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Xiang Huo,1 Zhongming Tan,1,2 Huimin Qian,1,2 Yuanfang Qin,1,2 Chen Dong,1,2 Chuchu Li,1,2 Xiaoxiao Kong,1,2 Jie Hong1,2 1National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Jie Hong, Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, 172 Jiangsu Road, Gulou Distrct, Nanjing, People’s Republic of China, Email hongjie@jscdc.cnBackground: Streptococcus pneumoniae is a significant etiological agent of infection and commonly inhabits the human nasopharynx, alongside other potentially pathogenic bacteria. In this study, S. pneumoniae strains were obtained from a community population and subjected to investigation of their phenotypes, genotypes, and vaccine coverage.Methods: S. pneumoniae was isolated from nasopharyngeal swab samples of a healthy population in the Guangfu Community. Capsular serotypes and genotypes were identified using Quellung reaction and multilocus sequence typing (MLST), respectively. The antimicrobial susceptibility was tested using minimum inhibitory concentrations.Results: In total, 500 unvaccinated people were sampled. Ninety-four S. pneumoniae strains were identified. Common serotypes were 19F, 6A, and 9V. The strain coverages of PCV13 and PPV23 were 61.7% and 58.5%, respectively. About 27.6% isolates were non-susceptible to penicillin, and over 80% were resistant to erythromycin and doxycycline. Among 27 novel sequence types (STs) identified in all strains, the most common STs were ST236 (6/94, 6.4%) and ST12669 (6/94, 6.4%). Nearly half of the strains were grouped into four clone complexes (CC12665, CC271, CC6011, and CC180), of which CC271 showed the highest resistance to PEN.Conclusion: In our study, various drug-resistant clone complexes of Streptococcus pneumoniae were found in the healthy population, the elderly, and children. Consequently, pneumococcal vaccines should be included in the national immunization schedule to prevent disease spread.Keywords: vaccine, Streptococcus pneumonia, serotype, antibiotics, STs

Minmin Shen,1– 3,* Qiaojing Lin,1,2,* Xi Zou,1– 3 Yufan Wu,1,2 Zhihong Lin,1,2 Linglong Shao,1,2 JinSheng Hong,1– 3 Jinmei Chen1– 3 1Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 3Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: JinSheng Hong; Jinmei Chen, Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Email hjs703@126.com; cjm1303@126.comPurpose: The aim of the present study was to assess the clinical outcomes and prognostic factors of lung adenocarcinoma patients with brain metastases (BMs) after intracranial local therapy.Patients and Methods: A total of 83 lung adenocarcinoma patients with BMs who underwent craniotomy combined with radiotherapy or intracranial radiotherapy alone were retrospectively analyzed. The intracranial tumor response was determined according to the Response Assessment in Neuro-Oncology of Brain Metastases (RANO-BM) criteria. The median overall survival (OS), intracranial progression-free survival (iPFS), and related prognostic factors were analyzed with the Kaplan‒Meier estimator method and Cox proportional hazards regression model.Results: Among 83 patients, 20 patients received craniotomy combined with radiotherapy, and 63 patients received intracranial radiotherapy alone. Following intracranial local therapy, 11 patients (13.3%) achieved complete response (CR); among them, 8 patients underwent neurosurgical resection. In addition, 32 patients (38.55%) achieved partial response (PR), 32 patients (38.55%) experienced stable disease (SD), and 8 (9.6%) experienced progressive disease (PD). The median follow-up period was 25.4 months (range 0.8– 49.6 months). The median follow-up time for the iPFS was 16.2 months (range 0.6– 41.2 months). The median OS, iPFS were 28.2 months and 24.7 months. Epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) mutations (HR 3.216, 95% confidence interval (CI) 1.269– 8.150, p = 0.014) and iPFS (HR 0.881, 95% CI 0.836– 0.929, p < 0.001) were found to be beneficial factors for OS. An intracranial-tumor CR was associated with a longer iPFS (PR: HR 0.052, 95% CI 0.009– 0.297, p = 0.001; SD: HR 0.081, 95% CI 0.025– 0.259, p < 0.001; PD: HR 0.216, 95% CI 0.077– 0.606, p = 0.004).Conclusion: Prolonged iPFS was associated with better OS in lung adenocarcinoma patients with BMs following intracranial local therapy, and mutations of EGFR / ALK or an intracranial-tumor CR are independent prognostic factors for prolonged survival.Keywords: lung adenocarcinoma, brain metastases, intracranial local therapy, survival, prognostic factors

Song Wang,1,&ast; Xiang Zhang,1,&ast; Bo Qu,2,&ast; Kunhai Yang,1 Yongrong Hu,1 Hao Liu,2 Juntao Hong,2 Hao Niu,3 Hongsheng Yang2 1School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Niu, Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Email 13438368112@139.com Hongsheng Yang, Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China, Email hongsheng228@163.comPurpose: This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality.Methods: PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores’ effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF.Results: In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718).Conclusion: The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.Keywords: muscle quality, osteoporosis, magnetic resonance imaging, dual-energy X-ray absorptiometry, vertebral bone quality score, osteosarcopenia

Jianwen Zhao,1– 5,&ast; Xintian Cai,1– 5,&ast; Junli Hu,1– 5 Shuaiwei Song,1– 5 Qing Zhu,1– 5 Di Shen,1– 5 Wenbo Yang,1– 5 Qin Luo,1– 5 Xiaoguang Yao,1– 5 Delian Zhang,1– 5 Jing Hong,1– 5 Nanfang Li1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang 830001 People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region ”Hypertension Research Laboratory”, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumuqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comBackground: A newly introduced obesity-related index, the weight-adjusted-waist index (WWI), emerges as a promising predictor of cardiovascular disease (CVD). Given the known synergistic effects of hypertension and obstructive sleep apnea (OSA) on cardiovascular risk, we aimed to explore the relationship between the WWI and CVD risk specifically within this high-risk cohort.Methods: A total of 2265 participants with hypertension and OSA were included in the study. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events. The restricted cubic spline (RCS) was used to further evaluate the nonlinear dose-response relationship.Results: During a median follow-up period of 6.8 years, 324 participants experienced a CVD event. Multivariate Cox regression analysis revealed that compared to the reference group, the HRs for the second, third, and fourth groups were 1.12 (95% CI, 0.79– 1.59), 1.35 (95% CI, 0.96– 1.89), and 1.58 (95% CI, 1.13– 2.22), respectively. Moreover, RCS analysis illustrated a clear J-shaped relationship between the WWI and CVD risk, particularly notable when WWI exceeded 11.5 cm/, signifying a significant increase in CVD risk.Conclusion: There was a J-shaped relationship between WWI and CVD in hypertensive patients with OSA, especially when the WWI was greater than 11.5 cm/, the risk of CVD was significantly increased.Keywords: hypertensive, obstructive sleep apnea, weight-adjusted-waist index, cardiovascular disease, visceral obesity

Shuaiwei Song,1– 5,&ast; Xintian Cai,1– 5,&ast; Junli Hu,1– 5 Qing Zhu,1– 5 Di Shen,1– 5 Huimin Ma,1– 5 Yingying Zhang,1– 5 Rui Ma,1– 5 Wenbo Yang,1– 5 Jing Hong,1– 5 Delian Zhang,1– 5 Nanfang Li1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, 830001, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region ”Hypertension Research Laboratory”, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8,564,818, Email lnanfang2016@sina.comObjective: While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health.Methods: Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions.Results: In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280– 0.588; post-match: OR 0.385, 95% CI, 0.259– 0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings.Conclusion: This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.Keywords: hypertensive, spironolactone, aldosterone, osteoporosis, FRAX score

Xichen Wan,1– 3 Tong Lin,1– 3 Yunzhen Luo,4 Jiaxu Hong,1– 3,5 Jingyi Cheng,1– 3,&ast; Keqing Zhao6,&ast; 1Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2NHC Key Laboratory of Myopia and Related Eye Diseases, Shanghai, People’s Republic of China; 3Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Zhao, Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email rhinoresearch@163.com Jingyi Cheng, Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email tippicjy@126.comPurpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis.Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer’s tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition.Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3– 4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= − 0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P> 0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P< 0.001).Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.Keywords: vidian neurectomy, ocular surface, dry eye

Fan Jiang,1 Jingzhen Hong,1 Juanjuan Jiang,1 Ling Li,1 Xianrui Zheng,1 Kun Zhao,2 Xuebin Wu1 1Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People’s Republic of China; 2Fujian Heze Biotechnology Company Limited, Fuzhou, 350000, People’s Republic of ChinaCorrespondence: Fan Jiang; Xuebin Wu, Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59, Shengli West Road, Zhangzhou City, Fujian Province, People’s Republic of China, Email jiangfan_dr2023@163.com; zzsyywxb@163.comObjective: To investigate the potential protective impact of miR-10a-modified HUMSCs-derived exosomes on both premature ovarian failure and the functionality of ovarian granulosa cells in a POF model.Methods: KGN cells were co-cultured with cisplatin-diaminedichloroplatinum (II) (10 μM) for 24 h to establish an in vitro POF model. The cells were distributed into three distinct groups: the control group, the POF group, and the POF + HUCMSC group. The plasmid sh-NC, sh-miR-10 a and miR-10 a mimic were transfected into KGN cells. After co-cultured with HUCMSC-EVs for 48 h, they were divided into HUCMSC group, sh-miR-10 a-HUMSCs-exosomes group and miR-10 a-HUMSCs-exosomes group. Flow cytometry was adopted to assess the impact of HUMSCs surface immune antigens and miR-10a-HUCMSCs-exosomes on KGN cell apoptosis. Additionally, the evaluation of cell proliferation was carried out through CCK-8 and EDU assays. Western blot analysis was utilized to detect the Caspase-3, Bax, and Bcl-2 proteins levels. Furthermore, the levels of TNF-α, IL-6, IL-10, MDA, SOD, and CAT were quantified using ELISA.Results: Compared with the Control group, the POF group inhibited the growth of ovarian granulosa cells (P< 0.01), reduced the number of EDU cells (P< 0.01), and increased the protein expression of Caspase-3 (P< 0.05) and Bax (P< 0.01). HUMSCs treatment significantly down-regulated the expression of IL-6, TNF-α and MDA, while up-regulating the expression of IL-10, SOD and CAT (P< 0.01); the overexpression of miR-10a promoted cell growth, besides, the introduction of miR-10a-HUMSCs-derived exosomes led to an elevation in the proliferation rate of OGCs affected by POF and concurrently suppressed the apoptosis rate.Conclusion: HUMSCs-derived exosomes modified by miR-10a have protective effects on premature ovarian failure and ovarian granulosa cell function in POF model.Keywords: miR-10a, premature ovarian failure, hUMSCs, cis-diaminedichloroplatinum, ovarian granulosa cells

Weiji Xie,1,&ast; Honglian He,2,&ast; Jishuang Hong,3 Chengfei Feng,1 Wei Li,1 Yongchun Li1 1Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Anesthesiology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People’s Republic of China; 3Department of Anesthesiology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongchun Li; Wei Li, Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email liyongch@sysucc.org.cn; liw@sysucc.org.cnPurpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery.Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 μg·kg− 1 (Group LN), and high-dose nalmefene 0.25 μg·kg− 1 (Group HN). Sufentanil 0.5 μg·kg− 1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery.Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181– 0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432– 0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups.Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.Keywords: nalmefene, general anesthesia, sufentanil, cough, breast surgery

Yi Zhang,1,&ast; Xinrui Wang,1,&ast; Chong Huang,2 Hui Yang,1 Chunguo Jiang,3 Xiaojia Yu,1 Jun Hong,2 Yi Zhang,1 Yushu Wang,1 Rui Zhao,1 Zhuoling An,1 Zhaohui Tong3 1Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuoling An, Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +00-86-010-85231362, Email anzhuoling@163.com Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +00-86-010-85231464, Email tongzhaohuicy@sina.comObjective: The efficacy of nirmatrelvir–ritonavir for hospitalized patients with COVID-19 has not been fully established.Methods: We conducted a retrospective analysis of hospitalized COVID– 19 patients with high risk for disease progression at Beijing Chaoyang Hospital from October 15, 2022, to March 31, 2023. Patients ≥ 18 years old who were hospitalized with COVID-19 within 5 days of symptom onset were included. Baseline data were obtained from the routine electronic health record database of the hospital information system. Outcomes were monitored at 28 days via electronic medical record reviews or telephone interviews.Results: We identified 1120 patients hospitalized with COVID-19 during the study period. After exclusions, 167 nirmatrelvir–ritonavir users and 132 controls were included. 28-day all-cause mortality rate was 12.0% (20/167) in the nirmatrelvir–ritonavir group, versus 22.7% (30/132) in the control group (unadjusted log-rank p = 0.010; HR = 0.49, 95% confidence interval [CI] = 0.28– 0.86, IPTW-adjusted HR = 0.58, 95% CI = 0.40– 0.86). The 28-day disease progression rates did not differ between the two groups (unadjusted HR = 0.59, 95% CI = 0.34– 1.02, IPTW-adjusted HR = 0.73, 95% CI = 0.50– 1.06). Nirmatrelvir–ritonavir significantly reduced all-cause mortality and disease progression within 28 days among patients aged ≥ 65 years without ≥ 2 vaccine doses.Conclusion: We found significantly reduced all-cause mortality in the nirmatrelvir–ritonavir group, particularly in elderly patients who were incompletely vaccinated. Future randomized controlled studies are needed to validate our findings.Keywords: nirmatrelvir–ritonavir, COVID-19, hospitalized

Jinni Hong,1,2 Tingting Fu,1,2 Weizhen Liu,1,2 Yu Du,1,2 Junmin Bu,1,2 Guojian Wei,1,2 Miao Yu,1,2 Yanshan Lin,1,2 Cunyun Min,1,2 Datao Lin3 1Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Guangdong Provincial Institute of Geriatric, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Parasitology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jinni Hong, Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel/Fax +86 02083827812, Email hongjinni@gdph.org.cn Datao Lin, Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel/Fax +86 02087330118, Email lindt5@mail.sysu.edu.cnAbstract: Ruminococcus gnavus (R. gnavus) is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked R. gnavus with various diseases, including inflammatory bowel disease (IBD), obesity, and diabetes mellitus (DM), which has become a growing area of investigation. The initial focus of research primarily centered on assessing the abundance of R. gnavus and its potential association with disease presentation, taking into account variations in sample size, sequencing and analysis methods. However, recent investigations have shifted towards elucidating the underlying mechanistic pathways through which R. gnavus may contribute to disease manifestation. In this comprehensive review, we aim to provide an updated synthesis of the current literature on R. gnavus in the context of IBD, obesity, and DM. We critically analyze relevant studies and summarize the potential molecular mediators implicated in the association between R. gnavus and these diseases. Across numerous studies, various molecules such as methylation-controlled J (MCJ), glucopolysaccharides, ursodeoxycholic acid (UDCA), interleukin(IL)-10, IL-17, and capric acid have been proposed as potential contributors to the link between R. gnavus and IBD. Similarly, in the realm of obesity, molecules such as hydrogen peroxide, butyrate, and UDCA have been suggested as potential mediators, while glycine ursodeoxycholic acid (GUDCA) has been implicated in the connection between R. gnavus and DM. Furthermore, it is imperative to emphasize the necessity for additional studies to evaluate the potential efficacy of targeting pathways associated with R. gnavus as a viable strategy for managing these diseases. These findings have significantly expanded our understanding of the functional role of R. gnavus in the context of IBD, obesity, and DM. This review aims to offer updated insights into the role and potential mechanisms of R. gnavus, as well as potential strategies for the treatment of these diseases. Keywords: Ruminococcus gnavus, inflammatory bowel disease, obesity, diabetes mellitus

IntroductionThrough the combined use of two nitrification inhibitors, Dicyandiamide (DCD) and chlorate with nitrogen amendment, this study aimed to investigate the contribution of comammox Nitrospira clade B, ammonia oxidizing bacteria (AOB) and archaea (AOA) to nitrification in a high fertility grassland soil, in a 90-day incubation study.MethodsThe soil was treated with nitrogen (N) at three levels: 0 mg-N kg-1 soil, 50 mg-N kg-1 soil, and 700 mg-N kg-1 soil, with or without the two nitrification inhibitors. The abundance of comammox Nitrospira, AOA, AOB, and nitrite oxidising bacteria (NOB) was measured using qPCR. The comammox Nitrospira community structure was assessed using Illumina sequencing.Results and DiscussionThe results showed that the application of chlorate inhibited the oxidation of both NH4+ and NO2- in all three nitrogen treatments. The application of chlorate significantly reduced the abundance of comammox Nitrospira amoA and nxrB genes across the 90-day experimental period. Chlorate also had a significant effect on the beta diversity (Bray-Curtis dissimilarity) of the comammox Nitrospira clade B community. Whilst AOB grew in response to the N substrate additions and were inhibited by both inhibitors, AOA showed litle or no response to either the N substrate or inhibitor treatments. In contrast, comammox Nitrospira clade B were inhibited by the high ammonium concentrations released from the urine substrates. These results demonstrate the differential and niche responses of the three ammonia oxidising communities to N substrate additions and nitrification inhibitor treatments. Further research is needed to investigate the specificity of the two inhibitors on the different ammonia oxidising communities.

Jinni Hong,1,2 Tingting Fu,1,2 Weizhen Liu,1,2 Yu Du,1,2 Junmin Bu,1,2 Guojian Wei,1,2 Miao Yu,1,2 Yanshan Lin,1,2 Cunyun Min,1,2 Datao Lin3 1Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Guangdong Provincial Institute of Geriatric, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jinni HongDepartment of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 2083827812, Fax +86 2083827812, Email hongjinni@gdph.org.cnDatao LinDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 2087330118, Fax +86 2087330118, Email lindt5@mail.sysu.edu.cnPurpose: This study aimed to elucidate the impact of Jiangtang decoction (JTD) on diabetic kidney disease (DKD) and its association with alterations in the gut microbiota.Methods: Using a diabetic mouse model (KK-Ay mice), daily administration of JTD for eight weeks was undertaken. Weekly measurements of body weight and blood glucose were performed, while kidney function, uremic toxins, inflammation factors, and fecal microbiota composition were assessed upon sacrifice. Ultra-structural analysis of kidney tissue was conducted to observe the pathological changes.Results: The study findings demonstrated that JTD improve metabolism, kidney function, uremic toxins and inflammation, while also exerting a modulatory effect on the gut microbiota. Specifically, the genera Rikenella, Lachnoclostridium, and unclassified_c_Bacilli exhibited significantly increased abundance following JTD treatment, accompanied by reduced abundance of norank_f_Lachnospiraceae compared to the model group. Importantly, Rikenella and unclassified_c_Bacilli demonstrated negative correlations with urine protein levels. Lachnoclostridium and norank_f_Lachnospiraceae were positively associated with creatinine (Cr), indoxyl sulfate (IS) and interleukin (IL)-6. Moreover, norank_f_Lachnospiraceae exhibited positive associations with various indicators of DKD severity, including weight, blood glucose, urea nitrogen (UN), kidney injury molecule-1 (KIM-1) levels, trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) and IL-17A production.Conclusion: These findings suggested that JTD possess the ability to modulate the abundance of Rikenella, Lachnoclostridium, unclassified_c_Bacilli and norank_f_Lachnospiraceae within the gut microbiota. This modulation, in turn, influenced metabolic processes, kidney function, uremic toxin accumulation, and inflammation, ultimately contributing to the amelioration of DKD.Graphical Abstract: Keywords: Chinese herbal medicine, gut microbiota, diabetic kidney disease, inflammation, uremic toxins

Xintian Cai,1,&ast; Shuaiwei Song,1,&ast; Junli Hu,2 Lei Wang,2 Di Shen,1 Qing Zhu,2 Wenbo Yang,2 Qin Luo,2 Jing Hong,2 Nanfang Li2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Hypertension Research Laboratory, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Hypertension Research Laboratory, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: This study aimed to evaluate the relationship between the systemic inflammation response index (SIRI) and the risk of stroke and its subtypes in elderly patients with hypertension and to explore its predictive accuracy and any potential effect modifiers.Methods: The study included 4749 participants with no history of stroke at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs). Interaction tests and subgroup analyses were conducted. The predictive performance of various inflammatory indicators for stroke was compared using the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: During a median follow-up period of 3.2 years, 640 strokes were recorded, of which 526 were ischemic and the remainder hemorrhagic. After adjustment for confounders, compared to the reference group, the HRs (95% CI) of stroke were 1.28 (95% CI, 1.01– 1.64) and 1.46 (95% CI, 1.14– 1.88) for participants in the second and third tertiles, respectively. We observed interactions between SIRI and homocysteine levels (< 15 vs. ≥ 15 μmol/L) (p for interaction = 0.014) on ischemic stroke risk. Furthermore, the AUC, NRI, and IDI analyses demonstrated that SIRI exhibited better predictive value for stroke risk when compared to other indicators. Similar results were observed for both ischemic and hemorrhagic strokes.Conclusion: Elevated SIRI levels were significantly associated with the risk of stroke and its subtypes in elderly patients with hypertension, suggesting its potential as a promising indicator for stroke risk in this population. However, larger prospective studies are needed to confirm these findings.Keywords: systemic inflammation response index, stroke, elderly, hypertension, inflammation, cohort study

Purpose To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. Methods An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥ 1.5 with a false discovery rate P < 0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. Results The diabetic rodent group exhibited a greater residual urine volume (4.0 ± 0.4 mL) than their control counterparts (0.7 ± 0.2 mL, P < 0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. Conclusions Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.

Jianfeng Hong,1 Xindong Chen,2 Lingli Chen,2 Yigang Wang,2 Biao Huang,2 Hongming Fang1 1Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Immunological Analysis Laboratory of Academy of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of ChinaCorrespondence: Hongming Fang, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 310016, People’s Republic of China, Tel + 86 0571-83865858, Email 3295988078@qq.com Biao Huang, Immunological Analysis Laboratory of Academy of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310016, People’s Republic of China, Tel +86 0571-86843187, Email jswxhb@163.comPurpose: The present study aimed to evaluate the clinical value of Combined Detection of serum soluble T-cell immunoglobulin 3 (sTim-3) with carcinoembryonic antigen (CEA) or glycotype antigen 19– 9 (CA19-9) for Postoperative Recurrence of Colorectal Cancer (CRC) Diagnosis.Patients and Methods: The serum sTim-3 was measured by highly sensitivity TRFIA, and serum CEA and CA19-9 were obtained through the collection of clinical data. Quantitative detection of serum sTim-3, CEA, CA19-9 in 90 patients after the CRC surgery (52 postoperative recurrence and 38 no-postoperative recurrence), 21 patients with colorectal benign tumors, and 67 healthy controls. To analyze the clinical diagnostic value of combined detection of sTim-3 with CEA or CA19-9 to test whether patients have recurrence after CRC surgery.Results: The sTim-3 (15.94± 11.24ng/mL) in patients after CRC surgery was significantly higher than in healthy controls (8.95± 3.34ng/mL) and colorectal benign tumors (8.39± 2.28ng/mL) (P < 0.05), and sTim-3 (20.33± 13.04ng/mL) in CRC postoperative recurrent group was significantly higher than in the group without recurrence after CRC surgery (9.94± 2.36ng/mL) (P < 0.05). In terms of detecting postoperative recurrence after CRC surgery, combined detection of sTim-3 and CEA (AUC: 0.819, sensitivity: 80.77%, specificity: 65.79%), sTim-3 and CA19-9 test (AUC: 0.813, sensitivity: 69.23%, specificity: 97.30%) was significantly better than the CEA single test (AUC: 0.547, sensitivity: 63.16%, specificity: 48.08%) and CA19-9 single test (AUC: 0.675 sensitivity: 65.38%, specificity: 67.57%), Delong test P < 0.05.Conclusion: The efficacy of CEA and CA19-9 single test was not optimal, and the combination of sTim-3 in serum could significantly improve the sensitivity and specificity of detecting patient recurrence after CRC surgery.Keywords: serum tumor markers, Tim-3, time-resolved fluorescence immunoassay, colorectal cancer recurrence

Junli Hu,1– 5,&ast; Xintian Cai,1– 6,&ast; Qing Zhu,1– 6 Mulalibieke Heizhati,1– 5 Wen Wen,1– 6 Qin Luo,1– 5 Jing Hong,1– 5 Yujie Dang,1– 6 Wenbo Yang,1– 5 Nanfang Li1– 5 1Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Hypertension Institute, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 6Graduate School, Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumuqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: To investigate the association between plasma aldosterone concentration (PAC) and non-alcoholic fatty liver disease (NAFLD) diagnosis in Chinese hypertensive patients.Methods: We conducted a retrospective study of all patients diagnosed with hypertension between January 1, 2010, and December 31, 2021. We included 3713 hypertensive patients based on the criteria for inclusion and exclusion. PAC measurement was performed using a radioimmunoassay. NAFLD was diagnosed using abdominal ultrasonography. Cox regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for univariable and multivariable models. A generalized additive model was used to identify nonlinear relationships between PAC and NAFLD diagnosis.Results: A total of 3713 participants were included in the analysis. Over a median follow-up of 30 months, 1572 hypertensive individuals developed new-onset NAFLD. When PAC was used as a continuous variable, the risk of NAFLD increased by 1.04 and 1.24-fold for each 1 ng/dL and 5 ng/dL increase in PAC, respectively. When PAC was considered a categorical variable, the HR for tertile 3 was 1.71 (95% CI, 1.47– 1.98, P < 0.001) compared to tertile 1. Overall, there was a J-shaped relationship between PAC and new-onset NAFLD. By fitting a two-piecewise linear regression model and using a recursive algorithm, we identified a PAC inflection point at 13 ng/dL (log-likelihood ratio test, P = 0.005). In adjusted model 3, for PAC ≥ 13 ng/dL, a 5 ng/dL increase in PAC was associated with a 30% increase in the risk of new-onset NAFLD (95% CI, 1.25– 1.35, P < 0.001).Conclusion: The study revealed a non-linear relationship between elevated PAC levels and the incidence of NAFLD in hypertensive patients. Notably, the risk of new-onset NAFLD was significantly increased when PAC levels were ≥ 13 ng/dL. Larger, prospective studies are necessary to confirm these findings.Keywords: plasma aldosterone concentration, non-alcoholic fatty liver disease, hypertension, cohort study

This study investigated the abundance of comammox bacteria and canonical ammonia-oxidizing bacteria (AOB) and archaea (AOA), and their relative contribution to nitrification along a chronosequence of deglaciated forelands. The results showed that nitrification related gene abundance tended to increase with glacier retreat, with comammox bacteria and AOA appearing to be the most critical drivers for soil nitrification rates. These findings provide new evidence for the presence of comammox bacteria in glacier forelands and enhance our understanding of the niche differentiation of canonical nitrifier and comammox bacteria.

Miao Wang,1,&ast; Jin Shi,2,&ast; Kepei Zhang,1,&ast; Jie Hong,2,&ast; Xinwei Peng,2 Yu Tian,1 Wei Lu,3 Ke Li,2 Zengliang Wang,4 Feng Li,1 Zhijie Zhang,2 Guojiang Mei1 1Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Fudan University, Shanghai, People’s Republic of China; 3Department of Nursing, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijie Zhang, Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Xuhui District, School of Medicine Road, 130, Shanghai, People’s Republic of China, Tel +86-21-54237410, Email epistat@gmail.com; Guojiang Mei, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Tel + 86-21-64385700, Email mgj_761014@sina.comPurpose: This study aimed to evaluate the clinical efficacy of Longyizhengqi granule, a traditional Chinese medicine, in patients with mild COVID-19.Patients and Methods: We conducted a prospective study including mild COVID-19 participants conducted at Mobile Cabin Hospital in Shanghai, China. Participants were assigned to receive Longyizhengqi granule or conventional treatment. The primary outcome was the time for nucleic acid to turn negative and the secondary outcomes are hospital stay and changes in cycle threshold (Ct) values for N gene and Orf gene. Multilevel random-intercept model was performed to analyze the effects of treatment.Results: A total of 3243 patients were included in this study (Longyizhengqi granule 667 patients; conventional treatment 2576 patients). Age (43.5 vs 42.1, p< 0.01) and vaccination doses (not vaccinated: 15.8% vs 21.7%, 1 dose: 3.5% vs 2.9%, 2 doses: 27.9% vs 25.6%, 3 doses: 52.8% vs 49.8%. p< 0.01) show statistical difference between Conventional treatment group and LYZQ granules group. The use of Longyizhengqi granule could significantly reduce the time for nucleic acid to turn negative (14.2 days vs 10.7 days, p< 0.01), shorten hospital stay (12.5 days vs 9.9 days, p< 0.01), and increase the changes in Ct value for N gene (8.44 vs 10.33, p< 0.01) and Orf gene (7.31 vs 8.44, p< 0.01) to approximately 1.5. Moreover, the difference in the changes of Ct values on the 4th, 6th, 8th, and 10th days seem to increase between two groups. No serious adverse events were reported.Conclusion: Longyizhengqi granule might be a promising drug for the treatment of mild COVID-19, and it might be beneficial to effectively shorten the negative transition time of nucleic acid, the total days of hospitalization, and increase the changes of Ct values. Long-term randomized controlled trials with follow-up evaluations are required to confirm its long-term efficacy.Keywords: COVID-19, Omicron variant, traditional Chinese medicine, prospective study

Wenbo Yang,1,&ast; Xintian Cai,1,2,&ast; Junli Hu,1 Wen Wen,1 Heizhati Mulalibieke,1 Xiaoguang Yao,1 Ling Yao,1 Qing Zhu,1 Jing Hong,1 Qin Luo,1 Shasha Liu,1 Nanfang Li1 1Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, NO. 91 TianChi Road, Urumqi, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA).Methods: A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models.Results: After a median follow-up of 6.80 years (interquartile range: 5.90– 8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52,-2.77), CHD (HR 1.96; 95% CI 1.35– 2.84), and stroke (HR 2.24; 95% CI 1.35– 3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results.Conclusion: METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.Keywords: cohort study, METS-IR, cardiovascular disease, hypertension, obstructive sleep apnoea

Lisha Wang,1 Shixiao Li,1 Jiajia Qin,1 Tianbin Tang,1 Jiawen Hong,1 Tao-Hsin Tung,2 Chunyan Xu,1 Sufei Yu,1 Jiao Qian1 1Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 2Evidence-Based Medicine Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, People’s Republic of ChinaCorrespondence: Sufei Yu; Jiao Qian, Email yusf@enzemed.com; qianj@enzemed.comPurpose: We analyzed the clinical concordance of mNGS test results from blood samples and improved the clinical efficiency of mNGS in the diagnosis of suspected sepsis pathogens.Patients and Methods: In this study, 99 samples of suspected blood flow infection were included for plasma mNGS, and the correlation between mNGS results and blood culture results, serum inflammatory indices, clinical symptoms and antibiotic treatment was analyzed, as well as the comparison with the detection rate of BALF pathogens, as well as the classification of different pathogens in the mNGS results were analyzed.Results: The mNGS pathogen detection rate was higher than that of traditional blood culture (83.02% vs 35.82%). The rate of the mNGS results being consistent with the clinical diagnosis was also higher than that of traditional blood culture (58.49% vs 20.75%). This study shows that bacteria and fungi are the main pathogens in sepsis, and viral sepsis is very rare. In this study, 32% of sepsis patients were secondary to pneumonia. Compared with the pathogen detection rate using alveolar lavage fluid, the detection rate from plasma mNGS was 62.5%. Samples were also easy to sample, noninvasive, and more convenient for clinical application.Conclusion: This study shows that compared with blood culture, the detection rate of mNGS pathogen that meets the diagnosis of sepsis is higher. We need a combination of multiple indicators to monitor the early diagnosis and treatment of sepsis.Keywords: clinical concordance, true positive rate, metagenomic next-generation sequencing, blood infection, sepsis

Lin Sun,1,2,&ast; Nan Meng,1,&ast; Zecheng Wang,1 Jiaxin Hong,1 Yuqi Dai,1 Zhenyu Wang,1 Jing Wang,1,2 Xinan Jiao1,2 1Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China; 2Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang; Xinan Jiao, Email wj1231@yzu.edu.cn; jiao@yzu.edu.cnPurpose: Limited data are available on the prevalence and antimicrobial resistance of extended spectrum β-lactamase- (ESBL) and AmpC β-lactamase-producing Escherichia coli in stray dogs. We aimed to investigate the genomic characteristics of ESBL/AmpC-producing E. coli isolated from stray dogs sheltered in Yangzhou, China.Methods: We collected 156 samples including 115 fecal swabs, 35 kennel floor swabs, two breeder hand and shoe sole swabs, and four feed samples. The isolates were tested for resistance by antimicrobial susceptibility testing and further analyzed for cefotaxime-resistant E. coli isolates by whole genome sequencing.Results: We identified 80 cefotaxime-resistant E. coli isolates (51.3%), 59 isolates (73.8%) from feces and 21 (26.2%) from the environment. Whole-genome sequencing analysis showed that blaCTX-M-15 (n=30) and blaCTX-M-55 (n=29) were the most prevalent genotypes. Two isolates only carried the AmpC β-lactamase gene blaCMY-2; one isolate had a combination of AmpC β-lactamase gene blaDHA-1 and ESBL β-lactamase gene blaCTX-M-14. Other important resistance genes such as blaOXA-10, blaTEM-1B, blaTEM-135, blaTEM-106, tet(A), qnrS1, qnrB4, and oqxAB were also detected. The serotype combination was highly abundant, with O10:H25 predominating (n=12). Most cefotaxime-resistant E. coli isolates belonged to phylogroup A (62.5%, n=50), followed by phylogroup B1 (26.3%, n=21). Thirty different sequence types (STs) and 27 distinct plasmid replicons were identified, among which ST2325 (n=12) and IncFII (n=38) was the most frequent ST and plasmid, respectively. ESBL/AmpC-producing isolates were divided into four major clades; clade IV was the primary lineage containing 37 isolates from feces and 13 from the environment. Three high-risk E. coli clone ST23 strains and one ST10 strain belonged to clades III and IV, respectively.Conclusion: Our study provides a comprehensive overview of resistance profiles and genomic characteristics in ESBL/AmpC-producing E. coli and highlights the possible role of stray dogs as an antibiotic resistance gene reservoir.Keywords: Escherichia coli, ESBL/AmpC, stray dogs, antimicrobial resistance, whole genome sequencing

Résumé Contexte En raison de la différenciation limitée de l’endothélium à partir de cellules souches mésenchymateuses, il a été fortement recommandé d’utiliser des cellules progénitrices endothéliales pour la régénération de l’endothélium endommagé des corps caverneux. Cette étude a été réalisée pour étudier les cellules endothéliales cérébrales humaines immortalisées, et leur capacité à réparer la dysfonction érectile dans un modèle de rat avec lésion du nerf caverneux. Les cellules progénitrices endothéliales circulantes ont été isolées du système vasculaire cérébral fœtal humain dans la région périventriculaire des tissus télencéphaliques. Plus de 95% des cellules CD31 positives ont été sélectionnées et cultivées pendant 10 jours. Des cellules progénitrices endothéliales cérébrales humaines ont été injectées dans les corps caverneux de rats présentant une lésion nerveuse des corps caverneux. La réponse érectile a ensuite été évaluée. Dans les essais in vivo, les rats ont été divisés en trois groupes: groupe 1, opération simulée; groupe 2, lésion bilatérale du nerf caverneux; et groupe 3, traitement par cellules endothéliales cérébrales humaines après lésion du nerf caverneux. Résultats Les cellules progénitrices endothéliales circulantes immortalisées établies ont montré l’expression de la transcription de la transcriptase inverse de la télomérase humaine par RT-PCR. Elles ont également montré l’expression du facteur de croissance de l’endothélium vasculaire, du facteur de von Willebrand, du récepteur du facteur de croissance de l’endothélium vasculaire, et de CD31, marqueurs spécifiques du type cellulaire par RT-PCR pour les cellules endothéliales. Dans les essais in vivo, la fonction érectile altérée des rats avec lésion du nerf caverneux s’est rétablie à 2, 4 et 12 semaines après transplantation de cellules endothéliales cérébrales humaines dans les corps caverneux. Conclusions Les cellules progénitrices endothéliales circulantes exprimant la transcriptase inverse de la télomérase, provenant du système vasculaire cérébral fœtal humain, pourraient réparer la dysfonction érectile de rats atteints de lésions des nerfs caverneux. Mots-clés Dysfonction érectile; Cellules endothéliales humaines; Transcriptase inverse de la Télomérase humaine.

Mengru Wang,1,&ast; Menghui Wang,1,&ast; Qing Zhu,1,2 Xiaoguang Yao,1 Mulalibieke Heizhati,1 Xintian Cai,1,2 Yue Ma,1 Run Wang,1 Jing Hong,1 Ling Yao,1 Le Sun,1 Na Yue,1 Yingli Ren,1 Nanfang Li1 1Hypertension Center, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China, Email lnanfang2016@sina.comPurpose: To develop and validate a risk prediction model for coronary heart disease (CHD) in snorers with hypertension, including traditional and new risk factors.Patients and Methods: Twenty factors were evaluated in the records of 2810 snorers with hypertension. Training (70%) and validation (30%) sets were created by random allocation of data, and a new nomogram model was developed. The model’s discrimination and calibration were measured by calculating the area under the receiver operating curve (AUC) and creating calibration charts. The performance of the nomogram model was compared with that of the Prediction for ASCVD Risk in China (China-PAR) and Framingham models by decision curve analysis. An optimal cutoff point for the risk score in the training set was computed to stratify patients.Results: In the nomogram model, the AUCs for predicting CHD at 5, 7 and 9 years in the training set were 0.706 (95% confidence interval [CI] 0.649– 0.763), 0.703 (95% CI 0.655– 0.751) and 0.669 (95% CI 0.593– 0.744), respectively. The respective AUCs were 0.682 (95% CI 0.607– 0.758), 0.689 (95% CI 0.618– 0.760) and 0.664 (95% CI 0.539– 0.789) in the validation set. The calibration chart showed that the predicted events from the nomogram score were close to the observed events. Decision curve analysis indicated that the nomogram score was slightly better than the Prediction for ASCVD Risk in China (China-PAR) and Framingham models for predicting the risk of CHD in snorers with hypertension. A cutoff point was identified for being CHD-free (a nomogram score of ≤ 121), which could be helpful for the early identification of individuals at high-risk of CHD.Conclusion: The nomogram score predicts the risk probability of CHD in snorers with hypertension at 5, 7 and 9 years, and shows good capability in terms of discrimination and calibration. It may be a useful tool for identifying individuals at high risk of CHD.Keywords: snorer, hypertension, coronary heart disease, prediction model

Joonki Hong,1,2 Hai Hong Tran,1 Jinhwan Jung,1 Hyeryung Jang,3 Dongheon Lee,1 In-Young Yoon,4,5 Jung Kyung Hong,4,5,&ast; Jeong-Whun Kim5,6,&ast; 1Asleep Inc., Seoul, Korea; 2Korea Advanced Institute of Science and Technology, Daejeon, Korea; 3Dongguk University, Seoul, Korea; 4Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Korea; 5Seoul National University College of Medicine, Seoul, Korea; 6Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea&ast;These authors contributed equally to this workCorrespondence: Jeong-Whun Kim, Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Korea, Email kimemails7@gmail.com Jung Kyung Hong, Department of Psychiatry, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, Korea, Email hongjk15@gmail.comPurpose: Nocturnal sounds contain numerous information and are easily obtainable by a non-contact manner. Sleep staging using nocturnal sounds recorded from common mobile devices may allow daily at-home sleep tracking. The objective of this study is to introduce an end-to-end (sound-to-sleep stages) deep learning model for sound-based sleep staging designed to work with audio from microphone chips, which are essential in mobile devices such as modern smartphones.Patients and Methods: Two different audio datasets were used: audio data routinely recorded by a solitary microphone chip during polysomnography (PSG dataset, N=1154) and audio data recorded by a smartphone (smartphone dataset, N=327). The audio was converted into Mel spectrogram to detect latent temporal frequency patterns of breathing and body movement from ambient noise. The proposed neural network model learns to first extract features from each 30-second epoch and then analyze inter-epoch relationships of extracted features to finally classify the epochs into sleep stages.Results: Our model achieved 70% epoch-by-epoch agreement for 4-class (wake, light, deep, REM) sleep stage classification and robust performance across various signal-to-noise conditions. The model performance was not considerably affected by sleep apnea or periodic limb movement. External validation with smartphone dataset also showed 68% epoch-by-epoch agreement.Conclusion: The proposed end-to-end deep learning model shows potential of low-quality sounds recorded from microphone chips to be utilized for sleep staging. Future study using nocturnal sounds recorded from mobile devices at home environment may further confirm the use of mobile device recording as an at-home sleep tracker.Keywords: respiratory sounds, sleep stages, deep learning, smartphone, polysomnography

Junli Hu,1– 5,&ast; Xintian Cai,1– 5,&ast; Nanfang Li,1– 5 Qing Zhu,1– 5 Wen Wen,1– 5 Jing Hong,1– 5 Delian Zhang,1– 5 Xiaoguang Yao,1– 5 Qin Luo,1 Le Sun1– 5 1Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Hypertension Institute, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 3National Health Committee Key Laboratory of Hypertension Clinical Research, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China, Tel/Fax +86 991-8564818, Email lnanfang2016@sina.comPurpose: This study aimed to investigate the association between triglyceride glucose index-waist circumference (TyG-WC) and the risk of first myocardial infarction (MI) in Chinese hypertensive patients with obstructive sleep apnoea (OSA).Methods: This study was an observational cohort study. A total of 2224 Chinese hypertensive patients with OSA without a history of MI were included in this study. Hazard ratio (HR) and 95% confidence interval (CI) were estimated using multivariable Cox proportion hazard models. A generalized additive model was used to identify nonlinear relationships. Additionally, we performed hierarchical analysis and test for interaction.Results: During a median follow-up of 7.15 years, 85 incidents of MI developed. Overall, there was a positive association between TyG-WC and the risk of first MI. In the multivariable-adjusted model, the risk of MI increased with quartiles of the TyG-WC, the HR in quartile 4 versus quartile 1 was 4.29. A generalized additive model and a smooth curve fitting showed that there existed a similar J-shaped association between TyG-WC and the risk of first MI, with an inflection point at about 785.Conclusion: Elevated levels of the baseline TyG-WC are associated with an increased risk of first MI. This finding indicates that the TyG-WC might be useful to identify the high risk of first MI in Chinese hypertensive patients with OSA.Keywords: triglyceride glucose index-waist circumference, myocardial infarction, hypertension, obstructive sleep apnoea, cohort study

Abstract Background Neural stem cells (NSCs) have the ability to generate a variety of functional neural cell types and have a high potential for neuronal cell regeneration and recovery. Thus, they been recognized as the best source of cell therapy for neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to the possibility of paracrine effect-based therapeutic mechanisms and easier clinical accessibility, extracellular vesicles (EVs), which possess very similar bio-functional components from their cellular origin, have emerged as potential alternatives in regenerative medicine. Material and methods EVs were isolated from human fibroblast (HFF) and human NSC (F3 cells). The supernatant of the cells was concentrated by a tangential flow filtration (TFF) system. Then, the final EVs were isolated using a total EV isolation kit. Results In this study, we demonstrate the potential protective effect of human NSC-derived EVs, showing the prevention of PD pathologies in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo mouse models. Human NSC and F3 cell (F3)-derived EVs reduced the intracellular reactive oxygen species (ROS) and associated apoptotic pathways. In addition, F3-derived EVs induced downregulation of pro-inflammatory factors and significantly decreased 6-OHDA-induced dopaminergic neuronal loss in vivo. F3 specific microRNAs (miRNAs) such as hsa-mir-182-5p, hsa-mir-183-5p, hsa-mir-9, and hsa-let-7, which are involved in cell differentiation, neurotrophic function, and immune modulation, were found in F3-derived EVs. Conclusions We report that human NSC-derived EVs show an effective neuroprotective property in an in vitro transwell system and in a PD model. The EVs clearly decreased ROS and pro-inflammatory cytokines. Taken together, these results indicate that NSC-derived EVs could potentially help prevent the neuropathology and progression of PD. Graphical Abstract

Xue-Jun Wang,1,&ast; Xiao-Ying Li,1,&ast; Xiao-Cong Guo,1,&ast; Li Liu,1 You-You Jin,1 Yun-Qiong Lu,1 Yao-Jia-Ni Cao,1 Jun-Yi Long,1 Huan-Gan Wu,2 Dan Zhang,2 Guang Yang,2 Jue Hong,2 Yan-Ting Yang,2 Xiao-Peng Ma1,2 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Peng Ma; Yan-Ting Yang, Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China, Email pengpengma@163.com; tcmyyt@126.comBackground: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn’s disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD.Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks.Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1.Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.Keywords: herb-partitioned moxibustion, Crohn’s disease, lncRNA, ceRNA, lncRNA LOC102550026/miR-34c-5p/Pck1 axis

Xintian Cai,1,2 Nanfang Li,1 Junli Hu,1 Wen Wen,1,2 Xiaoguang Yao,1 Qing Zhu,1,2 Mulalibieke Heizhati,1 Jing Hong,1 Le Sun,1 Guzailinuer Tuerxun,1 Delian Zhang,1 Qin Luo1 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Nanfang LiHypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China, Email lnanfang2016@sina.comPurpose: We aimed to investigate the relationship between the Chinese visceral adiposity index (CVAI) and the risk of new-onset myocardial infarction (MI) in patients with hypertension and obstructive sleep apnoea (OSA) and to inspect possible modifiers of the effect.Methods: The Cox regression model was used to evaluate the relationship between baseline CVAI and risk of new-onset MI. A generalized additive model was used to identify the nonlinear relationship. Besides, we conducted subgroup analyses and interaction tests.Results: A total of 2177 patients with hypertension and OSA undergoing polysomnography were enrolled in this study. During a median follow-up period of 87 months, 82 participants developed new-onset MI. Overall, CVAI was positively related to the risk of new-onset MI (per 1 SD increase; HR = 1.54, 95% CI: 1.28– 1.85). In multivariable-adjusted models, the risk of new-onset MI increased with quartiles of CVAI, with an HR of 3.64 (95% CI: 1.94– 6.83) for quartile 4 compared with quartile 1. The generalized additive model and smoothed curve fit revealed a nonlinear relationship between CVAI and risk of new-onset MI with an inflection point of approximately 112. None of the stratification variables had a significant effect on the relationship between CVAI and new-onset MI. Similar outcomes were observed in the sensitivity analysis. The addition of CVAI significantly improved reclassification and discrimination over the conventional model, with a category-free NRI of 0.132 (95% CI 0.021 to 0.236, P = 0.021) and an IDI of 0.012 (95% CI 0.005 to 0.023, P < 0.001).Conclusion: This study demonstrated a nonlinear relationship between CVAI and the risk of new-onset MI in patients with hypertension and OSA. Higher CVAI was significantly associated with the risk of new-onset MI when CVAI was ≥ 112.Keywords: Chinese visceral adiposity index, myocardial infarction, hypertension, obstructive sleep apnoea, cohort study

Jing Hong,1,&ast; Wen-Yue Liu,1,&ast; Xiang Hu,1 Wen-Wen Chen,2 Fei-Fei Jiang,1 Ze-Ru Xu,1 Fei-Xia Shen,1 Hong Zhu1 1Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Geriatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 577-55579622, Fax +86 577-55578522, Email zhuhong@wmu.edu.cnPurpose: Free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship.Methods: This retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables.Results: Log rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32– 0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32– 0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥ 65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality, after adjustment.Conclusion: Routine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.Keywords: FT3, FT3/FT4 ratio, mortality, diabetic foot ulcer

Mengyue Lin,1,2 Mulalibieke Heizhati,1 Lin Gan,1,2 Ling Yao,1 Wenbo Yang,1 Mei Li,1 Jing Hong,1 Zihao Wu,1 Hui Wang,1,2 Nanfang Li1 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region; Xinjiang Hypertension Institute; National Health Committee Key Laboratory of Hypertension Clinical Research; Key Laboratory of Xinjiang Uygur Autonomous Region “Hypertension Research Laboratory”; Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, People’s Republic of China; 2Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Nanfang Li, Email lnanfang2016@sina.comPurpose: Patients with hypertension and glucose metabolism disorder (GMD) are at high risk of developing kidney dysfunction (KD). Therefore, we aimed to develop a nomogram for predicting individuals’ 5-year risk of KD in hypertensives with GMD.Patients and Methods: In total, 1961 hypertensives with GMD were consecutively included. Baseline data were extracted from medical electronic system, and follow-up data were obtained using annual health check-ups or hospital readmission. KD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Subjects were randomly divided into training and validation sets with a ratio of 7 to 3. Least absolute shrinkage and selection operator method was used to identify potential predictors. Cox proportional hazard model was applied to build a nomogram for predicting KD risk. The discriminative ability, calibration and usefulness of the model were evaluated. The prediction model was verified by internal validation.Results: During the follow-up of 5351 person-years with a median follow-up of 32 (range: 3– 91) months, 130 patients developed KD. Age, sex, ethnicity, hemoglobin A1c, uric acid, and baseline eGFR were identified as significant predictors for incident KD and used for establishing nomogram. The prediction model displayed good discrimination with C-index of 0.770 (95% CI: 0.712– 0.828) and 0.763 (95% CI: 0.704– 0.823) in training and validation sets, respectively. Calibration curve indicated good agreement between the predicted and actual probabilities. The decision curve analysis demonstrated that the model was clinically useful.Conclusion: The prediction nomogram, including six common easy-to-obtain factors, shows good performance for predicting 5-year risk of KD in hypertensives with GMD. This quantitative tool could help clinicians, and even primary care providers, recognize potential KD patients early and make strategy for prevention and management.Keywords: kidney dysfunction, nomogram, hypertension, diabetes, prediction

Yiying Liu,1,&ast; Xin Wang,2,&ast; Linying Wang,1 Wenwen Chen,3 Wenyue Liu,1 Tingting Ye,1 Jing Hong,1 Hong Zhu,1 Feixia Shen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China; 3Department of Senile Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feixia ShenDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaEmail shenfeixia@wmu.edu.cnPurpose: Diabetic neurogenic bladder (DNB) has been widely recognized in recent years. It is common in patients with long-term diabetes and may also lead to many severe complications. Although there has been widespread evidence that inflammation is involved in the development of some diabetic complications, there is little evidence that this can also occur in the bladder. In recent years, platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been viewed as potential novel markers of inflammatory responses. This study was designed to evaluate the relationship between the presence of DNB and the PLR and NLR.Patients and Methods: A total of 371 cases of T2DM patients were included in this retrospective study. Patients were divided into two groups, with 115 diabetic subjects diagnosed with diabetic neurogenic bladder and 256 control subjects without DNB. The independent predictors of DNB were analyzed using logistic regression.Results: Compared with patients without DNB, the mean PLR and NLR were significantly higher in those with DNB (p < 0.001). Based on the logistic regression, PLR was found to be an independent risk factor for DNB (odds ratio [OR]: 1.408, 95% confidence interval [CI]: 1.248– 1.617). From the receiver operating characteristic (ROC) curve, using PLR as indicative of DNB was expected to be 101.1949, and it generated a sensitivity and specificity value of 89.6% and 23.4%, respectively. The area under the curve (AUC) was also found to be 0.899 (95% CI: 0.865– 0.932).Conclusion: In our study, PLR and NLR were significantly higher for patients with DNB. The PLR was found to be a risk factor in the presence of DNB after correcting for possible confounding factors. Considering the severe complications associated with DNB, patients with elevated PLR should be seriously cared for in clinics.Keywords: diabetic autonomic neuropathy, neurogenic bladder, oxidative stress, inflammatory response

Jung Kyung Hong,1,2,&ast; Taeyoung Lee,3,&ast; Roben Deocampo Delos Reyes,4 Joonki Hong,3,4 Hai Hong Tran,4 Dongheon Lee,4 Jinhwan Jung,4 In-Young Yoon1,2 1Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Korea; 2Seoul National University College of Medicine, Seoul, Korea; 3Korea Advanced Institute of Science and Technology, Daejeon, Korea; 4Asleep Inc., Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: In-Young YoonDepartment of Psychiatry, Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, KoreaTel +82-31-787-7433Fax +82-31-787-4058Email iyoon@snu.ac.krJinhwan JungR&D Division, Asleep Inc, Asleep, 15, Teheran-ro 82-gil, Gangnam-gu, Seoul, KoreaTel +82-10-6228-7137Email insomnia@asleep.aiStudy Objectives: Automated sleep stage scoring is not yet vigorously used in practice because of the black-box nature and the risk of wrong predictions. The objective of this study was to introduce a confidence-based framework to detect the possibly wrong predictions that would inform clinicians about which epochs would require a manual review and investigate the potential to improve accuracy for automated sleep stage scoring.Methods: We used 702 polysomnography studies from a local clinical dataset (SNUBH dataset) and 2804 from an open dataset (SHHS dataset) for experiments. We adapted the state-of-the-art TinySleepNet architecture to train the classifier and modified the ConfidNet architecture to train an auxiliary confidence model. For the confidence model, we developed a novel method, Dropout Correct Rate (DCR), and the performance of it was compared with other existing methods.Results: Confidence estimates (0.754) reflected accuracy (0.758) well in general. The best performance for differentiating correct and wrong predictions was shown when using the DCR method (AUROC: 0.812) compared to the existing approaches which largely failed to detect wrong predictions. By reviewing only 20% of epochs that received the lowest confidence values, the overall accuracy of sleep stage scoring was improved from 76% to 87%. For patients with reduced accuracy (ie, individuals with obesity or severe sleep apnea), the possible improvement range after applying confidence estimation was even greater.Conclusion: To the best of our knowledge, this is the first study applying confidence estimation on automated sleep stage scoring. Reliable confidence estimates by the DCR method help screen out most of the wrong predictions, which would increase the reliability and interpretability of automated sleep stage scoring.Keywords: confidence estimation, deep learning, electroencephalography, polysomnography, sleep stages, accuracy improvement

Jun Hong,&ast; Ji-Hua Han,&ast; Hong-Lei Luo, Ya-Qi Song Department of Radiation Oncology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Jiangsu, Huai’an, 223300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya-Qi Song; Hong-Lei LuoDepartment of Radiation Oncology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Jiangsu, Huai’an, 223300, People’s Republic of ChinaTel +86 18912089369Email songyaqi@111.com; luohonglei07@outlook.comPurpose: This study was designed to explore the optimal minimum segment width (MSW) in the intensity-modulated radiotherapy (IMRT) plan for esophageal cancer.Patients and Methods: The imaging data of 20 esophageal cancer patients were selected for this study. Four IMRT plans were designed for each patient with MSWs of 0.5, 1.0, 1.5, and 2.0 cm. The conformity index (CI) and homogeneity index (HI) of the planning target volumes (PTV), organs at risk (OARs), control points (CP), monitor units (MU), plan delivery time (DT), and gamma passing rates (GPR) were collected and compared to appraise the treatment plan quality and delivery efficiency.Results: Lower-MSW plans had larger CI and smaller HI values, and lower dose parameters of OARs and PTVs. The HI, CI, and dose parameter of OARs in the 0.5 and 1.0 cm MSW groups were similar and much better than those of the 1.5 and 2.0 cm MSW groups. Meanwhile, the plan in the 0.5 cm MSW group had significantly higher MUs, CPs, and DTs, and a significantly lower relative dose of GPR with a 3% dose difference and 3 mm distance to agreement criteria than the other three groups.Conclusion: The 0.5 and 1 cm MSW groups had better dosimetric parameters and IMRT plan quality than the other groups. However, plans with 0.5 cm MSW had worse delivery accuracy and efficiency than the other three groups. Thus, MSW of 1.0 cm was the optimal choice to ensure good quality, delivery accuracy, and treatment efficiency in IMRT plans for esophageal cancer.Keywords: esophageal cancer, minimum segment width, delivery efficiency, plan quality, intensity-modulated radiotherapy

The recent discovery of comammox Nitrospira, a complete ammonia oxidizer, capable of completing the nitrification on their own has presented tremendous challenges to our understanding of the nitrification process. There are two divergent clades of comammox Nitrospira, Clade A and B. However, their population abundance, community structure and role in ammonia and nitrite oxidation are poorly understood. We conducted a 94-day microcosm study using a grazed dairy pasture soil amended with urea fertilizers, synthetic cow urine, and the nitrification inhibitor, dicyandiamide (DCD), to investigate the growth and community structure of comammox Nitrospira spp. We discovered that comammox Nitrospira Clade B was two orders of magnitude more abundant than Clade A in this fertile dairy pasture soil and the most abundant subcluster was a distinctive phylogenetic uncultured subcluster Clade B2. We found that comammox Nitrospira Clade B might not play a major role in nitrite oxidation compared to the role of canonical Nitrospira nitrite-oxidizers, however, comammox Nitrospira Clade B is active in nitrification and the growth of comammox Nitrospira Clade B was inhibited by a high ammonium concentration (700 kg synthetic urine-N ha–1) and the nitrification inhibitor DCD. We concluded that comammox Nitrospira Clade B: (1) was the most abundant comammox in the dairy pasture soil; (2) had a low tolerance to ammonium and can be inhibited by DCD; and (3) was not the dominant nitrite-oxidizer in the soil. This is the first study discovering a new subcluster of comammox Nitrospira Clade B2 from an agricultural soil.

Xin-Tian Cai,1,2,&ast; Qing Zhu,1,2,&ast; Sha-Sha Liu,2 Meng-Ru Wang,2 Ting Wu,2 Jing Hong,2 Jun-Li Hu,2 Nanfang Li1,2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang LiGraduate School, Xinjiang Medical University; Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of ChinaEmail lnanfang2016@sina.comPurpose: The metabolic score for insulin resistance (METS-IR) index is an emerging surrogate predictor of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the METS-IR index and the risk of T2DM in non-obese Japanese adults.Methods: A total of 12,290 non-obese participants were selected from the NAGALA prospective cohort study conducted from 2004 to 2015. Cox proportional hazards models were used to assess the association between the baseline METS-IR index and risk of T2DM. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During a median follow-up of 2050 days, 176 (1.43%) incident T2DM occurred. The fully adjusted HR (95% CI) for the incidence of T2DM in non-obese adults was 1.17 (HR=1.17, 95% CI: 1.09– 1.27, P< 0.001) for every 1-unit increase in the METS-IR index. The risk of developing T2DM increased with the quartile of change in the METS-IR index, after adjustment for multiple potential confounding, the HRs for the Q4 group versus the Q1 group was 4.01 (95% CI, 1.39– 11.57). Generalized additive models also showed a cumulative increase in the risk of T2DM with increasing the METS-IR index. Time-dependent receiver operating curve suggested helpful discriminative power of the METS-IR index for T2DM. The C-statistics by the clinical risk factors significantly improve with the addition of the METS-IR index (from 0.862 to 0.875, P = 0.035); the discriminatory power and risk reclassification also appeared to be substantially better, with the category-free NRI of 0.216, and the IDI of 0.011.Conclusion: The METS-IR index was a significant and independent predictor for future T2DM development in non-obese adults. The METS-IR index may have clinical significance in identifying groups at high risk of T2DM.Keywords: metabolic score for insulin resistance index, type 2 diabetes mellitus, non-obese, population-based cohort study

Megan Mosca, Julie Hong, Edward Hadeler, Marwa Hakimi, Wilson Liao, Tina Bhutani Psoriasis and Skin Treatment Center, Department of Dermatology, University of California San Francisco, San Francisco, CA, USACorrespondence: Megan MoscaPsoriasis and Skin Treatment Center, Department of Dermatology, University of California San Francisco, 515 Spruce Street, San Francisco, CA, 94118, USAEmail mmosca@med.unr.eduAbstract: Psoriasis is a chronic inflammatory skin condition associated with immune dysregulation. The immunologic cascade mediated by the interleukin (IL)-17 pathway plays a critically important role in the pathogenesis of psoriasis. The IL-17 effectors (IL-17A, IL-17C, IL-17E, and IL17F) act on keratinocytes, endothelial cells, and immune cells to stimulate epidermal hyperplasia and the pro-inflammatory feed-forward cycle seen within plaque psoriasis. The IL-17 pathway is also hypothesized to modulate the inflammatory responses linking comorbid systemic diseases with psoriasis. Furthermore, the robust clinical response seen with current and emerging therapies targeting IL-17 emphasizes the importance of the IL-17 cytokines in the pathogenesis of psoriasis.Keywords: IL-17, plaque psoriasis, pathogenesis, biologics, immune pathway

Lingli Chen,1,&ast; Jianfeng Hong,2,&ast; Renjing Hu,3,&ast; Xiaomei Yu,1 Xindong Chen,1 Shaoxiong Zheng,1 Yuan Qin,1 Xiumei Zhou,1 Yigang Wang,1 Liping Zheng,2 Hongming Fang,2 Pengfei Liu,4 Biao Huang1 1Department of Immunoassay Laboratory, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of China; 2Department of Laboratory, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China; 3Department of Laboratory, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Gastroenterology, The Jiangyin Clinical College of Xuzhou Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao HuangImmunoassay Laboratory, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310016, People’s Republic of ChinaTel +86 571-86843187Email jswxhb@163.comHongming FangDepartment of Laboratory, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 310016, People’s Republic of ChinaTel +86 571 83865858Email 3295988078@qq.comPurpose: The present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis.Patients and Methods: The double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed.Results: Serum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL).Conclusion: sTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC.Keywords: T cell immunoglobulin and mucin domain molecule 3, time-resolved fluorescence immunoassay, biomarker, gastric cancer

Zhikang Yang,1– 3,&ast; Mulalibieke Heizhati,1– 3,&ast; Lin Wang,1– 3 Mei Li,1– 3 Fengyu Pan,1– 3 Zhongrong Wang,1– 3 Reyila Abudureyimu,1– 3 Jing Hong,1– 3 Ling Yao,1– 3 Wenbo Yang,1– 3 Shasha Liu,1– 3 Nanfang Li1– 3 1Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, People’s Republic of China; 3National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li Email Lnanfang2016@sina.comObjective: To explore the relationship of subjective sleep quality with blood pressure (BP) and hypertension by considering the influence of sleep disordered breathing (SDB) and age in the general population.Methods: We evaluated sleep quality using the Pittsburgh sleep quality index (PSQI) and SDB using NoSAS score and measured BP in randomly selected adults in China in 2019. Sleep quality is categorized into four groups as very good, fairly good, fairly bad and very bad. SDB is defined as NoSAS score ≥ 8. Hypertension is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medicine within previous 2 weeks. Multi-variable linear and logistic regression analyses were used to assess the association of global PSQI score and sleep quality with BP and prevalent hypertension.Results: In the 33,341 participants (53.4% women, median age: 48 years), prevalence of hypertension significantly increased from very good to very bad sleepers in total (34.3 vs 42.6 vs 50.3 vs 58.5%), SDB (61.2 vs 68.3 vs 73.3 vs 75.5%) and non-SDB participants (26.8 vs 33.1 vs 40.1 vs 50.9%). In multiple linear regression, PSQI global score showed significant positive association with BP levels in total, SDB and non-SDB participants, consistent in sensitivity analysis by excluding participants who were taking antihypertensives, and in participants aged < 60 years in age-stratified analysis. In multivariable logistic regression, odds ratio for presence of hypertension significantly increased from very good to very bad sleepers in total (1 vs 1.08 vs 1.22 vs 1.48), SDB (1 vs 1.17 vs 1.35 vs 1.28) and non-SDB participants (1 vs 1.05 vs 1.14 vs 1.53), consistent in participants aged < 60 years.Conclusion: Poor subjective sleep quality is significantly associated with higher BP and prevalent hypertension, independent of SDB in the young- and middle-aged general population, indicating potential of improving sleep quality to lower BP and optimize hypertension management at population level.Keywords: sleep quality, sleep disordered breathing, blood pressure, prevalent hypertension

A metastatic brain tumor is the most common type of malignancy in the central nervous system, which is one of the leading causes of death in patients with lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic brain tumors with lung cancer using neural stem cells (NSCs), which encode rabbit carboxylesterase (rCE) and the secretion form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human lung cancer cells were evaluated in vitro with the ligands and decoy receptor expression for sTRAIL in the presence of CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of lung cancer cells in the presence of CPT-11 in vitro. Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with CPT-11. In resting state, DR4 expression in lung cancer cells and DcR1 in NSCs increased to 70% and 90% after CPT-11 addition, respectively. The volumes of the tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL transplantation and CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus CPT-11 as well as F3.CE.sTRAIL plus CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different biological effects can be translatable to clinical application.

Fujun Zhou,1,* Cheng Cao,2,* Huiping Chai,2 Jingfang Hong,3 Min Zhu1 1Department of Health and Nursing, Anhui Vocational College of City Management, Hefei City, Anhui Province, People’s Republic of China; 2Department of Thoracic Surgery, 4th Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 3School of Nursing, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng CaoDepartment of Thoracic Surgery, 4th Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Hefei, 230022, Anhui Province, People’s Republic of ChinaTel/Fax +86 0551-66331040 Email caochengaysfy@163.comBackground: Smoking is the most common cause of chronic obstructive pulmonary disease (COPD), and the early diagnosis for COPD remains poor. Exploring the molecular mechanism and finding feasible biomarkers will be beneficial for clinical management of COPD. Circular RNAs (circRNAs) are noncoding RNAs that act as miRNA sponges to regulate the expression levels of genes, leading to the changes of cellular phenotypes and disease progression. CircRNA HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (circ-HACE1) was abnormally expressed after the induction of cigarette smoke extract (CSE) in cell model. This study was performed to explore its function and mechanism in COPD.Methods: Circ-HACE1, microRNA-485-3p (miR-485-3p) and toll-like receptor 4 (TLR4) detection was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis/cell cycle were respectively examined using cell counting kit-8 (CCK-8) and flow cytometry. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated through the measurement of malondialdehyde (MDA) and superoxide dismutase (SOD). The target binding analysis was conducted via dual-luciferase reporter assay. Western blot was employed for protein expression detection of TLR4.Results: Circ-HACE1 was overexpressed in smokers or smokers with COPD and CSE upregulated circ-HACE1 expression in 16HBE cells. Knockdown of circ-HACE1 attenuated CSE-stimulated cell viability and cell cycle repression, as well as the enhancement of cell apoptosis, inflammatory response and oxidative stress. MiR-485-3p was a target of circ-HACE1. Circ-HACE1 regulated CSE-induced cell injury via targeting miR-485-3p. TLR4 was a downstream target of miR-485-3p, and miR-485-3p inhibited the CSE-induced cell damages by directly downregulating the level of TLR4. Circ-HACE1/miR-485-3p regulated TLR4 expression in CSE-treated 16HBE cells, and TLR4 overexpression also reversed all effects of si-circ-HACE1 on CSE-treated 16HBE cells.Conclusion: These findings elucidated that circ-HACE1 contributed to the CSE-induced cell damages in COPD cell models via regulating TLR4 by acting as the sponge of miR-485-3p.Keywords: circ-HACE1, chronic obstructive pulmonary disease, cigarette smoke extract, miR-485-3p, TLR4

Ying Cao,1,* Du Tang,1,* Yining Xiang,1 Li Men,2 Chao Liu,1 Qin Zhou,1 Jun Wu,3 Lei Huo,3 Tao Song,3 Ying Wang,4 Zhanzhan Li,1 Rui Wei,1 Liangfang Shen,1 Zhen Yang,1 Jidong Hong1 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jidong HongDepartment of Oncology, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 731 8975 3733Fax +86 731 8975 3336Email hongjidong1966@126.comPurpose: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma.Methods: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT1/MRI1, CT2/MRI2, CT3/MRI3, and CT4/MRI4) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan1, plan2, plan3 and plan4) were made. The dose of the initial plan (plan1) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan1– 2 and plan1– 3) and by superimposing the doses to obtain the ART plans (plan10+20 and plan20+10), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans.Results: Compared with the projection plan, the D2 to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D2/Dmean to the brainstem, optic chiasm and pituitary, as well as the V20, V30, V40 and V50 to the normal brain decreased. The D2 to the pituitary and optic chiasm as well as the V20, V30, V40 and V50 to the normal brain in plan10+20 were lower than those in plan20+10, while the CI to the PTV was higher than that in plan20+10. The TCP of the PTV in plan10+20 was higher than that in plan20+10.Conclusion: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART.Keywords: adaptive radiotherapy, high-grade glioma, dosimetry, biophysical model

Wenwen Chen,1,* Kun Chen,2,* Zhixiao Xu,3 Yepeng Hu,1 Yiying Liu,1 Wenyue Liu,1 Xiang Hu,1 Tingting Ye,1 Jing Hong,1 Hong Zhu,1 Feixia Shen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feixia ShenDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaEmail shenfeixia@wmu.edu.cnPurpose: Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations.Patients and Methods: A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan–Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort.Results: All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively (p=0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% (p< 0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045– 1.104, p< 0.001), Wagner classification (HR 2.274, 95% CI 1.351– 3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014– 3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177– 3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001– 1.004, p< 0.001) and direct bilirubin (HR 1.154, 95% CI 1.081– 1.232, p< 0.001) were independent predictors of mortality following amputation.Conclusion: Postoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.Keywords: amputation, platelet-to-lymphocyte ratio, PLR, neutrophil-to-lymphocyte ratio, NLR, diabetic foot ulcer, mortality

Nicholas D Brownstone, Julie Hong, Megan Mosca, Edward Hadeler, Wilson Liao, Tina Bhutani, John Koo University of California, San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, San Francisco, CA, USACorrespondence: Nicholas D BrownstoneUniversity of California, San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, 515 Spruce Street, San Francisco, CA, 94118, USATel +1 415-476-4019Fax +1 415-502-4126Email Nicholas.Brownstone@ucsf.eduAbstract: The advent of biologic agents within the past two decades has dramatically improved the treatment of psoriasis and psoriatic arthritis. Given that there now exists 11 FDA approved biologic options available for psoriasis, with more in the pipeline, the therapeutic armamentarium has been greatly enhanced. However, the fact that there are so many available options has also caused confusion for providers. Therefore, this manuscript deliberately focuses on the most clinically useful facts (such as efficacy and safety data) about each and every FDA approved biologic agent (including pipeline agents) for psoriasis. Moreover, among the clinically relevant facts, this manuscript purposely emphasizes the unique merits and demerits of each agent to make it easier for the provider to select which one of these many options is the best for the particular patient on hand. The goal of this manuscript is to aid the busy practicing dermatologist in becoming more adept at using these agents with the ultimate aim of improving patient care.Keywords: biologic therapy, psoriasis, IL-17, TNF-alpha, IL 12/23, psoriatic arthritis, IL-23

Xiaoxian Pan,1,* Caihong Wang,1,* Rong Li,2 Li Su,1,3,4 Mingwei Zhang,1,3,4 Chuanshu Cai,1,3,4 Shiping Liu,1 Weijian Zhang,1,3,4 Jihong Song,2 Jinsheng Hong1,3,4 1Department of Radiotherapy, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2The School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Key Laboratory of Radiation Biology (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, People’s Republic of China; 4Fujian Provincial Key Laboratory of Precision Medicine for Cancer, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinsheng Hong Email 13799375732@163.comPurpose: This study aims to explore the applicability of the Nutrition Risk Screening 2002 (NRS2002) tool in screening nutritional risk and the Patient-Generated Subjective Global Assessment (PG-SGA) in determining nutrition status in nasopharyngeal carcinoma (NPC) patients.Materials and Methods: NRS2002 and PG-SGA were simultaneously applied to evaluate the nutritional status of NPC patients before induction chemotherapy, as well as before and after radiotherapy. The PG-SGA results were considered golden standard in evaluating nutrition status, and the ROC curve value and Youden index were applied to analyze NRS2002 effectiveness in screening nutritional risk.Results: A total of 102 NPC patients were included in this study. Patients with an NRS2002 score < 3 and PG-SGA score ≥ 4 accounted for 5.3% (5/95), 19.6% (18/92) and 94.8% (36/38) at the time before induction chemotherapy, before radiotherapy and at the end of radiotherapy, respectively. The cut-off values of NRS2002 scores all < 2 corresponded to the maximum Youden index at the three procedural times. And the area under curve (AUC) were 0.598 (P = 0.390), 0.665 (P = 0.015) and 0.940 (P = 0.034), respectively. At the end of radiotherapy, NRS2002 scores of < 3 and < 2 were used as cut-off values for nutritional risk screening, respectively. Additionally, the malnutrition-missed detection rates were 36.0% and 12.0% (χ2 = 15.789; P < 0.001).Discussion: NRS2002 nutritional risk screening combined with the PG-SGA nutritional assessment has certain applicability in NPC. NRS2002 score ≥ 2 can be considered as a new cut-off point for nutritional assessment.Keywords: nasopharyngeal carcinoma, nutritional risk screening, nutrition assessment, NRS2002, PG-SGA

Ya-Ping Wang, Jun Hong, Jian Wang, Yi-Bing Bei, Han-Kun Hao, Lu-Chun Hua Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of ChinaCorrespondence: Lu-Chun Hua Email 13391051806@189.cnAim: Gastric carcinoma with neuroendocrine differentiation (NEDGC) is a relatively rare pathologic diagnosis in clinical practice, which has no specific guidelines or treatment recommendations yet. In this study, we aim to investigate the clinicopathological characteristics and prognostic factors of this disease.Patients and Methods: We retrospectively analyzed clinicopathological data from a series of 82 NEDGC patients who underwent surgery for gastrectomy at Huashan Hospital Fudan University between January 2007 and December 2018. Furthermore, a series of 50 cases were used to analyze 3-year overall survival (OS).Results: Ages of the patients ranged from 26 to 83 years (M:F, 4.8:1). The majority of patients suffered from some symptoms (97.6%), as the most common one was abdominal pain (48.8%). Most of the tumors were ≥ 5 cm (53.7%), in the lower part of the stomach (47.5%), and with advanced T (87.8% ≥T3) and N (67.1% ≥N1) stage. As to the neuroendocrine markers, Syn showed a slight advantage on sensitivity than CgA (79.3 and 75.6%, respectively). The 3-year OS was 54%. Advanced T stage (≥T3) of the primary tumor, positive lymphovascular invasion (LVI), large tumor size (5.5cm), high neutrophil-to-lymphocyte ratio (NLR, 2.51), and low prealbumin level (173.87 mg/L) were associated with inferior OS based on the univariate analysis. Low preoperative hemoglobin level (113.87g/L), laparoscopic-assisted gastrectomy, and advanced N stage (N3) were three independent risk factors for 3-year OS of NEDGC patients in both univariate and multivariate analysis.Conclusion: The TN staging system for gastric adenocarcinoma also has a prognostic value for NEDGC patients, while N3 stage works as an independent predictor of patients’ survival. Since most of the NEDGC patients were in advanced stage, proper indications to perform operative laparoscopy should be selected.Keywords: gastric cancer, neuroendocrine cell differentiation, prognosis, surgical treatment

Background and Study Aim: This study aimed to determine if Judo and Taekwondo in a physical education (PE) setting could improve the fitness of university students. Material and Methods: Students who registered voluntarily for the courses were considered for the study (n=27, 18-22 years for Judo; n=39, 18-22 years for Taekwondo). The control group (n=32, 20-24 years) was composed of students who were not part of a physical education course. None of the participants were college athletes nor PE students. The duration of the courses was eight weeks, twice a week with 50 minutes per session. Both courses included training for muscular fitness, flexibility, explosive strength, and cardiovascular fitness. The courses also included sparring matches and sport-specific training. The following health-related fitness parameters were measured before and after eight weeks: cardiovascular fitness using the Cooper Test, muscular endurance using 60 seconds curl-up test, trunk flexibility using the sit-and-reach test, and explosive leg strength using the standing long jump test. Parametric tests were applied to detect any effect of the courses on the students. Differences with p ≤ 0.05 and Vargha-Delaney Common language effect size (VD) ≤ 42% or ≥ 58% were considered as evidence for any improvements in the fitness parameters. Results: Most of the tested parameters, apart from body composition, improved in both martial arts groups while those of the control group dropped. These changes were significantly different (p ≤ 0.05 and VD ≤ 42% or ≥ 58%). The regular curl-ups and sitting stretch done during the eight weeks improved the muscular endurance and trunk flexibility of the Judo group, respectively. Moreover, continuous practice of the rolling/falling technique may have contributed to the improvement in flexibility of the Judo students. Conclusions: There is evidence that eight weeks of Judo and Taekwondo in a PE context improves the health-related fitness of male university students.

Hyo Jung Shin,1,2 Hyewon Park,1,2 Nara Shin,1,2 Juhee Shin,1,2 Do Hyeong Gwon,1,2 Hyeok Hee Kwon,1,3 Yuhua Yin,1,2 Jeong-Ah Hwang,1,2 Jinpyo Hong,2 Jun Young Heo,1,4,5 Cuk-Seong Kim,1,6 Yongbum Joo,7 Youngmo Kim,7 Jinhyun Kim,8 Jaewon Beom,9 Dong Woon Kim1,2 1Department of Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea; 2Department of Anatomy and Cell Biology, Brain Research Institute, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea; 3Department of Pediatrics; 4Biochemistry; 5Infection Control Convergence Research Center; 6Physiology Chungnam National University College of Medicine, Daejeon, Republic of Korea; 7Department of Orthopedics, Chungnam National University College of Medicine, Daejeon, Republic of Korea; 8Division of Rheumatology, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea; 9Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of KoreaCorrespondence: Dong Woon Kim DVM., PhD.Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, 266 Munhwa-Ro, Chung-Gu, Daejeon 35015, Republic of KoreaTel +82-42-580-8201Fax +82-42-586-4800Email visnu528@cnu.ac.krJinhyun Kim, MD., PhD.Department of Internal Medicine, Chungnam National University College of Medicine, 266 Munhwa-Ro, Chung-Gu, Daejeon 35015, Republic of KoreaTel +82-42-338-2420Fax +82-42-586-4800Email jkim@cnuh.co.krBackground: Osteoarthritis (OA) is the most common type of joint disease associated with cartilage breakdown. However, the role played by mitochondrial dysfunction in OA remains inadequately understood. Therefore, we investigated the role played by p66shc during oxidative damage and mitochondrial dysfunction in OA and the effects of p66shc downregulation on OA progression.Methods: Monosodium iodoacetate (MIA), which is commonly used to generate OA animal models, inhibits glycolysis and biosynthetic processes in chondrocytes, eventually causing cell death. To observe the effects of MIA and poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles, histological analysis, immunohistochemistry, micro-CT, mechanical paw withdrawal thresholds, quantitative PCR, and measurement of oxygen consumption rate and extracellular acidification rate were conducted.Results: p-p66shc was highly expressed in cartilage from OA patients and rats with MIA-induced OA. MIA caused mitochondrial dysfunction and reactive oxygen species (ROS) production, and the inhibition of p66shc phosphorylation attenuated MIA-induced ROS production in human chondrocytes. Inhibition of p66shc by PLGA-based nanoparticles-delivered siRNA ameliorated pain behavior, cartilage damage, and inflammatory cytokine production in the knee joints of MIA-induced OA rats.Conclusion: p66shc is involved in cartilage degeneration in OA. By delivering p66shc-siRNA-loaded nanoparticles into the knee joints with OA, mitochondrial dysfunction-induced cartilage damage can be significantly decreased. Thus, p66shc siRNA PLGA nanoparticles may be a promising option for the treatment of OA.Keywords: osteoarthritis, monosodium iodoacetate, p66shc, ROS, mitochondrial dysfunction, PLGA-based nanoparticles

Jun Hong, 1, 2 Honghao Jiang, 1 Jianye Hu, 1 Lianzhe Wang, 1 Ruifang Liu 1 1College of Life Science and Engineering, Henan University of Urban Construction, Ping Dingshan 467036, People’s Republic of China; 2Henan Province Key Laboratory of Water Pollution Control and Rehabilitation Technology, Henan University of Urban Construction, Pingdingshan, Henan 467036, People’s Republic of ChinaCorrespondence: Lianzhe WangCollege of Life Science and Engineering, Henan University of Urban Construction, Ping Dingshan 467036, People’s Republic of ChinaTel +86-180 3758 0131Email jijy99@126.comBackground: Tachyplesin I is a cationic antimicrobial peptide with a typical cyclic antiparallel β-sheet structure. We previously demonstrated that long-term continuous exposure to increased concentration of tachyplesin I can induce resistant Gram-negative bacteria. However, no significant information is available about the resistance mechanism of Pseudomonas aeruginosa (P. aeruginosa) to tachyplesin I.Materials and Methods: In this study, the global gene expression profiling of P. aeruginosa strain PA-99 and P. aeruginosa CGMCC1.2620 (PA1.2620) was conducted using transcriptome sequencing. For this purpose, outer membrane permeability and outer membrane proteins (OMPs) were further analyzed.Results: Transcriptome sequencing detected 672 upregulated and 787 downregulated genes, covering Clusters of Orthologous Groups (COGs) of P. aeruginosa strain PA-99 compared with PA1.2620. Totally, 749 differentially expressed genes (DEGs) were assigned to 98 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and among them, a two-component regulatory system, a beta-lactam resistance system, etc. were involved in some known genes resistant to drugs. Additionally, we further attempted to indicate whether the resistance mechanism of P. aeruginosa to tachyplesin I was associated with the changes of outer membrane permeability and OMPs.Conclusion: Our results indicated that P. aeruginosa resistant to tachyplesin I was mainly related to reduced entry of tachyplesin I into the bacterial cell due to overexpression of efflux pump, in addition to a decrease of outer membrane permeability. Our findings were also validated by pathway enrichment analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). This study may provide a promising guidance for understanding the resistance mechanism of P. aeruginosa to tachyplesin I.Keywords: antibiotic resistance, tachyplesin I, P. aeruginosa, differentially expressed genes, outer membrane permeability, outer membrane proteins

Bacillus megaterium is well known as a plant growth-promoting rhizobacterium, but the relevant molecular mechanisms remain unclear. This study aimed to elucidate the effects of B. megaterium HT517 on the growth and development of and the control of disease in greenhouse tomato and its mechanism of action. A pot experiment was conducted to determine the effect of B. megaterium on tomato growth, and this experiment included the HT517 group (3.2×108 cfu/pot) and the control group (inoculated with the same amount of sterilized suspension). An antagonistic experiment and a plate confrontation experiment were conducted to study the antagonistic effect of B. megaterium and Fusarium oxysporum f.sp. lycopersici. Liquid chromatography–mass spectrometry was used to determine the metabolite composition and metabolic pathway of HT517. PacBio+Illumina HiSeq sequencing was utilized for map sequencing of the samples. An in-depth analysis of the functional genes related to the secretion of these substances by functional bacteria was conducted. HT517 could secrete organic acids that solubilize phosphorus, promote root growth, secrete auxin, which that promotes early flowering and fruiting, and alkaloids, which control disease, and reduce the incidence of crown rot by 51.0%. The complete genome sequence indicated that the strain comprised one circular chromosome with a length of 5,510,339 bp (including four plasmids in the genome), and the GC content accounted for 37.95%. Seven genes (pyk, aceB, pyc, ackA, gltA, buk, and aroK) related to phosphate solubilization, five genes (trpA, trpB, trpS, TDO2, and idi) related to growth promotion, eight genes (hpaB, pheS, pheT, ileS, pepA, iucD, paaG, and kamA) related to disease control, and one gene cluster of synthetic surfactin were identified in this research. The identification of molecular biological mechanisms for extracellular secretion by the HT517 strain clarified that its organic acids solubilized phosphorus, that auxin promoted growth, and that alkaloids controlled tomato diseases.