OBJECTIVE To establish a pharmaceutical management system for externally dispensed medicines in medical institutions， so as to improve medication safety and regulatory efficiency. METHODS Based on policy analysis and hospital practice， a pharmaceutical management system for externally dispensed medicines was constructed by integrating institutional frameworks， an information‑based platform and management procedures， and the management effectiveness was evaluated. RESULTS Our hospital formulated the Regulations on the Management of Externally Dispensed Medicines ， which standardized catalogue selection， prescription issuance， acceptance and use， supervision and evaluation. An information‑based management platform for externally dispensed medicines was built relying on the hospital information system， enabling electronic prescription circulation， intelligent prescription review and whole‑process traceability. Institutional requirements and platform functions were embedded into three core management procedures， namely catalogue selection， prescription issuance， and medicine acceptance and use， forming a closed‑loop working mechanism. After the implementation of the management system， compared with pre‑implementation， the qualified rate of externally dispensed prescriptions increased from 85.2% to 99.3% （ P ＜0.001）， the automatic prescription review pass rate exceeded 95%， the prescription review duration shortened from 7.2 min to 1.8 min （ P ＜0.001）. All dimensional satisfaction scores of patients and medical staff were significantly improved， the standardization awareness of medical staff reached 100%. CONCLUSIONS The construction of a pharmaceutical management system for externally dispensed medicines with standardized institutional frameworks， informatized platforms and standardized procedures effectively enhances the rationality and management efficiency of externally dispensed prescription medicines， and provides a replicable practical pathway for the management of externally dispensed medicines in medical institutions.

OBJECTIVE: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. METHODS: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. RESULTS: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. CONCLUSION These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective:To summarize the clinical phenotype and genetic features of patients with relapsing encephalopathy with cerebellar ataxia (RECA) caused by ATP1A3 gene R756 variants. Methods:A retrospective analysis was performed on patients carrying the ATP1A3 gene R756 variants, identified by whole-exome sequencing of family members, at Capital Center for Children′s Health, Capital Medical University and Children's Medical Center, Peking University First Hospital from August 2005 to February 2024. Their clinical, laboratory, neuroimaging, electrophysiological and genetic characteristics were summarized. Results:A total of 13 RECA patients were enrolled in this study, including 8 males and 5 females. The age of onset was 8 months to 5 years, with a median age of onset of 18 months. All of 13 patients presented paroxysmal episodes of neurological decompensations triggered by fever and residual symptoms following the acute phase. During acute attack stage, ataxia was observed in all 13 cases, muscle weakness in 12 cases, dysarthria in 12 cases, altered consciousness in 10 cases, dysphagia in 10 cases, dystonic episodes in 4 cases, abnormal eye movement in 2 cases, choreoathetosis in 2 cases, and epileptic seizures in 1 case. All 13 patients had residual symptoms during the nonparoxysmal period, of whom 9 patients had ataxia, 9 patients had dysarthria, 4 patients had dystonia, 3 patients had cognitive disorders, and 1 patient had epileptic seizures. All 13 cases had ATP1A3 missense variants, and variant c.2266C>T/p.R756C was found in 6 cases, c.2267G>A/p.R756H in 5 cases, and c.2267G>T/p.R756L in 2 cases. Nine cases carried de novo variants, 4 with inherited variants. Conclusions:RECA caused by variants of ATP1A3 in residue 756 typically presents with an acute onset during infancy or early childhood, precipitated by febrile episodes and characterized by recurrent episodes of ataxia, with bulbar paralysis, muscle weakness and altered consciousness. Recurrence is common, and the most common persistent symptoms are cerebellar ataxia and dysarthria. A few patients have cognitive impairment. Three types of ATP1A3 gene variants R756C, R756H and R756L are related with RECA, and R756C is the most common variant.

Objective:To investigate the diagnostic value of different conventional ultrasound-based radiomics models and their combination with clinical ultrasound features in the pathological subtyping of renal cell carcinoma.Methods:Retrospective data from 286 patients diagnosed with renal cell carcinoma by pathology at the Tenth Affiliated Hospital of Southern Medical University between May 1，2017 and June 7，2024 were collected. Among the 286 patients，203 were clear cell carcinoma，44 were papillary renal cell carcinoma，and 39 were chromophobe renal cell carcinoma. The patients were randomly divided into a training group（201 cases）and a validation group（85 cases）in a ratio of 7 to 3. Regions of interest（ROI）were delineated on conventional ultrasound images，and the radiomics features were extracted. Feature selection was performed using Student's t-test，Pearson correlation，and the least absolute shrinkage and selection operator（LASSO）. Six different machine learning methods included category gradient boosting（CatBoost），light gradient boosting machine（LightGBM），Logistic regression（LR），random forest（RF），support vector machine（SVM）and extreme gradient boosting（XGBoost）were used to establish radiomics models. Weight balancing was applied to correct for sample imbalance，and an imaging genomics model was constructed after balancing the samples. Independent predictors of renal cell carcinoma subtyping were selected from clinical ultrasound features using univariate and multivariate logistic regression analyses，and a clinical imaging model was constructed. The best-performing radiomics model was combined with the clinical independent predictors to construct a combined model. Receiver operating characteristic curves and the obuchowski index were plotted to evaluate model performance. Results:Among the radiomics models，the model constructed using Random Forest（RS RF）after balancing the samples exhibited the best predictive performance，with area under the curve（AUCs）of 0.918（micro-average ROC）and 0.903（macro-average ROC），and the obuchowski index was 0.885 in the validation group. The long and short axes of ultrasound image tumor masses were used as imaging independent predictors to construct a clinical imaging model. In the validation group，the AUCs of the clinical model were 0.886（micro-average ROC）and 0.606（macro-average ROC），and the obuchowski index was 0.569. The combined model achieved AUCs of 0.888（micro-average ROC）and 0.967（macro-average ROC），with an obuchowski index of 0.933，outperforming any single model. Conclusions:The combination of conventional ultrasound-based radiomics models with clinical ultrasound features demonstrates high diagnostic value in differentiating clear cell carcinoma，papillary renal cell carcinoma，and chromophobe renal cell carcinoma. It may serve as an auxiliary tool for providing timely and effective clinical guidance.

Objective To explore the status and trajectory of urinary incontinence in patients with bladder cancer after orthotopic neobladder surgery,and analyze the characteristics of different trajectory categories,to provide references for the intervention and management of urinary incontinence in patients after orthotopic neobladder surgery.Methods A prospective study design was adopted,and the convenience sampling was used to select 142 eligible patients who underwent in orthotopic neobladder surgery in a tertiary hospital from January 2019 to August 2022.Demographic and clinical data of the patients were collected.The continence status of patients was evaluated by the International Consultation on Incontinence Questionnaire-Short Form(ICI-Q-SF)at 1 month after surgery,3 months after surgery,6 months after surgery and 1 year after surgery.Additionally,postoperative physical condition scores,pelvic floor muscle training,and timed urination information were collected.The Group-Based Trajectory Model was used to identify the development trajectory of urinary incontinence,and the logistic regression was conducted to identify influencing factors of urinary incontinence trajectories.Results 142 cases were included.There are 3 distinct daytime and nocturnal incontinence trajectory groups that were respectively identified:the significantly improved group(21.83％,29.58％),the slowly alleviated group(52.82％,48.59％),and the risk fluctuation group(25.35％,21.83％).Multivariate logistic regression analysis indicated that age,preservation of neurovascular bundles,and adherence to timed voiding were factors significantly influencing urinary incontinence trajectory categories(P＜0.05).Conclusion The trajectory of urinary incontinence in patients undergoing orthotopic neobladder surgery showed an overall improvement trend within a year,with group differences.Clinical attention should be paid to the dynamic evaluation of postoperative urinary incontinence in older,unreserved nerves,and those who did not adhere to scheduled urination,and a phased matching postoperative rehabilitation plan should be developed to improve the urinary control level of patients.

Objective To construct an evaluation index system of organizational resilience of county medical alliance,and to propose countermeasures and suggestions for the enhancement of organizational resilience and operational effectiveness of county medical alliance.Methods The initial evaluation index system was constructed based on literature research and semi-structured interviews.Two rounds of Delphi expert consultation combined with critical value method refined the evaluation indexs.Evaluation index weights were determined via analytic hierarchy process and multiplicative weighting.The system was empirically tested using Zhejiang Province data.Results 21 experts completed consultations.Then the evaluation index system of county medical alliance organizational resilience was formed,which contains 5 first-level indexes,15 second-level indexes and 43 third-level indexes,containing 19 subjective and 24 objective evaluation indexs.The overall evaluation score of the organizational resilience of county medical alliance in Zhejiang Province was 73.97,which was at the average level of resilience.Conclusion The evaluation index system of organizational resilience of county medical alliance fits in with the national development plan to promote the construction of county high-quality,efficient and integrated medical and healthcare service system,and can provide effective measurement tools and theoretical references for the organizational capacity of county medical alliance and their maturity evaluation.