Gallstones is common and associated with substantial health and economic burden. We aimed to comprehensively evaluate the prevalence and incidence of gallstones in the 21^st century. We systematically searched PubMed and Embase to identify studies reporting the prevalence and/or incidence of gallstones between Jan 1, 2000 and Nov 18, 2023. Pooled prevalence and incidence were calculated using DerSimonian and Laird's random-effects model. We performed subgroup analyses and meta-regression based on age, sex, geographic location, population setting, and modality of detection to examine sources of heterogeneity. Based on 115 studies with 32,610,568 participants, pooled prevalence of gallstones was 6.1% (95% CI, 5.6-6.5) Prevalence was higher in females vs. males (7.6% vs. 5.4%), in South America vs. Asia (11.2% vs. 5.1%), in upper-middle income country vs. high-income country (8.9% vs. 4.0%) and with advancing age. On sensitivity analysis of population-based studies, prevalence of gallstones was 5.5% (95% CI, 4.1-7.4; n=44 studies), and on limiting to imaging-based detection modalities, prevalence was 6.7% (95% CI, 6.1-7.3; n=101 studies). Prevalence was stable over the last 20 years. Based on 12 studies, incidence of gallstones was 0.47 per 100 person-years (95% CI, 0.37-0.51), without differences between males and females, and with rising incidence in more recent studies. Globally, 6% of the population have gallstones, with higher rates in females and in South America. The incidence of gallstones may be rising. Our findings call for prioritizing research on prevention of gallstones.

Background: Tumor mutation burden (TMB) have been served as the most prevalent biomarkers to predict immunotherapy response. LRP1B (low-density lipoprotein receptor-related protein 1B) is frequently mutated in melanoma, non-small cell lung cancer (NSCLC) and other tumors; however, its association with TMB and survival in patients with immunotherapy remains unknown. Methods: We curated somatic mutation data and clinicopathologic information from 332 melanoma immunotherapy samples for discovery and 113 NSCLC samples for further corroboration. Bayesian variants non-negative matrix factorization was used to extract tumor mutational signatures. Multivariate Cox and logistic regression models were applied to adjust confounding factors. The CIBERSORT and GSEA algorithm were separately used to infer leukocyte relative abundance and significantly enriched pathways. Results: Patients with LRP1B mutation were identified to be associated with prolonged survival in both immunotherapy cohort. Higher tumor mutation burden was found in LRP1B mutated patients, and the association remained significant after controlling for age, gender, stage, mutations in TP53 and ATR, and mutational signatures. Immune response and cell cycle regulation circuits were among the top enriched pathways in samples with LRP1B mutations. Conclusion: Our studies suggested sequencing even a single, frequently mutated gene may provide insight into genome-wide mutational burden, and may serve as a biomarker to predict immune response.

Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.

BACKGROUND:Distant metastasis (DM) is a crucial problem in management of patients with gastric cancer. Identification of the risk factors for development of DM and the prognostic factors for patients with DM is essential in development of individualized treatment of patients at the advanced stage with specific metastasis. MATERIAL AND METHODS:Records of patients with gastric cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival duration of patients with specific DM was estimated, and the prognostic factors were investigated using the Cox proportional hazard regression model. The logistic regression model was used to reveal the inherent risk factors for development of DM. RESULTS:Eventually, 32.6% (11,918 out of 36,588) of gastric cancer patients were diagnosed with DM between 2010 and 2015, among whom 5,361, 1,778, 1,495, and 231 patients were diagnosed with liver, lung, bone, and brain metastasis, respectively. The median overall survival for patients with DM was 5.0 (95% CI: 4.8-5.2) months, with a 5-year survival rate of 3.9%. Primary tumor site, histology types, tumor grade, T stage, N stage, surgery, chemotherapy, and the number of metastases were associated with worse survival. Younger age and higher tumor grade were positively associated with the development of DM. CONCLUSIONS:Initial DM was found in 32.6% of patients with gastric cancer. Homogenous and heterogenous predictive factors were identified for patients with a specific metastatic site, which can be used in targeted screening and individualized treatment.

The purpose of the present study was to characterize the prevalence, associated factors, and to construct a nomogram for predicting bone metastasis (BM) with different histological types of lung cancer. This study was a descriptive study that basing on the invasive lung cancer patients diagnosed between 2010 and 2014 in Surveillance, Epidemiology, and End Results program. A total of 125,652 adult patients were retrieved. Logistic regression analysis was conducted to investigate homogeneous and heterogeneous factors for BM occurrence. Nomogram was constructed to predict the risk for developing BM and the performance was evaluated by the receiver operating characteristics curve (ROC) and the calibration curve. The overall survival of the patients with BM was analyzed using the Kaplan–Meier method and the survival differences were tested by the log-rank test. A total of 25,645 (20.9%) were reported to have BM, and the prevalence in adenocarcinoma, squamous cell carcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC), and non-small cell lung cancer/not otherwise specified lung cancer (NSCLC/NOS) were 24.4, 12.5, 24.7, 19.5 and 19.4%, respectively, with significant difference (P < 0.001). Male gender, more metastatic sites and lymphatic metastasis were positively associated with BM in all lung cancer subtypes. Larger tumor size was positively associated with BM in all the lung cancer subtypes except for NSCLC/NOS. Poorly differentiated histology was positively associated with adenocarcinoma, squamous cell carcinoma and NSCLC/NOS. The calibration curve and ROC curve exhibited good performance for predicting BM. The median survival of the bone metastatic lung cancer patients was 4.00 (95%CI: 3.89–4.11) months. With the increased number of the other metastatic sites (brain, lung and liver metastasis), the survival significantly decreased (p < 0.001). Different lung cancer histological subtypes exhibited distinct prevalence and homogeneity and heterogeneity associated factors for BM. The nomogram has good calibration and discrimination for predicting BM of lung cancer.

Corrigendum: Association of LRP1B Mutation With Tumor Mutation Burden and Outcomes in Melanoma and Non-small Cell Lung Cancer Patients Treated With Immune Check-Point Blockades