Objective:To explore mechanism of Caspase-11/GSDMD non-classical cell pyroptosis pathway in inflammatory response of RAW264.7 monocyte macrophages induced by ricin toxin.Methods:Cell pyroptosis model induced by LPS+Nigericin was used as a positive control,and cells were induced with 40 ng/ml and 80 ng/ml of ricin toxin for 8 hours.Cell release of lactate dehydro-genase(LDH)was measured by LDH cell release assay;cell viability was assessed by flow cytometry(Annexin Ⅴ/PI double staining);gene expressions of Caspase-11,GSDMD,IL-1β and IL-18 were measured by RT-qPCR;protein levels of Caspase-11 and GSDMD were measured by Western blot;secretion levels of inflammatory cytokines IL-1β and IL-18 in cell supernatant were measured by ELISA.Results:Compared with normal control group,RAW264.7 cells treated with ricin toxin showed swelling,cell membrane rupture,significantly increased LDH release(P<0.001),significantly increased pyroptosis rate(P<0.001),significantly increased expression of pyroptosis-related genes Caspase-11,GSDMD,IL-1β and IL-18(P<0.05),significantly increased protein expressions of Caspase-11 and GSDMD(P<0.05),and significantly increased secretion levels of IL-1β and IL-18 in cell supernatant(P<0.05).Results of ricin toxin treatment group were consistent with LPS+Nigericin cell pyroptosis positive control group.Conclu-sion:Ricin toxin may induce cell pyroptosis in RAW264.7 cells through Caspase-11/GSDMD non-classical pathway,thereby promoting inflammatory response.

OBJECTIVE T o explore the value of targeted next-generation sequencing(t-NGS)in diagnosis of respir-atory tract pathogens through meta-analysis so as to provide reference for clinical application.METHODS PubMed database,Web of Science database,Wanfang database,CNKI database and Sinomed database were retrieved,and the time period of retrieval ranged from Jan.2010 to May 2024.The literatures were screened out based on the es-tablished standards.The quality was assessed by QU ADAS-2,the risk of bias graph was drawn by Revman 5.4,and the statistical analysis was performed by Stata 16.0.RESULTS A total of 9 literatures were included in the study.The result of meta-analysis showed that the heterogeneity test Q for sensitivity was 268.21,P＜0.01,I2=97.02％,with the heterogeneity test Q for specificity 210.04,P＜0.01,I2=96.19％,the combined sensitivity 0.88(95％CI:0.62 to 0.97),combined specificity 0.68(95％CI:0.41 to 0.86),combined positive likelihood ratio 2.72(95％CI:1.44 to 5.15),combined negative likelihood ratio 0.18(95％CI:0.06 to 0.53),combined diagno-sis score 2.74(95％CI:1.68 to 3.80),and combined diagnostic odds ratio 15.44(95％CI:5.34 to 44.66).The area under synthesize receiver operating characteristic(SROC)curve(AUC)was 0.85(95％CI:0.82 to 0.88).The result of Deeks funnel plot showed that P was 0.99,indicating that there was no obvious publication bias.CONCLUSIONS The sensitivity of tNGS is high in detection of the pathogens causing acute respiratory tract infection,the specificity needs to be improved,but its comprehensive ability is satisfactory.It has certain val-ue in early clinical diagnosis.

Objective:To investigate changes in the density and spatial distribution of CD69 + T cells within hepatocellular carcinoma tissues following immune checkpoint blockade (ICB) therapy, and to explore their correlation with tumor infiltrating immune cell. Methods:Tumor specimens were collected from 12 patients with hepatocellular carcinoma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of People's Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from July 2023 to July 2024. There were 10 males and 2 females, aged (58.5±5.6) years. Of the 12 patients, 6 cases underwent radical surgery directly and 6 underwent radical surgery after immunotherapy. The maximum tumor diameter and tumor volume of the immunotherapy group were measured by imaging. The density and distribution of immune cells such as CD8 + CD69 + T, CD4 + CD69 + T and programmed death-1 (PD-1) were detected by immunohistochemistry and immunofluorescence. The number of immune cells around the target cells was calculated to evaluate the effective score, and the intercellular distance was measured to evaluate the intercellular interaction. Results:The maximum tumor diameter and tumor volume of 6 patients after immunotherapy were lower than before treatment, and the differences were statistically significant (all P<0.05). The density of PD1 + cells in the immunotherapy group was 36.6 (25.9, 55.9) cells/mm 2, which was less than that in the control group 53.9 (38.3, 84.5) cells/mm 2, and the difference was statistically significant ( Z=-2.66, P=0.008). In the control group, the number of CD8 + CD69 + T cells was positively correlated with CD8 + PD1 + T cells and CD8 + PD1 + CD103 + T cells, and the correlation coefficients were 0.42 and 0.40, respectively ( P=0.001, 0.002). The effective scores of CD8 + CD69 + T cells and CD8 + PD1 + T, CD4 + CD103 + T, CD4 + PD1 + CD103 + T and CD8 + PD1 + CD103 + T cells in the above three areas in the immunotherapy group were lower than those in the control group, with statistical significance (all P<0.05). The distance between CD8 + CD69 + T and CD4 + CD69 + CD103 + T cells in the interface area of the control group was closer than that of the immunotherapy group, and the difference was statistically significant ( t=2.67, P=0.009). Conclusion:After immunotherapy in hepatocellular carcinoma patients, PD-1+ cells and immune cells around CD8 + CD69 + T cells decreased, and this change was related to the distance between CD8 + CD103 + T cells.

Objective To study the effect and duration of point-of-use filters on the improvement of endoscopic fi-nal rinse water quality.Methods The final rinse water end at the gastroscope manual cleaning workstation in the Endoscopy Centre of the First Affiliated Hospital with Nanjing Medical University was selected to install a tap ter-minal filter;five specimens of final rinse water were collected consecutively before the installation,immediately after the installation,and 1-11 weeks after the installation.At each sampling time,the staff responsible for clea-ning and disinfecting were asked whether the flow rate of discharged water could satisfy the working demand;the final rinse water was inoculated on R2A culture medium with membrane filter method,bacterial colony forming unit(CFU)was calculated after 30℃ incubation for 5 days.Results The qualified rates of endoscopic final rinse water before point-of-use filter installation was 0,immediately after and 1-9 weeks after installation were both 100％,10 and 11 weeks after installation were 80.0％and 20.0％,respectively.The mean CFU of endoscopic final rinse wa-ter before point-of-use filter installation was 102 CFU/100 mL,immediately after and 1-9 weeks after installation were both ≤2 CFU/100 mL,10 and 11 weeks after installation were 8 and 18 CFU/100 mL,respectively.The feedback from the cleaning and disinfection staff before installation,immediately after installation,and 1-11 weeks after installation indicated that the flow rate of discharged water gradually slowed down over time,but could still meet the work requirements.Conclusion The point-of-use filter can quickly and effectively improve the quality of endoscopic final rinse water,with use duration of up to 9 weeks after installation;Its biggest advantage is that it can serve as the final barrier to all integrated measures,playing a supplementary role in case of any problems occu-rring in the front-end process,and ensuring the microbial quality of the final rinse water to the greatest extent possible.

Objective To investigate risk factors for the occurrence of an outbreak of surgical site infection(SSI)in the orthopedic department of a hospital.Methods Patients with SSI in the orthopedic department of a hospital in June-July 2017 were investigated,and the high-risk factors for infection were analyzed through case-control study.Specimens were taken from patients,health care workers(HCWs),environment and surgical devices for microbial detection.The homology between patients'and environmental isolates was analyze by pulsed-field gel electrophore-sis(PFGE).Results Staphylococcus aureus(S.aureus)were isolated from nasal secretion of four HCWs,including one doctor(D1)who was also isolated S.aureus from his forehead and hands.PFGE analysis found that S.aureus isolated from incision secretion of 2 patients were homologous to S.aureus isolated from the nasal cavity,forehead,and hands of doctor D1.Several targeted comprehensive infection control measures were implemented,including suspending sterile manipulation(such as surgery and dressing changes)of doctor D1;decolonization for all HCWs(including doctor D1)who carried S.aureus,requiring doctor D1 regularly trim nasal hair;strengthening the edu-cation and supervision of sterile manipulation and hand hygiene;implementing centralized isolation for SSI patients,et al.After timely implementation of the above comprehensive intervention measures,this SSI outbreak was effec-tively controlled in a short period of time.Conclusion Colonization of S.aureus in surgeons may lead to SSI in pa-tients,regular active screening and decolonization of surgeons involved in specific surgeries can be considered,and if necessary,nasal colonized people with dense nasal hair are required to regularly trim their nasal hair to reduce the occurrence of SSI.

OBJECTIVE To investigate the roles and mechanisms of γ-bungarotoxin(γ-BGT)in inducing respiratory distress in mice.METHODS Six male Kunming mice were selected and anesthe-tized before tracheal intubation and respiratory recording.After stabilizing respiration,the mice were intraperitoneally injected with γ-BGT at a dose of 6 mg·kg-1.Once a decrease in respiratory frequency was observed,the mice were intravenously injected with nikethamide at a dose of 12.5 mg·kg-1.Respi-ratory frequency was monitored using the BL420 signal acquisition and processing system.Male Kunming mice were randomly divided into the normal control group(saline,ip),γ-BGT group(6 mg·kg-1,ip),and γ-BGT+nikethamide group(γ-BGT 6 mg·kg-1,ip,followed by nikethamide 12.5 mg·kg-1,ip,when shal-low breathing and enhanced abdominal respiration were observed).The levels of Glu and GABA in the medulla oblongata were measured using ELISA.The protein expression levels of GAD65 and GAD67 in the medulla oblongata were determined by Western blotting.Primary mouse medullary neurons were cultured in vitro and divided into the following groups:cell control group,γ-BGT group,carbachol group,gallamine group,γ-BGT+H-89 group,and γ-BGT+Y-27632 group.The γ-BGT group,carbachol group,and gallamine group were incubated with γ-BGT(40 mg·L-1),carbachol(100 mmol·L-1),and gallamine(100 mmol·L-1),respectively,for 4 h.The γ-BGT+H-89 and γ-BGT+Y-27632 groups were pretreated with γ-BGT(40 mg·L-1)for 4 h,followed by incubation with the protein kinase A(PKA)inhibitor H-89(50 mmol·L-1)and the Ca2+channel inhibitor Y-27632(50 mmol·L-1)for another 2 h,respectively.ELISA was used to measure the levels of Glu,GABA,cAMP,and calpain in the primary mouse medul-lary neurons.Western blotting was employed to assess the protein expression levels of GAD65 and GAD67,and PKA phosphorylation levels.Fluo-4 fluorescent probe was used to detect the intracellular Ca2+level.RESULTS The respiratory rate of mice significantly decreased after iv administration of γ-BGT(γ-BGT group)(P<0.05).After treatment with nikethamide(nikethamide group),the respiratory rate significantly recovered(P<0.05).Compared with the normal control group,the γ-BGT group exhib-ited a significant decrease in Glu content(P<0.05),a significant increase in GABA content(P<0.05),and a significant decrease in the Glu/GABA ratio.Additionally,the protein expression levels of GAD65 and GAD67 were significantly elevated(P<0.05).Compared with the γ-BGT group,the γ-BGT+niketh-amide group showed a significant increase in Glu content(P<0.05),a significant decrease in GABA content(P<0.05),a significant increase in the Glu/GABA ratio,and a significant reduction in GAD65 and GAD67 protein expression levels(P<0.05).Compared to the cell control group,the γ-BGT group demonstrated a significant decrease in Glu content(P<0.05),a significant increase in GABA content(P<0.05),and a significant reduction in the Glu/GABA ratio.Furthermore,the protein expression levels of GAD65 and GAD67 were significantly elevated(P<0.05).Additionally,cAMP content,PKA phosphor-ylation levels,Ca2+levels,and calpain activity were all significantly increased(all P<0.05).Glu,GABA,Glu/GABA ratio,and GAD expression levels in the γ-BGT group changed in the same way as in the gallamine group;In the γ-BGT+Y-27632 group,calpain activity and expression levels of GAD65 and GAD67 were all significantly decreased(all P<0.05).In the γ-BGT+H-89 group,Ca2+levels and calpain activity were significantly reduced(all P<0.05).CONCLUSION γ-BGT-induced poisoning can lead to respiratory distress in mice,possibly through the antagonism of M2 muscarinic acetylcholine receptors in medullary neurons,activation of the cAMP/PKA signaling pathway,elevation of intracellular Ca2+levels,and increased expression and activity of GAD,resulting in an imbalance of Glu and GABA in the medulla.

Abdominoplasty combined with liposuction is the main treatment method for abdominal wall laxity. Abdominoplasty with concomitant liposuction removes excess subcutaneous fat through liposuction, which not only enhances the shaping effect, but also creates a good subcutaneous surgical dissection layer and avoids excessive damage to the perforating vessels of the abdominal wall, thereby reducing the incidence of high complications such as hematoma and skin necrosis that are easily seen after traditional abdominoplasty.With the development of weight loss surgery, the demand for abdominoplasty is increasing, and certain progress has been made in abdominal anatomy, abdominal wall aesthetics and abdominal wall plastic surgery techniques. This article summarizes the progress in the clinical treatment of abdominal wall laxity.

Objective:To compare the efficacy of surgical resection and radiofrequency ablation (RFA) treatment for China liver cancer staging (CNLC) Ia hepatocellular carcinoma (HCC) at difficult-to-reach locations.Methods:A retrospective analysis was conducted on the clinical data of 114 patients with CNLC Ia HCC at Ⅶ、Ⅷ、Ⅳb or Ⅰ segments that were difficult-to-reach locations who were admitted to People's Hospital of Zhengzhou University from December 2018 to December 2023. Among the patients, 85 were males and 29 were females, aged (58.1±1.0) years. The patients were divided into two groups: a RFA group with 31 cases and a surgical resection group with 83 cases. Compare the levels of alanine transaminase (ALT) and aspartate transaminase (AST) before and after surgery, the surgical time, intraoperative blood loss, postoperative hospital stay, postoperative complications, recurrence free survival rate, and cumulative survival rate between the two groups.Results:The comparison of age, gender, ALT, and AST between the two groups showed no statistically significant differences (all P>0.05). The differences in ALT and AST levels before and after surgery in the RFA group were (134.8±38.7) U/L and (195.1±53.9) U/L, respectively, which were significantly lower than those in the surgical resection group [(226.8±17.9) U/L and (229.5±16.2) U/L] ( t=-2.45 and -1.12, P=0.016 and 0.041). The RFA group had shorter operation time [(69.2±11.7) min vs. (210.6±8.9) min], less intraoperative blood loss [(8.7±3.8) ml vs. (238.6±20.8) ml], and shorter postoperative hospital stays [(6.4±1.0) d vs. (13.1±0.4) d] compared to the surgical resection group, with all differences statistically significant (all P<0.05). The overall complication rates were 19.4% (6/31) in the RFA group and 22.9% (19/83) in the surgical resection group, showing no significant difference ( χ2=0.16, P=0.685). No statistically significant diffe-rence was found in recurrence-free survival rates between the two groups ( χ2=0.13, P=0.717). Similarly, there was no statistically significant difference in cumulative survival rates between the groups ( χ2<0.01, P=0.978). Conclusion:For HCC at CNLC Ⅰa in challenging locations, RFA demonstrated shorter operation time and postoperative hospital stay, less intraoperative bleeding, and superior liver function recovery compared with surgical resection, while no significant difference was observed in survival outcomes between the two treatment groups.

OBJECTIVE To observe the impact of hospital-associated infections(HAIs)on length of hospital stay and medical costs of the patients with 10 single diseases included in the Performance Assessment of Tertiary Public Hospitals in China(referred to as the National Assessment)and evaluate the significance of infection control in the'National Assessment'.METHODS The data were collected from the patients with 10 single diseases covered by the National Assessment who were treated in The First Affiliated Hospital of Nanjing Medical University from Jan.2022 to Dec.2022.The incidence of HAIs and the infection sites of the patients with the single diseases were analyzed.Multivariate analysis was performed for the assessment of impact of the HAIs on the length of hospital stay and medical costs.RESULTS Among the patients with the single diseases,the incidence of HAIs was the highest(12.41％)in the patients undergoing coronary artery bypass grafting(CABG),followed by adult pneumo-nia(4.70％)and heart failure(2.25％).There was gathering of infection sites among the patients with the differ-ent single diseases:lower respiratory tract was the major infection site among the patients undergoing CABG,and the urinary tract was the major infection site among the patients undergoing hip replacement.Ther result of multi-variate analysis showed that the HAIs could extend the length of hospital stay of the patients with all the single diseases except for chronic obstructive pulmonary disease(COPD)and adult pneumonia(P＜0.05);the lengths of hospital stay of the patients undergoing hip replacement(with the increase of 22.05 days),the patients with heart failure(with the increase of 18.39 days)and those with myocardial infarction(with the increase of 17.15 days)in-creased most remarkably.The medical costs of the patients with CABG,COPD,hip replacement,cerebral infarc-tion,myocardial infarction and heart failure were increased due to the HAIs(P＜0.05),and the medical costs of the patients with heart failure increased most remarkably(with the increase of 251,662.92 yuan).CONCLUSIONS The HAIs have remarkable negative effects on the length of hospital stay and medical costs of most of the patients with single diseases.It is necessary to strengthen the prevention and control of HAIs so as to improve the medical quality,guarantee the safety of patients,effectively improve the performance assessment indexes for tertiary pub-lic hospitals and facilitate the high-quality development of medical institutions.

Objective To conduct a bibliometric and visual analysis of global literature on cardi-ovascular immune-related adverse events(irAEs)induced by immune checkpoint inhibitors(ICIs)in cancer treatment,and to explore the research status,hotspots,and future trends in this field.Meth-ods The Web of Science Core Collection(WOSCC)database was utilized to retrieve and screen rel-evant literature.CiteSpace software was employed for visual analysis of countries,institutions,au-thors,and keywords.Results A total of 1,350 articles were retrieved,with an annual increase in publication volume.The United States dominated in terms of national,institutional,and author contri-butions,while European countries and institutions demonstrated close collaborative networks.Keyword analysis and cited reference mapping revealed an evolution of research hotspots:from initial mechanistic investigations to monoclonal antibody applications,and subsequently to safety concerns.Current lre-search focuses on ICI monoconal antibody combination therapy for malignancies and cardiovascular irAEs,particularly fatal myocarditis,which has emerged as a prominent topic.Conclusion ICIs mon-oclonal antibody therapies and their associated cardiovascular irAEs,especially combination therapies and life-threatening myocarditis,represent key research frontiers.Investigations into drug combination strategies and fatal myocarditis may guide future research directions.