This article reports a case of an elderly male patient presenting with nephrotic syndrome. Renal biopsy pathology indicated membranous nephropathy, with both renal tissue staining for M-type phospholipase A2 receptor (PLA2R) and serum anti-PLA2R antibodies being negative. Nephrotic syndrome achieved remission following treatment with prednisone combined with tacrolimus; however, the patient relapsed during tacrolimus maintenance therapy. Subsequent laboratory evaluation revealed positive anti-nuclear antibodies and anti-double-stranded DNA antibodies, accompanied by decreased complement levels. Exostosin 1 and Exostosin 2 staining performed on the initial renal biopsy specimen yielded positive results, leading to a diagnosis of lupus nephritis. Due to the patient's history of rituximab-related allergic reactions, pulmonary infection, and acute kidney injury, the subsequent treatment regimen consisted of obinutuzumab sequentially combined with belimumab, in addition to prednisone 10 mg/d. During the two-year follow-up period, the patient's anti-double-stranded DNA antibodies converted to negative, complement levels normalized, proteinuria achieved complete remission, and no adverse events such as severe infection occurred. This article reviews the diagnosis, treatment, and relevant literature for this case, aiming to provide clinical insights for the early diagnosis and selection of therapeutic strategies for similar patients.

ObjectiveTo explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment（MCI）. MethodsBased on the baseline survey of the Hubei memory and aging cohort study（2018-2023）， the participants completed a thorough neuropsychological assessment and physical examination， and self-reported a history of general anesthesia and surgery. The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model. In addition， the stratification and interaction analysis of anesthesia history， anesthesia number and physical intellectual exercise were conducted separately. ResultsA total of 5 069 older adults aged 65 and above were included in this study， including 3 692 city dwellers and 1 377 rural people， among whom were 2 584 women （51%）. Out of the 1 472 participants with history of general anesthesia， 249 people （17.4%） had MCI. After controlling for confounding factors， there was a 39.6% increased risk of MCI in older adults who underwent general anesthesia ［OR=1.396，95%CI（1.169，1.668），P<0.001］， suggesting that general anesthesia may be an independent influence on MCI. For the older adults who had one general anesthesia ［OR=1.235，95%CI（1.001，1.523），P=0.049］， two general anesthesia ［OR=1.779，95%CI （1.292，2.450），P<0.001］， and three OR more general anesthesia ［OR=2.395，95%CI （1.589，3.610），P<0.001］， their risks of MCI were increased by 23.5%， 77.9%， and 139.5%， respectively. Compared with the older adults without a history of general anesthesia who did not exercise， the risk of developing MCI was significantly negatively correlated with the exercise group， cognitive exercise group， and combined exercise and cognitive exercise groups （all P<0.001）. The risk of developing MCI in the exercise group was 60.2% of that in the no exercise group ［OR = 0.602， 95% CI（0.456， 0.795）］， the risk in the cognitive exercise group was 42.4% of that in the no exercise group ［OR = 0.424， 95% CI（0.294， 0.613）］， and the risk in the combined exercise and cognitive exercise group was 27.0% of that in the no exercise group ［OR = 0.270， 95% CI （0.208， 0.353）］. In the older adults with a history of general anesthesia， compared with the no exercise group， the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group （all P < 0.05）. The risk of developing MCI in the cognitive exercise group was 47.7% of that in the no exercise group ［OR=0.477， 95% CI （0.256，0.892）］， the risk in the combined exercise and cognitive exercise group was 34.5% of that in the no exercise group ［OR=0.345， 95% CI （0.220， 0.540）］， while the risk in the exercise-only group did not show a significant difference. ConclusionThe risk of MCI increased significantly in older adults with a history of general anesthesia， and this risk increased with the times of anesthesia. Physical and mental exercise reduces the risk of MCI. it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.

In this study, serum metabolomics techniques and molecular biology methods were used to investigate the intervention effect of kaji-ichigoside F1 on chronic unpredictable mild stress(CUMS) depression mouse model and its mechanism. The CUMS depression mouse model was constructed, and the mice were divided into blank group, model group, escitalopram(ESC, 10 mg·kg~(-1)) group, and low-dose, medium-dose, and high-dose kaji-ichigoside F1 groups(1, 2, and 4 mg·kg~(-1)). CUMS modeling was performed on all mice except the blank group, and the cycle was four weeks. At the end of modelling, ESC and kaji-ichigoside F1 were administered by gavage once a day for 28 days. After the end of the administration, behavioral testing(sucrose preference test, open field test, forced swimming test, and tail suspension test) was conducted to evaluate the improvement of depression symptoms of different doses of kaji-ichigoside F1 on CUMS depression mouse model. The morphology of neurons and the number of Nissl bodies in the hippocampus were observed by Nissl staining. Metabolomics technique was used to analyze the changes in serum differential metabolites in mice. Protein expression levels of P2X7 purinergic receptor(P2X7R), adenosine A1 receptor(A1R), and adenosine receptor A2A(A2AR) in mouse hippocampus were detected by Western blot. The results showed that compared with that in the blank group, the body weight of mice in the model group was significantly decreased, and the sucrose preference rate was significantly decreased. The immobility time was significantly increased in the forced swimming and tail suspension tests, and the total moving distance was significantly decreased in the open field test. The number of Nissl bodies was significantly decreased, and the depression-like behavior and the number of Nissl bodies in the hippocampus of mice were significantly improved after administration of kaji-ichigoside F1. In the metabonomics analysis, the purine metabolism of serum after kaji-ichigoside F1 administration was involved in the metabolic passage of depression, and Western blot analysis verified the expression of P2X7R, A1R, and A2AR proteins in purine metabolic pathways. The results show that kaji-ichigoside F1 significantly decreases the expression of P2X7R and A2AR proteins in the hippocampus of CUMS model mice and increases the expression level of A1R proteins. It is suggested that kaji-ichigoside F1 may play an antidepressant role by regulating the expression of P2X7R, A1R, and A2AR proteins in the purine metabolism pathway.
Animals ; Mice ; Antidepressive Agents/administration & dosage* ; Metabolomics ; Depression/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Disease Models, Animal ; Hippocampus/metabolism* ; Behavior, Animal/drug effects* ; Humans

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

Objective Focusing on gynecological surgery,we constructed a prediction model for surgical duration by extracting features from unstructured surgical planning texts and integrating multimodal data via artificial intelligence technology.Methods The clinical data of 34 614 patients who underwent gynecologic surgeries at West China Second University Hospital,Sichuan University between January 2022 and October 2024 were collected.An embedding-transformer model was constructed to convert surgical planning texts into a one-dimensional numerical feature,referred to as the step feature.The predictive value of the step feature was assessed by comparing the performance improvements of linear regression,random forest,eXtreme Gradient Boosting(XGBoost),support vector regression,K-nearest neighbor regression,and artificial neural network algorithms in two scenarios—with and without the step feature as an input.The out-of-sample prediction accuracy of the models was assessed using mean absolute error(MAE),root mean squared error(RMSE),and R-squared(R2).Furthermore,the model interpretability was examined using SHapley Additive exPlanations(SHAP)values.Results SHAP results showed that the step feature had the highest predictive contribution.Temporal factors in surgical scheduling also influenced gynecological surgery duration.The XGBoost model demonstrated optimal performance on the test set,significantly improving prediction accuracy with a 40.43%increase in R2,while reducing MAE and RMSE by 21.27%and 20.13%,respectively,compared to the baseline model without the step feature.Conclusion The embedding-transformer model developed in this study effectively extracts features from surgical planning texts and enhances the predictive performance of machine learning models.The XGBoost prediction model can assist hospital administrators in implementing more refined management of gynecological surgeries and improving the utilization efficiency of surgical resources.

Objective To explore the effectiveness and safety of hypofractionated radiotherapy(HFRT)combined with transcatheter arterial chemoembolization(TACE)for metachronous hepatic oligometastasis from nasopharyngeal carcinoma(NPC).Methods The clinical data of patients with metachronous hepatic oligometastasis from NPC,who received HFRT combined with TACE treatment at the Sichuan Provincial Cancer Hospital of China from January 2012 to October 2022,were retrospectively analyzed.The 3-year and 5-year overall survival(OS),progression-free survival(PFS),local recurrence-free survival(LRFS),no extrahepatic distant metastasis survival(EMFS),and treatment-related adverse reactions were analyzed.Results A total of 55 patients were enrolled in this study,including 36 males and 19 females,the median age at the time of occurring metachronous hepatic oligometastasis was 44(27-75)years.The 3-year and 5-year OS,PFS,LRFS,EMFS were 67.8％and 40.0％,55.8％and 30.0％,72.7％and 56.5％,63.6％and 56.5％,respectively.The subgroup analysis indicated that the treatment course of TACE ≥3 cycles could significantly improve the PFS of patients with oligometastasis.HFRT combined with TACE treatment was well tolerated by all patients,and the incidence of Grade Ⅲ-Ⅳadverse reactions was quite low.Conclusion For the treatment of metachronous hepatic oligometastasis from NPC,HFRT combined with TACE is clinically effective,besides,the patients can well tolerate the therapeutic scheme.

In the field of healthcare service,it is crucial to optimize medical innovation services by combining the preferences of health service providers and demanders(i.e.,stakeholders).The best-worst scaling(BWS)method is a recently developed stated preference method for assessing preferences with distinctive advantages.Nevertheless,there is a lack of a comprehensive introduction to stakeholder preference assessment using BWS,thus constraining its applications and promotion.This paper introduces the process of using BWS to assess service providers'preferences for the Shared Medical Appointment for diabetes(SMART),an integrated healthcare service of medicine and health management,in the hope of providing reference for researchers for promoting the use of BWS in implementation research.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8(NEDD8)to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme(NAE)(E1),E2 NEDD8-conjugating enzyme(E2),and E3 NEDD8-ligase(E3).The most extensively studied substrates of neddylation are members of the cullin family,which act as scaffold components for cullin ring E3 ubiquitin ligases(CRLs).Since cullin neddylation activates CRLs,which are frequently overactive in tumors,inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies.This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions(PPIs)within the neddylation enzymatic cascade.