Guixin Zhao

Purpose: Severe community-acquired pneumonia (SCAP) causes high morbidity and mortality. Metagenomic next-generation sequencing (mNGS) data comparing pathogen profiles in SCAP between people living with human immunodeficiency virus (HIV) (PLWH) and HIV-uninfected individuals remain scarce. Patients and Methods: We retrospectively enrolled 72 SCAP patients at Kunming Third People’s Hospital. We compared alpha diversity of respiratory microbiota, pathogen spectrum and healthcare resource utilization (HRU) between the two groups. We also assessed whether HIV infection was an independent risk factor for 30-day mortality. Results: mNGS detected pathogens in 70 of 72 patients (97.2%). PLWH showed higher detection rates of Pneumocystis jirovecii (p < 0.001), Human gammaherpesvirus 4 (EBV) (p = 0.013), and Human betaherpesvirus 5 (CMV) (p < 0.001). Among the 54 SCAP patients who survived 30 days, HRU metrics did not differ between groups. Elevated D-dimer level was an independent risk factor for 30-day mortality in SCAP patients (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.004– 1.030; p = 0.0127). Conclusion: HIV co‑infection in SCAP patients is associated with a distinct pathogen spectrum but does not affect HRU or 30‑day mortality. Elevated D‑dimer level is an independent risk factor for 30‑day mortality in SCAP patients.

Purpose: To evaluate the survival outcomes of patients with intermediate to advanced hepatocellular carcinoma (HCC), patients who underwent transarterial chemoembolization (TACE) alone were compared with those who underwent a combination of TACE and ablation therapy. Patients and Methods: This study retrospectively evaluated 536 HCC patients in our hospital from July 2016 to November 2022. All patients underwent TACE, with a subset also receiving ablation therapy. To ensure comparability, propensity score matching (PSM) was performed. We then compared overall survival (OS) and progression-free survival (PFS) between these two groups. Survival outcomes were analyzed utilizing Kaplan-Meier curves and compared via the Cox regression. Results: 200 among these 536 HCC patients received TACE combined with ablation whereas the remaining 336 received TACE alone. With PFS analysis, the numbers were reduced to 176 in combination therapy group and 250 in TACE alone group. With and without PSM, the OS and PFS were consistently and significantly better in the former than the latter group. In patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C, those who received combination therapy demonstrated significantly higher OS compared to those treated with TACE alone. For stage B patients, PFS was also significantly longer in the combination therapy group, before and after PSM [hazard ratio (HR), 0.563; 95% CI: 0.360– 0.879; P = 0.012, HR, 0.613; 95% CI: 0.382– 0.985; P = 0.043]. However, after PSM, no statistical difference in survival outcomes was observed between the two groups for stage C patients (HR, 0.673; 95% CI: 0.395– 1.146; P = 0.145). Conclusion: Our data suggested that for OS, the combination therapy has sustained benefits for both patients with stage B and C, But for PFS, the benefits of the combination therapy among the stage C patients, could not be persistently demonstrated by the current datasets.

BackgroundEPHX1 gene polymorphisms were recently acknowledged as an important source of individual variability in carbamazepine metabolism, but the result of that association still remains controversial. Aim of the review To obtain a more precise estimation of the associations between EPHX1 polymorphisms and carbamazepine metabolism and resistance. Methods The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc and Wan fang Database were searched for appropriate studies regarding the rs1051740 and rs2234922 polymorphisms of EPHX1 up to September 2019. The meta-analysis was carried out using the Review Manager 5.3 software. The mean difference and 95% confidence interval were applied to assess the strength of the relationship. Results A total of 7 studies involving 1118 related epilepsy patients were included. EPHX1 rs1051740 polymorphism was significantly associated with adjusted concentrations of both carbamazepine (CC vs. TT: P = 0.02; CC vs. CT + TT: P = 0.005) and carbamazepine-10,11-epoxide (CC vs. CT + TT: P = 0.03). Furthermore, EPHX1 rs2234922 polymorphism was also observed to be significantly associated with decreased adjusted concentrations of carbamazepine-10,11-trans dihydrodiol (GG vs. GA + AA: P = 0.04) and CBZD:CBZE ratio (GG vs. AA: P = 0.008; GG vs. GA + AA: P = 0.0008). Nevertheless, the pooled analysis showed that the EPHX1 polymorphisms had no significant effect on CBZ resistance. Conclusion EPHX1 rs1051740 and rs2234922 polymorphisms may affect the carbamazepine metabolism; but carbamazepine resistance was not related to any of the single nucleotide polymorphisms investigated. These findings provided further evidence for individualized therapy of epilepsy patients in clinics.

Objective Fracture is a common consequence of osteoporosis and is associated with high morbidity and mortality. Recently, increasing evidence has suggested that polymorphisms in tumor necrosis factor‐α (TNF‐α) gene were associated with osteoporosis risk and bone mineral density (BMD), but results remain conflicting. We herein performed a meta‐analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. Methods The PubMed, EMBASE, Cochrane Library, CNKI (China National Knowledge Infrastructure) and Wan Fang databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed and all available data were accumulated. The pooled odds ratios (ORs) or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the relationships. Results A total of 15 studies involving 5273 subjects were included in our meta‐analysis. The GG genotype of TNF‐α G308A was associated with an increased risk of osteoporosis under a mutant model (GG vs GA+AA: OR = 0.63, 95% CI: 0.51‐0.77, P < 0.0001, I² = 31%). Additionally, we also observed a significant association between G308A polymorphism and BMD of lumbar spine (AA vs GG: P = 0.01, I² = 53%). However, TNF‐α T1031C, C857T and C863A polymorphisms had no obvious impacts on osteoporosis risk. Conclusions The present meta‐analysis demonstrated that TNF‐α G308A polymorphism may act as a potential candidate biomarker for screening, diagnosis, and treatment of osteoporosis, which will help improve individualized therapy of osteoporosis patients in clinics.