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Zi Wang,1 Xiaoyu Li,1 Qing Xu,1 Yao Yao,1 Xiaoye Li,1 Hongmei Yan,2 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Qianzhou Lv, Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email lv.qianzhou@zs-hospital.sh.cn Hongmei Yan, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email yan.hongmei@zs-hospital.sh.cnBackground: The influence of genetic variants on the glucose-lowering effects of dapagliflozin remains unclear. This study aims to investigate the impact of polymorphisms in solute carrier family 5 member 2 (SLC5A2), uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9), solute carrier family 2 member 2 (SLC2A2) and member 4 (SLC2A4) on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM).Methods: A total of 141 patients with T2DM were included in this prospective cohort study. Twenty-nine single nucleotide polymorphisms (SNPs) were selected and genotyped using the Sequenom MassArray platform or Sanger sequencing. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels were compared before and after the treatment with dapagliflozin.Results: Among the 29 SNPs selected, 27 were successfully analyzed. After three months of dapagliflozin treatment, FBG levels were significantly reduced (8.00 mmol/L (5.45– 10.71) mmol/L vs 6.40 mmol/L (5.45– 9.20) mmol/L, p = 0.003) in patients with T2DM. However, there was no significant change in HbA1c levels (8.10% (6.88– 10.00)% vs 8.10% (6.83– 10.00)%, p = 0.452). Analysis of covariance showed that patients with the minor allele homozygote or heterozygote of rs12471030 (CT/TT), rs12988520 (AC/CC) or rs2602381 (TC/CC) had higher FBG levels compared to those with the major allele homozygote (p = 0.014, p = 0.024, and p = 0.044, respectively). After adjusting for baseline FBG level, age, gender, body mass index, use of insulin and use of metformin, three SNPs—rs12471030, rs12988520 and rs2602381—were associated with the anti-hyperglycemic effect of dapagliflozin. However, using a stringent significance threshold (p < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment.Conclusion: After adjusting for confounding variables, polymorphisms in SLC5A2, UGT1A9, SLC2A2 and SLC2A4 genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population.Clinical Trial Registration Number: ChiCTR2200059645.Keywords: dapagliflozin, fasting blood glucose, glycated hemoglobin, polymorphisms, UGT1A9

Aiming Lv,1,2 Tong Ding,2 DeQiong,2 DaWaZhuoMa,2 Long Cai,2 Yutong Zhang,2 Jinyu Yin,2 SeZhen,2 Qiubo Lv1 1Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Women and Children’s Hospital of Tibet Autonomous Region, Lhasa, Tibet Autonomous Region, People’s Republic of ChinaCorrespondence: Qiubo Lv, Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 13801192185, Fax +86 10 85136220, Email lvqiubo@yeah.netPurpose: Pelvic floor disorder (PFD) seriously affects the everyday life of women. This cross-sectional study aimed to evaluate the prevalence and risk factors for postpartum PFD in women living in the Tibet Autonomous Region (TAR).Methods: Parous women who attended the outpatient gynaecology clinic at our hospital between June 2022 and August 2022 were screened in this study. The demographic and clinical data of these women were collected. Their pelvic floor functions were evaluated via a pelvic organ prolapse (POP) quantification examination, the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) and the Overactive Bladder Symptom Score (OABSS).Results: A total of 201 women were included in this study, of whom 81.09% (163/201) were Tibetan. Twenty-seven women (13.43%) were diagnosed with POP stage ≥ 2 and 27 women (13.43%) with an OABSS score ≥ 3. The median PFDI-20 total score was 4.17 (range 0– 43.75). Han women (n = 38) in the TAR had much lower PFDI-20 total scores, compared with Tibetan women (n = 163) (p < 0.05). The results of the multiple linear regression models showed that the PFDI-20 scores obtained from women living in the TAR were closely related to parity, history of heavy weight lifting, age, history of instrumental deliveries, ethnicity and number of caesarean sections.Conclusion: Pelvic floor disorder is common among parous women living in the TAR. Ethnicity, parity, history of heavy weight lifting, age, history of instrumental deliveries and number of caesarean sections are the factors closely related to the PFDI-20 scores.Keywords: pelvic floor disorder, Tibet Autonomous Region, pelvic organ prolapse, urinary incontinence, overactive bladder symptoms

Jing Zhou, Chunsong Yang, Qichen Xv, Liyun Wang, Liangjun Shen, Qingwei Lv Department of Neurosurgery, Shengzhou People’s Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Chunsong Yang, Department of Neurosurgery, Shengzhou People’s Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, Zhejiang, People’s Republic of China, Email ycs821005@163.comBackground: Translocator protein (TSPO) is a biomarker of neuroinflammation and brain injury. This study aimed to ascertain the potential of serum TSPO as a predictor of cognitive impairment after acute intracerebral hemorrhage (ICH).Methods: In this prospective observational cohort study, 276 patients with supratentorial ICH were randomly assigned to two groups (184 patients in the study group and 92 in the validation group) in a 2:1 ratio. Serum TSPO levels were gauged at admission, and cognitive status was assessed using the Montreal Cognitive Assessment Scale (MoCA) post-stroke 3 months. A MoCA score of < 26 was considered indicative of cognitive impairment.Results: Serum TSPO levels were inversely correlated with MoCA scores (ρ=− 0.592; P< 0.001). Multivariate linear regression analysis showed that serum TSPO levels were independently associated with MoCA scores (β, − 0.934; 95% confidence interval (CI), − 1.412--0.455; VIF, 1.473; P< 0.001). Serum TSPO levels were substantially higher in patients with cognitive impairment than in the remaining patients (median, 2.7 versus 1.6 ng/mL; P< 0.001). Serum TSPO levels were linearly correlated with the risk of cognitive impairment under a restricted cubic spline (P=0.325) and independently predicted cognitive impairment (odds ratio, 1.589; 95% CI, 1.139– 2.216; P=0.016). Subgroup analysis showed that the relationship between serum TSPO levels and cognitive impairment was not markedly influenced by other parameters, such as age, sex, drinking, smoking, hypertension, diabetes mellitus, body mass index, and dyslipidemia (all P for interaction > 0.05). The model, which contained serum TSPO, National Institutes of Health Stroke Scale scores and hematoma volume, performed well under the receiver operating characteristic curve, calibration curve and decision curve, and using the Hosmer–Lemeshow test. This model was validated in the validation group.Conclusion: Serum TSPO level upon admission after ICH was independently associated with cognitive impairment, substantializing serum TSPO as a reliable predictor of post-ICH cognitive impairment.Keywords: translocator protein, intracerebral hemorrhage, cognitive impairment, biomarkers

Qin Lv,1,&ast; Xinliang Zhang,1,&ast; Kucun Guo,1 Dezheng Hu,1 Zhuojun Deng2 1Department of Emergency, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050051, People’s Republic of China; 2Department of General Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinliang Zhang, Department of Emergency, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang City, Hebei Province, People’s Republic of China, 050051, Tel +86 18533112509 ; +86 311-88602030, Email zhangxinliangzhxl@126.comObjective: We analyzed the characteristics and risk factors for pulmonary infection in patients with spinal cord injury who underwent tracheostomy and propose measures to help in early detection and intervention to reduce mortality and improve prognosis.Methods: We collected data retrospectively from January 1, 2018, to December 31, 2022. The inclusion criteria were: Patients aged 18 years or more with a spinal cord injury who underwent tracheostomy, were treated with mechanical ventilation for over 48 hours, and were diagnosed as having a pulmonary infection. Sputum samples were cultured and analyzed.Results: 101 cases of pulmonary infection were analyzed, and the incidence was 32.17%. Diabetes (OR 2.302, 95% CI 1.285– 3.972), hypoproteinemia (OR 1.992, 95% CI 1.125– 3.101), administration of glucocorticoids (OR 2.934, 95% CI 1.412– 4.661), ASIA grade A (OR 3.672, 95% CI 1.988– 5.046), mechanical ventilation for ≥ 6 days (OR 2.108, 95% CI 1.385– 4.751), and length of hospital stay for ≥ 20 days (OR 2.137, 95% CI 1.092– 3.842) were risk factors for pulmonary infection in patients with spinal cord injury post-tracheostomy. Among 213 pathogenic bacteria, 52 (51.48%) were Gram-negative and 24 (23.76%) were Gram-positive. Klebsiella pneumoniae (15.84%) and Staphylococcus aureus (8.91%) were the most common pathogenic bacteria. The mortality rate of patients with gram-positive infection was higher than that of patients with gram-negative infection. K. pneumoniae and S. aureus were sensitive to cefoperazone, meropenem, and levofloxacin.Conclusion: Pulmonary infection is a complication post-tracheostomy in patients with spinal cord injury. Diabetes, hypoproteinemia, administration of glucocorticoids, mechanical ventilation for ≥ 6 days, length of hospital stay for ≥ 20 days were risk factors for pulmonary infection. Pulmonary infection was mainly caused by gram-negative bacteria. Timely and effective measures for managing risk factors are essential for improving the prognosis of pulmonary infection post-tracheostomy in patients with spinal cord injuries.Keywords: risk factors of pulmonary infection, spinal cord injury, tracheostomy

Jinyi Wan,1,2,&ast; Jingjing Song,1,&ast; Qingqing Lv,2 Hui Zhang,1 Qiangwei Xiang,1 Huan Dai,1 Hang Zheng,1 Xixi Lin,3 Weixi Zhang1 1Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2Department of Pediatric Internal Medicine, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, 317000, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xixi Lin; Weixi Zhang, Email lxx592604326@163.com; zhangweixi112@163.comPurpose: Recent studies had shown that gut microbiota played a significant role in the development of the immune system and may affect the course of airway allergic disease. We conducted this study to determine unique gut microbial associated with allergic disease in children by shotgun gene sequencing.Methods: We collected fecal samples from children with allergic asthma (n = 23) and allergic rhinitis (n = 18), and healthy control (n = 19). The gut microbiota of specimens was analyzed by high-throughput metagenomic shotgun gene sequencing.Results: The intestinal microbiota of children with allergic asthma and allergic rhinitis was characterized by increased microbial richness and diversity. Simpson and Shannon were significantly elevated in children with allergic asthma. Principal coordinates analysis (PCoA) showed that the gut microbial communities cluster patterns of children with asthma or rhinitis were significantly different from those of healthy controls. However, no significant difference was found between asthma group and rhinitis group At the phylum level, higher relative abundance of Firmicutes was found in the allergic rhinitis group and allergic asthma group, while the level of Bacteroidetes was significantly lower. At the genus level, Corynebacterium, Streptococcus, Dorea, Actinomyces, Bifidobacterium, Blautia, and Rothia were significantly enriched in the allergic asthma group. Finally, a random forest classifier model selected 16 general signatures to discriminate the allergic asthma group from the healthy control group.Conclusion: In conclusion, children in the allergic rhinitis group and allergic asthma group had altered gut microbiomes in comparison with the healthy control group. Compared to healthy children, the gut microbiome in children with allergic diseases has higher pro-inflammatory potential and increased production of pro-inflammatory molecules.Keywords: childhood, allergic asthma, allergic rhinitis, gut microbiome, metagenomic sequencing

Yu-Qing Sun,1 Qiang Lv,1 Dong Chen,2 Yuwei Da,3 Xiao-Yan Zhao,4 Jian-Zeng Dong1 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung & Blood Vessel Diseases, Beijing, People’s Republic of China; 2Department of Pathology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung & Blood Vessel Diseases, Beijing, People’s Republic of China; 3Department of Neurology, Beijing Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Jian-Zeng Dong, Email jz_dong@126.comAbstract: The clinical manifestations of Danon disease, which result from the primary deficiency of the lysosome-associated membrane protein 2 gene, include cardiomyopathy, skeletal myopathy, and different degrees of intellectual disability that vary greatly among patients. The present study reports on two cases of Danon disease in two patients who only presented cardiac symptoms. Cardiac symptoms usually occur in adolescence and during a patient’s twenties, and most patients die from heart failure. However, the lab results from these cases suggested that other systems were involved, despite no other clinical symptoms. Significantly, the two patients had elevated serum cardiac troponin I, which often manifests in the acute cardiac phase, especially in severely affected patients with rapidly fatal outcomes. Danon disease is a multi-system involvement disease. Therefore, clinicians must be aware of its complexity when evaluating newly diagnosed patients due to its vastly different clinical course and prognosis and the importance of multidisciplinary management.Keywords: Danon disease, cardiomyopathy, serum cardiac troponin I, management

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

YiFu Tian,1 CaiXia Zhou,1 XiaoYang Bu,1 Qian Lv,1 Qin Huang1,2 1Department of Physiology of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education & School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Qin Huang, Department of Physiology, Guangxi Medical University, Building 102, 22 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email hqgxmu@163.comBackground: Inflammation plays a crucial role in the development of diabetic cardiomyopathy (DCM), including inflammation caused by high-glucose and high-lipid (HGHL). Targeting inflammation may provide a useful strategy for preventing and treating DCM. Puerarin has been shown to reduce the inflammation, apoptosis and hypertrophy of cardiomyocytes induced by HGHL, in which this study aims to investigate the underlying mechanisms.Methods: H9c2 cardiomyocytes cultured with HGHL were used to establish a cell model of DCM. Puerarin was then placed to these cells for 24 hours. The effects of HGHL and puerarin on cell viability and apoptosis were investigated by the Cell Proliferation, Toxicity Assay Kit (CCK-8) and flow cytometry. Morphological changes of cardiomyocytes was observed by HE staining. CAV3 proteins in H9c2 cardiomyocytes were altered by transient transfection of CAV3 siRNA. IL-6 was detected by ELISA. The Western blot was performed to determine the CAV3, Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3, NF-κB (p65) and p38MAPK proteins.Results: Puerarin treatment reversed the cells viability, hypertrophy in morphology, inflammation (showed by p-p38 and p-p65 and IL-6) and apoptosis-related damage (showed by cleaved-Caspase-3/pro-Caspase-3/Bax, Bcl-2 and flow cytometry) of the H9c2 cardiomyocyte caused by HGHL. Puerarin treatment also restored the decrease of CAV3 proteins of the H9c2 cardiomyocyte caused by HGHL. When silenced the expression of CAV3 proteins with SiRNA, puerarin failed to decreased p-p38 and p-p65 and IL-6, and could not reversed cell viability and morphological damage. In contrast to the simple CAV3 silenced group, the CAV3 silenced with NF-κB pathway or p38MAPK pathway inhibitors, significantly downregulated the p-p38, p-p65 and IL-6.Conclusion: Puerarin upregulated CAV3 protein expression in H9c2 cardiomyocytes and inhibited the NF-κB and p38MAPK pathways, thereby reducing HGHL-induced inflammation and may related to the apoptosis and hypertrophy of cardiomyocytes.Keywords: puerarin, cardiomyocyte, inflammation, caveolin-3, siRNA, NF-κB, p38MAPK

Tianyu Yu,&ast; Jiangnan Dong,&ast; Qi Qi,&ast; Qiang Lv, Jun Li, Chaojun Huang, Xiaoyan Cai Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Cai, Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, People’s Republic of China, Tel/Fax +86-21-58858730, Email cxy6429@163.comPurpose: The Omicron variant of SARS-CoV-2 has emerged as a significant global concern, characterized by its rapid transmission and resistance to existing treatments and vaccines. However, the specific hematological and biochemical factors that may impact the clearance of Omicron variant infection remain unclear. The present study aimed to identify easily accessible laboratory markers that are associated with prolonged virus shedding in non-severe patients with COVID-19 caused by the Omicron variant.Patients and Methods: A retrospective cohort study was conducted on 882 non-severe COVID-19 patients who were diagnosed with the Omicron variant in Shanghai between March and June 2022. The least absolute shrinkage and selection operator regression model was used for feature selection and dimensional reduction, and multivariate logistic regression analysis was performed to construct a nomogram for predicting the risk of prolonged SARS-CoV-2 RNA positivity lasting for more than 7 days. The receiver operating characteristic (ROC) curve and calibration curves were used to assess predictive discrimination and accuracy, with bootstrap validation.Results: Patients were randomly divided into derivation (70%, n = 618) and validation (30%, n = 264) cohorts. Optimal independent markers for prolonged viral shedding time (VST) over 7 days were identified as Age, C-reactive protein (CRP), platelet count, leukocyte count, lymphocyte count, and eosinophil count. These factors were subsequently incorporated into the nomogram utilizing bootstrap validation. The area under the curve (AUC) in the derivation (0.761) and validation (0.756) cohorts indicated good discriminative ability. The calibration curve showed good agreement between the nomogram-predicted and actual patients with VST over 7 days.Conclusion: Our study confirmed six factors associated with delayed VST in non-severe SARS-CoV-2 Omicron infection and constructed a Nomogram which may assist non-severely affected patients to better estimate the appropriate length of self-isolation and optimize their self-management strategies.Keywords: SARS-CoV-2, COVID-19, Omicron, viral shedding time, nomogram

Ting Chen,1,2,&ast; Lei Zhang,3,&ast; Wenhua Huang,3,&ast; Huijun Zong,1,2 Qian Li,3 Yuling Zheng,3 Qingyu Lv,3 Decong Kong,3 Yuhao Ren,3 Yongqiang Jiang,3 Yan Li,1,2 Peng Liu3 1The PLA 307 Clinical College of Anhui Medical University, The Fifth Clinical Medical College of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Critical Care Medicine, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100071, People’s Republic of China; 3State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Li, The PLA 307 Clinical College of Anhui Medical University, The Fifth Clinical Medical College of Anhui Medical University, Hefei, 230032, People’s Republic of China, Email liyanmdhuxi@163.com Peng Liu, Beijing Institute of Microbiology and Epidemiology, Dongdajie Road 20, Beijing, 100071, People’s Republic of China, Tel +86-010-66948487, Email ammsliupeng@163.comBackground: The early identification of pathogens and their antibiotic resistance are essential for the management and treatment of patients affected by ventilator-associated pneumonia (VAP). However, microbiological culture may be time-consuming and has a limited culturability of many potential pathogens. In this study, we developed a rapid nanopore-based metagenomic next-generation sequencing (mNGS) diagnostic assay for detection of VAP pathogens and antimicrobial resistance genes (ARGs).Patients and Methods: Endotracheal aspirate (ETA) samples from 63 patients with suspected VAP were collected between November 2021 and July 2022. Receiver operating characteristic (ROC) curves were established to compare the pathogen identification performance of the target pathogen reads, reads percent of microbes (RPM) and relative abundance (RA). The evaluation of the accuracy of mNGS was performed comparing with the gold standard and the composite standard, respectively. Then, the ARGs were analyzed by mNGS.Results: ROC curves showed that RA has the highest diagnostic value and the corresponding threshold was 9.93%. The sensitivity and specificity of mNGS test were 91.3% and 78.3%, respectively, based on the gold standard, while the sensitivity and specificity of mNGS test were 97.4% and 100%, respectively, based on the composite standard. A total of 13 patients were virus-positive based on mNGS results, while the coinfection rate increased from 27% to 46% compared to the rate obtained based on clinical findings. The mNGS test also performed well at predicting antimicrobial resistance phenotypes. Patients with a late-onset VAP had a significantly greater proportion of ARGs in their respiratory microbiome compared to those with early-onset VAP (P = 0.041). Moreover, the median turnaround time of mNGS was 4.43 h, while routine culture was 72.00 h.Conclusion: In this study, we developed a workflow that can accurately detect VAP pathogens and enable prediction of antimicrobial resistance phenotypes within 5 h of sample receipt by mNGS.Keywords: mechanical ventilation, endotracheal aspirate, pathogen diagnosis, antibiotic resistance, NGS

Jing Peng,1,* Jiaming Su,2,* Lei Song,1 Qiuyi Lv,1 Ying Gao,1 Jingling Chang,1 Hua Zhang,1 Yihuai Zou,1 Xing Chen3 1Department of Encephalopathy, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Brain Function Examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing Chen, Department of brain function examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, No. 05 Haiyuncang Road, Beijing, People’s Republic of China, Tel +86 18610044016, Email yeahchency@sina.comObjective: Limb numbness is a frequent symptom of post-stroke somatosensory dysfunction, which may be alleviated by non-invasive therapy such as acupuncture. However, the precise mechanism via acupuncture remains unknown. The goal of this study was to investigate how the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) changed between stroke patients with limb numbness and healthy people, as well as how acupuncture might work.Methods: 24 stroke sequelae patients with unilateral limb numbness and 14 matched healthy controls were enrolled in the study. The patients with limb numbness received acupuncture therapy three days a week for four weeks. We mainly assessed the clinical outcomes via the visual analogue scale (VAS). In addition, fMRI data from patients with unilateral limb numbness at baseline and after treatment (4th week) were collected, as well as data from healthy controls at baseline.Results: Compared with the healthy subjects, the patient group demonstrated significantly decreased ALFF in several brain regions, mainly associated with the sensorimotor network (SMN) and default mode network (DMN), including left superior frontal gyrus (SFG), right temporal fusiform cortex (TFC), right middle frontal gyrus (MFG), bilateral middle temporal gyrus (MTG), right putamen (PUT), right precentral gyrus (preCG), right planum polare (PP), and left supplementary motor area (SMA). These regions were chosen as the seeds for investigating the FC alteration induced by acupuncture. Several sensorimotor-related brain regions were activated by acupuncture, and the FC of the left supramarginal gyrus (SMG) with right MTG, as well as brain-stem, cerebellum vermis 9 with right MFG showed enhancement following acupuncture in the patient group, which had a significant correlation with clinical outcomes.Conclusion: Acupuncture treatment may be used to stimulate brain areas associated with somatosensory processing and to strengthen the FC of sensorimotor and cognitive brain networks in order to achieve therapeutic effect.Keywords: acupuncture, stroke, somatosensory dysfunction, functional magnetic resonance imaging, amplitude of low-frequency fluctuation, functional connectivity

Tingting Chen,1 Yuzhu Wang,1 Dan Tian,1 Jieqing Zhang,1 Qing Xu,1 Qianzhou Lv,1 Xiaoyu Li,1 Jina Wang2,3 1Department of Pharmacy, ZhongShan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Organ Transplantation, Shanghai, People’s Republic of ChinaCorrespondence: Xiaoyu Li, Department of Pharmacy, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui, Shanghai, People’s Republic of China, Email li.xiaoyu@zs-hospital.sh.cn Jina Wang, Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, No. 180, Fenglin Road, Xuhui, Shanghai, People’s Republic of China, Email wang.jina@zs-hospital.sh.cnPurpose: Follow-up and immunosuppressive medication (ISM) adherence are both important for kidney transplant recipients postoperatively and whether follow-up factors affect the ISM adherence remains unclear. The aim of this study was to examine the relationship between follow-up factors and ISM adherence, and the factors associated with ISM adherence.Patients and Methods: An internet-based cross-sectional survey was conducted in a single kidney transplant center in China. The participants completed the internet-based questionnaire and the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS©) from January 12 to January 26, 2021.Results: Finally, 288 (66.7%) participants responded to this survey. The percentage of full adherence to immunosuppressant was 51.7% (149/288), with 33.3% of the participants reporting a problem in timing dimension. We found that follow-up with a fixed doctor was significantly positive to good adherence (OR=2.124, 95% CI=1.111– 4.062, P=0.023) after analyzing the survey data. Time since kidney transplantation and number of non-immunosuppressants were both associated with immunosuppressant adherence. No significant difference was found regarding the effect of the follow-up adherence on ISM adherence.Conclusion: Our study demonstrated an insufficient prevalence of adherence to immunosuppressant in Chinese renal transplant recipients and revealed that follow-up with a fixed doctor may be a way to improve the patients’ ISM adherence. This anonymous internet-based survey provides valuable insight into the actual adherence rate, factors associated with non-adherence, and situations that may improve medication-taking.Keywords: immunosuppressive medication, medication adherence, follow-up, internet-based survey, kidney transplantation

Yao Yao,1,&ast; Chunlai Shao,2,&ast; Xiaoye Li,1 Zi Wang,1 Chengchun Zuo,1 Yan Yan,3 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yan; Qianzhou Lv, Zhongshan Hospital, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86 13916088938, Fax +86 021-64041990, Email yan.yan@zs-hospital.sh.cn; 13916088938@163.comPurpose: The Global Registry of Acute Coronary Events (GRACE) score has proven value in predicting short-term prognosis in non-ST-elevation myocardial infarction (NSTEMI), but it has only moderate discrimination for long-term outcomes. The purpose of this study is to develop and test a multi-biomarker score for better risk stratification and indication of 2-year risk in patients with NSTEMI.Patients and Methods: A total of 6076 consecutive patients with NSTEMI (66 [59– 73] years, 73.1% males) admitted at Zhongshan Hospital, Fudan University were collected in this observational, prospective study between 2012 and 2018 with a 24-month follow-up. The primary endpoint was all-cause death and non-fatal major adverse cardiac events (MACE). A biomarker score ranged from 0 to 12 was constructed. The predictive power of the biomarker score was evaluated alone or combined with the GRACE score by C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI).Results: During a 2-year follow-up, all-cause death occurred in 159 patients (2.6%), and non-fatal MACEs were presented in 709 patients (11.7%). When added to the GRACE score, the biomarker score demonstrated better prognostic accuracy, patient reclassification and risk discrimination for both mortality and non-fatal MACEs at 2 years by improving the C-statistic from 0.714 (0.671– 0.756) and 0.623 (0.600– 0.646) to 0.851 (0.820– 0.882) and 0.721 (0.702– 0.741) with NRI > 25% (P< 0.001) and IDI > 0.30 (P< 0.001).Conclusion: The single use of biomarker score could markedly enhance the prognostic value of concurrent risk stratification tools for 2-year mortality and non-fatal MACEs in NSTEMI. The GRACE score with incorporation of the biomarker score led to more accurate risk reclassification and warrants more consideration in further NSTEMI management.Keywords: risk stratification, prognosis, net reclassification improvement, integrated discrimination improvement

Wei Tang,1,&ast; Qian Lv,1,&ast; Xiao Huang,2,&ast; Yuzhen Li,2 JunJie Zou,1 Jiaoyang Zheng,1 Liangliang Sun,1 Yi Bao,1 Haiyan Chen,1 Tuo Li,1 Bei Zhang,1 Song Xue,1 Yan Song,1 Xingxing Zhang,1 Xiangfang Chen,1 Jiping Cai,2 Yongquan Shi1 1Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangfang Chen; Yongquan Shi, Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, People’s Republic of China, Email chenxiangfang@smmu.edu.cn; young.stone@smmu.edu.cnObjective: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation.Methods: We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice.Results: Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO.Conclusion: We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.Keywords: thyroid-associated ophthalmopathy, miR-143, thyroid-stimulating hormone receptor, insulin-like growth factor 1 receptor, NLRP3

Juan Li,1,2 Qianwen Lv,1 Haili Sun,1 Yunyun Yang,1,3 Xiaolu Jiao,1,3 Song Yang,1 Huahui Yu,1,3 Yanwen Qin1,3 1Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, People’s Republic of China; 2Emergency Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, People’s Republic of ChinaCorrespondence: Yanwen Qin, Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-64456529, Fax +86-10-64456095, Email qinyanwen@vip.126.com; qinyanwen@ccmu.edu.cnPurpose: Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population.Patients and Methods: This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (ADIPOQ, PPARG, and TNF), from which each individual’s PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples.Results: The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, P = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393– 5.955, P = 0.004) and 5.402-fold (95% CI: 2.311– 12.624, P< 0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determination of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, P = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, P = 0.02).Conclusion: Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.Keywords: polygenic risk score, apnea-hypopnea index, single nucleotide polymorphisms, discriminatory accuracy

Junwei Tong,1– 3,&ast; Xiangui Meng,1– 3,&ast; Qingyang Lv,1– 3,&ast; Hongwei Yuan,1– 3 Weiquan Li,1– 3 Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaFax +86 85776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Increasing evidence indicated that the aberrant expression of the cytoplasmic FMR1-interacting protein (CYFIP) family might possess critical role and potential functions in cancer. But the role of CYFIP2 in clear cell renal cell carcinoma (ccRCC) is still uncharacteristic.Methods: We investigated the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for the expression profile, clinicopathological variables, clinical prognosis information, and promoter methylation levels of CYFIPs in ccRCC. The aberrant CYFIP2 protein expression was validated by the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to uncover CYFIP2 mRNA levels in 28 pairs of ccRCC cancer tissues. Kaplan–Meier analysis, univariate and multivariate Cox proportional hazard regression were performed to assess CYFIPs’ prognosis value. Gene set enrichment analysis (GSEA) was used to determined hallmark functions, gene ontology of CYFIP2. TIMER database was utilized to assess the correlation with immune infiltration in ccRCC.Results: Results showed CYFIP2 was downregulated in ccRCC, relative to paired normal tissues in TCGA-KIRC database and 28 pairs of clinical samples (P < 0.0001). Similarly, a decreased CYFIP2 protein expression was confirmed by ccRCC tissues. The results showed CYFIP2 was negatively regulated by promoter DNA methylation. Survival analysis results showed CYFIP2 could be an independent biomarker for ccRCC and its reduction predicted a poor overall survival (OS) and disease-free survival (DFS). GSEA showed CYFIP2 was involved in metabolic pathways and epithelial–mesenchymal transition (EMT). Immune infiltration analysis revealed that a list of immune markers was significantly correlated with CYFIP2 expression especially with CD4+ cells and CD8+ cells in ccRCC.Conclusion: These results show that CYFIP2 was downregulated in ccRCC patients and predicted an unfavorable prognosis. CYFIP2 might be a potential novel prognostic molecule, and related to immune infiltration, the metabolism, as well as EMT process in ccRCC. CYFIP2 could act as tumor suppressor gene in ccRCC and positive modulation of CYFIP2 might lead to development of a novel strategy for ccRCC treatment.Keywords: CYFIP2, ccRCC, methylation, prognosis, immune infiltration

Xiao Zhang,1,&ast; Juntao Wang,1,&ast; Aihua Sui,2 Nannan Zhang,1 Qiulan Lv,2 Zhenfang Liu3 1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 2Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 3Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenfang Liu Email liuzhenfangzf@outlook.comBackground and Objective: Neuropathic pain remains a clinical challenge with limited effective treatments. Previous studies have found that magnolol (Mag), an ingredient existing in some herbs, showed neuroprotective effect. However, it remains unclear whether Mag can alleviate neuropathic pain.Methods: Chronic constriction injury (CCI) is used as the neuropathic pain model. Mice were randomly divided into 5 groups: Sham, CCI, CCI + 5, 10, 30 mg/kg Mag groups. Thermal and mechanical paw withdrawal threshold were performed at baseline and on the 3rd, 5th, 7th, 14th days post-surgery. Lumbar spinal cord and blood samples were collected on the 14th day. Blood lipid profile, kidney and liver functions, as well as the activation of microglia were evaluated, along with the related signal pathway examined using multiple methods including immunohistochemistry, RT-PCR and Western blot.Results: Mag alleviated thermal and mechanical hypersensitivity in CCI mice. CCI activated microglia and upregulated the expression of P2Y12, while Mag inhibited microglial activation, and downregulated the expression of P2Y12. Mag also blocked the activation of p38 mitogen-activated protein kinase (MAPK) and other pain-related cytokines such as IL-6, TNF-α and IL-1β.Conclusion: The findings indicate that Mag has antinociceptive effect on neuropathic pain, probably mediated through P2Y12 receptors and p38 MAPK mediated pathways. With its relatively safe profile, Mag may be a potential therapeutic agent for neuropathic pain.Keywords: magnolol, neuropathic pain, P2Y12, CCI, MAPK, cytokines

Zetao Ma,1,2,&ast; Xizhi Wang,1,&ast; Qingbo Lv,1 Yingchao Gong,1 Minghong Xia,1 Lenan Zhuang,1 Xue Lu,1 Ying Yang,1 Wenbin Zhang,1 Guosheng Fu,1 Yang Ye,1 Dongwu Lai1 1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310016, People’s Republic of China; 2Department of Cardiology, Zhongshan People’s Hospital, Zhongshan, Guangdong Province, 528403, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongwu Lai; Yang YeKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang Province, 310016, People’s Republic of ChinaTel +86-571-86006241Fax +86-571-86006246Email laidw@zju.edu.cn; yeyang1222@zju.edu.cnBackground: Considered as one of the major reasons of sudden cardiac death, hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease. However, effective treatment for HCM is still lacking. Identification of hub gene may be a powerful tool for discovering potential therapeutic targets and candidate biomarkers.Methods: We analysed three gene expression datasets for HCM from the Gene Expression Omnibus. Two of them were merged by “sva” package. The merged dataset was used for analysis while the other dataset was used for validation. Following this, a weighted gene coexpression network analysis (WGCNA) was performed, and the key module most related to HCM was identified. Based on the intramodular connectivity, we identified the potential hub genes. Then, a receiver operating characteristic curve analysis was performed to verify the diagnostic values of hub genes. Finally, we validated changes of hub genes, for genetic transcription and protein expression levels, in datasets of HCM patients and myocardium of transverse aortic constriction (TAC) mice.Results: In the merged dataset, a total of 455 differentially expressed genes (DEGs) were identified from normal and hypertrophic myocardium. In WGCNA, the blue module was identified as the key module and the genes in this module showed a high positive correlation with HCM. Functional enrichment analysis of DEGs and key module revealed that the extracellular matrix, fibrosis, and neurohormone pathways played important roles in HCM. FRZB, COL14A1, CRISPLD1, LUM, and sFRP4 were identified as hub genes in the key module. These genes showed a good predictive value for HCM and were significantly up-regulated in HCM patients and TAC mice. We also found protein expression of LUM and sFRP4 increased in myocardium of TAC mice.Conclusion: This study revealed that five hub genes are involved in the occurrence and development of HCM, and they are potentially to be used as therapeutic targets and biomarkers for HCM.Keywords: hypertrophic cardiomyopathy, HCM, weighted gene coexpression network analysis, WGCNA, hub gene, biomarkers, bioinformatics analysis

Xiaoye Li,* Chengchun Zuo,* Qiuyi Ji, Ying Xue, Zi Wang, Qianzhou Lv Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qianzhou LvDepartment of Pharmacy, Zhongshan Hospital Fudan University, Shanghai, People’s Republic of ChinaTel +86-21-64041990Fax +86-21-34160880Email 13916088938@163.comBackground: Considering that the current fixed dose of direct oral anticoagulants (DOACs) might have insufficient anticoagulation effect for overweight patients, the aim of this study was to compare the effectiveness and safety of anticoagulation between dabigatran and rivaroxaban in different body mass index (BMI) population.Methods: We conducted a retrospective cohort study of 2402 DOAC anticoagulated patients with atrial fibrillation who underwent catheter ablation (1290 dabigatran, 53.7% and 1112 rivaroxaban, 46.3%) between January 2017 and December 2018. Patients were distributed based on the BMI into nonobese (1362, BMI < 25 kg/m2), preobese (521, BMI 25.0– 29.9 kg/m2), class I obese (344, BMI 30.0– 34.9 kg/m2) and class II+ obese (175, BMI ≥ 35.0 kg/m2). We collected information regarding clinical features, laboratory data, bleeding complications and systemic embolic events from the electrical medical records system during 12 months.Results: The incidence of systemic embolism and stroke complications was higher in the class II+ obese group (P=0.001 and P=0.003). The incidence of bleeding complications and the levels of anticoagulation parameters under the bleeding threshold were similar among the four groups (P> 0.05). Cumulative Kaplan–Meier analysis illustrated that rivaroxaban-treated patients who belonged to higher BMI subgroups were more likely to experience shorter time to thrombosis (TTT) (12-month TTT rates of 0.5% for nonobese vs 1.7% for class I obese patients, HR=3.716, P=0.005; 12-month TTT rates of 0.5%, for nonobese vs 4.0% for class II+ obese patients, HR=6.843, P=0.001). However, no statistical significant difference in terms of the time to bleeding complications and the time to cumulative events among the four groups was observed. By multivariate analysis, a higher BMI value (BMI ≥ 25 kg/m2) (P=0.019; OR=2.094, 95%CI: 1.129– 3.883) was an independent predictor for thrombosis in patients treated with dabigatran or rivaroxaban. Positive linear relationship was observed between BMI levels and occurrence rate of thrombosis and bleeding in under anticoagulation patients with NVAF (R2=0.451 and R2=0.383, respectively).Conclusion: The fixed dose of 15 mg rivaroxaban might carry a risk of under exposure, which would lead to an increase of thromboembolic complications in patients with high BMI. Therefore, rivaroxaban dose increase was suggested for obese patients. Use of DOACs appears to have considerable safety in obese patients.Keywords: body mass index, direct oral anticoagulants, thrombosis, bleeding, composite cardiovascular endpoints

Jiqiao Yang,1,2,* Qianru Yang,1,* Arjudeb Mukherjee,3 Qing Lv1 1Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Clinical Research Center for Breast Disease, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, 610041, People’s Republic of China; 3West China School of Medicine/West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing LvDepartment of Breast Surgery, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, People’s Republic of ChinaTel +86-18980601462Email lvqingwestchina@163.comPurpose: The possibility of axillary node metastasis via the lymphatics might be related to a cancer’s location within the breast. Previous studies of this topic had small sample sizes, inaccuracies because of subjective differences, and the inability to depict the entire three-dimensional structure of the breast. Here, we aimed to improve upon these existing drawbacks by retrospectively analysing whether tumour location (quadrants) and tumour–nipple distance can predict axillary node positivity.Patients and Methods: We identified 961 patients with invasive breast cancer between January 2000 and April 2016. The tumour–nipple distance was objectively measured intraoperatively and clinicopathological information was extracted from hospital database. The distance was measured radially from the nipple to the epicentre rather than the edge of tumour to obviate confounders resulting from tumour size variations.Results: A total of 847 breast cancers (839 patients) met the eligibility criteria and were included in the statistical analysis. The tumour–nipple distance was smaller in node-positive patients (n = 307; 2.76 ± 2.07 cm) than in node-negative patients (n = 297; 3.41 ± 2.18 cm) (p < 0.001). Tumour–nipple distance was an independent predictor of axillary involvement on logistic regression analysis. However, no statistically significant relationship was detected between node positivity and breast quadrant tumour location.Conclusion: Tumour–nipple distance can be used to predict axillary lymph node metastasis and assist in surgical decision-making and therapy planning. However, exploratory studies are required to increase our understanding of the mechanism.Keywords: axillary lymph node metastasis, breast cancer, tumour location, tumour–nipple distance

Pengcheng Liu,1,* Jie Tan,2,* Qiuwen Tan,1 Li Xu,1 Tao He,1 Qing Lv1 1Department of Breast Surgery, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Orthopaedic Surgery & Orthopaedic Institute, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing LvDepartment of Breast Surgery, Clinical Research Center for Breast, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, Sichuan, People’s Republic of ChinaEmail lvqingwestchina@163.comBackground: Accurate lymph node (LN) staging has considerably prognostic and therapeutic value in patients with colorectal cancer (CRC). The purpose of this study is to evaluate the feasibility of applying carbon nanoparticles (CNPs) to track LN metastases in CRC.Methods: Two researchers independently screened publications in PubMed, EMBASE, Cochrane and Ovid MEDLINE databases. The keywords were (carbon nanoparticles OR activated carbon nanoparticles) AND (colon cancer OR rectal cancer OR colorectal cancer). Titles and abstracts of the articles were meticulously read to rule out potential publications. Next, full texts of the ultimately obtained eligible publications were retrieved and analyzed in detail.Results: The search produced 268 publications, and 140 abstracts were identified after a bibliographic review. Finally, 20 studies relevant to our subject were obtained; however, only 14 papers met our inclusion criteria and were included for final review. All studies included have compared the control group with carbon nanoparticles group (control group, defined as nontattooed group; and carbon nanoparticles group, defined as administering carbon nanoparticles during surgery) for their efficacy in intraoperative detecting and positioning. After analysis, appreciably less amount of bleeding (3/5 trials), shorter operation time (2/4 trials), and shorter time to detect lesions and dissect LNs (2/2 trials) were revealed in CNPs group compared to control group. Thirteen studies have recorded the numbers of the harvested LNs in both groups; meanwhile, CNPs group shows superiority to control group in LN retrieval as well (11/13 trials), which also could effectively aid in locating and harvesting more LNs with diameter below 5 mm.Conclusion: The tracing technique for CNPs is a safe and useful strategy both in localizing tumor and tracing LNs in CRC surgery. But there is still a need for more randomized controlled trials to further establish its contribution to patient survival.Keywords: carbon nanoparticles, colorectal cancer, lymph nodes, trace, tumor location

Jiqiao Yang,1,2 Li Xu,1 Pengcheng Liu,1 Zhenggui Du,1 Jie Chen,1 Faqing Liang,1 Quanyi Long,1 Di Zhang,1,3 Helin Zeng,1 Qing Lv1 1Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Cancer Research Institute, Kanazawa University, Kanazawa, JapanCorrespondence: Qing LvDepartment of Breast Surgery, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, People’s Republic of ChinaTel +86-2885422873Email lvqingwestchina@163.comBackground: Radioisotopes and blue dyes are used as dual tracers in the current gold standard procedure of sentinel lymph node (SLN) biopsy (SLNB) performed for breast cancer. However, the blue dye or the radioisotope as a single tracer is also being applied in some institutes. We aimed to explore the risk factors for the miss-detection of SLNs with the radioisotope and the blue dye and to describe the distribution of SLNs missed by each tracer.Patients and Methods: Patients undergoing SLNB with radioisotope and blue dye as dual mapping agents were enrolled between August 2010 and August 2018. Radioactivity count, blue dye staining status, and size and location of each SLN were prospectively documented.Results: In total, 2382 SLNs from 1010 patients were included for statistical analyses. The sentinel node identification rate was 100% for dual tracers, 99.4% for radioisotope, and 89.1% for blue dye. SLN identification using the blue dye was more likely to fail in patients undergoing breast-conserving surgery (p < 0.001) and mastectomy with reconstruction (p = 0.005). Furthermore, miss-detection was significantly more frequent in smaller and uninvolved nodes. Among all SLNs, 8.2% were located in level II and one was in level III. Notably, single tracer of blue dye tended to fail in the detection of lymph nodes in higher levels (p < 0.001).Conclusion: This study explored the association between features and the incidence of the failure to detect SLNs using radioisotope and blue dye. The locations of the miss-detected SLNs are demonstrated to provide a reference for SLNBs conducted using blue dye or radioisotope as a single tracer.Keywords: breast cancer, sentinel lymph node, radioisotope, blue dye, single tracer

Both tea polyphenols (TP) and Lactobacillus rhamnosus have been shown to alleviate obesity, and regulate lipid metabolism. However, the combined effects and their underlying mechanisms of action remain elusive. In the present work, the effects of TP, Lactobacillus rhamnosus R5 (R5), and TP+R5 on blood lipids and the gut microbiota of mice fed with a high-fat diet were compared. Results showed that the combination of TP and R5 effectively increased the serum levels of high-density lipoprotein cholesterol (HDL-C), and decreased total cholesterol (TC) levels, low-density lipoprotein cholesterol (LDL-C) levels, and the atherosclerosis index (AI) in mice fed with a high-fat diet. The combination treatment resulted in a modification of the structure of the gut microbiota in mice, as evidenced by a decrease in the F/B ratio, and an increase in the abundance of beneficial genera, such as Akkermansia muciniphila, Faecalibaculum rodentium, and Ruminococcus_uncultured bacterium. Additionally, the contents of SCFAs (acetic, propionic, and butyric acids) in faeces also increased. These could provide new ideas for anti-obesity methods, and a theoretical basis for the development of foods combining probiotics and tea polyphenols. [ABSTRACT FROM AUTHOR]

Shanshan Gao, Baocheng Tian, Jingtian Han, Jing Zhang, Yanan Shi, Qingzhi Lv, Keke LiSchool of Pharmacy, Binzhou Medical University, Yantai, People’s Republic of chinaBackground: Nanostructured lipid carriers (NLCs) are emerging as attractive drug carriers in transdermal drug delivery. The surface modification of NLCs with cell-penetrating peptides (CPPs) can enhance the skin permeation of drugs.Purpose: The objective of the current study was to evaluate the ability of the cell-penetrating peptide (CPP) polyarginine to translocate NLCs loaded with lornoxicam (LN) into the skin layers and to evaluate its anti-inflammatory effect.Methods: The NLCs were prepared using an emulsion evaporation and low temperature solidification technique using glyceryl monostearates, triglycerides, DOGS-NTA-Ni lipids and surfactants, and then six histidine-tagged polyarginine containing 11 arginine (R11) peptides was modified on the surface of NLCs.Results: The developed NLCs formulated with LN and R11 (LN-NLC-R11) were incorporated into 2% HPMC gels. NLCs were prepared with a particle size of (121.81±3.61)–(145.72±4.78) nm, and the zeta potential decreased from (−30.30±2.07) to (−14.66±0.74) mV after the modification of R11 peptides. The encapsulation efficiency and drug loading were (74.61±1.13) % and (7.92±0.33) %, respectively, regardless of the surface modification. Cellular uptake assays using HaCaT cells suggested that the NLC modified with R11 (0.02%, w/w) significantly enhanced the cell internalization of nanoparticles relative to unmodified NLCs (P

Tianwen Lai,* Xiaoxia Wen,* Dong Wu,* Guomei Su, Yun Gao, Cuifen Chen, Weiquan Wu, Yingying Lv, Zhanghui Chen, Quanchao Lv, Wen Li, Dongming Li, Min Chen, Bin WuDepartment of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, People’s Republic of China*These authors contributed equally to this workPurpose: Particulate matter (PM) has been implicated as a risk factor for airway injury. However, the molecular mechanisms remain largely unclear. The goal of this study was to determine whether sirtuin1 (SIRT1), an anti-inflammatory and antiaging protein, protects against PM-induced airway inflammation.Methods: The effect of SIRT1 on PM-induced airway inflammation was assessed by using in vivo models of airway inflammation induced by PM and in vitro culture of human bronchial epithelial (HBE) cells exposed to PM, resveratrol (SIRT1 activator), or both.Results: PM-stimulated HBE cells showed a significant decrease in SIRT1 but a notable increase in inflammatory cytokines. SIRT1 gene silencing further enhanced PM-induced expression of inflammatory cytokines. In contrast, resveratrol, a SIRT1 activator, reduced the expression of these cytokines compared with the control cells. In vivo, SIRT1 expression was significantly decreased in lung tissues of PM-exposed mice. Interestingly, resveratrol treatment reversed the enhanced total cells, neutrophils and inflammatory cytokines in PM-induced mice. Moreover, SIRT1 mediated PM-induced inflammatory cytokines expression at least partly through MAPK pathways.Conclusion: These findings suggest that SIRT1 is involved in the pathogenesis of PM-induced airway inflammation and activation of SIRT1 could prevent airway disorders or disease exacerbations induced by airborne particulate pollution.Keywords: particulate matter, SIRT1, resveratrol, airway inflammation

Feng Chen,1 Yingfang Wang,1 Yan Guo,1 Jiabei Wang,1 Aolin Yang,2 Qingqing Lv,2 Yixuan Liu,1 Guojing Ma,1 Ying Liu,3 Difei Wang11Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of China; 2Department of Nutrition, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110122, People’s Republic of ChinaBackground and objective: Oxidative stress has been demonstrated to be a mechanism that leads to bone mass reduction, and according to many studies, serum uric acid (UA) is a strong endogenous antioxidant that can protect bone mineral density (BMD). To date, there have been no large-scale, cross-sectional studies based on the population in northeast China to assess the relationship between serum UA and BMD. Therefore, we examined the association between serum UA and BMD among a Chinese population older than 60 years old in northeast China.Methods: This research was a cross-sectional study of 3465 Chinese individuals over 60 years old in nine communities from the city of Shenyang, which is the capital of northeast China’s Liaoning Province. Participants were stratified into three groups by serum UA or BMD levels, and then Pearson’s correlation analysis and multiple regression analysis were used to study the relationship between serum UA and BMD.Results: We found that participants with higher serum UA levels had significantly greater BMD and T-values compared to those of participants with lower serum UA levels. After adjusting for confounding factors, Pearson’s correlation analysis and multiple regression analysis showed that higher serum UA levels remained associated with higher BMD levels (P

Xuqing Huang,1,* Junqi Zhu,2,* Yuyue Jiang,1 Changqing Xu,1 Qun Lv,1 Dongwei Yu,1 Kai Shi,1 Zhaoyang Ruan,1 Yan Wang11Department of Respiratory Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workBackground and aim: A potent and selective vascular endothelial growth factor receptor (VEGFR) inhibitor SU5416, has been developed for the treatment of solid human tumors. The binding of VEGF to VEGFR plays a crucial role in the pathophysiology of respiratory disorders. However, the impact of SU5416 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Thus, this study aimed to illuminate the biofunction of SU5416 in the mouse model of ALI.Methods: Wild-type (WT) and toll-like receptor 4 (TLR4)-deficient (TLR4−/-) C57BL/6 mice were used to establish LPS-induced ALI model. The primary pulmonary microvascular endothelial cell (PMVEC) was extracted for detection of endothelial barrier function.Results: LPS significantly increased the number of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid (BALF). In addition, LPS increased alveolar epithelial cells injury, inflammation infiltration and vascular permeability of PMVEC in WT and TLR4−/- mice. Western blotting experiment indicated VEGF/VEGFR and TLR4/NF-κB pathways were involved in the progression of LPS-stimulated ALI. Consistent with previous research, dexamethasone treatment appeared to be an effective therapeutic for mice with ALI. Moreover, treatment with SU5416 dramatically attenuated LPS-induced immune responses in mice lung tissues via inhibiting VEGF/VEGFR and TLR4/NF-κB pathways. Finally, SU5416 also decreased vascular permeability of PMVEC in vitro.Conclusion: SU5416 ameliorated alveolar epithelial cells injury and histopathological changes in mice lung via inhibiting VEGF/VEGFR and TLR4/NF-κB signaling pathways. We also confirmed that SU5416 could restrain vascular permeability in PMVEC through improving the integrity of endothelial cell. These findings suggested that SU5416 may serve as a potential agent for the treatment of patients with ALI.Keywords: SU5416, lipopolysaccharide, acute lung injury, inflammatory cytokines

Ding-Yun Feng,1,* Yu-Qi Zhou,1,* Yan-Fang Xing,2,* Chuang-Feng Li,3 Qing Lv,4 Jie Dong,5 Jie Qin,3 Yue-Fei Guo,3 Nan Jiang,6 Chencui Huang,7 Hai-Tao Hu,8 Xing-Hua Guo,9 Jie Chen,10 Liang-Hong Yin,11 Tian-Tuo Zhang,1 Xing Li12 1Department of Respiration, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 2Department of Nephrology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China; 3Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 4Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 5Department of Radiotherapy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 6Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 7The Associated Laboratory for AI, Cross-strait TsingHua Research Institute and Huiying Medical Technology, Dongsheng Science and Technology Park, HaiDian District, Beijing 100192, People’s Republic of China; 8Department of Surgery, ChanCheng District Center Hospital, Foshan 528000, People’s Republic of China; 9Department of Rheumatology, The LingNan Hospital of Sun Yat-sen University, Guangzhou 510000, People’s Republic of China; 10Department of Oncology, HengYang City Center Hospital, Hengyang 421001, People’s Republic of China; 11Department of Nephrology, The First Affiliated Hospital of JINAN University, Guangzhou 510630, People’s Republic of China; 12Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this work Purpose: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. Methods: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. Results: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%–60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. Conclusion: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy. Keywords: radiomics, connective tissue diseases, interstitial lung diseases, glucocorticoid

Weiwei Tong,1 Guanghui Tong,1 Dongyan Jin,1 Qingjie Lv2 1Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China Objective: To examine the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to lung cancer in a female Chinese population.Method: A hospital-based case-control study of 388 cases and 388 controls was conducted. Two polymorphisms in MTHFR were detected using TaqMan methods.Results: The MTHFR C677T polymorphism was associated with the risk of lung cancer and lung adenocarcinoma. Carriers with the TT genotype of C677T were observed to have an increased risk of lung cancer and lung adenocarcinoma (the ORs were 1.550 and 1.588, respectively). By contrast, the A1298C polymorphism had a negative relationship with the risk of lung cancer and lung adenocarcinoma; compared with the AA genotype carriers, the CC genotype carriers had a lower risk of lung cancer and adenocarcinoma in the female Chinese population (ORs were 0.302 and 0.215, respectively). In the stratified analyses, we observed only the A1298C polymorphism in the CC genotype carriers with a statistically significant reduction in the risk of non-small-cell lung cancer, compared to the AA genotype carriers. No significant statistical association was found between the MTHFR gene polymorphisms and risk of the residual subtype of lung cancer.Conclusion: This study provides evidence that the MTHFR C677T polymorphism may contribute to the development of lung cancer and lung adenocarcinoma in a female Chinese population. However, the MTHFR A1298C polymorphism may be associated with the decreasing risk of lung cancer. Keywords: MTHFR, single nucleotide polymorphism, lung cancer, genetic susceptibility