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Jiahao Guan,1,* Yihan Dong,1,2,* Wenli Zhang,3 Qiaodi Gui,1 Danxia Luo,4 Hongxia Wen,5 Xiaojun Dang,1 Daoyan Liang,1 Shuling Hu,1 Yaqin Zhang,1 Guimei Liao,2 Lixia Zhang,1 Zifan Lu6 1Department of Clinical Laboratory, Shaanxi Provincial People′s Hospital, Xi ′an, 710068, People’s Republic of China; 2Medical College, Yan’ an University, Yan’ an, Shaanxi, 716000, People’s Republic of China; 3Translational Medicine Center of Shaanxi Provincial People’s Hospital; Shaanxi Province Research Center of Cell Immunological Engineering and Technology, Xi’an, 710068, People’s Republic of China; 4The Gynecology Department of People’s Hospital of Shaanxi Province, Xi’an, 710068, People’s Republic of China; 5Department of Respiratory Medicine II, Shaanxi Provincial People’s Hospital, Xi’an, 710068, People’s Republic of China; 6Translational Medicine Center of Shaanxi Provincial People’s Hospital, Xi’an, 710068, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lixia Zhang; Zifan Lu, Shaanxi Provincial People′s Hospital, No. 256, Youyi West Road, Xi’an, Shaanxi Province, People’s Republic of China, Tel +86 029-85251331, Email 17791735548@163.com; pharmluzifan@163.comBackground: Vaginitis is a common disease of the reproductive system in women, causing discomfort in daily life. Many reports indicate that the causes of vaginitis are related to vaginal microecological disturbances. Therefore, treatment strategies to restore microecological balance have shown promising results in both basic research and clinical settings. Recent studies have highlighted the potential adjuvant role of vitamin D in the treatment of vaginitis while illustrating its role in maintaining microecological balance. Therefore, this study focused on the therapeutic effects of vitamin D on vaginitis.Methods: The study provided a statistical description of 5978 vaginitis patients who visited Shaanxi Provincial People’s Hospital, presenting data in absolute numbers (%) and mean ± standard deviation (median quartiles were used for non-normally distributed variables). The chi-square test and analysis of variance were employed to analyze the distribution of vitamin D levels among patients, factors influencing vitamin D levels, and the association between recurrence rates and vitamin D levels.Results: Vitamin D deficiency (57.74%) or insufficiency (22.20%) is prevalent among patients with vaginitis. Furthermore, vitamin D levels have an impact on the dominant bacterial species in the vagina, as well as catalase, acetylglucosaminidase, and the overall vaginal microecological status. Age and BMI have correlations with vitamin D levels. It is hypothesized that this relationship may be attributed to clinicians utilizing vitamin D as a supplementary treatment.Conclusion: This study examined the statistical findings of vitamin D-related data from 5978 vaginitis patients, revealing a positive correlation between vitamin D deficiency and vaginitis occurrence. Patients with vitamin D deficiency/severe deficiency showed weakly positive levels of catalase and mostly weakly positive levels of acetylglucosaminidase, and most of these vaginitis are trichomonas vaginalis (TV). Furthermore, older individuals and those with higher BMI were found to be more susceptible to symptoms of vitamin D deficiency.Keywords: Vitamin D, vaginal microecology, female reproductive system diseases

Dan Luo,1– 3,* Yonghui Hou,1– 3,* Jiheng Zhan,1,2,* Yu Hou,1– 3 Zenglu Wang,4 Xing Li,1,2 Lili Sui,5 Shudong Chen,1,2 Dingkun Lin1,2 1Research Laboratory of Spine Degenerative Disease, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Spinal Minimally Invasive Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3Laboratory of Osteology and Traumatology of Traditional Chinese Medicine, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4ICU Critical Care Medicine Department, Guangdong Second Provincial Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China; 5The First College of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dingkun Lin; Shudong Chen, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, People’s Republic of China, Tel +86-020-81887233, Email lindingkuntcm@126.com; chenshudong_med@163.comPurpose: Spinal cord injury (SCI) is an irreversible neurological disease that can result in severe neurological dysfunction. The Bu Shen Huo Xue Formula (BSHXF) has been clinically shown to assist in the recovery of limb function in patients with SCI. However, the underlying mechanisms of BSHXF’s therapeutic effects remain unclear. This study aimed to evaluate the effects of BSHXF in a mouse model of SCI and to identify potential therapeutic targets.Methods: The composition of BSHXF was analyzed using high-performance liquid chromatography (HPLC). In vivo, SCI was induced in mice following established protocols, followed by administration of BSHXF. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) and footprint tests. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were quantified with specific assay kits. Protein expression analysis was performed using Western blot and immunofluorescence. Additionally, reactive oxygen species (ROS) levels and apoptosis rates were evaluated with dedicated staining kits. In vitro, neurons were exposed to lipopolysaccharide (LPS) to investigate the effects of BSHXF on neuronal oxidative stress. The protective effects of BSHXF against LPS-induced neuronal injury were examined through RT-PCR, Western blot, and immunofluorescence.Results: The eight primary bioactive constituents of BSHXF were identified using HPLC. BSHXF significantly reduced tissue damage and enhanced functional recovery following SCI. Meanwhile, BSHXF treatment led to significant reductions in oxidative stress and apoptosis rates. It also reversed neuronal loss and reduced glial scarring after SCI. LPS exposure induced neuronal apoptosis and axonal degeneration; however, after intervention with BSHXF, neuronal damage was reduced, and the protective effects of BSHXF were mediated by the activation of the Nrf2 pathway.Conclusion: BSHXF decreased tissue damage and enhanced functional recovery after SCI by protecting neurons against oxidative stress and apoptosis. The effects of BSHXF on SCI may be related to the activation of the Nrf2 pathway.Keywords: Bu Shen Huo Xue formula, BSHXF, spinal cord injury, SCI, oxidative stress, neuroprotection, Nrf2 signaling pathway

Liubing Lan,1,2 Dandan Luo,1,2 Jianwen Lian,1 Lingna She,1,3 Bosen Zhang,1,3 Hua Zhong,1 Huaxian Wang,1 Heming Wu1 1Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Obstetrics, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Heming Wu, Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email wuheming1986@126.comObjective: Chromosomal microarray analysis (CMA) is a first-line test to assess the genetic etiology of fetal ultrasound abnormalities. The aim of this study was to evaluate the effectiveness of CMA in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities, including structural abnormalities and non-structural abnormalities.Methods: A retrospective study was conducted on 368 fetuses with abnormal ultrasound who received interventional prenatal diagnosis at Meizhou People’s Hospital from October 2022 to December 2023. Samples of villi, amniotic fluid, and umbilical cord blood were collected according to different gestational weeks, and karyotype and CMA analyses were performed. The detection rate of chromosomal abnormalities in different ultrasonic abnormalities was analyzed.Results: There were 368 fetuses with abnormal ultrasound, including 114 (31.0%) with structural abnormalities, 225 (61.1%) with non-structural abnormalities, and 29 (7.9%) with structural combined with non-structural abnormalities. The detection rate of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) of CMA in fetuses with structural abnormalities was 5.26% (6/114), the detection rate of karyotype was 2.63% (3/114), and the additional diagnosis rate of CMA was 2.63%. In the fetuses with ultrasonic non-structural abnormalities, the detection rate of karyotype was 6.22% (14/225), the detection rate of aneuploidy and P/LP CNVs in fetuses with ultrasonic structural abnormalities was 9.33% (21/225), and the additional diagnosis rate of CMA was 3.11%. There was no significant difference in chromosome abnormality detection rate of CMA among structural abnormality, non-structural abnormality, and structural abnormality combined with non-structural abnormality groups (5.3%, 9.3%, and 13.8%, p = 0.241), also among multiple ultrasonic abnormality and single ultrasonic abnormality groups (14.8%, and 7.3%, p = 0.105).Conclusion: CMA can significantly improve the detection rate of genetic abnormalities in prenatal diagnosis of ultrasonic abnormal fetuses compared with karyotype analysis. CMA is a more effective tool than karyotyping alone in detecting chromosomal abnormalities in fetuses with ultrasound abnormalities.Keywords: chromosomal microarray analysis, copy number variation, abnormal ultrasound fetus, prenatal diagnosis

Qiang Wang,* Pinduan Bi,* Ding Luo, Pingli Cao, Weihong Chen, Bin Yang Department of Hepatobiliary Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Yang, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, People’s Republic of China, Tel +86 013987642890, Email yangbin@kmmu.edu.cnBackground: Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression.Methods and Results: Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR.Conclusion: Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone.Keywords: gallstone, gallbladder cancer, long non-coding RNA, next-generation sequencing analysis, computational biology

Xiaoqing Wei,1,* Junying Zhang,2,* Youwen Mei,3 Eqiong Li,4 Qianling Dai,1 Xiaoli Yang,1 Dan Luo,5 Biao Li,6 Ping Hua,7 Jian Cai,7 Hua Lai,8 Dongfeng Qi,9 Sha Lai,10 Mi Qin,11 Yonghong Lin4 1Department of Cervical Disease and Cervical Cancer Prevention and Treatment, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2Clinical Laboratory Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Reproduction and Infertility, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 5Department of Obstetrics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 6Department of Neonatal Intensive Care Unit, Chengdu Women’ and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 7Department of Pathology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 8Department of Radiation and Interventional Therapy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 9Department of Ultrasonics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 10Dermatology Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 11Department of Pediatric Surgery, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong Lin; Xiaoqing Wei, Email linyhcd2011@163.com; xqcherry@163.comObjective: We report a case of Carmi Syndrome in a neonate.Aim: To share our lessons in diagnosis of the case of Carmi Syndrome.Case Report: Carmi Syndrome is an extremely rare autosomal recessive genetic disorder characterized the coexistence of pyloric atresia and junctional epidermolysis bullosa, and with aplasia cutis congenita in approximately 28% patients. In this case, a full-term male neonate was born to a G4P2+1L1 multipara through cesarean section delivery in hospital in a non-consanguineous marriage with 4000mL of II°meconium-stained amniotic fluid. He was found extensive skin loss over lower legs and other parts, with scattered blisters and bilateral microtia. Plain abdominal X-ray revealed a large gastric air bubble with no gas distally. The mother had an intrauterine fetal loss previously for reasons unknown. The dermatologist diagnosed the newborn with Bart Syndrome, while the pediatric surgeon diagnosed congenital pyloric atresia(CPA). The parents refused further treatment and the neonate passed away about 30 hours after birth.Outcome: The neonate passed away about 30 hours after birth.Conclusion: Lessons from this case:①.Rule out Carmi Syndrome in patients with PA, and differentiate Bart syndrome and Carmi Syndrome in patients with abnormal skin manifestations. ②. For rare and/or severe diseases, multidisciplinary teams(MDTs) should be establish. ③. Genetic counseling and prenatal diagnosis are necessary prior to subsequent childbearings. ④.Termination of pregnancy might be contemplated if certain indicators are revealed.Keywords: Carmi syndrome, bart syndrome, epidermolysis bullosa, EB, junctional epidermolysis bullosa, JEB, congenital pyloric atresia, CPA, aplasia cutis congenita, ACC, congenital localized absence of skin, CLAS, pyloric atresia, PA, epidermolysis bullosa with pyloric atresia, EB-PA, multidisciplinary teams, MDT

Xin Chen,1– 3,&ast; Xing Zhong,1,4,&ast; Dan Luo,1– 3,&ast; Yuhua Lei,1– 3 Rui Huang1– 3 1Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshii, Hubei Province, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshii, Hubei Province, People’s Republic of China; 4Department of Medicine, Hubei Minzu University, Enshi, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhua Lei; Rui Huang, Email yuhualei0319@163.com; henry0923@whu.edu.cnBackground: Heart failure (HF) is a chronic disease with a poor prognosis, making it extremely important to assess the prognosis of patients with HF for accurate treatment. Secreted modular calcium-binding protein 2 (SMOC2) is a cysteine-rich acidic secreted protein that plays a pathophysiological role in many diseases, including regulation of vascular growth factor activity. It has previously been found that SMOC2 plays an essential role in cardiac fibrosis in our previous preclinical study, but whether it can be used as a clinical marker in heart failure patients remains unclear. The purpose of this research was to evaluate the correlation between plasma levels of SMOC2 and the prognosis for individuals with HF.Methods: HF patients diagnosed with ischemic cardiomyopathy were enrolled from January to December 2021. Baseline plasma levels of SMOC2 were measured after demographic and clinical features were collected. Linear and nonlinear multivariate Cox regression models were used to determine the association between plasma SMOC2 and patient outcomes during follow-up. All analysis was performed using SPSS, EmpowerStats, and R software.Results: The study included 188 patients, and the average follow-up time was 489.5± 88.3 days. The plasma SMOC2 concentrations were positively correlated with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), left ventricular end-diastolic diameter (LVEDd), and length of hospital stay and were negatively correlated with left ventricular ejection fraction (LVEF) at baseline. A total of 53 patients (28.2%) were rehospitalized due to cardiac deterioration, 14 (7.4%) died, and 37 (19.7%) developed malignant arrhythmias. A fully adjusted multivariate COX regression model showed that SMOC2 is associated with readmission (HR = 1.02, 95% CI:1.012– 1.655). A significant increase in rehospitalization risk was observed in group Q2 (HR =1.064, 95% CI: 1.037, 3.662, p=0.005) and group Q3 (HR =1.085, 95% CI:1.086, 3.792, p=0.009) in comparison with group Q1. The p for trend also shows a linear correlation across the three models (P < 0.001). SMOC2 was associated with the severity of HF in patients, but not with all-cause deaths and arrhythmias during follow-up.Conclusion: Plasma SMOC2 is associated with the severity of HF and readmission rate, and is a good predictor of the risk of readmission in patients.Keywords: SMOC2, heart failure, ischemic cardiomyopathy, readmission rate, myocardial fibrosis

Jiao Chen, Danmei Luo, Chengxia Sun, Xiaolan Sun, Changmao Dai, Xiaohong Hu, Liangqing Wu, Haiyan Lei, Fang Ding, Wei Chen, Xueping Li Geriatric Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xueping Li, Chengdu University of Traditional Chinese Medicine, No. 37, Shier Bridge Road, Chengdu, Sichuan, People’s Republic of China, Tel +86-18380251086, Email 3173907@qq.comPurpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults.Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a “non-re-positive” group and a “re-positive” group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model’s goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively.Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was > 8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was > 80%, the positive estimated value was closer to the actual number of cases.Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.Keywords: malnutrition, COVID-19, re-positive, clinical prediction model

Dan Luo,1,2,&ast; Bo-Yi Yang,3,&ast; Kai Qin,4 Chong-Yu Shi,3 Nian-Sa Wei,4 Hai Li,1 Yi-Xiang Qin,1 Gang Liu,1 Xiao-Ling Qin,1 Shi-Yi Chen,1 Xiao-Jing Guo,1 Li Gan,1 Ruo-Lan Xu,1 Bai-Qing Dong,1 Jing Li5 1Department of Biostatistics, School of Public Health and Management of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 3The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4The Second Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Deparment of Physiology, School of Basic Medical Sciences of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bai-Qing Dong, Guangxi University of Chinese Medicine, 13 Wuhe Road, Nanning, Guangxi, 530200, People’s Republic of China, Tel/Fax +86-771-4928360, Email 764937318@qq.com Jing Li, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +86-771-5358212, Email lijing@gxmu.edu.cnPurpose: Distinguishing latent tuberculosis infection (LTBI) from active tuberculosis (ATB) is important to control the prevalence of tuberculosis; however, there is currently no effective method. The aim of this study was to discover specific metabolites through fecal untargeted metabolomics to discriminate ATB, individuals with LTBI, and healthy controls (HC) and to probe the metabolic perturbation associated with the progression of tuberculosis.Patients and Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to comprehensively detect compounds in fecal samples from HC, LTBI, and ATB patients. Differential metabolites between the two groups were screened, and their underlying biological functions were explored. Candidate metabolites were selected and enrolled in LASSO regression analysis to construct diagnostic signatures for discriminating between HC, LTBI, and ATB. A receiver operating characteristic (ROC) curve was applied to evaluate diagnostic value. A nomogram was constructed to predict the risk of progression of LTBI.Results: A total of 35 metabolites were found to exist differentially in HC, LTBI, and ATB, and eight biomarkers were selected. Three diagnostic signatures based on the eight biomarkers were constructed to distinguish between HC, LTBI, and ATB, demonstrating excellent discrimination performance in ROC analysis. A nomogram was successfully constructed to evaluate the risk of progression of LTBI to ATB. Moreover, 3,4-dimethylbenzoic acid has been shown to distinguish ATB patients with different responses to etiological tests.Conclusion: This study constructed diagnostic signatures based on fecal metabolic biomarkers that effectively discriminated HC, LTBI, and ATB, and established a predictive model to evaluate the risk of progression of LTBI to ATB. The results provide scientific evidence for establishing an accurate, sensitive, and noninvasive differential diagnosis scheme for tuberculosis.Keywords: feces, latent tuberculosis infection, active tuberculosis, biomarkers, progression, metabolomics

Kui Liu,1,&ast; Mengdie Zhang,2,&ast; Dan Luo,3 Yan Zheng,4 Zhenye Shen,4 Bin Chen,1 Jianmin Jiang1,5 1Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Social Medicine of School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Tuberculosis Control and Prevention, Fenghua Center for Disease Control and Prevention, Ningbo, Zhejiang Province, People’s Republic of China; 5Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Chen; Jianmin Jiang, Email Bchen@cdc.zj.cn; Jmjiang@cdc.zj.cnBackground: Pulmonary tuberculosis (PTB) is a serious infectious disease, and the factors and pathways that influence final treatment outcomes are unclear. Here, we aimed to assess the factors that influence treatment outcomes in patients with PTB using a structural equation model.Methods: Participants completed a questionnaire covering demographics, understanding of PTB, psychological status, and history of medical treatment. Exploratory factor analysis and reliability testing were performed, and a structural equation model was constructed using the SPSS and Amos software.Results: A total of 251 participants were enrolled. Symptoms of depression were observed in 94.4% of participants, whereas 6% showed mild or greater anxiety. Through factor rotation, four common factors were extracted with a total variation of 66.15%. The structural equation model indicated that regular tuberculosis-related follow-up behaviour had a direct and positive effect on the final treatment outcome, with a path coefficient value of 0.20; the level of PTB understanding had a direct positive effect on the testing behaviour for PTB, with a path coefficient of 0.26; patients’ psychological characteristics had a direct negative impact on regular testing behaviour, with a path coefficient of − 0.13. The psychological characteristics and level of disease understanding of patients exerted indirect effects on the treatment outcome by affecting the way patients approached tuberculosis detection behaviour.Conclusion: Interventions aimed at improving the treatment outcomes of patients with PTB should mainly focus on financial support and improvements in psychological status in addition to a greater understanding and knowledge of PTB. Furthermore, patients should be encouraged to undergo regular PTB testing during the follow up period, as this mediates the effect of other factors on treatment outcomes and also helps in achieving favourable treatment outcomes.Keywords: pulmonary tuberculosis, structural equation model, treatment outcome, depression

Dabin Liang,1,2,&ast; Zexuan Song,3,&ast; Xiaoyan Liang,1,2,&ast; Huifang Qin,1,2 Liwen Huang,1,2 Jing Ye,1,2 Rushu Lan,4 Dan Luo,5 Yanlin Zhao,3 Mei Lin1,2 1Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi, People’s Republic of China; 2Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Nanning, Guangxi, People’s Republic of China; 3National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China; 5School of Public Health and Management, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlin Zhao, National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing, 102206, People’s Republic of China, Email zhaoyl@chinacdc.cn Mei Lin, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, 530023, People’s Republic of China, Email gxlinmei@126.comBackground: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health issue in China. Nevertheless, the prevalence and drug resistance characteristics of isolates vary in different regions and provinces. In this study, we investigated the population structure, transmission dynamics and drug-resistant profiles of Mtb in Guangxi, located on the border of China.Methods: From February 2016 to April 2017, 462 clinical M. tuberculosis isolates were selected from 5 locations in Guangxi. Drug-susceptibility testing was performed using 6 common anti-tuberculosis drugs. The genotypic drug resistance and transmission dynamics were analyzed by the whole genome sequence.Results: Our data showed that the Mtb in Guangxi has high genetic diversity including Lineage 1 to Lineage 4, and mostly belong to Lineage 2 and Lineage 4. Novelty, 9.6% of Lineage 2 isolates were proto-Beijing genotype (L2.1), which is rare in China. About 12.6% of isolates were phylogenetically clustered and formed into 28 transmission clusters. We observed that the isolates with the high resistant rate of isoniazid (INH, 21.2%), followed by rifampicin (RIF, 13.2%), and 6.7%, 12.1%, 6.7% and 1.9% isolates were resistant to ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and kanamycin (KAN), respectively. Among these, 6.5% and 3.3% of isolates belong to MDR-TB and Pre-XDR, respectively, with a high drug-resistant burden. Genetic analysis identified the most frequently encountered mutations of INH, RIF, EMB, SM, OFL and KAN were katG_Ser315Thr (62.2%), rpoB_Ser450Leu (42.6%), embB_Met306Vol (45.2%), rpsL_Lys43Arg (53.6%), gyrA_Asp94Gly (29.0%) and rrs_A1401G (66.7%), respectively. Additionally, we discovered that isolates from border cities are more likely to be drug-resistant than isolates from non-border cities.Conclusion: Our findings provide a deep analysis of the genomic population characteristics and drug-resistant of M. tuberculosis in Guangxi, which could contribute to developing effective TB prevention and control strategies.Keywords: tuberculosis, Mycobacterium tuberculosis, drug-resistance, genetic diversity, whole genome sequencing

Jiafa Wu,1 Dongping Luo,2 Jiayun Xu2 1School of Food and Bioengineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, People’s Republic of ChinaCorrespondence: Jiafa Wu, School of Food and Bioengineering, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, People’s Republic of China, Email wujiafa@haust.edu.cn Jiayun Xu, The First Affiliated Hospital, Henan University of Science and Technology, Guanlin Avenue 636, Luoyang, People’s Republic of China, Email xujy_haust@163.comBackground: Breast cancer is a highly malignant tumor that affects a large number of women worldwide. Sesamol, a natural compound, has been shown to exhibit inhibitory effects on various tumors, including breast cancer. However, the underlying mechanism of its action has not been fully explored. In this study, we aimed to investigate the effect of sesamol on the transcriptome of MCF-7 breast cancer cells, in order to better understand its potential as an anti-cancer agent.Methods: The transcriptome profiles of MCF-7 breast cancer cells treated with sesamol were analyzed using Illumina deep-sequencing. The differentially expressed genes (DEGs) between the control and sesamol-treated groups were identified, and GO and KEGG pathway analyses of these DEGs were conducted using ClueGO. Protein–protein interaction (PPI) network of DEGs was mapped on STRING database and visualized by Cytoscape software. Hub genes in the network were screened by Cytohubba plugin of Cytoscape. Prognostic values of hub genes were analyses by the online Kaplan–Meier plotter and validated by qRT-PCR in MCF-7 cells.Results: The results of the study showed that sesamol treatment had a significant effect on the transcriptome of MCF-7 cells, with a total of 351 DEGs identified. Functional enrichment analyses of DEGs revealed their involvement in extracellular matrix (ECM) remodeling, fatty acid metabolism and monocyte chemotaxis. The protein–protein interaction (PPI) network analysis of DEGs resulted in the identification of 10 hub genes, namely IGF2, MMP1, MSLN, CXCL10, WT1, ITGAL, PLD1, MME, TWIST1, and FOXA2. Survival analysis showed that MMP1 and ITGAL were significantly associated with overall survival (OS) and recovery-free survival (RFS) in breast cancer patients.Conclusion: Sesamol may play important roles in extracellular matrix (ECM) remodeling, fatty acid metabolism and cell cycle of MCF-7.Keywords: breast cancer cells, sesamol, transcriptome, differentially expressed genes, GO and KEGG pathway analyses

Yamei Cui,&ast; Ying Yang,&ast; Wenqiang Tao, Wei Peng, Deqiang Luo, Ning Zhao, Shuangyan Li, Kejian Qian, Fen Liu Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fen Liu, Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Dong Lake District, Nanchang, 330000, People’s Republic of China, Tel +86 0791 88692533, Email liufen9934@163.comBackground: Uncontrolled inflammation is a typical feature of sepsis-related lung injury. The key event in the progression of lung injury is Caspase-1-dependent alveolar macrophage (AM) pyroptosis. Similarly, neutrophils are stimulated to release neutrophil extracellular traps (NETs) to participate in the innate immune response. This study aims to illustrate the specific mechanisms by which NETs activate AM at the post-translational level and maintain lung inflammation.Methods: We established a septic lung injury model by caecal ligation and puncture. We found elevated NETs and interleukin-1b (IL-1β) levels in the lung tissues of septic mice. Western blot and immunofluorescence analyses was utilized to determine whether NETs promote AM pyroptosis and whether degrading NETs or targeting the NLRP3 inflammasome had protective effects on AM pyroptosis and lung injury. Flow cytometric and co-immunoprecipitation analyses verified intracellular reactive oxygen species (ROS) levels and the binding of NLRP3 and ubiquitin (UB) molecules, respectively.Results: Increased NETs production and IL-1β release in septic mice were correlated with the degree of lung injury. NETs upregulated the level of NLRP3, followed by NLRP3 inflammasome assembly and caspase-1 activation, leading to AM pyroptosis executed by the activated fragment of full-length gasdermin D (FH-GSDMD). However, the opposite effect was observed in the context of NETs degradation. Furthermore, NETs markedly elicited an increase in ROS, which facilitated the activation of NLRP3 deubiquitination and the subsequent pyroptosis pathway in AM. Removal of ROS could promote the binding of NLRP3 and ubiquitin, inhibit NLRP3 binding to apoptosis-associated spotted proteins (ASC) and further alleviate the inflammatory changes in the lungs.Conclusion: In summary, these findings indicate that NETs prime ROS generation, which promotes NLRP3 inflammasome activation at the post-translational level to mediate AM pyroptosis and sustain lung injury in septic mice.Keywords: sepsis, neutrophil extracellular traps, macrophage pyroptosis, NLRP3 inflammasomes, ubiquitination, oxidative stress

Jiafa Wu,1 Dongping Luo,2 Shengnan Li3 1School of Food and Bioengineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3School of Medicine, Henan Polytechnic University, Jiaozuo, People’s Republic of ChinaCorrespondence: Jiafa Wu, School of Food and Bioengineering, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, People’s Republic of China, Email wujiafa@haust.edu.cnBackground: Breast cancer stem cells (BCSCs) are associated with tumor initiation, invasion, metastasis and drug resistance. It is known that many proteins and signaling pathways are involved in the regulation of BCSCs, however, much more efforts are needed to understand BCSCs comprehensively. Tumor-infiltrating immune cells are important in cancer treatment efficacy and patient prognosis. We tried to identify potential suppressor of BCSCs and analyze its correlation with various immune cells infiltration by bioinformatic and experimental methods.Methods: Expression level and methylation state of OVOL2 were analyzed by tools from bc-GenExMiner v4.8 and UALCAN databases. The Kaplan–Meier plotter was applied to evaluate the prognostic values of OVOL2. Gene expression datasets (GSE7515, GSE15192) were selected to analyze differentially expressed genes (DEGs) related to BCSCs. GO and KEGG pathway analyses of DEGs were conducted. MCODE app plugin of Cytoscape was used to screen modules in PPI network of downregulated DEGs. Correlation of OVOL2 expression with infiltrating immune cells was evaluated by TIMER 2.0. Experiments were conducted to verify whether OVOL2 could inhibit stemness traits of breast cancer cell MDA-MB-231.Results: The expression level of OVOL2 in basal/TNBC was significantly lower than that of other subtypes. Survival analyses indicated that high expression of OVOL2 was associated with favorable prognosis. GO and KEGG pathway analyses for upregulated and downregulated DEGs were conducted. The top three clusters of downregulated DEGs showed that tight junction and chemokines may play important roles in BCSCs. OVOL2 is one module of clusters. OVOL2 expression is correlated with various immune cells infiltration. Experiments showed that OVOL2 suppresses CD44+/CD24− ratio and mammospheres formation of MDA-MB-231.Conclusion: OVOL2 may play an important role in the regulation of breast cancer stemness and immune cell infiltration, and is likely to be a target for the treatment of breast cancer.Keywords: OVOL2, gene ontology, KEGG pathway, BCSCs, immune cell infiltration

Songyang Liu,1,&ast; Dongmei Luo,2,&ast; Jie Luo,2 Hanyin Liang,2 Yunfei Zhi,1 Dong Wang,3 Na Xu2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 2Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 3Department of Bioinformatics, Basic Medical College of Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang, Department of Bioinformatics, Basic Medical College of Southern Medical University, 1838 Guangzhou Da Dao North, Guangzhou, Guangdong, 510515, People’s Republic of China, Email wangdong79@smu.edu.cn Na Xu, Department of Hematology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Da Dao North, Guangzhou, 510515, Guangdong, People’s Republic of China, Email sprenaa@163.comBackground: Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood.Methods: We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups.Results: The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients’ OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups.Conclusion: A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.Keywords: acute myelogenous leukemia, pyroptosis, gene signature, tumor immune micro-environment, prognosis

Yinhua Luo,1,&ast; Shengyu Cui,2,&ast; Changjiang Zhang,2 Rui Huang,2 Jinbo Zhao,3 Ke Su,3 Dan Luo,3 Yuanhong Li3 1Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, People’s Republic of China, Email lyh0101@vip.163.comObjective: In-stent restenosis (ISR) is regarded as a critical limiting factor in stenting for coronary heart disease (CHD). Recent research has shown that fasting residual cholesterol (RC) has been shown to have a substantial impact on coronary heart disease. Unfortunately, there have not been much data to bear out the relationship between RC and ISR. Then, the predictive value of RC for in-stent restenosis in patients with coronary heart disease was analyzed.Patients and Methods: Aiming to explore the relationship between RC and ISR, we designed a retrospective study of patients with CHD after drug-eluting stent (DES) implantation, combining the data from a public database and selecting the best-fitting model by comparing the optical subset with least absolute shrinkage and selection operator (LASSO) regression.Results: Analysis of the abovementioned two models showed that the optical subset optimal subset model, which was based on RC, creatine, history of diabetes, smoking, multi-vessel lesions (2 vessels or more lesions), peripheral vascular lesions (PAD), and blood uric acid, had a better fit (AUC = 0.68), and that RC was an independent risk factor for ISR in the abovementioned two models. Notwithstanding its limitation, this study does suggest that RC has good predictive value for ISR.Conclusion: Remnant cholesterol is an independent risk factor for in-stent restenosis after percutaneous coronary intervention (PCI) and is a reliable predictor of ISR.Keywords: in-stent restenosis, ISR, percutaneous coronary intervention, PCI, remnant cholesterol, RC, drug-eluting stents, DES, least absolute shrinkage and selection operator, LASSO

Ni Zeng,1,2 Yueyue Li,2 Qian Wang,3 Yihe Chen,2 Yan Zhang,1 Lanfang Zhang,1 Feng Jiang,4,5 Wei Yuan,1 Dan Luo2 1Department of Dermatology, Affiliated Hospital of Zunyi Medical University,149 Dalian Road, Huichuan District, Guizhou, 563003, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, People’s Republic of China; 4Neonatal Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 5Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 21000, People’s Republic of ChinaCorrespondence: Wei YuanDepartment of Dermatology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Guizhou, 563003, People’s Republic of ChinaTel/Fax +86 13655187928Email dryuanweihua@sina.comDan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of ChinaTel/Fax +86 13655187928Email daniluo2005@163.comPurpose: To identify potential risk factors for herpes zoster infection in type 2 diabetes mellitus in southeast Chinese population.Patients and Methods: We built a model involving 266 herpes zoster patients collecting data from January 2018 to December 2019. The least absolute shrinkage and selection operator (Lasso) predictive model was used to test herpes zoster virus risk using the patient data. Multivariate regression was conducted to decide which variable would be the strongest to decrease the Lasso penalty. The predictive model was tested using the C-index, a calibration plot, and decision curve study. External validity was verified by bootstrapping by counting probabilities.Results: In the prediction nomogram, the prediction variables included age, sex, weight, length of hospital stay, infection, and blood pressure. The C-index of 0.844 (0.798– 0.896) indicated substantial variability and thus the model was adjusted appropriately. A score of 0.825 was achieved somewhere in the above interval. Examination of the decision curve estimated that herpes zoster nomogram was useful when the intervention was determined at the 16 percent of the herpes zoster infection potential threshold.Conclusion: The herpes zoster nomogram combines age, weight, position of the rash, 2-hour plasma glucose, glycosuria, serum creatinine, length of the hospital stay, and hypertension. This calculator can be used to assess the individual herpes zoster risks in patients diagnosed with type 2 diabetes mellitus.Keywords: glycemic status, herpes zoster, nomogram, type 2 diabetes mellitus, infection

Linjue Shangguan,1,&ast; Peipei Zhang,1 Shengwei Fang,1 Kaili Xiang,1 Yawen Geng,1 Dingcun Luo,2,&ast; Chunlei Zhao1,&ast; 1Department of Nuclear Medicine, Hangzhou Cancer Hospital, Hangzhou, 310002, People’s Republic of China; 2Department of Tumor Surgery, Hangzhou First People’s Hospital, Hangzhou, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlei ZhaoDepartment of Nuclear Medicine, Hangzhou Cancer Hospital, 34 Yanguan Lane, Shangcheng District, Hangzhou, 310002, People’s Republic of ChinaEmail clzhaocl@hotmail.comDingcun LuoDepartment of Tumor Surgery, Hangzhou First People’s Hospital, 261 Huansha Road, Shangcheng District, Hangzhou, 310000, People’s Republic of ChinaEmail ldc65@163.comObjective: To investigate the relationship of BRAF mutation with the outcome of the first postoperative 131I treatment and malignant biological characteristics in papillary thyroid carcinoma (PTC).Methods: Thirty-three patients with PTC who underwent their first 131I treatment after total thyroidectomy were enrolled in this study. BRAF mutation in postoperative tumor tissue and circulating tumor DNA (ctDNA) in peripheral blood at the time of 131I treatment were detected. According to the status of BRAF mutation, all patients were divided into 2 groups in each category of tumor tissues and ctDNA, respectively: 1) BRAF mutation, 2) BRAF wild-type. The Fisher’s exact test was performed to analyze the relationship of BRAF mutation in either tumor tissue or ctDNA with the outcome of the first 131I treatment and malignant characteristics of PTC.Results: BRAF mutation was detected in tumor tissues in 25 patients (25/33,75.8%), and all the patients had single mutation site. In ctDNA, BRAF mutation was detected in 5 patients (5/33, 15.2%), and all the patients had single mutation site. In both tumor tissues and ctDNA, BRAF mutation showed no relationship with the outcome of first 131I treatment and the malignant biological characteristics (P> 0.05).Conclusion: The value of BRAF mutation alone might be limited in predicting therapeutic outcome of the first 131I treatment in PTC. No definitive relevance was found between BRAF mutation and malignant biological features in PTC.Keywords: gene mutation, BRAF, radiotherapy, papillary thyroid carcinoma

Wantai Dang,1,&ast; Xiaohui Xu,2,&ast; Danling Luo,2 Hui Luo,2 Jin Hu,2 Jingguo Zhou,1 Jian Liu,2 Lanlan You2 1Department of Rheumatism and Immunity, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 2Department of Ultrasound, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lanlan You Email 17027279@qq.comObjective: To explore the effects of different blood uric acid levels in gout patients on the two-dimensional image of the kidney and the risk factors for gout-related kidney damage for providing clinical evidence to enable early prevention and treatment of gout-related kidney damage.Methods: We obtained information of 227 patients with primary gout and estimated the association between two-dimensional kidney images and clinical indicators using binary logistic regression.Results: Our study showed that different uric acid levels, age, disease course, cystatin C (CysC) level, and γ-glutamyl transpeptidase level were correlated with echo of the renal medulla (P < 0.05). CysC level was correlated with the renal cortex thickness and kidney stones in different uric acid-level groups (P < 0.05). Disease course, aspartate transaminase (AST) level, creatinine (CREA) level, and tophi were risk factors for renal cortex thinning in gout patients (P = 0.045, 0.026, 0.004, 0.006, respectively). The disease course, platelet (PLT) count, and high-density lipoprotein (HDL-C) level were risk factors for kidney stone formation in gout patients (P = 0.037, 0.022, 0.023, respectively), while CysC level and C-reactive protein (CRP) level were risk factors for increased renal medulla echo in these patients (P = 0.022, 0.028, respectively).Conclusion: Our study revealed disease course, AST level, CREA level, tophi, PLT count, HDL-C level, CysC level and CRP level may be important predictors of renal image changes.Keywords: gout, two-dimensional ultrasound, renal medulla, renal cortex, kidney stones

Ni Zeng,1,2 Liwen Ma,3 Yuxin Cheng,1 Qingyue Xia,1 Yueyue Li,1 Yihe Chen,1 Zhiyu Lu,1 Qian Lu,1 Feng Jiang,4 Dan Luo1 1Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 3Department of Dermatology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Dan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, People’s Republic of ChinaEmail daniluo2005@163.comFeng JiangDepartment of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People’s Republic of ChinaEmail dxyjiang@163.comObjective: In this research, we studied the genes associated with ferroptosis to develop a prognostic model and find out an association with tumor immune microenvironment in skin cutaneous melanoma (SKCM) patients.Methods: To find SKCM-related ferroptosis genes, we used Cox regression and LASSO approach on 60 genes related to ferroptosis and SKCM-related RNA-seq. Following that, a ferroptosis-related gene signature was created. Time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its capability of prediction. Besides, several assessments were used to evaluate overall survival (OS), accompanied by the creation of a nomogram for the clinicopathologic factors and the ferroptosis-related gene signature we established. We also investigated the relationship between ferroptosis-related gene signature with three immune checkpoints and immune cell infiltration.Results: Our prognostic model included two genes (ALOX5, CHAC1). In both TCGA and GEO cohorts, OS was lower in high-risk category. Using our gene signature, we can reliably predict OS. Additionally, our gene signature can predict immune cell infiltration and SKCM immunotherapy response.Conclusion: Our gene signature has shown to be a reliable predictor of OS, reflect the immune microenvironment, and predict the effectiveness of immunotherapy for SKCM patients.Keywords: skin cutaneous melanoma, SKCM, ferroptosis, immune microenvironment, immune checkpoint

Peijing Li,1,2,&ast; Qun Zhang,3,&ast; Donghua Luo,4– 6 Feng Jiang,1,2 Qifeng Jin,1,2 Yonghong Hua,1,2 Ting Jin,1,2 Xiaozhong Chen1,2 1Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310000, People’s Republic of China; 2Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, 310000, People’s Republic of China; 3Department of Radiation Oncology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China; 4Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 5State Key Laboratory of Oncology in South China, Guangzhou, 510060, People’s Republic of China; 6Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaozhong Chen; Ting JinDepartment of Radiation Oncology, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022 Email chenxiaozhong2016@163.com; jinting22222@163.comPurpose: Patients with T3-4N0M0 nasopharyngeal carcinoma (NPC) are a unique subgroup of locoregional advanced NPC, which generally have a better prognosis than others and are often excluded in most randomized controlled clinical trials focusing on locoregional advanced NPC. The management of this population is still controversial. This study aims to evaluate the outcomes of T3-4N0M0 NPC patients treated with sequential induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT) or chemoradiotherapy (CCRT) alone.Patients and Methods: We included 362 patients diagnosed with T3-4N0M0 NPC from two hospitals between December 2005 and December 2014. All patients were received IC + CCRT (n=146) or CCRT (n=216). Locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were retrospectively estimated.Results: The median follow-up was 95 (range: 11– 168) months. Univariable analyses have shown that 5-year LRFFS, DFS and OS in the IC+CCRT group and the CCRT group were 87.4% vs 93.4% (P = 0.035), 80.4% vs 87.0% (P = 0.047) and 86.3% vs 93.0% (P = 0.040). Multivariate analyses demonstrated that only the T stage was the independent prognostic factor for LRFFS, DFS, and OS in the entire group analysis. Subgroup analysis revealed that patients with T3 tumors who received IC+CCRT had significantly lower LRFFS, DFS, and OS than those treated with CCRT. For T4 patients, the outcomes had no significant difference between the two groups.Conclusion: This retrospective study showed that T3N0M0 patients who received CCRT had better prognosis than those treated with IC+CCRT. In terms of T4N0M0 disease, treatment outcomes are similar in both treatment groups. However, these results require further confirmation of large sample size, prospectively, randomized controlled trials.Keywords: nasopharyngeal carcinoma, chemotherapy, intensity-modulated radiation therapy

Qiuyue Guo,1 Yunsheng Xu,2 Jie Li,3 Wenrong An,3 Dan Luo,4 Chengcheng Huang,4 Yanqin Huang4 1Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Endocrinology, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of China; 3First Clinical Medical College, Jingshi Rd. Campus, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Yanqin Huang Email huangyanqin2020@126.com; 20137125@sdutcm.deu.cnPurpose: To analyze the effect and potential therapeutic targets of liraglutide in type 2 diabetes through miRNA expression profiling.Methods: Ten of 30 SPF Wistar rats, males at 4 weeks old, were randomly selected as the control group and given conventional feed, the other rats adopted high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish a T2DM model. One unsuccessful rat was excluded, and the remaining rats were randomized to the model and the liraglutide group. Liraglutide group was subcutaneously injected with liraglutide 0.11 mg/kg for 8 weeks. The biochemical indicators and staining HE were detected. The expression of miRNA in pancreatic tissue was detected by miRNA sequencing. The intersection of miRNA difference was used to predict the target gene, then functional enrichment was performed to identify its possible biological functions and signal transduction paths. Finally, qRT-PCR was used to verify the results.Results: Compared to the model group, the level of fasting blood glucose (FBG), glucagon and insulin resistance index (HOMA-IR) in the liraglutide group were significantly decreased, fasting insulin (FINS) and insulin sensitivity index (ISI) were increased. Nine differential miRNAs (miR-135a-5p, miR-144-5p, miR-21-3p, miR-215, miR-451-5p, miR-486, miR-122-5p, miR-181d-5p and miR-345-5p) were identified at the intersection through two miRNA sequencing. A total of 3359 related target gene predictions were obtained. GO and pathway analyses demonstrated that differentially expressed genes were closely related to cell proliferation, angiogenesis, and proteolysis. Significant signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway.Conclusion: Liraglutide could improve islet function by regulating nine miRNAs, and the related signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Our study provided the basis and direction for further exploring the molecular mechanism of liraglutide on T2DM.Keywords: liraglutide, type 2 diabetes, miRNA expression profile, target gene, signaling pathway

Xiacan Chen,1 Wanjun Guo,2 Liangming Yu,2 Dan Luo,2 Leling Xie,2 Jiajun Xu2 1Institute of Forensic Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 2Mental Health Centre, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Jiajun XuMental Health Centre, West China Hospital, Sichuan University, 610041, People’s Republic of ChinaEmail xujiajun120@126.comObjective: The findings of olfaction are inconsistent in anxiety disorders, and few studies have reported on the olfactory performance in generalized anxiety disorder (GAD). Therefore, we aim to investigate the olfactory function of patients with GAD and the association between olfactory function and anxiety symptoms.Methods: We conducted a case–control study by selecting 107 patients with GAD and 107 healthy controls matched for sex and age, to investigate olfaction deficits in GAD and the association between anxiety severity and olfaction. All patients were treatment-naïve prior to the inclusion. Anxiety severity and olfaction were assessed by the Hamilton anxiety rating scale (HAM-A) and the Sniffin’ Sticks test (SST), respectively. Partial correlations were used to analyze the relationship between olfaction and anxiety severity. False discovery rate (FDR) correction was used in multi-correlation analyses.Results: Compared with healthy controls, patients in the GAD group demonstrated odor threshold, discrimination and identification deficits. In the moderate/severe anxiety subgroup, discrimination score was significantly and inversely correlated with the somatic anxiety score (γ=− 0.44, q = 0.03), and identification score was significantly and inversely correlated with the HAM-A total score (γ=− 0.42, q= 0.04). The TDI score (the sum of threshold, discrimination and identification scores) was significantly and inversely correlated with the somatic (γ=− 0.44, q = 0.04) and psychic (γ=− 0.45, q = 0.04) anxiety scores in the moderate/severe anxiety subgroup.Conclusion: This study demonstrated the olfactory impairment in patients with GAD and that poorer odor discrimination was correlated with greater severity of somatic anxiety.Keywords: GAD, olfaction, symptom

Hong Zhou,1 Dan Luo,2 Dan Chen,2 Xi Tan,1 Xichen Bai,1 Zhi Liu,1 Xiangliang Yang,1,2 Wei Liu1,2 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, People’s Republic of China; 2National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430075, Hubei, People’s Republic of ChinaCorrespondence: Wei LiuCollege of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan, 430075, Hubei, People’s Republic of ChinaTel/Fax +86 27 8779 2147Email wliu@hust.edu.cnAbstract: Nanocarrier technology has been effectively applied to the development of drug delivery systems to overcome the limitations of traditional preparation. Its application has been extended to various pharmaceutical fields from injection preparation to oral preparation and external preparation, and now it has appeared in the field of cosmetics for beauty applications. The widespread influence of nanocarrier in the cosmetics industry is due to the fact that nanocarrier can effectively promote the percutaneous penetration and significantly increase skin retention of active components in functional cosmetics. Meanwhile, nanocarrier can effectively improve the water dispersion of insoluble active cosmetic ingredients, enhance the stability of efficacy components and achieve the codelivery of diverse cosmetics active ingredients. In this review, we summarized the current progress of nanocarrier technology in the functional cosmetics, including the types and the routes of dermal/transdermal drug delivery nanocarriers used in the functional cosmetics, the mechanism of nanocarriers promoting the percutaneous penetration of active cosmetic ingredients, the application and efficacy evaluation of different active cosmetic ingredients in nanocarriers and discussing the potential risks to human. This will provide a useful reference for the further development of nanocarriers in the field of functional cosmetics.Keywords: nanocarrier technology, functional cosmetics, active cosmetic ingredients, skin penetration and positioning, efficacy evaluation, codelivery nanocarriers

Dandan Luo,1 Meilian Peng,2 Xizhen Wei,1 Diling Pan,3 Huifeng Xue,4 Yuying Xu,1 Binhua Dong2 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Pathology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Binhua DongDepartment of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, People’s Republic of ChinaTel +86-591-87558732Fax +86-591- 87551247Email dbh18-jy@126.comYuying XuDepartment of Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, People’s Republic of ChinaTel +86-591-87279515Fax +86-591-87551247Email yyxu703@163.comPurpose: The status of human papillomavirus (HPV) infection in pregnant and non-pregnant women in China remains unclear. This study aimed to compare the prevalence and genotype distributions of HPV between pregnant and non-pregnant women in China.Patients and Methods: A case-control study was conducted of pregnant women during the second trimester and age-matched non-pregnant women attending the Fujian Maternity and Child Health Hospital between January 1, 2017 and December 31, 2018. Participants underwent cervical cytology testing and HPV genotyping. The genotyping test was able to identify 14 high-risk HPV (HR-HPV), four possible HR-HPV, and five low-risk HPV (LR-HPV) types. Further colposcopy and a cervical biopsy were performed if indicated. The primary outcomes were HPV prevalence and genotype distribution.Results: In total, 1077 pregnant and 1077 non-pregnant women were enrolled. Compared with non-pregnant women, pregnant women had a higher prevalence of HPV (24.2% vs 14.8%), HR-HPV (20.2% vs 11.7%), and LR-HPV (8% vs 4.5%) infection. In pregnant women, the most prevalent HPV genotypes were HPV-52 (6.0%), -16 (3.5%), -58 (2.6%), -53 (2.5%), and -51 (2.5%), while in non-pregnant women the most prevalent genotypes were HPV-52 (3.6%), -81 (1.9%), -51 (1.8%), -68 (1.4%), and -16 (1.3%). In women aged ≥ 35 years, HR-HPV (P=0.002) and LR-HPV (P=0.001) prevalence were significantly higher in pregnant women. However, in women aged < 35 years, only HR-HPV prevalence was higher in pregnant women. Pregnant and non-pregnant women with HPV-16 and HPV-58 infection had a high prevalence of high-grade squamous intra-epithelial lesions (HSIL) (HPV-16: P< 0.001 and P=0.005, HPV-58: P=0.043 and P=0.005); but with other HR-HPV genotypes, only non-pregnant women had an increased HSIL prevalence.Conclusion: In China, the HPV prevalence is higher in pregnant women than that in non-pregnant women and is also age- and genotype-dependent. HPV-infected pregnant women aged ≥ 35 years and those with HPV-16 should be closely monitored to enable rapid clinical intervention.Keywords: human papillomavirus, genotype, squamous intraepithelial lesions, cervical cytology, China, pregnant

Guiying Jiang,1,* Xueqian Wang,1,* Ying Zhou,1 Chenming Zou,2,3 Ling Wang,1 Wei Wang,1 Danya Zhang,1 Hanjie Xu,1 Jie Li,1 Fei Li,1 Danfeng Luo,1 Xiangyi Ma,1 Ding Ma,1 Songwei Tan,2 Rui Wei,1 Ling Xi1 1Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 2Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 3School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Xi; Rui WeiDepartment of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People’s Republic of ChinaTel/Fax +86 27 83662688Email lxi@tjh.tjmu.edu.cn; weirui2018@tjh.tjmu.edu.cnBackground and Purpose: Cisplatin–paclitaxel (TP) combination chemotherapy as the first-line therapy for numerous cancers is hindered by its inadequate accumulation in tumors and severe side effects resulting from non-specific distribution. The aim of this study is to explore whether TMTP1-modified, cisplatin and paclitaxel prodrugs co-loaded nanodrug could improve cervical cancer chemotherapy and relieve its side effects through active and passive tumor targeting accumulation and controlled drug release.Methods: TDNP, with capacities of active targeting for tumors and controlled drug release, was prepared to co-deliver cisplatin and paclitaxel prodrugs. The characteristics were investigated, including the diameter, surface zeta potential, stability and tumor microenvironment (TME) dependent drug release profiles. Cellular uptake, cytotoxicity, drug accumulation in tumors, antitumor effects and safety analysis were evaluated in vitro and in vivo.Results: The oxidized cisplatin and the paclitaxel linked to the polymer achieved a high loading effciency of over 80% and TME-dependent sustained drug release. Moreover, TMTP1 modification enhanced cellular uptake of TDNP and further improved the cytotoxicity of TDNP in vitro. In vivo, TDNP showed an extended blood circulation and increased accumulation in SiHa xenograft models with the aid of TMTP1. More importantly, TDNP controlled tumor growth without life-threatening side effects.Conclusion: Our study provided a novel TP co-delivery platform for targeted chemotherapy of cervical cancer, which was promising to improve the therapeutic effcacy of TP and may also have application in other tumors.Keywords: TME-responsive, targeted co-delivery, combined chemotherapy, cervical cancer

Hangqi Shen,1– 6,* Hui Zhang,7,8,* Wei Gong,1– 6 Tianwei Qian,1– 6 Tianyu Cheng,1– 6 Li Jin,7,8 Xiaofeng Wang,7– 10 Dawei Luo,1– 6 Xun Xu1– 6 1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, People’s Republic of China; 3Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, People’s Republic of China; 4Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, People’s Republic of China; 5National Clinical Research Center for Eye Diseases, Shanghai, People’s Republic of China; 6Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai, People’s Republic of China; 7Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 8Human Phenome Institute, Fudan University, Shanghai, People’s Republic of China; 9Shanghai Key Laboratory of Clinical Geriatric Medicine and Huadong Hospital Clinical Research Center for Geriatric Medicine, Shanghai, People’s Republic of China; 10National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dawei Luo; Xun XuDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaEmail dr-davie@yeah.net; drxuxun@sjtu.edu.cnPurpose: This study aimed to explore the current prevalence, causes, and factors associated with visual impairment in a Chinese elderly population.Methods: A random sample of 2164 candidates aged ≥ 70 years was selected. Among them, 1914 participants (response rate: 88.4%) underwent comprehensive eye examinations. The prevalence and causes of visual impairment were estimated, and the associated factors were identified.Results: The standardized prevalence of mild visual impairment (< 6/12 to ≥ 6/18), moderate to severe visual impairment (MSVI) (< 6/18 to ≥ 3/60), and blindness (< 3/60) in the better eye were 20.5%, 25.8%, and 3.4%, respectively. The leading cause of visual impairment was cataract (49.7%), followed by uncorrected refractive error (26.5%), myopic maculopathy (5.8%), and posterior capsular opacification (5.5%). Optical coherence tomography revealed that vitreoretinal interface abnormalities were the third most common cause of monocular mild visual impairment (2.2%) and MSVI (4.4%) in the elderly population. A large number of patients with visual impairment (81.7%) were amenable to undergo the interventions. Visual impairment was associated with advanced age (odds ratio [OR], 1.09 per year; p< 0.001), female sex (OR, 1.59; p=0.003), self-reported visual impairment (OR, 1.91; p< 0.001), cognitive impairment (OR, 1.40, p=0.005), and high educational level (OR, 0.75; primary, p=0.045; and OR, 0.53, secondary or higher; p< 0.001).Conclusion: Visual impairment was common in the Chinese elderly population and a severe health and social problem. Practicable policies are urgently needed to popularize eye health knowledge and promote treatments for visual impairment in elderly people in rural China.Keywords: visual impairment, blindness, elderly, aging

Xiaojin Feng,1,2 Jialing Hu,1 Fenfang Zhan,1 Deqiang Luo,3 Fuzhou Hua,1,2 Guohai Xu1,2 1Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi 330006, People’s Republic of China; 3Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Guohai Xu; Fuzhou HuaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaTel +86-791-86299131Email xuguohai1@sina.com; 415134607@qq.comPurpose: Neuroinflammation is an essential causative factor in the pathogenesis and progression of cognitive impairment. The present study aims to evaluate the critical role of microRNA-138-5p (miR-138-5p) in hippocampal neuroinflammation and cognitive impairment through the NLRP3/caspase-1 signaling pathway in rats.Material and Methods: We established the cognitive impairment rat model and RM (Rat microglia) microglial cellular inflammation model by intracerebroventricular (icv) injection or stimulation of lipopolysaccharide (LPS). Morris water maze (MWM) and Y-maze tests were performed to assess the cognitive behaviors. Quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme-linked immune-sorbent assay (ELISA) and Western blot analysis were utilized to evaluate mRNA or protein expression. Bioinformatic analysis and dual-luciferase reporter gene assay were performed to verify the targeting relationship between NLRP3 and miR-138-5p. Besides, Hematoxylin and eosin (H&E) staining and immunohistochemistry were applied to observe the neuronal morphology and detect the positive cells of the hippocampus, respectively.Results: Compared to the control groups, LPS-treated rats exhibited significantly impaired learning and memory in MWM and Y-maze tests. The expression of NLRP3, caspase-1 and pro-inflammation cytokines (IL-1β and IL-18) were upregulated, while miR-138-5p was downregulated both in rat hippocampus and RM cells treated with LPS. MiR-138-5p is downregulated in microarray data of cognitive impairment animals and could directly target the 3ʹ-UTR of NLRP3. Furthermore, upregulation of miR-138-5p improved impaired cognitive functions, while inhibited hippocampal neuroinflammation demonstrated by decreased expression of NLRP3/caspase-1 axis, pro-inflammation cytokines and microglial activation. This study demonstrates for the first time that miR-138-5p suppresses the hippocampal NLRP3/caspase-1 signaling pathway activation in cognition impaired rats.Conclusion: The low expression of miR-138-5p after LPS administration may contribute to the activation of the NLRP3/caspase-1 pathway, leading to hippocampal neuroinflammation and cognitive impairment in rat models. These findings indicate a promising therapeutic avenue for cognitive disorders.Keywords: microRNA-138-5p, NLRP3/caspase-1, neuroinflammation, cognitive impairment, microglial activation

Deqiang Luo,1,2 Fen Liu,1 Jianguo Zhang,1 Qiang Shao,1 Wenqiang Tao,1 Rui Xiao,1 Wei Dai,2 Chengzhi Ding,1 Kejian Qian1 1Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Department of Intensive Care Unit, The Fifth People’s Hospital of Shangrao City, Shangrao, 334000, People’s Republic of ChinaCorrespondence: Kejian QianDepartment of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Dong Lake District, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaEmail ndyfyicu@email.ncu.edu.cnPurpose: To explore the molecular mechanism and search for candidate lncRNA and mRNA associated with pyroptosis in the gene expression profile of LPS-induced acute lung injury (ALI).Methods: We investigated lncRNA and mRNA expression in lipopolysaccharide (LPS)-induced ALI at an early stage. RNA sequencing (RNA-Seq) was carried out to analyze lncRNA and mRNA expression profiles between the LPS-induced and control groups. We used bioinformatics analysis to predict target genes of early differential lncRNAs among obtained the differential mRNAs.Results: A total of 78 lncRNAs and 248 mRNAs were upregulated at 2 hours and downregulated at 9 hours, and 21 lncRNAs and 107 mRNAs were downregulated at 2 and upregulated at 9 hours in early ALI models. We predicted 7 cis-and trans-regulated target genes of the top 20 lncRNAs. Gene Ontology (GO) analysis indicated that the target genes for the screened lncRNAs were most enriched in three-terms: regulation of protein serine/threonine kinase activity, pertussis, and cellular response to LPS. Additionally, target genes of lncRNAs were the top three enriched in pertussis, osteoclast differentiation, and cAMP signaling pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also identified vital mRNAs and lncRNAs. Protein-protein interaction (PPI) network analysis suggested that Tnf, Jun, and Atf3 were the top three key genes. Hub lncRNA4344 (NONRATT004344.2) and cis-regulated target mRNA (NLRP3) were validated in vitro. Finally, luciferase assay results confirmed that lncRNA4344 sponged miR‐138-5p to promote pyroptosis in inflammatory responses to LPS‐induced acute lung injury by targeting NLRP3.Conclusion: Based on analysis of lncRNA and mRNA expression profiles by RNA-Seq and experimental verification, this study is the first to reveal that lncRNA4344 sponged miR‐138-5p to promote pyroptosis in inflammatory responses of LPS‐induced acute lung injury by targeting NLRP3. These newly identified lncRNA, miRNA, and mRNA might be novel potential targets for early treatment and prevention in early ALI.Keywords: acute lung injury, alveolar macrophage, ceRNA network long noncoding RNAs, pyroptosis, RNA sequencing

Luna Liu,1,2 Shuang Liu,1,2 Qianmei Song,1,2 Dandan Luo,1,2 Yu Su,1,2 Xiangyu Qi,1,2 Qian Wang,3 Jing Ning,1,2 Youyuan Lv,1,2 Qingbo Guan1,2,4 1Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, People’s Republic of China; 2Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, People’s Republic of China; 3Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of China; 4Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of ChinaCorrespondence: Qingbo Guan Tel +86-531-68776375Fax +86-531-87068707Email doctorguanqingbo@163.comObjective: Obesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population.Methods: We performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40– 75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI< 25.0) and overweight/obesity (BMI≥ 25.0) with or without metabolic syndrome.Results: We collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414– 3.911) and 3.294 (2.631– 4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups.Conclusion: Obesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.Keywords: metabolic obesity phenotypes, testosterone, metabolically healthy overweight/obese, metabolically unhealthy normal weight, hypotestosteronemia

Jiafa Wu,1,2 Dongping Luo,3 Shengnan Li4 1School of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 2Henan Engineering Research Center of Food Microbiology, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 3The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 4School of Medicine, Henan Polytechnic University, Jiaozuo, Henan, People’s Republic of ChinaCorrespondence: Jiafa WuSchool of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, Henan, People’s Republic of ChinaEmail wujiafa@haust.edu.cnPurpose: The compound traditional Chinese medicine Xihuang pill (XHP) has been adopted to treat breast cancer (BC) for centuries, but its specific mechanism of action is unclear.Materials and Methods: The active ingredients and related targets of XHP were screened using the TCMSP and TCMID databases. GSE139038 was downloaded from the GEO database, and differentially expressed genes (DEGs) were analyzed. The intersection of targets and DEGs were chosen to build an ingredients–target genes network. Protein–protein interaction network construction and functional enrichment analysis of target genes were conducted.Results: A PPI network of 37 targets was constructed, and seven core nodes (FOS, MYC, JUN, PPARG, MMP9, PTGS2, SERPINE1) were identified. Functional enrichment analysis revealed that the aforementioned targets were mainly enriched in the IL-17, toll-like receptor, and tumor necrosis factor signaling pathways, which are deeply involved in the inflammatory microenvironment of tumors.Conclusion: This network pharmacology study indicated that XHP can inhibit the development of BC by targeting a variety of proteins and signaling pathways involved in the inflammatory microenvironment.Keywords: traditional Chinese medicine, Xihuang pill, breast cancer, network pharmacology

Yong Wang, Xiao-jiao Zhang, Hong-wei Zhao, Chengfu Wang, Defeng Luo, Qingkun Meng, Yu Zhu, Jie Tao, Baojun Chen, Yi Li, Aijie Hou, Bo Luan Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaCorrespondence: Bo Luan; Aijie HouDepartment of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, No. 33, Wenyi Road, Shenhe District, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaTel +86-17702488970Email luanbo2016@163.com; 1758624242@qq.comBackground: Retrograde microcatheter collateral channel (CC) tracking after successful wiring of septal CC is crucial for retrograde revascularization of coronary chronic total occlusion (CTO). However, the incidence, predictors, and strategies for failure of retrograde microcatheter CC tracking after successful wiring of septal CC remain unclear.Methods: In total, 298 patients with CTO who underwent retrograde septal CC PCI between January 2015 and May 2019 were retrospectively analyzed. Clinical data were compared to investigate the predictors of initial microcatheter tracking failure.Results: The initial and final microcatheter tracking success rates were 79.2% (236/298) and 96.6% (288/298), respectively. The procedural success rate was 94.0% (280/298). The right coronary artery-to-left anterior descending artery septal ratio (48.4% vs 33.1%, p=0.037) and CC tortuosity (34.6% vs 20.8%, p=0.045) were significantly higher in the initial microcatheter CC tracking failure group than in the successful tracking group. Multivariate logistic regression analysis revealed that severe collateral tortuosity (odds ratio [OR]: 13.241, 95% confidence interval [CI]: 3.429– 27.057, p=0.038), CC entry angle of < 90° (OR:4.921, 95% CI: 1.128– 9.997, p=0.002), CC exit angle of < 90° (OR:5.037, 95% CI: 2.237– 11.182, p=0.004), use of Finecross MG as initial microcatheter (OR:1.826, 95% CI: 1.127– 3.067, p=0.035), and shunning initial retrograde application of Guidezilla (OR:0.321, 95% CI: 0.267– 0.915, p=0.024) were variables independently associated with initial microcatheter CC tracking failure in patients with CTO undergoing retrograde septal CC PCI.Conclusion: The overall initial microcatheter CC tracking failure was 20.8%. Severecollateral tortuosity, CC entry, and exit angle of < 90°, use of Finecross MG as initial microcatheter, and shunning initial retrograde application of Guidezilla were variables independently associated with initial microcatheter CC tracking failure in patients with CTO undergoing retrograde septal PCI.Keywords: coronary chronic total occlusion, retrograde microcatheter tracking, collateral channel, predictor

Xiao-kun Liu,1– 3 Shui-yuan Xiao,2,4 Dan Luo,4 Jiang-hua Zhang,5 Lu-lu Qin,6 Xun-qiang Yin4 1The First Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 2Mental Health Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 3Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province; 4Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China; 5Student Affairs Office of Central South University, Hunan, People’s Republic of China; 6Department of Social Medicine and Health Management, School of Medicine, Hunan Normal University, Changsha, People’s Republic of ChinaCorrespondence: Shui-yuan Xiao Mental Health Center, Xiangya Hospital, 87 Xiangya Road, Changsha 410087, Hunan, People’s Republic of ChinaFax +86-0731-84327332Email shuiyuanxiao1503@163.comPurpose: The aim of this study was to develop a scale to quantify the negative life events of graduate students; and to identify the associations between negative life events and emotional disorders among them.Methods: Based on a literature review, qualitative interviews and direct consultation with experts in relevant fields, the study served to identify the items that could be included in the Negative Life Events Scale for graduates (LES-GS). Psychometrics was used to analyze the items for reliability and validity. A cross-sectional survey was conducted in Changsha, China to explore the association between negative life events and emotional disorders among master’s and PhD students. LES-GS, Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder Scale-7 (GAD-7) were utilized in the survey.Results: The LES-GS exhibited acceptable reliability and validity. A total of 13.24% of master’s and 16.60% of PhD students experienced moderate to severe depression symptoms. Additionally, a total of 9.04% of master’s students and 15.47% of PhD students experienced moderate to severe anxiety symptoms. Among the master’s students, five long-term events and one short-term event life events (these included “tension with family members”; “the graduation project is not going well”; “not interested in the major”; “poor relationship with partner or spouse”, “long-term financial stress”, and “dispute with the mentor”) were associated with an increased likelihood of emotional disorders among them. Among the PhD students, “death of a close family member” and “the publication of academic papers fails to meet the graduation requirements” were associated with an increased likelihood of emotional disorders.Conclusion: The LES-GS could be used to assess life events for graduate students. The treatment of emotional problems for the master’s students and the doctorial students should be designed differently.Keywords: graduate students, negative life events, emotional disorders, depression, anxiety

Yong Wang, Hong-wei Zhao, Cheng-fu Wang, Xiao-jiao Zhang, Jie Tao, Chun-sheng Cui, Qing-kun Meng, Yu Zhu, De-feng Luo, Ai-jie Hou, Bo Luan Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province, 110016, People’s Republic of ChinaCorrespondence: Ai-jie Hou; Bo LuanDepartment of Cardiology, The People’s Hospital of China Medical University, the People’s Hospital of Liaoning Province, No. 33, Wenyiroad, Shenhe District, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaTel +86-17702488970Email 1758624242@qq.com; luanbo2016@163.comBackground: The incidence and prognosis of coronary slow-flow (CSF) and no-reflow phenomenon (NRP) in patients with coronary chronic total occlusion (CTO) who underwent percutaneous coronary intervention (PCI) remain unclear.Methods: This single-center prospective study aimed to investigate the incidence of CSF/NRP during CTO interventional therapy, determine predictors of CSF/NRP, and evaluate its effect on patient outcomes.Results: In this study, 552 patients with CTO who underwent PCI were included. CSF/NRP occurred in 16.1% of them. They had higher incidences of diabetes mellitus (53.9% vs 36.3%, p=0.002) and hypertension (50.6% vs 37.1%, p=0.018) and a lower incidence of retrograde filling grade > 2 (34.8% vs 47.1%, p=0.036). Patients with CSF/NRP had a higher neutrophil ratio (55.6± 19.4 vs 52.4± 18.3, p=0.038) and levels of low-density lipoprotein (LDL; 3.0± 0.8 vs 2.8± 0.6, p=0.029), fasting glucose (FG; 8.3± 1.3 vs 6.8± 1.1, p=0.005), uric acid (332.6± 82.9 vs 308.2± 62.8, p=0.045), and high-sensitivity C-reactive protein (Hs-CRP; 9.8± 4.8 vs 7.3± 3.9, p=0.036). A multivariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 1.962; 95% confidence interval [CI]: 1.198– 2.721; p=0.042), mean platelet volume (MPV; OR,1.284; 95% CI, 1.108– 1.895; p=0.046), LDL cholesterol (LDL-C; OR, 1.383; 95% CI, 1.105– 2.491; p=0.036), FG (OR, 2.095; 95% CI, 1.495– 2.899; p=0.018), Hs-CRP(OR, 2.218; 95% CI, 1.556– 3.519; p=0.029), and retrograde filling of grade > 2 (OR, 0.822; 95% CI, 0.622– 0.907; p=0.037) were independent predictors of CSF/NRP in CTO patients who underwent PCI. Kaplan-Meier analysis revealed that the patients in the CSF/NRP group had a significantly lower cumulative major cardiac and cerebrovascular events (MACCE)-free survival than those in the non-CSF/NRP group (p< 0.0001).Conclusion: Of the patients with CTO who underwent PCI, 16.1% developed CSF/NRP and had a significantly lower cumulative MACCE-free survival rate. Diabetes mellitus; higher levels of MPV, LDL-C, FG, and Hs-CRP; and a lower incidence of retrograde filling grade > 2 were independent predictors of CSF/NRP in CTO patients who underwent PCI. Thus, they can be used for risk stratification.Keywords: coronary slow-flow, no-reflow phenomenon, coronary chronic total occlusion, PCI, prognosis

Dongbo Luo,1,* Zhenyi Huang,2,* Hongbo Lv,1 Yang Wang,1 Wei Sun,1 Xiaohong Sun1 1Department of Thoracic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830011, People’s Republic of China; 2The Third Clinical Medicine College of Xinjiang Medical University, Urumqi 830011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong Sun Email doctorsunxiaohong@hotmail.comIntroduction: MicroRNA-21 (miRNA-21) and lncRNA SNHG1 (small nucleolar RNA host gene 1) are known to be aberrantly upregulated and promote tumor progression in various cancers. Nevertheless, very few studies have determined the roles of tissue and circulating miRNA-21 and SNHG1 in ESCC patients. Particularly, knowledge about the characteristics of miRNA-21 and SNHG1 expression and their correlations with survival rates, as well as their interaction with each other remains inadequate in ESCC.Methods: Thse expression level of miRNA-21 and SNHG1 of tissues, serum and cell lines were detected by qRT-PCR, and the characteristics of their expression and clinicopathology were analyzed. Then, the diagnostic and prognosis value of serum and tissue miRNA-21 and SNHG1 were evaluated, respectively. In addition, the interaction with each other between miRNA-21 and SNHG1, as well as the effect on ESCC cell proliferation were further clarified.Results: The expression level of miRNA-21 and SNHG1 are significantly upregulated in tissues, serum and cell lines of ESCC, and tissue miRNA-21 and SNHG1 significantly correlates with lymph node metastasis, TNM stage, tumor size, and poor overall survival in ESCC patients. The receiver operating characteristic (ROC) curves show that areas under the ROC curve (AUC) for serum miRNA-21 and SNHG1 are 0.928 and 0.850, respectively. Pearson correlation coefficient indicated that the expression levels of miRNA-21 and SNHG1 in frozen cancerous tissues are significantly associated with their respective serum levels. Further, Cox univariate and multivariate analyses reveal that miRNA-21 and SNHG1 are independent prognostic factors for overall survival (OS) and disease-free survival (DFS) in ESCC patients. In addition, our in vitro data revealed a novel regulatory pathway, in which miRNA-21 is probably a unidirectional upstream positive regulator of SNHG1 in ESCC cells, and the interaction between miRNA-21 and SNHG1 plays an important role in the proliferation of ESCC cells.Discussion: In summary, our data show that SNHG1 may be a novel downstream target of miRNA-21 and not vice versa in ESCC cells and contributes significantly toward the proliferation of ESCC cells. These findings suggest that miRNA-21 and SNHG1 may serve as potential diagnostic, prognostic biomarkers and therapeutic targets for ESCC patients.Keywords: MicroRNA-21, lncRNA SNHG1, esophageal squamous cell carcinoma, diagnosis, prognostic biomarker, cell proliferation

Li P, Zhang Q, Luo D, et al. Cancer Manag Res. 2021;13:7067–7076. The authors have advised the affiliation list on page 7067 is incorrect. The correct author list and affiliations are as follows. Peijing Li1,2,*Qun Zhang3,*Donghua Luo4–6Feng Jiang2Qifeng Jin2Yonghong Hua2Ting Jin2Xiaozhong Chen2 1Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People’s Republic of China; 2Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) and Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, 310000, People’s Republic of China; 3Department of Radiation Oncology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China; 4Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 5State Key Laboratory of Oncology in South China, Guangzhou, 510060, People’s Republic of China; 6Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China Read the original article

Xin Liu,1 Xiaoning He,1 Jing Wu,1 Da Luo1,2 1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China; 2Tianjin Health Development Research Center, Tianjin, People’s Republic of ChinaCorrespondence: Jing WuSchool of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, People’s Republic of ChinaTel +862227405176Fax +862287401830Email jingwu@tju.edu.cnDa LuoSchool of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of ChinaEmail vividvigorous@163.comObjectives: To investigate the initiation and persistence of antiplatelet agents and the associated factors for patients with acute coronary syndromes (ACS) in Tianjin, China.Methods: Data were obtained from Tianjin Urban Employee Basic Medical Insurance database (2011–2015). Adult patients who were discharged alive after the first ACS-related hospitalization (index hospitalization) between January 2012 and December 2014 were included. Patients who initiated with antiplatelet therapy, including aspirin monotherapy, clopidogrel monotherapy, or dual antiplatelet with aspirin and clopidogrel at discharge or within the initial 30-day follow-up after discharge were further identified. Patients with no gaps of ≥30 days in antiplatelet therapy were deemed persistent. The logistic model and Cox model were used to explore the associated factors of initiation and persistence with antiplatelet agents, respectively.Results: In total, 21,450 patients (64.6±10.7 years; 46.0% female) were included. Only 70.3% (N=15,071) of them initiated with antiplatelet agents within the initial 30-day follow-up; 85.0% (N=12,809) of the initial users discontinued their antiplatelet therapy, and the average time to discontinuation was 117.4±119.7 days. The patients who had prior antiplatelet agents utilization (Odds ratio [95% CI]=1.93 [1.78–2.09]; hazard ratio [95% CI]=0.78 [0.74–0.81]), received percutaneous coronary intervention (PCI) during the baseline period (OR=1.47 [1.26–1.73]; HR=0.91 [0.84–0.97]) or index hospitalization (OR=22.40 [18.63–26.92]; HR=0.51 [0.49–0.53]) were more likely to initiate and persist with antiplatelet agents, while the female (OR=0.75 [0.70–0.81]; HR=1.22 [1.88–1.27]) patients were less likely to initiate and persist with antiplatelet agents.Conclusion: The initiation and persistence with antiplatelet agents are poor among the ACS patients in Tianjin. Females are associated with poorer initiation and persistence, while prior antiplatelet agents use and receiving PCI during baseline period or index hospitalization are associated with better initial use and better persistence.Keywords: acute coronary syndromes, antiplatelet agents, initiation, persistence, China

Shaojian Lin,* Langping Tan,* Dingyuan Luo,* Xinzhi Peng, Yue Zhu, Honghao Li Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Honghao LiDepartment of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 of Yanjiangxi Road, Guangzhou 510120, Guangdong, People’s Republic of ChinaEmail lihonghao63@163.comPurpose: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has continuously increased in recent years. Therefore, it is essential to develop more useful therapeutic strategies.Methods: We collected 56 pairs of PTC tissues and adjacent normal tissues and determined the expression patterns of linc01278, miR-376c-3p and DNM3. In addition, we analyzed the relationship between linc01278 expression and pathological information of PTC patients. Furthermore, the effects of linc01278, miR-376c-3p and DNM3 overexpression on proliferation, clonality, apoptosis, migration and invasion of PTC cell lines TPC1 and BCPAP were evaluated. The dual luciferase reporter assay was used to confirm the direct interaction between miR-376c-3p and linc01278.Results: Linc01278 and DNM3 were remarkably down-regulated in PTC tissues and cell lines, whereas miR-376c-3p was significantly up-regulated. In addition, lower linc01278 expression was associated with increased tumor size, lymph node metastasis and higher clinical stage. Linc01278 inhibited cell proliferation of PTC cells by inducing apoptosis, and demonstrated attenuating effects on migration and invasion abilities of PTC cells by regulating the EMT process. More importantly, dual luciferase reporter experiments demonstrated the direct interaction between miR-376c-3p and linc01278, which revealed that DNM3 was a novel target of miR-376c-3p. The miR-376c-3p mimic significantly promoted the proliferation, migration and invasion of PTC cells, and inhibited cell apoptosis. Overexpression of DNM3 abolished the effects of the miR-376c-3p mimic on PTC cells. DNM3 expression was negatively correlated with miR-376c-3p expression, but was positively correlated with linc01278 expression.Conclusion: Overall, we found that linc01278 can act as a competing endogenous RNA (ceRNA) to sponge miR-376c-3p, thereby positively regulating DNM3 expression and ultimately acting as a tumor suppressor gene in PTC progression.Keywords: linc01278, papillary thyroid carcinoma, ceRNA, DNM3

Liwan Fu,1 Ya-nan Li,1 Dongmei Luo,1,2 Shufang Deng,1 Yue-Qing Hu1,31State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 2Department of Information and Computing Science, School of Mathematics and Physics, Anhui University of Technology, Maanshan, Anhui, People’s Republic of China; 3Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, People’s Republic of ChinaObjective: Numerous studies have explored the role of methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism and homocysteine (Hcy) concentration in obesity, but the results are inconsistent. Hence, we performed a meta-analysis implementing Mendelian randomization approach to test the assumption that the increased Hcy concentration is plausibly related to the elevated risk of obesity.Methods: Eligible studies were selected based on several inclusion and exclusion criteria. Correlations between MTHFR C677T and obesity risk, MTHFR C677T and Hcy concentration in obesity, Hcy concentration, and obesity were estimated by ORs, effect size and standard mean difference with their corresponding 95% CIs, respectively. Furthermore, Mendelian randomization analysis was performed to estimate the relationship between Hcy level and obesity.Results: Consequently, this meta-analysis implemented with Mendelian randomization approach was conducted among 8,622 cases and 29,695 controls. The results indicated that MTHFR C677T is associated with an increased risk of obesity (for T vs C: OR=1.06, 95% CI=1.02–1.10; for TT vs CC: OR=1.13, 95% CI=1.03–1.24). Moreover, in obese subjects, the pooled Hcy concentration in individuals of TT genotype was 2.91 mmol/L (95% CI: 0.27–5.55) higher than that in individuals of CC genotype. Furthermore, the pooled Hcy concentration in subjects with obesity was 0.74 mmol/L (95% CI: 0.36–1.12) higher than that in controls. The evaluated plausible OR associated with obesity was 1.23 for 5 μmol/L Hcy level increase.Conclusions: Through this meta-analysis, we emphasize a strong relationship between Hcy level and obesity by virtue of MTHFR C677T polymorphism.Keywords: homocysteine, MTHFR, obesity, polymorphism

Yi Xiao,1–3,* Xingyu Zhang,4,* Dan Luo,4 Yehong Kuang,1–3 Wu Zhu,1–3 Xiang Chen,1–3 Minxue Shen1–3 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; 2Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China; 3Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China; 4Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China *These authors contributed equally to this work Background: Previous observational studies have shown comorbidity between psoriasis and psychological disorders. However, the evidence of the efficacy of psychological interventions, including cognitive behavioral therapy (CBT) and other treatments, on psoriasis is still debated.Objectives: The aim of this study was to systematically review the psychological interventions used in the treatment of psoriasis and to meta-analyze the efficacy of psychological interventions on psoriasis with respect to area and severity reduction.Materials and methods: A systematic review and meta-analysis were conducted. PubMed, Web of Science, EMbase, and major Chinese academic journal databases were searched for articles published before January 2018. Studies of randomized controlled trials (RCTs) that applied psychological interventions in the treatment of psoriasis and used area and severity as the outcome measures were meta-analyzed. The pooled mean difference between groups was estimated using either fixed-effects models or random-effects models in the presence of heterogeneity. Subgroup analysis was performed by method of intervention and severity of psoriasis.Results: Out of the 4,152 potentially relevant studies, 8 RCTs were included. The pooled mean difference was –1.36 (95% CI: –2.52 to –0.19; P=0.02). The pooled estimate was –1.80 (95% CI: –2.57 to –1.03; P

Wuguo Tian, Shuai Hao, Bo Gao, Yan Jiang, Xiaohua Zhang, Shu Zhang, Lingji Guo, Jianjie Zhao, Gang Zhang, Yi Chen, Zhirong Li, Donglin Luo Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Army Military Medical University, Chongqing 400042, China Objective: Lobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression.Patients and methods: Clinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression.Results: We found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis.Conclusion: Lobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH. Keywords: breast cancer, lobaplatin, proliferation, apoptosis, MTDH

Nian Chen, Qin Qin, Ke-Dai Sun, Dan Luo, Qiong-Hui Cheng Department of Dermatology, Daping Hospital, Army Medical University, Chongqing 400042, China Introduction: Primary cutaneous nocardiosis is a rare suppurative or granulomatous inflammation disease caused by Nocardia infection. Because of nonspecific clinical findings, it is always misdiagnosed as common pyogenic infection. Sulfonamides have been the standard treatment for nocardiosis, but the outcome is always poor due to the high rates of misdiagnosis and refractoriness of the disease. Cases presentations: The presented cases are patients of acute suppurative cutaneous infection without involvement of other organs. We report four cases, of which two cases were localized cutaneous nocardiosis and the other two were lymphocutaneous type of nocardiosis. All cases were diagnosed with pus culture which turned out to be Nocardia brasiliensis. We report an improvement of primary cutaneous nocardiosis symptoms in the four patients treated with non-sulfonamides. All patients were cured and recovered without recurrence during follow-up. Conclusion: Our results suggest that non-sulfonamides are effective treatment for the patients with primary cutaneous nocardiosis who are resistant or intolerant to sulfonamides. Keywords: primary cutaneous nocardiosis, treatment, non-sulfonamides

Dan Luo,* Jiajun Xu,* Li Hu, Liangming Yu, Leling Xie, Jing Li Department of Psychiatry, Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: N2O, or laughing gas, is generally used for anesthesia, especially in stomatology and pediatrics but is also commonly used recreationally. Cognitive dysfunction induced by the recreational use of N2O is rare. Here, we present the case of an 18-year-old female with a history of having used N2O recreationally for 5 months who suffered from encephalatrophy and severe cognitive dysfunction. All of the symptoms gradually subsided with ~20 days of treatment by hyperbaric oxygenation. We hypothesize that the long-term use of N2O may have induced a chronic state of systemic hypoxia that further induced cerebral atrophy with impaired cognitive function. Hyperbaric oxygen therapy (HBOT) is reported here for the first time as an important therapeutic element for treating N2O toxicity due to recreational use. Keywords: N2O, recreational use, cognitive dysfunction, encephalatrophy, hyperbaric oxygen therapy

Qi Liu,1,2 Dakui Luo,1,2 Sanjun Cai,1,2 Qingguo Li,1,2 Xinxiang Li1,2 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Aim: This study focused on improving the American Joint Committee on Cancer TNM staging system and demonstrated an improvement in prognostic accuracy and clinical management of colon cancer using the P–TNM staging system. Patients and methods: Eligible patients (N=56,800) were identified from the Surveillance, Epidemiology, and End Results database between January 1, 2010, and December 31, 2014. The P-stage (P0 or P1) was assigned to each patient based on age at diagnosis, tumor grade, and tumor size. The outcome of interest was cancer-specific survival (CSS). The Cox proportional hazards regression analyses were used to identify independent prognostic factors and analyze the CSS probabilities of patients with colon cancer having different P–TNM stages, respectively. Results: A total of 29,627 patients were assigned to P0-stage and 27,173 patients were assigned to P1-stage. The P1-stage was associated with a 98.1% increased risk of cancer-specific mortality (hazard ratio =1.981, 95% confidence interval =1.891–2.076, P

Lu Zhang,1,* Xingxing Xie,1,* Yigang Zhou,2,* Dainan Yu,1 Yu Deng,1 Jiexiu Ouyang,3 Bei Yang,1 Dan Luo,1 Dalei Zhang,1 Haibin Kuang1,3 1Department of Physiology, Basic Medical College, Nanchang University, Nanchang, 2Department of Color Ultrasonic Room, No 96716 Hospital of PLA, 3Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Medical Experimental Teaching Center, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Background: Titanium dioxide nanoparticles (TiO2 NPs) have recently found applications in a wide variety of consumer goods. TiO2 NPs exposure significantly increases fetal deformities and mortality. However, the potential toxicity of TiO2 NPs on the growth and development of placenta has been rarely studied during mice pregnancy.Purpose: The objective of this study was to investigate the effects of maternal exposure of TiO2 NPs on the placentation.Methods: Mice were administered TiO2 NPs by gavage at 0, 1 and 10 mg/kg/day from gestational day (GD) 1 to GD 13. Uteri and placentas from these mice were collected and counted the numbers of implanted and resorbed embryo and measured the placental weight on GD 13. Placental morphometry was observed by hematoxylin and eosin staining. The levels of Hand1, Esx1, Eomes, Hand2, Ascl2 and Fra1 mRNA were assessed by qRT-PCR. Uterine NK (uNK) cells were detected by using DBA lectin. Laminin immunohistochemical staining was to identify fetal vessels. Western blotting and transmission electron micrograph (TEM) were used to assess the apoptosis of placenta.Results: No treatment-related difference was observed in the numbers of implanted and resorbed embryos and weight of placenta between the groups. However, 1 mg/kg/day TiO2 NPs treatment significantly reduced the ratio of placenta/body weight on GD 13. The proportion of spongiotrophoblast in the 10 mg/kg/day dose group became higher than that in the control group, yet that of labyrinth was significantly lower in 10 mg/kg/day mice. The expression levels of Hand1, Esx1, Eomes, Hand2, Ascl2 and Fra1 mRNA markedly decreased in TiO2 NP treated placentas. Furthermore, TiO2 NPs treatment impaired the formation of intricate networks of fetal vessels and reduced the number of uNK cells, and inhibited proliferation and induced apoptosis of placenta by nuclear pyknosis, the activation of caspase-3 and upregulation of Bax protein and downregulation of Bcl-2 protein on GD 13.Conclusion: Gestational exposure to TiO2 NPs significantly impairs the growth and development of placenta in mice, with a mechanism that seems to be involved in the dysregulation of vascularization, proliferation and apoptosis. Therefore, our results suggested the need for great caution while handling of the nanomaterials by workers and specially pregnant consumers. Keywords: nanoparticles, titanium dioxide, placenta, proliferation, apoptosis, vascularization

Numerous studies have documented that soil respiration and nitrogen cycling show a distinct seasonal dependence regulated by environmental factors (e.g., soil temperature and soil water content). The mechanisms controlling the seasonal dependence of these two key ecosystem processes have rarely been linked to both soil microbial community and soil environmental factors. Here, we present results on the seasonal patterns of soil respiration and gross nitrification rates in three subtropical plantations of Pinus massoniana, Castanopsis hystrix and Erythrophleum fordii over a period of 11 months. Turnover rates were measured with the Barometric Process Separation technique (BaPS). We elucidated how soil respiration and gross nitrification are controlled by the soil microbial community and by soil environmental factors. Soil respiration and gross nitrification showed strong seasonal dynamics, although no significant differences were observed among plantations. The turnover rates were the highest during the wet season and the lowest during the dry season. Microbial biomass, total phospholipid fatty acids (PLFAs), fungal PLFAs and bacterial PLFAs peaked during the dry season. Both soil respiration and gross nitrification rates were positively correlated with soil temperature and soil water content. Microbial biomass decreased with increasing turnover rates. Our findings highlight that carbon and nitrogen turnover rates were mostly controlled by soil temperature and soil water content.

LinLi Luo,* Juan Ni,* Lan Wu, Dong Luo Department of Anesthesiology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China *These authors contributed equally to this work and should be considered co-first authors Abstract: Anesthetic management of patients with preexisting diseases is challenging and individualized approaches need to be determined based on patients' complications. We report here a case of ultrasound-guided epidural anesthesia in combination with low-dose ketamine during cesarean delivery on a parturient with severe malformations of the skeletal system and airway problems. The ultrasound-guided epidural anesthesia was performed in the L1–L2 space, followed by an intravenous administration of ketamine (0.5 mg/kg) for sedation and analgesia. Satisfactory anesthesia was provided to the patient and spontaneous ventilation was maintained during the surgery. The mother and the baby were discharged 5 days after surgery, no complications were reported for either of them. Our work demonstrated that an ultrasound-guided epidural anesthesia combined with low-dose ketamine can be used to successfully maintain spontaneous ventilation and provide effective analgesia during surgery and reduce the risk of postoperative anesthesia-related pulmonary infection. Keywords: anesthesia, regional, cesarean delivery, ketamine, ultrasound-guided

ZhiQiang Yin,1,* JiaLi Xu,2,* BingRong Zhou,1 Di Wu,1 Yang Xu,1 JiaAn Zhang,1 Dan Luo1 1Department of Dermatology, 2Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background: Topical pimecrolimus has been shown to reverse epidermal CD1a+ Langerhans cell reduction induced by high-dose ultraviolet (UV)B irradiation, but the mechanism is still unclear. This study aimed to investigate the possible mechanism of the effect of pimecrolimus on high-dose UVB-irradiated epidermal Langerhans cells.Methods: Forty human foreskin tissues were divided into four groups: control; pimecrolimus-only; UVB-only; and UVB + pimecrolimus. All tissues were cultured, and each tissue was cut into four pieces, corresponding to four time points (0 hours, 18 hours, 24 hours, and 48 hours). We collected the tissues and culture medium at each time point. The percentage of CD1a+ cells in medium was detected by flow cytometry. The tissues were detected for messenger (m)RNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and E-cadherin, by reverse-transcription polymerase chain reaction (PCR) and western blot.Results: At 18 hours, 24 hours, and 48 hours, the CD1a+ cells in the culture medium of the UVB-only group and the UVB + pimecrolimus group were significantly more than in the control group, while the CD1a+ cells of the UVB + pimecrolimus group was less than of the UVB-only group. For both the UVB-only group and UVB + pimecrolimus group, TNF-α expression (by both reverse-transcription PCR and western blot) of the tissues was clearly higher and E-cadherin expression was significantly lower compared with the control group, at 18 hours, 24 hours, and 48 hours. For the UVB + pimecrolimus group, TNF-α was clearly lower and E-cadherin was significantly higher compared with the UVB-only group.Conclusion: Topical pimecrolimus inhibited epidermal Langerhans cell migration induced by high-dose UVB irradiation, via regulation of TNF-α and E-cadherin. Keywords: pimecrolimus, UVB, Langerhans cell, TNF-α, E-cadherin

ZhiQiang Yin,1,* LiWen Ma,1,* JiaLi Xu,2,* JiPing Xia,1 Dan Luo1 1Department of Dermatology, 2Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Jiangsu, People's Republic of China *These authors contributed equally to this work Abstract: Panax notoginseng saponins (PNS) are a patented product in the People's Republic of China, and have extensive effects on the cardiovascular system. Here we report on four elderly patients (one male and three female) with drug eruption induced by PNS injection. All developed a sudden skin rash with pruritus from head to foot, and subsequently accepted hospitalization. In each case, PNS had been used for less than 1 week before appearance of the rash. No specific short-term medications or changes in diet or exposure to environmental factors immediately prior to appearance of the rash were identified. These four patients had some interesting features in common, ie, pustules, fever, and elevated circulating neutrophil counts, which required high-dose, long-term glucocorticoid therapy. To our knowledge, this is the first report of pustular drug eruption induced by PNS and provides a useful reference and warning for clinicians. Keywords: pustule, drug eruption, acute generalized exanthematous pustulosis, Panax notoginseng saponins