP, which leads to activation of NLRP3, is considered as a potential target of miR-17-5p, and the miR-17-5p/TXNIP/NLRP3 axis has been shown to play a major role in the occurrence and development of many metabolic diseases but has not been validated in GDM.Methods: MiR-17-5p was detected by RT-qPCR. The expression of TXNIP and NLRP3 in placenta was detected by immunofluorescence, RT-qPCR and Western blot. To explore the effect of miR-17-5p on TXNIP and NLRP3 and glucose uptake of HTR8/SVneo cells, miR-17-5p mimic and miR-17-5p inhibitor were transfected to achieve overexpression and inhibition. The interaction between miR-17-5p and TXNIP was confirmed by dual-luciferase reporter assay. Besides, glucose consumption of trophoblast cells was detected by glucose assay kit.Results: MiR-17-5p expression was down-regulated, while the expression of TXNIP and NLRP3 was up-regulated in GDM placental tissues. MiR-17-5p targeted TXNIP and inhibited its expression. MiR-17-5p also regulated NLRP3 expression and glucose uptake of HTR8/SVneo cells, which could be reversed by overexpression of TXNIP, suggesting that miR-17-5p improved glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis. The results were consistent with the above findings in high-glucose treated HTR8/SVneo cells.Conclusion: Our results suggested that miR-17-5p ameliorates the glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis, which may provide a new idea for offspring health of GDM patients.Keywords: diabetes, gestational, microRNAs, pregnancy, inflammation

YingLu Wang,1,&ast; Chang Liu,1,&ast; Liping Liu,1,&ast; Xiaoli Chen,1 Lu Wei,1 Jie Liu,1 Sheng Peng,2 Jingjiang Pi,3 Qi Zhang,3 Brian Tomlinson,4 Paul Chan,5 Lin Zhang,1 Huimin Fan,1 Liang Zheng,1 Zhongmin Liu,1 Yuzhen Zhang1 1Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 5Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuzhen Zhang; Zhongmin Liu, Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Tel +86 21-61569673, Email yzzhang-tj@tongji.edu.cn; liu.zhongmin@tongji.edu.cnPurpose: With increase of population aging, the prevalence of atherosclerotic cardiovascular disease (ASCVD) and elevated serum thyroid stimulating hormone (TSH) in elderly is increasing. High TSH level was reported to be associated with ASCVD and CVD mortality; however, few are studied in Chinese population, especially in the elderly. This study aimed to investigate the prevalence of elevated serum TSH and ASCVD in an elderly population of Chinese community and to explore the association between high serum TSH and ASCVD or CVD mortality.Patients and Methods: We conducted a study involving 3814 adults who were at least 60 years of age. Questionnaires, physical examinations, and laboratory blood samples were collected in 2014, and a 78-months follow-up for cardiovascular and all-cause mortality was performed till December of 2020. Logistics regression was used to analyze the association between TSH and ASCVD. We used Cox models to assess the hazard ratios (HRs) for all-cause and CVD mortality across changes in serum TSH.Results: In this study, the prevalence of the elevated serum TSH was 19.8%, and significantly higher in women than in men (24.5% vs 13.9%, p < 0.001). The prevalence of ASCVD was 21.7%. In logistics regression models, elevated TSH was associated with ASCVD after adjusting for the risk factors of ASCVD in people over the age of 70 years (adjusted OR 1.054, P = 0.014). After a follow-up of 6.5 years, total 441 (11.6%) all-cause death and 174 (4.6%) death of CVD were observed. In Cox regression model, no significant correlation was found between TSH and all-cause mortality or CVD mortality in the elderly population.Conclusion: In the elderly population, there is high prevalence of elevated serum TSH and ASCVD. Elevated TSH seemed to be not associated with risk of all-cause or CVD mortality.Keywords: cardiovascular disease, thyroid stimulating hormone, mortality, community-dwelling elderly

Lina Wei,1 Xulei Gou,2 Baoning Su,3 Haiqiong Han,4 Tingting Guo,5 Liang Liu,5 Lei Wang,5 Lina Zhang,3 Weibin Chen6 1Children’s Medical Center, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, People’s Republic of China; 2Department of Pediatrics, Beijing Daxing District Maternal and Child Health Care Hospital, Beijing, 102600, People’s Republic of China; 3Department of Pediatrics, Shanghai Jiading Traditional Chinese Medicine Hospital, Shanghai, 201800, People’s Republic of China; 4Department of Rehabilitation Medicine, Community Health Service Center of Jiangqiao Town in Jiading District, Shanghai, 201803, People’s Republic of China; 5Changchun University of Traditional Chinese Medicine, Changchun, 130017, People’s Republic of China; 6Department of Pediatrics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of ChinaCorrespondence: Lina Zhang, Department of Pediatrics, Shanghai Jiading Traditional Chinese Medicine Hospital, No. 222, Bole Road, Jiading District, Shanghai, 201800, People’s Republic of China, Tel +86-18930568760, Email lina1988zhang@163.com Weibin Chen, Department of Pediatrics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110, Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +86-18621863233, Email weibin1965chen@163.comBackground/Purpose: Mahuang decoction (MHD) is a classic famous traditional Chinese medicine and has various pharmacological effects, including anti-inflammation and anti-asthma. In this study, we aimed to investigate the potential protective effect of MHD against asthma and elucidated the underlying mechanism.Materials and Methods: A mouse model of asthma was induced by ovalbumin (OVA) treatment, and then treated with MHD to evaluate its effect on the asthma. Gain- or loss-of-function approaches were performed in SP1 and FGFR3 to study their roles in asthma via measurement of airway inflammation, airway remodeling and airway smooth muscle cell (ASMC) proliferation-related factors.Results: MHD reduced airway inflammation and remodeling. Additionally, MHD contributed to diminished expression of SP1, which was shown to repress airway inflammation and remodeling. Furthermore, SP1 bound to the FGFR3 promoter, resulting in the FGFR3 transcription promotion and ASMC proliferation. Conversely, FGFR3 knockdown abolished airway inflammation and remodeling, the mechanism of which was related to suppression of the PI3K/AKT signaling pathway. Meanwhile, MHD hindered airway inflammation and remodeling following asthma by suppressing the SP1/FGFR3/PI3K/AKT axis.Conclusion: Taken together, MHD may retard airway inflammation and remodeling by suppressing the SP1/FGFR3/PI3K/AKT axis, which contributes to an extensive understanding of asthma and may provide novel therapeutic options for this disease.Keywords: Mahuang decoction, asthma, SP1, FGFR3, PI3K/AKT signaling pathway, airway inflammation, airway remodeling

Leiomyosarcoma with heterologous differentiation is relatively rare. To date, only 19 cases have been reported in the English literature. Heterologous components frequently show histological pleomorphism, while those exhibiting well-differentiated morphology are seldom reported. Here, we report a 34-year-old female diagnosed with leiomyosarcoma and developed abdominal wall recurrence 8 years after primary surgery. The recurrent tumor mainly comprised well-differentiated chondrosarcoma except a single focus of leiomyosarcoma. Due to the rarity and prolonged onset of such a transition, our case provides insight into the understanding of this phenomenon.

Jingyuan Li,1 Qingbin Han,2 Hui Chen,3 Tingting Liu,1 Jiahui Song,1 Meng Hou,4 Lingling Wei,1 Hui Song1 1School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Shandong Linyi People’s Hospital, Linyi, People’s Republic of China; 3Department of Endodontics, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 4School of Stomatology, Jining Medical College, Jining, People’s Republic of ChinaCorrespondence: Hui Song, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, People’s Republic of China, Tel +86-531-88382912, Fax +86-531-88382923, Email songhui@sdu.edu.cnPurpose: Bone marrow-derived mesenchymal stem cells (BMSCs) are hopeful in promoting bone regeneration as their pluripotency in differentiation. Our previous study showed that carbon monoxide-releasing molecule-3 (CORM-3) increased the osteogenic differentiation of rat BMSCs in vitro. However, the mechanism remained unclear. MicroRNAs (miRNAs) play a very important role in modulating the osteogenic differentiation of BMSCs. Therefore, we researched the miRNAs involved in CORM-3-stimulated osteogenic differentiation.Methods: The CORM-3-stimulated osteogenic differentiation of rat BMSCs was further studied in vivo. Based on the gene sequencing experiment, the rat BMSCs were transfected with miR-195-5p mimics and inhibitor, pcDNA3.1-Wnt3a and Wnt3a siRNA. The osteogenic differentiation of rat BMSCs was measured by quantitative real-time polymerase chain reaction, Western blot and alizarin red staining. Additionally, the targeting relationship between miR-195-5p and Wnt3a was confirmed by the dual-luciferase assay.Results: MiR-195-5p was down-expressed during the CORM-3-stimulated osteogenic differentiation of rat BMSCs. CORM-3-stimulated osteogenic differentiation of rat BMSCs was inhibited with miR-195-5p overexpression, evidenced by significantly reduced mRNA and protein expressions of runt-related transcription factor 2 and osteopontin, and matrix mineralization demonstrated. On the contrary, the osteogenic differentiation was enhanced with inhibition of miR-195-5p. CORM-3-stimulated osteogenic differentiation of rat BMSCs was increased by overexpression of Wnt3a, while the opposite was observed in the Wnt3a-deficient cells. Moreover, the decreased osteogenic differentiation capacity by increased expression of miR-195-5p was rescued by Wnt3a overexpression, showing miR-195-5p directly targeted Wnt3a.Conclusion: These results demonstrate that CORM-3 promoted osteogenic differentiation of rat BMSCs via miR-195-5p/Wnt3a, which bodes well for the application of CORM-3 in the treatment of periodontal disease and other bone-defect diseases.Graphical Abstract: Keywords: carbon monoxide-releasing molecule-3, microRNA-195-5p, Wnt3a, osteogenic differentiation, bone marrow mesenchymal stem cells

Haifeng Li,1,&ast; Hongsen Liang,2,&ast; Li Wei,2 Donglei Shi,2 Xin Su,3 Fajun Li,4 Junhang Zhang,2 Zhaojun Wang2 1Department of Anesthesiology, Guangdong Provincial People’s Hospitall, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 4Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhang Zhang; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, People’s Republic of China, Tel/Fax +86-755-81206874, Email zhangjh33@mail.sysu.edu.cn; wangzhj55@gmail.sysu.edu.cnBackground: This study assessed health inequality in the global burden of chronic obstructive pulmonary disease (COPD) between 1990 and 2019 using data extracted from the Global Burden of Diseases (GBD 2019) study.Methods: Data were extracted from the GBD 2019 study. A series of comparative and descriptive analyses of the disease burden between women and men in countries with different socioeconomic development (SDI) status were performed. The slope index of inequality (SII), relative index of inequality (RII), and concentration index (CI) were calculated to measure the socioeconomic-related cross-national health inequity between 1990 and 2019.Results: The global health burden caused by COPD increased by 25.7% in terms of disability-adjusted life years (DALY) from 59.2 million years in 1990 to 74.4 million years in 2019. Global age-standardized DALY rate (ASDR) associated with COPD decreased by 40.0%, from 1537.7 per 100,000 population in 1990 to 926.1 per 100,000 population in 2019. The highest sex-specific DALY number was at age 70– 74 in male and female, and female is lower than male. However, after controlling for population size, the burden of COPD is more concentrated in the population living in low SDI countries, relative health inequality indicators (RII and CI) supported this conclusion.Conclusion: The health inequalities caused by the disparity of socioeconomic status are increasing, and the increasing concentration of wealth worldwide is likely to aggravate health inequalities associated with COPD.Keywords: chronic obstructive pulmonary disease, disease burden, health inequality

Chao Tu, Liangzhi Wang, Lan Wei Department of Internal Medicine, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213000, People’s Republic of ChinaCorrespondence: Lan Wei, Department of Internal Medicine, the Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 0519 68871132, Email weilan06082021@163.comAbstract: Diabetic microangiopathy is among the most common complications affecting patients with diabetes, and includes both diabetic retinopathy (DR) and diabetic nephropathy (DKD). Diabetic microangiopathy remains a persistent threat to the health and quality of life of affected patients. Mechanistically, the severity of DR and DKD is tied to mitochondrial and glucose metabolism abnormalities, with the activation of the glycolytic enzyme pyruvate kinase M2 (PKM2) contributing to mitochondrial and glomerular dysfunction, abnormal renal hemodynamics, and retinopathy. PKM2 can activate inflammatory bodies in macrophages to promote the release of inflammatory mediators, and serves as a key regulator of inflammatory factors, chemokines and adhesion molecules. As such, there is sufficient evidence that PKM2 can be used as a biomarker for the diagnosis of diabetes and diabetic microangiopathy. Here, we survey the mechanisms whereby PKM2 contributes to diabetes-related microvascular diseases, associated regulatory roles, post-translational modifications, and the potential utility of PKM2 as a therapeutic target. Through this literature review, we have determined that PKM2 offers promise as both a diagnostic marker and therapeutic target with direct relevance to research pertaining to diabetic microangiopathy.Keywords: pyruvate kinase M2, inflammation, diabetic retinopathy, diabetic nephropathy, diabetic microangiopathy

Chao Tu,1 Lan Wei,1 Liangzhi Wang,1 Ying Tang2 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213000, People’s Republic of ChinaCorrespondence: Ying Tang, Department of Rehabilitation Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 0519 68872146, Email tyczfph@yeah.netBackground: Diabetic nephropathy (DN) is the common cause of renal diseases such as end-stage renal disease (ESRD) and chronic kidney disease (CKD). Various diagnostic applications and treatment methods are used for clinical but remain some prognosis issues. To avoid morbidity and mortality related to DN, early detection of disease complications as well as targeted therapeutic strategies is essential. Considerable evidence indicates that non-coding RNA plays a vital role in the biological processes of various diseases, used as biomarkers and therapeutic targets. And the most known ncRNAs are the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs).Materials and Methods: Our study aimed to identify potential prognostic ncRNAs involved in DN by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. Our research focuses on differential expression miRNAs (DEmiRNAs) in DN and their interactions with critical genes.Results: We identified 8 up-regulated DEmiRNAs, including miR-103a-2-5p, miR-297, miR-548x-3p, miR-604, miR-644a, miR-1256, miR-3911 and miR-5047 finally. We further validated these miRNAs in a murine model.Conclusion: Identifying these up-regulated genes and elucidating these miRNAs regulatory network will contribute to a better understanding of the molecular mechanism of DN and how they can be used as new biomarkers and potential therapeutic targets for DN.Graphical Abstract: Keywords: diabetic nephropathy, microRNAs, bioinformatics, biomarkers

Jiayan Lou, Lingjia Wei, He Wang Department of Gynecology and Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: He Wang, Department of Gynecology and Oncology, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 13481138393, Email wanghe10430@126.comIntroduction: Ovarian cancer (OV) is a common malignancy affecting women globally; recognizing useful biomarkers has been one of the key priorities. Since SCNN1A was reported to be relevant to tumor progression in a variety of cancers, but rarely in ovarian cancer, we explored the roles of SCNN1A in OV.Methods: RNA sequencing data from TCGA and GEO were utilized to analyze the expression of SCNN1A and related differentially expressed genes (DEGs) in ovarian cancer. We performed GO, GSEA and immune cell infiltration analysis on SCNN1A-associated DEGs. Correlation of SCNN1A methylation levels and its mRNA expression was analyzed by cBioPortal and UCSC Xena databases. To assess the prognostic impact of SCNN1A, Kaplan–Meier plot analysis and Cox regression analysis were performed; ROC curves and nomogram were also plotted.Results: Compared to normal tissues, SCNN1A was highly expressed in ovarian cancer. The methylation level of SCNN1A negatively correlated with the SCNN1A expression. Moreover, high expression of SCNN1A was correlated with poor prognosis in OV patients and associated with immune infiltrates.Conclusion: High SCNN1A expression could be a promising biomarker for poor outcomes in OV and correlated with tumor immune cells infiltration. The findings might help illuminate the function of SCNN1A in tumorigenesis and lay a foundation for further research.Keywords: ovarian cancer, SCNN1A, biological function, prognostic biomarker, immune infiltrates

Lan Wei, Ling Hou, Yan-Qin Ying, Xiao-Ping Luo Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Yan-Qin YingDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Jiefang Avenue 1095#, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86 27 83662684Email yingyanqin@126.comBackground: Perrault syndrome (PRLTS) is a rare autosomal recessive disorder characterized by sensorineural hearing loss in both sexes and ovarian dysfunction in females. In some cases, patients present with a diversity of neurological signs. Six genes are known to cause Perrault syndrome.Case Report: We report an 11-year-old Chinese girl with delayed gonadal development, sensorineural hearing loss, and neurologic manifestations. Genetic etiology was identified by whole-exome sequencing and confirmed via Sanger sequencing. Compound heterozygous variants with one novel variant c.1752C>A (p.D584E) and one known pathogenic variant c.1172G>A (p.R391H) in TWNK were discovered in the child and inherited from her parents, respectively.Conclusion: The compound heterozygous variants c.1172G>A (p.R391H) and c.1752C>A (p.D584E) of the TWNK gene probably underlie PRLTS type 5 (PRLTS5). This study expands the mutation spectrum of TWNK pathogenicity in the PRLTS5 phenotype.Keywords: Perrault syndrome, TWNK gene, Chinese, whole-exome sequencing

Li-Qiang Cai,1,2 Lei Huang,1,2 Li-Li Wei,1,2 Jia-Shu Yao,1,2 Luo-Yi Xu,1,2 Wei Chen1,2 1Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Center for Sleep Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Wei ChenDepartment of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3, Hangzhou, Zhejiang, 310016, People’s Republic of ChinaTel +86-571-87887800Email srrcw@zju.edu.cnObjective: This study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods.Methods: A total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea–hypopnea index (AHI)≥ 5) (OSA vs non-OSA). The correlation between estradiol levels and apnea–hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone.Results: Among the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p< 0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875– 0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826– 0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012– 1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389– 4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136– 2.353, p = 0.008) are correlated with OSA.Conclusion: The ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.Keywords: major depressive disorder, estradiol, obstructive sleep apnea, menopause, polysomnography