Background: Inflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive. Objective: This study aimed to evaluate the association between inflammatory cytokines and NAFLD. Methods: PubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out. Results: The search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-β (TGF-β) with NAFLD. Our results also showed that CRP, IL-1β, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Conclusions: Our results indicated that increased CRP, IL‐1β, IL-6, TNF‐α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.

There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota, glucose, and lipid. However, the function of water-electrolyte metabolism remains undefined in children with NAFLD. Therefore, the aim of this case-control study was to better understand these interactions. The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without NAFLD. These groups were matched by age, sex, and body mass index. Data were collected between June, 2019 and December, 2019 at the Hunan Children’s Hospital, in China. Microbiome composition in fecal samples was assessed using 16S ribosomal RNA amplicon sequencing. In the clinical indices, 12 glucose and lipid metabolism indices were included, and six water-electrolyte metabolism indices were included. The results indicated that microbiomes of NAFLD children had lower alpha diversity but higher beta diversity index than the other two groups. Specifically, anti-inflammatory and probiotics abundance (e.g., Faecalibacterium, Akkermansia, and Bifidobacterium_adolescentis) was significantly decreased in NAFLD, whereas the abundance of harmful bacteria (e.g., Staphylococcaceae) was increased. Moreover, the abundance of butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia_inulinivorans, Roseburia_intestinalis, and Coprococcus_comes) was significantly decreased in NASH. The abundance of these bacteria were associated with glucose, lipid, and water-electrolyte metabolism (e.g., glucose, triglyceride, cholesterol, inorganic salt, total body water, etc.), implying that the NAFLD and its severity were associated with glucose, lipid, and water-electrolyte metabolism dysbiosis. Therefore, these findings suggest that the gut microbiome, especially butyrate-producing bacteria, play an important role in the development of NAFLD in children.

This study aims to explore the recurrence rate and overall survival for patients with cervical cancer after the first treatment and the related risk factors. A retrospective cohort study was conducted on cervical cancer patients enrolled in a cancer specialist hospital in Hunan Province, China from January 1992 to December 2005 and followed up until December 2010. Kaplan–Meier survival analysis was used to estimate the cumulative recurrence rate, and Cox proportional hazards model was utilized to identify risk factors associated with prognosis. A total of 4358 patients were enrolled with a median follow-up of 7.4 years (range 5–19 years), and 372 (8.5%) patients had cancer recurrence. The cumulative recurrence rate showed a rapid increase from 3.8% in the first year after discharge to 8.0% in the fifth year, and the recurrence rate remained relatively stable afterward reaching 9.7% and 10.8% in the 10th and the 15th year, respectively. The median time to recurrence was 15.5 months with an IQR of 5.5–40.0 months. The Cox regression showed that miscarriage, clinical stage, and treatment received were significantly associated with cervical cancer recurrence after adjustment for confounders. Patients with recurrence showed a significantly higher risk for mortality than those without recurrence (HR 2.79, 95% CI 2.42–3.22). This study depicted the long-term recurrence rate and survival after recurrence for patients with cervical cancer after the first treatment, and reported time to recurrence and risk factors related to recurrence. These findings may provide important evidence for designing targeted interventions for the treatment of cervical cancer.

Background: This study aimed to evaluate the incidence rates and risks of pregnancy complications among nulliparous and multiparous women with advanced maternal age (AMA, ≥35 years) in China.Methods: We performed a community-based prospective cohort study of 10,171 pregnant women in selected two sub-districts and 11 towns of Liuyang from 2013 to 2015. All subjects were followed up from the first prenatal care (at ≤12 weeks) to delivery, and risks of pregnancy complications were compared by parity and maternal age groups.Results: Among nulliparas, women with AMA showed significantly increased risks for gestational hypertension (OR 8.44, 95%CI 1.68–2.88), preeclampsia/eclampsia (OR 9.92, 95%CI 4.87–18.78), premature rupture of membrane (OR 6.84, 95%CI 2.00–17.69), as compared to women in the 20–29-year age group. Among multiparas with AMA, increased risks were found for gestational diabetes mellitus (OR 3.29, 95%CI 1.76–5.94), anemia (OR 1.85, 95%CI 1.25–2.69), polyhydramnios (OR 3.29, 95%CI 1.56–6.64), premature rupture of membrane (OR 5.14, 95%CI 2.12–12.29), and preterm labor (OR 1.89, 95CI 1.42–2.50).Conclusions: Women with AMA were associated with increased risks of pregnancy complications, and complications with increased risks differed in nulliparas and multiparas. Women with AMA should be identified as a high-risk group in clinical practice.

The magnitude of the effect of fetuin-A and fetuin-B on non-alcoholic fatty liver disease (NAFLD) remains undefined. Therefore, the aim of this study was to synthesize previous findings to obtain a reliable estimation of this relationship. This study was registered in PROSPERO with the number CRD42019126314. Studies published not later than March 2019, examining the relationship between fetuin-A, fetuin-B, and NAFLD, were identified by a systematic search in the electronic databases of the Web of Science, PubMed, Embase, and Cochrane Library. Pooled estimates of standardized mean difference (SMD), calculated using the random-effects model in a meta-analysis, were applied to estimate the strength of the association between fetuin-A, fetuin-B, and NAFLD. Thirty publications were identified and analyzed based on specified inclusion criteria. Collectively, they consisted of 3800 NAFLD participants and 3614 controls. Compared with the controls, significant higher values of the fetuin-A (SMD = 0.83, 95% CI: 0.59 to 1.07, Z = 6.82, p < 0.001) and fetuin-B (SMD = 0.18, 95% CI: 0.02 to 0.33, Z = 2.27, p = 0.023) were observed in NAFLD patients. Meanwhile, in the subgroup analysis, the effect value of fetuin-A in the NASH group was significantly higher than that in the NAFL group (p = 0.036). The findings of this study suggest that elevated fetuin-A and fetuin-B may independently indicate the occurrence of NAFLD. Nevertheless, further research is needed to confirm these results.

Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.