Objective To explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF). Methods A total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n＝60, standard treatment combined with dapagliflozin) and the control group (n＝60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A_1C (HbA_1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed. Results A total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P＜0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P＝0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA_1C levels showed statistical differences between the two groups (P＜0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment. Conclusions Dapagliflozin improves patients’ quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To systematically evaluate the effects of total intravenous anesthesia and inhalational anesthesia on postoperative recovery in patients undergoing transsphenoidal pituitary tumor resection.Methods A comprehensive search was conducted in international biomedical databases including Ovid Medline,Embase,CINAHL(EBSCO),Cochrane Library,and Web of Science,from inception to July 4,2023.Additionally,ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing and completed trials.The randomized controlled trials(RCT)comparing total intravenous anesthesia and inhalational anesthesia in patients undergoing transsphenoidal surgery for pituitary tumors were included.The methodological quality of the included studies was evaluated by the Cochrane Collaboration tool.Relevant data were extracted and synthesized for analysis.Results A total of 327 records were identified,of which eight RCTs met the inclusion criteria.Four studies showed that the patients receiving desflurane or sevoflurane anesthesia experienced faster emergence from anesthesia than those receiving propofol.Two studies indicated that patients in the propofol group had lower levels of emergence agitation and a lower incidence of early postoperative nausea and vomiting.The results on postoperative cognitive function were inconsistent across studies.No differences were found between the groups in terms of postoperative complications or overall recovery quality during hospitalization.Conclusions Inhalational anesthesia appears to provide an advantage in promoting faster emergence following transsphenoidal pituitary surgery,whereas total intravenous anesthesia may contribute to smoother and more stable recovery.Further high-quality studies are needed to clarify the effects of different anesthetic techniques on both short- and long-term postoperative recovery.
Humans ; Anesthesia, Intravenous ; Pituitary Neoplasms/surgery* ; Anesthesia, Inhalation ; Randomized Controlled Trials as Topic ; Anesthesia Recovery Period ; Pituitary Gland/surgery* ; Postoperative Period

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective To clarify and analyze the reasons for failure in screening healthy menopausal female in a bioequivalence trial.Methods To summarize and clarify the data of 185 healthy menopausal female subjects participating in a bioequivalence trial of estradiol valerate conducted,and summarize the reasons for screening failure.Results The main reasons for screening failure include laboratory tests(32.04％),gynecological transvaginal color Doppler ultrasound(16.57％),vital signs(14.36％),chest computed tomography(CT,11.60％),and medical history/medication history(7.73％).Conclusion Screening failures in healthy menopausal female subjects were characterized mainly by abnormal gynecological transvaginal color Doppler ultrasound and non-compliance with basal hormone levels compared to generally healthy subjects.

The incidence of gastric cancer ranks fifth among malignant tumors worldwide, with the fourth highest mortality rate. A noteworthy characteristic of our country is the high prevalence of advanced-stage patients of approximately 40%. Advanced-stage gastric cancer carries an unfavorable prognosis with median survival of around one year. Diagnosis methods for advanced-stage gastric cancer (such as laparoscopic exploration, molecular profiling, and artificial intelligence) are still being continuously improved, while chemotherapy remains the primary treatment. With the rapid development of medical science, the role of surgical intervention in advanced-stage gastric cancer is becoming increasingly prominent. Therefore, as gastric tumor surgeons, we should consider how to use a combination of treatments, including surgery, chemotherapy, targeted therapy, immunotherapy, and interventional therapy, based on different pathological stages and the heterogeneity of tumors. With a multidisciplinary approach involving experts from various fields, we can collectively improve the survival rate and quality of life for advanced-stage patients. This article provides a brief overview of the current advances in the diagnosis and treatment of advanced-stage gastric cancer, and discusses therapeutic decision primarily from the perspective of surgeons.

Objective:To establish a three-tier review rule for parenteral nutrition orders by pharmacists,improve the qualification rate of parenteral nutrition orders,and promote the rational and standardized use of parenteral nutrition.Method:Pharmacists from different positions participate in a manual review intervention model for parenteral nutrition orders at three-tier review,establishing standardized and simplified parenteral nutrition review rules to reduce review difficulty and improve review efficiency.Result:After implementation,the qualified rate for parenteral nutrition orders increased from 71.09%to 95.59%,with a qualified rate of 100%for an industrial multi-cavity bag.The simplicity of parenteral nutrition components,cation concentration,carbohydrate-to-lipid ratio,non-protein calorie-to-nitrogen ratio and route of administration have been significantly improved.Conclusion:The involvement of pharmacists in the three-tier review of parenteral nutrition can reduce the risk of single-tier review,promote collaboration between pharmacists in different roles,improve the accuracy and efficiency of review,and reduce the risk of inappropriate use of parenteral nutrition.

Objective To conduct visualization analysis on research about Taraxaci Herba;To understand the research status,hotspots and trend of this field;To provide references for relevant research and clinical application.Methods The literature related to Taraxaci Herba was retrieved from CNKI,Wanfang Data,VIP and CBM from January 1,2000 to October 25,2023.NoteExpress 3.9 software was used to organize the bibliothems,and CiteSpace 6.2.R5 software was used to perform visualization analysis on the authors,research institutions and keywords.Results After screening,a total of 1 286 articles were included,with an overall upward trend in the number of annual publications.There were 518 source journals,and the journal with the most articles was Lishizhen Medicine and Materia Medica Research(33 articles);724 authors were involved,including Li Xifeng with the most articles(24 articles),and the core authors included Li Xifeng,Du Yunfeng,Hao Zhe,etc.;core research institutions included Henan University of Chinese Medicine,Yanbian University,Jiamusi University,etc.;high-frequency keywords included"Taraxaci Herba","caffeic acid","flavone","chlorogenic acid","Chinese materia medica"and so on.The research frontier involved breast cancer,inflammatory factors,Taraxaci Herba root,proliferation and antioxidant.Conclusion The current research hotspots in Taraxaci Herba focus on chemical composition,mechanism,compatibility application and disease treatment.In-depth study of the chemical constituents,refinement of the relevant mechanisms and disease treatment are the research trends in this field.