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Ting Liu,1,* Chao Lei,1,* Qinhong Huang,2,* Weiqi Song,3 Chen Li,1 Ning Sun,4,5 Zhihua Liu6 1Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510799, People’s Republic of China; 2The First Clinical College, Guangzhou Medical University, Guangzhou, 511400, People’s Republic of China; 3Department of Public Health, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Guangzhou 11th People’s Hospital, Guangzhou Cadre and Talent Health Management Center, Guangzhou, 510530, People’s Republic of China; 5The State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, 999077, Hong Kong, China; 6Department of Anorectal Surgery, the Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihua Liu; Ning Sun, Email liuzhihua83@hotmail.com; ning.sun@connect.polyu.hkIntroduction: Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may be safe and effective anti-obesity solutions.Methods: We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT.Results: Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNFα, IL-6, IL-1βand iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes.Conclusion: We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.Keywords: hesperidin, high-fat diet, obesity, gut microbiota, fecal microbiota transplantation

Chunyan Lei,1,2,* Qibo Ran,1,2,* Jianan Duan,1,2 Meixia Zhang1,2 1Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meixia Zhang, Department of Ophthalmology and Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 18980602236, Email zhangmeixia@scu.edu.cnIntroduction: Extensive studies have studied the factors associated with subfoveal choroidal thickness (SFCT). However, studies of the association between lipid profile and SFCT in patients with proliferative diabetic retinopathy (PDR) in type 2 diabetes remain limited. Thus, we aimed to investigate the relationship between lipid profile and SFCT in patients with PDR.Materials and Methods: This was a retrospective cross-sectional study. The included participants were inpatients who underwent vitrectomy for PDR with type 2 diabetes and contralateral eyes of PDR patients meeting the criteria. Multivariate linear regression analysis was used to determine the independent association between lipid profile and SFCT.Results: A total of 131 participants with PDR were enrolled in the final analysis. The average age of the participants was 55.76 ± 9.88 years, and the average SFCT was 276.10 ± 92.92 μm. Multivariate linear regression model results showed that in the fully adjusted model, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) had a negative association with SFCT (β = − 16.51, 95% CI: − 29.57, − 3.46; P = 0.0148; β = − 42.65, 95% CI: − 82.60, − 2.70; P = 0.0390; β = − 17.89, 95% CI: − 33.24, − 2.54; P = 0.0245, respectively), while triglyceride was not significantly associated with SFCT (β = 5.23, 95% CI: − 18.57, 29.02; P = 0.6678). Furthermore, the results of stratified analysis showed that except for triglyceride, the trends of total cholesterol, HDL-C, LDL-C, and SFCT were consistent among different stratifications in participants.Conclusion: The cholesterol profile had a significant negative association with SFCT in Chinese PDR patients, but triglyceride was not significantly associated with SFCT. This suggests that these systemic imbalances contribute to choroidal changes, and often coexist in diabetic patients.Keywords: cholesterol, subfoveal choroidal thickness, proliferative diabetic retinopathy, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol

Na Wang,1,* Minghua Zhan,2,* Teng Wang,3 Jinlu Liu,1 Caiqing Li,1 Baoliang Li,1 Xuying Han,1 Huiying Li,4 Shuting Liu,5 Jing Cao,1 Xinran Zhong,1 Chunmei Lei,1 Wei Zhang,1 Zhihua Zhang6 1Microbiology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 2Clinical Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 3Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 4Obstetrics and Gynecology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 5Hemodialysis Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 6Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang; Zhihua Zhang, Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, No. 14, Changqing Road, Zhangjiakou City, Hebei Province, 075000, People’s Republic of China, Tel +86-03138043503, Fax +86-1088326317, Email 15369318318@163.com; zzh19641229@163.comPurpose: Through long-term and large sample size statistical analysis, we revealed the pattern of Klebsiella pneumoniae (KP) infection and drug resistance and provided epidemiological data for the treatment and prevention and control of multidrug-resistant bacterial infection in our hospital.Patients and Methods: Strains were identified using the BD PhoenixTM 100 system, minimal inhibitory concentration of antibiotics were determined by the broth method, and data were statistically analyzed using WHONET 5.6 and SPSS27.0.Results: The isolation rate of KP from Enterobacteriaceae (26.2%, 4547/17358) in our hospital showed an increasing annual trend, ranking second only to Escherichia coli. Carbapenem-resistant KP (CRKP) accounted for the highest proportion of carbapenem-resistant Enterobacteriaceae (72.2%, 431/597), showing an upward trend. Infected patients had a male-to-female ratio of approximately 2:1 and were mainly > 60 years of age (66.2%), with intensive care units being the most commonly distributed department. Sputum was the most common specimen type (74.0%). Compared with spring and summer, autumn and winter were the main epidemic seasons for KP and extended-spectrum β-lactamase KP (ESBL-KP). The resistance rate of KP to common antibiotics was low, but all showed an increasing trend each year. ESBL-KP was > 90% resistant to piperacillin, amoxicillin/clavulanic acid, and cefotaxime and less resistant to other common antibiotics, but showed an increasing trend in resistance to most antibiotics. CRKP resistance to common antibiotics was high, with resistance rates > 90%, excluding amikacin (64.1%), gentamicin (87.4%), cotrimoxazole (44.3%), chloramphenicol (13.6%), and tetracycline (30.5%).Conclusion: KP in our hospital mainly caused pulmonary infection in older men, which occurred frequently in autumn and winter, and the isolation and drug resistance rates showed an increasing trend. Age over 70 years, admission to intensive care unit, and urinary tract infection were found to be the risk factors for CRKP and ESBL-KP-resistance.Keywords: Klebsiella pneumoniae, antibacterial drugs, resistance trends, carbapenem-resistant, extended-spectrum β-lactamase, antimicrobial susceptibility surveillance

Yixuan Bai,1 Chenggang Lei,2 Na Zhang,1 Yuhui Liu,1 Zhengyu Hu,3 Yan Li,4 Ran Qi5 1Department of Digestive Internal Medicine, Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Hepatobiliary Surgery, Qingdao Municipal Hospital, Qingdao, People’s Republic of China; 3Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Gastroenterology, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Department of General Surgery, Tongji Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Ran Qi, Department of General Surgery, Tongji Hospital of Tongji University, School of Medicine, Tongji University, 389 Xincun Road, Putuo District, Shanghai, 200092, People’s Republic of China, Email 2011070@tongji.edu.cnAim: The aim of this study was to identify clinical endoscopic indicators related to peri-ulcerative mucosal inflammation and to analyze whether the degree of peri-ulcerative mucosal inflammation appearance is an independent risk factor for gastric ulcer rebleeding.Methods: We conducted a retrospective study that included patients with gastric ulcer bleeding who were hospitalized at three medical centers in China from January 1, 2016 to December 31, 2019. Ulcer rebleeding that occurred within 30 days of successful initial hemostasis was analyzed to determine whether this event was related to the degree of peri-ulcerative mucosal inflammation appearance or other mucosal inflammation-related factors.Results: We enrolled 1111 patients and determined that GBS-Rebleeding-ROC (P< 0.001), age (P=0.01), use of NSAIDs (P=0.001), bile reflux (P< 0.001), and Helicobacter pylori (P< 0.001) are all risk factors for peri-ulcerative mucosal inflammation appearance. Through multivariate analysis, we determined that severe peri-ulcerative mucosal inflammation appearance (P=0.002) was an independent risk factor for ulcer rebleeding within 30 days. Finally, we developed a risk assessment model using factors associated with mucosal inflammation that may be useful for early prediction of rebleeding.Conclusion: The risk factors for peri-ulcerative mucosal inflammation appearance were identified. Severe peri-ulcerative mucosal inflammation appearance is an independent risk factor for ulcer rebleeding.Keywords: gastric ulcer, peptic ulcer bleeding, risk factors, rebleeding, peri-ulcerative mucosal inflammation

Binyi Yang,1– 3,* Cheng Lei,1– 3,* Danhui Yang,1– 3 Chenyang Lu,1– 3 Yingjie Xu,1– 3 Lin Wang,1– 3 Ting Guo,1– 3 Rongchun Wang,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongchun Wang; Hong Luo, Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email 198202060@csu.edu.cn; luohonghuxi@csu.edu.cnBackground: OFD1 encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. OFD1 was reported to be associated with X-chromosome linked dysmorphology syndrome in early studies and recent studies reported a few cases with primary ciliary dyskinesia (PCD) caused by OFD1 deficiency.Case Presentation: We report a 31-year-old man who suffered from recurrent respiratory infections with typical manifestations of primary ciliary dyskinesia. In addition to respiratory manifestations, the patient also had situs inversus, obesity, gastroesophageal reflux, and hearing impairment. Clubbing fingers and mild streblomicrodactyly were also observed.Examination Result: We performed whole-exome sequencing to identify a novel variant c.2795delA:p.(Lys932Argfs*3) in OFD1. The hemizygous variant was predicted to be likely pathogenic by bioinformatic analysis software and ACMG guideline. High-speed video microscopy (HSVM), transmission electron microscopy (TEM), and immunofluorescence were performed to analyze the respiratory cilia. A high beating frequency and a stiff beating pattern were observed under HSVM, while there were no significant abnormalities in TEM and immunofluorescence. The sperm flagella examinations were also generally normal.Conclusion: Our study identified a novel frameshift variant in OFD1 causing PCD, enriched the genetic spectrum of OFD1 variants, and verified that OFD1 mutation can lead to only a PCD characteristic phenotype, while other OFD1-associated syndromic symptoms such as dysmorphic features and renal symptoms were not present.Keywords: OFD1, primary ciliary dyskinesia, cilia, situs inversus

Tianyong Han,1,&ast; Tao Cheng,1,&ast; Ye Liao,2 Qiang Lai,1 Shiyuan Tang,1 Bofu Liu,1 Yarong He,1 Chenxi Lei,1 Yuling Cao,3 Yu Cao1 1Emergency Department, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Medical Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Operations Management Department, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cao, Emergency Department, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 28-85422288, Email caoyu@wchscu.cnPurpose: The thrombo-inflammatory prognostic score (TIPS) and the bedside index for severity in acute pancreatitis (BISAP) are both scoring systems that enable the rapid prognostic assessment of early-stage acute pancreatitis (AP) patients, but the overall prognostic utility of these individual systems is limited. This study was thus developed to explore whether a combination of TIPS and BISAP scores would offer better insight to facilitate the risk stratification of AP patients.Methods: This single-center retrospective cohort research evaluated AP cases referred to the emergency department from January 1, 2017 to September 30, 2017. The ability of TIPS scores to improve BISAP-based AP patient risk stratification was appraised employing the curves of receiver-operating characteristic (ROC) and decision curve analysis (DCA) approaches. The initial endpoint for this research was 28-day mortality, while secondary endpoints comprised intensive care unit admission (AICU) and mechanical ventilation (MV) over a 28-day follow-up period.Results: Totally, 440 cases enrolled in the current study were divided at a ratio of 1:1 to derivation and validation cohorts. When estimating 28-day mortality, the combination of TIPS and BISAP (T-BISAP) improved the area under the curve (AUC) value in the derivation group from 0.809 to 0.903 (P

Yingjie Xu,1– 3,* Binyi Yang,1– 3,* Cheng Lei,1– 3 Danhui Yang,1– 3 Shuizi Ding,1– 3 Chenyang Lu,1– 3 Lin Wang,1– 3 Ting Guo,1– 3 Rongchun Wang,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongchun Wang; Hong Luo, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Furong District, Changsha, Hunan, 410011, People’s Republic of China, Email 198202060@csu.edu.cn; luohonghuxi@csu.edu.cnAbstract: Primary ciliary dyskinesia (PCD) is a rare genetic disease caused by mutations of genes coding motile-cilia-related proteins. CCDC40 variants can cause PCD via disrupting the assembling of inner dynein and dynein regulating complex in cilia and flagella, but none has been reported associated with multiple morphological abnormalities of the sperm flagella (MMAF). We identified and validated the disease-causing variants in our patient via whole-exome and Sanger sequencing. We used high-speed video microscopy analysis (HSVA) and immunofluorescence to analyze the functional and structural deficiency of respiratory cilia. Papanicolaou staining and scanning electron microscope was applied to analyze the morphological sperm defects resulted from the PCD associated variants. We identified novel compound variants (c.901C>T, p.(Arg301*); c.2065_2068dup, p.(Ala690Glyfs*67)) in CCDC40 in a male patient with male infertility. HSVA revealed the rigid and stiff ciliary beating pattern. Immunofluorescence indicated loss of inner dynein arm protein DNAH2 both in cilia and the sperms of the patient. Diagnosis of MMAF was confirmed through sperm Papanicolaou staining and scanning electron microscope. We first describe a patient with a combination of PCD and MMAF associated with novel compound heterozygous variants in CCDC40. Our results present initial evidence that CCDC40 associated with MMAF, which expands the genetic spectrum of PCD and MMAF and provides precise clinical genetic counseling to this family.Keywords: PCD, MMAF, CCDC40, male infertility

Tianyong Han,1,&ast; Tao Cheng,1,&ast; Ye Liao,2 Shiyuan Tang,1 Bofu Liu,1 Yarong He,1 Zhihan Gu,1 Chenxi Lei,1 Yuling Cao,3 Yu Cao1 1Emergency Department, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Medical Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Operations Management Department, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cao, Emergency Department, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan, People’s Republic of China, Tel +028-85422288, Email caoyu@wchscu.cnPurpose: At present, simple, accurate, and efficient prognostic tools for the evaluation of cases with early-stage sepsis in the emergency department (ED) are lacking. An increased blood urea nitrogen to albumin ratio (BAR) has previously been shown to be a valuable biomarker with predictive utility in several diseases. The relationship between BAR and sepsis patient outcomes, however, is not well-understood. This exploration was thus developed for the exploration of the link between BAR values and the short-term prognosis of cases with sepsis.Methods: This was a retrospective cohort research of sepsis cases admitted to the West China Hospital of Sichuan University ED from July 2015 to June 2016. Laboratory data were collected upon ED admission, and 7-day all-cause mortality was the primary study endpoint. Relationships between BAR values and APACE II and SOFA scores were generated assessed with correlation coefficient heatmaps. Independent risk factors were identified through multivariate analyses, with the curves of receiver operating characteristic (ROC) being employed to gauge the value of BAR as a predictor of the risk of mortality in sepsis cases.Results: In sum, 801 patients participated in the present investigation. BAR values were strongly correlated with APACHE II and SOFA scores. In a multivariate logistic regression assessment, BAR was identified as an independent predictor of mortality among patients with sepsis (HR=1.032, 95% CI: 1.010– 1.055, P=0.004). BAR exhibited an AUC of 0.741 (95% CI: 0.688– 0.793, P< 0.001) when used to predict patient mortality risk, with 5.27 being the optimal BAR cut-off.Conclusion: We found that BAR can be used as a reliable biomarker to predict mortality in patients with sepsis.Keywords: sepsis, blood urea nitrogen-to-albumin ratio, risk factors, prognosis

Tianyong Han,1,&ast; Tao Cheng,1,&ast; Ye Liao,2 Yarong He,1 Bofu Liu,1 Qiang Lai,1 Pan Pan,1 Junzhao Liu,1 Chenxi Lei,1 Yu Cao1 1Emergency Department, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Medical Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu CaoEmergency Department, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan, People’s Republic of China, Tel +86 28-85422288, Email caoyu@wchscu.cnBackground: Acute pancreatitis (AP) is a multifactorial disease that is associated with substantial morbidity and mortality. Thrombosis and inflammation are involved in the development and progression of AP.Aim: To develop and validate a novel and simple scoring system for predicting 28-day adverse outcomes in AP patients based on a thrombotic and an inflammatory biomarker.Methods: A single-center, retrospective cohort study was used to establish the new scoring system (thrombo-inflammatory prognostic score; TIPS), and another study was used to verify it. The study end points were 28-day mortality, requirement for mechanical ventilation (MV), persistent organ failure (POF), and admission to the intensive care unit (AICU). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the TIPS. The performance of the TIPS was compared with that of conventional predictive scoring systems. Logistic regression models were used to investigate the relationship between the TIPS and the different end points.Results: Among 440 patients with AP in the derivation group, 27 patients died within the 28-day follow-up period. Prothrombin time (PT) and interleukin-6 (IL-6) were used to calculate the TIPS. The TIPS (AUC=0.843) showed a performance comparable to that of the more established APACHE II (AUC=0.841), SOFA (AUC=0.797), BISAP (AUC=0.762), and Balthazar CT (AUC=0.655) in predicting 28-day mortality in AP. The 28-day mortality and the incidence of MV, POF, and AICU were significantly higher among patients with a higher TIPS (P< 0.001). The results of logistic regression analyses indicated that the TIPS was independently associated with the risks of 28-day mortality, AICU, MV and POF.Conclusion: The TIPS can enable prediction of 28-day adverse clinical outcomes with AP patients in the ED.Keywords: acute pancreatitis, prognosis, clinical outcomes, thrombosis, inflammation

Chenyang Lu,1– 3,* Danhui Yang,1– 3,* Cheng Lei,1– 3 Rongchun Wang,1– 3 Ting Guo,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, People’s Republic of China; 3Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Luo; Ting GuoDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Furong District, Changsha, Hunan, 410011, People’s Republic of ChinaEmail luohonghuxi@csu.edu.cn; guotingxy@csu.edu.cnBackground: Dynein axonemal assembly factor 2 (DNAAF2) is involved in the early preassembly of dynein in the cytoplasm, which is essential for motile cilia function. Primary ciliary dyskinesia (PCD) associated with DNAAF2 variants has rarely been reported in females with infertility. Moreover, there is no report linking DNAAF2 to scoliosis in human.Materials and Methods: We recruited patients from two consanguineous families with a clinical diagnosis of PCD and collected their clinical history, laboratory tests, and radiographic data. Sequencing and bioinformatics analysis were then performed. Immunofluorescence and high-speed microscope analysis were used to support the pathogenicity of the variant.Results: Proband 1, a 26-year-old female from family I, exhibited scoliosis, bronchiectasis, sinusitis, situs inversus, and infertility. We found a novel homozygous missense variant in DNAAF2, c.491T>C, p.(Leu164Pro) in this patient. Subsequent immunofluorescence indicated the absence of outer dynein arm and inner dynein arm of cilia, and high-speed microscopy analysis showed that the most of the cilia are static, which support the pathogenicity of this variant. Proband 2, a 53-year-old female, presented with bronchiectasis, sinusitis, and infertility. In this patient, a new homozygous frameshift variant DNAAF2, c.822del, p.(Ala275Profs*10) was identified. The disease-causing variants mentioned above are not included in the current authorized genetic databases.Conclusion: Our findings expand the spectrum of DNAAF2 variants and link DNAAF2 to female infertility and likely scoliosis in patients with PCD.Keywords: primary ciliary dyskinesia, scoliosis, DNAAF2, bronchiectasis, situs inversus, female infertility

Yun Lan,&ast; Xizi Deng,&ast; Linghua Li, Weiping Cai, Junbin Li, Xiaoli Cai, Feng Li, Fengyu Hu, Chunliang Lei, Xiaoping Tang Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunliang Lei; Xiaoping TangGuangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou, 510030, People’s Republic of ChinaEmail gz8hlcl@126.com; tangxp@gzhmu.edu.cnBackground: Guangdong, located in South China, is one of the areas heavily affected by HIV-1 in China. The transmission of HIV-1 among men who have sex with men (MSM) has gradually been increasing in Guangdong.Objective: To investigate the characteristics of the HIV-1 drug resistance, and genetic transmission networks in MSM with antiretroviral therapy (ART) failure from 2014 to 2019 in Guangdong.Methods: HIV-1 pol gene sequences were amplified. An online subtyping tool was used to determine the genotype, and a maximum likelihood phylogenetic tree was reconstructed to confirm the genotype results. The Stanford University HIV Drug Resistance Database was used to analyse the sequences of drug resistance mutations (DRMs) and drug resistance profiles. A pairwise Tamura-Nei 93 genetic distance-based method was used to analyse the genetic transmission networks.Results: Of 393 sequences isolated from HIV-infected MSM with ART failure, CRF01_AE (47.3%), CRF07_BC (21.4%) and CRF55_01B (21.4%) were the top three strains. 55.2% individuals harboured NRTI DRMs, whereas 67.4% carried NNRTI DRMs. 96.8% cases harboured mutations resistance to NRTIs or NNRTIs at high-level. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). Of the subtype B sequences, no sequence fell into a cluster. Of the CRF01_AE, CRF55_01B, and CRF59_01B sequences, 14.5%, 61.9%, and 33.3% fell into clusters, respectively. Of the CRF07_BC sequences, 39.3% fell into clusters. The majority of MSM in transmission networks were concentrated at age below 35 years old, with multiple links. Moreover, approximately 54.8% of MSM had more than 2 potential transmission partners.Conclusion: Drug resistance mutations more frequently occurred in NNRTIs among MSM with ART failure in Guangdong Province. Transmission network analysis revealed a complex transmission pattern, and more attention should be given to younger HIV-1-infected MSM with multiple links.Keywords: HIV-1, drug resistance, genetic transmission networks, MSM

Chunhong Shi,1 Zhihua Guo,2 Chan Luo,3 Changbin Lei,4 Pan Li1 1School of Nursing, Xiangnan University, Chenzhou 423000, People’s Republic of China; 2Nursing Department, Changsha Health Vocational College, Changsha 410100, People’s Republic of China; 3Nursing Department, The First Affiliated Hospital of University of South China, Hengyang 421001, People’s Republic of China; 4Clinical Medicine Research Center, Affiliated Hospital of Xiangnan University, Chenzhou 423000, People’s Republic of ChinaCorrespondence: Changbin LeiClinical Medicine Research Center, Affiliated Hospital of Xiangnan University, No. 25 Renmin West Road, Beihu District, Chenzhou, 423000 Hunan, People’s Republic of ChinaTel +86 13762563779Fax +86-735-2223633Email leichangbin@xnu.edu.cnPan LiSchool of Nursing, Xiangnan University, 889 Chenzhou Avenue, Suxian District, Chenzhou, 423000 Hunan, People’s Republic of ChinaTel +86 17773560292Fax +86-735-2325007Email lipan1020@xnu.edu.cnPurpose: This study aimed to assess the psychological impact of the COVID-19 pandemic among the general public in Hunan Province, China, which could help develop psychological interventions and mental health programs.Participants and Methods: This online cross-sectional study recruited 571 participants through snowball sampling between February 2 and February 5, 2020. Data were collected through a general information questionnaire, the Public Emergency Psychological State Questionnaire, the Simple Coping Style Questionnaire, and the Public Disease Awareness on COVID-19 Scale.Results: The total mean score of the public emergency psychological state of the sample was 0.27 (0.31) points, with only 5.78% of participants (n = 33) developing psychological distress. Avoidant coping style and disease awareness were weakly positively correlated (rs = 0.257, p < 0.01) and weakly negatively correlated (rs = − 0.124, p < 0.01) with psychological responses, respectively. There were significant psychological differences among the following variables: occupation, symptoms of fever or fatigue, discernment of the authenticity of COVID-19 information, and level of concern regarding COVID-19 (p < 0.05).Conclusion: The COVID-19 pandemic appears to have had a minor psychological impact on the general population in Hunan Province. However, psychological health promotion in the general public is still required, especially for employees (such as company employees, migrant workers, and businessmen), individuals with COVID-19-like symptoms, limited discernment competence and unconcerned attitudes.Implications: The initiatives for improving psychological health among the general public could focus on delivering COVID-19 knowledge and alleviating avoidant coping styles. Our findings could provide important insight for the development of psychological support strategies in China, as well as in other places affected by the epidemic.Keywords: coping style, coronavirus disease 2019, disease awareness, psychological health, public health emergency

Xiuying Shan,1,* Wenjun Yu,1,* Xuejun Ni,1,* Tingting Xu,1 Chen Lei,1 Zhaoliang Liu,1 Xuefeng Hu,2 Yanding Zhang,2 Beichen Cai,1 Biao Wang1 1Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2College of Life Sciences, Fujian Normal University, Fuzhou 350108, People’s Republic of China*These authors contributed equally to this workCorrespondence: Biao Wang Email wangbiao@fjmu.edu.cnPurpose: Angiopoietin-2 (Ang-2) has been proven to be a potential agent for malignant cancer treatment. The aim of the current study was to investigate the inhibitory effects of chitosan magnetic nanoparticles (CMNPs) loaded with Ang-2 small interfering RNA (Ang2-siRNA) plasmids (Ang2-CMNPs) on malignant melanoma.Materials and Methods: Melanoma-bearing nude mice were treated with Ang2-CMNPs and control CMNPs. Tumor volumes in each group were recorded. Real-time fluorescence quantitative-PCR was used to measure the relative Ang-2gene expression. Angiogenesis and Ang-2 expression in tumors were measured by immunohistochemistry. Cell apoptosis in each group was measured by TUNEL staining, and the expression of Bax, Bcl-2 and cleaved caspase-3 was analyzed by immunohistochemistry.Results: The progression of melanoma was significantly inhibited by Ang2-CMNP treatment. Ang2-CMNP treatment efficiently inhibited tumor growth and in-situ Ang-2 expression compared with those of the control group. Furthermore, Ang2-CMNP treatment significantly inhibited tumor angiogenesis and promoted cell apoptosis by regulating the Bax/Bcl-2 ratio and increasing cleaved caspase-3 expression in vivo.Conclusion: In summary, Ang2-CMNP treatment increased the regression of normal-appearing vessels in the tumor microenvironment and induced the melanoma cells apoptosis through the mitochondrial apoptotic pathway, suggesting the potential clinical use of Ang2-CMNPs in malignant melanoma treatment.Keywords: angiopoietin-2, small interfering RNA, malignant melanoma, chitosan magnetic nanoparticles, apoptosis

Xueli Zhao,1 Xuanying Wang,1 Jing Wang,1 Jiani Yuan,1 Juan Zhang,1 Xiaoli Zhu,1 Changhui Lei,1 Qianli Yang,1 Bo Wang,1 Feng Cao,2 Liwen Liu1 1Department of Ultrasound of Xijing Hospital, Xijing Hypertrophic Cardiomyopathy Center, Fourth Military Medical University, Xi’an 710032, People’s Republic of China; 2Department of Cardiology, Chinese PLA General Hospital, Beijing 100700, People’s Republic of ChinaCorrespondence: Liwen Liu Email liuliwen@fmmu.edu.cnIntroduction: Currently, the unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin has been demonstrated to ameliorate cardiac hypertrophy and its accompanied fibrosis in previous studies. But it is not clinically appealing due to its short-lasting time against the hostile microenvironment when administered orally.Methods: Herein, to address this, poly (lactide) polycarboxybetaine (PLGA-COOH) accompanied by cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) were used to establish a novel drug delivery and transportation strategy for melatonin via a facile two-step emulsion method. This study characterized these nanoparticles (CHP-mel@SPIONs) and tested their delivery to the hypertrophied heart and their effect on myocardial hypertrophy and fibrosis in an animal model of pressure overload-induced cardiac hypertrophy.Results: The engineered magnetic nanoparticles of CHP-mel@SPIONs were spherical (diameter = 221 ± 13 nm) and had a negative zeta potential of − 19.18 ± 3.27 mV. The CHP-mel@SPIONs displayed excellent drug encapsulation capacities of SPIONs (75.27 ± 3.1%) and melatonin (77.69 ± 6.04%) separately, and their magnetic properties were characterized by constructing magnetic hysteresis curves and exhibited no remnant magnetization or coercivity. The animal experiments showed that compared with mel@SPIONs, CHP-mel@SPIONs accumulated more in the heart, especially in the presence of an external magnetic field, with in vivo echocardiography and RT-PCR and histological assessments confirming the amelioration of the myocardial hypertrophy and fibrosis with low drug doses.Conclusion: This simple biocompatible dual-targeting nanoagent may be a potential candidate for the guided clinical therapy of heart disease.Keywords: magnetic targeting, cardiac homing peptide, cardiac hypertrophy, melatonin, myocardial fibrosis

Changjiang Lei,1,* Yao Yao,2,* Bin Shen,3,* Junru Liu,2,* Qingyun Pan,4,* Ning Liu,1 Lei Li,1 Jianbin Huang,1 Zhixiong Long,2 Liwei Shao1 1Department of General Surgery, Fifth Hospital in Wuhan, Wuhan, Hubei 430050, People’s Republic of China; 2Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430050, People’s Republic of China; 3Department of Hepatobiliary Surgery, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing 314001, Zhejiang, People’s Republic of China; 4Department of Blood Endocrinology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhixiong LongDepartment of Oncology, The Fifth Hospital of Wuhan, No. 122, Xian Zheng street, Hanyang District, Wuhan 430000, Hubei, People’s Republic of ChinaTel +86 1 850 719 9619Email 2428850630@qq.com Liwei ShaoDepartment of General Surgery, The Fifth Hospital of Wuhan, No. 122, Xian Zheng street, Hanyang District, Wuhan 430000, Hubei, People’s Republic of ChinaTel +86 1 387 105 8697Email b18310715028@163.comBackground: Colon cancer is one of the most common malignancies worldwide. Because of the side effects and defects in tolerance of chemotherapy, it is necessary to discover new drugs for colon cancer treatment. Columbamine has been identified as an effective anti-osteosarcoma compound with only minor side effects. In this study, we analyzed the anticancer effect of columbamine on colon cancer.Methods: Human colon cancer cell lines were treatment with columbamine. MTT assay, colony formation assay, apoptosis detection and tumorigenicity assay were performed to detect the protective effect of columbamine on colon cancer development. Western blot assay and luciferase reporter assay were conducted to investigate the potential mechanism of the columbamine treatment.Results: Columbamine significantly inhibited the proliferation, migration, invasion process of colon cancer cells, and dramatically promoted the apoptosis rate of colon cancer cells to further suppress the development of colon cancer to tumor. Both the signaling transducing and key factors expression of Wnt/β-catenin signaling pathway were obviously repressed by columbamine treatment in a dose-dependent manner.Conclusion: The present study indicated that columbamine exerts its anti-tumor effect in colon cancer cells through abolishing Wnt/β-catenin signaling pathway. Columbamine may be a new therapy compound for colon cancer.Keywords: colon cancer, cells growth, apoptosis, HCT116, LoVo

Yak (Bos grunniens) is a unique livestock animal originating from the Qinghai-Tibet Plateau in China. In the current study, we investigated the maternal genetic diversity, differentiation and phylogeny of wild yak population and four domestic yak breeds (Qinghai-Gaoyuan, Huanhu, Xueduo, and Yushu) in Qinghai, China by analyzing 166 mitochondrial cytochrome b (Cytb) gene sequence variations. The results showed that the five yak breeds/populations had high genetic diversity (Hd = 0.501 ± 0.088–0.770 ± 0.053) and each yak breed/population owned unique haplotypes. Estimates of FST values showed a moderate genetic differentiation between wild yak and Huanhu yak (FST = 0.0577) as well as that between Huanhu yak and Yushu yak breeds (FST = 0.0520), but a weak genetic differentiation was observed between the other yak breeds/populations (–0.0209 < FST < 0.0372). Additionally, the clustering analysis based on RST values showed that Xueduo yak and Huanhu yak were clustered into one group, and each of the other three yak breeds/populations was separated into one group, respectively. Overall, the clustering relationship between wild yak and Yushu yak was closer. Maternal phylogenetic analysis showed that wild yak and four domestic yak breeds/populations in Qinghai represented in three maternal lineages (Mt-I, Mt-II, and Mt-III), indicating three maternal origins in yak. Our study would provide valuable information for the conservation and utilization of wild yak and Qinghai domestic yak breeds. [ABSTRACT FROM AUTHOR]