Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Objective To explore the effect of a multicomponent exercise and cognitive stimulation program in elderly patients with mental disorders and sarcopenia,so as to provide references for reducing the risk of falls,preventing and improving sarcopenia,and enhancing cognitive function in patients.Methods The multi-component exercise and cognitive stimulation program was formulated through literature review and expert meeting.In this quasi-experimental study,76 elderly patients with mental disorders and sarcopenia who were hospitalized in a tertiary mental health center in Shanghai from January 2023 to February 2024 were selected as research subjects.They were randomly divided into an experimental group and a control group according to their hospitalization building number(38 cases in each group).The experimental group was treated with multicomponent exercise combined with cognitive stimulation program based on routine nursing,and the control group was treated with routine nursing.The risk of falls,skeletal muscle mass,muscle strength,physical function,cognitive function,and incidence of adverse events were compared between 2 groups after 12 weeks of intervention.Results A total of 75 patients with 37 in the control group and 38 in the experimental group completed the study.The TUG time,6M walking speed and the score of Short Physical Performance Bettery of the experimental group were all lower than those of the control group(P＜0.05),and the scores of skeletal muscle mass,muscle strength,calf circumference,physical function and cognitive function of the experimental group were all higher than those of the control group(P＜0.05).Neither group experienced any adverse events.Conclusion The application of this multicomponent exercise combined cognitive stimulation program developed for elderly patients with mental disorders and sarcopenia can effectively reduce the risk of falls,enhance the skeletal muscle mass and muscle strength and improve the cognitive function in elderly patients with mental disorders and sarcopenia.

Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Objective To explore the effect of a multicomponent exercise and cognitive stimulation program in elderly patients with mental disorders and sarcopenia,so as to provide references for reducing the risk of falls,preventing and improving sarcopenia,and enhancing cognitive function in patients.Methods The multi-component exercise and cognitive stimulation program was formulated through literature review and expert meeting.In this quasi-experimental study,76 elderly patients with mental disorders and sarcopenia who were hospitalized in a tertiary mental health center in Shanghai from January 2023 to February 2024 were selected as research subjects.They were randomly divided into an experimental group and a control group according to their hospitalization building number(38 cases in each group).The experimental group was treated with multicomponent exercise combined with cognitive stimulation program based on routine nursing,and the control group was treated with routine nursing.The risk of falls,skeletal muscle mass,muscle strength,physical function,cognitive function,and incidence of adverse events were compared between 2 groups after 12 weeks of intervention.Results A total of 75 patients with 37 in the control group and 38 in the experimental group completed the study.The TUG time,6M walking speed and the score of Short Physical Performance Bettery of the experimental group were all lower than those of the control group(P＜0.05),and the scores of skeletal muscle mass,muscle strength,calf circumference,physical function and cognitive function of the experimental group were all higher than those of the control group(P＜0.05).Neither group experienced any adverse events.Conclusion The application of this multicomponent exercise combined cognitive stimulation program developed for elderly patients with mental disorders and sarcopenia can effectively reduce the risk of falls,enhance the skeletal muscle mass and muscle strength and improve the cognitive function in elderly patients with mental disorders and sarcopenia.

Aortic endovascular stent infection(AEI)is a rare and potentially fatal complication following endovas-cular aortic repair(EVER).Its occurrence involves multiple factors.Actively preventing the colonization and ad-hesion of pathogenic microorganisms on the stent can significantly reduce the incidence rate of AEI.The clini-cal manifestations of AEI are nonspecific.Patients who develop unexplained fever,fatigue,pain or elevated in-flammatory markers after EVER should be alerted to the possibility of AEI and require laboratory and imaging ex-aminations to be improved actively for further clarification.For patients diagnosed with AEI who can tolerate sur-gery,the preferred treatment is to thoroughly remove infected materials and tissues,and to reconstruct blood sup-ply and administer antibacterial therapy according to the patient's condition.For those who cannot tolerate surger-y,long-term or lifelong antibacterial drug therapy is required,which can be supplemented by percutaneous punc-ture drainage.Strict screening of EVER patients,active prevention of pathogen colonization,early diagnosis and multidisciplinary combination treatment can significantly reduce the incidence and fatality rate of AEI,there-by improving patient prognosis.

Objective:To explore the application of contrast-enhanced ultrasound in the preoperative evaluation of carotid body tumor (CBT).Methods:The clinical data of 13 CBT patients undergoing contrast enhanced ultrasound test and surgical treatment at Peking Union Medical College Hospital from Nov 2017 to Aug 2021 was retrospectively analyzed.Results:Among the 13 patients, 7 patients had bilateral lesions. 18 tumors were identified by contrast enhanced ultrasound, which showed rich blood supply, with marked enhancement in 13 tumors and moderate enhancement in 5 tumors. The origins of the arterial supply for tumors were identified by contrast enhanced ultrasound. Time-intensity curve analysis showed that the tumors had enhancement characteristics of fast wash in and slow wash out. The mean contrast wash in time was (3.33±1.40) s, the mean peak intensity was (10.41±1.74) dB, and the mean wash out time was (56.47±22.28) s. A total of 13 cases underwent successful surgical removal. Five cases of external carotid artery ligation and 2 cases of internal carotid artery reconstruction were performed during surgery. Postoperative transient neurological injury occurred in 5 cases. There were no cases of cerebral infarction or death in the perioperative period. Mean postoperative follow-up was 14.31 months. Five cases of neurological injury had satisfactory recovery and no other adverse events occurred.Conclusions:Contrast enhanced ultrasound is an effective method of preoperative imaging assessment for CBT, which helps the surgical planning and preoperative preparation.

Background: The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. Methods: We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. Results: CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P = 0.002). Conclusions CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.