Association between alcohol consumption and all-cause mortality, cardiovascular disease, and chronic kidney disease: A prospective cohort study.

In recent years, significant progress has been achieved in comprehending the impact of alcohol consumption on adverse health outcomes. However, the quality of evidence remains limited. Our objective was to conduct a prospective study examining the relationship between different types of alcoholic beverages and the risk of all-cause mortality, cardiovascular disease (CVD), and chronic kidney disease (CKD), and identifying the thresholds of safe dose stratified by sex using data from the UK Biobank. 502,490 participants were enrolled. These participants were initially registered between 2006 and 2010, and underwent reassessment between 2012 and 2013. All participants completed a detailed questionnaire on their alcohol consumption, including total alcohol consumption yesterday, weekly consumption of red wine, champagne plus white wine, beer, spirits, and fortified wine. All-cause mortality and the incidence of CVD and CKD were considered as the primary outcomes. 2852 participants reported CKD during a median follow-up period of 11.94 years, while 79,958 participants reported CVD over a median follow-up period of 11.35 years. Additionally, 18,923 participants died over a median follow-up period of 11.89 years. After adjusting for variables such as age, sex, education level, smoking status, diet score, and exercise score, total alcohol consumption showed a U-shaped relationship with the risk of CVD and all-cause mortality, but showed an inverse association with the risk of CKD. Upon further classification of alcoholic beverages, our analysis revealed that red wine, champagne plus white wine, beer, spirits, and fortified wine presented a U-shaped relationship with the risk of all-cause mortality and CKD. However, spirits were positively associated with the risk of CVD, only red wine, champagne plus white wine, beer, and fortified wine showed a U-shaped relationship with the risk of CVD. The safe doses of total alcohol consumption should be < 11 g/d for males and < 10 for females, red wine consumption should be < 7 glasses/week for males and < 6 for females, champagne plus white wine consumption should be < 5 glasses/week, and fortified wine consumption should be < 4 glasses/week. Red wine, champagne plus white wine, beer, and fortified wine below the corresponding thresholds of safe dose in our analysis were significantly associated with a lower risk of all-cause mortality, CVD, and CKD. And these alcoholic beverages under safe doses exhibited a protective effect against conditions like diabetes, depression, dementia, epilepsy, liver cirrhosis, and other digestive diseases, while didn't increase the risk of cancer.

Qingfei mixture mitigates immunosuppression of tumor microenvironment in non-small cell lung cancer by blocking stat1/Ido1-mediated tryptophan-kynurenine pathway.

Programmed death-1 (PD-1) acts as a T cell checkpoint and is important in controlling T cell exhaustion. Blocking the intercommunication across PD-1 and PD-L1 is promising for advanced lung cancer treatment. However, the response rate requires being strengthened. This study aimed to determine whether the combination treatment of Qingfei mixture (QFM) and PD-1 inhibitor could improve the sensitivity of monoclonal antibody by regulating STAT1/IDO1-mediated tryptophan (Trp)-kynurenine (Kyn) pathway. The in vivo imaging system, immunofluorescence, hematoxylin-eosin staining, TUNEL, flow cytometry, HPLC, and ELISA were used to estimate the anti-tumor effects in LLC-luc tumor-bearing C57BL/6 mice treated with QFM, PD-1 inhibitor, 2-NP (enhancer of STAT1 transcription), and FICZ (AhR agonist) alone or in combination. IFN-γ-mediated A549 and LLC cells were treated with QFM-containing serum and fludarabine (FLU, STAT1 inhibitor), and cell viability, apoptosis, and Kyn content were then evaluated using CCK-8 assays, flow cytometry, and HPLC assays, respectively. Additionally, the expressions of STAT1, IDO1, AhR, NFATc1, TRIP12, PD-1, and PD-L1 were measured in vivo and in vitro. We found QFM increased the anti-cancer actions of PD-1 inhibitors by increasing the CD8+IFNγ+ T cells infiltration and decreasing the ratio of Kyn/Trp. Besides, QFM-containing serum suppressed the proliferation and promoted apoptosis in A549 and LLC cells, meanwhile, FLU boosted the effects of QFM-containing serum. Moreover, the suppression of tumor growth in the combination therapy was attenuated in the mice receiving 2-NP or FICZ. The occurrence of the above results was accompanied by a decrease in STAT1, IDO1, AhR, PD-1, and PD-L1 expressions. Collectively, the findings suggested that QFM may increase the influences of PD-1 inhibitors at least partially by blocking the STAT1/IDO1-mediated tryptophan-kynurenine pathway in lung cancer.

Association Between the Improvement of Knowledge, Attitude and Practice of Hypertension Prevention and Blood Pressure Control-A Cluster Randomized Controlled Study.

BACKGROUND: Hypertension-related knowledge, attitude and practice (KAP) of hypertensive patients can affect the awareness, treatment and control of hypertension. However, little attention has been paid to the association between the change of hypertension preventive KAP and blood pressure (BP) control in occupational population using longitudinal data. We assess the effectiveness of a workplace-based multicomponent hypertension intervention program on improving the level of KAP of hypertension prevention, and the association between improvement in KAP and BP control during intervention. METHODS: From January 2013 to December 2014, workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20) using a cluster randomized control method. All employees in each workplace were asked to complete a cross-sectional survey to screen for hypertension patients. Hypertension patients in the intervention group were given a 2-year workplace-based multicomponent hypertension intervention for BP control. The level of hypertension prevention KAP and BP were assessed before and after intervention in the two groups. RESULTS: Overall, 3331 participants (2658 in the intervention group and 673 in the control group) were included (mean [standard deviation] age, 46.2 [7.7] years; 2723 men [81.7%]). After 2-year intervention, the KAP qualified rate was 63.2% in the intervention groups and 50.1% in the control groups (odds ratio = 1.65, 95% CI, 1.36∼2.00, P < .001). Compared with the control group decreased in the qualified rate of each item of hypertension preventive KAP questionnaire, all the items in the intervention group increased to different degrees. The increase of KAP score was associated with the decrease of BP level after intervention. For 1 point increase in KAP score, systolic blood pressure (SBP) decreased by .28 mmHg and diastolic blood pressure (DBP) decreased by .14 mmHg [SBP: ß = -.28, 95%CI: -.48∼-.09, P = .004; DBP: ß = -.14, 95%CI: -.26∼-.02, P = .024]. SBP and DBP was significantly in manual labor workers (SBP: ß = -.34, 95%CI: -.59∼-.09, P = .008; DBP: ß = -.23, 95%CI: -.38∼-.08, P = .003), workers from private enterprise, state-owned enterprise (SOE) (SBP: ß = -.40, 95%CI: -.64∼-.16, P = .001; DBP: ß = -.21, 95%CI: -.36∼-.06, P = .005) and a workplace with an affiliated hospital (SBP: ß = -.31, 95%CI: -.52∼-.11, P = .003; DBP: ß = -.16, 95%CI: -.28∼-.03, P = .016). The improvement of knowledge (SBP: ß = -.29, 95%CI: -.56∼-.02, P = .038; DBP: ß = -.12, 95%CI: -.29∼.05, P = .160), as well as attitude (SBP: ß = -.71, 95%CI: -1.25∼-.18, P = .009; DBP: ß = .18, 95%CI: -.23∼.59, P = .385) and behavior (SBP: ß = -.73, 95%CI: -1.22∼-.23, P = .004; DBP: ß = -.65, 95%CI: -.97∼-.33, P < .001) was gradually strengthened in relation to BP control. CONCLUSION: This study found that workplace-based multicomponent hypertension intervention can effectively improve the level of hypertension preventive KAP among employees, and the improvement of KAP levels were significantly associated with BP control. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641.

Effects of loneliness and isolation on cardiovascular diseases: a two sample Mendelian Randomization Study.

BACKGROUND: Loneliness and isolation are associated with multiple cardiovascular diseases (CVDs), but there is a lack of research on whether they were causally linked. We conducted a Mendelian Randomization (MR) study to explore causal relationships between loneliness and isolation and multiple CVDs. METHODS: Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study (GWAS) of 455,364 individuals of European ancestry in the IEU GWAS database. Summary data for 15 CVDs were also obtained from the IEU GWAS database. We used three MR methods including inverse variance weighting, MR-Egger, and weighted median estimation to assess the causal effect of exposure on outcomes. Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy. RESULTS: MR analysis showed that loneliness and isolation were significantly associated with essential hypertension (OR = 1.07, 95% CI: 1.03-1.12), atherosclerotic heart disease (OR = 1.04; 95% CI: 1.02-1.06), myocardial infarction (OR = 1.02; 95% CI: 1-1.04) and angina (OR = 1.04; 95% CI =1.02-1.06). No heterogeneity and pleiotropy effects were found in this study. CONCLUSIONS: Causal relationship of loneliness and isolation with CVDs were found in this study.

Preparation of functional geopolymers from municipal solid waste incineration fly ash: An approach combining experimental and computational simulation studies.

This study aims to evaluate the feasibility and safety of using municipal solid waste incineration fly ash (MSW-IFA) in the development of geopolymer-based solidification/stabilization (S/S) treatments. Geopolymers have garnered attention as a sustainable alternative to traditional cement, owing to their high strength, stability, and minimal CO2 emissions. In this study, a combination of experimental and simulation calculations was used to investigate the setting time, mechanical properties, environmental risks, hydration mechanisms and processes of municipal solid waste incineration fly ash-based polymeric functional cementitious materials (GFCM). The results demonstrate that the mechanical properties of GFCM are related to the changes in the mineral phases and the degree of compactness. Quantum chemical calculations indicate that the hydration products may be [Si(OH)4], [Al(OH)3(OH2)] and [Al(OH)4]-. It is possible that the heavy metals are embedded in the hydrated silica-aluminate by electrostatic interaction or chemisorption. Heavy metals may be embedded in hydrated silica-aluminate by electrostatic action or chemisorption. This study provides a feasible method for resource utilization and heavy metal stabilization mechanism of MSW-IFA.

Genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus.

X chromosome inactivation can balance the effects of the two X chromosomes in females, and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation. The mechanisms of escape include modification of DNA, RNA, histone, epitope, and various regulatory proteins, as well as the spatial structure of chromatin. The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases, particularly autoimmune diseases. It has been demonstrated that the presence of TLR7, CD40L, IRAK-1, CXCR3, and CXorf21 significantly contributes to the prevalence of SLE (systemic lupus erythematosus) in females. This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus. Therefore, elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease, but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.

Essential genes analysis reveals small ribosomal subunit protein eS28 may be a prognostic factor and potential vulnerability in osteosarcoma.

Background: Osteosarcoma, the most common primary malignant bone tumor, is currently treated with surgery combined with chemotherapy, but the limited availability of targeted drugs contributes to a poor prognosis. Identifying effective therapeutic targets is crucial for improving the prognosis of osteosarcoma patients. Methods: We screened the DepMap database to identify essential genes as potential therapeutic targets for osteosarcoma. Gene Set Enrichment Analysis (GSEA) was employed to elucidate the biological roles of these essential genes. Promising candidates were filtered through univariate and multivariate Cox analyses, as well as Kaplan-Meier survival analyses using the GSE21257-OSA and TARGET-OSA datasets. The functional role of the target gene was assessed through cell experiments. Additionally, an in situ nude mice model was established to observe the gene's function, and RNA sequencing was utilized to explore the underlying molecular mechanism. Results: A total of 934 essential genes were identified based on their effects (Chronos) using the DepMap database. These genes were primarily enriched in the ribosome pathway according to GSEA analysis. Among them, 195 genes were associated with the ribosome pathway. Rps28, Rps7, and Rps25 were validated as promising candidates following univariate and multivariate Cox analyses of the TARGET-OSA and GSE21257-OSA datasets. Kaplan-Meier survival analyses indicated Rps28 represented an especially promising target, with high expression correlating with poor prognosis. Knockdown of small ribosomal subunit protein eS28, the protein of Rps28, inhibited proliferation, migration, and invasion in both in vitro and in vivo experiments. Silencing RPS28 affected the MAPK signaling pathway in osteosarcoma. Conclusion: In summary, Rps28 has been identified as an essential gene for osteosarcoma cell survival and eS28 may serve as a potential vulnerability in osteosarcoma.

Effects of Perioperative Music Therapy on Patients with Postoperative Pain and Anxiety: A Systematic Review and Meta-Analysis.

Background: As a mind-body therapy, music may have a positive effect on patients with postoperative pain and anxiety. Objective: The aim of this systematic review and meta-analysis was to explore the effects of perioperative music therapy on postoperative pain and anxiety based on existing clinical trials. Methods: The Cochrane Library, PubMed, and Embase were searched from their inception to August 2022, selected the literature according to the inclusion and exclusion criteria, and completed the meta-analysis using RevMan 5.3. Results: A total of 19 eligible randomized controlled trials were enrolled, including 1803 patients. The results of the meta-analysis showed that the scores of pain (standardized mean difference [SMD], -0.90; 95% confidence interval [CI], -1.26 to -0.53; p < 0.00001) and anxiety (SMD, -0.75; 95% CI, -1.19 to -0.31; p = 0.0008) decreased in the music group on postoperative day 1. The blood pressure (mean difference [MD], -5.29; 95% CI, -9.53 to -1.06; p = 0.01) and heart rate (MD, -6.13; 95% CI, -11.69 to -0.58; p = 0.03) also decreased on the same day. Further, the score of change in pain (SMD, 0.35; 95% CI, 0.01 to 0.68; p = 0.04) and anxiety (SMD, 1.35; 95% CI, 0.01 to 2.69; p = 0.05) increased between preoperative and postoperative days in the music group. However, the scores of hospital satisfaction (MD, -0.07; 95% CI, -1.40 to 1.27; p = 0.92) and incidences of postoperative nausea and vomiting (risk ratio, 0.41; 95% CI, 0.13 to 1.34; p = 0.14) did not decrease in the music group. Conclusion: Perioperative music therapy can significantly reduce postoperative pain and anxiety and avoid fluctuations in blood pressure and heart rate but does not improve patient hospital satisfaction or incidences of postoperative nausea and vomiting.

Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Fibroblast growth factor 21 (FGF21) regulates metabolism and protects cells against stress. Efruxifermin is a bivalent Fc-FGF21 analogue that replicates FGF21 agonism of fibroblast growth factor receptor 1c, 2c, or 3c. The aim of this phase 2b study was to assess its efficacy and safety in patients with non-alcoholic steatohepatitis (NASH) and moderate (F2) or severe (F3) fibrosis. METHODS: HARMONY is a multicentre, randomised, double-blind, placebo-controlled, 96-week, phase 2b trial that was initiated at 41 clinics in the USA. Adults with biopsy-confirmed NASH, defined by a non-alcoholic fatty liver disease activity score (NAS) of 4 or higher and scores of 1 or higher in each of steatosis, ballooning, and lobular inflammation, with histological stage F2 or F3 fibrosis, were randomly assigned (1:1:1), via an interactive response system, to receive placebo or efruxifermin (28 mg or 50 mg), subcutaneously once weekly. Patients, investigators, pathologists, site staff, and the sponsor were masked to group assignments during the study. The primary endpoint was the proportion of patients with improvement in fibrosis of at least 1 stage and no worsening of NASH, based on analyses of baseline and week 24 biopsies (liver biopsy analysis set [LBAS]). A sensitivity analysis evaluated the endpoint in the full analysis set (FAS), for which patients with missing biopsies were considered non-responders. This trial is registered with ClinicalTrials.gov, NCT04767529, and is ongoing. FINDINGS: Between March 22, 2021, and Feb 7, 2022, 747 patients were assessed for eligibility and 128 patients (mean age 54·7 years [SD 10·4]; 79 [62%] female and 49 male [38%]; 118 [92%] white; and 56 [41%] Hispanic or Latino) were enrolled and randomly assigned to receive placebo (n=43), efruxifermin 28 mg (n=42; two randomised patients were not dosed because of an administrative error), or efruxifermin 50 mg (n=43). In the LBAS (n=113), eight (20%) of 41 patients in the placebo group had an improvement in fibrosis of at least 1 stage and no worsening of NASH by week 24 versus 15 (39%) of 38 patients in the efruxifermin 28 mg group (risk ratio [RR] 2·3 [95% CI 1·1-4·8]; p=0·025) and 14 (41%) of 34 patients in the efruxifermin 50 mg group (2·2 [1·0-5·0]; p=0·036). Based on the FAS (n=128), eight (19%) of 43 patients in the placebo group met this endpoint versus 15 (36%) of 42 in the efruxifermin 28 mg group (RR 2·2 [95% CI 1·0-4·8]; p=0·033) and 14 (33%) of 43 in the efruxifermin 50 mg group (1·9 [0·8-4·3]; p=0·123). The most frequent efruxifermin-related adverse events were diarrhoea (16 [40%] of 40 patients in the efruxifermin 28 mg group and 17 [40%] of 43 patients in efruxifermin 50 mg group vs eight [19%] of 43 patients in the placebo group; all events except one were grade 1-2) and nausea (11 [28%] patients in the efruxifermin 28 mg group and 18 [42%] patients in the efruxifermin 50 mg group vs ten [23%] patients in the placebo group; all grade 1-2). Five patients (two in the 28 mg group and three in the 50 mg group) discontinued due to adverse events. Serious adverse events occurred in four patients in the 50 mg group; one was defined as drug related (ulcerative esophagitis in a participant with a history of gastro-oesophageal reflux disease). No deaths occurred. INTERPRETATION: Efruxifermin improved liver fibrosis and resolved NASH over 24 weeks in patients with F2 or F3 fibrosis, with acceptable tolerability, supporting further assessment in phase 3 trials. FUNDING: Akero Therapeutics.

ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer.

Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.

Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis.

Liver cancer is one of the most lethal malignant cancers worldwide. However, the therapeutic options for advanced liver cancers are limited and reveal scant efficacy. The current study investigated the effects of nivolumab (Niv) and escitalopram oxalate (Esc) in combination on proliferation of liver cancer cells both in vitro and in vivo. Significantly decreased viability of HepG2 cells that were treated with Esc or Niv was observed in a dose-dependent manner at 24 h, 48 h, and 72 h. Administration of Esc (50 µM) + Niv (20 µM), Esc (75 µM) + Niv (5 µM), and Esc (75 µM) + Niv (20 µM) over 24 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Additionally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) over 48 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Finally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) for 72 h exhibited synergistic effects, inhibiting HepG2 survival. Com-pared with controls, HepG2 cells treated with Esc (50 µM) + Niv (20 µM) exhibited significantly increased sub-G1 portion and annexin-V signals. In a xenograft animal study, Niv (6.66 mg/kg) + Esc (2.5 mg/kg) significantly suppressed the growth of xenograft HepG2 tumors in nude mice. This study reports for the first time the synergistic effects of combined administration of Niv and Esc for inhibiting HepG2 cell proliferation, which may provide an alternative option for liver cancer treatment.

Workplace-based primary prevention intervention reduces incidence of hypertension: a post hoc analysis of cluster randomized controlled study.

BACKGROUND: A workplace-based primary prevention intervention be an effective approach to reducing the incidence of hypertension (HTN). However, few studies to date have addressed the effect among the Chinese working population. We assessed the effect of a workplace-based multicomponent prevention interventions program for cardiovascular disease on reducing the occurrence of HTN through encouraging employees to adopt a healthy lifestyle. METHODS: In this post hoc analysis of cluster randomized controlled study, 60 workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20). All employees in each workplace were asked to complete a baseline survey after randomization for obtaining sociodemographic information, health status, lifestyle, etc. Employees in the intervention group were given a 2-year workplace-based primary prevention intervention program for improving their cardiovascular health, including (1) cardiovascular health education, (2) a reasonable diet, (3) tobacco cessation, (4) physical environment promotion, (5) physical activity, (6) stress management, and (7) health screening. The primary outcome was the incidence of HTN, and the secondary outcomes were improvements of blood pressure (BP) levels and lifestyle factors from baseline to 24 months. A mix effect model was used to assess the intervention effect at the end of the intervention in the two groups. RESULTS: Overall, 24,396 participants (18,170 in the intervention group and 6,226 in the control group) were included (mean [standard deviation] age, 39.3 [9.1] years; 14,727 men [60.4%]). After 24 months of the intervention, the incidence of HTN was 8.0% in the intervention groups and 9.6% in the control groups [relative risk (RR) = 0.66, 95% CI, 0.58 ~ 0.76, P < 0.001]. The intervention effect was significant on systolic BP (SBP) level (ß = - 0.7 mm Hg, 95% CI, - 1.06 ~ - 0.35; P < 0.001) and on diastolic BP (DBP) level (ß = - 1.0 mm Hg, 95% CI, - 1.31 ~ - 0.76; P < 0.001). Moreover, greater improvements were reported in the rates of regular exercise [odd ratio (OR) = 1.39, 95% CI, 1.28 ~ 1.50; P < 0.001], excessive intake of fatty food (OR = 0.54, 95% CI, 0.50 ~ 0.59; P < 0.001), and restrictive use of salt (OR = 1.22, 95% CI, 1.09 ~ 1.36; P = 0.001) in intervention groups. People with a deteriorating lifestyle had higher rates of developing HTN than those with the same or improved lifestyle. Subgroup analysis showed that the intervention effect of BP on employees with educational attainment of high school above (SBP: ß = - 1.38/ - 0.76 mm Hg, P < 0.05; DBP: ß = - 2.26/ - 0.75 mm Hg, P < 0.001), manual labor workers and administrative worker (SBP: ß = - 1.04/ - 1.66 mm Hg, P < 0.05; DBP: ß = - 1.85/ - 0.40 mm Hg, P < 0.05), and employees from a workplace with an affiliated hospital (SBP: ß = - 2.63 mm Hg, P < 0.001; DBP: ß = - 1.93 mm Hg, P < 0.001) were significantly in the intervention group. CONCLUSIONS: This post hoc analysis found that workplace-based primary prevention interventions program for cardiovascular disease were effective in promoting healthy lifestyle and reducing the incidence of HTN among employees. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641.

Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis.

The efficacy of immune checkpoint inhibitors (ICIs) on KRAS-mutant advanced non-small cell lung cancer (NSCLC) remains controversial. This retrospective study compared the effects of ICIs treatment and chemotherapy on the prognosis of patients with KRAS-mutant advanced NSCLC and different mutant subtypes in the real world. The study included 95 patients with KRAS-mutant advanced NSCLC. Patients treated with first-line ICIs plus platinum-containing chemotherapy had better progression-free survival (PFS) (7.4 vs 4.5 months, P = 0.035) and overall survival (OS) (24.1 vs 13.2 months, P = 0.007) than those receiving platinum-containing chemotherapy alone, and second-line ICI monotherapy was associated with better PFS (4.8 vs 3.0 months, P = 0.043) and OS (18.0 vs 13.8 months, P = 0.013) than chemotherapy monotherapy. There was no significant difference in PFS (5.267 vs 6.734 months, P = 0.969) and OS (19.933 vs 20.933 months, P = 0.808) between patients with KRAS-mutant and KRAS-wild-type NSCLC treated with ICIs or between KRAS G12C and KRAS non-G12C patients (PFS: 8.1 vs 4.8 months, P = 0.307; OS: 21.3 vs 21.8 months, P = 0.434). In summary, patients with advanced NSCLC with KRAS mutations can benefit from ICIs, but no difference between KRAS mutant subtypes was observed.

Identifying the Risk Factors for Postoperative Sore Throat After Endotracheal Intubation for Oral and Maxillofacial Surgery.

Objective: To identify risk factors for postoperative sore throat (POST) after general anesthesia in oral and maxillOfacial surgery. Material and Methods: This study is a retrospective cohort design study. We enrolled patients with oral and maxillofacial surgery who underwent endotracheal intubation under general anesthesia in the Stomatology Hospital, Zhejiang University School Of Medicine between April 2020 and April 2021. They were divided into the POST group and the without POST group. The distribution Of various characteristics in the two groups was firstly analyzed. Then, logistic regression analysis was performed to explore the independent predictors for POST occurrence. Following this, logistic regression and random forest models were constructed and their performance was evaluated to predict POST occurrence. Results: A total of 891 participants were enrolled in the study. Female gender and cough during extubation were significantly associated with increased POST occurrence in multivariate analysis (all P <0.05). Stratified logistic regression analysis results showed that the female gender was an independent predictor for POST occurrence in the 4≤age≤14 and 1460 group after adjusting American Society of Anesthesiologists status and throat and lung disease (all P <0.05). The logistic regression model had a similar effect to the random forest model in predicting POST occurrence. Interestingly, the female gender had a higher important weight compared to the cough during extubation. Conclusion: This research reveals female gender and cough during extubation as potential risk factors for POST occurrence, which may provide guidance for the effective prevention of POST in oral and maxillofacial surgery.

Effect of a Multicomponent Intervention Delivered on a Web-Based Platform on Hypertension Control: A Cluster Randomized Clinical Trial.

Importance: The prevalence of hypertension is high and still increasing across the world, while the control rate remains low in many countries. Emerging technology, such as telemedicine, may offer additional support to change the unsatisfactory situation. Objective: To establish a multicomponent intervention delivered on a web-based telemedicine platform and oriented with the Chinese hypertension management guidelines and to evaluate the effect of the intervention on blood pressure (BP) control for patients with hypertension. Design, Setting, and Participants: This cluster randomized clinical trial of a hypertension management program was conducted at 66 community health centers in China from October 1, 2018, to May 31, 2020, with a 12-month follow-up. Patients with hypertension were blinded to randomization and were randomized to either the intervention group or control group. Hypertension was diagnosed at mean systolic BP (SBP) and diastolic BP (DBP) readings higher than 140 and 90 mm Hg or with use of antihypertensive medication. Evaluation of the intervention effect was based on the principle of modified intention to treat. Interventions: Multicomponent intervention was delivered on a web-based platform and consisted of a primary prevention program for cardiovascular disease and standardized management for hypertension. Main Outcomes and Measures: The primary outcome was the change in BP control rate (SBP and DBP levels <140 and 90 mm Hg, or <130 and 80 mm Hg for patients with diabetes) from baseline to the 12-month follow-up among patients with hypertension in the intervention and control groups. Results: A total of 4118 patients (mean [SD] age, 61.6 [9.4] years; 2265 women [55.0%]) were included in the analysis, with 2985 in the intervention group and 1133 in the control group. The BP control rate at baseline was 22.8% in the intervention group and 22.5% in the control group. After 12 months of the intervention, the BP control rate for the intervention group compared with the control group was significantly higher (47.4% vs 30.2%; odds ratio, 1.18; 95% CI, 1.13-1.24; P < .001). The intervention effect on SBP level was -10.1 mm Hg (95% CI, -11.7 to -8.5 mm Hg; P < .001) and on DBP level was -1.8 mm Hg (95% CI, -2.8 to -0.8 mm Hg; P < .001). Conclusions and Relevance: Results of this trial showed that a multicomponent intervention delivered on a web-based platform improved BP control rate and lowered BP level more than usual care alone. Such a telemedicine program may provide a new, effective way to treat patients with hypertension in the community and may generate public health benefits across diverse populations. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017791.

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer.

Objective: This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics. Methods: Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan-Meier technique, Cox regression analysis, LinkedOmics, Pearson's correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein-protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors. Results: In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors. Conclusion: FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

Neoadjuvant immunotherapy in non-small cell lung cancer: a narrative review on mechanisms, efficacy and safety.

Background and Objective: Immune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC. Methods: Relevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms "non-small-cell lung cancer", "NSCLC", "neoadjuvant", "immunotherapy", "immune checkpoint inhibitors", "mechanisms", and "toxicity". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022. Key Content and Findings: After reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent. Conclusions: Neoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.

The prevalence and characteristics of metabolic syndrome according to different definitions in China: a nationwide cross-sectional study, 2012-2015.

BACKGROUND: Metabolic syndrome (MetS) is characterized by a cluster of signs of metabolic disturbance and has caused a huge burden on the health system. The study aims to explore the prevalence and characteristics of MetS defined by different criteria in the Chinese population. METHODS: Using the data of the China Hypertension Survey (CHS), a nationally representative cross-sectional study from October 2012 to December 2015, a total of 28,717 participants aged 35 years and above were included in the analysis. The MetS definitions of the International Diabetes Federation (IDF), the updated US National Cholesterol Education Program Adult Treatment Panel III (the revised ATP III), and the Joint Committee for Developing Chinese Guidelines (JCDCG) on Prevention and Treatment of Dyslipidemia in Adults were used. Multivariable logistic regression was used to identify factors associated with MetS. RESULTS: The prevalence of MetS diagnosed according to the definitions of IDF, the revised ATP III, and JCCDS was 26.4%, 32.3%, and 21.5%, respectively. The MetS prevalence in men was lower than in women by IDF definition (22.2% vs. 30.3%) and by the revised ATP III definition (29.2% vs. 35.4%), but the opposite was true by JCDCG (24.4%vs 18.5%) definition. The consistency between the three definitions for men and the revised ATP III definition and IDF definition for women was relatively good, with kappa values ranging from 0.77 to 0.89, but the consistency between the JCDCG definition and IDF definition (kappa = 0.58) and revised ATP III definition (kappa = 0.58) was poor. Multivariable logistic regression showed that although the impact and correlation intensity varied with gender and definition, area, age, education, smoking, alcohol use, and family history of cardiovascular disease were factors related to MetS. CONCLUSIONS: The prevalence and characteristics of the MetS vary with the definition used in the Chinese population. The three MetS definitions are more consistent in men but relatively poor in women. On the other hand, even if estimated according to the definition of the lowest prevalence, MetS is common in China.