ObjectiveTo investigate whether visceral fat area （VFA） is an independent risk factor for significant liver fibrosis in patients with nonalcoholic fatty liver disease （NAFLD） based on clinical data， and to establish an effective diagnostic model. MethodsA total of 222 NAFLD patients who attended Department of Hepatology， Guangdong Provincial Hospital of Traditional Chinese Medicine， from January 2021 to April 2025 were enrolled， and according to liver stiffness measurement （≥8 kPa or not）， they were divided into significant fibrosis group and non-significant fibrosis group. Propensity score matching （PSM） was performed at a ratio of 1∶1 to balance the baseline data between the two groups. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to determine the correlation of VFA and other indicators with significant liver fibrosis； univariate and multivariate logistic regression analyses were used to identify whether VFA was an independent risk factor for significant liver fibrosis in NAFLD patients， and the receiver operating characteristic （ROC） curve was plotted to assess the predictive performance of related indicators. ResultsA total of 45 patients with significant liver fibrosis and 177 patients without significant liver fibrosis were enrolled， and after PSM， 90 patients （45 pairs） were finally included in analysis. Compared with the non-significant fibrosis group， the significant fibrosis group had significantly higher levels of body mass index （BMI）， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， uric acid （UA）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， controlled attenuation parameter （CAP）， and VFA， as well as a significantly higher proportion of patients with visceral fat obesity or three or more metabolic risk factors （all P<0.05）. VFA， BMI， AST， and HbA1c were strongly correlated with significant liver fibrosis （all r>0.5， all P <0.05）， and ALT， GGT， UA， FBG， and CAP were significantly positively correlated with significant liver fibrosis （r=0.3　—　0.5， all P<0.05）. VFA （odds ratio ［OR］=1.040， 95% confidence interval ［CI］： 1.018　—　1.062， P<0.05）， FBG （OR=2.372， 95%CI： 1.199　—　4.691， P<0.05）， and AST （OR=1.032， 95%CI： 1.003　—　1.058， P<0.05） were independent risk factors for significant liver fibrosis in NAFLD patients. The new diagnostic model based on VFA， FBG， and AST （with an area under the ROC curve ［AUC］ of 0.907） had a significantly better performance than aspartate aminotransferase-to-platelet ratio index （AUC=0.834）， fibrosis-4 （AUC=0.660）， triglyceride-glucose index （AUC=0.656）， and NAFLD fibrosis score （AUC=0.768） in predicting significant liver fibrosis in NAFLD patients （all P<0.05）. ConclusionVFA is an independent risk factor for significant liver fibrosis in NAFLD patients， and the noninvasive diagnostic model based on VFA， FBG， and AST can effectively predict the onset of significant liver fibrosis in NAFLD patients.

[摘 要] 目的：探讨麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）通过诱导免疫原性细胞死亡（ICD）对三阴性乳腺癌（TNBC）的免疫调节机制。方法：体外实验采用CCK-8法检测MMR对TNBC细胞4T1和MDA-MB-231存活率的影响，免疫荧光法检测MDA-MB-231细胞中钙网蛋白（CALR）表达，磷钼酸比色法检测MDA-MB-231细胞内ATP的含量，ELISA检测细胞上清液中高迁移率族蛋白B1（HMGB1）的表达水平，通过GEPIA网站分析CALR和HMGB1对乳腺癌患者生存期的影响。体内实验中经皮下注射4T1-Luc细胞于雌性BALB/c小鼠乳腺脂肪垫构建TNBC小鼠模型。设Control组、盐酸阿霉素（Dox）组、MMR组，按照分组每两天静脉给药1次，连续给药3次。动物活体成像系统观察肿瘤体积变化；记录小鼠体质量及各器官指数初步评估疫苗安全性；H-E染色观察肿瘤病理变化；免疫组化和Western blotting检测肿瘤中CALR和HMGB1蛋白的表达。流式细胞术分析小鼠脾T淋巴细胞亚群及肿瘤树突状细胞和巨噬细胞比例；免疫组化检测肿瘤CD8+ T淋巴细胞浸润；ELISA检测血清中促炎细胞因子IL-6和TNF-α含量。结果：MMR对4T1细胞的活性抑制作用较弱；MMR对MDA-MB-231细胞抑制率达90.39%（P < 0.001）。与Control组相比，MMR组MDA-MB-231细胞中ICD相关蛋白（CALR、ATP、HMGB1）表达上调（P < 0.001）。GEPIA网站分析表明，CALR和HMGB1高表达的患者总生存期有所延长。MMR延缓了荷瘤小鼠肿瘤体积增长（P < 0.001），延长小鼠的生存期，且28 d内MMR组荷瘤小鼠体重与Control组无显著性差异（P > 0.05）；H-E染色显示，与Control组相比，MMR组小鼠肿瘤组织坏死区域扩大且有免疫细胞浸润；MMR上调肿瘤ICD相关蛋白CALR、HMGB1的表达水平；MMR组脾CD4+、CD8+ T淋巴细胞及肿瘤树突状细胞和M1型巨噬细胞的比例增加（P < 0.05），CD8+ T淋巴细胞在肿瘤组织中的浸润增加（P < 0.001），且促炎细胞因子IL-6和TNF-α水平升高（P < 0.01）。结论：MMR减毒活疫苗对TNBC的抗肿瘤作用可能与诱导肿瘤发生ICD进而激活抗肿瘤免疫相关。

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Objective To explore the relationship between the coagulation and fibrinolysis function in the early pregnancy and the occurrence of gestational diabetes mellitus(GDM)in women with different pre pregnancy body mass indexes(BMI).Methods 290 pregnant women undergoing the prenatal check ups at the Second Affiliated Hospital of Kunming Medical University from September 2023 to February 2024 were selected.Pre pregnancy BMI,age,family genetic history,parity,parity,and early pregnancy coagulation and fibrinolysis function test results were collected.Based on whether GDM had occurred,they were divided into GDM group(n=72)and non GDM group(n=218),and further divided into low weight GDM group(n=8),low weight non GDM group(n=29),normal weight GDM group(n=39),normal weight non GDM group(n=145),overweight/obesity GDM group(n=25),overweight/obesity non GDM group(n=44)based on pre pregnancy BMI.Basic data comparison was conducted on the total population and BMI groups.Independent sample t-test or Mann Whitney U test was used for quantitative data,and chi square test or Fisher's exact probability method was used for qualitative data.Multivariate logistic regression was used to correct the influencing factors.Results After adjusting the confounding factors such as age,family history,and pre pregnancy BMI,APTT was negatively correlated with the occurrence of GDM in the overall population(P<0.05,OR=0.840),while FIB was positively correlated with GDM(P<0.01,OR=2.598).In low body weight recombination,APTT was negatively correlated with GDM(P<0.05,OR=0.483),FIB was positively correlated with GDM(P<0.05,OR=82.501),while there was no significant correlation between APTT,FIB and GDM after adjusting the age,family history,and pre pregnancy BMI;In the normal weight group,APTT was negatively correlated with GDM(P<0.01,OR=0.786)and FIB was positively correlated with GDM(P<0.05,OR=2.413).However,after adjusting the age,family history,and pre pregnancy BMI,APTT remained negatively correlated with GDM(P<0.05,OR=0.812)and FIB remained positively correlated with GDM(P<0.05,OR=2.391);In the overweight/obese group,TT was negatively correlated with GDM(P<0.05,OR=0.510),while there was no significant correlation between TT and GDM after adjusting the age,family history,and pre pregnancy BMI.Conclusion In the normal weight population,APTT is negatively correlated with the occurrence of GDM,while FIB is positively correlated with the occurrence of GDM;In the low weight and overweight/obese populations,coagulation and fibrinolysis related indicators are greatly influenced by BMI and have no significant correlation with the occurrence of GDM.

Patients suffering from stage Ⅳ periodontitis manifest substantial alveolar bone destruction and pronounced tooth loss,fre-quently accompanied by masticatory dysfunction,occlusal disorder and tooth displacement or torsion.Standard periodontal interventions alone are insufficient to stabilize the condition,address masticatory dysfunction,and enhance patients'quality of life.Hence,intricate reconstructive and interdisciplinary regimens,encompassing orthodontic treatment,are often indispensable.Orthodontic therapy can op-timize the masticatory function and esthetic appearance of patients,and promote periodontal well-being.However,individuals with stageⅣ periodontitis present with inadequate periodontal support tissue and a heightened risk profile,rendering their orthodontic management a considerable clinical challenge.This article reviews the orthodontic considerations and optimal timing for intervention in patients with stage Ⅳ periodontitis and presents a representative case of combined periodontal-orthodontic-orthognathic treatment for pe-riodontitis(stage Ⅳ,grade C),in order to provide reference for periodontists and orthodontists.

Objective To compare the safety and efficacy of minimally invasive coronary artery bypass grafting (MICS CABG) and traditional CABG in patients with coronary heart disease (CHD) and diabetes mellitus (DM). Methods From 2019 to 2021, the patients who received CABG by the same medical group in the Minimally Invasive Cardiac Surgery Center of Beijing Anzhen Hospital were retrospectively enrolled. According to the surgery methods, the patients were divided into two groups: a MICS CABG group and a conventional group. The perioperative and postoperative follow-up data of patients were collected. The main observation results included all cause death events, myocardial infarction, cerebrovascular, revascularization, and adverse wound healing. Results According to the inclusion and exclusion criteria, 140 patients were enrolled, including 66 patients in the MICS CABG group [56 males and 10 females, aged (61.83±8.94) years], and 74 patients in the conventional group [55 males and 19 females, aged (58.61±8.26) years]. Compared with the conventional group, patients in the MICS CABG group had longer median surgical time (4.50 h vs. 4.00 h, P=0.005), less intraoperative bleeding (600.00 mL vs. 700.00 mL, P=0.020), and a lower rate of secondary debridement and suturing of surgical wounds (4.5% vs. 16.2%, P=0.023). The median follow-up time was 2.54 years. There was no statistically significant difference in the cumulative incidence of major adverse cardiac and cerebrovascular events (7.6% vs. 5.4%), all-cause mortality (0.0% vs. 0.0%), myocardial infarction (3.0% vs. 2.7%), cerebrovascular events (4.5% vs. 2.7%), or revascularization (0.0% vs. 0.0%) between the two groups of patients during the postoperative follow-up (P>0.05). Conclusion MICS CABG can achieve the same revascularization effect as traditional CABG in patients with CHD and DM. MICS CABG can effectively reduce adverse clinical outcomes or complications such as adverse chest wound healing and slow postoperative recovery of body function in patients with DM.

Objective:To investigate the application of the parameters of multimodal ultrasound elastography in differential diagnosis for thyroid nodules of patients with diffuse thyroid lesions.Methods:A total of 103 patients with diffuse thyroid lesions who underwent treatment at Affiliated Baoji Hospital of Xi′an Medical University from January 2023 to January 2024 were retrospectively selected,whose thyroid nodules were confirmed by fine needle aspiration biopsy or surgical pathology.They were grouped according to the benign or malignant nodules.56 patients with benign nodules were included in the benign nodule group,while the other 47 patients were included in the malignant nodule group.All patients were examined by conventional ultrasound and multimodal ultrasound elastography,and the relevant parameters were recorded to compare the differences between the two groups.The value of each indicator in diagnosing benign and malignant thyroid nodules was investigated.Results:There were no statistically significant differences between the benign and malignant nodule groups in terms of gender,length diameter of nodule,nodule location,functional abnormalities of thyroid,exposure history of radiation,and the presence of acoustic halos(P＞0.05),the age of patients in the malignant nodule group was lower than that of the benign nodule group(t=-3.121,P＜0.05),and the percentage of nodules with blood flow(14.89%),the percentage of aspect ratio＜1(74.47%),and the percentage of nodules with clear boundary(27.66%)in the malignant nodule group were all lower than those of the benign nodule group,with statistically significant differences(x2=25.634,5.112,12.465,P＜0.05).The ratio of lymphatic metastasis(27.66%)and that of calcification(65.96%)in the malignant nodule group were lower than those in the benign nodule group,and the differences were all statistically significant(x2=11.917,9.350,P＜0.05).The ratios of centripetal enhancement(76.60%),inhomogeneous enhancement(68.09%),low/equal enhancement(87.23%),early obvious discharge(63.83%),unclear boundary after enhancement(91.49%),and fast discharge(59.57%)in the malignant nodule group were higher than that of the benign nodule group,and the differences were statistically significant(x2=33.409,26.695,9.079,12.853,17.798,12.649,P＜0.05),respectively.The intensity and time to peak of the malignant nodule group were respectively lower and long than these of the benign nodule group,and the differences were statistically significant(t=-12.381,4.958,P＜0.05).However,the mean passage time of the two groups was not statistically significant(P＞0.05).The maximum value,minimum value and mean value of Young's modulus,the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section in the malignant nodule group were all higher than those in the benign nodule group,and the differences were statistically significant(t=13.997,9.100,12.191,7.616,6.310,4.679,5.355,P＜0.05).The result of receiver operating characteristic(ROC)curve analysis indicated that both ultrasonography parameters and shear wave elastography(SWE)parameters had higher diagnostic value for the benign and malignant nature of thyroid nodules in patients.The area under curve(AUC)values of intensity to peak,time to peak,and the maximum value,minimum value and mean value of Young's modulus,and the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section were respectively 0.976,0.759,0.974,0.837,0.989,0.872,0.805,0.732 and 0.749.Conclusion:Multimodal ultrasound elastography parameters has significant application value in differential diagnosis for thyroid nodules in patients with diffuse thyroid lesions.In these parameters,the diagnostic AUC values of intensity to peak,time to peak,and the maximum value and mean value of Young's modulus are higher for malignant thyroid nodules of patients,which have higher diagnostic efficiency.It can effectively help clinical doctor to accurately identify the benign and malignant nodules for patients with diffuse thyroid lesions.

The medical insurance payment system is an essential component of the healthcare security system.In the new era,China has adjusted its medical insurance payment methods,gradually promoting Diagnosis Related Groups(DRG)and Diagnosis-Intervention Packet(DIP)payment systems.While enhancing resource allocation efficiency,these reforms have also introduced new challenges to the doctor-patient relationship,leading to new characteristics in doctor-patient conflicts.It reviews the origins and evolution of such conflicts,summarizes their relationship with institutional changes,and examines China's healthcare reform through literature review and case analysis.It explores the new characteristics and causes of doctor-patient conflicts under the DRG/DIP payment context.From perspectives such as improving payment policy design,strengthening accountability and balancing interests,promoting humanistic education and media supervision,and ensuring consistency in medical treatment,the paper proposes governance solutions to address the new characteristics of doctor-patient conflicts.The aim is to achieve a dual goal of harmonious doctor-patient relationships and improved medical service efficiency under the reformed payment system.