ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

Objective:Endoscopic resection of giant submucosal tumors (SMTs) in the esophagus and gastric cardia is challenging. The aim of this study was to investigate the safety and efficacy of various endoscopic procedures for resection of esophageal or gastric cardia SMTs with longitudinal diameter ≥7 cm and/or transverse diameter ≥3.5 cm.Methods:In this retrospective cohort study, we analyzed data of 109 patients with giant esophageal/cardia SMTs originating in the muscularis propria who had undergone endoscopic resection in Zhongshan Hospital from July 2017 to February 2022. Inclusion criteria were as follows: (1) SMT diameter ≥7 cm longitudinally or ≥3.5 cm transversely; (2) presence of symptoms requiring intervention; and (3) tumor originating in the muscularis propria. Exclusion criteria included severe comorbidities, coagulation disorders, prior surgery, or tumor adjacent to vital organs precluding endoscopic treatment. The primary outcomes were en bloc and piecemeal resection rates, whereas secondary outcomes comprised adverse events and long-term survival.Results:Among the 109 patients who had successfully undergone endoscopic resection, the median tumor diameters were 7.5 (4.0-15.0) cm, and 4.5 (1.5-7.0) cm. Submucosal tunneling endoscopic resection, endoscopic full-thickness resection, and endoscopic submucosal excavation were performed on 77, 22, and 10 patients, respectively. The median duration of the procedures was 90 (30-300) minutes. The overall en bloc resection rate was 78.9% (86/109), and piecemeal resection rate 21.1% (23/109). Major adverse events occurred in 12.8% of patients (14/109), comprising pneumothorax or pleural effusion ( n=12), esophageal-pleural fistula ( n=3), severe delayed bleeding ( n=1), tunnel infection with abdominal abscess ( n=1), pulmonary abscess ( n=1), abdominal abscess ( n=1), and postoperative esophageal stricture ( n=1). During a median follow-up period of 33.6 (15.4-70.4) months, no tumor recurrences or metastases were detected. Multivariate analysis revealed that transverse diameter ≥4.5 cm was an independent risk factor for piecemeal resection (OR=6.016, 95%CI: 2.180-16.597, P<0.001); longitudinal diameter ≥9.0 cm (OR=2.728, 95%CI: 1.005-7.405, P=0.049) and transverse diameter ≥4.5 cm (OR=2.942, 95%CI: 1.099-7.874, P=0.032) were independent risk factors for prolonged operation time; and longitudinal diameter ≥9.0 cm (OR=5.040, 95%CI: 1.425-17.828, P=0.012) and piecemeal resection (OR=6.280, 95%CI: 1.741-22.656, P=0.005) were independent risk factors for major adverse events. Conclusion:Endoscopic resection is a safe and effective treatment modality for giant esophageal or gastric cardia SMTs of longitudinal diameter ≥9.0 cm and transverse diameter ≥4.5 cm.

OBJECTIVES: Cardiovascular disease (CVD) poses a major threat to global health. Evaluating atherosclerosis in asymptomatic individuals can help identify those at high risk of CVD. This study aims to establish an individualized nomogram prediction model to estimate the risk of vascular plaque formation in asymptomatic individuals. METHODS: A total of 5 655 participants who underwent CVD screening at the Health Management Center of The Third Xiangya Hospital, Central South University, between January 2022 and June 2024 we retrospectively enrolled. Using simple random sampling, participants were divided into a training set (n=4 524) and a validation set (n=1 131) in an 8꞉2 ratio. Demographic and clinical data were collected and compared between groups. Multivariate logistic regression analysis was used to identify independent factors associated with vascular plaques and to construct a nomogram prediction model. The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA). RESULTS: The mean age of participants was 52 years old. There were 3 400 males (60.12%). The overall detection rate of vascular plaque in the screening population was 49.87% (2 820/5 655). No statistically significant differences were observed in clinical indicators between the training and validation sets (all P>0.05). Multivariate Logistic regression analysis identified age, systolic blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein(a), male sex, smoking history, hypertension history, and diabetes history as independent risk factors for vascular plaque in asymptomatic individuals (all P<0.05). The area under the curve (AUC) of the nomogram model for predicting vascular plaque risk were 0.778 (95% CI 0.765 to 0.791, P<0.001) in the training set and 0.760 (95% CI 0.732 to 0.787, P<0.001) in the validation set. The Hosmer-Lemeshow goodness-of-fit test indicated good model calibration (training set: P=0.628; validation set: P=0.561). The calibration curve plotted using the Bootstrap method demonstrated good agreement between predicted probabilities and actual probabilities. DCA showed that the nomogram provided a clinical net benefit for predicting vascular plaque risk when the threshold probability ranged from 0.02 to 0.99. CONCLUSIONS The nomogram prediction model for vascular plaque risk, constructed using readily available and cost-effective physical examination indicators, exhibited good predictive performance. This model can assist in the early identification and intervention of asymptomatic individuals at high risk for cardiovascular disease.
Humans ; Male ; Middle Aged ; Female ; Nomograms ; Retrospective Studies ; Risk Factors ; Plaque, Atherosclerotic/diagnosis* ; Aged ; Adult ; Physical Examination ; Logistic Models ; Cardiovascular Diseases/epidemiology* ; ROC Curve

Objective:Endoscopic resection of giant submucosal tumors (SMTs) in the esophagus and gastric cardia is challenging. The aim of this study was to investigate the safety and efficacy of various endoscopic procedures for resection of esophageal or gastric cardia SMTs with longitudinal diameter ≥7 cm and/or transverse diameter ≥3.5 cm.Methods:In this retrospective cohort study, we analyzed data of 109 patients with giant esophageal/cardia SMTs originating in the muscularis propria who had undergone endoscopic resection in Zhongshan Hospital from July 2017 to February 2022. Inclusion criteria were as follows: (1) SMT diameter ≥7 cm longitudinally or ≥3.5 cm transversely; (2) presence of symptoms requiring intervention; and (3) tumor originating in the muscularis propria. Exclusion criteria included severe comorbidities, coagulation disorders, prior surgery, or tumor adjacent to vital organs precluding endoscopic treatment. The primary outcomes were en bloc and piecemeal resection rates, whereas secondary outcomes comprised adverse events and long-term survival.Results:Among the 109 patients who had successfully undergone endoscopic resection, the median tumor diameters were 7.5 (4.0-15.0) cm, and 4.5 (1.5-7.0) cm. Submucosal tunneling endoscopic resection, endoscopic full-thickness resection, and endoscopic submucosal excavation were performed on 77, 22, and 10 patients, respectively. The median duration of the procedures was 90 (30-300) minutes. The overall en bloc resection rate was 78.9% (86/109), and piecemeal resection rate 21.1% (23/109). Major adverse events occurred in 12.8% of patients (14/109), comprising pneumothorax or pleural effusion ( n=12), esophageal-pleural fistula ( n=3), severe delayed bleeding ( n=1), tunnel infection with abdominal abscess ( n=1), pulmonary abscess ( n=1), abdominal abscess ( n=1), and postoperative esophageal stricture ( n=1). During a median follow-up period of 33.6 (15.4-70.4) months, no tumor recurrences or metastases were detected. Multivariate analysis revealed that transverse diameter ≥4.5 cm was an independent risk factor for piecemeal resection (OR=6.016, 95%CI: 2.180-16.597, P<0.001); longitudinal diameter ≥9.0 cm (OR=2.728, 95%CI: 1.005-7.405, P=0.049) and transverse diameter ≥4.5 cm (OR=2.942, 95%CI: 1.099-7.874, P=0.032) were independent risk factors for prolonged operation time; and longitudinal diameter ≥9.0 cm (OR=5.040, 95%CI: 1.425-17.828, P=0.012) and piecemeal resection (OR=6.280, 95%CI: 1.741-22.656, P=0.005) were independent risk factors for major adverse events. Conclusion:Endoscopic resection is a safe and effective treatment modality for giant esophageal or gastric cardia SMTs of longitudinal diameter ≥9.0 cm and transverse diameter ≥4.5 cm.

To establish a fluorescence-labeled Corynebacterium pseudotuberculosis(Cp),the super-folded green fluorescent protein gene(sfGFP)fused to the red fluorescent protein gene(mCher-ry)was cloned into pXMJ19 and expressed in Cp.The fluorescent signals of recombinant Cp cul-tured under different pH values,and the visualized detection of bacteria in the macrophages J774A.1 or mice infected with recombinant Cp were evaluated.The results showed that a double fluores-cence labeled XH02-pXMJ19-sfGFPmCherry(XH02-sfGFPmCherry)was successfully construc-ted by electrotransformation of Cp with pXMJ19-sfGFPmCherry,which containing sfGFP fused to mCherry.The colony morphology of XH02-sfGFPmCherry on fresh blood agar plates was pink.The XH02-sfGFP mCherry showed green and red fluorescence when observed under the fluo-rescence microscope.Compared with cultivation at pH7.0,XH02-sfGFPmCherry showed a signifi-cant decrease in green fluorescence intensity(fluorescence intensity/D600)at pH5.0,but signifi-cantly increased in red fluorescence intensity at pH5.0.Green and red fluorescences of Cp were ob-served in the XH02-sfGFPmCherry-infected J774A.1 in vitro or in the liver and kidney of XH02-sfGFPmCherry-infected mice in vivo,and with good overlap of two kinds of fluorescences.This study demonstrates that the constructed dual fluorescent labeled Cp can efficiently express both red and green fluorescent proteins,and express the dominant fluorescent signals under different pH value conditions,which can be used for Cp monitoring in vitro infection of macrophages and in vivo infection of mice by this pathogen,and providing potential tool for the localization and tracing research of Cp infection.

To establish a fluorescence-labeled Corynebacterium pseudotuberculosis(Cp),the super-folded green fluorescent protein gene(sfGFP)fused to the red fluorescent protein gene(mCher-ry)was cloned into pXMJ19 and expressed in Cp.The fluorescent signals of recombinant Cp cul-tured under different pH values,and the visualized detection of bacteria in the macrophages J774A.1 or mice infected with recombinant Cp were evaluated.The results showed that a double fluores-cence labeled XH02-pXMJ19-sfGFPmCherry(XH02-sfGFPmCherry)was successfully construc-ted by electrotransformation of Cp with pXMJ19-sfGFPmCherry,which containing sfGFP fused to mCherry.The colony morphology of XH02-sfGFPmCherry on fresh blood agar plates was pink.The XH02-sfGFP mCherry showed green and red fluorescence when observed under the fluo-rescence microscope.Compared with cultivation at pH7.0,XH02-sfGFPmCherry showed a signifi-cant decrease in green fluorescence intensity(fluorescence intensity/D600)at pH5.0,but signifi-cantly increased in red fluorescence intensity at pH5.0.Green and red fluorescences of Cp were ob-served in the XH02-sfGFPmCherry-infected J774A.1 in vitro or in the liver and kidney of XH02-sfGFPmCherry-infected mice in vivo,and with good overlap of two kinds of fluorescences.This study demonstrates that the constructed dual fluorescent labeled Cp can efficiently express both red and green fluorescent proteins,and express the dominant fluorescent signals under different pH value conditions,which can be used for Cp monitoring in vitro infection of macrophages and in vivo infection of mice by this pathogen,and providing potential tool for the localization and tracing research of Cp infection.

Objective To construct a postoperative lung infection preventive care program for lung cancer patients and carry out preliminary validation,so as to provide a reference basis that can be used in clinical practice.Methods Literature analysis was carried out to search domestic and international databases,guideline networks,and association websites,with a search timeframe of January 2011 to December 2021,to obtain relevant evidence,to construct a preliminary draft of a preventive care program for postoperative lung infections in patients with lung cancer,and to use the Delphi method of correspondence with experts from Guangdong Province,Henan Province,and Sichuan Province,September-December 2022,to determine the content of the program.Correspondence to determine the content of the program.In November-December 2023,15 thoracic surgery nurses and 15 lung cancer patients in a tertiary hospital in Shantou City were selected for the initial application of the program and evaluated the effectiveness of the program through the nurses'clinical significance,applicability,feasibility,and patient satisfaction.Results A total of 21 experts completed 2 rounds of correspondence.95.65％and 95.45％of questionnaires were retumed in the 2 rounds of correspondence;the authority coefficients of the experts were 0.941 and 0.948;the Kendall's harmony coefficients were 0.176 and 0.310;the coefficients of variation for each item in the 2nd round of correspondence were 0.04～0.25.The final draft of the program included 10 aspects and 37 measures,such as teamwork,health education,risk assessment,rehabilitation training,fluid management,oral manage-ment,airway management,nutritional management,pain management,line management,and other 10 areas with 37 measures.After the initial application of the program,100％of the nurses thought that the program was meaningful,87％of the nurses thought that the program was clinically applicable and feasible,and 100％of the patients indicated that they were satisfied with the program,of which 80％were very satisfied.Conclusion The constructed nursing program for preventing postoperative lung infection in lung cancer patients is scientific,relevant and feasible,and can provide references for clinical health care personnel to develop measures for preventing postoperative lung infection in lung cancer patients.

Background:Esophageal neuroendocrine neoplasms(E-NENs)are rare and highly aggressive malignancies.Although endoscopic resection(ER)has demonstrated efficacy in managing gastrointestinal neuroendocrine tumors,ER for E-NENs lacks systematic evidence.Aims:To evaluate the feasibility and safety of ER in E-NENs,establish risk-stratified follow-up strategies based on tumor grade,invasion depth,and margin status,and define indications for ER.Methods:A retrospective analysis was conducted for 8 E-NEN patients treated with ER at the Endoscopy Center,Zhongshan Hospital,Fudan University from November 2017 to July 2021.The clinicopathological data,procedural parameters,adverse events,and follow-up outcomes were collected to summarize the diagnostic and therapeutic insights.Results:The cohort included 8 patients,with male-to-female ratio of 1:1;the mean age was(71.4±8.5)years.Half of the cases were incidentally detected during asymptomatic endoscopic screening.All tumors were confined to the submucosa:4 were small cell neuroendocrine carcinomas(SCNECs),and 4 were mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs).Endoscopic submucosal dissection(ESD)was performed in 6 cases and submucosal tunneling endoscopic resection(STER)in 2 cases.Self-limiting fever was reported in one case.One cases required additional surgery due to horizontal margin involving(no recurrence over 67 months follow-up).The median hospitalization was 4.5 days.With a median follow-up of 66 months,the recurrence and all-cause mortality rates were both 25.0%(2/8).Conclusions:MiNENs≤2.5 cm with complete ER exhibit favorable prognoses,whereas SCNECs with high mitotic indices or elevated Ki-67 proliferation indices correlate with poorer outcomes.Post-ER surveillance for E-NENs should meet or exceed esophageal squamous cell carcinoma standards.As the largest single-center ER cohort for E-NENs,this study provides critical evidence for minimally invasive management,though multicenter validation is needed.

Background:Esophageal neuroendocrine neoplasms(E-NENs)are rare and highly aggressive malignancies.Although endoscopic resection(ER)has demonstrated efficacy in managing gastrointestinal neuroendocrine tumors,ER for E-NENs lacks systematic evidence.Aims:To evaluate the feasibility and safety of ER in E-NENs,establish risk-stratified follow-up strategies based on tumor grade,invasion depth,and margin status,and define indications for ER.Methods:A retrospective analysis was conducted for 8 E-NEN patients treated with ER at the Endoscopy Center,Zhongshan Hospital,Fudan University from November 2017 to July 2021.The clinicopathological data,procedural parameters,adverse events,and follow-up outcomes were collected to summarize the diagnostic and therapeutic insights.Results:The cohort included 8 patients,with male-to-female ratio of 1:1;the mean age was(71.4±8.5)years.Half of the cases were incidentally detected during asymptomatic endoscopic screening.All tumors were confined to the submucosa:4 were small cell neuroendocrine carcinomas(SCNECs),and 4 were mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs).Endoscopic submucosal dissection(ESD)was performed in 6 cases and submucosal tunneling endoscopic resection(STER)in 2 cases.Self-limiting fever was reported in one case.One cases required additional surgery due to horizontal margin involving(no recurrence over 67 months follow-up).The median hospitalization was 4.5 days.With a median follow-up of 66 months,the recurrence and all-cause mortality rates were both 25.0%(2/8).Conclusions:MiNENs≤2.5 cm with complete ER exhibit favorable prognoses,whereas SCNECs with high mitotic indices or elevated Ki-67 proliferation indices correlate with poorer outcomes.Post-ER surveillance for E-NENs should meet or exceed esophageal squamous cell carcinoma standards.As the largest single-center ER cohort for E-NENs,this study provides critical evidence for minimally invasive management,though multicenter validation is needed.

Rheumatic fever is an autoimmune disease characterized by recurring acute or chronic systemic connective tissue inflammation caused by group A streptococcal infection in the throat. Although rheumatic fever is common in China, there is a lack of standardized criteria for the diagnosis and treatment of this condition. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association developed standardized criteria for the diagnosis and treatment of this disease in China. The aim was to standardize rheumatic fever diagnosis methods, treatment opportunities, and strategies for both short-and long-term treatment, so as to reduce irreversible damage and improve prognosis.