Objective:To analyze the effect of different doses of estrogen on endometrial blood flow after tran-scervical resection of adhesion(TCRA)surgery in patients with intrauterine adhesion(IUA).Methods:A total of 70 moderate and severe IUA patients who underwent TCRA in the General Hospital of Ningxia Medical University from 2021 to 2023 were divided into group A(4 mg/day)and group B(6 mg/day)according to the dosage of es-trogen after operation.Reexamination of hysteroscopy was performed 2 months later,menstrual volume was fol-lowed up,uterine parameters in secretory phase were detected by B-ultrasound,and factors related to prolifera-tion,fibrosis and blood flow were detected by immunofluorescence after 3 months.Results:① In the severe IUA group,there was no difference in the rate of intrauterine re adhesion between group A2 and group B2.The satis-faction rate of endometrial epithelialization and endometrial glandular duct density in group B2 was higher than that in group A2,and the difference was statistically significant(P＜0.05).There was no significant difference in the three indicators within the moderate IUA group(P＞0.05).②Three months after operation,in the severe IUA group,there were statistically significant differences(P＜0.05)in menstrual flow,endometrial thickness ET,endo-metrial volume EV,endometrial blood flow values(VI,FI,VFI),and uterine artery blood flow values(PI,RI)be-tween the two groups;The above indicators showed no statistically significant differences within the moderate IUA group(P＞0.05).③Detection of endometrial markers:the expression of proliferation marker(Ki-67)and angio-genesis marker(CD31,CD34,CD146,b-FGF,VEGF)in group B2 was higher than that in group A2,while the ex-pression of fibrosis marker(α-SMA,TGF-β1)was lower,with statistical significance(P＜0.05).There was no sig-nificant difference in the expression of above indexes between group A,and group B,in moderate IUA group(P＞0.05).Conclusions:Short-term application of relatively high dose estrogen(6 mg/day)after TCRA can pro-mote better endometrial repair by improving endometrial blood flow in patients with severe IUA,while in patients with moderate IUA there is no significant difference in the effect on endometrial repair.

This study aims to clarify the incidence and prevention status of dairy cow mastitis in 79 large-scale pastures in China in 2022,reduce the incidence of dairy cow mastitis,and provide scien-tific basis for formulating prevention and control strategies for dairy cow mastitis in large-scale pastures suitable for China's national conditions.The research team relied on the large-scale ranch of the Comprehensive Experimental Station of National Dairy Industry Technology System to car-ry out research.A total of 79 questionnaires were received.The information on the stock of large-scale farms,the proportion of cows in the herd,the level of cow yields,the incidence and cure rate of cow mastitis,the prevention and control of cow mastitis,diagnosis and treatment programs of cow mastitis,the cost of treating cow mastitis,and the culling rate of farms was collected.Chi-square test and correlation analysis were carried out on the incidence of mastitis in dairy cows and the prevention and control plan,treatment plan,yield level and elimination rate of mastitis in dairy cows by descriptive statistical cross table.The incidence of cow mastitis in some pastures was con-trolled between 5％and 10％,and the cure rate was mostly as high as 98％.According to the co-hort analysis,the importance of prevention and control measures for dairy cow mastitis was as fol-lows:DMT＞DHI＞milk yield＞milk traits＞breast apparent change＞electrical conductivity＞CMT.The importance of treatment measures for dairy cow mastitis is as follows:DMT＞DHI＞milk yield＞milk traits＞breast apparent changes＞electrical conductivity＞CMT.The importance of treatment measures for mastitis is as follows:traditional Chinese medicine＞pathogen detection and drug sensitivity test＞non-steroidal anti-inflammatory drugs＞regular maintenance of milking equipment＞normal milking without treatment＞broad-spectrum antibiotics.The incidence of mas-titis in dairy cows is moderately positively correlated with the yield per unit area,that is,the in-crease in the incidence of mastitis in dairy cows has a certain impact on the yield per unit area of dairy cows.Economic analysis shows that the treatment cost of mastitis is closely related to the in-cidence rate,and the treatment cost of pasture with higher incidence rate is higher.Pastures with higher yields usually have more efficient means of disease prevention and control,and the corre-sponding treatment costs are lower.In conclusion,China's large-scale pastures should strengthen the scientific feeding management level,improve the prevention and control methods to reduce the incidence of cow mastitis,improve the cure rate,and reduce the cost of pasture treatment.

Objective:To evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) .Methods:A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph + patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results:According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) ( n=4), B/myeloid MPAL ( n=7), and ALAL- not otherwise specified ( n=2). Of the seven patients with B/myeloid MPAL, four were Ph + and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion:Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.

Objective:To explore the characteristics of the brain functional networks in children with spastic cerebral palsy (SCP) while at rest and to correlate them with motor functioning.Methods:Thirty-six children with SCP were enrolled as the SCP group, while thirty-four age-matched healthy children were recruited as the control group (the HC group). Functional near-infrared spectroscopy was used to detect changes in the concentration of oxygenated hemoglobin in the children′s cerebral cortex while at rest. The left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), and right motor cortex (RMC) were selected as regions of interest. Phase locking values (PLVs) were used to evaluate the strength of functional connectivity (FC) among these brain regions, and graph theory methods were applied to analyze the topological properties of the brain networks. Motor functioning was assessed using the gross motor function measure (GMFM).Results:The analyses of FC strength revealed that the SCP group had significantly weaker FC among all of the regions of interest while at rest compared to the HC group. Their PLVs for LPFC-RPFC, LPFC-RMC, RPFC-RMC and LMC-RMC connectivity were all significantly smaller. Graph theory analysis showed that the SCP group had significantly lower global efficiency (GE) and smaller clustering coefficients (CCs) and network density (D), while their characteristic path lengths were significantly longer. According to the correlation analysis, the PLVs for LMC-RMC connections in the SCP group were positively correlated with their scores on dimensions D and E of the GMFM ( r=0.496 and r=0.579 respectively). GE ( r=0.587 and r=0.642) and CC ( r=0.318 and r=0.759) showed similar significant positive correlations with GMFM dimensions D and E. Conclusions:At rest, the functional networks in the brains of children with SCP exhibit abnormalities closely associated with their motor dysfunction.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

A UHPLC-Q-Orbitrap/MS method was developed to identify the related substances in apixaban tablets. Complete separation was accomplished with a Waters Xbridge C18 (250 mm×4.6 mm, 5 μm) column by linear gradient elution using a mobile phase consisting of 30 mmol/L ammonium acetate buffer solution (pH 4.50) and acetonitrile. The related substances were successfully characterized through the accurate mass and elemental composition of the parent ions and their product ions determined by electrospray positive ionization high-resolution Q-Orbitrap/MS methods. Under the established analytical condition, apixaban and its related substances were well separated, and 30 related substances were detected and identified by hyphenated techniques in apixaban tablets and their stressed samples. Among them, 11 were known impurities and the rest 19 were unknown related substances identified for the first time in this study. The results obtained are valuable for apixaban manufacturing process optimization and quality control.

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Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P＜0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.

Trauma or surgical intervention in peripheral nerves can lead to traumatic nerve scarring and adhesions, which could hinder nerve regeneration and potentially cause functional impairment. Extensive scarring and adhesions may compress nerves, impair the essential gliding ability and result in fibrosis within the nerves and surrounding tissues. Therefore, searching for effective anti-adhesion strategies to prevent scar formation has become a significant clinical challenge. Currently, the mechanisms underlying the formation of peripheral nerve adhesions are not yet fully understood, and there are limited clinical methods available to prevent the adhesions. This review summarise the preclinical research findings and potential mechanisms of various anti-adhesion strategies, including pharmacological approaches, physical barriers, physical methods, and the combination of them. Additionally, clinical trials and case-control data are evaluated to assess the effectiveness of anti-adhesion strategies that have been applied in clinical settings, providing insights into the potential for future clinical applications of the strategies in prevention of peripheral nerve adhesions.

Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P＜0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.