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Chen Xiong,1 Yaru Wang,1 Xiaoqiao Xie,1 Yixin Huang,2 Meilan Liu,2 Xiaofang Zou1 1Department of Nursing, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xiaofang Zou, Department of Nursing, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China, Tel +8618998321627, Fax +86-20-81292949, Email 1037189214@qq.comPurpose: To examine how coping style mediates the relationship between risk perception of diabetic complications and self-management, so as to provide evidence for improving the self-management level of patients with type 2 diabetes.Patients and Methods: We recruited patients with type 2 diabetes mellitus and conducted a cross-sectional survey using a general information questionnaire, the risk perception survey-diabetes mellitus (RPS-DM), the medical coping modes questionnaire (MCMQ), and the summary of Diabetes Self-Care Activities (SDSCA). Descriptive analysis and Pearson correlation analysis were carried out with SPSS 25.0 software, and a structural equation model was constructed with AMOS 24.0 software to verify the mediating effect.Results: A total of 343 valid questionnaires were collected. Diabetes patients’ risk perception of complications has a positive impact on self-management behavior. Cope style was analyzed in three dimensions: confrontation, avoidance and acceptance-resignation, where the confrontation dimension is positively correlated with risk perception of complications and self-management behavior, and the acceptance-resignation dimension is negatively correlated with risk perception of complications and self-management behavior. These two dimensions have partial mediating effects (β=0.115, 95% CI = 0.041– 0.225; β = 0.147, 95% CI = 0.056– 0.283) between risk perception of complications and self-management behaviors, accounting for 15.9% and 20.3% of the total effects, respectively.Conclusion: Our study discovered that the risk perception of complications can affect self-management behavior via various coping styles, suggesting that clinical medical staff should assist patients with type 2 diabetes in facing the perceived risk of complications positively, and thus improve their self-management behavior.Keywords: type 2 diabetes mellitus, risk perception, complications, coping style, self-management, mediation analysis

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

Chuanhao Xiong,1,&ast; Jingzhu Wu,1,&ast; Yuhang Ma,1,&ast; Na Li,1 Xuejiao Wang,1 Yao Li,2 Xiaoying Ding1 1Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Ding, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Email xiaoyingding@126.com Yao Li, Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, People’s Republic of China, Email yao.li@shsmu.edu.cnPurpose: Polycystic ovary syndrome (PCOS) is a frequent cause of infertility in reproductive-age women. Our work aims to evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on gut microbiota, with metabolic parameters including body weight and the hormone profile in PCOS.Patients and Methods: Dehydroepiandrosterone (DHEA)-induced PCOS mice were established and then treated with two GLP-1RAs: liraglutide and novel form semaglutide for four weeks. Changes in body weight and metabolic parameters were measured. Fecal samples were collected and analyzed using metagenomic sequencing.Results: Liraglutide and semaglutide modulated both alpha and beta diversity of the gut microbiota in PCOS. Liraglutide increased the Bacillota-to-Bacteroidota ratio through up-regulating the abundance of butyrate-producing members of Bacillota like Lachnospiraceae. Moreover, liraglutide showed the ability to reverse the altered microbial composition and the disrupted microbiota functions caused by PCOS. Semaglutide increased the abundance of Helicobacter in PCOS mice (p < 0.01) which was the only bacteria found negatively correlated with body weight. Moreover, pathways involving porphyrin and flavonoids were increased after semaglutide intervention.Conclusion: Liraglutide and semaglutide improved reproductive and metabolic disorders by modulating the whole structure of gut microbiota in PCOS. The greater efficacy in weight loss compared with liraglutide observed after semaglutide intervention was positively related with Helicobacter. The study may provide new ideas in the treatment and the underlying mechanisms of GLP-1RAs to improve PCOS.Keywords: PCOS, GLP-1 receptor agonists, gut microbiota, metabolism

Yinhui Deng,1 Na Li,2 Yaru Wang,2 Chen Xiong,2 Xiaofang Zou1 1Department of Nursing, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2School of Nursing, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xiaofang Zou, Department of Nursing, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China, Tel +8618998321627, Fax +86-20-81292949, Email 1037189214@qq.comPurpose: Diabetes is a well-recognized risk factor for cognitive frailty. This study aimed to investigate the influencing factors of cognitive frailty in elderly patients with diabetes and develop a nomogram for its assessment.Methods: We collected the clinical data of diabetic patients aged 60 years or older and the patients were divided into training and validation cohorts at a ratio of 7:3. In the training cohort, logistic regression was used to screen out the influencing factors of cognitive frailty in elderly diabetic patients, and a risk prediction model and nomogram were constructed and verified in the validation cohort. The performance of the model was evaluated using various measures, including the area under the receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test and decision curve analysis.Results: A total of 315 elderly diabetic patients were included, of which 87 (27.6%) patients had cognitive frailty. Age, albumin levels, calf circumference, duration of diabetes, intellectual activity, and depressive state were identified as independent risk factors for cognitive frailty in older patients with diabetes (P < 0.05). The training cohort and validation cohort demonstrated area under curve (AUC) values of 0.866 and 0.821, respectively.Conclusion: Older patients with diabetes have a higher prevalence of cognitive frailty. The nomogram model exhibited satisfactory calibration and identification, providing a reliable tool for assessing the risk of cognitive frailty in individuals with diabetes.Keywords: cognitive frailty, diabetes, nomogram, prediction, risk factors

Rui Zhou,&ast; Yanhua Peng,&ast; Xuemeng Chen,&ast; Chao Xiong, Wenhu Zhai, Xianjie Zhang, Leqiang Xia, Yukai Zhou Department of Anesthesiology, Deyang People’s Hospital, Deyang City, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yukai Zhou, Department of Anesthesiology, Deyang People’s Hospital, NO. 173, Section 1 of Taishan North Road, Deyang City, Sichuan Province, People’s Republic of China, Tel +8618781054070, Email christianziege@163.comPurpose: Parturients suffer severe pain during the stages of labor, especially the first and second. Epidural anesthesia is an effective method to alleviate labor pain. L2-3, L3-4 and L4-5 spaces have been reported to be the recommendable puncture points owing to the adequate analgesia effect and high safety. However, the speed of pain alleviation via the three points has hardly been determined, which is of great importance to parturients. Thus, the aim of this study is to compare the onset time of parturients’ painless uterine contraction after epidural labor analgesia through different puncture points.Study Design and Methods: It is a prospective, randomized, controlled, and subject- and assessor-blinded study. Totally, 150 subjects scheduled for vaginal delivery are going to be randomly assigned into the L2-3 and L3-4 group. Puncture point in L2-3 group is lumbar 2– 3 space, while in L3-4 group it is lumbar 3– 4 space. Analgesia initiation and maintenance are the same between the two groups. Primary outcome will be percentage of painless uterine contraction 15 min after epidural labor analgesia initiation. Secondary outcomes will be the sensory blocking level, motor blocking score, adverse effects of parturients, drug liquid consumption in unit interval, apgar score and degree of satisfaction of the parturients.Discussion: This study estimates the onset time of parturients’ painless uterine contraction after epidural labor analgesia through L2-3 or L3-4 space. The results may provide a better choice to relieve labor pain as soon as possible.Keywords: labor analgesia, epidural anesthesia, puncture points, rapid analgesia

Xiang-Zhe Shi,1,2 Sheng Zhao,3 Yan Wang,1,2 Meng-Yao Wang,1,2 Su-Wen Su,1,2 Yan-Zhao Wu,3 Chen Xiong1,2 1The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 2The Key Laboratory of Pharmacology and Toxicology for New Drugs, Department of Pharmacology, Hebei Medical University, Shijiazhung, 050017, People’s Republic of China; 3Department of Otorhinolaryngology-Head and Neck Surgery, 4th Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Chen Xiong; Yan-Zhao Wu, Email bearmorning@sina.com; wyz315@163.comIntroduction: Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid carcinoma. Doxorubicin (DOX) is the only drug approved for anaplastic thyroid cancer treatment, but its clinical use is restricted due to irreversible tissue toxicity. Berberine (BER), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been proposed to have antitumor activity in many cancers. However, the underlying mechanisms by which BER regulates apoptosis and autophagy in ATC remain unclear. Thus, the present study aimed to assess the therapeutic effect of BER in human ATC cell lines CAL-62 and BHT-101 as well as the underlying mechanisms. In addition, we assessed the antitumor effects of a combination of BER and DOX in ATC cells.Methods: The cell viability of CAL-62 and BTH-101 with treatment of BER for different hours was measured by CCK-8 assay, and cell apoptosis was assessed by clone formation assay and flow cytometric analysis. The protein levels of apoptosis protein, autophagy-related proteins and PI3K/AKT/mTORpathway were determined Using Western blot. Autophagy in cells was observed with GFP-LC3 plasmid using confocal fluorescent microscopy. Flow cytometry was used to detect intracellular ROS.Results: The present results showed that BER significantly inhibited cell growth and induced apoptosis in ATC cells. BER treatment also significantly upregulated the expression of LC3B-II and increased the number of GFP-LC3 puncta in ATC cells. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed BER-induced autophagic cell death. Moreover, BER induced the generation of reactive oxygen species (ROS). Mechanistically, we demonstrated that BER regulated the autophagy and apoptosis of human ATC cells through the PI3K/AKT/mTOR pathways. Furthermore, BER and DOX cooperated to promote apoptosis and autophagy in ATC cells.Conclusion: Taken together, the present findings indicated that BER induces apoptosis and autophagic cell death by activating ROS and regulating the PI3K/AKT/mTOR signaling pathway.Keywords: anaplastic thyroid carcinoma, berberine, autophagy, apoptosis, PI3K/AKT/mTOR, reactive oxygen species

Ling Feng,1,2,&ast; Tong Chen,3,&ast; Xuan Wang,1 Chongxiang Xiong,1,4 Jianhui Chen,1 Shiquan Wu,3 Jing Ning,3 Hequn Zou1,3 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Nephrology, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hequn Zou, Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou, 510630, People’s Republic of China, Email Hequnzou@hotmail.comPurpose: Metabolic disorders are closely related to the occurrence and development of chronic kidney disease (CKD). We explored the prospective association between the Metabolic Score for Visceral Fat (METS-VF) and CKD in a 5-year follow-up study.Patients and Methods: In this cohort study, 631 adults not suffering from CKD from Wanzhai Town, in China in 2012 were included at baseline and followed up in 2017 and 2018. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between METS-VF and CKD risk. Area under the receiver operating characteristic curve (AUC) analyses were used to evaluate the ability of METS-VF, waist-to-height ratio (WhtR), visceral adiposity index (VAI), homeostatic model assessment of insulin resistance (HOMA-IR), body mass index (BMI) to predict CKD risk.Results: We identified 103 CKD cases during follow-up. After adjustment for confounding factors, comparing the lowest quartile of METS-VF, the OR (95% CI) of CKD risk in the highest quartile was 3.04 (1.39– 6.64). The per Standard deviation (SD) increase in METS-VF was positively correlated with CKD risk. The AUC of METS-VF for predicting CKD risk was, in general, higher than that for WhtR, VAI, HOMA-IR, and BMI.Conclusion: METS-VF may be an indicator for predicting CKD risk.Keywords: CKD, METS-VF, visceral obesity

Xiaolin Li,1,2 Ting Su,3 Hua Xiao,1 Peichun Gao,4 Chongxiang Xiong,1 Jinghua Liu,3 Hequn Zou1 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China; 2Department of Endocrinology, Hunan University of Medicine, Huaihua 418000, Hunan, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4School of Public Health, Southern Medical University, Guangzhou 510080, People’s Republic of ChinaCorrespondence: Jinghua LiuGuangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaTel +86 20 61648392Fax +86 20 61648231Email liujhua@smu.edu.cnHequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183 Zhongshan Dadao, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 62784393Fax +86 20 62784399Email hequnzou@hotmail.comPurpose: To explore the association between the anti-inflammatory and renal protective roles of high-density lipoprotein cholesterol (HDL-c) and its different levels in type 2 diabetes mellitus (T2D), hypertension (HTN), and chronic kidney disease (CKD) and to lay a theoretical basis for precise, maximum-benefit HDL-c-raising therapy for patients with these diseases.Patients and Methods: A total of 2127 participants (195 with T2D, 618 with HTN, 162 with CKD, and 1152 controls) were selected and divided into four groups according to their baseline HDL-c level, namely, low HDL-c (L-HDL-c, ≤ 1.03 mmol/L), medium HDL-c (M-HDL-c, 1.04– 1.55 mmol/L), high HDL-c (H-HDL-c, 1.56– 2.05 mmol/L) and extremely high HDL-c (E-HDL-c, ≥ 2.06 mmol/L). Serum and morning urine samples were collected to analyze the correlation between high-sensitivity C-reactive protein (HsCRP), interleukin-6 (IL-6), urine n-acetyl-β-d-glucosidase (U-NAG), retinol binding protein (RBP), and cystatin c (Cys-C) levels with the HDL-c levels.Results: The HDL-c levels of patients with T2D, HTN and CKD were universally lower than those in the control group in both sexes (p< 0.05), while male patients also manifested a lower level of HDL-c than female patients. However, although they had lower values of the renal impairment index, female patients were found to have anomalously higher amounts of proinflammatory cytokines. In addition, the correlations between HsCRP and RBP levels and HDL-c levels were most significant in patients with HTN (p< 0.05), whereas in patients with T2D and CKD, such relevance was less significant.Conclusion: Existence of substantial differences in HDL-c levels between different types of disease and sex highlighted that a higher HDL level does not always predict a better clinical outcome of patients. Moreover, we found that both HsCRP and RBP correlated negatively with HDL-c in HTN patients, indicating that monitoring HsCRP and RBP may serve as indicators for therapeutic efficacy of HDL-c-raising medications in HTN patients.Keywords: high-density lipoprotein cholesterol, anti-inflammation, renal protection, sex difference, functional heterogeneity

Ling Feng,* Haishan Chen,* Jianhui Chen, Chongxiang Xiong, Xiaofei Shao, Xin Wang, Jing Ning, Zhicong Xiang, Xuan Wang, Tong Chen, Hua Xiao, Hongjuan Tang, Xiaolin Li, Guobao Hong, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this work.Correspondence: Hequn Zou; Xiaofei ShaoDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.com; 413151187@qq.comObjective: To explore whether the red blood cell count multiplied by hematocrit index (RBCHct) in blood routine parameters can indicate the risk of impaired fasting blood glucose (IFG), and whether it is related to insulin resistance and inflammation.Methods: In this cross-sectional study, previous history of diabetes was excluded, and people with normal and impaired IFG were included. We use Spearman analysis to evaluate the correlation between RBCHct index and fasting plasma glucose, insulin resistance homeostasis model assessment (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP). Binary logistic regression analysis was used to evaluate the RBCHct index for assessing the potential risk of IFG, and the receiver operating characteristic (ROC) curve was used to evaluate the RBCHct index for diagnosing insulin resistance and chronic low-grade inflammatory efficacy among those with IFG.Results: Correlation analysis showed that the RBCHct index and fasting plasma glucose (r=0.088, P=0.003); HOMA-IR (r=0.199, P< 0.001); and hs-CRP (r=0.097, P=0.001) were positively correlated. After adjusting for confounding factors, the risk of IFG in the third and fourth quartiles of the RBCHct index increased to 1.889 and 3.048 times. The area under the ROC curve of the RBCHct index for diagnosis of insulin resistance state (HOMA-IR) was 0.695 (p< 0.001), and the area under the ROC curve of the RBCHct index for the diagnosis of chronic low-inflammatory state (hs-CRP) was 0.641 (P=0.010).Conclusion: The RBCHct index may be a potential indicator for assessing the risk of prediabetes and is closely related to whether the body is in a state of insulin resistance and inflammation under IFG.Keywords: diabetes mellitus, erythrocyte, RBCHct index, insulin resistance, inflammation

Xin Wang,1,* Jin Deng,2,* Chongxiang Xiong,1 Haishan Chen,1 Qin Zhou,1 Yue Xia,1 Xiaofei Shao,1 Hequn Zou1 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn Zou Tel +86 020-62784391Email zhq1962@smu.edu.cnPurpose: Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved.Methods: An HN rat model was established by oral administration of a mixture of adenine and potassium oxonate daily for 3 weeks. Twenty-four rats were divided into 4 groups: sham treatment, sham treatment plus RGTZ, HN, and HN treated with RGTZ.Results: Administration of RGTZ effectively preserved renal function, decreased urine microalbumin, and inhibited interstitial fibrosis and macrophage infiltration in a rat HN model. RGTZ treatment also inhibited TGF-β and NF-κB pathway activation, decreased expression of fibronectin, collagen I, α-SMA, vimentin, MCP-1, RANTES, TNF-α, and IL-1β, and increased E-cadherin expression in the kidneys of HN rats. Furthermore, RGTZ treatment preserved expression of OAT1 and OAT3 in the kidney of HN rats.Conclusion: RGTZ attenuates the progression of HN through inhibiting TGF-β signaling, suppressing epithelial-to-mesenchymal transition, reducing inflammation, and lowering serum uric acid levels by preserving expression of urate transporters.Keywords: hyperuricemic nephropathy, peroxisome proliferator-activated receptor-gamma, rosiglitazone, renal fibrosis, epithelial-to-mesenchymal transition, inflammation

Jing Ning, Zhicong Xiang, Chongxiang Xiong, Qin Zhou, Xin Wang, Hequn Zou Department of Nephropathy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaCorrespondence: Hequn ZouDepartment of Nephropathy, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria.Patients and Methods: UEVs were isolated from the urine of healthy subjects, pre-diabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α 1-AT) by Western blot. To explore the function of α 1-AT in the inflammatory process leading to DKD, we silenced the expression of α 1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR.Results: There was no expression of α 1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α 1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α 1-AT in tubular epithelial cells was inhibited under high glucose stimulation.Conclusion: Our results suggest that α 1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.Keywords: diabetic kidney disease, urinary extracellular vesicles, biomarker, alpha1-antitrypsin, inflammation, tubular epithelial cell

Yu Hei,1 Binhong Teng,2,3 Ziqian Zeng,2,3 Siqi Zhang,3 Qian Li,3 Jijia Pan,3 Zuyuan Luo,3 Chunyang Xiong,1 Shicheng Wei2,3 1Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University, Beijing, People’s Republic of China; 3Laboratory of Biomaterials and Regenerative Medicine, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Chunyang XiongDepartment of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, People’s Republic of ChinaTel +86 10 62757940Email cyxiong@pku.edu.cnShicheng WeiDepartment of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University, Beijing, People’s Republic of ChinaTel +86 10 82195780Email sc-wei@pku.edu.cnBackground: Immune checkpoint blockades (ICBs) are a promising treatment for cancers such as melanoma by blocking important inhibitory pathways that enable tumor cells to evade immune attack. Programmed death ligand 1 monoclonal antibodies (aPDL1s) can be used as an ICB to significantly enhance the effectiveness of tumor immunotherapy by blocking the PD-1/PD-L1 inhibitory pathway. However, the effectiveness of aPDL1s may be limited by low selectivity in vivo and immunosuppressed tumor microenvironment including hypoxia.Purpose: To overcome the limitations, we develop a multifunctional immunoliposome, called CAT@aPDL1-SSL, with catalase (CAT) encapsulated inside to overcome tumor hypoxia and aPDL1s modified on the surface to enhance immunotherapeutic effects against melanoma.Methods: The multifunctional immunoliposomes (CAT@aPDL1-SSLs) are prepared using the film dispersion/post-insertion method. The efficacy of CAT@aPDL1-SSLs is verified by multiple experiments in vivo and in vitro.Results: The results of this study suggest that the multifunctional immunoliposomes preserve and protect the enzyme activity of CAT and ameliorate tumor hypoxia. Moreover, the enhanced cellular uptake of CAT@aPDL1-SSLs in vitro and their in vivo biodistribution suggest that CAT@aPDL1-SSLs have great targeting ability,resulting in improved delivery and accumulation of immunoliposomes in tumor tissue.Finally, by activating and increasing the infiltration of CD8+ T cells at the tumor site, CAT@aPDL1-SSLs inhibit the growth of tumor and prolong survival time of mice,with low systemic toxicity.Conclusion: In conclusion, the multifunctional immunoliposomes developed and proposed in this study are a promising candidate for melanoma immunotherapy, and could potentially be combined with other cancer therapies like radiotherapy and chemotherapy to produce positive outcomes.Keywords: immunotherapy, programmed death ligand 1 monoclonal antibodies, aPDL1s, tumor hypoxia, melanoma, liposomes

Xin Wang,* Haishan Chen,* Xiaofei Shao, Chongxiang Xiong, Guobao Hong, Jianhui Chen, Xiaolin Li, Xu You, Peichun Gao, Yunying Chen, Ziliang Zou, Jing Ning, Hua Xiao, Hequn Zou, Lixin Wei Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.comLixin WeiDepartment of Nephrology, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail lixinwei66@126.comObjective: To investigate which plasma lipid parameters are useful for detecting chronic kidney disease (CKD) in a Chinese population without known CKD or renal impairment.Methods: This was a prospective study. In southern Chinese cities from 2012 to 2013, a total of 1037 subjects aged ≥ 18 years old received a survey. Logistic regression and multiple linear regression analyses were performed. The lipid parameters studied included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (nHDL-C), TG/HDL-C ratio, TC/HDL-C ratio and nHDL-C/HDL-C ratio.Results: After adjusting for confounding factors, the fourth percentile of logTG/HDL-C was observed to be an independent risk factor for CKD (OR = 2.453, P < 0.001), and the highest quantile of the logTG/HDL-C ratio was associated with a higher prevalence of CKD (P < 0.05). This risk was reduced when the model was adjusted with Insulin resistance (IR) (OR = 2.034, P < 0.05). In the group of women, glucose metabolism disorders, high uric acid, and obesity, this risk was increased. Multiple regression models showed that log TG and nonHDL-C/HDL-C were negatively correlated with eGFR (P < 0.05), while log TG and TC were positively correlated with logACR (P < 0.05). The area under the curve (ROC) of lgTG/HDL was 0.623 (p < 0.001).Conclusion: The serum logTG/HDL-C ratio is the only suitable predictor of CKD, and IR may be the mechanism. This risk needs to be controlled in a specific population. Log TG and nonHDL-C/HDL-C were negatively correlated with eGFR, while log TG and TC were positively correlated with logACR.Keywords: lipid, chronic kidney disease, CKD, urinary albumin to creatinine ratio, ACR, estimated glomerular filtration rate, eGFR

Guo-bao Hong,1,2 Pei-chun Gao,1,3 Yun-yin Chen,1 Yue Xia,1 Xiao-su Ke,1 Xiao-fei Shao,1 Chong-xiang Xiong,1 Hai-shan Chen,1 Hua Xiao,1 Jing Ning,1 He-qun Zou1 1Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, People’s Republic of China; 2Department of Nephrology, The Affiliated Nanhai Hospital of Southern Medical University, Foshan 528200, People’s Republic of China; 3School of Public Health, Southern Medical University, Guangzhou, Guangdong 510630, People’s Republic of ChinaCorrespondence: He-qun ZouDepartment of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, People’s Republic of ChinaTel +86-20-6278-4391Email hequnzou@hotmail.comPurpose: Metabolic syndrome (MetS), characterized by a constellation of insulin resistance, central obesity, hypertension, and hyperlipidemia, is a global health threat. High-sensitivity C-reactive protein (hs-CRP) has been shown to be associated with type 2 diabetes and cardiovascular disease; however, its association with incident MetS is less known. Therefore, the aim of this study was to examine the prospective association between hs-CRP and MetS among a Chinese population in a 5-year follow-up study.Patients and Methods: The levels of hs-CRP were measured using serum samples collected at baseline recruitment in 2012 from 886 participants without MetS. Follow-up interviews were conducted in 2018, and MetS was diagnosed by 2017 criteria from the Chinese Diabetes Society. Multivariate logistic regression models were used to assess the overall and sex-specific associations between hs-CRP and incident MetS. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed with adjustment for demographic, socioeconomic, clinical, and lifestyle factors.Results: After a mean follow-up duration of 5.40 ± 0.56 years, 116 (13.3%) participants developed MetS. In the total study population, increased hs-CRP levels were associated with a higher risk of MetS (OR comparing extreme quartiles of hs-CRP: 4.06 [95% CI: 1.91– 8.65]) in the fully-adjusted model. When stratified by sex, the positive association was only observed in women (OR: 4.82 [1.89– 12.3]) but not in men (OR: 3.15 [0.82– 12.1]; P-interaction = 0.039).Conclusion: In this study of a Chinese population, a positive association between hs-CRP and incident MetS was found only in women and not in men. Sex-specific prediction and intervention of MetS using hs-CRP as a target should be further evaluated.Keywords: inflammation, high-sensitivity C-reactive protein, metabolic syndrome, cohort study, follow up

Hua Xiao,* Chongxiang Xiong,* Xiaofei Shao,* Peichun Gao, Haishan Chen, Jing Ning, Yunying Chen, Ziliang Zou, Guobao Hong, Xiaolin Li, Xu You, Jieli Sheng, Fan Wu, Xin Wang, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: To investigate the correlation between visceral obesity and pathogenesis of chronic kidney disease (CKD) among non-diabetic individuals, and to evaluate the potential of visceral adiposity index (VAI) as a predictor of CKD.Patients and Methods: From December 2017 to March 2018, 1877 non-diabetic participants (male n=699, female n=1208) in southern China were recruited for a cross-sectional survey. Males and females were divided into four groups according to gender-specific quartiles of VAI scores. A logistic regression model was established to analyze the correlation between visceral adiposity index and CKD.Results: Visceral adiposity index was positively correlated with CKD and was negatively associated with estimated glomerular filtration rate (eGFR). Using group one as the control, odds ratios (ORs) were calculated to determine the risk of developing CKD as VAI increased (male: group four 2.73 [P< 0.005]; female: Group three 1.76 [P< 0.05], Group four 2.88 [P< 0.005]). When related factors such as history of hypertension, smoking, alcohol use, and physical inactivity were normalized in the logistic model before calculation, ORs became 2.73 (male: P< 0.05), and 2.18 (female: P< 0.05), respectively. The results differed after normalizing further for systolic blood pressure (SBP), diastolic blood pressure (DBP), hypersensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), homocysteine (Hcy), superoxide dismutase (SOD), and retinol-binding protein (RBP). There were no significant differences in ORs among the female groups.Conclusion: Visceral adiposity index was significantly associated with CKD in non-diabetic individuals. It may be a good predictor of the pathogenesis of CKD and was dependent on hsCRP, IL-6, Hcy, SOD, RBP, and blood pressure levels in females and males with VAI scores of 1.41 and higher. Visceral adiposity index may be used to predict CKD in males with VAI less than 0.983.Keywords: visceral adiposity index, chronic kidney disease, non-diabetic population

Haishan Chen,* Chongxiang Xiong, Xiaofei Shao,* Jing Ning, Peichun Gao, Hua Xiao, Yunying Chen, Ziliang Zou, Guobao Hong, Xiaolin Li, Mengjiao Shao, Jieli Sheng, Xingyan Yang, Xu You, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.comPurpose: Metabolic syndrome (MetS), which is a global public health problem, is a state of chronic low-grade inflammation. This study looked at the changes in hematological parameters and the predictive value of the lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR) as a new index in subjects with and without MetS in coastal cities in southern China.Patients and methods: In this cross-sectional study, there were 852 participants (n = 598 with MetS and n = 254 without MetS). MetS was defined in accordance with the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III) criteria.Results: MetS was positively correlated with white blood cell count, total lymphocyte count, neutrophil count, red blood cell count, hematocrit, hemoglobin, and high-sensitivity C-reactive protein levels (p

Yang Liu,1,* Wei Huang,2,* Chuanfeng Xiong,2 Yuxian Huang,2 Benny J Chen,2,3 Luigi Racioppi,2,4 Nelson Chao,2,3 Tuan Vo-Dinh1,3,5–61Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA; 2Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; 3Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; 4Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples 80131, Italy; 5Fitzpatrick Institute for Photonics, Duke University, Durham, NC 27708, USA; 6Department of Chemistry, Duke University, Durham, NC 27708, USA*These authors contributed equally to this work Aim: To quantitatively and sensitively investigate the biodistribution of immune cells after systemic administration.Methods: Immune cells were loaded with plasmonic gold nanostars (GNS) tracking probes. Inductively coupled plasma mass spectrometry (ICP-MS) was used for quantitative gold mass measurement and two-photon photoluminescence (TPL) was used for high-resolution sensitive optical imaging.Results: GNS nanoparticles were loaded successfully into immune cells without negative effect on cellular vitality. Liver and spleen were identified to be the major organs for macrophage cells uptake after systematic administration. A small amount of macrophage cells were detected in the tumor site in our murine lymphoma animal model.Conclusion: GNS has great potential as a biocompatible marker for quantitative tracking and high-resolution imaging of immune cells at the cellular level.Keywords: GNS, ICP-MS, two-photon microscopy, immune cells, biodistribution

Martin Kuete,1,2 HongFang Yuan,1 Aude Laure Tchoua Kemayou,2 Emmanuel Ancel Songo,2 Fan Yang,1 XiuLan Ma,1 ChengLiang Xiong,1 HuiPing Zhang1 1Obstetrics and Gynecology, Reproductive Center, Family Planning and Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Main Maternity of Obstetrics and Gynecology, Yaounde Central Hospital, Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon Background: Integration of family planning services (FPS) into human immunodeficiency virus (HIV) care for HIV-infected women is an important aspect of the global prevention of mother-to-child transmission (PMTCT) strategy. We assessed the integration of FPS into routine care of HIV-infected mothers by evaluating the uptake and barriers of contraception and PMTCT services. Methods: We conducted an interventional study using the interrupted time series approach in the health care facilities located in Yaounde, Cameroon. First, structured questionnaires related to family planning use, PMTCT services use, and infection risk of the sexual partner were administered to the first trimester pregnant women who were HIV infected and living with uninfected partners. Second, 2 weeks before the delivery date, the women were interviewed according to the prior counseling interventions received, in order to assess their behavior on FPS, antiretroviral therapy (ART) use, delivery option, and infant nourishment to be adopted. P-values below 0.05 were considered statistically significant in the statistical analyses. Results: Of 94 HIV-infected women, 69% were stable couples. Only 13% of women had attended FPS before conception. Although the vast majority were knowledgeable about modern and traditional contraception methods, only 19% had experienced effective contraceptive methods. However, 66% preferred condom use, 45% having three children still expressed a desire to conceive, while 44% reported abortions, 65% had tried to avoid the current pregnancy, and 12% of women were ART naïve. Several predictors such as education, abortion rate, unplanned pregnancies, and partners’ decision were associated with the nonuse of effective contraceptive methods. Moreover, barriers including sex inequity, lack of partner support, ART shortages, and lack of HIV viral load monitoring were prevalent among the participants (P=0.001). However FPS use, ART compliance, and safe options to PMTCT significantly increased after the educational counseling interventions (P=0.001).Conclusion: Scaling up the FPS by incorporating routine PMTCT services into reproductive health care should contribute to preventing both horizontal and vertical transmission of HIV. Keywords: contraception, HIV infected women, transmission, interventions, education

Ten years after sociologist Mary Romero lamented the “ideological and theoretical gulf between immigration research and the sociology of race,” researchers have begun to bridge this theoretical gulf by centering critical race theory in studies of migration. Building on these analyses, this article argues that migration flows and immigrant incorporation are shaped not only by white supremacy but also by patriarchy and global capitalism. Insofar as migrants, predominantly from the Global South, are usually racialized as non-white, and come to work in a labor market shaped by exploitation, oppression, and patriarchy, it is critical to think of migrant flows and settlement within the context of what bell hooks describes as a White supremacist capitalist patriarchy. We draw from examples from our research with a broad spectrum of migrants and their children to elucidate how these three systems of oppression shape the experiences of migrants.

Significant efforts have been devoted to developing trace-level quantification of Hg2+. In this work, a novel fluorescence detection (FD) approach combined with preconcentration of Hg2+ in ionic liquid (IL), N-octylpyridinium tetrafluoroborate ([OPy]+[BF4]-), was developed for the determination of trace Hg2+ in water. The temperature-controlled ionic liquid dispersive liquid-liquid microextraction (TC-IL-DLLME) technique was used to improve the enrichment factor. After extraction and centrifugal separation, precipitated IL was diluted with water and acetonitrile containing the fluorescent probe. Under optimum conditions, the photoluminescence intensity of the fluorescence emission peak was found to be linear with the concentration of Hg2+ in the range from 0.1 to 0.5 μg L-1. The limit of detection for the TC-IL-DLLME-FD method was calculated to be 0.0342 μg L-1 (S/N = 3). Further, the selectivity of the sensor was measured by evaluating its response to other heavy-metal ions and was shown to be excellent. Recoveries were assessed by spiking water samples with different Hg2+ standard stock solutions, giving satisfactory recoveries from 80 to 110%.