The genomic variant features (mutations, deletions, structural variants, etc.) within gastric cancer impact its evolution and immunogenicity. The tumor has developed several coping strategies to respond to these changes by DNA repair and replication (DRR). However, the intrinsic relationship between the associated DRR-related genes and gastric cancer progression remained unknown. This study selected DRR-related genes with tumor mutation burden based on the TCGA (The Cancer Genome Atlas) database of gastric cancer transcriptome and mutation data. The prognosis model of seven genes (LAMA2, CREB3L3, SELP, ABCC9, CYP1B1, CDH2, and GAMT) was constructed by a univariate and LASSO regression analysis and divided into high-risk and low-risk groups with the median risk score. Survival analysis showed that overall survival (OS) was lower in the high-risk group than that in the low-risk group. Moreover, patients with gastric cancer in the high-risk group have worse survival in different subgroups, including age, gender, histological grade, and TNM stage. The nomogram that included risk scores for DRR-related genes could accurately foresee OS of patients with gastric cancer. Interestingly, the tumor mutation burden score was higher in the low-risk group than that in the high-risk group, and the risk score for DRR-related genes was negatively correlated with tumor mutation burden in gastric cancer. Next, we further combined the risk score and tumor mutation burden to evaluate the prognosis of gastric cancer patients. The low-risk cohort had a better prognosis than the high-risk cohort in the high tumor mutation burden subgroup. The number of mutation types in the high-risk group was lower than that in the low-risk group. In the immune microenvironment of gastric cancer, more naïve B cells, memory resting CD4+ T cells, Treg cells, monocytes cells, and resting mast cells were infiltrated in the high-risk group. At last, PD-L1 and IAP expressions were negatively correlated with the risk scores; patients with gastric cancer in the low-risk group showed better immunotherapy outcomes than those in the high-risk group. Overall, the DRR-related gene signature based on tumor mutation burden is a novel biomarker for prognostic and immunotherapy response in patients with gastric cancer.

Background: Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Centronuclear myopathy is a kind of disease difficult to diagnose due to its genetic diversity. Since the discovery of the SPEG gene and disease‐causing variants, only a few additional patients have been reported. Methods: A radiograph test, ultrasonic test, and biochemical tests were applied to clinical diagnosis of CNM. We performed trio medical exome sequencing of the family and conservation analysis to identify variants. Results: We report a pair of severe CNM twins with the same novel homozygous SPEG variant c. 8710A>G (p.Thr2904Ala) identified by clinical trio medical exome sequencing of the family and conservation analysis. The twins showed clinical symptoms of facial weakness, hypotonia, arthrogryposis, strephenopodia, patent ductus arteriosus, and pulmonary arterial hypertension. Conclusions: Our report expands the clinical and molecular repertoire of CNM and enriches the variant spectrum of the SPEG gene in the Chinese population and helps us further understand the pathogenesis of CNM.

We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR). A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], p < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], p < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], p < .001; ≥5%: 0.62 [0.52, 0.74], p < .001; ≥10%: 0.42 [0.30, 0.59], p < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], p = .02), with liver metastases (OS: 1.16 [1.02,1.32], p = .02) and antibiotics (OS: 3.13 [1.25,7.84], p < .001; PFS: 2.54 [1.38, 4.68], p = .003). The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.

Background. To determine if the use of the Proton Pump Inhibitors (PPI) impacts the clinical efficacy of Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC), a meta-analysis was conducted. Method. Eleven studies from PubMed, EMBASE, Cochrane Library, Web of Science, and other databases up to May 2022, were selected. The pertinent clinical outcomes were assessed by applying the Progression-free survival (PFS), Overall Survival (OS), Hazard Ratio (HR), and 95 Confidence Interval (CI). Result. This study included eleven articles containing 7,893 NSCLC patients. The result indicated that PPI use was dramatically related to poor OS (HR: 1.30 [1.101.54]), and poor PFS (HR: 1.25 [1.091.42]) in case of patients treated with ICIs. With regard to the subgroup analysis, PPI use was dramatically associated with poor OS (Europe: HR=1.48 [1.26, 1.74], Worldwide: HR=1.54 [1.24, 1.91]), and poor PFS (Europe: HR=1.36 [1.18, 1.57], Worldwide: HR=1.34 [1.16, 1.55]) in patients from Europe and multi-center studies across the world, poor OS in patients with age less than or equal to 65 (HR=1.56 [1.14, 2.15]), poor PFS in patients aged more than 65 (HR=1.36 [1.18, 1.57]), poor OS for patients receiving with PD-1 (HR=1.37 [1.04, 1.79]), poor PFS for patients receiving with PD-L1 (HR=1.33 [1.19, 1.49]), and poor OS (30: HR=1.89 [1.29, 2.78], ±30: HR=1.44 [1.27, 1.64]) and poor PFS (30: HR=1.51 [1.11, 2.05], ±30: HR=1.32 [1.20, 1.45]) for patients who received PPI at 30 days before and/or after starting the ICIs treatment. Conclusion. Our meta-analysis indicated that PPI combined with ICIs in the treatment of NSCLC patients could result in poor OS and PFS. PPI use should be extremely cautious in clinical practices to avoid the impact on the efficacy of the ICIs.

Depression is a prevalent mental health disorder affecting millions of people worldwide, imposing a significant economic burden on society. Despite the progress in treatment, many individuals with depression still face challenges in accessing appropriate care. Therefore, effectively preventing depression has become an area of focus. The purpose of this study is to explore the impact of sedentary behaviour and varying dose-response relationships on the risk of depression. A systematic search of relevant studies published up to 15 August 2024 was performed using the PubMed, Embase, and Web of Science databases. We selected original studies that reported a relationship between sedentary behaviour and the risk of depression. Two authors used pre-filled forms to independently extract the trial characteristics and intervention details. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a random effects analysis was conducted. Clinical outcomes were assessed according to odds ratios (ORs) and 95% confidence intervals (CIs). The quality of the included studies was evaluated using the Eight-component Rating scale and the Cochrane Risk of Bias tool. Twenty-five studies involving 252,503 participants were included. Compared with participants with less sedentary behaviour, those with more sedentary behaviour had a significantly increased risk of depression (OR 1.35 [95% CI 1.20–1.52], p < 0.001; I2 = 83.3%, p < 0.001). Furthermore, we found that among participants with sedentary behaviour, those aged 16–20 had the highest risk of depression (OR 1.69, p < 0.001), followed by those under the age of 16 (OR 1.43, p < 0.001) and those aged 20–40 (OR 1.05, p = 0.032). In contrast, participants > 40 years showed no significant difference (OR 1.14, p = 0.073). Participants from developed countries had a lower risk of depression than the risk in those from developing countries. Lastly, sedentary behaviour of varying intensities was associated with a higher risk of depression. Sedentary behaviour greatly increases the risk of depression. Participants under the age of 20 were at a higher risk of developing depression owing to sedentary behaviour. Appropriate exercise can be effective for preventing depression.