OBJECTIVE To investigate the application status of prescription pre-review systems in healthcare institutions of Yunnan province， evaluate their system functions and management capabilities， and provide a practical basis for promoting rational drug use. METHODS A questionnaire survey was conducted among public healthcare institutions at or above the secondary level in Yunnan province to investigate the deployment status of the systems. A capability maturity assessment framework was constructed， encompassing 6 dimensions and 39 indicators， including real-time prescription review， prescription correlation review， rule setting， evidence-based information support， prescription authority management， and system operation management. This framework was then used to evaluate the institutions that had implemented the pre-review systems. RESULTS A total of 100 valid questionnaires were collected， with 37 institutions having adopted prescription pre-review systems， mainly tertiary hospitals. The system predominantly adopted a modular architecture and was embedded into the hospital information system through application programming interfaces and middleware， providing certain capabilities for real-time prescription risk identification. Evaluation results indicated that basic functions such as reviewing indications， contraindications， and drug compatibility performed well， while deficiencies remained in functions related to parenteral nutrition prescription， review of drug dosage for specific diseases， individual patient characteristic recognition， and rule setting. Moreover， the construction of review centers and establishment of management systems were also not well-developed. CONCLUSIONS The overall application rate of prescription pre-review systems in Yunnan province remains low. System functions and management mechanisms require further improvement. It is recommended to enhance information infrastructure in lower-level institutions and explore regionally unified review models to promote standardized and intelligent development of prescription review practices.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Objective: To provide evidence for improving emergency blood supply protocols by analyzing the clinical characteristics and disease distribution of emergency transfusion patients, especially those receiving≥10 units of red blood cells (RBCs). Methods: The data of 4 157 patients who urgently applied for large-volume blood transfusion in various hospitals in Shanghai from May 2024 to April 2025 were selected and analyzed statistically. Results: Tertiary gradeA hospitals accounted for the largest proportion of total transfusion volume (U) (48.79%, 8 420/17 256.5), with no statistically significant differences in RBC transfusion volumes among hospitals of different grades (P>0.05). All blood products are most widely used in tertiary hospitals. Obstetric blood transfusion (U)(19.07%, 3 277.5/17 190.5) was the most frequent. A-mong the hospitals of patients who received emergency blood transfusion with red blood cell suspension≥10 U, tertiary gradeA hospitals also had the largest transfusion volume (U)(47.19%, 1 107/2 346). In terms of disease types, the top three diseases in terms of blood transfusion volume (U) were obstetric transfusion (24.59%, 572/2 326), digestive diseases (14.53%, 338/2 326) and tumors (14.19%, 330/2 326). Conclusion: Tertiary grade A hospitals are the main demand units for emergency blood transfusion, with pregnant women and cancer patients being the core blood-using groups. It is suggested that the safety, timeliness and sufficiency of emergency blood transfusion be guaranteed by establishing a hierarchical blood supply mechanism, formulating single-disease blood transfusion plans and promoting precise blood transfusion guided by thromboelastography.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.