This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

This study aims to explore the specific mechanism by which puerarin inhibits ferroptosis and improves the myocardial contractile function in myocardial hypertrophy through the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1) signaling pathway. The hypertrophic cardiomyocyte model was established using phenylephrine, and H9c2 cells were divided into control group, model group, puerarin group, and puerarin+ML385 group. Cell viability and surface area were detected by cell counting kit-8(CCK-8) and immunofluorescence experiments. The mitochondrial membrane potential and Ca~(2+) concentration were measured. The ferroptosis-related indicators were detected by biochemical and fluorescence staining methods. The expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway was detected by Western blot. A myocardial hypertrophy model was established, and 40 rats were randomly divided into sham group, model group, puerarin group, and puerarin+Nrf2 inhibitor(ML385) group, with 10 rats in each group. Echocardiogram, hemodynamic parameters, and myocardial hypertrophy parameters were measured. Histopathological changes of myocardial tissues were observed by hematoxylin and eosin(HE) staining and Masson staining. Biochemical methods, enzyme-linked immunosorbent assay(ELISA), and fluorescence staining were used to detect inflammatory factors and ferroptosis-related indicators. Immunohistochemistry was used to detect the expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway. Cell experiments showed that puerarin intervention significantly enhanced the viability of hypertrophic cardiomyocytes, reduced their surface area, and restored mitochondrial membrane potential and Ca~(2+) homeostasis. Mechanism studies revealed that puerarin promoted Nrf2 nuclear translocation, upregulated the expression of HO-1, solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4), and decreased malondialdehyde(MDA), reactive oxygen species(ROS), and iron levels. These protective effects were reversed by ML385. In animal experiments, puerarin improved cardiac function in rats with myocardial hypertrophy, alleviated myocardial hypertrophy and fibrosis, inhibited inflammatory responses and ferroptosis, and promoted nuclear Nrf2 translocation and HO-1 expression. However, combined intervention with ML385 led to deterioration of hemodynamics and a rebound in ferroptosis marker levels. In conclusion, puerarin may inhibit cardiomyocyte ferroptosis through the Nrf2/ARE/HO-1 signaling pathway, thereby improving myocardial contractile function in myocardial hypertrophy.
Animals ; NF-E2-Related Factor 2/genetics* ; Rats ; Ferroptosis/drug effects* ; Signal Transduction/drug effects* ; Isoflavones/pharmacology* ; Male ; Rats, Sprague-Dawley ; Cardiomegaly/genetics* ; Myocytes, Cardiac/metabolism* ; Antioxidant Response Elements/drug effects* ; Myocardial Contraction/drug effects* ; Heme Oxygenase-1/genetics* ; Cell Line

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Purpose To explore whether tryptanthrin(TRYP)can inhibit the malignant behavioral ability of glio-ma cells,and to elucidate the specific mechanism of its action.Methods MTT assay was performed to detect the effect of TRYP on the proliferation of glioma cells;Transwell assay was performed to detect the effect of TRYP on the migration and invasion of glioma cells;AnnexinV-FITC/PI apoptosis assay was performed to detect the effect of TRYP on the apoptosis of glioma cells;PI/RNase cell cycle assay was performed to detect the effect of TRYP on the cell cycle distribution of glioma cells;Western blot assay was performed to detect the effect of TRYP on the protein expressions of p-ERK and c-Myc in glioma cells.The effect of TRYP on the proliferation of glioma cells in vivo was verified by con-structing a subcutaneous transplantation tumor model in nude mice,and the effect of TRYP on the apoptotic ability of cells in the transplantation tumor was detected by TUNEL assay.Immunohistochemistry was used to detect the effect of TRYP on the expression of Ki67,BRAF,c-Myc,and p-ERK proteins in transplanted tumor tissues.Results MTT assay showed that TRYP could effectively inhibit the proliferation of glioma cells(P＜0.001).Transwell assay showed that TRYP could inhibit the invasion and migration of glioma cells(P＜0.001).AnnexinV-FITC/PI cell apoptosis as-say showed that TRYP could promote the apoptosis of glioma cells(P＜0.001).The results of PI/RNase cell cycle as-say showed that TRYP was able to promote the G2 phase block of glioma cells(P＜0.001).Western blot results showed that the expression levels of c-Myc and p-ERK proteins in the glioma cells were significantly reduced after TR-YP treatment(P＜0.001).The results of subcutaneous transplantation tumor model in nude mice showed that TRYP could effectively inhibit the growth rate(P＜0.01)and weight(P＜0.05)of transplanted tumor.TUNEL assay showed that TRYP could promote the apoptosis of tumor cells in transplanted tumor(P＜0.001).Immunohistochemis-try results showed that TRYP could effectively inhibit the protein expression of Ki67(P＜0.01),BRAF,c-Myc,and p-ERK(P＜0.001).Conclusion TRYP can inhibit the proliferation,invasion,and migration ability of glioma cells,promote apoptosis of glioma cells,and block the cell cycle of glioma cells.TRYP may inhibit the malignant pro-gression of glioma cells by suppressing the protein expression of BRAF,c-Myc and p-ERK1/2 in the MAPK/ERK sig-naling pathway.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective To investigate the correlation between skeletal muscle fat content and diabetic peripheral neuropathy(DPN)in patients with type 2 diabetes mellitus(T2DM).Methods 290 patients with T2DM admitted to our hospital were enrolled in this study from January 2023 to February 2024 and divided into two groups according to whether they were complicated with DPN:simple T2DM group(T2DM,n=98)and T2DM with DPN group(DPN,n=192).The general data,biochemical indexes and fat distribution indexes measured based on quantitative CT were compared between the two groups.Spearman correlation was used to analyze the relationship between fat distribution indexes and DPN,logistic regression analysis of influencing factors of T2DM complicated with DPN.Results Age,DM duration,WHR,FIns,insulin resistance index(HOMA-IR)and FF were higher in DPN group than in T2DM group(P<0.05).Ca,subcutaneous abdominal fat area(SFA)and liver fat content were lower in DPN group than in T2DM group(P<0.05).Spearman correlation analysis showed that DPN was negatively correlated with SFA and liver fat content(r=-0.127,-0.123,P<0.05),and positively correlated with FF(r=0.117,P<0.05).Logistic regression analysis showed that without adjusting for confounding factors and adjusting for DM duration,WHR,HOMA-IR,Ca,SFA and liver fat content,FF was an influential factor for DPN in T2DM patients.Conclusions Skeletal muscle FF was associated with DPN in patients with T2DM.

Objective:To evaluate the safety and efficacy of combined inflatable mediastinoscopy with laparoscopy guided by the concept of “reduced field and port” during esophagectomy for esophageal cancer.Methods:This is a retrospective cohort study. The clinical data of 497 patients with esophageal squamous cell carcinoma who underwent minimally invasive esophagectomy at the Center of Minimally Invasive Thoracic Surgery, the Second Affiliated Hospital of Naval Medical University, between January 2017 and December 2024 were retrospectively analyzed. There were 416 male and 81 female patients, with an age of (68.3±8.0) years (range: 44 to 89 years). Patients were divided into the traditional video-assisted thoracoscopic surgery group (Group A, n=354) and the combined inflatable mediastinoscopy with laparoscopic surgery group(Group B, n=143) based on the surgical approach. Furthermore, Group B was subdivided into the multiport laparoscopic group (Group B1, n=81) and the single-incision laparoscopic surgery plus one port group (Group B2, n=62). Perioperative indicators and postoperative survival differences were compared between the groups. Inter-group comparisons were performed using the independent sample t-test, χ2 test, or Fisher′s exact probability test. Survival curves were plotted using the Kaplan-Meier method, and the Log-rank test was used to analyze the survival differences between groups. Results:Compared with Group A, Group B demonstrated a significantly shorter operative time ((181.8±11.4) minutes vs. (196.7±8.1)minutes, t=16.09, P<0.01), a lower incidence of postoperative pulmonary complications (8.4% (12/143) vs. 17.8% (63/354), χ2=6.27, P=0.012), lower perioperative mortality (0 vs. 3.1%(11/354), P=0.039), and a shorter postoperative hospital stay ((16.2±2.2)days vs. (18.9±4.1)days, t=8.56, P<0.01). There was no significant difference in the anastomotic leak rate, number of lymph nodes dissected, or intraoperative blood loss between the two groups (all P>0.05). Overall survival time and recurrence-free survival time showed no significant difference between the two groups (all P>0.05). Subgroup analysis revealed no significant differences in perioperative indicators or postoperative complication rates between Group B1 and Group B2. Conclusions:Compared with traditional thoracoscopic combined with laparoscopic surgery, inflatable mediastinoscopy offered advantages in terms of lower postoperative pulmonary complication rates, shorter operative time, reduced postoperative hospital stay, and lower perioperative mortality. The “reduced field and port” concept could further minimize surgical trauma during the transmediastinal approach for esophagectomy while ensuring surgical safety and efficacy.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.