Managing Comorbidities, Determinants and Disability at Start and End of TB Treatment under Routine Program Conditions in China.

Many patients with tuberculosis (TB) have comorbidities, risk determinants and disability that co-exist at diagnosis, during and after TB treatment. We conducted an observational cohort study in 11 health facilities in China to assess under routine program conditions (i) the burden of these problems at the start and end of TB treatment and (ii) whether referral mechanisms for further care were functional. There were 603 patients registered with drug-susceptible TB who started TB treatment: 84% were symptomatic, 14% had diabetes, 14% had high blood pressure, 19% smoked cigarettes, 10% drank excess alcohol and in 45% the 6 min walking test (6MWT) was abnormal. Five patients were identified with mental health disorders. There were 586 (97%) patients who successfully completed TB treatment six months later. Of these, 18% were still symptomatic, 12% had diabetes (the remainder with diabetes failed to complete treatment), 5% had high blood pressure, 5% smoked cigarettes, 1% drank excess alcohol and 25% had an abnormal 6MWT. Referral mechanisms for the care of comorbidities and determinants worked well except for mental health and pulmonary rehabilitation for disability. There is need for more programmatic-related studies in other countries to build the evidence base for care of TB-related conditions and disability.

Exploring Key Genes with Diagnostic Value for Nonalcoholic Steatohepatitis Based on Bioinformatics Analysis.

We aimed to screen specific genes in liver tissue samples of patients with nonalcoholic steatohepatitis (NASH) with clinical diagnostic value based on bioinformatics analysis. The datasets of liver tissue samples from healthy individuals and NASH patients were retrieved for consistency cluster analysis to obtain the NASH sample typing, followed by verification of the diagnostic value of sample genotyping-specific genes. All samples were subjected to logistic regression analysis, followed by the establishment of the risk model, and then, the diagnostic value was determined by receiver operating characteristic curve analysis. NASH samples could be divided into cluster 1, cluster 2, and cluster 3, which could predict the nonalcoholic fatty liver disease activity score of patients. A total of 162 sample genotyping-specific genes were extracted from patient clinical parameters, and the top 20 core genes in the protein interaction network were obtained for logistic regression analysis. Five sample genotyping-specific genes (WD repeat and HMG-box DNA-binding protein 1 [WDHD1], GINS complex subunit 2 [GINS2], replication factor C subunit 3 (RFC3), secreted phosphoprotein 1 [SPP1], and spleen tyrosine kinase [SYK]) were extracted to construct the risk models with high diagnostic value in NASH. Compared with the low-risk group, the high-risk group of the model showed increased lipoproduction and decreased lipolysis and lipid ß oxidation. The risk models based on WDHD1, GINS2, RFC3, SPP1, and SYK have high diagnostic value in NASH, and this risk model is closely related to lipid metabolism pathways.

Randomized control study of the use of faropenem for treating patients with pulmonary tuberculosis.

OBJECTIVES: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. METHODS: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. RESULTS: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). CONCLUSIONS: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).

Differential expression and significance of 5-hydroxymethylcytosine modification in hepatitis B virus carriers and patients with liver cirrhosis and liver cancer.

BACKGROUND: The relationship between hepatitis B surface antigen (HBsAg)-positive carrier status and liver cancer has been extensively studied. However, the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown. The epigenetic modification of DNA hydroxymethylation is critical in tumor development. Further, 5-hydroxymethylcytosine (5hmC) is an important base for DNA demethylation and epigenetic regulation. It is also involved in the assembly of chromosomes and the regulation of gene expression. However, the mechanism of action of 5hmC in HBsAg-positive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated. AIM: To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma (HCC) progression from cirrhosis. METHODS: Forty HBsAg-positive carriers, forty patients with liver cirrhosis, and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants. Free DNA was extracted using a cf-DNA kit. cfDNA was extracted by 5hmC DNA sequencing for principal component analysis, the expression profiles of the three groups of samples were detected, and the differentially expressed genes (DEGs) modified by hydroxymethylation were screened. Bioinformatic analysis was used to enrich DEGs, such as in biological pathways. RESULTS: A total of 16455 hydroxymethylated genes were identified. Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients, of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers. Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes, of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis. These genes may have potential loci that are undiscovered or unelucidated, which contribute to the development and progression of liver cancer. Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion. The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2. CONCLUSION: The occurrence and development of liver cancer involves multiple genes and pathways, which may be potential targets for preventing hepatitis B carriers from developing liver cancer.

Serum CHI3L1 as a diagnostic marker and risk factor for liver fibrosis in HBeAg-negative chronic hepatitis B.

Chronic hepatitis B (CHB) as the major inducement of hepatocellular carcinoma and cirrhosis, imposes a heavy health burden upon patients. This research aims to investigate the diagnostic value of serum chitinase 3-like 1 (CHI3L1) in hepatitis B e antigen (HBeAg)-negative CHB liver fibrosis (LF) and to analyze the risk factors. We selected 78 patients with HBeAg-negative CHB admitted to our hospital between October 2018 and October 2019, and grouped them (F0,1 group, n=38; F2-4 group, n=40) based on their stages evaluated by the METAVIR scoring system. Cubital venous blood was collected from patients in both groups to quantify the content of CHI3L1 after serum extraction. The correlation of CHI3L1 in CHB with LF diagnostic markers fibrosis 4 (FIB-4) and γ-glutamyltranspeptidase (GGT) to platelet (PLT) ratio (GPR) as well as LF staging was analyzed. The diagnostic value of serum CHI3L1 in HBeAg-negative CHB fibrosis staging was analyzed by receiver operating characteristic (ROC) curve, and the multivariate analysis of the risk factors for FB in HBeAg-negative CHB patients was performed using the Logistic regression model. This study found that serum CHI3L1 was positively correlated not only with LF markers (FIB-4, GPR), but also with LF staging. Serum CHI3L1 had high diagnostic efficiency for LF staging, with the sensitivity and specificity of 80.00% and 71.05%, respectively. In addition, CHI3L1, FIB-4, and GPR were identified to be the risk factors for LF in HBeAg-negative CHB. In conclusion, serum CHI3L1 can be used as a diagnostic marker and risk factor for LF in patients with HBeAg-negative CHB.

Atypical pneumonia caused by Chlamydia psittaci during the COVID-19 pandemic.

OBJECTIVES: Here, we retrospectively described the diagnosis and treatment of 32 cases diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic. METHODS: Clinical information was collected from all the patients. Reverse transcription-PCR and ELISAs were conducted for the detection of COVID-19 using nasal swabs and bronchoalveolar lavage fluid (BALF) samples. Metagenomic next-generation sequencing (mNGS) was performed for the identification of causative pathogens using BALF, peripheral blood and sputum samples. End-point PCR was performed to confirm the mNGS results. RESULTS: All 32 patients showed atypical pneumonia and had infection-like symptoms that were similar to COVID-19. Results of reverse transcription-PCR and ELISAs ruled out COVID-19 infection. mNGS identified C. psittaci as the suspected pathogen in these patients within 48 hours, which was validated by PCR, except for three blood samples. The sequence reads that covered fragments of C. psittaci genome were detected more often in BALF than in sputum or blood samples. All patients received doxycycline-based treatment regimens and showed favorable outcomes. CONCLUSION: This retrospective study, with the highest number of C. psittaci pneumonia enrolled cases in China so far, suggests that human psittacosis may be underdiagnosed and misdiagnosed clinically, especially in the midst of the COVID-19 pandemic.

The correlation of the miR-29a/MMP9 axis with Helicobacter pylori infection in gastric cancer.

OBJECTIVE: This study was designed to investigate the association between the miR-29a/MMP9 axis expression levels and Helicobacter pylori (HP) infection in gastric cancer patients. METHODS: A total of 100 gastric cancer patients referred to our hospital from June 2017 to June 2019 were recruited as the study cohort. Among them, 50 HP-positive patients were included in the experimental group and 50 HP-negative patients were included in the control group. The changes in the patients' conditions were compared, the miR-29a/MMP9 axis expression levels were recorded, and the correlation between the miR-29a/MMP9 axis and the HP infections was analyzed. All the discharged patients were followed up for one year to analyze the correlation between the HP infections and the serum miR-29a and MMP9 expression levels with the disease progression. RESULTS: The experimental group had higher miR-29a expression levels and higher MMP9 chromogenic scores than the control group (P<0.05). A negative correlation was found between the miR-29 expression level and the MMP9 expression level (r=-5.369, P<0.05). One year after discharge, there were 27 patients with severe disease in the experimental group and 6 in the control group, with a significant difference between the two groups. Moreover, the expression levels of the miR-29a/MMP9 axis were significantly higher in the discharged patients than in the patients with severe disease (P<0.05). A receiver operating characteristic (ROC) curve was used to analyze the predictive value of miR-29/MMP9 in the diagnosis of gastric cancer, and the area under the curve was found to be 0.97. CONCLUSION: The miR-29a/MMP9 axis levels were increased in the HP positive patients but not in the HP negative patients. HP infection is considered to be closely related to gastric cancer cell spread, disease relapse, and high miR-29a/MMP9 axis expression levels.

Gene subtype analysis of Treponema pallidum for drug resistance to azithromycin.

Azithromycin has been widely used for the treatment of Treponema pallidum. However, the drug resistance of T. pallidum for azithromycin is currently increasing. The aim of the present study was to analyze the association between gene subtypes of T. pallidum and drug resistance for azithromycin. The gene subtypes of T. pallidum were assayed by a polymerase chain reaction technique. Drug resistance of T. pallidum was analyzed using an antimicrobial susceptibility test. The results demonstrated that gene type tpr presented higher drug resistance compared with arp and tp0548 gene types of T. pallidum. Gene type tpr was identified as eight gene subtypes (14a/f, 14e/f, 12e/f, 12d/f, 6d/f, 11d/f, 14j/f and 8d/f) among 324 cases. It was identified that 23S rRNA A2058G mutation was observed in gene subtypes 14a/f, 14e/f and 12e/f. A2059G mutation occurred in the gene subtypes 8d/f, 12d/f, 6d/f, 11d/f and 14j/f. The proportions of azithromycin-resistant genotypes harboring either the A2058G or the A2059G mutation among the T. pallidum strains were 34.2 and 65.8%, respectively. The antimicrobial susceptibility test demonstrated that A2059G mutations exhibited a higher drug resistance for azithromycin compared with A2058G mutations. In conclusion, these results indicate that azithromycin resistance in T. pallidum is associated with gene subtype, which may contribute to the treatment of T. pallidum.