Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

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.

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.

Objective:To explore the mechanism of Shenfu Injection in treating chronic heart failure (CHF) based on Fas/FasL apoptosis signaling pathway.Methods:A total of 70 SPF male C57BL/6 mice were divided into blank group (15 mice) and model group (55 mice) according to random number table. The CHF model was prepared by intraperitoneal injection of isoproterenol. After 4 weeks, the successfully modeled mice were randomly divided intoa model group, Shenfu Injection group, and Western medicine group using a random number table method. After adfministration for 15 d, the left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVFS) of each group of mice were measured by heart color ultrasound 1; serum NT-proBNP was detected by enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin staining (HE) was used to observe the changes of myocardial tissue morphology; TUNEL pod method was used to detect apoptosis; the mRNA transcription levels of tumor necrosis factor-α (TNF-α), Fas, Fas ligand (FasL), Caspase-3 and Caspase-8 were detected by RT-PCR; protein expression levels of TNF-α, Fas, FasL, Caspase-3 and Caspase-8 in myocardial tissue were detected by Western blot. The logarithmically grown H9c2 cells were divided into blank group, model group and Shenfu Injection group. The cells in blank group were cultured for 48 hours; cells in the model group were exposed to 80 μmol/L isoproterenol for 48 hours; cells in Shenfu Injection group were pretreated with 5 μl/ml Shenfu injection for 3 hours and exposed to 80 μmol/L isoproterenol for 48 h. The cell growth was observed under microscope. Western blot and RT-PCR were used to detect the expression of related proteins and mRNA transcription. TUNEL pod and flow cytometry were used to detect apoptosis.Results:Compared with the model group, the cardiac function improved in the model group and Shenfu Injection group, serum NT ProBNP levels decreased ( P<0.01 or P<0.05), myocardial cell injury and apoptosis were reduced ( P<0.01 or P<0.05), and the mRNA and protein expression of TNF-α, Fas, FasL, Caspase-3, Caspase-8 in myocardial tissue decreased ( P<0.01 or P<0.05). The H9c2 cells in the blank group were spindle shaped with clear structure; the myocardial cells in the model group shrank and became shorter, with blurred cell boundaries and exhibiting apoptotic and necrotic morphology; Most H9c2 cells in the reference group were spindle shaped, with reduced cell death and increased density. Compared with the model group, the levels of TNF-α, Fas, FasL, Caspase-3, Caspase-8 protein and mRNA in H9c2 cells of the Shenfu Injection group decreased ( P<0.01 or P<0.05), and the apoptosis rate decreased ( P<0.01). Conclusion:Shenfu Injection may improve cardiac function and cardiomyocyte apoptosis of CHF mice through Fas/FasL signaling pathway.

Objective To investigate the postoperative efficacy of laparoscopic hiatal hernia repair(LHHR)combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia(HH).Methods A retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet(Toupet group,n=53)and Dor(Dor group,n=53)fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital.Intraoperative and postoperative recovery outcomes of both groups were observed.We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire(GERD-Q)scores at preoperative and postoperative intervals of 1 month,6 months,and 1 year.The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups.Additionally,factors influencing postoperative dysphagia within the first month were examined.Results The differences between the two groups in operation time,intraoperative bleeding,postoperative ventilation time,postoperative extubation time and hospitalization time were not statistically significant(P>0.05).There was no significant difference in the incidence of immediate postoperative dysphagia in two groups(P>0.05).Furthermore,the differences between the two groups in the incidence of postoperative complications,such as bloating,abdominal pain and diarrhea,were not statistically significant(P>0.05).The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively,and the difference was statistically significant(P=0.017);but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant(P=0.767,1.000).The results of binary logistic regression analysis showed that both surgical procedure(OR=2.613,95%CI 1.141-5.983,P=0.023)and esophageal contractile reserve function(OR=2.921,95%CI 1.203-7.095,P=0.018)were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery.Compared with the preoperative period,the GERD-Q symptom scores were lower in both groups at 1 month,6 months,and 1 year postoperatively,and the difference was statistically significant(P<0.05);but there was no statistically significant difference between the groups at the same time point(Fintergroup=0.334,P=0.565).The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant(P>0.05).Conclusions LHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH,with excellent reflux control,fewer complications and lower recurrence rates,but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.