Objective: To analyze the characteristics of alcohol poisoning cases among minors receiving pre hospital 120 emergency services in Zhengzhou, providing evidence for regional management strategies of alcohol poisoning among minors. Methods: A retrospective study was conducted on 1 630 alcohol poisoning cases (aged 0-18 years) from Zhengzhou s 120 emergency system during 2017-2019 and 2023. Data on gender, age, occurrence timeframes were analyzed using t-test and χ 2 test for intergroup comparisons. Results: Annual cases were 291 (2017), 353 (2018), 483 (2019), and 503 (2023). Compared with 2017, male alcohol poisoning cases increased by 66.94% while female cases surged 104.35% by 2023. The peak incidence of alcohol poisoning among minors occurred among 16-18 year olds (85.40%), followed by 13-15 year olds (13.74%). Most cases clustered between 21:01-03:00 (60.43%), with male cases peaking at 22:01-23:00 (12.73%) and female cases peaking at 02:01-03:00 ( 11.25 %). Between 00:01-03:00, male cases progressively decreased while female cases increased. Severity distribution showed 355 mild cases (21.78%), 1 035 moderate cases (63.50%), and 240 severe cases (14.72%). Conclusions Zhengzhou region has experienced sustained growth in underage alcohol poisoning cases, predominantly occurring from evening to early morning with moderate severity, female cases demonstrate faster growth rates. Multifaceted regulatory measures should be implemented to strengthen supervision of underage drinking behaviors.

Objective:To analyze the concentration of formic acid,propionic acid and butyric acid in gingival crevicular fluid(GCF)of patients with stages Ⅲ and Ⅳ periodontitis,and their relationship with periodontitis.Methods:The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology,Peking University School and Hospital of Sto-matology from February 2008 to May 2011.Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant.Periodontal clinical parameters,including plaque index(PLI),probing depth(PD),bleeding index(BI),and attachment loss(AL).Concentrations of formic acid,propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capil-lary electrophoresis(HPCE).The prediction ability of formic acid,propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed.Results:In this study,32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled,including 9 patients with grade B and 28 patients with grade C.Clinical periodontal variables in the patients with pe-riodontitis were significantly higher than those in the control group(P＜0.001).Formic acid was signifi-cantly lower in periodontitis than that in the control group[5.37(3.39,8.49)mmol/L vs.12.29(8.35,16.57)mmol/L,P＜0.001].Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group:Propionic acid,10.23(4.28,14.90)mmol/L vs.2.71(0.00,4.25)mmol/L,P＜0.001;butyric acid,2.63(0.47,3.81)mmol/L vs.0.00(0.00,0.24)mmol/L,P＜0.001.There was no significant difference in formic acid,propionic acid and butyric acid concentrations between grade B and grade C periodontitis(P＞0.05).Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket,while the concentration of formic acid decreased with the increase of PD.Propionic acid(OR=1.51,95％CI:1.29-1.75)and butyric acid(OR=3.72,95％CI:1.93-7.17)were risk factors for periodontitis,while formic acid(OR=0.87,95％CI:0.81-0.93)might be a protective factor for periodontitis.Propionic acid(AUC=0.852,95％CI:0.805-0.900),butyric acid(AUC=0.889,95％CI:0.841-0.937),f(formic acid,AUC=0.844,95％CI:0.793-0.895)demonstrated a good predictive capacity for the risk of periodontitis.Conclusion:The concentration of formic acid decrease in the GCF of periodontitis patients,which is a protective factor for periodontitis,its reciprocal have good predictive capacity.However,propionic acid and butyric acid increase,which are risk factors for periodontitis and have good predictive capacity.The concentration of formic acid,propionic acid,and butyric acid vary with probing depth,but there is no significant difference between grade B and grade C periodontitis.

As cell aggregates in three-dimensional culture derived from primary tissues or stem cells, organoids possess the ability to self-organize into organotypic structures, mimic the cellular microenvironment, and represent tissue physiology. The thyroid′s follicular tissue plays a crucial role in thyroid hormone biosynthesis. Despite prolonged in vitro expansion of thyroid follicles from adult tissues and pluripotent stem cells have been expanded for a long time, the development of thyroid organoid technology still encounters numerous challenges. Establishing a comprehensive thyroid organoid that closely mimics the human body′s actual conditions remains a research challenge. This article reviews the development process of thyroid, the related applications of existing thyroid organoid models and the methods employed in the construction.

Objective:To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support.Methods:It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results:Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO 2/FiO 2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH 2O (1 cmH 2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis ( P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO ( P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO ( P<0.05) and gradually increased from 24 h after ECMO. Conclusions:The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Objective To investigate the effect of hypoxia-induced factor 1α and 2α(HIF-1α and HIF-2α)on ethanol-in-duced intestinal epithelium cellular barrier dysfunction of colorectal adenocarcinoma cell(Caco-2)monolayers and its mechanism.Methods Intestinal epithelium monolayer cellular barrier model was obtained by Caco-2 in vitro and induced by ethanol with different concentrations.The cell viability was measured by MTT method.Caco-2 cells were treated with or without ethanol according to the opti-mum concentration and time.The secretions of interleukin 1 β(IL-1 β)and interleukin 6(IL-6)were detected by ELISA.The expres-sions of HIF-lα,HIF-2α,and Neu3 were analyzed by Western blot and RT-PCR.The permeability of Caco-2 cell monolayers was evaluated by transepithelial electrical resistance(TEER).Next,Caco-2 cells were transfected with small interfering RNA(siRNA)to knock down the expression of HIF-1α and HIF-2α.The cell viability,the levels of IL-1 β and IL-6,and the expression of Neu3 and TEER in each group were detected,respectively.Then,the expression of Neu3 was inhibited with siRNA to assess the permeability of Ca-co-2 cell monolayers by TEER.Results The inhibitory effect of ethanol on Caco-2 cells was dose-dependent when the concentration of ethanol was higher than 5％.When Caco-2 cells were treated with ethanol with a concentration of 5％for one hour,the levels of proinflammatory cytokines IL-1 β and IL-6 were promoted.Compared to the control group,ethanol also induced the expression of HIF-1α,HIF-2α,Neu3 and reduced TEER values(P＜0.05).After HIF-1α or HIF-2α siRNA interference in ethanol-induced Caco-2 cells,the cell viability was inhibited,the secretions of IL-1 β and IL-6 were significantly elevated and the values of TEER were decreased(P＜0.05).Interestingly,the expression of Neu3 was inhibited when HIF-2α was deleted but not HIF-1α(P＜0.05).Furthermore,TEER analysis showed an increased cellular permeability when the expression of Neu3 was inhibited(P＜0.05).Conclusion The HIF-1α or HIF-2α signal pathway may be involved regulation process of ethanol-induced increased permeability of the intestinal epithelium cellular barrier.In this process,Neu3 may be mediated by HIF-2α but not HIF-1α,contributing to intestinal epithelium cellular barrier dysfunction in ethanol-induced Caco-2.

Diabetes mellitus(DM)is a chronic metabolic disease characterized by sustained elevation of blood glucosedue toin sulin resistance and islet β cell damage.Rheb1 regulates cell growth and metabolism,promotes islet β cell growth,proliferation and insulin secretion through the mTORC1 pathway,affects the function of vascular endothelial cells,macrophages and glomerular podocytes,and participates in the occurrence and development of atherosclerosis and diabetic kidney disease.This article reviews the research progress on the role of Rheb1 in DM and its complications.

This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Objective:To systematically evaluate the efficacy and safety of iGlarLixi in the treatment of type 2 diabetes, providing evidence-based support for rational clinical medication.Methods:A systematic review was conducted by retrieving articles from PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang, and VIP databases to collect randomized controlled trials comparing the efficacy and safety of iGlarLixi(intervention group) with placebo or other anti-hyperglycemic drugs(control group) in the treatment of type 2 diabetes. The search was conducted from the inception of the databases up to August 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using RevMan 5.4 software. Results:A total of 11 studies with 6 392 patients were included in the meta-analysis. The results of the meta-analysis showed that in terms of efficacy, compared to insulin and GLP-1RAs, iGlarLixi demonstrated better reduction in patients′ HbA 1C levels(Insulin group WMD=-0.40, 95% CI -0.54--0.27, P<0.001; GLP-1RAs group WMD=-0.86, 95% CI -1.05--0.68, P<0.001), increased HbA 1C target rate(Insulin group OR=2.83, 95% CI 2.00-3.99, P<0.001; GLP-1RAs group OR=6.45, 95% CI 4.81-8.64, P<0.001), increased HbA 1C control rate without weight gain(Insulin group OR=3.00, 95% CI 2.43-3.71, P<0.001; GLP-1RAs group OR=2.67, 95% CI 1.76-4.06, P<0.001). Furthermore, iGlarLixi showed an advantage in weight reduction compared to the insulin group and demonstrated superior reduction in fasting plasma glucose compared to the GLP-1RAs group. In terms of safety, the incidence of hypoglycemic events in the iGlarLixi group was similar to that in the insulin group, but the incidence of gastrointestinal adverse events was higher than that in the insulin group. There was no difference in the incidence of gastrointestinal adverse events compared with GLP-1RAs, but the incidence of hypoglycemic events was higher in the iGlarLixi group. The incidence of serious adverse events was similar to that in the insulin and GLP-1RAs groups(Insulin group OR=0.94, 95% CI 0.71-1.23, P=0.640; GLP-1RAs group OR=0.97, 95% CI 0.61-1.52, P=0.880). Conclusion:iGlarLixi is superior to insulin but inferior to GLP-1RAs in reducing body weight, and the overall incidence of adverse events is not significantly different from that of insulin and GLP-1RAs, indicating that iGlarLixi is well tolerated and safe, and has a good clinical application prospect.

Transcatheter aortic valve implantation (TAVI) has become the main treatment for elderly patients with middle and high risk aortic stenosis. However, coronary artery occlusion (CAO) related to TAVI is a very serious complication, which often leads to poor prognosis. Therefore, active preoperative prevention is particularly important. Preoperative computed tomography evaluation, bioprosthetic or native aortic scallop intentional laceration and chimney stent implantation technology can prevent TAVI-related coronary orifice obstruction. Ensuring commissural alignment during operation can reduce the occurrence of coronary occlusion, but its long-term prognosis needs further study. In addition, percutaneous coronary intervention is the main treatment, but there are problems such as difficult coronary access after TAVI. This article summarized the research progress in the mechanism, prevention and treatment of CAO related to TAVI.