Preventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury: A randomized controlled trial.

BACKGROUND AND AIM: Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury (ATLI). However, their biological mechanisms have not yet been clearly demonstrated. This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China. METHODS: A randomized controlled trial was performed in Jiangsu, China. Tuberculosis patients were randomly allocated to the experimental group (anti-tuberculosis therapy plus S. marianum capsule) or the control group (anti-tuberculosis therapy plus vitamin C tablet). The primary outcomes were the occurrence of probable and possible ATLI, the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase. RESULTS: The final analysis comprised 183 cases in the experiment group and 187 cases in the control group. The risk of developing probable ATLI was not significantly different between the two groups. During the follow-up period, 43.72% of cases in the experiment group and 35.83% of cases in the control group were determined to have possible ATLI (relative risk = 1.23, 95% confidence interval: 0.94-1.54). When using a more strict definition of possible ATLI, the adjusted relative risk (95% confidence interval) was 1.76 (1.14-2.56). The risks of adverse drug reactions, prolonged treatment length, taking second-line tuberculosis drugs, and the clearance of tuberculosis bacteria were similar between the two groups. CONCLUSIONS: No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes. Worse, we even found a potential risk of liver damage caused by the hepatoprotectant.

Repeated influenza vaccination induces similar immune protection as first-time vaccination but with differing immune responses.

BACKGROUND: Recent seasonal epidemics of influenza have been caused by human influenza A viruses of the H1N1 and H3N2 subtypes and influenza B viruses. Annual vaccination is recommended to prevent infection; however, how annual influenza vaccination influences vaccine effectiveness is largely unknown. METHODS: To investigate the impact of repeated vaccination on immune and protective effect, we performed a prospective seroepidemiologic study. Participants with or without prior vaccination (2018-2019) were enrolled during the 2019-2020 influenza season. Inactivated quadrivalent influenza vaccine (IIV4) was administered through the intramuscular route, and venous blood samples were collected regularly to test hemagglutination inhibition (HAI) titers. RESULTS: The geometric mean titers and proportion with titers ≥40 against the influenza vaccine components peaked at 30 days post-vaccination. At Day 30, the geometric mean titer and proportion with titers ≥40 in participants who had been previously vaccinated were higher for H3N2 but similar for both B lineages (Victoria and Yamagata) as compared with participants vaccinated for the first time. As for H1N1, the geometric mean titer was lower in repeated vaccinated participants, but the proportion with titers ≥40 was consistent in both groups. CONCLUSIONS: Repeated vaccination provides similar or enhanced protection as compared with single vaccination in first-time vaccinees.

Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013.

OBJECTIVE: To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China. METHODS: We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC). The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test. RESULTS: The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years) in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years) in 2013, with an APC of -2.5% (95% confidence interval (CI): -3.4%, -1.5%) for males and -4.9% (95% CI:-5.8%, -3.9%) for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years) in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years) in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7%) for males and -4.8% (95% CI: -5.7%, -3.9%) for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis. CONCLUSIONS: The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades.

Genetic polymorphisms of the P2X7 gene associated with susceptibility to and prognosis of pulmonary tuberculosis.

In this population-based case control study, we recruited 1601 pulmonary tuberculosis cases and 1526 healthy controls, aiming to investigate the association of genetic polymorphisms of the P2X7 gene with the susceptibility to and prognosis of pulmonary tuberculosis in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs) in the P2X7 gene were genotyped. The odds ratio (OR) or relative risk (RR) together with 95% confidence interval (CI) were used to estimated the effect of genetic polymorphisms on the disease. After correction for multiple comparisons, the SNP rs1718119 remained significant. The allele A of rs1718119 was related to a reduced risk for all active tuberculosis (OR for each additional allele A: 0.81, 95% CI: 0.69-0.94) and sputum smear-positive cases (OR for each additional allele A: 0.78, 95% CI: 0.66-0.93). The effects of these genetic variations were more evident among smokers. Survival analysis showed a weak association between rs7958311 and treatment outcome, where each additional allele A of the SNP rs7958311 contributed to a 59% increase in the probability of a successful treatment outcome (adjusted RR: 1.59, 95% CI: 1.05-2.40, P=0.028); but it wasn't significant after the Bonferroni correction. We demonstrated that genetic variations of the P2X7 gene might be involved in the risk and prognosis of human tuberculosis.

Aberrant promoter methylation of cancer-related genes in human breast cancer.

The clinical relevance of aberrant DNA methylation is being increasingly recognized in breast cancer. The present study aimed to evaluate the promoter methylation status of seven candidate genes and to explore their potential use as a biomarker for the diagnosis of breast cancer. A total of 70 Chinese patients with breast cancer were recruited, and matched with 20 patients with benign breast disease (BBD). Methylation-specific polymerase chain reaction was performed to measure the methylation status of selected genes. The protein expression of candidate genes was determined by immunohistochemistry. Hypermethylation of Breast cancer 1, early onset; DNA repair associated (BRCA1), glutathione S-transferase pi 1 (GSTP1), cyclin dependent kinase inhibitor 2A, O-6-methylguanine-DNA methyltransferase, phosphatase and tensin homolog, retinoic acid receptor beta 2 and cyclin D2 was observed to be more common in cancerous tissues (24.3, 31.4, 40.0, 27.1, 48.6, 55.7 and 67.1%, respectively) as compared with BBD controls (0.0, 0.0, 20.0, 25.0, 40.0, 40.0 and 45.0%, respectively). Immunohistochemical analysis demonstrated a correlation between the methylation of the target gene and downregulation of protein expression. When BRCA1 and GSTP1 were combined as the biomarker, the area under the receiver operating characteristic curve reached 0.721 (95% confidence interval, 0.616-0.827). The present findings indicated that promoter methylation of cancer-related genes was frequently observed in patients with breast cancer and was associated with various clinical features. Hypermethylation of BRCA1 and GSTP1 may be used as promising biomarkers for breast cancer.

Massive Endoscopic Screening for Esophageal and Gastric Cancers in a High-Risk Area of China.

OBJECTIVE: This study aims to describe the findings from a massive endoscopic screening program in a high-risk area of China and to evaluate the prognosis of patients diagnosed through endoscopic screening compared with those diagnosed at usual hospital visits because of illness. METHODS: In 2006, an early detection and treatment program was initiated in Yangzhong county, China. Local residents aged 40-69 years were eligible for free endoscopic screening. Endoscopic examination was performed with Lugol's iodine staining, followed by biopsies. Patients diagnosed with esophageal or gastric cancer were referred for treatment and followed to assess their long-term survival status. RESULTS: From 2006 through 2012, we screened 12453 participants, including 5334 (42.8%) men and 7119 (57.2%) women. The average age was 52.8 ± 8.0 years. We detected 166 patients with upper digestive tract cancers, including 106 cancers in the esophagus (detection rate: 0.85%) and 60 cancers in the stomach (detection rate: 0.48%). Of these patients, 98.11% with esophageal cancer and 100% with gastric cancer were defined as at the early stage. In the process of follow-up, 17 patients died from cancer-related causes, and the median survival time was greater than 85 months. The overall survival rates for 1, 3 and 5 years were 98.0%, 90.0% and 89.0%, respectively. A significant positive effect was observed for the long-term survival of patients diagnosed through massive endoscopic screening. CONCLUSIONS: In a high-risk population, massive endoscopic screening can identify early stage carcinoma of esophageal and gastric cancers and improve patients' prognosis through early detection and treatment.

Is tuberculosis treatment really free in China? A study comparing two areas with different management models.

OBJECTIVE: China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. METHODS: There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. RESULTS: The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983-6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. CONCLUSION: Under the current "free of diagnosis and treatment" policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients.