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BackgroundThe current landscape of acne therapeutics is notably lacking in targeted treatments, highlighting a critical need for the discovery of new drug targets to improve treatment outcomes.ObjectivesThis study aims to investigate the connections between proteomics and genetics in relation to acne across extensive population cohorts, aspiring to identify innovative preventive and therapeutic approaches.MethodsEmploying a longitudinal cohort of 54,306 participants from the UK Biobank Pharmacological Proteomics Project (UKB-PPP), we performed an exhaustive evaluation of the associations between 2,923 serum proteins and acne risk. Initial multivariate Cox regression analyses assessed the relationship between protein expression levels and acne onset, followed by two-sample Mendelian Randomization (TSMR), Summary-data-based Mendelian Randomization (SMR), and colocalization to identify genetic correlations with potential protein targets.ResultsWithin the UKB cohort, we identified 19 proteins significantly associated with the risk of acne. Subsequent analysis using Two-Sample Mendelian Randomization (TSMR) refined this to two specific proteins: FSTL1 and ANXA5. Each one-standard deviation increase in the expression levels of FSTL1 and ANXA5 was associated with a 24% and 32% increase in acne incidence, respectively. These results were further validated by additional Summary-data-based Mendelian Randomization (SMR) and differential expression analyses.ConclusionsOur comprehensive analysis of proteomic and genetic data from a European adult cohort provides compelling causal evidence that several proteins are promising targets for novel acne treatments.

Introduction: This study focuses on investigating the characteristics of overburden failure and ground pressure behavior in shallow coal seam mining beneath a gully. The research is conducted at the 135201 working face of Shaliang Coal Mine in the Shenfu Mining Area.Methods: The study employs physical similarity simulation tests, theoretical analysis, and field measurements to analyze the ground pressure and overburden failure characteristics at the working face.Results: The research findings indicate that the ground pressure is stronger in the uphill section compared to the gully bottom and downhill sections. The weighting interval in the uphill section is the smallest. A mechanical analysis model for the failure structure of the key stratum in the uphill section is established based on monitored ground pressure data and physical simulation test results. A calculation formula for the weighting interval in the uphill section is derived. The relationship between the caving interval, the thickness of the key stratum in the uphill section, and the gully slope is also analyzed. The on-site measurements align well with the theoretical results.Discussion: The study proposes a prediction method for ground pressure and suggests hazard prevention and control measures for shallow coal seam mining beneath a gully based on the research findings.

BackgroundHepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and m metastasis that does not respond well to current therapies and has a very poor prognosis. Disulfidptosis is a novel mode of cell death that has been analyzed as a novel therapeutic target for HCC cells.MethodsThis study integrated bulk ribonucleic acid (RNA) sequencing datasets, spatial transcriptomics (ST), and single-cell RNA sequencing to explore the landscape of disulfidptosis and the immune microenvironment of HCC cells.ResultsWe developed a novel model to predict the prognosis of patients with HCC based on disulfidptosis. The model has good stability, applicability, and prognostic and immune response prediction abilities. N-myc downregulated gene1 (NDRG1) may contribute to poor prognosis by affecting macrophage differentiation, thus allowing HCC cells to evade the immune system.ConclusionOur study explores the disulfidptosis of HCC cells through multi-omics and establishes a new putative model that explores possible targets for HCC treatment.

This study aimed to establish three-dimensional models of the biliary tract of Chinese people using the Hisense computer-aided surgery (CAS) system and to explore the branching patterns and variation types of the biliary system under the study of 3D reconstruction of the biliary tract. Three-dimensional models of the biliary tract were reconstructed in 50 patients using the Hisense CAS system. The branching patterns of intrahepatic bile ducts were observed. The biliary tract was classified according to the confluence of the right posterior sectoral duct (RPSD), right anterior sectoral duct (RASD) and left hepatic duct (LHD), and the presence or absence of accessory hepatic ducts. The 3D models of the bile ducts were successfully reconstructed in 50 Chinese patients. The branching patterns of the bile ducts were classified into seven types. The anatomy of the bile ducts was typical in 54% of cases (n = 27), showed triple confluence in 10% (n = 5), and crossover anomaly in 14% (n = 7), which means anomalous drainage of the RPSD into the LHD, anomalous drainage of the RPSD into the common hepatic duct (CHD) in 10% (n = 5), anomalous drainage of the RPSD into the cystic duct (CD) in 2% (n = 1), absence of left main hepatic duct in 1% (n = 1), presence of accessory duct in 8% (n = 4). Among them, there were three cases of accessory hepatic ducts coexisting with other variation types. By using the Hisense CAS system to establish 3D models of the biliary tract of the Chinese people, we established the branching model of the second-order bile ducts, which has important value for the classification of the biliary system and its variation types.

BackgroundThe clinical benefit of hepatectomy in patients with liver metastases from gastrointestinal stromal tumors (GIST) has not been well defined in this era of tyrosine kinase inhibitor (TKI). Our study aims to demonstrate the survival advantage of adding hepatectomy in patients with GIST liver metastases.MethodsInformation on patients with metastatic GIST treated or consulted between January 2006 and December 2018 was retrieved. Patients without extrahepatic metastases were included and classified into the surgical (S group) and non-surgical (NS group). Clinicopathological features were compared and their association with survival was assessed.ResultsA total of 119 patients were included in this retrospective analysis, 62 in the S group and 59 in the NS group. Comparison of clinicopathological features showed that a markedly higher proportion of patients in the S group had ≤3 hepatic lesions (79.0% vs. 29.8%, p

BackgroundIt is controversial whether adjuvant treatment could be recommended for hepatocellular carcinoma (HCC) after curative hepatectomy. Thus, we performed a network meta-analysis (NMA) to assess adjuvant treatment’s benefit and determine the optimal adjuvant regimen.MethodsWe systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing adjuvant therapy versus no active treatment after curative hepatectomy among patients with HCC. Pooled data on recurrence and overall survival (OS) were analyzed within pairwise meta-analysis and NMA.ResultsTwenty-three eligible trials (3,940 patients) reporting eight treatments were included. The direct meta-analysis showed that adjuvant therapy prevented the recurrence (OR = 0.65; 95% CI: 0.55, 0.77; P = 0.177; I2 = 21.7%) and contributed to OS (HR = 0.63; 95% CI: 0.54, 0.73; P = 0.087; I2 = 31.1%) in comparison to the observation. In the NMA, internal radiotherapy (IRT; OR = 0.55; 95% CI: 0.39, 0.77; SUCRA = 87.7%) followed by hepatic artery infusion chemotherapy (HAIC; OR = 0.6; 95% CI: 0.36, 0.97; SUCRA = 77.8%), and HAIC (HR = 0.44; 95% CI: 0.21, 0.87; SUCRA = 82.6%) followed by IRT (HR 0.54; 95% CI:0.36, 0.81; SUCRA = 69.7%) were ranked superior to other treatments in terms of preventing recurrence and providing survival benefit, respectively.ConclusionsThe addition of adjuvant therapy lowers the risk of recurrence and provide survival benefit after surgical resection for HCC. HAIC and IRT are likely to be the two most effective adjuvant regimens.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-11-0039/.