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Objectives: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. Methods: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. Results: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47–32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20–12.70, P = 0.024). Conclusions: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the characteristics and prognostic factors for coronavirus disease 2019 (COVID-19) patients on maintenance hemodialysis (HD). Methods: All admitted HD patients who were infected with SARS-CoV-2 from December 1, 2022, to January 31, 2023, were included. Patients with pneumonia were further classified into the mild, moderate, severe, and critical illness. Clinical symptoms, laboratory results, radiologic findings, treatment, and clinical outcomes were collected. Independent risk factors for progression to critical disease and in-hospital mortality were determined by the multivariate regression analysis. The receiver operating characteristic analysis with the area under the curve was used to evaluate the predictive performance of developing critical status and in-hospital mortality. Results: A total of 182 COVID-19 patients with HD were included, with an average age of the 61.55 years. Out of the total, 84 (46.1%) patients did not have pneumonia and 98 (53.8%) patients had pneumonia. Among patients with pneumonia, 48 (49.0%) had moderate illness, 26 (26.5%) severe illness, and 24 (24.5%) critical illness, respectively. Elder age [HR (95% CI): 1.07 (1.01–1.13), p <0.01], increased levels of lactate dehydrogenase (LDH) [1.01 (1.003–1.01), p <0.01], and C-reactive protein (CRP) [1.01 (1.00–1.01), p = 0.04] were risk factors for developing critical illness. Elder age [1.11 (1.03–1.19), p = 0.01], increased procalcitonin (PCT) [1.07 (1.02–1.12), p = 0.01], and LDH level [1.004 (1–1.01), p = 0.03] were factors associated with increased risk of in-hospital mortality. Conclusion: Age, CRP, PCT, and LDH can be used to predict negative clinical outcomes for HD patients with COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Methods: Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. Results: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). Conclusion: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment. [ABSTRACT FROM AUTHOR]

Colistin is an important antimicrobial agent in the treatment of infections caused by multidrug resistant (MDR) Gram-negative bacteria. The horizontal transfer of mobile colistin resistance gene (mcr) poses a major threat to the public health worldwide. In this study, a total of thirteen mcr-carrying Escherichia coli (MCREC) strains were recovered from a tertiary hospital in Zhejiang, China, between 2016 and 2019. The minimum inhibitory concentration (MIC) of antimicrobial agents, epidemiological characteristics, and transmission dynamics of mcr-carrying isolates were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and southern blotting analysis. All strains were discovered to be resistant to colistin, and the majority displayed MDR phenotype. However, none of the 13 MCREC strains were resistant to carbapenems. The 13 MCREC isolates were divided into 10 different STs, including ST744, ST156, ST453, ST410, ST57, ST131, ST7034, ST2599, ST457, and ST13239, in which ST13239 was discovered for the first time. Based on core genome single nucleotide polymorphism (cgSNP) analysis, no clear epidemiological link was discovered in these strains with the exception of EC2118 and EC3807, which differ by just one SNP. A total of 35 antimicrobial resistance genes which can be divided into 14 classes were identified from the 13 MCREC isolates. According to S1-PFGE and southern blotting analyses, all 13 MCREC strains had plasmid-mediated mcr-1, and nine of them carried conjugative plasmids. In conclusion, our study revealed the emergence and dissemination of colistin-resistant E. coli isolates carrying mcr-1 in a Chinese hospital, which poses a potential risk to anti-infective therapy. More efforts should be taken to monitor the prevalence of mcr-1-carrying bacteria in China. [ABSTRACT FROM AUTHOR]

Purpose: Recurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method. Method: A population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection. Results: A total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode. Conclusion: Relapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary bypass (CPB) during open-heart surgery triggers an inflammatory response that can cause significant morbidity and mortality. Human monocytes and regulatory T (Treg) cells are phenotypically and functionally heterogeneous and have been shown to play a significant role in the inflammatory dysfunction triggered by CPB. Glucocorticoids (GCs) have been widely administered for decades in patients undergoing CPB to reduce this inflammatory response. However, it has not been clearly established how routine prophylactic administration of glucocorticoids (GCs) affects monocyte and Treg subsets. Methods: Thirty-six patient who underwent heart surgery with CPB were randomly assigned to a methylprednisolone group (MG, N = 18; 500 mg in the CPB priming) and a non-methylprednisolone group (NMG, N = 18). The circulating monocyte and Treg subsets were analyzed by flow cytometry. Results: The MG and NMG groups had comparable percentages of monocyte subsets and similar expression levels of HLA-DR, CD86, CD64 and toll-like receptor 4 (TLR4). Remarkably, methylprednisolone increased the percentage of CD4+CD25+ Treg cells among CD4+ T cells in patients undergoing CPB, but did not increase the proportion of suppressive Treg cells, either resting or activated, in these patients undergoing CPB. Conclusions: Our results showed that prophylactic administration of methylprednisolone neither decreased the percentages and counts of inflammatory monocyte subsets nor did it induce the expansion of suppressive Treg cells in patients undergoing CPB. These results clarified the effects of GCs on cell-mediated immune responses and provided additional evidence in practice. Trial registration: Clinicaltrials.gov: NCT01296074. Registered 14 February 2011. [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacteria (NTM) have been reported to be increasing worldwide and its geographic distribution differs by region. The aim of this study was to describe the epidemiology and distribution of NTM in the eastern part of China. Methods: Sputum samples were collected from 30 surveillance sites for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008. Identification was performed using a biochemical test, multiplex PCR and GenoType Mycobacterium CM/AS assay. Results: A total of 1779 smear positive clinical isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM were identified; M. intracellulare was the predominated species (68.33%), followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%), M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%). Conclusion: M. intracellulare was the main species of NTM in the eastern part of China and clinical physicians should pay more attention to NTM induced pulmonary disease. Author Summary: Nontuberculous mycobacteria (NTM) exist ubiquitously in the environment and cause many kinds of diseases including pulmonary infection. Despite this, NTM does not match compulsory report policy in many countries, such as China. Thus, the epidemiology of NTM is generally unknown. Furthermore, misdiagnosis of nontuberculous mycobacterium disease as multi-drug resistant tuberculosis (MDR-TB) frequently occurs in clinical settings because of similar clinical manifestations. Therefore, elucidating the epidemiology and distribution of NTM species is important and may have a profound and lasting impact on the prevalence of pulmonary NTM disease. In our study, we enrolled smear-positive sputum samples during 2008 from Jiangsu province in the eastern region of China. Traditional biochemical tests and molecular biological methods were performed to distinguish NTM isolates to species/complex level. For the first time, we provide a snapshot of the epidemiology and geographic distribution of NTM in Jiangsu province. The proportion of NTM was 3.37% of all the Mycobacterium isolates and the species of NTM differed by area. [ABSTRACT FROM AUTHOR]

Background: The genotypes of Mycobacterium tuberculosis (MTB) have been found to be related to the risk of transmission and the development of drug resistance of this pathogen. Thus, exploring the molecular characteristics of MTB is helpful for understanding and controlling the spread of strains in areas with a high incidence of tuberculosis. Methods: We recruited 512 sputum smear-positive tuberculosis patients from 30 counties from 1 April to 30 June 2010; 503 MTB strains were isolated and 497 were successfully genotyped. We genotyped the strains based on a new 15-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) method in combination with spacer-oligonucleotide typing (spoligotyping) technology. Results: Based on spoligotyping, 487 strains displayed known patterns, and 10 were absent from the current global spoligotyping database (SpolDB4). The predominant spoligotypes belonged to the Beijing or Beijing-like family (81.1%). When we used the new 15-locus (MIRU-15) set for the MIRU-VNTR analysis, 388 different patterns were identified, including 46 clusters and 342 unique patterns. The combination of spoligotyping and MIRU-15 demonstrated a high discriminatory power. The proportion of clusters varied significantly between the Beijing and non-Beijing family strains, but no significant association was observed between multidrug resistance and Beijing family strains. Conclusions: The present study demonstrated that the Beijing family strains are the most prevalent in rural China. Spoligotyping in combination with the new MIRU-15 technique is useful for the epidemiological analysis of MTB transmission and could be used as a first-line method for the large-scale genotyping of MTB. [ABSTRACT FROM AUTHOR]

Tuberculosis recurrence after an initial successful treatment episode can occur from either reinfection or relapse. In a population-based sample and whole genome sequencing in eastern China, we aimed to evaluate risk factors for tuberculosis recurrence and assess the proportion of recurrence because of either reinfection or relapse. Successfully treated pulmonary tuberculosis patients with sputum culture positive results were recruited from five cities in Jiangsu Province from 2013 to 2015 and followed for 2 years for tuberculosis recurrence. Among patients developing a second tuberculosis episode, whole genome sequencing was performed to distinguish relapse or reinfection through a distance threshold of 6-single-nucleotide polymorphisms. We analyzed risk factors for recurrence and epidemiological characteristics of different types of recurrent patients. Of 1897 successfully treated tuberculosis patients, 7.4% (141/1879) developed recurrent tuberculosis. Compared with nonrecurrent tuberculosis, patients were at higher risk of recurrence in older age (adjusted odds ratio, 1.02 for each additional year; 95% CI, 1.01 to 1.03, p = 0.003), patients previously treated for tuberculosis (adjusted odds ratio = 2.22; 95% CI, 1.52 to 3.26, p < 0.001), or with bilateral cavities (adjusted odds ratio, 1.56; 95% CI, 1.05 to 2.32, p = 0.029). Among 27.0% (38/141) recurrent tuberculosis patients with successfully sequenced pairs, relapse was substantially more common than reinfection (71.1% vs 28.9%, p = 0.014). Endogenous relapse was significantly more common than exogenous reinfection in the first 2 years after treatment in eastern China. Prioritization of high-risk groups for recurrence, such as the elderly, with a previous tuberculosis diagnosis, or with bilateral cavities, may provide opportunities to reduce post-tuberculosis morbidity. [ABSTRACT FROM AUTHOR]

Background: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy.Methods: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546.Findings: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported.Interpretation: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer.Funding: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical.Translation: For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Mutations in pncA gene contributing to PZA resistance was not clearly elucidated in China. To reveal the correlated mutations of pncA gene on pyrazinamide (PZA) resistance. 148 Mycobacterium tuberculosis clinical isolates were included from multi-drug resistant tuberculosis suspects. The MGIT 960 test and microscopic observation drug susceptibility (MODS) assay were adopted for PZA phenotype drug susceptibility test. 120 isolates with consistent MGIT 960 and MODS results were selected for pncA gene sequencing. 68 samples (56.7%) were resistant to PZA while leaving 52 PZA susceptible samples. Out of the 68 PZA resistant isolates, 49 (72.1%) harbored mutations of pncA , and 4 (7.7%) of the 52 PZA susceptible samples harbored mutations of pncA as well. Compared to the phenotype drug resistant pattern of PZA, the mutations of pncA gene reached a sensitivity of 0.72 to report PZA resistance and a specificity of 0.92 to predict PZA susceptibility. Those mutations, Gln10Pro, Asp12Ala, Tyr41Stop, Gly97Asp, Val128Gly and FSC131(ins) exceeding 5% of the total PZA resistant isolates of each, might be helpful but not adequate in PZA molecular susceptibility test design and development. • Mutations of pncA gene greatly contributed to PZA resistance for MTBC. • The mutations of pncA reached a sensitivity of 0.72 to report PZA resistance. • The mutations of pncA reached a specificity of 0.92 to predict PZA susceptibility. • Nearly 30% PZA resistant strains containing wildtype pncA gene. [ABSTRACT FROM AUTHOR]

Limited resident's participation in the stock market has become a key constraint to the capital market development. Utilizing the 2019 China Household Financial Survey (CHFS) data, our paper designs probit models to examine the peer effects of residents' stock market participation and explore the intermediary mechanisms with a multiple intermediary model. We find that: (1) Resident involvement in stock market decision-making exhibits significant peer effects. (2) Heterogeneity analysis reveals that males and rural residents display more pronounced peer effects than females and urban residents. Additionally, middle-aged residents demonstrate more potent peer effects than their younger and older counterparts, with the intensity of peer effects correlating with education levels. (3)We observe that the peer effects of market participation operate by altering economic expectations and enhancing residents' financial literacy. (4) Further investigation establishes that individuals engaging in stock market investments manifest peer effects when deciding whether to diversify their stock portfolio. This study holds reference value for analyzing the impact of social interaction on financial behaviors and regulating individuals' financial conduct., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two most common subtypes of lung cancer. Previously, they were categorized into one histological subtype known as non-small cell lung cancer (NSCLC) and often treated similarly. However, increasing evidence suggested that LUAD and LUSC should be classified and treated as different cancers. But yet, detailed differences in clinical features between LUAD and LUSC have not been well described., Methods: A cohort of 142 Chinese patients with 111 LUAD and 31 LUSC cases were consecutively enrolled from April 2019 to October 2020 in Hunan Provincial People's Hospital. The clinical features of the patients were retrospectively analyzed and compared in the terms of general information, clinicopathologic characteristics, imaging findings and laboratory data., Results: In comparison with LUAD, LUSC patients had a significantly higher proportion of males, smokers, drinkers, higher-stage cases. The mean tumor size in LUSC patients was significantly larger than that in LUAD patients. Compared with LUAD patients, more of patients with LUSC had cough, fever and abundant sputum symptoms. Besides that, more bacterial infections and fungal infections were found in LUSC patients than that in LUAD patients. Imaging data shows that ground-glass opacity and patchy shadows in radiological films were more frequent in LUAD patients than that in LUSC patients. In addition to initial laboratory data, LUSC patients had higher levels of leukocytes, platelets, and creatinine that of LUAD patients., Conclusions: Together, these results suggested that there exist distinct differences between LUAD and LUSC subtypes; LUSC may be a more malignant type in comparison with LUAD. Our findings may have potential implications in clinical settings. However, further multicenter studies are needed to validate these findings in a larger sample size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Liu and Li.)

Objectives: The current situation of isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) and associated genetic factors is not clear in China., Methods: A retrospective cohort study was conducted from 2013 to 2018 in Jiangsu Province, China. Phenotypic Hr-TB were identified by drug susceptibility testing on Lowenstein-Jensen medium and using a Mycobacterium Growth Indicator Tube 960 (MGIT 960) system, and mutations in the katG 315 codon and inhA promoter nucleotides -8, -15 and -16 were determined by GenoType MTBDRplus and sequencing. All of the Hr-TB patients enrolled were followed up until June 2019., Results: A total of 1416 smear-positive sputum samples were collected, of which 57 were excluded due to the presence of nontuberculous mycobacteria. Finally, 63/1359 (4.6%) were determined as Hr-TB. After follow-up, 11 Hr-TB patients (17.5%) showed an unfavourable outcome, of whom 5 (7.9%) relapsed, 4 (6.3%) had treatment failure and 2 (3.2%) died. A total of 52 isolates (82.5%) were detected with either katG 315 or inhA promoter nucleotide -8, -15 or -16 mutations, whereas no canonical mutations were found in 8 isolates (12.7%); 3 isolates failed in mutation detection. TB history was found to be associated with unfavourable outcomes for Hr-TB (odds ratio = 6.13, 95% confidence interval 1.05-35.82; P = 0.04). However, mutations in katG 315 and the inhA promoter region were not found to be associated with Hr-TB unfavourable outcomes (P = 0.15)., Conclusion: Unfavourable outcomes for Hr-TB are serious in eastern China, especially for previously treated patients. Meanwhile, current genetic determination of Hr-TB is inadequate., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The serum tumor markers has been widely used in ovarian cancer diagnosis. BRCA1/2 germline mutations are the most common predisposing factors for ovarian cancer development. This study aimed to comprehensively investigate serum tumor markers and BRCA1/2 germline mutations and analyze their associations with ovarian cancer., Methods: Levels of 11 serum tumor markers were examined in ovarian cancer patients and controls with benign gynecologic diseases. By integrating multiplex PCR and next-generation sequencing technologies, BRCA1/2 germline mutations were analyzed and confirmed by Sanger sequencing. The discriminative models with serum tumor markers and BRCA1/2 mutation status were constructed for ovarian cancer detection and patient stratification., Results: Among 11 markers, six of them were significantly elevated and only beta-human chorionic gonadotropin (β-HCG) was significantly reduced in ovarian cancer patients. A total of 54 (23.3%) ovarian cancer patients were found to harbor BRCA1/2 deleterious mutations, and BRCA1/2 mutations were significantly associated with Hereditary Breast and Ovarian Cancer-related tumors and family history of cancer. Carbohydrate antigen 125 showed a good performance in ovarian cancer detection as a single marker (AUC = 0.799), while a panel of eight markers showed a good performance in BRCA1 mutation detection with an AUC value of 0.974. In addition, a panel of five serum tumor markers combined with BRCA1/2 mutation status showed a good performance in lymph node metastasis prediction (AUC = 0.843)., Conclusions: We found the association between BRCA1/2 germline mutation status and serum tumor marker levels, and identified discriminative models that combined serum tumor markers with BRCA1/2 mutation status for ovarian cancer detection and patient stratification., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: ASAP1 (also known as AMAP1 or DDEF1) encodes an Arf GTPase-activating protein (Arf GAP), a multifunctional scaffold protein that induces hydrolysis of GTP bound to the ADP-ribosylation factor (Arf) family GTP-binding proteins. Reduction of ASAP1 expression in vitro was related to suppression of cell migration and invasiveness. The genetic variant rs4733781 of the ASAP1 gene was revealed as a significant locus for tuberculosis (TB) susceptibility, but the results still need to be validated., Methods: Blood samples from a total of 1914 active TB and healthy controls (HC) were collected to evaluate rs4733781 and the risk of TB. Meanwhile, a total of 48 noninfected HC, latent TB-infected (LTBI) controls, and active TB were collected to assay ASAP1 expression difference among the three groups. The QuantiFERON-TB Gold In-Tube was adopted to identify noninfected HC and LTBI., Results: The genetic variant of rs4733781 was found to be significantly associated with TB, and the A allele of rs4733781 (C>A) was 0.38 and 0.43 among TB cases and HC, respectively ( P = 0.0035). Meanwhile, the peripheral blood monocyte RNA fold changes for the ASAP1 gene among the 16 HC, 16 LTBI, and 16 active TB were 1.088 ± 0.4919, 2.237 ± 0.6505, and 10.12 ± 10.98 ( F = 9.559, P = 0.0003), respectively, and the expression of ASAP1 was increased by 2.06-fold ( P < 0.0001) and 9.30-fold ( P < 0.0052) for LTBI and active TB, when compared to the HC., Conclusions: Our data indicated that the A allele of rs4733781 for the ASAP1 gene was in association with a decreased risk of TB. But not only that, the overexpression of the ASAP1 gene among LTBI and TB was related to the progression of TB, which further implies that the expression of ASAP1 would be a potential biomarker for LTBI and TB diagnoses.

Breast cancer, one of the most frequently occurring cancers worldwide, is the leading cause of cancer-related death among women. AKT1, PIK3CA, PTEN and TP53 mutations were common observed in breast cancer representing potential clinical biomarkers for cancer classification and treatment. A comprehensive knowledge of AKT1, PIK3CA, PTEN and TP53 mutations in breast cancer was still insufficient in Chinese population. In this study, the complete coding regions and exon-intron boundaries of AKT1, PIK3CA, PTEN and TP53 genes were sequenced in paired breast tumor and normal tissues from 313 Chinese breast cancer patients using microfluidic PCR-based target enrichment and next-generation sequencing technology. Total 120 somatic mutations were identified in 190 of the 313 patients (60.7%), with the mutation frequency of AKT1 as 3.2%, PIK3CA as 36.4%, PTEN as 4.8%, and TP53 as 33.9%. Among these mutations, 1 in PIK3CA (p.I69N), 3 in PTEN (p.K62X, c.635-12&#95;636delTTAACCATGCAGAT and p.N340IfsTer4) and 5 in TP53 (p.Q136AfsTer5, p.K139&#95;P142del, p.Y234dup, p.V274LfsTer31 and p.N310TfsTer35) were novel. Notably, PIK3CA somatic mutations were significantly associated with ER-positive or PR-positive tumors. TP53 somatic mutations were significantly associated with ER-negative, PR-negative, HER2-positive, BRCA1 mutation, Ki67 high expression and basal-like tumors. Our findings provided a comprehensive mutation profiling of AKT1, PIK3CA, PTEN and TP53 genes in Chinese breast cancer patients, which have potential implications in clinical management., Competing Interests: Xinwu Guo, Ming Chen, Limin Peng, Xunxun Xu, Jinliang Li, Lizhong Dai and Jun Wang are employees of Sanway Gene Technology Inc. Julia Xiaoning Day is a student from La Jolla Country Day School (La Jolla, CA, USA), who worked as an intern at Sanway Gene Technology Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Genome-wide association studies (GWASs) have yet to be conducted for tuberculosis (TB) susceptibility in China. Two previously identified single nucleotide polymorphisms (SNPs) from tuberculosis GWASs, rs2057178 and rs4331426, were evaluated for TB predisposition. The associations between SNPs and gene expression levels were analyzed using the genomic data and corresponding whole-genome expression of the Han Chinese in Beijing, China. Genotyping was successfully completed for 763 pulmonary TB patients and 763 healthy controls. The T allele of the rare variant rs2057178 was significantly associated with TB predisposition (χ(2) = 14.07, P = 0.0002). Meanwhile, the CT genotype of rs2057178 was associated with a decreased risk of TB (adjusted OR = 0.52, 95% CI, 0.34-0.78). The CT genotype of rs2057178 was also associated with decreased expression levels of infection-related gene, suppressor of cytokine signaling 2 (SOCS2), and increased expression levels of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB). No gene expression levels were found to be associated with the genotype of rs4331426. We found that the rare variant rs2057178 was significantly associated with TB in the Han Chinese population. Moreover, the expression levels of MAFB and SOCS2 correlated with rs2057178 and might be potential candidates for assessing TB susceptibility.

Background: Drug-resistant tuberculosis (TB) has emerged as a major challenge toward TB control and prevention. In Lianyungang city, the extent and trend of drug resistant TB is not well known. The objective of the survey was to assess drug resistance pattern of MTB and risk factors for drug resistant TB, including multidrug resistance tuberculosis (MDR-TB) in this area., Methods: We performed drug susceptibility testing on Mycobacterium tuberculosis (MTB) isolates with first- and second-line anti-tuberculosis drugs of 1012 culture positive TB cases by using the proportion method, who were consecutively enrolled from January 2011 to December 2012 in Lianyungang city, China. The patterns of drug resistance in MTB were investigated and multiple logistic regression analysis was performed to assess the risk factors for drug resistant TB., Results: Among the 1012 strains tested, 308 (30.4%) strains were resistant to at least one first-line drug; the prevalence of MDR-TB was 88 (8.7%), 5 (0.5%) strains were found to be extensively drug-resistant tuberculosis (XDR-TB). Female gender was a risk factor for MDR-TB (adjusted odds ratio (aOR) 1.763, 95% CI (1.060-2.934). The aged 28-54 years was significantly associated with the risk of MDR-TB with an aOR: 2.224, 95% CI (1.158-4.273) when compared with those 65 years or older. Patients with previous treatment history had a more than 7-fold increased risk of MDR-TB, compared with those never previously treated., Conclusions: The burden of drug resistant TB cases is sizeable, which highlights an urgent need to reinforce control, detection and treatment strategies for drug resistant TB.

Objective: To evaluate a biochip system in determining isoniazid and rifampicin resistances of Mycobacterium tuberculosis in sputum samples in a Chinese population., Methods: We assembled 907 sputum smeared positive specimens of tuberculosis patients in total. Each sample would be separated into two parts for culture and biochip assay simultaneously. And those cultured positive and having full drug resistance results would be used as reference. The McNemar χ² test was adopted for evaluating the paired 2×2 table., Results: Compared with drug sensitivity test, the agreement rates of the two methods in detecting rifampicin and isoniazid resistances were 93.37% and 94.49%, respectively. The sensitivity and specificity of biochip in detecting isoniazid were 74.31% and 96.92%, respectively. Meanwhile, the sensitivity and specificity for rifampicin were 79.76% and 96.53%, respectively. For multi-drug resistance, the sensitivity and specificity were 64.62% and 97.75%, respectively., Conclusions: The biochip system is a rapid and accurate method for drug resistant tuberculosis diagnosis using sputum samples directly, especially for rifampicin resistance detection.

Background: Globally, China is the second place with high burden of tuberculosis (TB). To explore the characteristics of the pathogens of Mycobacterium tuberculosis (MTB) circulating in this area is helpful for understanding and controlling the spread of the strains. Recent developments in molecular biology have allowed prompt identification and tracking specific strains of MTB spreading through the population., Methods: Spacer-oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) were performed in combination to yield specific genetic profiles of 260 MTB strains isolated from 30 counties of Jiangsu province in China between June and July 2010. The spoligotyping results were in comparison to the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4). Drug susceptibility test (DST) was performed on all strains by proportion method on Lowenstein-Jensen (LJ) culture media., Results: Based on the spoligotyping method, 246 strains displayed known patterns and 14 were absent in the database. Predominant spoligotypes belonged to the Beijing family (80.4%). By using the 24-loci VNTR typing scheme, 224 different patterns were identified, including 20 clusters and 204 unique patterns. The largest clade comprised 195 strains belonging to the Beijing family. The combination of spoligotyping and 24-loci MIRU-VNTR demonstrated maximal discriminatory power. Furthermore, we observed a significant association between Beijing family strains and drug-resistant phenotypes. The Beijing family strains presented increased risks for developing multi-drug resistant TB, with the OR (95% CI) of 11.07(1.45-84.50)., Conclusions: The present study demonstrated that Beijing family isolates were the most prevalent strains circulating in Jiangsu province of China. The utility of spoligotyping in combination with 24-loci MIRU-VNTR might be a useful tool for epidemiological analysis of MTB transmission.