Modeling methods for busulfan-induced oligospermia and asthenozoospermia in mice: a systematic review and meta-analysis.

OBJECTIVE: Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time. METHODS: We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis. RESULTS: Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 106/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle. CONCLUSION: The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.

The screening value of RT-LAMP and RT-PCR in the diagnosis of COVID-19: systematic review and meta-analysis.

The purpose of this systematic review is to evaluate the test accuracy of reverse-transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription-PCR (RT-PCR) for the diagnosis of coronavirus disease 2019 (COVID-19). We comprehensively searched PUBMED, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until September 1, 2021. We included clinical studies assessing the sensitivity and specificity of RT-PCR and RT-LAMP using respiratory samples. Thirty-three studies were included with 9360 suspected cases of SARS-CoV-2 infection. The RT-PCR or other comprehensive diagnostic method was defined as the reference method. The results showed that the overall pooled sensitivity of RT-PCR and RT-LAMP was 0.96 (95 % CI, 0.93-0.98) and 0.92 (95 % CI, 0.85-0.96), respectively. RT-PCR and RT-LAMP had a 0.06 (95 % CI, 0.04-0.08) and 0.12 (95 % CI, 0.06-0.16) false-negative rates (FNR), respectively. Moreover, subgroup analysis showed mixed sampling and multiple target gene diagnosis methods had better diagnostic value than single-site sampling and a single target gene. The sensitivity and FNR were also significantly affected by the reference method. Comparing RT-LAMP with established suboptimal RT-PCR may exaggerate the performance of RT-LAMP. RT-PCR and RT-LAMP showed high values in the diagnosis of COVID-19, but there was still a FNR of about 6%-12%.

Effects of metformin in obesity treatment in different populations: a meta-analysis.

OBJECTIVE: Some studies have shown that metformin can reduce body weight. However, metformin has not been officially approved as a medicine for weight loss because its effect on different populations remains inconsistent. This meta-analysis aimed to summarize the weight loss effect of metformin quantitatively. METHOD: The randomized controlled and high-quality case-control trials of metformin monotherapy in obesity treatment were eligible. Baseline body mass index (BMI) was chosen as a self-control to compare the changes in BMI of different populations before and after treatment. All changes were calculated as differences between the final and initial BMI values (with negative values indicating a decrease). Results were presented as weighted mean difference (WMD) with a 95% confidence interval (CI 95%). Subgroup analysis was performed based on baseline BMI, age, daily dose, and duration of medication. RESULTS: A total of 21 trials (n = 1004) were included, and the meta-analysis of metformin treatment in different populations showed that metformin has a modest reduction in the BMI of included participants (WMD -0.98; 95% CI, -1.25 to -0.72), and the reduction of BMI was most significant in the simple obesity population (WMD -1.31; 95% CI, -2.07 to -0.54). The subgroup analysis showed that metformin treatment significantly reduced BMI in obesity patients with a BMI >35kg/m2 (WMD -1.12; 95% CI, -1.84 to -0.39) compared with before treatment. BMI in the high dose group decreased by 1.01 units (WMD-1.01; 95% CI, -1.29 to -0.73) and BMI did not continue to decrease significantly after treatment of more than 6 months. CONCLUSION: Patients treated with metformin experienced about a one-unit reduction in BMI at the end of treatment. But whether this decreased value produced enough weight loss (5% of baseline body weight) to qualify as a "weight loss drug" as current guidelines require, requires larger specific randomized control trials.

Liver Enzymes, Fatty Liver and Type 2 Diabetes Mellitus in a Jinchang Cohort: A Prospective Study in Adults.

OBJECTIVES: It is unclear whether liver enzymes or the interactions of various liver enzymes is a predictor of type 2 diabetes mellitus (T2DM), which is independent of fatty liver. METHODS: A total of 48,001 subjects participated in baseline examinations. Among the subjects, 33,355 were followed for an average of 2.2 years. Cox proportional hazard models were used to examine the adjusted associations of AST, GGT and ALT with T2DM. RESULTS: The cumulative incidence of T2DM was 8.05% to 9.02% for fatty liver and 2.25% to 4.10% for non-fatty liver, both showing statistically significant differences. Compared with the normal liver enzyme levels in the group with fatty liver, the adjusted incident hazard ratios in T2DM were: ALT 1.23 (95% CI 1.10 to 1.50); AST 1.30 (95% CI 1.07-1.59); and GGT 1.34 (95% CI 1.08 to 1.65). In addition, compared with the normal liver enzyme levels in the group with non-fatty liver, the adjusted incident hazard ratios in type 2 diabetes were: ALT 1.27 (95% CI 1.02 to 1.59); AST 1.33 (95% CI 1.02 to 1.59); and GGT 1.53 (95% CI 1.19 to 1.98). There are significant interactions of T2DM hazard ratios between GGT and ALT and between GGT and AST in addition to ALT and AST. CONCLUSIONS: Our results suggest that the incidence of T2DM in the group with fatty liver is significantly higher than that in the normal population, and the rise of serum AST, GGT and ALT levels are risk factors independent of fatty liver for the development of T2DM after adjusting for confounding factors.