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Jue-Xin Wang,1– 3,* Shi-Jia Yu,4,* Gang Huang,1,2 Yan-Bo Yu,1,2 Yan-Qing Li1,2 1Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 2Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Weifang Medical College, Weifang People’s Hospital, Weifang, Shandong Province, People’s Republic of China; 4Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Bo Yu, Email yuyanbo2000@126.comAbstract: The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.Keywords: intestinal barrier, apolipoprotein A-I, dietary fat, gut microorganism, angiogenesis

Dong Wang,* Shi-Jun Wang,* Ying-Jie Li, Chun-Hui Liu, Yong-Qiang Li, Yin-Sheng Zhang, Su Yan Department of Urology, Peking Union Medical College Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Su Yan, Department of Urology, Peking Union Medical College Hospital, No. 1 of Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 13801326306, Fax +86 10 69152520, Email yansudrob@outlook.comBackground: Phosphodiesterase 5 inhibitors (PDE5Is) and other more invasive options merely provide symptomatic relief rather than a permanent improvement in erectile dysfunction (ED), whereas the long-term improvement in ED via low-intensity extracorporeal shockwave therapy (Li-ESWT) has been confirmed. So far, no comparative study of sildenafil versus Li-ESWT has been conducted with respect to treatment satisfaction.Objective: In this study, we aim to compare erectile function status and satisfaction rates in patients who received sildenafil or Li-ESWT for ED.Methods: Patients complaining of ED were considered candidates. Participants chose to enter one of two active treatment groups according to their treatment intention—either a 9-week Li-ESWT regimen or 100 mg on-demand sildenafil. The erectile function was evaluated using the erectile function domain of the International Index of Erectile Function questionnaires (IIEF-EF), while the treatment satisfaction was evaluated using the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaires (EDITS).Results: We enrolled 72 participants in the study (42 in the Li-ESWT group and 30 in the sildenafil group). Patients in both groups were young men. Four weeks after the last session, the IIEF-EF score for Li-ESWT and sildenafil was 16.3± 5.5 and 18.3± 6.5 (P > 0.05), respectively. The total EDITS index of the patient version and the partner version were similar in the two groups. Among EDITS questions measuring overall satisfaction and efficacy duration, the score was higher in the Li-ESWT group.Conclusion: We found that Li-ESWT may have better satisfaction than on-demand sildenafil for young ED patients. However, further studies are needed to determine the factors influencing satisfaction.Keywords: erectile dysfunction, Erectile Dysfunction Inventory of Treatment Satisfaction, low-intensity extracorporeal shock wave therapy, sildenafil

Zhen-Hua Li,1,&ast; Jie Wang,1,&ast; Xin Cheng,1,&ast; Yi-Cheng Mao,1 Kang-Di Zhang,1 Wen-Jie Yu,1 Ying-Qing Li,1 Kai Huang,1,2 Kun Ding,1 Xiao-Jing Yang,1 Cheng-Yang Hu,3 Xiu-Jun Zhang1,4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Hospital Infection Prevention and Control, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Humanistic Medicine, School of Humanistic Medicine, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Center for Evidence-Based Practice, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng-Yang Hu; Xiu-Jun Zhang, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Tel/Fax +86 551 65167031 ; +86 551 65169635, Email cy.hu@ahmu.edu.cn; zhangxiujun@ahmu.edu.cnBackground: There is growing evidence that the COVID-19 pandemic has had a dramatic impact on public mental health. However, less attention has been paid to left-behind experience college students (LBEs). This online study aimed to investigate the relationship between psychological capital (PsyCap) and anxiety among LBEs during COVID-19 pandemic, and further analyze the mediation role of self-esteem between them.Methods: A total of 9990 students were chosen using the stratified cluster sampling method. Three self-reported questionnaires were used to assess the PsyCap, self-esteem, and anxiety, respectively. All the statistical analyses were conducted using SPSS 23.0 and R, and to further investigate the mediation effect of self-esteem in the association of PsyCap with anxiety, AMOS 23.0 was used to build a structural equation model.Results: PsyCap, self-esteem, and anxiety were significantly correlated among LBEs during the COVID-19 pandemic. PsyCap affects anxiety directly (β = – 0.22, SE = 0.051, 95% CI: – 0.27, – 0.17, P < 0.05). In addition, self-esteem partially mediated the relationship between PsyCap and anxiety (mediating effect value = – 0.16, 95% CI: – 0.20, – 0.13, P < 0.05).Conclusion: During the pandemic of COVID-19, left-behind experience had a negative influence on the PsyCap and self-esteem of college students. In addition, for LBEs, self-esteem plays an important mediating role between PsyCap and anxiety. Therefore, from the perspective of PsyCap and self-esteem, schools should translate them into practical educational strategies to enhance the mental health and mitigate the anxiety levels of LBEs.Keywords: left-behind experience, COVID-19, psychology, mental health

Hong-Fu Li,1,2,&ast; Li-Xia Zhang,2,&ast; Wen-Lan Zhang,2,&ast; Jing Li,2,&ast; Ya-Qian Li,2,&ast; Tong-Ping Hu2 1Department of Clinical Laboratory, Zhuhai Third People’s Hospital, Zhuhai, People’s Republic of China; 2Department of Clinical laboratory, the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tong-Ping Hu, Department of Clinical laboratory, the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, No. 41, of Linyin Road, Kundulun District, Baotou City, Baotou, 014000, People’s Republic of China, Tel +86 13296922365, Email hutongping1976@126.comObjective: The purpose of this study was to analyse the clinical, microbiological and molecular epidemiological characteristics of patients with pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae (KPN) in Inner Mongolia, China.Methods: The KPN isolates from 78 KPN-PLA cases admitted to a tertiary teaching hospital in Baotou, Inner Mongolia, from 2016 to 2019 were studied systematically and described comprehensively. The virulence factors, drug resistance and sequence types of KPN in different samples were identified by a wire-drawing test, polymerase chain reaction, a drug susceptibility test and multi-site sequence typing.Results: There were more male than female KPN-PLA patients (P< 0.05). The mortality rate was 2.5%, and KPN-PLA was significantly associated with diabetes mellitus (P< 0.05). Most of the KPN isolates in the puncture fluid of patients with KPN-PLA were hypervirulent KPN (HvKP). The positive rate of the KPN-PLA specimens was higher than that of the blood and urine specimens. The KPN isolates of the urine specimens had higher drug resistance than the other two (P< 0.05). The hypermucoviscous KPN, aerobic actin (aero) (+), K1 and K2 serotypes accounted for 80.8%, 89.7%, 56.4% and 26.9%, respectively. In addition to ironB (3.8%), the detection rates of virulence factors rmpA, irp2, entB, iucD, aero, wcaG, iutA, kfu, ybtA, iron, fimH and mrkD were higher (69.2%– 100.0%). The positive rate of KPN isolates of the KPN-PLA puncture fluid was higher than that of the blood and urine samples (P< 0.05). In addition, ST23 was found to be the dominant ST (32.1%) of KPN-PLA in the Baotou region.Conclusion: In the KPN-PLA specimens, the KPN isolates were more virulent than those in the blood and urine specimens, and a carbapenem-resistant HvKP strain emerged. This research will help improve the understanding of HvKP and provide useful suggestions for KPN-PLA treatments.Keywords: Klebsiella pneumoniae, virulence factor, capsular serotype, bacterial drug resistance, multilocus sequence typing

Jian ming Wang,1 Yong qiang Li2 1School of Business Administration, Zhejiang University of Finance & Economics, Hangzhou, Zhejiang Province, 310018, People’s Republic of China; 2China Institute of Regulation Research, Zhejiang University of Finance & Economics, Hangzhou, Zhejiang Province, 310018, People’s Republic of ChinaCorrespondence: Yong qiang Li, Email 1836514269@qq.comPurpose: To explore the effects of “soft” behavioral intervention policies (eg, green emotions, social norms) and “soft” economic incentive policies (eg, high-intensity subsidies, low-intensity subsidies) and their combinations on the public’s green product purchasing behavior.Participants and Methods: An online questionnaire experiment was conducted on Chinese users using Credamo online questionnaire platform to explore the effects of different “soft” intervention policies on consumers’ green purchasing behavior, and the sample data were examined using multiple regression. In Study 1, a total of 460 valid samples were collected to explore the differences in the effects of single intervention policies; in Study 2, a total of 556 valid samples were collected to explore the effects of a combination of soft policies.Results: In the area of green product purchasing, both behavioral interventions and economic incentives alone can promote green consumption behavior; economic incentives have a more positive impact on guiding consumers to green consumption; the combination of “soft” behavioral interventions and “soft” economic incentives has a positive impact on green consumption. The combination of “soft” behavioral intervention policies and “soft” economic incentive policies is more effective than the individual policies.Conclusion: The experimental results of Study 1 show that the policy effects of both behavioral intervention policies and economic incentive intervention policies are evident for goods with different value attributes. Meanwhile, comparing the two types of soft intervention policies, we find that the effect of economic incentive intervention policies is stronger than that of soft behavioral intervention policies. In Study 2, the empirical analysis of the policy mix shows that the policy mix is more effective. The combination of “soft” economic incentive policies and “soft” behavioral intervention policies can effectively increase the salience of policy instruments, and the effect of policy combinations is greater than that of single policies.Keywords: green consumption, intervention policy, policy mix

Meng-Na Wang,1,* Hai-Tao Yu,2,* Ya-Qian Li,1 Yun Zeng,1 Shuang Yang,3 Guo-Ping Yang,1,3– 6 Qi Pei,6 Jie Huang1,3 1Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Research and Development Center, Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd., Nanjing 210038, People’s Republic of China; 3Research Center of Drug Clinical Evaluation of Central South University, Changsha, Hunan 410013, People’s Republic of China; 4XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of China; 5National-Local Joint Engineering Laboratory of Drug Clinical Evaluation Technology, Changsha, Hunan 410013, People’s Republic of China; 6Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Huang; Qi PeiThe Third Xiangya Hospital, Central South University, Yinpenling Street, Yuelu District, Changsha, Hunan 410013, People’s Republic of ChinaTel +86 15116469024Fax +86 731 8861 8326Email cellahuang1988@163.com; peiqi1028@126.comObjectives: This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and OcalivaTM under fasting and fed conditions and to determine the effects of food on the pharmacokinetic (PK) profiles of OCA in healthy Chinese subjects.Methods: A randomized, single-dose, three-sequence, three-period, partial replicated crossover study was conducted with a 21-day washout interval between periods under fasting (n=48) and fed (n=48) conditions. Blood samples for OCA and its metabolites Glyco-OCA and Tauro-OCA were collected up to 168 hours after administration in each period. PK parameters were calculated using the non-compartmental method. Geometric mean ratios for PK parameters of the test to reference drug under fasting and fed conditions and their 90% confidence intervals were estimated. Safety evaluations were carried out all through the study.Results: A total of 91 subjects completed the study with 45 in a fasted state and 46 receiving a high-fat diet. There were no serious or unexpected drug-related adverse events occurring during the study. There was no significant difference in the main PK parameters of the two preparations, irrespective of the fasting or fed conditions. Under fasting and fed conditions, the SWR of lnCmax, lnAUC0-t and lnAUC0-∞ were 0.445, 0.370, 0.448, 0.340, 0.168, and 0.180, respectively. Thus, the average BE or the reference-scaled average BE was used to verify that the two preparations were bioequivalent under fasting and fed conditions. Compared with the fasting state, the AUC0-t of the test drug, the AUC0-t, and AUC0-∞ of the reference drug were higher in the fed state.Conclusion: The test drug and the reference drug were BE and well tolerated in Chinese healthy subjects under both fasting and fed conditions. Food-intake may cause a significant difference in the main PK parameters of the two preparations.Keywords: obeticholic acid, bioequivalence, pharmacokinetics, food effect

Hao Xu,1,2,* Sha-Jie Dang,3,4,* Yuan-Yuan Cui,1 Zhen-Yu Wu,1 Jun-Feng Zhang,2 Xiao-Peng Mei,5 Yu-Peng Feng,1 Yun-Qing Li1 1Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi’an, Shaan Xi, People’s Republic of China; 2Institution of Basic Medical Science, Xi’an Medical University, Xi’an, Shaan Xi, People’s Republic of China; 3Department of Anesthesiology, Shaanxi Provincial Cancer Hospital, Xi’an, Shaan Xi, People’s Republic of China; 4The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaan Xi, People’s Republic of China; 5Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaan Xi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun-Qing Li; Yu-Peng FengDepartment of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi’an, Shaan Xi, People’s Republic of ChinaEmail deptanat@fmmu.edu.cn; fengyp@fmmu.edu.cnBackground and objective: Thalidomide (Tha) has been shown to exert immunomodulatory and anti-inflammatory properties. Whether Tha can alleviate spinal nerve ligation (SNL)-induced neuropathic pain (NP) is still unclear. This study aimed to investigate the therapeutic effect of Tha on the SNL-induced NP and further explore the potential analgesic mechanisms of Tha.Methods: The effects of Tha on SNL-induced mechanical allodynia were assessed by pain behavioral testing. The expressions of the astrocyte marker glial fibrillary acidic protein (GFAP) and the microglia marker Iba1 in the spinal dorsal horn were evaluated by immunofluorescence histochemistry. Protein expressions of the tumor necrosis factor alpha (TNF-α) in the spinal dorsal horn were tested by Western blot assay. Data were analyzed using one-way ANOVA or two-way ANOVA.Results: By the pretreatment with a single intraperitoneal injection, the PWMT in SNL+Tha group was significantly increased from day 1 to day 2 after SNL (P < 0.05 compared with SNL+Veh group). By the posttreatment with a single intraperitoneal injection, the PWMT in SNL+Tha group was also significantly increased from day 3 to day 4 after SNL (P < 0.05 compared with SNL+Veh group). By the posttreatment with multiple intraperitoneal injection, both the PWMT and the PWTL in SNL+Tha group were similarly significantly increased from day 3 to day 14 after SNL (P < 0.05 compared with SNL+Veh group). Furthermore, the GFAP and Iba1 expressions and TNF-α levels of the ipsilateral spinal dorsal horn in SNL+Tha group were significantly weaker from day 3 to day 14 after SNL than those in SNL+Veh group (P < 0.05).Conclusion: Tha can significantly alleviate NP induced by SNL. The analgesic mechanism may be related to inhibition of astrocyte and microglia activation as well as down-regulation of TNF-α levels in the spinal dorsal horn.Keywords: Tha, neuropathic pain, Glia, TNF-α, spinal nerve ligation

Zhuo Fu,1 Yan Jiao,2 Yan-Qing Li,3 Jian-Ji Ke,2 Yan-Hui Xu,4 Bao-Xing Jia,2 Bin Liu1 1Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 3Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People’s Republic of China; 4Department of Digestive, China-Japan Union Hospital Affiliated to Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaCorrespondence: Bin LiuDepartment of Hand and Foot Surgery, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin 130021, People’s Republic of ChinaEmail blwork@126.comPurpose: Liver cancer has a high incidence of mortality. DNA replication and posttranscriptional modifications play important roles in the development of liver cancer. Pescadillo (PES1) is a nuclear protein that is involved in embryonic development, ribosome synthesis, DNA replication, and cell cycle progression. Recently, abnormal PES1 expression was reported in several tumors, including neuroblastoma, colon cancer, gastric cancer, and breast cancer. Based on bio-informatic analysis, cell experiments and animal models, the aim of this study is to investigate the expression patterns and specific roles of PES1 in liver cancer.Patients and methods: PES1 expression was represented by boxplots. The correlation between PES1 expression and clinical features was assessed by the chi-squared test and Fisher’s exact tests. Kaplan–Meier curves compared overall survival between different levels of PES1 expression, and Cox analysis selected potential variables associated with overall survival. The MTT assay investigated the proliferation rate, the scratch assay assessed the migratory ability, and the Transwell assay evaluated the invasion capacity of tumor cells in vitro. Animal models were used to confirm the tumorigenic roles of PES1 in vivo. GSEA illustrated the molecular mechanisms that PES1 participated in.Results: We found that PES1 was highly expressed in liver cancer tissues, served as a diagnostic marker, and correlated with poor overall survival (OS) and relapse-free survival (RFS) in patients. In vitro studies indicated that PES1 promoted tumor cell proliferation (P=0.0034), migration (P=0.0026), and invasion (P=0.0008), and this tumorigenic role was confirmed in animal models. GSEA further illuminated molecular mechanisms that PES1 participated in liver cancer occurrence and progression.Conclusion: This study suggested that PES1 was upregulated in liver cancer and correlated with poor prognosis, by promoting tumor cell proliferation, migration, and invasion, and PES1 may be a novel diagnostic and prognostic bio-marker and a promising therapeutic target in liver cancer.Keywords: liver cancer, PES1, diagnosis, tumorigenesis, prognosis

Jian-Wei Lin,1 Le-He Yang,2 Zhuo-Chao Ren,3 De-Guang Mu,3 Ya-Qing Li,3 Jian-Ping Yan,3 Liang-Xing Wang,4 Chun Chen31Department of Cardiology, Xiasha Campus, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310018, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, Wenzhou Medical University, Wenzhou 325600, Zhejiang, People’s Republic of China; 3Department of Respiratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People’s Republic of China; 4Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of ChinaBackground: To evaluate the effects of resveratrol to monocyte chemoattractant protein-1 (MCP-1) and the role of p38 mitogen-activated protein kinase (MAPK) in this process in vitro.Materials and methods: Animal acute pulmonarythromboembolism (PTE) model: rat model was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. One hundred and thirty-two rats were randomly and equally divided into ten groups: rats-control (untreated), rats-1% DMSO, rats-TNF-α, rats-TNF-α + resveratrol, rats-TNF-α +C1142, rats-TNF-α+SB203580, rats-TNF-α+resveratrol + SB203580, rats-resveratrol only, rats-C1142 only, and rats-SB203580 only. Rat pulmonary artery endothelial cells (RPAs) tests: RPAs were isolated from above animal and designated as: RPAs-control, RPAs-1% DMSO control, RPAs-TNF-α, RPAs-TNF-α + resveratrol, RPAs-TNF-α + C1142, RPAs-TNF-α + SB203580, RPAs-TNF-α + resveratrol + SB203580, RPAs-resveratrol only, RPAs-C1142 only, and RPAs-SB203580 only. Each group was further divided into 1, 4, and 8 hrs time point for evaluation (n=6 rats per time point) except RPAs-TNF-α + SB203580, RPAs-TNF-α + resveratrol + SB203580, RPAs-C1142 and RPAs-SB203580 only, which were evaluated at 8 hrs time point. At each time point, mRNA and protein expressions of RPAs of MCP-1 were measured. The phosphorylation of p38 MAPK (p-pMAPK) of RPAs was also detected.Results: We found that the RPAs-TNF-α elicited significant increases in MCP-1 expression and phosphorylation of p38 mitogen-activated protein kinase (p-p38 MAPK). Furthermore, the MCP-1 expressions of RPAs-Resveratrol, RPAs-C1142, and RPAs-SB203580 were significantly down-regulated, which was associated with robustly suppressed TNF-α-induced p-p38MAPK expression.Conclusion: Our findings suggested that MCP-1 was involved in the formation of TNF-α-induced inflammatory response, and resveratrol could down-regulate the expression of MCP-1 via TNF-α- inhibition, which might contribute to the decline of acute PTE-induced PH in vivo.Keywords: inflammation, pulmonary artery endothelial cells, pulmonary hypertension, pulmonary thromboembolism, resveratrol

Yuanbo Lan,1,* Yuqin Li,1,* Ling Chen,1 Jianyong Zhang,1 Hong Zhang1,2 1Department of Respiratory Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, China; 2Z-BioMed, Inc., Rockville, MD 20855, USA *These authors contributed equally to this work Objectives: Tuberculosis (TB) is the leading cause of death from infectious diseases in the world, with an estimated 1.6 million deaths from TB in 2017. The objectives of this study were to determine drug resistance profiles of Mycobacterium tuberculosis clinical isolates and to analyze the trends in drug-resistant and multidrug-resistant tuberculosis (MDR-TB) from 2008 to 2015 at a major hospital in Guizhou, a high-TB burden and resource-limited province of China. Patients and methods: A total of 462 clinical isolates were collected from patients with pulmonary TB during the period from January 2013 to December 2015 and used for determining drug resistance profiles against four first-line and six second-line anti-TB drugs, and the results were compared with those of two previous studies. Results: Exactly 4.4% of new and 44.1% of previously treated TB cases were MDR/rifampicin-resistant TB (RR-TB), which were higher than the 2017 global average numbers of 3.5% and 18%, respectively. There were many drug-resistant patterns among MDR-TB isolates and most of them were resistant to three or four anti-TB drugs. The trends in drug-resistant and MDR-TB declined at the hospital from 2008 to 2015. Conclusion: Results of this study show that the prevalence of MDR/RR-TB at a major hospital in Guizhou is higher than the global average and confirm the existence of heterogeneity in drug resistance patterns of MDR-TB isolates. Additionally, three practical measures have played an important role in the overall decline of MDR-TB at the hospital from 2008 to 2015. Keywords: Mycobacterium tuberculosis, anti-TB drugs, drug resistance patterns, trends

Mingzhi Xie,1 Yufeng Lv,2 Zhihui Liu,1 Jingyan Zhang,1 Chaoyong Liang,1 Xiaoli Liao,1 Rong Liang,1 Yan Lin,1 Yongqiang Li1 1First Department of Chemotherapy, Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, P.R. China; 2Department of Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, P.R. China Purpose: Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers with high mortality worldwide. However, biomarkers for predicting prognosis in ccRCC are limited. In this study, we attempted to identify potential prognostic biomarkers of ccRCC. Methods: Clinical information and the preprocessed ccRCC mature miRNA expression profiles in The Cancer Genome Atlas database were downloaded from UCSC Xena. The miRNAs differentially expressed between ccRCCs and matched normal tissues were analyzed using the “limma” package. A miRNA-based signature was constructed using the multivariate Cox regression model with prognosis index (PI) formula. Patients with ccRCC were divided into low-risk and high-risk subgroups according to median PI. The survival times were compared between the two groups using Kaplan–Meier analysis with log-rank test. The training set was used to construct a miRNA-based signature for predicting prognosis. The test set was used to verify the signature. Target gene prediction and functional enrichment analysis of the four miRNAs were performed using miRNet. Results: We identified four miRNAs, miRNA-21-5p, miRNA-9-5p, miR-149-5p, and miRNA-30b-5p, as independent prognostic indicators. Next, we used these four miRNAs to construct a four-miRNA PI for each patient. Results revealed that patients in the high-risk group (n=119) had significantly shorter survival time than those in the low-risk group (n=118) (high-risk/low-risk group log-rank P=0.000). This four-miRNA signature is an independent prognostic factor compared with routine clinicopathological features in the test set. These miRNAs targeted 1,634 genes, and a miRNA-target gene network was constructed using miRNet. The target genes of these four miRNAs were involved in various pathways related to cancer. Conclusion: Our observations suggest that the four-miRNA signature correlated with the survival of patients with ccRCC and can be used as a prognostic biomarker of ccRCC. Keywords: ccRCC, miRNA signature, overall survival, prognostic biomarkers

Yonghui An,1,2 Jia Li,1,2 Yongqian Li,1,2 Yong Shen1,2 1Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China Background: The purpose of this study was to evaluate characteristics of Modic changes in cervical kyphosis (CK) and their association with axial neck pain. Methods: Study participants included 286 asymptomatic or symptomatic patients with CK (mean age = 54.2 ± 12.2 years) who were consecutively enrolled from March 2009 to October 2015. Clinical and radiographic evaluations were performed at a university outpatient department. CK was classified as global type, reverse sigmoid type, or sigmoid type. Results: There were 138 participants with global type CK, 103 with reverse sigmoid type CK, and 45 with sigmoid type CK. Of the 286 participants, 102 had Modic changes (Modic-1 in 38 segments and Modic-2 in 75 segments). Spinal cord compression grade and disc degeneration occurred more frequently in the group with axial neck pain compared to the group without pain. Angular motion was decreased in those with axial neck pain (mean ± standard deviation [SD] 7.8°±4.6°) compared to those who were asymptomatic (mean ± SD 8.9°±5.1°; P

Ya-Ru Wang,1,* Fei-Long Tian,2,* Ming-Xian Yan,1 Jin-Hua Fan,1 Li-Yun Wang,1 Rong-Guang Kuang,1 Yan-Qing Li3 1Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, 2Shandong University School of Medicine, 3Department of Gastroenterology, Qilu Hospital, Shandong University, Ji’nan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain.Purpose: To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis.Methods: Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting.Results: Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse tran­scription polymerase chain reaction showed increased levels of NF-κB/p65, ICAM-1, TNF-α, α-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-κB/p65, ICAM-1, and α-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2, and DS3 rats.Conclusion: SF inhibits pancreatic inflammation and fibrogenesis via NF-κB signaling pathway. Keywords: sulfasalazine, pancreatic injury, inflammation, fibrogenesis, NF-κB

Zhan-Wen Xu,1 Ya-Qin Li,1 Li-xia Liu,2 Bing-Juan Zhou3 1Department of Cardiology, 2Department of Ultrasound, Affiliated Hospital of Hebei University, 3Department of Pathology, Baoding First Central Hospital, Baoding, People’s Republic of China Abstract: Light-chain amyloidosis is a relatively rare multisystem disorder. The disease often is normally difficult to diagnose due to its broad range of characters without specific symptoms. A 62-year-old male patient presented with heart failure after experiencing a long period of unexplained and untreated gastrointestinal symptoms. Clinical examination and laboratory findings indicated a systemic process with cardiac involvement. Echocardiography revealed concentric left ventricular hypertrophy with enhanced echogenicity and preserved ejection fraction. Rectum biopsy confirmed amyloid deposition. The side effect of delayed diagnosis on prognosis and the appropriate diagnostic strategy has been discussed. Keywords: light-chain amyloidosis, cardiac amyloidosis, echocardiography, autonomic neuropathy, peripheral neuropathy

Yuqian Li,1,* Wei Fang,1,* Lei Tao,2,* Min Li,1 Yanlong Yang,1 Yafei Gao,1 Shunnan Ge,1 Li Gao,1 Bin Zhang,1 Zhihong Li,1 Wei Zhou,1 Boliang Wang,3 Lihong Li11Department of Neurosurgery, 2Department of Anesthesiology, 3Department of Emergency, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this studyBackground: Nicardipine (NC) is the most commonly used antihypertensive drug in neurological patients with hypertension. Although nimodipine (NM) is widely used to treat cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage, trials exploring its antihypertensive effect after intravenous administration in subjects with intracerebral hemorrhage (ICH) are scarce.Methods: A retrospective study was carried out to compare the safety and efficacy of NC and NM administered intravenously in patients with ICH. Therapeutic responses were assessed by achievement of goal blood pressure (BP); use of additional medications for BP control; proportion of time spent within goal; variability in BP; time to goal BP; number of dose adjustments; variability in ICH volume, Glasgow Coma Scale score, and intracranial pressure; and drug-related complications.Results: A total of 87 patients were eligible for analysis (n=46 [NC]; n=41 [NM]), and baseline characteristics between groups were similar. Both agents were effective in achieving goal BP during infusion, with 93.5% and 87.8% patients in the NC and NM groups achieving goal, respectively. Fewer additional medications were needed to control BP in the NC group. BP variability was similar and no differences were observed in the mean time to goal BP and mean numbers of dose adjustments between both groups. Interestingly, intracranial pressure declined (P=0.048) during NC administration but increased (P=0.066) after NM treatment. Finally, the incidences of hematoma expansion, neurological deterioration, and adverse drug events were similar in both groups.Conclusion: NM is effective and safe for BP control in patients with ICH.Keywords: nicardipine, blood pressure, intravenous infusion

Qiushi Wang,1 Jianghong Mou,1 Xin Yang,1 Yong He,2 Zengpeng Li,1 Qingya Luo,1 Yanqing Li,1 Li Lin,1 Yu Ma,1 Hualiang Xiao11Department of Pathology, 2Department of Respiration, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of ChinaBackground: The clinical characteristics of epidermal growth factor receptor (EGFR) hotspot mutations, such as deletions in exon 19, substitution of L858R in exon 21, and mutations in exon 20, have been widely reported in nonsmall cell lung cancer. However, the clinical features of other low frequency EGFR mutations in these four exons (especially the relationship with smoking history), eg, substitutions of G719S/A/C in exon 18 and L861Q in exon 21, remain unclear. This study investigated the relationship between G719S/A/C and L861Q mutations (in exon 18 and 21) and smoking history.Methods: Specimens from 194 patients with lung adenocarcinoma were analyzed for EGFR mutations in exons 18–21 by high-resolution melting curve analysis and amplification refractory mutation technology to establish the relationship between G719S/A/C and L861Q mutations and smoking history.Results: Ninety-six of 194 tumors (49.5%) were confirmed to be EGFR mutation-positive. Among these mutations, 71 of 104 (68.3%) were from never smokers, six of 17 (35.3%) were from former smokers, and 19 of 73 (26.0%) were from current smokers (P < 0.001). The mutation rate in heavy smokers (5/23, 21.7%) was significantly lower than in light smokers (20/67, 29.9%) and never smokers (71/104, 68.3%, P < 0.001). Seven low frequency EGFR mutations (four substitutions of G719S, and G719 A, respectively, and three of L861Q in exon 21) were identified. Five of these mutations were derived from smokers (one former light smoker, one current heavy smoker, and three current light smokers). Four of these patients had been treated with tyrosine kinase inhibitors and all had a partial response, with median overall survival (14.5 months) and median progression-free survival (6.8 months), being longer than in patients with similarly staged lung adenocarcinoma without EGFR mutation or treatment with tyrosine kinase inhibitors (6.8 and 3.1 months, respectively, according to data from an as yet unpublished study at our institution).Conclusion: This study provides further evidence that smoking status, include years of smoking and number of cigarettes smoked per day, plays an important role in EGFR mutation in patients with lung adenocarcinoma. Five of seven specimens with G719S/A or L861Q mutations coming from smokers indicates that there may be a relationship between G719S/A or L861Q mutation and smoking history. However, regardless of the influence of smoking, the effectiveness of tyrosine kinase inhibitors was satisfactory in four patients harboring G719S/A and L861Q EGFR mutation.Keywords: EGFR, lung adenocarcinoma, G719S/A, L861Q, smoking history

ZhiQiang Yin,1,* JiaLi Xu,2,* YongQiang Li,3,* JiPing Xia,1 Dan Luo1 1Department of Dermatology, 2Department of Oncology, 3Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China *These authors contributed equally to this work Abstract: This study reports a case of an 80-year-old male who suffered from drug eruption due to oral allopurinol for the treatment of gout. This patient complained of widespread erythema and maculopapule with itch, and small quantities of purplish-red rash with diffused distribution on four limbs were noted. After he was hospitalized, the area with purpuric rash increased in size, and hypofibrinogenemia was found. After treatment with intravenous infusion of fibrinogen and cryoprecipitate, and continued treatment with high-dose methylprednisolone, the skin rash gradually went away. This is the first report of purpura and hypofibrinogenemia induced by allopurinol and the pathophysiology underlying this reaction remained unknown. Keywords: purpura, fibrinogen, drug eruption, gout