Since it was first described in 1968, immunoglobulin (Ig)A nephropathy (IgAN) has become the most commonly diagnosed form of primary glomerular disease worldwide. A number of reports have shown that toll‑like receptor 9 (TLR9) and B‑cell activating factor (BAFF) may be associated with IgAN; however, sufficient evidence has not yet to be delivered. In the present study, serum levels of BAFF as well as TLR9 mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) were assessed. Expression of TLR9 mRNA in PBMCs was examined by quantitative polymerase chain reaction and the TLR9 protein was determined by western blot analysis. The levels of serum BAFF and IgA1 were determined by specific ELISA. Serum levels of BAFF and IgA1 as well as levels of TLR9 mRNA and protein in PMBCs were significantly higher in patients with IgAN compared with patients with minimal glomerular abnormalities (P<0.05, P<0.01, P<0.01 and P<0.01, respectively) and normal controls (P<0.01, P<0.01, P<0.05 and P<0.01, respectively). A correlation and regression analysis was performed to determine the pathogenesis of IgAN. In patients with IgAN, serum levels of BAFF were positively correlated with IgA1 levels (rp, 0.515; P<0.01) and mesangial IgA deposition density (rp, 0.746; P<0.01). Expression levels of TLR9 protein in PBMCs of IgAN patients were positively correlated with levels of serum BAFF (rp, 0.444; P<0.05) and IgA1 (rp, 0.633; P<0.01). These results suggested that overexpression of TLR9 mRNA and protein in PBMCs and elevated levels of serum BAFF may be associated with overexpression of serum IgA1, and, furthermore, may have a role in the development of IgAN.

Background and Aim Although endoscopic ultrasound‐guided fine‐needle biopsy is widely applied, there is no clear consensus on the optimal biopsy technique. We described a modified wet suction technique (MWEST) with the aim to compare the efficacy and safety between MWEST and the dry suction technique (DST). Methods In this prospective, randomized, crossover, single‐blinded study, patients with suspected pancreatic malignancy were randomized to the DST (group A) or MWEST (group B) for the first pass, and the two techniques were performed alternately. The primary outcome was the comparison of specimen adequacy and diagnostic yield between the techniques. Secondary outcomes included the macroscopic visible core length, blood contamination of specimens, and adverse events of both techniques. Results From January 2019 to September 2019, 216 passes were performed in 50 patients. The specimen adequacy was significantly higher in “per‐lesion” (P = 0.026), “per‐pass” (cytology: P = 0.034; histology: P = 0.042), and first‐pass analysis (P = 0.034) for MWEST than for DST. In diagnostic yield, MWEST showed significantly superior histological yield (P = 0.014) and first‐pass analysis (κ: MWEST: 0.743 and DST: 0.519) compared with DST. The median macroscopic visible core lengths were 8 mm (interquartile range: 3.25–15 mm) and 10 mm (interquartile range: 5.25–15 mm) for DST and MWEST, respectively (P = 0.036). Blood contamination was significantly more serious in DST than in MWEST (cytology: P = 0.021; histology: P = 0.042). Conclusions Endoscopic ultrasound‐guided fine‐needle biopsy with MWEST resulted in significantly better quality of specimen, histological, and first‐pass diagnostic yields and comparable safety compared with the DST. MWEST is preferred for endoscopic ultrasound‐guided fine‐needle biopsy in pancreatic solid lesions.

Background Although the association between shift work and individual cardiometabolic diseases has been well studied, its role in the progression to cardiometabolic multimorbidity (CMM) remains unclear. In this study, we investigate the association between shift work and the incidence of CMM in patients with hypertension. Methods and Results This study is a population‐based and prospective cohort study on 36 939 UK Biobank participants. We used competing risk models to examine the association between shift work and the risk of CMM, which was defined as coexistence of hypertension and diabetes, coronary heart disease, or stroke in our study. We also investigated the association between the frequency and duration of shift work and CMM risks. In addition, we conducted a cross‐classification analysis with the combination of frequency and duration of shift work, chronotype and sleep duration as the exposure metrics. During a median follow‐up of 11.6 years, a total of 5935 participants developed CMM. We found that usually/always night shift workers were associated with a 16% higher risk of CMM compared with day workers (hazard ratio [HR], 1.16 [95% CI, 1.02–1.31]). We also found that a higher frequency of night shifts (>10/month) was associated with increased risk of CMM (HR, 1.19 [95% CI, 1.06–1.34]) that was more pronounced for >10/month in combination with a morning chronotype or <7 hours or >8 hours of sleep duration (HR, 1.26 [95% CI, 1.02–1.56]; HR, 1.43 [95% CI, 1.19–1.72], respectively). Conclusions We find that night shift work is associated with higher CMM risk in patients with hypertension.

Disruption of the circadian rhythm is a risk factor for cancer, while glioma is a leading contributor to mortality worldwide. Substantial efforts are being undertaken to decrypt underlying molecular pathways. Our understanding of the mechanisms through which disrupted circadian rhythm induces glioma development and progression is incomplete. We, therefore, examined changes in the expression of glioma-related genes in the mouse brain after chronic jetlag (CJL) exposure. A total of 22 candidate tumor suppressor (n= 14) and oncogenes (n= 8) were identified and analyzed for their interaction with clock genes. Both the control and CJL groups were investigated for the expression of candidate genes in the nucleus accumbens, hippocampus, prefrontal cortex, hypothalamus, and striatum of wild type, Bmal1-/- and Cry1/2 double knockout male mice. We found significant variations in the expression of candidate tumor suppressor and oncogenes in the brain tissues after CJL treatment in the wild type, Bmal1-/- and Cry1/2 double knockout mice. In response to CJL treatment, some of the genes were regulated in the wild type, Bmal1-/- and Cry1/2 similarly. However, the expression of some of the genes indicated their association with the functional clock. Overall, our result suggests a link between CJL and gliomas risk at least partially dependent on the circadian clock. However, further studies are needed to investigate the molecular mechanism associated with CJL and gliomas.

Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N1‐methyladenosine (m1A), 5‐methylcytosine (m5C), N6‐methyladenosine (m6A)‐related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m1A‐, m5C‐ and m6A‐related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single‐sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator‐related prognostic signature. The nine‐gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high‐risk group was correlated with T‐cell suppression, while the low‐risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m1A‐, m5C‐ and m6A‐related regulators may also be promising biomarkers for future research.

Progressive loss of physiological integrity and accumulation of degenerative changes leading to functional impairment and increased susceptibility to diseases are the main features of aging. The ovary, the key organ that maintains female reproductive and endocrine function, enters aging earlier and faster than other organs and has attracted extensive attention from society. Ovarian aging is mainly characterized by the progressive decline in the number and quality of oocytes, the regulatory mechanisms of which have yet to be systematically elucidated. This review discusses the hallmarks of aging to further highlight the main characteristics of ovarian aging and attempt to explore its clinical symptoms and underlying mechanisms. Finally, the intervention strategies related to aging are elaborated, especially the potential role of stem cells and cryopreservation of embryos, oocytes, or ovarian tissue in the delay of ovarian aging.

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Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data of 72,242 participants in UK Biobank, we derived a circadian relative amplitude variable, which to some extent reflected the degree of circadian rhythm disruption. Records of brain disorder incidents were obtained from a wide range of health outcomes across self-report, primary care, hospital inpatient data, and death data. Using multivariate Cox proportional hazard ratio regression, we created two models adjusting for different covariates. Then, linear correlations between relative amplitude and several brain morphometric measures were examined in participants with brain MRI data. After a median follow-up of around 6.1 years, 72,242 participants were included in the current study (female 54.9%; mean age 62.1 years). Individuals with reduced relative amplitude had increasing risk of all-cause dementia (Hazard ratio 1.23 [95% CI 1.15 to 1.31]), PD (1.33 [1.25 to 1.41]), stroke (1.13 [1.06 to 1.22]), MDD (1.18 [1.13 to 1.23]), and anxiety disorder (1.14 [1.09 to 1.20]) in fully adjusted models. Additionally, significant correlations were found between several cortical regions and white matter tracts and relative amplitude that have been linked to dementia and psychiatric disorders. We confirm CRD to be a risk factor for various brain disorders. Interventions for regulating circadian rhythm may have clinical relevance to reducing the risk of various brain disorders.