Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Objective:To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified “overlap” technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation.Methods:This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified “overlap” technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m2 (range:20.0 to 33.0 kg/m2). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the “overlap” technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t tests were used for intergroup comparisons. Results:All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3) points postoperatively ( t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1) points preoperatively to (77.6±8.3) points postoperatively ( t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively ( t=-4.85, P<0.01). Conclusion:TKA combined with the modified “overlap” technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.

Objective To explore the safety and management mode of hysteroscopy in three different modes:outpatient,daily and inpatient.Methods The quality control data of patients who underwent hysteroscopic surgery in Hysterscopy Centre,Obstetrics and Gynecology Hospital,Fudan University from Jan 2019 to Dec 2021 were collected through the electronic information system of the hospital and the monthly quality control report of hysteroscopy center.The amount of surgery,the proportion of grade Ⅳsurgery,the analysis of operation types,the indicator including complications,and unanticipated secondary surgery were retrospectively analyzed.Results From 2019 to 2021,5 162 outpatient hysteroscopic patients,15 331 daily hysteroscopic patients and 5 942 inpatient hysteroscopic patients were admitted in our hospital.The age of inpatient hysteroscopic patients was significantly older than those of outpatient and daily patients(P<0.001).In the past three years,the proportion of daily hysteroscopy gradually increased,and the proportion of inpatient hysteroscopy gradually decreased(P<0.001).The total percentage of grade Ⅳ hysteroscopic surgery was 12.9%,in which inpatient was higher than daily,and daily was higher than outpatient(P<0.001).The incidence of complications and accidents during hysteroscopy was 0.117%(31/26 435),including 17 cases of uterine perforation,7 cases of hysteroscopy failure,3 cases of excessive intraoperative bleeding,2 cases of fluid overload,1 case of intestinal injury,and 1 case of anesthesia accident.The incidence of hysteroscopy in outpatient,daily and inpatient were 0.020%(1/5 162),0.137%(21/15 331)and 0.151%(9/5 942)respectively.Conclusion Hysteroscopy in outpatient,daily and inpatient are all safe and reliable.Outpatient and daily hysteroscopy can improve the efficiency of medical services,which has gradually become a trend.

Objective:To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified “overlap” technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation.Methods:This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified “overlap” technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m2 (range:20.0 to 33.0 kg/m2). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the “overlap” technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t tests were used for intergroup comparisons. Results:All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3) points postoperatively ( t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1) points preoperatively to (77.6±8.3) points postoperatively ( t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively ( t=-4.85, P<0.01). Conclusion:TKA combined with the modified “overlap” technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.

Objective:Abnormal programmed cell death in immune cells is associated with autoimmune diseases,but the patterns of programmed cell death in systemic lupus erythematosus(SLE)and especially lupus nephritis(LN)remain unclear.This study aims to explore the association between SLE,LN,and immune cell death patterns. Methods:Bulk RNA sequencing(bulk RNA-seq)and single-cell RNA sequencing(scRNA-seq)data were downloaded from the Gene Expression Omnibus(GEO)database.Bioinformatic analysis was conducted to explore the expression levels of genes related to 3 cell death patterns in peripheral blood mononuclear cells of SLE patients.Key cell subsets involved in the imbalance of cell death patterns were identified through scRNA-seq.Immunofluorescence was used to detect the expression levels of receptor interacting serine/threonine kinase 3(RIPK3),mixed-lineage kinase domain-like protein(MLKL),phosphorylated MLKL(pMLKL),caspase 1(CASP1),CD1c molecule(CD1C),C-type lectin domain containing 9A(CLEC9A),and X-C motif chemokine receptor 1(XCR1)in dendritic cells(DC).scRNA-seq was performed on kidney tissues collected from LN patients and healthy controls(HC)at the Third Xiangya Hospital of Central South University,followed by bioinformatic analysis to identify key cell subsets involved in the imbalance of cell death patterns.Pseudotime analysis and ligand-receptor analysis were used to explore the differentiation direction and cell communication of different DC subsets.Transient transfection was used to transfect RAW264.7 cells with empty plasmid,empty plasmid+dsDNA(HSV-DNA),empty plasmid+200 μmol/L tert-butyl hydroperoxide(TBHP),stimulator of interferon genes(STING)shRNA plasmid,STING shRNA plasmid+dsDNA(HSV-DNA),and STING shRNA plasmid+200 μmol/L TBHP.Annexin V-mCherry and SYTOX Green staining were used to detect cell death in each group.Western blotting was used to detect the activation of CASP1,gasdermin D(GSDMD),RIPK3,and MLKL in each group. Results:Bioinformatic analysis showed an imbalance in 3 cell death patterns in SLE and LN patients:Pro-inflammatory pyroptosis and necroptosis were activated,while anti-inflammatory apoptosis was inhibited.The key cell subsets involved were DC subsets,particularly focusing on CLEC9A+cDC1.Immunofluorescence results showed that the expression levels of RIPK3,MLKL,and CASP1 in DCs were higher in the SLE group compared to the HC group.pMLKL and CASP1 expression levels in renal cDC1 marked by CLEC9A and XCR1 were higher in the LN group than in the HC group.Pseudotime analysis and ligand-receptor analysis suggested that the CLEC9A+cDC1 subset in LN kidney tissues originated from peripheral circulation.Annexin V-mCherry and SYTOX Green staining results showed that the number of dead cells decreased in the STING shRNA transfection group compared to the empty plasmid group in RAW264.7 cells.Western blotting results showed that the activation of CASP1,GSDMD,RIPK3,and MLKL was decreased in the STING shRNA transfection group compared to the empty plasmid group. Conclusion:This study provides novel insights into the role of CLEC9A+cDC1 in the imbalance of cell death patterns in SLE and LN.

Objective:To explore the diagnostic value of thromboelastography (TEG) combined with conventional coagulation test (CCT) for trauma-induced coagulopathy (TIC) in patients with electric burns in the early stage.Methods:This study was a retrospective case series research. From February 2018 to February 2024, the clinical data of 128 electric burn patients and 118 thermal burn patients who met the inclusion criteria and admitted to the Department of Burn Surgery of the Third Affiliated Hospital of Inner Mongolia Medical University were collected, including 224 males and 22 females, aged (38±14) years. The patients were divided into electric burn group (128 cases) and thermal burn group (118 cases) according to their injuries. The incidence of TIC, the indicators of CCT, including prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen level, D-dimer level, platelet count, and the detection indicators of TEG, including coagulation reaction time, K value, coagulation angle, maximum thrombus amplitude, comprehensive coagulation index, and lysis rate at 30 minutes after maximum amplitude within 8 hours of admission were compared between the two groups of patients. The Kappa test was used to analyze the consistency between CCT and TEG in diagnosing TIC in patients with electric burns in the early stage after burns. The receiver operating characteristic curves of CCT, TEG, and TEG combined with CCT in diagnosing TIC in 128 patients with electric burns were drawn, and the area under the curve (AUC), the maximum Jordan index, and sensitivity and specificity at this time were calculated.Results:The proportion of patients diagnosed with TIC in electric burn group was 19.5% (25/128) within 8 hours of admission, which was significantly higher than 10.2% (12/118) in thermal burn group ( χ2=4.21, P<0.05). Compared with those in thermal burn group, prothrombin time was significantly shortened ( t=-2.32, P<0.05), D-dimer level, fibrinogen level, and platelet count were significantly increased (with Z values of -2.11 and -4.16, respectively, t=4.69, P<0.05), the coagulation reaction time was significantly shortened ( t=-2.51, P<0.05), and the maximum thrombus amplitude and lysis rate at 30 minutes after the maximum amplitude were significantly increased (with t values of 2.50 and 2.10, respectively, P<0.05) in patients in electric burn group within 8 hours of admission. There were no statistically significant differences in the other CCT indicators and TEG detection indicators between the two groups of patients ( P>0.05). The CCT and TEG showed high consistency in the diagnosis of TIC in patients with electric burns in the early stage after burns (Kappa=0.63, P<0.05). The AUCs of TEG combined with CCT, TEG, and CCT in diagnosis of TIC in 128 patients with electric burns were 0.92, 0.84, and 0.77 (with 95% confidence intervals of 0.86-0.97, 0.71-0.97, and 0.71-0.97, respectively), with the maximum Jordan indexes of 0.86, 0.57, and 0.65. At this time, the specificity was 93.7%, 83.2%, and 88.2%, respectively, and the sensitivity was 92.3%, 87.5%, and 76.5%, respectively. Conclusions:Patients with electric burns are in a state of hypercoagulability of coagulation system and hyperfunction of fibrinolysis system in the early stage after burns, and TEG combined with CCT can increase the diagnostic rate of TIC in patients with electric burns.

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos (n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Objective:To construct a nomogram prediction model for predicting the risk of death in patients with sepsis-associated thrombocytopenia (SAT) in intensive care unit (ICU) for early indentification and active intervention.Methods:Clinical data of SAT patients admitted to ICU of the First Affiliated Hospital of Nanjing Medical University from December 2019 to August 2021 were retrospectively collected, including demographic data, laboratory indicators, etc. According to the prognosis at 28 days, the patients were divided into the death group and the survival group, and the differences of clinical variables between the two groups were compared. Multivariate Logistic regression analysis was performed to analyze the independent risk factors influencing mortality of patients within 28 days, then a nomogram predictive model was constructed and its performance was verified with internal data. Receiver operator characteristic curve (ROC curve) was used to evaluate the diagnostic effectiveness of the nomogram model, and the clinical applicability of this model was evaluated by clinical decision curve analysis (DCA).Results:A total of 275 patients were included, with 95 deaths at 28 days and a 28-day mortality of 34.5%. Compared with the survival group, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), sequential organ failure assessment (SOFA), lactic acid (Lac), platelet distribution width (PDW) on day 5 of ICU admission, blood urea nitrogen (BUN), total bilirubin (TBIL), aspartate aminotransferase (AST), C-reactive protein (CRP) of patients in the death group were higher, activated partial thromboplastin time (APTT) and prothrombin time (PT) were longer, platelet count (PLT) on day 3 and day 5 of ICU admission, direct bilirubin (DBIL), fibrinogen (FIB) were lower, the history of chronic lung disease, mixed site infection, lung infection, bloodstream infection, Gram-negative bacterial infection and fungal infection accounted for a higher proportion, the history of diabetes mellitus, urinary tract infection and no pathogenic microorganisms cultured accounted for a lower proportion, and the proportion of the use of vasoactive drugs, mechanical ventilation (MV), continuous renal replacement therapy (CRRT), bleeding events and platelet transfusion were higher. Multivariate Logistic regression analysis showed that APACHEⅡ score at the day of ICU admission [odds ratio ( OR) = 1.417, 95% confidence interval (95% CI) was 1.153-1.743, P = 0.001], chronic lung disease ( OR = 72.271, 95% CI was 4.475-1?167.126, P = 0.003), PLT on day 5 of ICU admission ( OR = 0.954, 95% CI was 0.922-0.987, P = 0.007), vasoactive drug ( OR = 622.943, 95% CI was 10.060-38?575.340, P = 0.002), MV ( OR = 91.818, 95% CI was 3.973-2?121.966, P = 0.005) were independent risk factors of mortality in SAT patients. The above independent risk factors were used to build a nomogram prediction model, and the area under the curve (AUC), sensitivity and specificity were 0.979, 94.7% and 91.7%, respectively, suggesting that the model had good discrimination. The Hosmer-Lemeshow goodness of fit test showed a good calibration with P > 0.05. At the same time, DCA showed that the nomogram model had good clinical applicability. Conclusions:Patients with SAT has a higher risk of death. The nomogram model based on APACHEⅡ score at the day of ICU admission, chronic lung disease, PLT on day 5 of ICU admission, the use of vasoactive drug and MV has good clinical significance for the prediction of 28-day mortality, and the discrimination and calibration are good, however, further verification is needed.