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Suebsarn Ruksakulpiwat,1 Chitchanok Benjasirisan,1 Kedong Ding,2 Lalipat Phianhasin,1 Sutthinee Thorngthip,3 Anuoluwapo D Ajibade,4 Jai Thampakkul,5 Amy Y Zhang,6 Joachim G Voss6 1Department of Medical Nursing, Faculty of Nursing, Mahidol University, Bangkok, Thailand; 2Jack, Joseph and Morton Mandel School of Applied Social Sciences, Case Western Reserve University, Cleveland, OH, USA; 3Department of Nursing Siriraj Hospital, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 4College of Art and Science, Department of Anthropology, Case Western Reserve University, Cleveland, OH, USA; 5Case School of Engineering, Case Western Reserve University, Cleveland, OH, USA; 6Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USACorrespondence: Suebsarn Ruksakulpiwat, Email Suebsarn25@gmail.comIntroduction: Ischemic strokes and their recurrence create an immense disease burden globally. Therefore, preventing recurrent strokes by promoting medication adherence is crucial to reduce morbidity and mortality. In addition, understanding the barriers to medication adherence related to the social determinants of health (SDoH) could promote equity among persons with ischemic stroke.Objective: To explore the barriers to medication adherence among patients with ischemic stroke through the SDoH.Methods: This systematic review included studies published between January 2018 and December 2022 identified through PubMed, MEDLINE, Web of Science, and CINAHL Plus Full Text. The descriptions of the studies were systematically summarized and discussed based on the SDoH from the US Healthy People 2030 initiative.Results: Eight studies met the inclusion criteria and were included in this review. The most common barrier to adherence was inappropriate medication beliefs, medication side effects, and patient-physician relationship, which relate to the dimensions of healthcare access and quality. Health literacy and health perception, dependent on education access and quality, frequently influenced adherence. Other social determinants, such as financial strain and social and community context, were found to alter adherence behaviors. No study addressed the neighborhood and built environment domain. We found that cognitive impairment is another factor that impacts adherence outcomes among stroke patients.Conclusion: Multifaceted approaches are needed to address the SDoH to improve medication adherence among patients with ischemic stroke. This review emphasized strategies, including patient education, provider-patient communication, social support, health literacy, technology, and policy advocacy to enhance adherence.Keywords: ischemic stroke, medication adherence, social determinants of health, systematic review

Zhen-Hua Li,1,&ast; Jie Wang,1,&ast; Xin Cheng,1,&ast; Yi-Cheng Mao,1 Kang-Di Zhang,1 Wen-Jie Yu,1 Ying-Qing Li,1 Kai Huang,1,2 Kun Ding,1 Xiao-Jing Yang,1 Cheng-Yang Hu,3 Xiu-Jun Zhang1,4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Hospital Infection Prevention and Control, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Humanistic Medicine, School of Humanistic Medicine, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Center for Evidence-Based Practice, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng-Yang Hu; Xiu-Jun Zhang, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Tel/Fax +86 551 65167031 ; +86 551 65169635, Email cy.hu@ahmu.edu.cn; zhangxiujun@ahmu.edu.cnBackground: There is growing evidence that the COVID-19 pandemic has had a dramatic impact on public mental health. However, less attention has been paid to left-behind experience college students (LBEs). This online study aimed to investigate the relationship between psychological capital (PsyCap) and anxiety among LBEs during COVID-19 pandemic, and further analyze the mediation role of self-esteem between them.Methods: A total of 9990 students were chosen using the stratified cluster sampling method. Three self-reported questionnaires were used to assess the PsyCap, self-esteem, and anxiety, respectively. All the statistical analyses were conducted using SPSS 23.0 and R, and to further investigate the mediation effect of self-esteem in the association of PsyCap with anxiety, AMOS 23.0 was used to build a structural equation model.Results: PsyCap, self-esteem, and anxiety were significantly correlated among LBEs during the COVID-19 pandemic. PsyCap affects anxiety directly (β = – 0.22, SE = 0.051, 95% CI: – 0.27, – 0.17, P < 0.05). In addition, self-esteem partially mediated the relationship between PsyCap and anxiety (mediating effect value = – 0.16, 95% CI: – 0.20, – 0.13, P < 0.05).Conclusion: During the pandemic of COVID-19, left-behind experience had a negative influence on the PsyCap and self-esteem of college students. In addition, for LBEs, self-esteem plays an important mediating role between PsyCap and anxiety. Therefore, from the perspective of PsyCap and self-esteem, schools should translate them into practical educational strategies to enhance the mental health and mitigate the anxiety levels of LBEs.Keywords: left-behind experience, COVID-19, psychology, mental health

Yiben Huang,1,&ast; Keke Ding,2,&ast; Zicong Dai,2,&ast; Jianing Wang,2 Binbin Hu,2 Xianjing Chen,1 Yage Xu,1 Beibei Yu,1 Lingzhi Huang,1 Chunyan Liu,1 Xiaodiao Zhang1 1Department of Respiratory and Critical Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodiao Zhang; Chunyan Liu, Department of Respiratory and Critical Medicine, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou, 325000, People’s Republic of China, Tel +86-577-65866223, Fax +86-577-65866586, Email xiaodiao_zhang@126.com; 786977811@qq.comBackground: Chronic Obstructive Pulmonary Disease (COPD) has been a concern all over the world because of its high prevalence and mortality. The ratio of low-density-lipoprotein to lymphocyte (LLR) has been widely used to predict the prognosis of cerebral infarction, but its association with COPD is less known. We aim to explore the relationship between LLR and COPD and to investigate its indicative role in the severity and prognosis of COPD.Methods: In this study, 279 participants (n = 138 with COPD and n = 138 age- and sex-matched health control) were recruited. COPD patients were divided into two groups according to the optimal cut-off value of LLR determined by the receiver operating characteristic curve (ROC). We collected the clinical characteristics, pulmonary function, LLR, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and other data of all subjects. t-test, Pearson correlation test, logistic regression analysis and other statistical analysis were carried out.Results: Compared with the healthy control group, COPD patients had a significantly higher LLR level (p < 0.001). The disease was more serious in the high LLR group, which was reflected by Global Initiative for Chronic Obstructive Lung Disease (GOLD) and BMI, airway obstruction, dyspnoea, severe exacerbations (BODE) index and St. George’s Respiratory Questionnaire (SGRQ) index (p = 0.001, p = 0.013, p = 0.011, respectively). The forced expiration volume in 1 second (FEV₁) (p = 0.033) and forced expiratory volume in 1 second in percent of the predicted value (FEV₁%) (p = 0.009) in high LLR group were lower. Univariate and multivariate logistic regression analysis showed that LLR was an independent factor affecting the severity of COPD patients (odds ratio [OR] = 2.599, 95% CI: 1.266-5.337, p = 0.009).Conclusion: We found that LLR is a novel biomarker in predicting the severity of patients with COPD. Further studies with larger database were recommended to verify our findings.Keywords: low-density-lipoprotein, lymphocyte, COPD, biomarker

Wengao Li,1,&ast; Yining Xu,2,&ast; Xian Luo,3,&ast; Youlu Wen,1 Kairong Ding,4,5 Wenjing Xu,6,7 Samradhvi Garg,8 Yuan Yang,5 Hengwen Sun7 1Department of Psychiatry, Guangdong 999 Brain Hospital, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Nursing, Guangzhou First People’s Hospital, the Second Affiliated Hospital, South China University of Technology, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Psychiatry, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, 510515, People’s Republic of China; 4Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangdong Mental Health Center,Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, 510080, People’s Republic of China; 6The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 7Department of Radiotherapy, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, 510080, People’s Republic of China; 8School of Health in Social Science, University of Edinburgh, Edinburgh, EH8 9BL, UK&ast;These authors contributed equally to this workCorrespondence: Hengwen Sun, Department of Radiotherapy, Cancer Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, 510080, People’s Republic of China, Email sunrise761114@foxmail.com Yuan Yang, Guangdong Mental Health Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, 510080, People’s Republic of China, Email 306850475@qq.comObjective: Anxiety, depression, and pain are highly interactive with each other in adolescent and young adult (AYA) cancer patients. This study aims to map out the connectivity between anxiety, depression and pain symptoms amongst Chinese AYA cancer patients from the perspective of a network model.Methods: Two hundred and eighteen AYA patients, aged between 15 and 39 years at diagnosis; completed the Patient Health Questionnaire (PHQ), Generalized Anxiety Disorder (GAD), and McGill Pain Questionnaire-Visual Analogue Scale (MPQ-VAS). Network analyses were performed.Results: In all, 38.07% (95% CI = 31.58– 44.57%) of the participants reported depression, 30.73% (95% CI = 24.56– 36.91%) reported anxiety, and 14.22% (95% CI = 9.55– 18.89%) reported current pain. The generated network illustrated that anxiety, depression and pain community were well connected. In the network, “having trouble relaxing” (GAD4, node strength = 1.182), “uncontrollable worry” (GAD2, node strength = 1.165), and “sad mood” (PHQ2, node strength = 1.144) were identified as the most central symptoms, while “uncontrollable worry” (GAD2, bridge strength = 0.645), “guilty” (PHQ6, bridge strength = 0.545), and “restlessness” (GAD5, bridge strength = 0.414) were the key bridging symptoms that connected different communities.Conclusion: Anxiety, depression and pain symptoms are highly interactive with each other. Alleviating AYA cancer patient’s excessive worries might be helpful in improving the patient’s co-occurring anxiety, depression and pain symptoms.Keywords: adolescent, anxiety, cancer, depression, network, pain, young adult

Ke Ding,1 Wei Wang,2 Ye Kang,3 Lei Zhang,2 Shuo Tan,1 Zhengyan Tang1 1The Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2The Department of Urology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3The Department of Urology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Shuo Tan; Zhengyan Tang, Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Street, Changsha, Hunan, 410008, People’s Republic of China, Tel +8615273133018 ; +8613507318268, Email tanshuo@csu.edu.cn; xytzyan@163.comBackground: To illustrate the transperitoneal laparoscopic unroofing (TLU) and compare the efficacy and safety of TLU to fenestration under seminal vesiculoscopy (FUSV) in treating symptomatic seminal vesicle cyst (SVC).Methods: We retrospectively reviewed all patients with symptomatic SVC who underwent TLU or FUSV between 2008 and 2020 at 3 institutions in Hunan. The two groups were evaluated with reference to radiological failure-free survival (R-FFS), fertility outcome, symptoms, and complications at a median 33.5-month follow-up.Results: Of the 98 males, 58 (59.2%) received TLU, and 40 (40.8%) underwent FUSV. Baseline characteristics were comparable. Semen analysis, prostatitis-like symptoms, and the maximum diameter of cyst were partially improved after both surgeries at 12-month follow-up. The TLU groups suggested a higher incidence rate of fertility for SVC patients with comorbid infertility compared with the FUSV group (82.4% vs 70.3%, p = 0.041), as well as better R-FFS of cysts at five-year follow-up (Log rank test, p = 0.021). In addition, the number of patients with NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index) scores higher than 15 decreased more significantly after TLU (p = 0.004). Except for hematospermia within 3 months, no significant difference in adverse events was observed in the two groups during the long-term follow-up.Conclusion: TLU was superior for patients with large and symptomatic SVC to FUSV, with more relieved symptoms, better R-FFS of cysts and fertility outcomes.Registration Number of Clinical Trial: ChiCTR2100053850 in Chinese Clinical Trial Registry Platform (ChiCTR).Keywords: seminal vesicle cyst, laparoscopic unroofing, seminal vesiculoscopy, radiological failure-free survival, male infertility

Jiangfan Yu,1 Rui Tang,2 Ke Ding3 1Department of Dermatology, Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Rheumatology and Immunology, Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 3Department of Urology, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Ke Ding, Department of Urology, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China, Email dingke@csu.edu.cnAbstract: Systemic sclerosis is a rare chronic autoimmune disease, which mainly manifests as immune disorders, vascular damage, and progressive fibrosis. The etiology of SSc is complex and involves multiple factors. Both genetic and environmental factors are involved in its pathogenesis. As one of the molecular mechanisms of environmental factors, epigenetic regulation plays an important role in the occurrence and development of systemic sclerosis, which involves DNA methylation, histone modification and non-coding RNA regulation. This review summarizes research advances in epigenetics, including exosomes, lncRNA, and mentions possible biomarkers and therapeutic targets among them.Keywords: systemic sclerosis, pathogenesis, epigenetics, biomarkers

Yihong Sun,1 Xia Tang,1 Bo Ye,1 Keyue Ding1,2 1Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, 410006, People’s Republic of China; 2Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital, Henan Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defect Prevention, Henan Provincial People’s Hospital of Henan University, People’s Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450003, People’s Republic of ChinaCorrespondence: Keyue DingDepartment of Bioinformatics, School of Basic Medicine, Chongqing Medical University, #1 Road Yixueyuan, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 23 6389 2759Email ding.keyue@igenetics.org.cnAim: Metabolic reprogramming has recently attracted extensive attention for understanding cancer development. We aimed to demonstrate a genomic and transcriptomic landscape of metabolic reprogramming underlying liver cancer cell lines.Methods: We investigated metabolic aberrant at both the transcriptome and genome levels using transcriptome and whole-exome sequencing data from 12 human liver cancer cell lines (hLCCLs) and one normal liver cell line.Results: Three subgroups of hLCCLs characterized from transcriptome sequencing data exhibit significantly different aberrations in various metabolic processes, including amino acid, lipid, energy, and carbohydrate metabolism. Furthermore, whole-exome sequencing revealed distinct mutational signatures among different subgroups of hLCCLs and identified a total of 19 known driver genes implicated in metabolism.Conclusion: Our findings highlighted differential metabolic mechanisms in the development of liver cancer and provided a resource for further investigating its metabolic mechanisms.Keywords: human liver cancer cell lines (hLCCLs), transcriptome, whole-exome, sequencing, tumor metabolism

Yiben Huang,1,* Jianing Wang,1,2,* Jiamin Shen,1,2,* Jiedong Ma,1,2 Xiaqi Miao,1,2 Keke Ding,1,2 Bingqian Jiang,1,2 Binbin Hu,1,2 Fangyi Fu,1,2 Lingzhi Huang,1 Meiying Cao,3 Xiaodiao Zhang1 1Department of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Cardiology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodiao ZhangDepartment of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaTel +86-577-65866223Fax +86-577-65866586Email xiaodiao_zhang@126.comMeiying CaoDepartment of Cardiology, The Third Affiliated Hospital of Wenzhou Medical University Email 519243591@qq.comBackground: We aimed to investigate the association between red cell index (RCI) and the severity of Chronic Obstructive Pulmonary Disease (COPD), and compare predictive value of RCI, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) for the severity of COPD.Methods: A total of 207 participants were recruited (100 COPD patients and 107 healthy controls). COPD patients were divided into two groups according to the optimal cut-off value of RCI determined by the receiver operating characteristic (ROC) curve. Pearson’s correlation test, logistic regression analysis and other tests were performed.Results: Compared with low RCI group, the forced expiration volume in 1 second (FEV1) and FEV1 in percent of the predicted value (FEV1%) in high RCI group were lower (p = 0.016, p = 0.001). There was a negative correlation between RCI and FEV1% (r = − 0.302, p = 0.004), while no correlation between FEV1% and NLR as well as PLR were found. RCI showed higher predictive value than NLR and PLR for predicting Global Initiative for Chronic Obstructive Lung Disease classification (GOLD), with a cut-off value of 1.75 and area under the curve (AUC) of 0.729 (p = 0.001). Multivariate logistic regression analysis proved that RCI was an independent factor for lung function in COPD patients (odds ratio [OR] = 4.27, 95% CI: 1.57– 11.63, p = 0.004).Conclusion: RCI is a novel biomarker that can better assess pulmonary function and severity of COPD than NLR and PLR. Higher RCI is related to deterioration of pulmonary function.Keywords: COPD, pulmonary function, RCI, biomarker

Kai-qi Ding,* Ze-hua Lai,* Yu Zhang, Guo-yuan Yang, Ji-rong He, Li-li Zeng Department of Neurology and Institute of Neurology, Ruijin Hospital/Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-li Zeng No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, People’s Republic of ChinaTel +86-13816290607Email llzeng@126.comJi-rong He No. 149 Chongqing South Road, Huangpu District, Shanghai, People’s Republic of ChinaTel +86-13162762045Email kyo3shao@aliyun.comPurpose: To explore the relationship between the monocyte-to-lymphocyte ratio (MLR) and depression three months after acute ischemic stroke.Patients and Methods: From May 2013 to September 2014, 203 patients with acute ischemic stroke were recruited within 7 days post-stroke from Shanghai Ruijin Hospital and blood samples were collected after admission. The Hamilton Depression Scale and Clinical Review were evaluated at 3 months after stroke. Based on the Diagnostic and Statistical Manual of Mental Disorders-IV diagnostic criteria, we divided patients into post-stroke depression (PSD) and non-PSD groups. We analyzed the intergroup difference in MLR and the contributing factors. Moreover, dynamic changes in monocytes, lymphocytes and MLR at four different time intervals for all the stroke patients and their relationship with PSD patients were also studied.Results: The NIHSS scores and MLR in the PSD group were significantly higher than in the non-PSD group (p< 0.05). Logistic regression analysis revealed MLR was an independent risk factor for PSD (odds ratio: 18.020, 95% confidence interval: 1.127‒288.195, p=0.041). MLR correlated negatively with cholesterol and low-density lipoprotein (r=− 0.160 and − 0.165, respectively, p< 0.05). Within 7 days post-acute ischemic stroke, monocytes gradually increased while lymphocytes remained unchanged for all the stroke patients. The MLR value was significantly higher in the PSD group than in the non-PSD group within 24 h post-stroke (p< 0.05), but there was no difference in the other three time-intervals between the two groups.Conclusion: The admission MLR, particularly within 24 h post-stroke, was associated with PSD at 3 months, implying that the MLR might be involved in the PSD inflammatory mechanism.Keywords: MLR, depression, inflammation, acute ischemic stroke

Yiben Huang,1,* Bingqian Jiang,1,2,* Xiaqi Miao,1,2,* Jiedong Ma,1,2 Jianing Wang,1,2 Keke Ding,1,2 Xianjing Chen,1 Qiaoming Hu,1,2 Fangyi Fu,1,2 Tian Zeng,1,2 Jingyu Hu,1,2 Binbin Hu,1,2 Dehao Yang,3 Xiaodiao Zhang1 1Department of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehao YangDepartment of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009 Zhejiang, People’s Republic of ChinaTel +8613566209652Email dehao_yang@zju.edu.cnXiaodiao ZhangDepartment of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou 325000 Zhejiang, People’s Republic of ChinaTel +86-577-65866223Fax +86-577-65866586Email xiaodiao_zhang@126.comPurpose: This study aimed to explore the relation between lymphocyte to high-density lipoprotein ratio (LHR) and pulmonary function of chronic obstructive pulmonary disease (COPD) patients compared with neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR).Patients and Methods: In total, 154 participants (n = 77 with COPD and n = 77 without COPD) were recruited. LHR, NLR, PLR, lung function and other data were collected and compared. Pearson’s correlation test and the receiver operating characteristics curves were used to compare the utility of LHR, NLR and PLR. Besides, univariate and multivariate logistic regression analyses were conducted.Results: COPD patients with poorer lung function had a lower LHR level (P < 0.001). In low LHR group, more patients underwent greater airflow limitation than the other group (P = 0.006). LHR positively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV1%) (r = 0.333, P = 0.003). At a cut-off value of 2.08, the sensitivity and specificity of LHR in predicting FEV1% < 50 were 93.2% and 55.6%, respectively, with an AUC of 0.770 (P = 0.001) better than NLR and PLR. Based on logistic regression analyses, it was proved that LHR was associated with decreased risk of FEV1 < 50% predicted in COPD patients (odds ratio = 0.198, 95% CI: 0.048– 0.811, P = 0.024).Conclusion: In contrast with NLR and PLR, LHR has higher accuracy for predicting pulmonary function in COPD; lower LHR level is independently associated with poorer pulmonary function.Keywords: COPD, pulmonary function, lymphocytes, high-density lipoprotein

Shujuan Xu,1,* Lianjun He,2,* Keke Ding,3 Lingling Zhang,4 Xinhui Xu,5 Sheng Wang,6 Xueyi Qian2 1Department of Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Precision Medicine Centre, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 3Department of Urology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 4School of Pharmacy, Southwest Medical University, Luzhou, People’s Republic of China; 5School of Pharmacy, Wannan Medical College, Wuhu, People’s Republic of China; 6Department of Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyi Qian Tel +86-18756907022Email 18756907022@163.comPurpose: Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza, can improve type II diabetes, while the molecular mechanisms underlying Tan IIA-mediated protective effects in diabetic nephropathy are unclear. This study explored the protective actions of Tan IIA on renal tissues in streptozotocin (STZ)-induced diabetic nephropathy.Materials and Methods: Tan IIA (2, 4, 8 mg/kg/day) was daily administered to STZ-treated rats by intraperitoneal injection for 42 days. The morphologic pathology was evaluated by hematoxylin-eosin and Masson’s trichrome staining, and transmission electron microscopy. The protein expression levels in renal tissues were evaluated by Western blotting and immunohistochemistry; the mRNA expression level was determined by quantitative real-time PCR.Results: Tan IIA at 2 and 4 mg/kg attenuated the increase in the levels of uric acid and blood urea nitrogen and restored the reduction in the superoxide dismutase activity in the serum of the diabetic rats. Tan IIA at 2 and 4 mg/kg, but not 8 mg/kg, ameliorated the thickening of renal tubule in the diabetic rats; Tan IIA at 2 and 4 and 8 mg/kg attenuated the thickening of glomerular basement membrane and the collagen deposition in the renal tissues of the diabetic rats. Tan IIA treatment at 2, 4, 8 mg/kg decreased the expression levels of transforming growth factor-beta1, TSP-1, Grp78 and CHOP in the diabetic rats. Tan IIA at 2 and 4 and 8 mg/kg attenuated the increase in the protein levels of p-PERK, p-elf2α and ATF-4 from the renal tissues of diabetic rats, while the protein level of AFT-6 and the mRNA expression levels of XBP-1t, XBP-1s and p58IPK in the renal tissues were not affected by STZ or Tan IIA treatment.Conclusion: Tan IIA-mediated protective effects on the STZ-induced diabetic nephropathy may be associated with the reduced endoplasmic reticulum stress via attenuating PERK signaling activities.Keywords: diabetic nephropathy, streptozotocin, tanshinone IIA, renal tissues, endoplasmic reticulum stress, PERK signaling

Shugao Han,1 Yao Ye,2 Jianjun Wu,1 Bin Li,1 Guangqiang Zhang,1 Kai Jin,1 Rui Tang,1 Wei Huang,1 Ming Chao,1 Kefeng Ding2 1Department of Radiology, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, People’s Republic of China; 2Department of Surgical Oncology, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, People’s Republic of ChinaCorrespondence: Kefeng Ding Department of Surgical OncologySecond Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou 310009, Zhejiang Province, People’s Republic of ChinaTel/Fax +86 57187784820Email dingkefeng@zju.edu.cnPurpose: This study aimed to evaluate the value of serum procalcitonin (PCT) levels in the diagnosis of abscess and sepsis following transarterial chemoembolization (TACE) therapy among patients with hepatocellular carcinoma (HCC).Patients and Methods: In this study, a retrospective review of patient charts was performed in 2221 patients who suffered from hepatocellular carcinoma and had undergone 8656 TACE procedures from January 2012 to January 2018. According to the diagnosis of infection and abscess after TACE, these participants were divided into infection group (group A, n=48) and abscess group (group B, n=35). Group B included subgroup B1 (suffered from liver abscess but no sepsis, n=16) and subgroup B2 (suffered from liver abscess and sepsis, n=19). The main observational indexes included sociodemographic characteristics and laboratory and clinical parameters.Results: The results showed that the mean PCT and C-reactive protein (CRP) levels were higher in group B, but receiver-operating characteristic (ROC) analysis showed low sensitivity and specificity. Only the mean PCT level was higher in subgroup B2 than in subgroup B1 (P< 0.001); the ROC analysis had high sensitivity and specificity. However, all other data such as NEUT (neutrophil count) and NEUTP (neutrophil percentage) showed no significant differences.Conclusion: Serum PCT level was a promising inexpensive marker for the diagnosis of liver abscess and sepsis following TACE therapy among patients with primary liver cancer. A cutoff level of 5.1 ng/mL for PCT had high sensitivity and specificity in predicting liver abscess with sepsis.Keywords: hepatocellular carcinoma, abscess, C-reactive protein, procalcitonin, sepsis, transarterial chemoembolization

Chao Chen,1,* Jian Wang,1,* Yamei Zhao,1 Xiaoxu Ge,1,2 Zhanhuai Wang,1 Shaojun Yu,1 Yongmao Song,1 Kefeng Ding,1 Suzhan Zhang,1,2 Shu Zheng,1,2 Lifeng Sun1 1Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifeng SunThe Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang 310009, People’s Republic of ChinaTel +86-571-87783586Email sunlifeng@zju.edu.cnPurpose: To analysis factors prognostic for peritoneal metastases (PM) from colorectal cancer (CRC) treated with surgery using data from two sources and investigate the origin and effective treatment of ovarian metastases (OM).Patients and Methods: Data from CRC patients with PM who had undergone surgery were collected from the Surveillance, Epidemiology, and End Results (SEER) database (n = 639) and a single Chinese institution (n = 60). Cumulative survival was evaluated by Kaplan–Meier analysis. Factors associated with overall survival (OS) and progression-free survival (PFS) prognosis were assessed using Cox’s proportional hazard regression models.Results: Median OS values for patients who underwent surgery were 19 and 32 months in the SEER database and Chinese center, respectively. Age was an independent predictor of OS in both datasets. Signet-ring cell cancer and perineural invasion were independent predictors of inferior OS only in the SEER dataset, while completeness of cytoreduction (CC) and peritoneal carcinomatosis index were independent predictors for OS and PFS only in the Chinese center. Median OS was 24 months in CRC patients with PM alone and 36 months in those with both PM and OM (p = 0.181). Further, median PSF in patients with PM alone was 10 months, while that in individuals with both PM and OM was 20 months (p = 0.181).Conclusion: Surgical treatment of the primary and metastatic sites is effective and safe for CRC patients with PM. CC-0 is recommended for improved prognosis. Moreover, OM should be recognized as a feature of PM, and cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is beneficial for CRC patients with OM.Keywords: ovarian metastases, prognosis factors, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy

Kai Ding ,* Hong Yu ,* Yuan-Yuan Shao, Li-Yan Li, Chao-Meng Wang, Jia Song, Li-Juan Li, Rong Fu Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Fu Tel +86-18622008752Email florai@sina.comObjective: To assess the short-term efficacy and safety of ixazomib in Chinese multiple myeloma (MM) patients in the real world.Methods: Fifty-nine MM patients who received at least one cycle of ixazomib-based therapy between 1 June 2018 and 30 September 2019 were retrospectively analyzed in Tianjin Medical University General Hospital. Thirteen newly diagnosed MM (NDMM), 13 refractory/relapsed MM (RRMM) and 33 continuous therapy (27 bortezomib peripheral neuritis (PN) intolerant and six maintenance therapy) MM patients were included. The indicated overall response rate (ORR), time to overall response (TOR), and adverse events (AEs) were investigated.Results: The ORR in NDMM was 76.9%, with one complete response (CR), five very good partial response (VGPR), four partial response (PR), median PFS, and TOR were 122 (66– 272) days and 49 (22– 108) days. The ORR in RRMM was 46.2%, with one CR, two VGPR, three PR, median PFS, and TOR were 79 (28– 169) days and 59 (23– 88) days. The ORR in continuous therapy MM patients was 100%, with nine stringent CR, 15 CR, six VGPR and three PR, median TOR was 75 (25– 141) days. There were no significant differences regarding ORR between patients with cytogenetic high risk and standard risk in three subgroups (all P> 0.05). The most frequent hematological AEs were anemia (13.6%) and thrombocytopenia (10.2%). The most common nonhematological AEs were PN (25.0%) and diarrhea (13.6%).Conclusion: The real-world data demonstrated that ixazomib-based therapy was generally effective and safe in the short term for MM patients.Keywords: multiple myeloma, ixazomib, real world, overall response rate, adverse events

Steven R Sarkisian,1 Basil Mathews,2 Kai Ding,2 Aashka Patel,2 Zachary Nicek2 1University of Oklahoma College of Medicine, Dean McGee Eye Institute, Oklahoma City, OK, USA; 2University of Oklahoma, Oklahoma City, OK, USA Purpose: The purpose of this study was to evaluate the safety and efficacy of microinvasive glaucoma surgery (MIGS) with 360° ab-interno trabeculotomy using the TRAB360 device as a stand-alone procedure in patients with refractory primary open-angle glaucoma (POAG) and preoperative IOP ≥18 mmHg.Setting: This study evaluated patients treated in a tertiary-referral clinical practice setting.Design: This study is a retrospective analysis of 81 eyes.Methods: Patients with refractory open-angle glaucoma underwent stand-alone 360° ab-interno trabeculotomy using the TRAB360 device. Effectiveness was determined by reduction in medicated IOP and the use of medications from baseline. Safety was determined by the rate of adverse events and secondary surgical interventions. The time points assessed were baseline and postoperative day 1, week 1, and months 1, 3, 6, and 12. A subgroup analysis was performed on eyes with medicated preoperative IOP values of ≥25 mmHg.Results: The reductions in IOP from 1 day to 12 months postoperatively were statistically significant compared to baseline values. The mean reduction in IOP at 12 months was 7.3±6.7 mmHg from baseline. At 12 months, 59% eyes achieved ≥20% reduction in IOP and IOP

Liubo Chen,1,2,* Kai Jiang,1,2,* Haiyan Chen,1,3,* Yang Tang,1,2 Xinyi Zhou,1,2 Yinuo Tan,1,4 Ying Yuan,1,4 Qian Xiao,1,2 Kefeng Ding1,2 1Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; 2Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; 3Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; 4Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China *These authors contributed equally to this work Objectives: Deguelin, a rotenoid extracted from Mundulea sericea (Leguminosae), exhibits antitumor effects on several types of human cancers. Due to the limited studies of deguelin on colorectal cancer (CRC), the present study was designed to investigate the antitumor effect of deguelin and to explore the underlying mechanism in CRC. Materials and methods: Cell viability was assessed by the cell counting kit-8 (CCK-8) assay, and cell apoptosis was determined by the annexin v-propidium iodide staining using flow cytometry and Western blot in CRC cell lines after incubation with deguelin. The antitumor effect of deguelin was further evaluated in tumor xenograft models. Moreover, SB203580, a specific inhibitor of p38 MAPK, was used to confirm the involvement of p38 MAPK pathway in deguelin-induced apoptosis. Results: Deguelin significantly inhibited cell proliferation and induced apoptosis in CRC cell lines (SW620 and RKO) in a time-dependent and dose-dependent manner. Western blot analysis also showed that the expression of proapoptotic proteins (cleaved caspase 3 and cleaved PARP) was upregulated, while that of antiapoptotic proteins (Bcl-2 and survivin) was downregulated after deguelin treatment in CRC cell lines. Moreover, oral administration of deguelin significantly suppressed tumor growth and induced apoptosis in subcutaneous xenograft mouse models without obvious toxicity. Additionally, Western blot revealed that deguelin-induced apoptosis might be regulated by the p38 MAPK pathway and inhibition of p38 MAPK could attenuate deguelin-induced proliferative inhibition and apoptosis in CRC cells. Conclusion: Collectively, these results demonstrated that deguelin inhibited CRC cell growth by inducing apoptosis via activation of p38 MAPK pathway. Keywords: deguelin, colorectal cancer, apoptosis, p38 MAPK pathway

Yuan Zhou,1 Han-dong Wang,1 Xiao-ming Zhou,2 Jiang Fang,2 Lin Zhu,2 Ke Ding2 1Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Jiangsu, China; 2Department of Neurosurgery, Jinling Hospital, Jiangsu, China Background: Increasing evidence demonstrate N-acetylcysteine amide (NACA) provides neuroprotection and attenuated oxidative stress in rats following traumatic brain injury (TBI). The nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) signal pathway is activated after TBI and provides a protective effect against TBI. However, the function and mechanism of NACA in mice after TBI remain unknown. This study was to evaluate the neuroprotection of NACA and the potential action of the Nrf2-ARE pathway in a weight-drop mouse model of TBI. Materials and methods: Four groups of animals were randomly divided into sham, TBI, TBI+vehicle, and TBI+NACA (100 mg/kg, administered intraperitoneally). The protein levels of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO1), cleaved caspase-3 and the mRNA levels of HO-1 and NQO1 were detected. The neurobehavior, neuronal degeneration, apoptosis and oxidative stress were also assessed. Results: Treatment with NACA significantly improved neurologic status at days 1 and 3 following TBI. Moreover, NACA promoted Nrf2 activation a day after TBI. The protein and mRNA levels of HO-1 and NQO1 were upregulated by NACA. Meanwhile, NACA treatment significantly reduced the level of malondialdehyde (MDA) and enhanced the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx), which indicated NACA attenuated oxidative stress following TBI. NACA prominently reduced the protein level of cleaved caspase-3 and TUNEL-positive cells, indicating its antiapoptotic effect. Additionally, Fluoro-Jade C staining showed NACA alleviated neuronal degeneration a day after TBI. Conclusions: Our study reveals that NACA potentially provides neuroprotection via the activation of the Nrf2-ARE signaling pathway after TBI in mice. Keywords: N-acetylcysteine amide, traumatic brain injury, nuclear factor erythroid 2-related factor 2, heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1, oxidative stress

The objective of this study was to describe the treatment experience of patients with recurrent epithelial ovarian cancer who are retreated with an inhibitor of poly(ADP-ribose)-polymerase (PARPi). We conducted a multi-institutional, retrospective review of ovarian cancer patients who received ≥2 lines of therapy containing a PARPi. Demographic, clinical, and pathological data were analyzed with descriptive statistics. Twenty-two patients were identified. For initial PARPi (PARPi1), 12 patients (54.5%) received veliparib, 7 (31.8%) olaparib and 3 (13.6%) rucaparib resulting in 10 patients who had no evidence of disease at the completion of therapy (NED), 3 partial responses (PR), 4 stable disease (SD), and 3 progressive disease (PD). (All 10 CRs involved veliparib given in conjunction with cytotoxic chemotherapy). PARPi1 was used as maintenance in 2 patients. PARPi1 was discontinued because planned number of cycles was reached (n = 10), progression (n = 8), toxicity (n = 2), other (n = 2). For second PARPi (PARPi2), 10 patients (45.4%) received niraparib, 6 (27.3%) olaparib, and 6 (27.3%) rucaparib resulting in 3 PR, 13 SD, and 3 PD. PARPi2 was used as maintenance in 3 patients. The 3 patients who experienced a PR to PARPi2 had a BRCA mutation and were NED following PARPi1. PARPi2 was discontinued because of progression (n = 13), toxicity (n = 6), other (n = 2). One patient currently remains on PARPi2. Toxicity after PARPi1 was not associated with toxicity from PARPi2 (p > 0.05). With 3 approved PARPi for different indications including frontline and recurrence, the opportunity to reuse PARPi has increased. Characterizing those who should be re-challenged is an important initiative moving forward.

Plankton are the foundation of the food chain in aquatic environments, and changes in phytoplankton community structure and function could pose risks to human health through their impacts on pollutant activity. We studied the correlation of plankton community and functional groups to the environmental factors in the Fuhe River, China. Water quality was evaluated based on Qr-index of phytoplankton diversity and functional group biomass. From September 2020 to August 2021, a total of 304 phytoplankton and 158 zooplankton species were collected. The phytoplankton were divided into 30 functional groups, whereas zooplankton were divided into nine functional groups. Phytoplankton functional groups were mainly composed of groups H1, MP, and W1. Among them, functional group MP had the greatest biomass, accounting for 34.37% of the phytoplankton biomass, followed by H1 (10.61%), and W1 (10.10%). The zooplankton functional groups mainly consisted of RF, RC, and SCF functional groups. The functional group RC accounted for 48.81% of the total zooplankton biomass, followed by RF (20.46%), and SCF (19.65%). The major environmental factors influencing phytoplankton functional groups were water temperature (WT), dissolved oxygen (DO), oxidationreduction potential (ORP), and transparency (TS), whereas the major environmental factors influencing zooplankton functional groups were WT, pH, and DO. Overall, water quality of Fuhe River Basin was good, being slightly polluted or pollution-free. [ABSTRACT FROM AUTHOR]

Multi-phase fluid flow is a common occurrence in magmatic hydrothermal systems; and extensive modeling efforts using currently established P-V-T-x properties of the NaCl-H2O system are impending. We have therefore performed hydrothermal flow experiments (360-465°C) to observe vapor-liquid partitioning of alkaline earth and first row transition metals in NaCl-dominated source solutions. The data allow extraction of partition coefficients related to the intrinsic changes in both chlorinity and density along the two-phase solvus. The coefficients yield an overall decrease in vapor affinity in the order Cu(I)>Na>Fe(II)>Zn>Ni(II)≥Mg≥Mn(II)>Co(II)>Ca>Sr>Ba, distinguished with 95% confidence for vapor densities greater than ~0.2g/cm3. The alkaline earth metals are limited to purely electrostatic interactions with Cl ligands, resulting in an excellent linear correlation (R2>0.99) between their partition coefficients and respective ionic radii. Though broadly consistent with this relationship, relative behavior of the transition metals is not well resolved, being likely obscured by complex bonding processes and the potential participation of Na in the formation of tetra-chloro species. At lower densities (at/near halite saturation) partitioning behavior of all metals becomes highly non-linear, where M/Cl ratios in the vapor begin to increase despite continued decreases in chlorinity and density. We refer to this phenomenon as "volatility", which is broadly associated with substantial increases in the HCl/NaCl ratio (eventually to >1) due to hydrolysis of NaCl. Some transition metals (e.g., Fe, Zn) exhibit volatility prior to halite stability, suggesting a potential shift in vapor speciation relative to nearer critical regions of the vapor-liquid solvus. The chemistry of deep-sea hydrothermal fluids appears affected by this process during magmatic events, however, our results do not support suggestions of subseafloor halite precipitation recorded in currently available field data. Ca-Cl systematics in vent fluids are specifically explored, revealing behavior consistent with partitioning due to phase separation. Interestingly, the effect of variable chloride on dissolved Na/Ca ratios associated with plagioclase solubility (in single-phase solutions) appears fundamentally similar to that of phase separation on vapor compositions such that vapors evolved in hydrothermal systems may naturally remain near equilibrium with the host lithology. Conversely, residual liquids/brines left behind in the crust may be undersaturated with metals, enhancing the rate and extent of hydrothermal alteration.