Search

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

Linan Ren,1,2 Feng Ju,3 Siyuan Liu,1,2 Yunjia Cai,1,2 Xiaokun Gang,1 Guixia Wang1 1Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 3Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of ChinaCorrespondence: Xiaokun Gang; Guixia Wang, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email gangxk@jlu.edu.cn; gwang168@jlu.edu.cnAbstract: Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues. Keywords: Obesity-related nephropathy, pathophysiology, diagnostics, therapeutics

Lijie Ren,1 Ye Chen,2 Xianguo Han,3 Ziyi Chen,2 Zhi Wang,4 Wenxiao Li,2 Hongyuan Chen2 1Mental Health Center, Shanghai Customs University, Shanghai, People’s Republic of China; 2School of Customs and Public Administration, Shanghai Customs University, Shanghai, People’s Republic of China; 3School of Psychology, Shanghai Normal University, Shanghai, People’s Republic of China; 4School of Customs and Public Economics, Shanghai Customs University, Shanghai, People’s Republic of ChinaCorrespondence: Xianguo Han, School of Psychology, Shanghai Normal University, 100 Guilin Street, Xuhui District, Shanghai, 200234, People’s Republic of China, Email hanxg.psy@aliyun.comBackground: Suicide is a global public health issue. This study examined the role of COVID-19 burnout and reappraisal in suicidal ideation caused by depressive symptoms among Chinese college students.Methods: 587 students (261 boys, Mage = 19.53, SD = 1.42) were assessed using the Short Depression-Happiness Scale (SDHS), Positive and Negative Suicide Ideation (PANSI) inventory, and Emotion Regulation Scale (ERS).Results: Correlation analysis indicated depressive symptoms were negatively correlated with reappraisal and positively correlated with suicidal ideation and COVID-19 burnout. Reappraisal was negatively correlated with suicidal ideation and COVID-19 burnout. The moderated mediation model showed COVID-19 burnout enhanced the direct effect of depressive symptoms on suicidal ideation and indirectly enhanced this effect by weakening the protective role of reappraisal.Conclusion: These finding show that reappraisal acts as a protective factor against suicidal ideation in individuals with depressive symptoms, while COVID-19 burnout exacerbates this effect by weakening reappraisal’s protective role.Keywords: depressive symptoms, suicidal ideation, reappraisal, COVID-19 burnout, moderated mediation model

Lijing Huo,1 Xuexin Liu,2 Changmei Wei,1 Fang Yu,1 Luping Ren,3 Yanqing Tie1 1Department of Medical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 2Health Check-up Centers, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Lijing Huo, Department of Medical Laboratory, Hebei General Hospital, 348 Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, People’s Republic of China, Email huolijing1979@126.comAim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations.Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations.Results: We found that gender were associated with 25(OH)D, OC, β-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P< 0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in β- CTX levels between seasons.Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.Keywords: 25-hydroxyvitamin D, 25(OH)D, osteocalcin, OC, β-carboxy-terminal cross-linking telopeptide of type I collagen, β-CTX, N-terminal procollagen of type I collagen, P1NP, parathyroid hormone 1-84, PTH1-84

Liyuan Ren, Jinjin Yang, Yanshuang Li, Yanping Wang Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yanping Wang, Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, People’s Republic of China, Tel +86-371-13526857360, Email 282243756@qq.comPurpose: To investigate and quantify the effect of continuous esketamine infusion at different doses on the bispectral index (BIS) during sevoflurane anesthesia.Methods: A total of 120 patients scheduled for elective laparoscopic renal surgery were randomly divided into three groups. Under steady anesthesia and surgical situations, the patient was started on continuous infusion of the study drug: 0.125 mg/kg/h esketamine (group E1), 0.25 mg/kg/h esketamine (group E2), and the same volume of saline (group C). The primary outcome was changes in BIS value after 15 min (T15), 30 min (T30), 45 min (T45), and 60 min (T60) of drug infusion. The secondary outcomes were 95% spectral edge frequency (SEF95), electromyogram (EMG), heart rate (HR), and mean arterial pressure (MAP) from T0 to T60. Furthermore, postoperative pain, postoperative recovery, and perioperative adverse events were evaluated.Results: Compared with group C, group E1 exhibited significant BIS elevation at T30–T60 and group E2 at T15–T60 (P < 0.001). Compared with group E1, group E2 showed a more significant BIS elevation at T15–T60 (P < 0.001). The area under the curve (AUC) of BIS and SEF95 were significantly higher in group E2 than in groups C and E1 (P < 0.05). BIS value for any of the three groups was significantly correlated with SEF95 (P < 0.001). No significant differences were observed in the AUC of EMG, HR, and MAP among the three groups. Intraoperative remifentanil consumption and postoperative NRS of pain on movement were significantly reduced in group E2 compared with groups C and E1 (P < 0.05).Conclusion: Continuous infusion of both 0.125 and 0.25 mg/kg/h of esketamine increased the BIS value during sevoflurane anesthesia, and the BIS value gradually stabilized with the prolongation of the infusion time.Keywords: esketamine, bispectral index, 95% spectral edge frequency, sevoflurane

Li Ren, Zhaoling Li, Ji Wu, Lian Duan, Jialiang Gao Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Li Ren, Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Address: No. 5, Beixiange, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86 18600697916, Email renlirl7961@hotmail.comObjective: This study aimed to assess the knowledge, attitudes and practices (KAP) among elderly coronary heart disease (CHD) patients toward self-perceived health abilities.Methods: This web-based study was carried out between April 2023 and September 2023 at Guang’anmen Hospital, China Academy of Chinese Medical Sciences. A self-developed questionnaire was utilized to collect demographic information from elderly CHD patients, and evaluate their KAP towards self-perceived health abilities.Results: A total of 568 valid questionnaires were collected. Among the participants, the average age was 65.97± 5.50 years, and 298 (52.46%) were female, and the mean scores for knowledge, attitudes, and practices were 6.34± 2.29 (possible range: 0– 9), 35.24± 4.99 (possible range: 9– 45), and 27.79± 10.09 (possible range: 9– 45), respectively. The structural equation model demonstrated that elderly CHD patients’ knowledge directly affects attitudes and practices, with path coefficient of 0.93 (P< 0.001) and 0.39 (P=0.033), respectively. Moreover, attitudes play an intermediary role between knowledge and practice with path coefficient of 0.75 (P< 0.001). Furthermore, residence directly affects knowledge with path coefficient of 0.67 (P< 0.001), cardiac function directly affects knowledge with path coefficient of − 0.97 (P< 0.001) and history of interventional therapy directly affects practice with path coefficient of 4.23 (P< 0.001).Conclusion: Elderly CHD patients demonstrated sufficient knowledge, positive attitudes, and proactive practices towards self-perceived health abilities. However, educational programs and behavior modification are recommended, particularly for elderly with lower age and education, living in rural areas, lacking interventional therapy, obese, or taking multiple CHD medications.Keywords: knowledge, attitudes, practices, cross-dimensional study, coronary heart disease, self-perceived health abilities

Qing Wang,1 Ke Liu,1 Tian Zhang,1 Ting Wang,2 Huan Li,1 Chang Wang,1 Jinhu Chen,1 Luping Ren1 1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Clinical laboratory, Nanjing Medical College, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Luping Ren, Email renluping1122@163.comBackground: The study estimated the association between NAFLD and SUA/Cr in Chinese non-obese patients with type 2 diabetes mellitus (T2DM) and also investigated mediating effect of TG.Methods: All patients were divided into NAFLD group (n = 420) and non-NAFLD group (n = 347). The differences of biochemical indicators between the two groups were compared. The link between SUA/Cr and other parameters was checked through Spearman correlation analysis. Differences in the incidence rate of NAFLD between SUA/Cr and TG 3 tertile subgroups were tested by chi-squared. To explore the independent influence of SUA/Cr and TG on NAFLD, logistic regression was performed. The predictive value of SUA/Cr and SUA/Cr combined with BMI for NAFLD was analyzed using ROC curves. In addition, to confirm whether TG has a mediating effect on the link of SUA/Cr and NAFLD, we conducted a mediating analysis.Results: NAFLD group had higher SUA/Cr values than individuals without NAFLD (P < 0.01). SUA/Cr was linked with TC and TG (r = 0.081, 0.215 respectively). NAFLD prevalence increased progressively from quartile 1 to quartile 3 of SUA/Cr (44% vs 57% vs 62%). Prevalence of NAFLD increased from quartile 1 to quartile 3 of TG (35.8% vs 58.7% vs 69.9%). Analysis of the logistic regression revealed that SUA/Cr and TG were statistically linked with NAFLD. The ROC curve pointed out that the area under the curve (AUC), sensitivity and specificity of SUA/Cr were 0.59, 0.629 and 0.522, respectively. The AUC, sensitivity and specificity for SUA/Cr combined with BMI were 0.719, 0.644 and 0.677, separately. The mediation analysis showed a statistically direct effect of SUA/Cr on NAFLD (β=0.148, 95% CI: 0.0393, 0.2585). The function of SUA/Cr on NAFLD partially mediated by TG (β=0.1571, 95% CI: 0.0704, 0.2869).Conclusion: SUA/Cr was significantly associated with NAFLD in non-obese T2DM patients, and TG partially mediated this association. SUA/Cr can be applied to predict for NAFLD.Keywords: nonalcoholic fatty liver disease, type 2 diabetes mellitus, serum uric acid to creatinine ratio

Li An,1,2,&ast; Xiaomei Ren,1,&ast; Ye Pan,2 Wei Gao,1 Liqun Ren,1 Jing Wang,3 Yao Wang2 1Department of Geriatrics, ZhongDa Hospital, Southeast University School of Medicine, Nanjing, 210009, People’s Republic of China; 2Department of Endocrine, ZhongDa Hospital, Southeast University School of Medicine, Nanjing, 210009, People’s Republic of China; 3Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang; Yao Wang, Tel/Fax +86-25- 83272111, Email wang_yao100@163.com; yz3466599@hotmail.comBackground: The impact of inflammatory factors on the risk of diabetic nephropathy (DN) is inconsistent. Two-sample Mendelian randomization (MR) analyses were used to detect the causal role of inflammatory factors in DN risk.Methods: Inflammatory factor GWAS summary data were collected from a meta-analysis including 8,293 Finnish participants, and DN information was extracted from a GWAS of 213,746 individuals from FinnGen. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) outlier test was used for the removal of horizontal pleiotropic outliers. Multivariable MR analysis was also used to adjust for pleiotropy.Results: IFN-γ [ORIVW: 1.33; 95% CI: 1.09– 1.63; p=0.005] and SCF [ORIVW: 1.25, 1.02– 1.52; p = 0.027] were associated with an increased risk of DN. MIP1b [ORIVW: 0.92; 95% CI: 0.85– 0.98; p = 0.022] and IL-16 [ORIVW: 0.89, 0.81– 0.99; p = 0.043] showed negative associations with the risk of DN. We validated our MR results with MR-PRESSO analyses. Significant horizontal pleiotropy was not found. Moreover, in the multivariable MR analysis, the associations between cytokines and DN risk remained.Conclusion: Our MR results based on genetic data contribute to a better understanding of the pathogenesis of DN and provide evidence for a causal effect of inflammatory factors on DN. These findings support targeting specific inflammatory factors to alleviate DN risk.Keywords: causal association, diabetic nephropathy, inflammatory factors, Mendelian randomization

Honghua Shen,1,2 Yiming Xu,2 Yin Zhang,2 Lei Ren,2 Rui Chen1 1Department of Respiratory Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Respiratory Rehabilitation, the Fourth Rehabilitation Hospital of Shanghai, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Rui Chen, Department of Respiratory Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China, Email chenruigood@126.comPurpose: We assess the predictive value of diaphragm excursion (DE) in enhancing exercise tolerance following pulmonary rehabilitation (PR) among patients with COPD-OSA overlap syndrome.Material and Methods: This prospective cohort study enrolled 63 patients diagnosed with COPD-OSA overlap syndrome who actively participated in a PR program from January 2021 to May 2023. Among these, 58 patients successfully completed the 20-week PR program, with exercise tolerance assessed through the measurement of six-minute walk distance (6MWD), and DE evaluated by ultrasonography. The responder to PR in terms of exercise ability was defined as a patient who showed an increase of > 30m in 6MWD. The cutoff value for predicting PR response based on DE was determined using receiver operating characteristic (ROC) curves.Results: Following the PR program, significant improvements were observed in mMRC, 6MWD, DE during deep breathing, and diaphragm thickness fraction (DTF). Of the participants, 33 patients (57%) were classified as responders, while 25 patients (43%) were considered non-responders. Baseline values of FEV1% predicted, 6MWD, DE during deep breathing, DTF, and PaO2 exhibited a significant elevation in responders as compared to non-responders. The changes of 6MWD were positively associated with the baseline values of DTF and DE during deep breathing, FEV1% predicted and PaO2, while negatively correlated with baseline value of mMRC. The predictive performance in terms of the area under the ROC curve for determining responder’s DTF was found to be 0.769, accompanied by a sensitivity of 85% and specificity of 68%, using a cutoff value at 17.26%. Moreover, it was observed that DE during deep breathing could predict the area under the ROC curve for responders to be 0.753, with a sensitivity of 91% and specificity of 56% at a cutoff value of 3.61cm.Conclusion: Diaphragm excursion serves as a valuable predictor for determining the enhancement of exercise tolerance following PR in patients with COPD-OSA overlap syndrome.Trial Registration: ChiCTR1800020257, www.chictr.org.cn/index.aspx.Keywords: pulmonary rehabilitation, COPD-OSA overlap syndrome, diaphragm excursion, diaphragm thickness fraction, six-minute walk distance

Linyuan Gui,1,&ast; Qingyuan Ye,2,&ast; Lu Yu,3 Geng Dou,1 Yang Zhou,1 Yang Liu,4 Yanqi Zhang,5 Xiaoshan Yang,1,6 Fang Jin,5 Shiyu Liu,1 Yan Jin,1 Lili Ren1 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Dentistry Center, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3Department of Periodontology, 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, Jinan, Shandong, 250012, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 6Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Ren; Yan Jin, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China, Email lanyangddgy@qq.com; yanjin@fmmu.edu.cnBackground: Osteoporosis is a highly prevalent disease that causes fractures and loss of motor function. Current drugs targeted for osteoporosis often have inevitable side effects. Bone marrow mesenchymal stem cell (BMSCs)-derived apoptotic extracellular vesicles (ApoEVs) are nanoscale extracellular vesicles, which has been shown to promote bone regeneration with low immunogenicity and high biological compatibility. However, natural ApoEVs cannot inherently target bones, and are often eliminated by macrophages in the liver and spleen. Thus, our study aimed to reconstruct ApoEVs to enhance their bone-targeting capabilities and bone-promoting function and to provide a new method for osteoporosis treatment.Methods: We conjugated a bone-targeting peptide, (Asp-Ser-Ser)6 ((DSS)6), onto the surface of ApoEVs using standard carbodiimide chemistry with DSPE-PEG-COOH serving as the linker. The bone-targeting ability of (DSS)6-ApoEVs was determined using an in vivo imaging system and confocal laser scanning microscopy (CLSM). We then loaded ubiquitin ligase RING finger protein146 (RNF146) into BMSCs via adenovirus transduction to obtain functional ApoEVs. The bone-promoting abilities of (DSS)6-ApoEVs and (DSS)6-ApoEVsRNF146 were measured in vitro and in vivo.Results: Our study successfully synthesized bone-targeting and gained functional (DSS)6-ApoEVsRNF146 and found that engineered ApoEVs could promote osteogenesis in vitro and exert significant bone-targeting and osteogenesis-promoting effects to alleviate osteoporosis in a mouse model.Conclusion: To promote the bone-targeting ability of natural ApoEVs, we successfully synthesized engineered ApoEVs, (DSS)6-ApoEVsRNF146 and found that they could significantly promote osteogenesis and alleviate osteoporosis compared with natural ApoEVs, which holds great promise for the treatment of osteoporosis. Keywords: osteoporosis, mesenchymal stem cells, apoptotic extracellular vesicles, bone-targeting, bone regeneration

Mingxuan Zou,1,2,&ast; Bin Liu,2,&ast; Jing Ji,1 Lei Ren,3,4 Xiuchao Wang,2 Fengzhan Li2 1Public Health School, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 2Department of Military Medical Psychology, Air Force Medical University, Xi’ an, 710032, People’s Republic of China; 3Military Psychology Section, Logistics University of PAP, Tianjin, 300309, People’s Republic of China; 4Military Mental Health Services & Research Center, Tianjin, 300309, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengzhan Li; Xiuchao Wang, Email psyfengzhan@126.com; Wangxiuchao1984@163.comBackground: Military personnel experience prolonged exposure to high-stress environments. Positive coping styles can assist in maintaining their mental and behavioral well-being, whereas negative coping styles cannot. Health behavior change theory specifies that an individual can transition from a negative to a positive coping style. The psychological resilience concept may prove vital in this transition.Methods: In a longitudinal study design, two questionnaires were administered to 233 military personnel twice, the first at T1 in April 2023 and the second at T2 in July 2023. The questionnaire measured individual negative coping style, positive coping style and psychological resilience.Results: The data showed that the negative coping style at T1 negatively predicted the level of psychological resilience at T2 (γ= - 0.26, p < 0.001) and the positive coping style at T2 (γ= - 0.16, p < 0.001). The level of psychological resilience at T1 positively predicted the positive coping style at T2 (γ= 0.22, p < 0.01). Psychological resilience played a mediating role between negative coping style and positive coping style. In addition, there was an interaction between psychological resilience and positive coping style in military personnel at the two time points.Conclusion: The negative coping styles that presently exist among military personnel have the potential to diminish their future positive coping styles by lowering their psychological resilience. This highlights the need to focus on the development and training of psychological resilience for military personnel, as it can effectively counteract negative coping styles and promote positive coping styles.Keywords: military personnel, coping style, resilience, cross-lagged analysis

Hongmei Xue,1 Jiquan Li,1 Li Ma,1 Xuxin Yang,1 Lingling Ren,1 Zhijun Zhao,1 Jianling Wang,1 Yuanbo Zhao,1 Zhongzhi Zhao,1 Xuefei Zhang,1 Zhiguo Liu,2 Zhenjun Li2 1Department of Brucellosis Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xining, Qinghai, People’s Republic of China; 2National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of ChinaCorrespondence: Zhiguo Liu; Zhenjun Li, Email wlcblzg@126.com; lizhenjun@icdc.cnObjective: Brucellosis is a serious public health issue in Qinghai (QH), China. Surveying the seroprevalence and isolation of B. abortus strains from marmots is key to understanding the role of wildlife in the maintenance and spread of brucellosis.Methods: In this study, a set of methods, including a serology survey, bacteriology, antibiotic susceptibility, molecular genotyping (MLST and MLVA), and genome sequencing, were employed to characterize the two B. abortus strains.Results: The seroprevalence of brucellosis in marmots was 7.0% (80/1146) by serum tube agglutination test (SAT); one Brucella strain was recovered from these positive samples, and another Brucella strain from a human. Two strains were identified as B. abortus bv. 1 and were susceptible to all eight drugs examined. The distribution patterns of the accessory genes, virulence associated genes, and resistance genes of the two strains were consistent, and there was excellent collinearity between the two strains on chromosome I, but they had significant SVs in chromosome II, including inversions and translocations. MLST genotyping identified two B. abortus strains as ST2, and MLVA-16 analysis showed that the two strains clustered with strains from northern China. WGS-SNP phylogenetic analysis showed that the strains were genetically homogeneous with strains from the northern region, implying that strains from a common lineage were spread continuously in different regions and hosts.Conclusion: Seroprevalence and molecular clues demonstrated frequent direct or indirect contact between sheep/goats, cattle, and marmots, implying that wildlife plays a vital role in the maintenance and spread of B. abortus in the Qinghai–Tibet Plateau.Keywords: Brucella abortus, marmots, isolated, MLST, MLVA, WGS-SNP, QH

Huan Li, Chang Wang, Qing Wang, Xuehua Liu, Juanjuan Zhang, He Zhang, Wenjie Fei, Hang Zhao, Luping Ren Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Luping Ren, Email renluping1122@163.comObjective: Previous studies have shown that oxymatrine (OMT) can improve high-fat-high-fructose-diet-induced non-alcoholic fatty liver disease (NAFLD), and our study aimed to explore its possible metabolic potential mechanisms.Methods: Wistar rats were fed a high-fat-high-fructose diet for 8 weeks and treated with oxymatrine by gavage for the last 4 weeks. We measured biochemical indicators and pathological changes in each group and used liquid chromatography-mass spectrometry (LC-MS) to analyze changes in metabolites in the serum and liver of the rats.Results: The results showed that OMT can alleviate the high-fat-high-fructose-induced weight gain and hepatic lipid deposition in rats. Metabolomic analysis showed that the level of eicosapentaenoic acid (EPA) was downregulated and levels of desmosterol and d-galactose were upregulated in livers fed with HFDHFr. The levels of L-isoleucine, L-valine, arachidonic acid (AA), taurocholic acid (TCA), chenodeoxycholyltaurine (TDCA), isocitrate, and glutathione (GSH) were downregulated in the liver, whereas those of linoleic acid (LA), phosphocholine (PC), glycerophosphocholine (GPC), and oxidized glutathione (GSSG) were upregulated in the serum treated with OMT.Conclusion: In summary, OMT can improve HFDHFr-induced NAFLD, and metabolomic analysis can provide an early warning for the development of NAFLD as well as provide a rationale for therapeutic targets.Keywords: high-fat-high, fructose, fatty liver, oxymatrine, metabonomics

Tingxue Zhang,1,2 Yilin Hou,1,2 Min Liu,2 Xiaoyu Hou,1,2 Yong Tang,2 Luping Ren,2 Guangyao Song1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guangyao Song, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: To investigate the effects of different angiopoietin-like proteins (ANGPTLs) on postprandial hypertriglyceridemia (PPT) by analyzing changes in serum lipid, ANGPTL3, ANGPTL4, and ANGPTL8 levels before and after a high-fat diet in individuals with normal fasting lipid and oral glucose tolerance test results.Patients and Methods: Exactly 103 volunteers were recruited for an oral fat tolerance test (OFTT). Blood samples were obtained at 0, 2, and 4 h after eating to detect relevant indicators. PPT was defined as triglyceride (TG) levels ≥ 2.5 mmol/L. According to the test results, the participants were divided into two groups: postprandial normal triglycerides (PNT) and PPT. The levels of blood lipids and ANGPTL3, ANGPTL4, and ANGPTL8 were compared between the two groups.Results: There were differences in the body mass index (BMI), waist circumference (WC), fasting total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), triglyceride-rich lipoprotein cholesterol (TRL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), ApoA1/ApoB, fasting blood glucose (FBG), fasting insulin (FINS), ANGPTL4, and ANGPTL8 between the two groups. In the PNT group, the TG level increased from baseline at 2 and 4 h, TRL-C increased from baseline at 4 h, and ANGPTL8 decreased from baseline at 2 and 4 h. After OFTT, the levels of TG, TRL-C, ANGPTL3, and ANGPTL4 in the PPT group gradually increased; ANGPTL8 gradually decreased. Fasting ANGPTL3 was positively associated with age, TC, HDL-C, TRL-C, and ApoA1, and negatively associated with systolic blood pressure. Fasting ANGPTL4 was positively correlated with weight, WC, BMI, TC, TG, LDL-C, TRL-C, non-HDL-C, ApoB, FBG, and FINS, and negatively correlated with ApoA1/ApoB and fasting ANGPTL8. Binary logistic regression analysis indicated that ANGPTL4 and ANGPTL8 were significant predictors of PPT.Conclusion: PPT occurrence is closely associated with changes in ANGPTL4 and ANGPTL8 levels.Keywords: dyslipidemia, serum lipid, ANGPTL proteins, oral fat tolerance test, postprandial normal triglyceride

Jie Li,1 Jiangtao Long,1 Zheng Zhao,2 Qianqian Wang,1 Wang Bo,2 Liang Ren,1 Yan Fan,3 Peng Wang,1 Yi Cheng,1 Binbin Liu,1 Xinkui Cheng,1 Hongwei Xi2 1Department of Orthopedics, Children’s Hospital Affiliated to Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of General Surgery, Children’s Hospital Affiliated to Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Burn and Plastic Surgery, Children’s Hospital affiliated to Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Hongwei Xi, Email xihongwei148@sina.comBackground: Multiple stages including hemostasis, inflammation, proliferation, and remodeling were involved in the wound healing process. The increase in nanomaterials in recent years has extended the scope of tools for wound healing; however, it is still difficult to achieve the four multistage procedures simultaneously.Materials and Methods: In this study, graphene-spiky silica heterostructured nanoparticles (GS) were synthesized for the procedural acceleration of the multistage in wound healing process. The nanobridge effect of GS was analyzed through the adhesion of two skins, the antibacterial effect was assessed in Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, cell proliferation and migration were investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the in vivo wound healing effect was examined in female BALB/c mice with a cutting wound and E. coli or S. aureus bacteria infection on the back.Results: First, GS has a strong nanobridge effect on the rapid closure of wounds because the spiky architecture on the surface of GS facilitates the adhesion of skins, promoting the hemostasis stage. Second, graphene exhibits antimicrobial activities both in chemical and physical interactions, especially under simulated sunlight irradiation. Third, graphene plays an important role in scaffolding function, together with the spiky topographical architecture of GS, accelerating the proliferation and maturation stages.Conclusion: By periodically promoting every stage of wound healing, GS combined with simulated sunlight irradiation could significantly accelerate wound healing. With a simple composition and compact structure but multiple functions, this strategy will be the guideline for the development of ideal wound-healing nanomaterials.Keywords: graphene-spiky silica heterostructured nanoparticles, wound healing, multistage

Xiaoyu He,1,2 Yu Luo,2 Jianan Hao,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Luping Ren2 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Luping Ren, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86 311 859 889 75, Email renluping1122@163.comPurpose: Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS.Patients and Methods: A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters.Results: The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (β = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (β = – 0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients.Conclusion: Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.Keywords: ketosis onset, ketosis-prone type 2 diabetes, lipid metabolism, atherosclerosis, atherogenic index of plasma

Kuiliang Li,1 Xiaomei Ren,2 Lei Ren,3 Xuejiao Tan,1 Mengxue Zhao,2 Chang Liu,4 Xi Luo,1 Zhengzhi Feng,2 Qin Dai2 1Department of Medical English, School of Basic Medical Sciences, Army Medical University, Chongqing, People’s Republic of China; 2Department of Medical Psychology, Army Medical University, Chongqing, People’s Republic of China; 3Department of Clinical Psychology, Air Force Medical University, Xi’an, People’s Republic of China; 4BrainPark, Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Clayton, VIC, AustraliaCorrespondence: Zhengzhi Feng, Department of Medical Psychology, Army Medical University, Chongqing, People’s Republic of China, Tel +86 023-68771480, Email fzz@tmmu.edu.cn Qin Dai, Department of Medical Psychology, Army Medical University, Chongqing, 400038, People’s Republic of China, Tel +86 16623460852, Email daiqin101@hotmail.comBackground: Previous studies have explored the relationship between negative life events and depression, but little is known about the bidirectional relationship between negative life events and depression, particularly in specific groups of medical cadets.Purpose: This study aimed to explore the relationship between negative life events and depressive symptoms among medical cadets during their four years of college.Methods: An analysis of 4-wave longitudinal data collected from 2015– 2018 was conducted using a cross-lagged panel network (CLPN) model to explore the complex causal relationship between negative life events and depressive symptoms in medical cadets (N=433).Results: We found differences in negative life events and depressive symptoms among medical cadets across four network models over four years of university. Nodes A-21, A-20, A-23 and A-24, and depressive symptoms D-6 showed greater lagged effect values.Conclusion: Our findings suggest that there is a lagged and mutually causal interaction between negative life events and depressive symptoms in medical cadets over 4 years of college, but that the predictability of negative life events is more important. However, more attention needs to be paid to the predictive role of depressive symptoms, especially those in early life which are often overlooked. Our study provides new insights into the relationship between negative life events and depressive symptoms in university students and helps to refine strategies for prevention and intervention of depression.Keywords: depression, negative life events, CLPN, longitude relationship, vicious circle, network analysis

Jiangfen Wu,1 Lingyan Ren,2 Xinyi Huang,3 Li Hu,2 Liangliang Zhang,2 Dan Xie,1 Zhimin Li,4 Naijian Han,4 Shengwen Huang1,2,5 1GuiZhou University Medical College, Guiyang, Guizhou, People’s Republic of China; 2Prenatal Diagnosis Center, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 3School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4Annoroad Gene Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 5NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial, People’s Hospital, Guiyang, People’s Republic of ChinaCorrespondence: Shengwen Huang, Guizhou Provincial People’s Hospital, Nanming District, Guiyang, People’s Republic of China, Tel +8615185134701, Fax +86-851-85937194, Email hsw713@sina.comBackground: Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the DMD gene encoding a large structural protein in muscle cells.Methods: Two probands, a 6-year old boy and a 1-month old infant, respectively, were clinically diagnosed with DMD based on elevated levels of creatine kinase and creatine kinase isoenzyme. CNVplex and whole exome sequencing (WES) were performed for causal variants, and Sanger sequencing was used for verification.Results: CNVplex found no large deletions or duplications in the DMD gene in both patients, but WES discovered a single-nucleotide deletion in exon 48 (NM_004006.2:c.6963del, p.Asp2322ThrfsTer16) in the proband of pedigree 1, and a nonsense mutation in exon 27 (NM_004006.2:c.3637A>T, p.K1213Ter) in the proband of pedigree 2.Conclusion: The results of our study expand the mutation spectrum of DMD and enrich our understanding of the clinical characteristics of DMD. Genetic counseling was provided for the two families involved in this study.Keywords: DMD gene, exon 48, exon 27, whole exome sequencing, Duchenne muscular dystrophy

Haiyang Chen,1,&ast; Chenlin Wu,2,&ast; Qin Lv,2 Mingjie Li,1 Lu Ren2,3 1Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 2Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 3Mental Disorders Research Laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Ren, Email lnzxkc@sina.comBackground: Depression is a common mental health disorder characterized by persistent feelings of sadness, loss of interest or pleasure, and a range of physical and cognitive symptoms. It affects people of all ages and can significantly impact their daily functioning and quality of life. Mitochondrial homeostasis plays an important role in the pathogenesis of depression. Mitochondrial homeostasis includes mitophagy, mitochondrial oxidative stress, mitoptosis, mitochondrial biogenesis, and mitochondrial dynamics. The regulation of mitochondrial homeostasis is the key link in the prevention and treatment of depression.Methods: In this article, we focus on the core link of depression-mitochondrial homeostasis and summarize the research progress of acupuncture targeting mitochondrial homeostasis in the treatment of depression in recent years, so as to provide ideas and experimental basis for the research and formulation of more appropriate depression treatment strategies.Results: Acupuncture has been found to regulate mitochondrial homeostasis (by modulating mitochondrial autophagy, reducing mitochondrial oxidative stress, inhibiting mitochondrial fission, inducing mitochondrial biogenesis, and maintaining mitochondrial dynamics), alleviate depression-like behavior, and regulate signal pathways and key proteins.Conclusion: Here, we highlight the role of acupuncture in the treatment of depression. A comprehensive exploration of the impact of acupuncture on mitochondrial homeostasis could potentially present a novel mechanism for treating depression and offer fresh perspectives for the treatment of patients with clinical depression.Keywords: depression, mitochondria, homeostasis, acupuncture, mitophagy, review

Yilin Hou,1,2 Xiaoyu Hou,1,2 Qian Nie,3 Qiuyang Xia,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Guangyao Song,2,4 Luping Ren2,4 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3Health Examination Center, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 4Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Guangyao Song; Luping Ren, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email sguangyao2@163.com; renluping1122@163.comPurpose: The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications.Methods: A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were sub-classified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and β-crosslaps (β-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications.Results: After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [O, p < 0.001] and increased serum P1NP levels , p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, β-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and β-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD.Conclusion: Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.Keywords: bone turnover markers, type 2 diabetes mellitus, microvascular complications

Xiaoyu Pan,1,2 Xueqing Zhang,2 Jiangli Ban,2 Lin Yue,3 Lin Ren,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, the Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comBackground: Neutrophils and high-density lipoprotein cholesterol (HDL-C) are significantly linked to cardiovascular disease (CVD). This study investigates the correlation of neutrophil count to HDL-C ratio (NHR) with cardiac ultrasound parameters and cardiovascular risk in healthy populations.Materials and Methods: Firstly, NHR was calculated based on neutrophils and HDL-C. Then, the differences in basic clinical characteristics and cardiac ultrasound parameters were compared between the high and low NHR groups, males and females. Subsequently, cardiovascular risk was predicted according to the Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool for people aged 35– 60 years. Finally, the correlation between NHR and cardiac ultrasound parameters and cardiovascular risk was calculated.Results: A total of 3020 healthy participants, 1879 males and 1141 females, were included. Participants in the high NHR group had significantly increased Aorta (AO), Left Atrium (LA), Right Atrium (RA), Right Ventricle (RV), End Systolic Diameter of Left Ventricle (ESD), End Diastolic Diameter of Left Ventricle (EDD), Main Pulmonary Artery (MPA), Right Ventricular Outflow Tract (RVOT), Interventricular Septum (IVS), Left Ventricular Posterior Wall (LVPW), and cardiovascular risk and decreased E/A values compared to those in the low NHR group. The same results were found in males participants compared to females. A total of 1670 participants underwent ICVD risk assessment tool. Cardiovascular risk was significantly higher in those with high NHR and in males than in those with low NHR and in females. Correlation analysis showed that NHR was positively correlated with AO, LA, RA, RV, ESD, EDD, MPA, RVOT, IVS, LVPW and cardiovascular risk, and negatively correlated with E/A values.Conclusion: Our study demonstrates that NHR is significantly associated with cardiac ultrasound parameters and cardiovascular risk in healthy populations. NHR may serve as a useful indicator for the early diagnosis and treatment of cardiovascular disease among healthy populations.Keywords: neutrophils, high-density lipoprotein cholesterol ratio, cardiovascular risk, cardiac ultrasound, cardiovascular disease

Xiaoyu Pan,1,2 Xueqing Zhang,2 Jiangli Ban,2 Lin Yue,3 Lin Ren,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comPurpose: To investigate the effect of high-fat diet on protein expression in mouse heart and aorta using proteomic techniques.Methods: A high-fat diet was used to construct an obese mouse model, and body weight was checked regularly. After the experiment, serum lipid and oxidative stress levels were measured. Proteomic detection of cardiac and aortic protein expression. Cardiac and aortic common differentially expressed proteins (Co-DEPs) were screened based on proteomic results. Subsequently, functional enrichment analysis and screening of key proteins were performed.Results: A high-fat diet significantly increased body weight in mice. Obese mice had considerably higher levels of TC, TG, LDL-C, ROS, and MDA. In the heart and aorta, 17 Co-DEPs were discovered. The results of functional analysis of these proteins indicated that they were mainly related to lipid metabolism. Ech1, Decr1, Hsd17b4, Hsdl2 and Acadvl were screened as key proteins. In mice, a high-fat diet causes lipid metabolism to become disrupted, resulting in higher levels of oxidative stress and lipid peroxidation products.Conclusion: Ech1, Decr1, Hsd17b4, Hsdl2 and Acadvl as cardiac and aortic Co-DEPs are closely related to lipid metabolism and may serve as potential diagnostic and therapeutic targets for obesity-induced cardiovascular disease.Keywords: high-fat diet, obesity, proteomics, cardiovascular disease, lipid

Tiantian Sun,1,&ast; Chang Wang,1,2,&ast; Lijing Huo,3 Yichao Wang,1 Ke Liu,1 Changmei Wei,3 Hang Zhao,1 Shuchun Chen,1 Luping Ren1 1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2North China University of Science and Technology, Tangshan, People’s Republic of China; 3Department of Clinical Laboratory, Hebei General Hospital, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luping Ren, No. 348 Heping West Road, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86 0311-85988975, Email renluping1122@163.comPurpose: To evaluate serum cortistatin (CST) levels in type 2 diabetes mellitus (T2DM) patients with or without non-alcoholic fatty liver disease (NAFLD) and to examine the relationship between CST and NAFLD.Methods: A total of 90 T2DM patients, which included 56 NAFLD patients (referred to as DM+NAFLD group) and 34 patients without NAFLD (DM-only group), and 83 non-diabetes individuals that included 39 NAFLD patients (NAFLD-only group) and 44 without NAFLD that acted as the normal-control group (NC group). The differences in the serum CST levels between the groups were compared, and the correlations between CST and other variables were calculated by applying both correlational analysis and multiple linear regression analysis.Results: The mean serum CST levels were significantly lower in the DM+NAFLD and DM groups than in the NC group (P < 0.05). In addition, the CST levels were lower in the DM group relative to that in the NAFLD group (P < 0.05). However, no statistical difference was noted in the serum CST between diabetic patients with and without NAFLD (P > 0.05). Similarly, in the non-diabetic group, the serum CST level was not significantly different between individuals with and without NAFLD (P > 0.05). Furthermore, the serum CST levels were negatively associated with the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), and insulin cell function index (HOMA-β). Conversely, the serum CST levels were positively associated with high-density lipoprotein cholesterol (HDL-C). The data obtained through multiple linear regression implied that LDL-C and HOMA-β, but not HOMA-IR, were closely related to serum CST levels.Conclusion: T2DM was related to decreased serum CST. However, serum CST was correlated with HOMA-β in T2DM patients, while HOMA-IR was not. There was no correlation between CST and NAFLD.Keywords: type 2 diabetes mellitus, cortistatin, nonalcoholic fatty liver disease

Yu Luo,1 Cuiyu Wang,1,2 Tian Zhang,1,3 Xiaoyu He,1,4 Jianan Hao,1,4 Andong Shen,3,5 Hang Zhao,1 Shuchun Chen,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Graduate School, Hebei North University, Zhangjiakou, People’s Republic of China; 3Graduate School, North China University of Science and Technology, Tangshan, People’s Republic of China; 4Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Gastroenterology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Luping Ren, Email renluping1122@163.comPurpose: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are frequently co-occurring diseases. Liver fibrosis (LF), with increasing incidence, has a prognostic value for NAFLD mortality. Our study aimed to investigate the relevant factors for FL in T2DM individuals with NAFLD.Patients and Methods: A total of 565 T2DM patients with NAFLD from Hebei General Hospital participated in the study. Patients underwent an abdominal ultrasound, a questionnaire and laboratory tests. The fibrosis-4 index (FIB-4) was used to evaluate LF, with FIB ≥ 1.3 indicating LF and FIB ≥ 2.67 indicating F3-4 fibrosis.Results: Compared with NLF group, LF group had higher levels of systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT). The glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL), glycated hemoglobin (HbA1c), and platelets (PLT) in LF patients were lower than those without LF. Patients with LF were older than those without LF. ALT, AST, and GGT in patients with severe LF were higher than those with mild LF, while platelet was lower. Age, SBP, duration of diabetes, ALT, AST, and GGT were positively correlated with FIB-4, while eGFR, TC, LDL, and HbA1c were negatively correlated with FIB-4. Logistic regression showed that age, SBP, ALT, GGT, LDL, and PLT were independently associated with LF.Conclusion: For T2DM patients combined with NAFLD, older age, higher SBP, higher ALT, higher GGT, lower LDL, and lower PLT were relevant factors for LF.Keywords: type 2 diabetes mellitus, non-alcoholic fatty liver disease, fibrosis-4 index, liver fibrosis

Jianan Hao,1,2,&ast; Yichao Wang,1,&ast; Lijing Huo,3 Tiantian Sun,1 Yunfeng Zhen,1 Zhe Gao,1 Shuchun Chen,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Laboratory Department, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luping Ren, Endocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renluping1122@163.comObjective: We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD.Methods: One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed.Results: Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P< 0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P< 0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor.Conclusion: Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.Keywords: bone morphogenetic protein-9, type 2 diabetes mellitus, non-alcoholic fatty liver disease, insulin resistance, glucose and lipid metabolism

Yaning Li,1 Junfang Nie,1 Jie Dai,1 Jun Yin,1 Binbin Huang,1 Jia Liu,1 Guoguang Chen,1 Lili Ren1,2 1School of Pharmacy, Nanjing Tech University, Nanjing, People’s Republic of China; 2Department of Microbiology and Immunology, Stanford University, Stanford, CA, USACorrespondence: Guoguang Chen; Lili Ren, School of Pharmacy, Nanjing Tech University, Nanjing, People’s Republic of China, Tel +86-2558-139-416, Email ggchen@njtech.edu.cn; renlili@njtech.edu.cnPurpose: Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor.Methods: A graded response micelle (RPPssD@IR780/DOC) was designed to self-assemble by cRGD-poly(β-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor.Results: In vitro and in vivo experimental results suggested that RPPssD@IR780/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility.Conclusion: A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects.Graphical Abstract: Keywords: micelles, drug delivery, ligand hidden, size variable, photo-chemotherapy

Xiaoyu Pan,1,2 Lin Yue,1,2 Jiangli Ban,2 Lin Ren,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 31185988406, Fax +86 31185988406, Email chenshuc2014@163.comPurpose: Using proteomics to study the effect of semaglutide on cardiac protein expression in obese mice. Assessment of the effect of semaglutide on cardiac function in obese mice.Materials and Methods: The mice were randomly divided into three groups: the control group (WC), the high-fat group (WF), and the high-fat diet with semaglutide intervention group (WS). Serum samples were collected, and lipids, blood glucose, inflammatory and oxidative stress markers, and cardiac ultrasound, were examined. The cardiac weight of each group of mice was measured, and pathological alterations were examined. Inflammation and oxidative stress levels in heart tissue were evaluated. The labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was used to find differentially expressed proteins (DEPs) and screen for related pathways and key proteins in a proteomics study.Results: Semaglutide greatly alleviated obesity-induced lipid metabolism abnormalities, improved cardiac ventricular wall thickening, and significantly reduced myocardial collagen content in obese mice. Semaglutide significantly reduces obesity-induced inflammation and oxidative stress. There were 64 DEPs in the WF/WC group, with 39 upregulated proteins and 25 downregulated proteins. The WS/WC group, on the other hand, had 83 DEPs, including 57 upregulated and 26 downregulated proteins. Following functional analysis, DEPs were shown to be largely associated with lipid metabolism and peroxisomes. Apolipoprotein A-II, catalase, diazepam-binding inhibitor, paraoxonase-1, and hydroxysteroid 17-dehydrogenase-4 were all upregulated in the WF group but significantly downregulated in the WS group. A high-fat diet increases the expression of lipid synthesis and transport proteins while increasing inflammation and oxidative stress damage.Conclusion: Semaglutide decreases lipid synthesis alleviates inflammation and oxidative stress and prevents lipid peroxidation and cardiac impairment.Keywords: semaglutide, lipid metabolism, DEPs, obesity, inflammation, oxidative stress

Xiaoyu Pan,1,2 Lin Yue,3 Lin Ren,2 Jiangli Ban,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, the Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comPurpose: To investigate the correlation between Triglyceride-glucose (TyG) index and liver function parameters in healthy obese civil servants in Shijiazhuang, China.Materials and Methods: This was an outpatient-based cross-sectional study in which 6452 participants were recruited. A total of 784 participants were analyzed according to inclusion and exclusion criteria. A TyG index was calculated based on fasting glucose and triglycerides. All patients were divided into a high TyG index group and a low TyG index group, using the median TyG index as a cut-off. Finally, patients were further divided into two subgroups: males and females.Results: While AST/ALT and direct bilirubin levels were lower in the high TyG index group compared to the low TyG index group, ALT, AST, total protein, and albumin levels were greater. Particularly in male participants, TyG index was inversely connected with AST/ALT and direct bilirubin levels and favorably correlated with ALT, AST, total protein, and albumin levels. These connections persisted in the multilinear regression study even after adjusting for confounding variables.Conclusion: This study describes the correlation between TyG index and liver function parameters in obese populations without co-morbid diseases, providing a new idea for early interventional treatment in this group.Keywords: TyG index, obesity, NAFLD, ALT, AST

Yu Luo,1 Jianan Hao,1,2 Xiaoyu He,1,2 Cuiyu Wang,1 Hang Zhao,1 Zhimei Zhang,1 Liqun Yang,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Luping Ren, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +18633021149, Fax +86 311 85988406, Email renluping1122@163.comPurpose: The triglyceride–glucose index (TyG) is positively correlated with serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). However, whether this relationship exists in non-obese T2DM patients remains unknown. The study investigated the relationship between TyG and SUA in Chinese non-obese T2DM patients and examined the prognostic value of TyG in hyperuricemia (HUA).Patients and Methods: In total, 719 T2DM patients who were not obese were enrolled from among those who visited the Hebei General Hospital. The patients were categorized into groups according to their SUA levels. The relationship between TyG and clinical parameters was examined through correlation analysis. To consider covariates and examine the independent impact of TyG on HUA, logistic regression was performed. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of TyG and homeostasis model assessment of insulin resistance (HOMA-IR) for HUA.Results: The HUA prevalence was 12.10%. TyG was statistically different among the four SUA groups, with lower TyG levels in the Q1, Q2, and Q3 groups than that in the Q4 group. TyG was positively correlated with SUA (r = 0.176, P < 0.001). Logistic regression exhibited that TyG and SUA were independently correlated (OR = 2.427, 95% CI = 1.134-5.195, P = 0.022) even after adjustment for confounding factors. The ROC curve showed that the predictive value of TyG for HUA was higher than that of HOMA-IR (AUROC = 0.613, P = 0.001).Conclusion: TyG was positively correlated with SUA in non-obese T2DM patients. TyG may better predict HUA in non-obese T2DM patients than HOMA-IR.Keywords: type 2 diabetes mellitus, insulin resistance, uric acid, hyperuricemia, TyG, HOMA-IR, inflammation

Lei Ren,1 Xiaobin Zhang,1 Peihu Chen,1 Qingqing Liu2 1School of Business, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2School of Business, Jiangnan University, Wuxi, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaobin Zhang, School of Business, Soochow University, 50 Donghuan Road, Gusu District, Suzhou, 215021, People’s Republic of China, Tel + 86-136-7497-1218, Email xiaobinws@163.comPurpose: The purpose of this research is to explore the effect of empowering leadership on employee improvisation, including the mediating roles of challenge stress and hindrance stress as well as the moderating role of psychological availability.Methods: Four proposed hypotheses were tested using hierarchical regression analysis and the bootstrapping method by reference to two waves of data collected in 2021 from 248 employees working for organizations located in southern China.Results: The results showed that empowering leadership had a positive effect on employee improvisation, which was mediated by challenge stress and hindrance stress. That is, empowering leadership promoted challenge stress and decreased hindrance stress, thereby stimulating employee improvisation. Furthermore, psychological availability strengthened the positive effect of challenge stress on employee improvisation and weakened the negative effect of hindrance stress on employee improvisation. Psychological availability also moderated the indirect relationships among empowering leadership, challenge/hindrance stress and employee improvisation.Conclusion: In theoretical terms, this study identifies a new antecedent of employee improvisation: empowering leadership. This study also advances knowledge concerning the mechanism by which empowering leadership exerts its influence by drawing on cognitive transactional theory. Moreover, this study’s exploration of the moderating role of psychological availability enriches the literature concerning the boundary conditions of the challenge-hindrance stress model. In practical terms, this study provides useful insights that can help organizations activate employee improvisation and manage employees’ work pressure.Keywords: empowering leadership, employee improvisation, challenge stress, hindrance stress, psychological availability

Xiaoyu Pan,1,2 Xiaoyi Chen,2 Lin Ren,2 Zelin Li,1,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: To study the effects of obesity and overweight on carotid vascular function among healthy populations by carotid ultrasound (CAU) and transcranial Doppler (TCD).Materials and Methods: Basic clinical characteristics, CAU and TCD parameters were collected from recruited healthy individuals. Firstly, all participants were divided into three groups: normal, overweight and obese. Then, the variability of basic clinical characteristics and lipids between the three groups was calculated. Subsequently, CAU and TCD parameters were compared between the three groups. Finally, the correlation between body mass index (BMI) and neck vascular function was analyzed.Results: A total of 613 healthy participants were included, of whom 241 were normal, 264 were overweight, and 108 were obese. Overweight and obesity significantly decreased systolic, diastolic and mean flow velocities in the basilar, vertebral and internal carotid arteries, but had no effect on pulsatility index. In addition, BMI was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and remained correlated after adjusting for other factors. There was no effect of overweight and obesity on carotid plaques.Conclusion: Our study revealed that overweight and obesity decreased carotid vascular flow velocity and showed a decreasing trend in vascular flow velocity with increasing BMI. Overweight and obesity appear to have no effect on carotid plaques.Keywords: obesity, overweight, basilar artery, vertebral artery, internal carotid artery

Guanglin Li,1,2 Chenxu Shang,3 Qingqing Li,4 Lifang Chen,1,2 Zejun Yue,1,2 Lingxuan Ren,3 Jianjun Yang,3 Jiye Zhang,4 Weirong Wang1,2 1Department of Medical Laboratory Animal Science, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China; 2Institute of Cardiovascular Science, Translational Medicine Institute, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China; 3Department of Pharmacology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China; 4School of Pharmacy, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of ChinaCorrespondence: Weirong Wang, Xi’an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi’an, 710061, People’s Republic of China, Tel/Fax +86 29 82655362, Email szb2013072@xjtu.edu.cnIntroduction: Shikonin is well known for its anti-inflammatory activity in cardiovascular diseases. However, the application of shikonin is limited by its low water solubility and poor bioavailability. Methoxy poly (ethylene glycol)-b-poly (&epsiv;-caprolactone) (MPEG-PCL) is considered a promising delivery system for hydrophobic drugs. Therefore, in this study, we prepared shikonin-loaded MPEG-PCL micelles and investigated their effect on endothelial-to-mesenchymal transition (EndMT) induced by inflammatory cytokines.Methods: Shikonin was encapsulated in MPEG-PCL micelles using an anti-solvent method and the physiochemical characteristics of the micelles (particle size, zeta potential, morphology, critical micelle concentration (CMC), drug loading and encapsulation efficiency) were investigated. Cellular uptake of micelles in human umbilical vein endothelial cells (HUVECs) was evaluated using fluorescence microscopy. In vitro EndMT inhibition was explored in HUVECs by quantitative real-time PCR analysis.Results: The average particle size of shikonin-loaded MPEG-PCL micelles was 54.57± 0.13 nm and 60 nm determined by dynamic light scattering and transmission electron microscopy, respectively. The zeta potential was − 6.23± 0.02 mV. The CMC of the micelles was 6.31× 10− 7mol/L. The drug loading and encapsulation efficiency were 0.88± 0.08% and 43.08± 3.77%, respectively. The MPEG-PCL micelles significantly improved the cellular uptake of cargo with low water solubility. Real-time PCR analysis showed that co-treatment with TNF-α and IL-1β successfully induced EndMT in HUVECs, whereas this process was significantly inhibited by shikonin and shikonin-loaded MPEG-PCL micelles, with greater inhibition mediated by the shikonin-loaded MPEG-PCL micelles.Conclusion: Shikonin-loaded MPEG-PCL micelles significantly improved the EndMT-inhibiting effect of the free shikonin. MPEG-PCL is suitable for use more generally as a lipophilic drug carrier.Keywords: shikonin, shikonin-loaded MPEG-PCL micelles, inflammation, EndMT

Yunfan Xia,1 Ruohan Sun,1 Rongrong Li,1 Leilei Ren,1 Yiyi Wang,1 Jianqiao Fang2 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of ChinaCorrespondence: Jianqiao Fang, 23 Qingchun Road, Hangzhou City, People’s Republic of China, Tel +86(0)571-87238254, Fax +86(0)571-87238005, Email fangjianqiao7532@163.comBackground: Accumulate evidence indicated that moxibustion has a positive effect on pain treatment. However, the bibliometric analysis of moxibustion on pain remains uncertain. Herein, this study aimed to explore the current hotspots and the research trends over the past decade to bring a great panorama in this field.Methods: Publications were retrieved from the database Web of Science Core Collection (WoSCC) related to moxibustion therapy for pain treatment from January 1, 2012, to December 31, 2021. CiteSpace and Excel were applied to analyze the volume of publications, journals, cited journals, dual-map analysis, countries, institutes, authors, references, and keywords with citation bursts.Results: A total of 360 publications were retrieved from 2012 to 2021. The annual number of publications increased steadily with some fluctuations over the past 10 years. “The Evid Based Complement Alternat Med” and “the Gut” were the top-cited journals in frequency and centrality. China and Shanghai University of Traditional Chinese Medicine were the most prolific country and institutions, respectively. Among authors, Huangan Wu was the most active author with the highest cited frequency. Jun Xiong, Fanrong Liang and Guixing Xu held the articles with higher centrality. In the ranking of frequency and centrality in cited references, the top one was the article published by Shamseer L and Deng HY, respectively. “Acupuncture” was the keyword with the highest frequency. Pain disease (including rheumatoid arthritis, knee osteoarthritis, herpes zoster), research method (including randomized controlled trial), and risk (including quality of life, economic burden, physical and psychological problems) were the hotspots and frontier trends in this field.Conclusion: This bibliometric study reveals the current status and research trend in the treatment of pain with moxibustion. The formulation with bibliometric analysis further elicits hot spots and frontier issues in this field.Keywords: moxibustion, pain, CiteSpace, bibliometric analysis

Zelin Li,1,2 Cuijuan Qi,1 Zhuoya Jia,1,2 Ruoxi Zhen,1,2 Lin Ren,1,3 Yujiao Jia,1,2 Shuchun Chen1,2,4 1Graduate School of Hebei Medical University, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, People’s Republic of China; 3North China University of Science and Technology, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, 050051, People’s Republic of China, Tel +86 031185988406, Fax +86 031185988406, Email chenshuc2014@163.comPurpose: To study the correlation between estimated glucose disposition rate (eGDR) and coagulation parameters in type 2 diabetes patients (T2DM).Materials and Methods: A total of 948 patients suffering from T2DM were enrolled for this research. Various blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were assessed. Body mass index (BMI), hypertension, and the levels of glycated hemoglobin (HbA1c) were used to calculate the patients’ eGDRs. All patients were sorted into two groups: those with high eGDRs (eGDR≥ 7.5) and those with low eGDRs (eGDR< 7.5). The patients were then separated into groups of men and women. The connection between eGDR and coagulation indexes was examined using Spearman correlation, Pearson correlation, and multiple linear regression analysis.Results: In comparison to the high-eGDR group, reduced PT and APTT levels with increased FIB levels were observed in the low-eGDR group (P =0.006, P < 0.001, and P = 0.035, respectively). The eGDR showed a positive relation with APTT (r = 0.142, P < 0.001), a negative relation with FIB (r = − 0.082, P = 0.012), and no correlation with PT (r =0.064, P =0.050) in the all patients. As well as, the eGDR demonstrated a positive relation with APTT (r = 0.173, P < 0.001), a negative relation with FIB (r = − 0.093, P = 0.03), and no relation with PT (r = 0.045, P = 0.300) in the male subgroups. Additionally, this correlation persisted following the adjustment of other factors in multilinear regression analysis. However, the female subgroup demonstrated no correlation among eGDR and PT, APTT or FIB (r = 0.086, P = 0.083, r = 0.097, P = 0.05;r = − 0.058, P = 0.240, respectively).Conclusion: Our study is the first to prove that eGDR demonstrates a correlation with coagulation indexes in T2DM patients. And, this correlation is gender-specific.Keywords: estimated glucose disposal rate, coagulation indexes, type 2 diabetes mellitus

Miaomiao Zhao,1,2 Longbing Ren,3 Zhitong Zhou,3 Tao Wang,3 Jue Li2 1School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 2Department of Epidemiology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Institute of Clinical Epidemiology and Evidence-Based Medicine, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jue Li, Department of Epidemiology, Tongji Hospital Affiliated to Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200442, People’s Republic of China, Tel +86-21-65986735, Fax +86-21-65980448, Email jueli@tongji.edu.cnPurpose: The effects of statins on renal outcomes have already been studied in patients with chronic kidney disease (CKD); however, data on the general population are limited. We evaluated the association between statin use and risk of CKD in community-dwelling older people in Shanghai, China.Patients and Methods: This registry-based cohort study was conducted in four communities in four districts in Shanghai. Participants with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 in 2016 were eligible for the study, and new-onset CKD in 2017, 2018, and 2019 was recorded. Poisson generalized linear models were conducted to examine the relationships among statin therapy, dyslipidemia, and CKD; linear mixed-effects models were conducted to examine the relationships between statin therapy and changes in eGFR. All analyses were performed with both conventional adjustment and propensity score-matching methods.Results: Of the study cohort of 2455 participants (41.1% men; average age, 68.06 years), 624 (25.4%) were treated with stains. Two propensity score-matched cohorts of 604 participants each were analyzed (statin users and nonusers). Statin use was significantly associated with a decreased risk of new-onset CKD with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.73 (0.59 to 0.91) (p< 0.01) in the unmatched cohort and 0.75 (0.59 to 0.97) (p=0.02) in the matched cohort. There were significant differences in the eGFR decline between statin users and nonusers from baseline to 3 years in the unmatched and matched cohorts (both p< 0.05). In addition, both statin users and nonusers with dyslipidemia experienced more new-onset CKD (both p< 0.05).Conclusion: Statin use was significantly associated with a decreased risk of new-onset CKD and a slower decline in eGFR in community-dwelling older people. Meanwhile, dyslipidemia was a risk factor for CKD progression among both statin users and nonusers.Keywords: chronic kidney disease, statins, dyslipidemia, community-dwelling older people

Ruohan Sun,1,2,&ast; Shimin Li,1,&ast; Leilei Ren,2 Yunfan Xia,2 Yiyi Wang,2 Zhiyuan Bian,2 Jianqiao Fang,2 Zuyong Zhang1 1Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuyong Zhang, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, No. 38 West Lake Road, Hangzhou, Zhejiang, People’s Republic of China, Email zzynwk@126.com Jianqiao Fang, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 23 Qinchun Road, Hangzhou, Zhejiang, People’s Republic of China, Email fangjianqiao7532@163.comIntroduction: Postherpetic neuralgia (PHN) is a severe complication of herpes zoster (HZ), representing an important burden of disease in the elderly. Electroacupuncture (EA) has become growingly appreciated as a therapy of PHN with the situation that effectiveness of conventional therapy of PHN is less than ideal. Owing to its low price, no side effects, high safety and high patients acceptance, EA has been used in treating PHN more frequently. Therefore, the randomized controlled trial which is to evaluate the effectiveness and safety of EA in patients with PHN and whether EA could be an alternative therapy of medication is needed.Patients and Methods: A total of 88 patients with PHN will be recruited from 2 hospitals and randomized assigned to EA group or Medication group in a 1:1 ratio, utilizing a central randomization system. The trial will involve a 4-week treatment period, and a 4-week follow-up period. All variables will be evaluated at week 0 (baseline), week 2 (treatment), week 4 (treatment), week 8 (follow-up) and week 16 (follow-up). Primary outcomes will be pain intensity. Secondary outcomes will contain quality of life, mood state and sleep quality. All adverse effects will be assessed during the trial.Conclusion: This study will provide significant evidence that whether EA therapy is effective and safe for patients with PHN and whether EA could be an alternative therapy of medication.Ethics and Dissemination: Ethics approval has been obtained from the Ethics Committee of the Hangzhou Third People’s Hospital (No. 2021KAO43). Informed consent will be signed before enrolment. Results of this trial will be presented to international journals for publication and be reported in relevant international conferences.Trial Registration Number: This protocol has been registered in the Chinese Clinical Trial registry with the identification code ChiCTR2100054592.Keywords: postherpetic neuralgia, electroacupuncture, pain, randomized controlled trial, protocol

Tingfeng Xu,1,&ast; Liying Ren,1,&ast; Minjun Liao,1,2,&ast; Bigeng Zhao,1 Rongyu Wei,1 Zhipeng Zhou,3 Yong He,4 Hao Zhang,3 Dongbo Chen,5 Hongsong Chen,5 Weijia Liao1 1Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 3Department of Radiology, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China; 5Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weijia Liao, Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China, Tel +86 773 2833021, Fax +86 773 2822703, Email liaoweijia288@163.com Hongsong Chen, Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, No. 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China, Tel +86 10 88325724, Email chenhongsong2999@163.comPurpose: Microvascular invasion (MVI) impairs long-term prognosis of patients with hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict MVI and patients’ prognosis based on radiomic features of contrast-enhanced CT (CECT).Patients and Methods: HCC patients who underwent curative resection were enrolled. The radiomic features were extracted from the region of tumor, and the optimal MVI-related radiomic features were selected and applied to construct radiomic signature (Rad-score). The prediction models were created according to the logistic regression and evaluated. Biomarkers were analyzed via q-PCR from randomly selected HCC patients. Correlations between biomarkers and radiomic signature were analyzed.Results: A total of 421 HCC patients were enrolled. A total of 1962 radiomic features were extracted from the region of tumor, and the 11 optimal MVI-related radiomic features showed a favor predictive ability with area under the curves (AUCs) of 0.796 and 0.810 in training and validation cohorts, respectively. Aspartate aminotransferase (AST), tumor number, alpha-fetoprotein (AFP) level, and radiomics signature were independent risk factors of MVI. The four factors were integrated into the novel nomogram, named as CRM, with AUCs of 0.767 in training cohort and 0.793 in validation cohort for predicting MVI, best among radiomics signature alone and clinical model. The nomogram was well-calibrated with favorable clinical value demonstrated by decision curve analysis and can divide patients into high- or low-risk subgroups of recurrence and mortality. In addition, gene BCAT1, DTGCU2, DOCK3 were analyzed via q-PCR and serum AFP were identified as having significant association with radiomics signature.Conclusion: The novel nomogram demonstrated good performance in preoperatively predicting the probability of MVI, which might guide clinical decision.Keywords: hepatocellular carcinoma, microvascular invasion, preoperative noninvasive diagnosis, contrast-enhanced CT, biologic correlation

Rui-Qin Yang,1– 3 Min Chen,3,4 Qiang Zhang,5 Yi-Yang Gao,1– 3 Kang-Liang Lou,1– 3 Tong-Tong Lin,5 Wen-He Huang,1,2 Yun-Zhu Zeng,6 Yong-Qu Zhang,1– 3 Yong-Ying Dang,1– 3 Lei Ren,5,&ast; Guo-Jun Zhang1,2,4,&ast; 1Cancer Center & Department of Breast and Thyroid Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Key Laboratory for Endocrine-Related Cancer Precision Medicine of Xiamen, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 3Clinical Central Research Core, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 5State Key Lab of Physical Chemistry of Solid Surface, College of Materials, Xiamen University, Xiamen, Fujian, People’s Republic of China; 6The Pathology department, Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Jun Zhang, Tel +86-592-2889988, Fax +86-592-2889202, Email gjzhang@xah.xmu.edu.cnPurpose: Tumor-free surgical margin is crucial but challenging in breast-conserving surgery (BCS). Fluorescence imaging is a promising strategy for surgical navigation that can reliably assist the surgeon with visualization Of the tumor in real-time. Notably, finding an optimized fluorescent probe has been a challenging research topic. Herein, we developed a novel near-infrared (NIR) fluorescent probe based on tailored Hepatitis B Core virus-like protein (HBc VLP) and presented the preclinical imaging-guided surgery.Methods: The RGD-HBc160 VLP was synthesized by genetic engineering followed encapsulation of ICG via disassembly-reassembly. The applicability of the probe was tested for cell and tissue binding capacities through cell-based plate assays, xenograft mice model, and MMTV-PyVT mammary tumor transgenic mice. Subsequently, the efficacy of RGD-HBc160/ICG-guided surgery was evaluated in an infiltrative tumor-bearing mouse model. The protein-induced body’s immune response was further assessed.Results: The prepared RGD-HBc160/ICG showed outstanding integrin αvβ3 targeting ability in vitro and in vivo. After intravenous administration of probe, the fluorescence guidance facilitated more complete tumor resection and improved overall survival Of the infiltrative tumor-bearing mice. The probe also showed the excellent capability to differentiate between benign and malignant breast tissues in the mammary tumor transgenic mice. Interestingly, the ingenious tailoring of HBc VLP could not only endow its tumor-targeting ability towards integrin αvβ3 but also significantly reduce the humoral and cellular immune response.Conclusion: The RGD-HBc160/ICG holds promise as an effective tool to delineate tumor margin. These results have translational potential to achieve margin-negative resection and improve the stratification of patients for a potentially curative.Graphical Abstract: Keywords: breast Cancer, tumor margin, NIR fluorescence imaging, imaging-guided surgery, Hepatitis B core virus-like particles

Tianyu Liu,1,&ast; Wenju Chang,1,2,&ast; Hao Wang,3,&ast; Qi Lin,1,2,&ast; Ye Wei,1,2 Wentao Tang,1 Yu Liu,1 Yijiao Chen,1 Zhengchuan Niu,1 Yudong Jiang,1 Li Ren,1,2 Jianmin Xu1,2 1Colorectal Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive Technology, Shanghai, People’s Republic of China; 3Department of Thoracic Surgery; Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianmin Xu; Li RenColorectal Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-64041990Email xujmin@aliyun.com; ren.li@zs-hospital.sh.cnPurpose: This study aimed to evaluate the role of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) and to investigate clinically relevant prognostic factors.Patients and Methods: The medical records of 350 consecutive patients who underwent LM of CRC from 2011 to 2019 were reviewed. The patients were designated into AR group (lobectomy and segmentectomy), and non-anatomical resection (NAR) group (wedge resection), respectively. Kaplan–Meier method was used to analyze disease-free survival (DFS), pulmonary-specific disease-free survival (PDFS) and overall survival (OS). Cox proportional hazards regression model was performed to analyze the factors associated with DFS, PDFS and OS.Results: A total of 92 (31.2%) patients were enrolled in AR group and 203 (68.8%) in non-anatomical resection (NAR) group. AR significantly improved the 3-year DFS (64.1% vs 46.8%, HR 0.587, 95% CI 0.397– 0.867, P = 0.007) and PDFS (75.0% vs 60.1%, HR 0.565, 95% CI 0.356– 0.899, P = 0.016) compared with NAR. However, the extent of resection did not significantly impact the 3-year OS (AR 92.4% vs NAR 85.7%, HR 0.511, 95% CI 0.224– 1.165, P = 0.110). In multivariate analysis, AR was identified as a protective factor for DFS (HR 0.576, 95% CI 0.356– 0.934, P = 0.025) and PDFS (HR 0.631, 95% CI 0.409– 0.973, P = 0.037). Preoperative abnormal CA19-9 was identified as the only prognostic factor for OS.Conclusion: AR was superior to NAR for DFS and PDFS after LM from CRC.Keywords: pulmonary metastasis, lobectomy, wedge resection, prognosis

Yue Zhang, Lianping Ren, Jinyuan Sun, Fengfeng Han, Xuejun Guo Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Xuejun GuoDepartment of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, People’s Republic of ChinaTel +86-21-25078999-7373Email guoxuejun@xinhuamed.com.cnBackground: This study aimed to reveal the correlation between serum soluble interleukin-2 receptor (sIL-2R) and prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: A total of 315 patients diagnosed with AECOPD between December 2017 and June 2020 were enrolled. The patients were divided into the good and adverse groups based on the outcomes. An adverse outcome in COPD exacerbation was defined by the presence of at least one of the following: (1) death from a respiratory cause during hospitalisation or within 1 month of follow-up; (2) intensive care unit admission; (3) invasive or non-invasive mechanical ventilation; and (4) COPD-related emergency visit or readmission within 1 month of follow-up. A good outcome was considered as the absence of all the aforementioned issues. The patients underwent lung function (spirometry) assessment, and clinical and inflammatory profiles were collected. Univariate and multivariate analyses were performed to identify the correlation between serum sIL-2R concentration and other variables related to adverse outcomes of AECOPD. The receiver operating characteristic curve was used to show the predictive ability of sIL-2R for adverse outcomes of AECOPD.Results: We enrolled 315 patients, of whom 161 and 154 had good and adverse outcomes, respectively. We demonstrated that patients with adverse outcomes of AECOPD had a higher concentration of serum sIL-2R than patients with good outcomes (p < 0.001). The increased serum sIL-2R was positively associated with mMRC scores (p < 0.001), GLOD grades (p < 0.001), frequent exacerbation (p < 0.001), and smoking (p < 0.001) in patients with AECOPD and negatively correlated with pulmonary function (p < 0.001). An elevated sIL-2R level was a predictor for the risk of adverse outcomes in AECOPD with a cut-off value of 860 U/mL.Conclusion: Increased serum sIL-2R concentration correlated with the risk of the adverse outcomes in AECOPD, indicating that it can be a predictive factor contributing to the diagnosis and assessment of adverse outcomes in patients with AECOPD.Keywords: chronic obstructive pulmonary disease, acute exacerbation, soluble interleukin-2 receptor, predictive factor

Shujing Huang,1,&ast; Hongyan Sun,2,&ast; Jia Yu,3 Hongfei Shi,2 Liyun Ren,3 Yan He,3 Mingzhi Zhang,3 Hao Peng,3,4 Heng Guo1 1Department of Public Health, School of Medicine, Shihezi University, Shihezi, People’s Republic of China; 2Center for Disease Prevention and Control of Tianning District, Changzhou, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People’s Republic of China; 4Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heng GuoDepartment of Public Health, School of Medicine, Shihezi University, North 2nd Road, Shihezi, 832000, People’s Republic of ChinaTel +86 993 205 7153Email shzuguoheng@foxmail.comHao PengDepartment of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of ChinaTel +86 512 6588 0078Fax +86 512 6588 0052Email penghao@suda.edu.cnPurpose: Sleep duration was associated with large artery atherosclerosis, but its association with atherosclerosis in lower extremity arteries was not well studied. Together with sleep, physical activity constitutes main component of our daily life and influences sleep. Here, we aimed to examine the independent and joint associations of sleep duration and physical activity with peripheral artery disease (PAD) in Chinese adults.Patients and Methods: In Tianning cohort, night-time sleep duration and physical activity were assessed by the Pittsburgh Sleep Quality Index and the Global Physical Activity Questionnaire, respectively, for 5130 participants (51.0± 15.6 years, 58.7% female). PAD was defined as ankle-brachial index (ABI) < 0.9. General linear, and logistic regression models were used to assess the associations of sleep duration and physical activity with PAD. The biological interaction between sleep duration and physical activity on PAD was examined using additive model.Results: Compared to participants sleeping 6– 8.9 h, those sleeping ≥ 9 h had a 0.02 lower ABI (β=− 0.02, P=0.007) and 38% higher odds of PAD (OR=1.38, P=0.035). Compared to physically active participants sleeping 6– 8.9 h, among ≥ 9 h group, physically inactive individuals had significantly increased odds of PAD (OR=2.40, P< 0.001), whereas physically active individuals did not (OR=1.15, P=0.472). On additive scale, attributable proportion due to interaction (0.40, 95% CI: 0.07, 0.73) indicated a significant interaction between sleep duration and physical activity on PAD.Conclusion: Being physically active may attenuate the detrimental association between prolonged sleep duration and PAD. Moreover, we found a significant interaction between prolonged sleep duration and physical inactivity in the prevalence of PAD.Keywords: lower extremity disease, Tianning cohort, sleep duration, joint association, physical activity

Yu Wei, Jiayao Fu, Wenjing Wu, Pengfei Ma, Le Ren, Zimei Yi, Junhua Wu Department of Prosthodontics, School and Hospital of Stomatology, Tongji University and Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, People’s Republic of ChinaCorrespondence: Junhua WuDepartment of Prosthodontics, School and Hospital of Stomatology, Tongji University and Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, People’s Republic of ChinaTel +86 21-66313729Email wujunhua_sh@tongji.edu.cnPurpose: Emerging evidence has indicated that oxidative stress (OS) contributes to periodontitis. Periodontal ligament cells (PDLCs) are important for the regeneration of periodontal tissue. Quercetin, which is extracted from fruits and vegetables, has strong antioxidant capabilities. However, whether and how quercetin affects oxidative damage in PDLCs during periodontitis remains unknown. The aim of this study was to assess the effects of quercetin on oxidative damage in PDLCs and alveolar bone loss in periodontitis and underlying mechanisms.Materials and Methods: The tissue block culture method was used to extract human PDLCs (hPDLCs). First, a cell counting kit 8 (CCK-8) assay was used to identify the optimal concentrations of hydrogen peroxide (H2O2) and quercetin. Subsequently, a 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe, RT-qPCR, Western blotting and other methods were used to explore the effects of quercetin on OS in hPDLCs and the underlying mechanism. Finally, quercetin was administered to mice with periodontitis through gavage, and the effect of quercetin on the level of OS and alveolar bone resorption in these mice was observed by immunofluorescence, microcomputed tomography (micro-CT), hematoxylin and eosin staining (H&E) staining and so on.Results: Quercetin at 5 μM strongly activated NF-E2–related factor 2 (NRF2) signaling, alleviated oxidative damage and enhanced the antioxidant capacity of hPDLCs. In addition, quercetin reduced cellular senescence and protected the osteogenic ability of hPDLCs. Finally, quercetin activated NRF2 signaling in the periodontal ligaments, reduced the OS level of mice with periodontitis, and slowed the absorption of alveolar bone in vivo.Conclusion: Quercetin can increase the antioxidant capacity of PDLCs and reduce OS damage by activating the NRF2 signaling pathway, which alleviates alveolar bone loss in periodontitis.Keywords: periodontitis, periodontal ligament cells, oxidative stress, cellular senescence and quercetin

Yingyi Zhang,1 Libin Ren,1 Min Ren,2 Hua Yang,1 Kunmeng Li,1 Hongliang Cong,1 Zhigang Guo3 1Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of China; 2Tianjin Cardiovascular Institute, Tianjin, 300222, People’s Republic of China; 3Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of ChinaCorrespondence: Hongliang CongDepartment of Cardiology, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of ChinaTel +86 13702102871Email chlcong@163.comZhigang GuoDepartment of Cardiac Surgery, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of ChinaTel +86 13821002900Email zgguohosp@163.comObjective: This study aims to investigate the correlation between triglyceride–glucose index (TyG) and the risk of cardiovascular disease (CVD).Methods: A total of 102,061 permanent residents of Tianjin, China, aged 35– 75 years were surveyed. A questionnaire, physical examination, and blood tests for biochemical markers were conducted for all subjects. The risk of CVD was judged based on the results, identifying the population with a high risk of CVD. TyG was calculated for all subjects who were then grouped into TyG quartiles. The correlation between TyG and the detection rate of subjects with a high risk of CVD was analyzed using the chi-square test and Pearson’s correlation analysis. The cut-off points and the magnitude of the predictive effect of TyG in determining a high risk of CVD were identified by calculating the TyG through analysis of the receiver operator characteristic (ROC) curve.Results: The surveyed population consisted of 39,598 males (38.8%) and 62,463 females (61.2%). The average age was 55.84 ± 10.27 years. A statistically significant difference in the incidence of a high CVD risk between subjects in the four groups divided by the TyG levels was identified (p < 0.01). Pearson’s correlation analysis showed that TyG was correlated with all risk factors for CVD (p < 0.01). The maximum Youden’s J statistic for determining the high risk of CVD was found at a TyG of 9.04 (specificity 0.575, sensitivity 0.754). The area under the ROC curve was 0.780 (confidence interval [CI]: 0.777, 0.783, p < 0.01).Conclusion: TyG index is closely related to the aggregation of cardiovascular risk factors and is correlated with the judgment results of the screening population’s high risk of CVD, suggesting that more attention should be paid to the identification and control of multiple risk factors in the population with significantly elevated TyG.Keywords: triglyceride–glucose index, cardiovascular disease, risk, insulin resistance

Xiaolin Wu,1,2 Yingjuan Liu,2 Lin Zhu,2 Yue Wang,2 Yuqian Ren,2 Baohe Cheng,3 Leiming Ren,4 Keli Ge,2 Hongyun Li1 1Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People’s Republic of China; 2Institute of Integrative Medicine, School of Basic Medicine, Qingdao University, Qingdao, Shandong, 266021, People’s Republic of China; 3Shandong Haoyun Guoji Stem Cells Hospital, Jinan, Shandong, 250001, People’s Republic of China; 4Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Hongyun LiDepartment of Neurology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Shinan District, Qingdao, Shandong, People’s Republic of ChinaEmail 18661808653@163.comKeli GeInstitute of Integrative Medicine, School of Basic Medicine, Qingdao University, No. 38, Dengzhou Road, Shibei District, Qingdao, Shandong, People’s Republic of ChinaEmail ntfadu@163.comIntroduction: Vascular dementia (VaD), one of the brain injuries, is difficult to be cured, so it is important to take active neuroprotective treatment after its occurrence. Many studies have shown that apoptosis serves an important role in VaD occurrence; therefore, inhibition of apoptosis may contribute to the recovery of neurological function after VaD occurrence. Cerebroprotein hydrolysate-I (CH-I), a neuropeptide preparation which consists of several amino acids and small molecular peptides as the main active constituent, is extracted using a method similar to cerebrolysin (CBL) which has neuroprotective and neurotrophic effects.Methods: In the present study, a VaD model which was constructed using bilateral common carotid artery occlusion (BCCAO) in Kunming mice was applied to examine the neuroprotective effects of CH-I.Results: The results show that CH-I treatment could attenuate the decrease of learning and memory ability, cell apoptosis in the hippocampal CA1 region and inhibit the activation of caspase-3 and caspase-9 in VaD mice. Furthermore, CH-I treatment could also upregulate Bcl-2 protein levels and activate PI3K and Akt.Discussion: We speculate that CH-I may induce a neuroprotective effect activating PI3K/Akt signaling pathway in VaD mice.Keywords: vascular dementia, cerebroprotein hydrolysate-I, apoptosis, PI3K/Akt

Yuqian Ren,1 Xiaoqing Ma,1 Tingting Wang,1 Baohe Cheng,2 Leiming Ren,3 Zehua Dong,4 Hongling Liu5 1Institute of Cerebrovascular Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Shandong Haoyun International Hospital of Stem Cells, Jinan, Shandong, 250001, People’s Republic of China; 3Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 4Department of Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 5Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Zehua Dong; Hongling Liu Tel +86-139 63958230; +86-18661808612Email gonewithwind18@163.com; lhl3798@126.comObjective: To investigate the neuroprotective effect and mechanism of cerebroprotein hydrolysate-I (CH-I) on cerebral ischemia/reperfusion injury in rats.Methods: A total of 100 adult healthy male SD rats were randomly divided into a sham group, model group, CH-I treated group, and cerebrolysin (CBL) positive group, consisting of 20 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model of rats was built by inserting a suture into the left external carotid artery (ECA) through the internal carotid artery (ICA). Treatment was performed by intraperitoneal injection of CH-I (20 mg/kg). The neurobehavioral function of rats was evaluated by modified neurological severity scores (mNSS). TTC staining was used to detect the cerebral infarction volume (CIV) of rats. The morphological and structural changes of nerve cells were observed by HE staining and the neuronal apoptosis was counted by TUNEL assay. Immunohistochemical (IHC) analysis was used to detect BDNF and pMEK1/2 expressions. The expressions of BDNF, pMEK1/2, pERK1/2, and pCREB were determined with Western blotting.Results: After treatment with CH-I, the mNSS and CIV of rats were improved (P< 0.05). And the CH-I can reduce the degeneration and apoptosis of nerve cells in rats (P< 0.01). Western blotting showed that the expressions of pMEK1/2, pERK1/2, and pCREB in rats were increased, while the expression of BDNF was decreased after modeling (P< 0.05). After treatment, the expressions of pMEK1/2, pERK1/2, and pCREB in the CH-I group were decreased (P< 0.05), while the expression of BDNF was significantly increased (P< 0.05) compared with the model group. IHC showed that the expression of BDNF and pMEK1/2 was consistent with Western blotting.Conclusion: It is suggested that the CH-I might play a neuroprotective role by inhibiting the expression of MEK-ERK-CREB and enhancing the expression of BDNF after cerebral ischemia/reperfusion injury, thus improving the neurobehavioral function of MCAO/R rats.Keywords: cerebroprotein hydrolysate-I, cerebral ischemia/reperfusion injury, apoptosis, MAPK/ERK1/2 signaling pathway, rats

Yu Liu,1,2,* Wenju Chang,1– 3,* Wentao Tang,1– 3,* Ye Wei,1– 3 Tianyu Liu,1,2 Yijiao Chen,1,2 Meiling Ji,1– 3 Fei Liang,4 Li Ren,1– 3 Jianmin Xu1– 3 1Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People’s Republic of China; 4Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianmin XuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaTel +86 13501984869Email xujmin@aliyun.comBackground: Rectal gastrointestinal stromal tumors (GISTs) are rare digestive tumors. The treatment methods of rectal GISTs are diverse, while no standardized treatment was recommended. The aim of this study was to report the treatment mode of rectal GISTs in our center.Methods: Patients with pathologically confirmed rectal GISTs who received neoadjuvant therapy and surgical resection were retrospectively collected. Perioperative complications and long-term prognosis were evaluated.Results: From January 2010 to December 2019, 36 patients were pathologically diagnosed with primary rectal GISTs. After excluding patients who were treated with surgery or imatinib alone, 21 patients received neoadjuvant therapy and surgery was enrolled. During neoadjuvant treatment, tumors shrank significantly (6.53cm to 4.68cm, p< 0.001) without toxicities over grade 2. The total postoperative complication rate was 42.9% (all grade). R0 resection was achieved in 76.2% patients. Transanal resection had advantages on anus preservation and postoperative recovery. No patients died during the follow-up period, 4 patients relapsed and the relapse-free survival was 81.0%.Conclusion: The combination of neoadjuvant therapy and surgical resection was a safe and effective treatment for rectal gastrointestinal stromal tumors.Keywords: rectal gastrointestinal stromal tumors, GISTs, neoadjuvant therapy, surgical resection

Qian Wei, Ze Li, Honglei Feng, Li Ren Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Li RenDepartment of Laboratory, Tianjin Medical University Cancer Institute and Hospital, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, People’s Republic of ChinaEmail lirentj@163.comBackground: Pancreatic cancer (PC) is one of the worst prognoses amongst all malignant diseases. It is therefore of great significance to identify biomarkers with predictive clinical value for the prognosis and recurrence of PC.Methods: In our study, enzyme-linked immunosorbent assays (ELISA) were used to detect the expression of Exo-EphA2 in the serum of PC patients and controls. Kaplan–Meier curve and Cox regression analyses were used to evaluate the prognostic value of Exo-EphA2 expression in patients with primary and recurrent PC.Results: The level of serum Exo-EphA2 was significantly higher in the PC group when compared to that of the control group. High expression of Exo-EphA2 in PC was associated with shorter overall survival (OS) and proved to be a significant negative prognostic factor in the multivariate analysis (HR = 1.04, 95% CI: 1.00– 1.09, P < 0.001). Additionally, we found that the level of serum Exo-EphA2 in recurrent PC patients (first recurrence < 12 months) was positively correlated with the level of Exo-EphA2 at primary diagnosis. Multivariate analysis showed that a high expression of Exo-EphA2 in recurrent PC was associated with shorter recurrence-free survival (RFS) (HR = 1.41, 95% CI: 1.10– 1.70, P < 0.001).Conclusion: High expression of serum Exo-EphA2 represents a novel biomarker for a poor prognosis in PC patients.Keywords: pancreatic cancer, exosome, EphA2, prognosis

Longbing Ren,1,2 Yan Gao,3 Yuting Jiang,3 Gege Wang,1,2 Qi Li,1,2 Yijun Gu,1,2 Han Yu,1,2 Jue Li,1,2 Lijuan Zhang1,2 1Shanghai East Hospital, Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Tongji University, Shanghai, 200120, People’s Republic of China; 2Institute of Clinical Epidemiology and Evidence-Based Medicine, Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 3Community Health Service Center of Anting Town Affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 201805, People’s Republic of ChinaCorrespondence: Jue Li; Lijuan Zhang Email jueli@tongji.edu.cn; zhangxiaoyi@tongji.edu.cnBackground and Aim: Any single discrete blood pressure (BP) measurement is not enough to estimate adverse cardiovascular events. We aim to comprehensively investigate the association between BP indicators and stroke.Methods: An observational cohort study was conducted among 2888 Shanghai community-aged residents from 2014 to 2018, and a nested case-control study was designed to identify the association between BP indicators and stroke. In total 415 cases of stroke detected during the study period were selected as the case group and 415 non-stroke subjects, matched with factors of age and gender, were randomly selected from the cohort as control group.Results: Multivariate logistic regression analysis revealed that systolic blood pressure (SBP) (adjusted odds ratio [AOR] 1.02, 95% confidence interval [CI] 1.02– 1.03), pulse pressure (PP) (AOR 1.03, 95% CI 1.02– 1.04), mean arterial pressure (MAP) (AOR1.02, 95% CI 1.01– 1.04) and pulse pressure index (PPI) (AOR 25.68, 95% CI 3.19– 206.90) increased the risk of stroke, respectively. After fitting both BP indicators and covariates, isolated abnormal SBP (AOR 2.55, 95% CI 1.74– 3.72) or PP ≥ 50 mmHg (AOR 1.66, 95% CI 1.08– 2.56) independently increased risk of stroke.Conclusion: Besides SBP, PP and multiple factors, assessment should be taken into account comprehensively for stroke prevention and management.Keywords: blood pressure; BP, stroke, nested case-control study, primary care

Hang Zhao,1 Yong Tang,1 Chong Zheng,2 Luping Ren,1,* Guangyao Song1,* 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Pediatric Orthopaedics, Shijiazhuang the Third Hospital, Shijiazhuang, Hebei, 050011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luping Ren; Guangyao Song 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaTel +8631185988975; +8631185988556Email renluping1122@163.com; sguangyao2@163.comPurpose: This study aimed to examine whether 25-hydroxyvitamin D (25OHD) levels (an indicator of vitamin D status) are independently associated with insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This was a cross-sectional study. Participants with T2DM were recruited from the Department of Endocrinology in Hebei General Hospital according to inclusion and exclusion criteria. Data on basic characteristics and blood parameters were collected. We used the IR index (20/[fasting C-peptide × fasting plasma glucose]) to evaluate IR. Potential confounding factors were selected from comparisons among different IR index groups of quartiles and were adjusted in different models.Results: We included 172 subjects (121 men and 51 women) whose mean age was 53.2± 10.6 years. Body mass index (BMI), DM course, insulin use, glycated hemoglobin (HbA1c), fasting blood glucose, fasting C-peptide, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and albumin were differed among different IR-index groups (all P value < 0.05). In models 1 and 2, no or some confounding factors were adjusted for, and we found that there was no relationship between 25OHD and the IR index. In model 3, when all confounding factors (DM course, insulin use, BMI, HbA1c, TG, HDL-C, ApoA1, albumin and other bone turnover markers) were adjusted for, the IR index was increased by 5.6% when 25OHD levels increased by 1 ng/mL (odds ratio: 1.056; 95% confidence interval: 1.009, 1.105).Conclusion: Vitamin D is independently associated with IR in patients with T2DM.Keywords: diabetes mellitus, type 2, vitamin D, insulin resistance

Jia Yu,1,* Hongyan Sun,2,* Jinhua Zhu,3,* Xintong Wei,1 Hongfei Shi,2 Bin Shen,3 Liyun Ren,1 Yan He,1 Rongyan Zhang,3 Mingzhi Zhang,1 Hao Peng1,4 1Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Center for Disease Prevention and Control of Tianning District, Changzhou, People’s Republic of China; 3Center for Disease Prevention and Control of Wujiang District, Suzhou, People’s Republic of China; 4Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao PengDepartment of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of ChinaTel +86 512 6588 0078Fax +86 512 6588 0052Email penghao@suda.edu.cnObjective: The relationship between obesity and hyperuricemia has been demonstrated by many studies. However, whether or to what extent metabolic condition influents the association between obesity and hyperuricemia was not clear. Here, we aimed to examine the association between obese-metabolic phenotype and hyperuricemia in a large sample of Chinese adults.Methods: According to BMI and metabolic syndrome, obese-metabolic phenotype was defined as metabolically unhealthy obesity (MUO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically healthy non-obesity (MHNO)in the Tianning cohort (N=5072). We conducted a cross-sectional analysis between obese-metabolic phenotype and hyperuricemia, followed by a Mendelian Randomization analysis using GWAS summary data to confirm the causality between uric acid and BMI.Results: The average level of serum UA showed 41.87-higher μmol/L in participants with MHO (β=41.87, P< 0.001) and 63.18-higher μmol/L in participants with MUO (β=63.18, P< 0.001), compared to those with MHNO. Compared to participants with MHNO, those with MUO had the highest likelihood to have hyperuricemia (OR=4.56, P< 0.001), followed by those with MHO (OR=3.32, P< 0.001). Mendelian randomization analysis indicated that uric acid was more likely to be a consequence of BMI (β=0.059, P=6.54× 10− 154).Conclusion: MUO, in comparison with MHO, was significantly associated with hyperuricemia in Chinese adults.Keywords: metabolic syndrome, obesity, serum uric acid, hyperuricemia