Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

Objective To analyze the effect of different lateral occlusion patterns on the stress distribution of All-on-4 implanted fixed dentures.Methods A model of All-on-4 implant fixed denture was established,and lateral balanced occlusion,group functional oc-clusion,and canine protection occlusion was simulated by changing the loading method.The selected loading force was 200 N vertically and 30 N horizontally.Results The maximum stress values of each part of the simulated balanced occlusion model were the smallest,while the maximum stress values of each part of the canine protection model were the largest.The maximum stress values of each part of the group functional occlusion model were slightly larger than those of the balanced occlusion model,but significantly smaller than those of the canine protection model.Conclusion Group function occlusion could be selected for the lateral occlusion in the final restoration of All-on-4 implant prosthesis.

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.

Objectives:To investigate the relationship between locations of ventricular septal perforation and 30-day prognosis in patients with acute myocardial infarction complicated by ventricular septal perforation.Methods:Clinical data of 150 acute myocardial infarction patients with ventricular septal perforation admitted to Fuwai Hospital of Chinese Academy of Medical Sciences and People's Hospital of Xinjiang Uygur Autonomous Region from January 2009 to October 2023 were retrospectively analyzed.Kaplan-Meier method was used to compare the difference in 30-day survival rate among patients with different sites of ventricular septal perforation.The impact of locations of ventricular septal perforation on 30-day prognosis of acute myocardial infarction patients was evaluated by multivariate Cox regression analysis(forward stepwise).Results:In acute myocardial infarction patients,the occurrence of anterior ventricular septal perforation was higher than that of posterior ventricular septal perforation(79.5%vs.20.5%,P<0.001).In the anterior ventricular septal perforation patients,females were more common(50.0%vs.22.6%,P=0.006),the blood glucose level was higher([10.51±5.99]mmol/L vs.[8.02±2.81]mmol/L,P=0.026),the left ventricular end-diastolic diameter was smaller([50.7±6.1]mm vs.[55.1±5.0]mm,P<0.001),the ventricular septal aperture was also smaller([9.8±4.6]mm vs.[12.6±5.4]mm,P=0.004),30-day mortality was higher(55.8%vs.35.5%,P=0.043)compared with posterior ventricular septal perforation patients.Multivariate Cox regression analysis(forward stepwise)showed that no transthoracic surgery or transcatheter closure(HR=26.344,95%CI:8.261-84.009,P<0.001)and anterior ventricular septal perforation(HR=2.432,95%CI:1.281-4.619,P=0.007)were associated with increased risk of 30-day all-cause mortality in patients with acute myocardial infarction complicated by ventricular septal perforation.Conclusions:In patients with acute myocardial infarction complicated by ventricular septal perforation,the incidence of anterior ventricular septal perforation is higher than posterior ventricular septal perforation and the 30-day all-cause mortality of anterior ventricular septal perforation patients is also higher.No transthoracic surgery or transcatheter closure and anterior ventricular septal perforation are the independent influential factors of 30-day all-cause mortality in patients with acute myocardial infarction and ventricular septal perforation.

Objective To analyze the effect of different lateral occlusion patterns on the stress distribution of All-on-4 implanted fixed dentures.Methods A model of All-on-4 implant fixed denture was established,and lateral balanced occlusion,group functional oc-clusion,and canine protection occlusion was simulated by changing the loading method.The selected loading force was 200 N vertically and 30 N horizontally.Results The maximum stress values of each part of the simulated balanced occlusion model were the smallest,while the maximum stress values of each part of the canine protection model were the largest.The maximum stress values of each part of the group functional occlusion model were slightly larger than those of the balanced occlusion model,but significantly smaller than those of the canine protection model.Conclusion Group function occlusion could be selected for the lateral occlusion in the final restoration of All-on-4 implant prosthesis.

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.

Objectives:To investigate the relationship between locations of ventricular septal perforation and 30-day prognosis in patients with acute myocardial infarction complicated by ventricular septal perforation.Methods:Clinical data of 150 acute myocardial infarction patients with ventricular septal perforation admitted to Fuwai Hospital of Chinese Academy of Medical Sciences and People's Hospital of Xinjiang Uygur Autonomous Region from January 2009 to October 2023 were retrospectively analyzed.Kaplan-Meier method was used to compare the difference in 30-day survival rate among patients with different sites of ventricular septal perforation.The impact of locations of ventricular septal perforation on 30-day prognosis of acute myocardial infarction patients was evaluated by multivariate Cox regression analysis(forward stepwise).Results:In acute myocardial infarction patients,the occurrence of anterior ventricular septal perforation was higher than that of posterior ventricular septal perforation(79.5%vs.20.5%,P<0.001).In the anterior ventricular septal perforation patients,females were more common(50.0%vs.22.6%,P=0.006),the blood glucose level was higher([10.51±5.99]mmol/L vs.[8.02±2.81]mmol/L,P=0.026),the left ventricular end-diastolic diameter was smaller([50.7±6.1]mm vs.[55.1±5.0]mm,P<0.001),the ventricular septal aperture was also smaller([9.8±4.6]mm vs.[12.6±5.4]mm,P=0.004),30-day mortality was higher(55.8%vs.35.5%,P=0.043)compared with posterior ventricular septal perforation patients.Multivariate Cox regression analysis(forward stepwise)showed that no transthoracic surgery or transcatheter closure(HR=26.344,95%CI:8.261-84.009,P<0.001)and anterior ventricular septal perforation(HR=2.432,95%CI:1.281-4.619,P=0.007)were associated with increased risk of 30-day all-cause mortality in patients with acute myocardial infarction complicated by ventricular septal perforation.Conclusions:In patients with acute myocardial infarction complicated by ventricular septal perforation,the incidence of anterior ventricular septal perforation is higher than posterior ventricular septal perforation and the 30-day all-cause mortality of anterior ventricular septal perforation patients is also higher.No transthoracic surgery or transcatheter closure and anterior ventricular septal perforation are the independent influential factors of 30-day all-cause mortality in patients with acute myocardial infarction and ventricular septal perforation.

Objective To establish biparameter MRI stepwiese discriminant models based on T2WI and diffusion-weighted imaging(DWI),and to observe their value for detecting clinically significant prostate cancer(CSPCa)in transitional zone.Methods Totally 224 patients with pathologically confirmed prostatic transitional zone lesions were retrospectively collected and divided into CSPCa group(n=81)and non-CSPCa group(n=143)according to pathological results and Gleason scores.Single factor and stepwise discriminant analysis were used to analyze T2WI and DWI manifestations of lesions in both groups,so as to screen the independent impact factors for distinguishing CSPCa from non-CSPCa.Discriminant functions models for CSPCa and non-CSPCa were established,respectively,and the diagnostic efficiency of models were verified using cross-verification method,while correct discriminant rate≥80％was considered as having differential diagnostic value.Results The maximum diameter,boundary,DWI signal of lesions,prostate capsule being complete or not,as well as the minimum apparent diffusion coefficient were all independent impact factors for distinguishing CSPCa from non-CSPCa,and the discriminant function models for CSPCa and non-CSPCa were established based on the above factors,respectively,with correct discrimination rates of discriminant function model for CSPCa and non-CSPCa of 90.11％and 88.81％,respectively,and the overall correct discrimination rate of 89.31％.Conclusion Biparameter MRI stepwise discriminant models could be used to detect CSPCa in transitional zone.

Objective:To conduct a scoping review on the application of family resilience intervention in adults with chronic disease.Methods:Related studies published from database establishment to October 30, 2023 were systematically searched on PubMed, Web of Science, Cochrane Library, PsycINFO, CINAHL, Scopus, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biomedical Database. The included literature was summarized and analyzed.Results:A total of 9 articles were included. The intervention elements for family resilience included increasing awareness of diseases and family characteristics, solving and responding to family problems, engaging in family interaction and communication, integrating internal and external resources, and providing psychological and technical support. The outcome indicators were the level of family resilience and effectiveness.Conclusions:The intervention of family resilience in adults with chronic disease has certain effectiveness and clinical significance, but research is still in the exploratory stage. Further high-quality research is needed to verify the long-term intervention effect and feasibility, and to construct a diversified family resilience intervention program suitable for China.

This case report described an 80-year-old male patient with Parkinson disease(PD)complicated with myasthenia gravis(MG).Six years ago,the patient was diagnosed with PD based on the motor symptoms including bradykinesia and static tremor and treated with levodopa-benserazide and piribedil sustained-release tablets.He was admitted to the hospital due to left eyelid ptosis one month ago.The result of Neostigmine test was positive and anti-acetylcholine receptor(AChR)antibodies of serum was positive,which met the diagnostic criteria for myasthenia gravis(MG).The symptom of MG improved significantly after treatment with glucocorticoid and pyridostigmine but the PD symptoms worsened.The symptoms of PD were improved after withdrawal of pyridostigmine and use of the levodopa-benserazide and his condition maintained stable at 3 years of follow-up.The PD complicated with MG was fairly rare.We also reviewed the literature on the possible comorbidity mechanism and treatment strategies to improve the comprehensive understanding and ability of diagnosis and treatment of clinicians.