Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

T helper cells (Th cells) play an important role in periodontitis. During the progression of periodontitis, the levels of pro-inflammatory cytokines such as INF-γ and IL-17, which are produced by Th1 and Th17 cells, are elevated, while the levels of anti-inflammatory cytokines such as IL-4 and TGF-β, which are secreted by Th2 cells and regulatory T cells (Tregs), are diminished. Interventions using mesenchymal stem cells (MSCs) or their exosomes can alter the dynamics of helper T cell populations and their associated cytokine profiles, thereby mitigating the bone loss associated with periodontitis or even promoting bone regeneration. Mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to directly modulate Th cell activity through the proteins and microRNAs they transport. Recent studies indicate that MSC-exos carry immune-suppressive protein molecules: PD-L1 and IDO contribute to regulating the balance between Th17 and Tregs; TGF-β inhibits the proliferation of T lymphocytes while facilitating differentiation into Tregs by sustaining forkhead box protein O3 (FOXP3) and Smad expression; and CD73 catalyzes the conversion of monophosphate adenosine into adenosine, which interacts with A2A receptors on Th1 cells to induce apoptosis in Th1 cells. In addition, microRNAs exhibit immunoregulatory functions: periodontal ligament stem cell-derived exosomes contain miRNA-155-5p, which targets sirtuin-1 to suppress Th17 cell differentiation. Furthermore, evidence in rat models of periodontitis suggests that these exosomes may also carry miR-205-5p targeting XBP1 to restore the balance between Th17 and Tregs. Dental pulp stem cell-derived exosomes reestablish this balance via the miR-1246/Nfat5 axis. Bone marrow mesenchymal stem cell-derived exosomes harbor miR-1246, which targets ACE2 to promote differentiation towards Tregs. Moreover, MSC-exos can indirectly enhance the differentiation of Tregs through interactions with other immune entities, such as antigen-presenting cells or macrophages. This article reviews the changes and roles of helper T cells in periodontitis, as well as the regulatory role of exosomes on helper T cells, hoping to provide new ideas for immunotherapy in the treatment of periodontitis.

BACKGROUND: Lung cancer is the leading malignancy in China in terms of both incidence and mortality. With increased health awareness and the widespread use of low-dose computed tomography (CT), early diagnosis rates have been steadily improving. Surgical intervention remains the primary treatment option for early-stage lung cancer, and video-assisted thoracoscopic surgery (VATS) has become a common approach due to its minimal invasiveness and rapid recovery. However, post-discharge recovery remains incomplete, underscoring the importance of postoperative care. Traditional follow-up methods, lack standardization, consume significant medical resources, and increase the burden of the patients. Artificial intelligence (AI)-driven disease management platforms offer a novel solution to optimize postoperative follow-up. This study followed 463 lung cancer surgery patients using an AI-based platform, aiming to identify common postoperative issues, propose solutions, improve quality of life, reduce recurrence-related costs, and promote AI integration in healthcare. METHODS: Using the AI disease management platform, this study integrated educational videos, collaboration between healthcare teams and AI assistants, daily health logs, health assessment forms, and personalized interventions to monitor postoperative recovery. The postoperative rehabilitation status of the patients was assessed by the Leicester Cough Questionnaire (LCQ-MC). Two independent t-test and one-way ANOVA were used to analyze the causes of postoperative cough in lung cancer. RESULTS: Most issues occurred within 7 d post-discharge, significantly declined on 14 d post-discharge. Factors such as gender, smoking history, and surgical approaches were found to influence cough recovery. The incidence of cough on 7 d post-discharge in females was higher than that in males (P<0.01), while the incidence of cough on 14 d post-discharge in elderly patients was lower than that in young patients (P=0.03). The AI-based platform effectively addressed cough, pain, and sleep disturbances through phased interventions. CONCLUSIONS The AI-based platform significantly enhanced postoperative management efficiency and the self-care capabilities of the patients, particularly in phased cough management. Future integration with wearable devices could enable more precise and personalized postoperative care, further advancing the application of AI technology across multidisciplinary healthcare domains.
Humans ; Lung Neoplasms/rehabilitation* ; Male ; Female ; Middle Aged ; Aged ; Patient Discharge ; Artificial Intelligence ; Adult ; Postoperative Care ; Postoperative Period ; Disease Management ; Quality of Life

Aging involves the accumulation of various forms of molecular and cellular damage over time. Key features of aging, such as mitochondrial dysfunction, dysbiosis, and oxidative stress, are closely linked and largely driven by inflammation. This study examines the role of succinate, a key metabolite produced and utilized by cells of both host and microbes, and its receptor, succinate receptor 1 (SUCNR1), in age-related oral dysbiosis and inflammation. We examined young and aged wild-type (WT) and SUCNR1 knockout (KO) mice for this analysis. Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice, along with notable changes in the oral microbiome. Conversely, aged KO mice showed reduced bone loss, lower succinate levels, less inflammation, and better-maintained microbial function. These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation, oral dysbiosis, and inflammation. Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice, with the functional potential being preserved in the KO-aged group. This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation, alveolar bone loss, and shifts in the oral microbiome, offering potential targets for therapeutic interventions in age-related oral health issues.
Animals ; Dysbiosis/metabolism* ; Mice ; Succinic Acid/metabolism* ; Mice, Knockout ; Receptors, G-Protein-Coupled/metabolism* ; Inflammation/metabolism* ; Aging ; Alveolar Bone Loss/metabolism* ; Mouth/microbiology* ; Mice, Inbred C57BL ; Male ; Microbiota

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective Explore the correlation among difference of skin temperature(ΔT)between proximal and distal ends,peripheral serum indicators and cardiac function,to screen the influencing factors of the main syndrome of"reverse coldness of limbs"in Sini decoction.Methods The clinical data of 134 critically ill patients who visited the emergency department of the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2022 to September 2023 were collected,including echocardiographic indicators[ejection fraction(EF),anterior-posterior diameter of the aortic sinus,left atrial anterior-posterior diameter,right ventricle left-right diameter,right atrial left-right diameter,left ventricular diastolic end anterior-posterior diameter,interventricular septum thickness,left ventricular posterior wall thickness,left ventricular posterior wall movement amplitude,main pulmonary artery inner diameter,pulmonary artery valve flow velocity,aortic valve flow velocity,mitral valve flow velocity,pulmonary artery systolic pressure],blood routine[white blood cell count(WBC),red blood cell count(RBC),platelet count(PLT),hemoglobin(Hb)],myocardial markers[troponin(cTnI,cTnT),MB isoenzyme of creatine kinase(CK-MB),myoglobin(MYO),N-terminal pro-brain natriuretic peptide(NT-proBNP)],D-dimer,blood gas analysis[pH value,arterial oxygen partial pressure(PaO2),arterial partial pressure of carbon dioxide(PaCO2),lactic acid(Lac),arterial oxygen saturation(SaO2)],coagulation function indicators[prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),fibrinogen(Fib)],infection indicators[C-reactive protein(CRP),procalcitonin(PCT)],biochemical indicators[K+,Na+,Cl-,Ca2+,P3+,total protein(TP),albumin(Alb),aspartate aminotransferase(AST),creatine kinase(CK),α-hydroxybutyrate dehydrogenase(α-HBDH),lactate dehydrogenase(LDH),urea,creatinine(Cr),uric acid(UA)],mean arterial pressure(MAP),and the top 10 disease types.These data were used as independent variables,and the ΔT value was used as the dependent variable for univariate linear regression analysis.Variables with statistically significant differences in the univariate analysis were subjected to multivariate linear regression analysis to identify the influencing factors causing an increase in the ΔT value.Results The univariate analysis analysis showed that variables such as shock,MAP,WBC,MYO,Lac,PT,APTT,TT,CRP,K+,P3+,Alb,urea,Cr,right ventricular left-right diameter,left ventricular posterior wall motion amplitude,main pulmonary artery diameter,pulmonary artery valve velocity,and aortic valve velocity were all risk factors influencing the increase of ΔT between the left axilla and the left hand in critically ill patients(all P<0.05);shock,respiratory failure,MAP,WBC,cTNI,MYO,Lac,PT,APTT,TT,CRP,Ca2+,P3+,Alb,urea,Cr,right ventricular left-right diameter,interventricular septum motion amplitude,left ventricular posterior wall motion amplitude,and main pulmonary artery inner diameter were all risk factors influencing the increase of ΔT between the left axilla and the left foot in critically ill patients(all P<0.05).Multivariate linear regression analysis showed that APTT,Lac,right ventricular left and right diameters,and urea were independent risk factors for the increase of ΔT in the left axilla and left hand[95%confidence interval(95%CI)was 0.016-0.036,0.024-0.095,-0.031 to-0.003,0.002-0.029,respectively;P values were 0.000,0.001,0.015,0.028,respectively],while PT,right ventricular left and right diameters,interventricular septal motion amplitude,and MYO were independent risk factors for the increase of ΔT left axilla and left foot(95%CI was 0.023-0.178,-0.103 to-0.019,0.031-0.245,0.000-0.002,respectively;P values were 0.012,0.006,0.013,0.015,respectively).Conclusion APTT,PT,Lac,MYO,urea,the right ventricular diameter and interventricular septal motion amplitude are key factors affecting the ΔT value of critically ill patients,which can cause reverse coldness of limbs.

Objective:To investigate the operation opportunity for vascular rings in infants and assess the impact of prenatal and postnatal integrated management strategies on treatment outcomes.Methods:A retrospective analysis was conducted on the clinical data of 75 infants with vascular rings who underwent surgical treatment at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, 54 were males and 21 were females, with a median age at surgery of 1.7 (0.7-6.9) months and a median weight of 5.3 (3.5-8.0) kg. Vascular rings malformation was diagnosed by real-time three-dimensional color doppler echocardiography during pregnancy in 51 cases. Preoperatively, 28 cases presented with respiratory or digestive system-related symptoms, and 26 cases had a history of hospitalization due to related symptoms. All patients underwent preoperative cardiac CTA+ CTVE and three-dimensional reconstruction examinations, and 56 cases showed varying degrees of airway compression and stenosis on imaging. Among them, 10 patients presented with preoperative stridor and respiratory distress; fiberoptic bronchoscopy performed after anesthesia induction confirmed significant tracheal compression/stenosis. One patient was ventilator-dependent preoperatively, and bronchoscopy revealed main bronchomalacia. The cohort included: Complete vascular rings (62 cases of double aortic arch, 10 cases of right aortic arch with aberrant left subclavian artery and left-sided ductus arteriosus/ligamentum) and incomplete vascular rings (3 cases of pulmonary artery sling). Additionally, 5 cases had associated Kommerell’s diverticulum, and 12 had intracardiac malformation. All patients successfully completed surgery, and those with intracardiac malformation underwent extracorporeal circulation and primary radical surgery concurrently. Based on prenatal diagnosis and implementation of prenatal and postnatal integrated management, patients were divided into an observation group (prenatal and postnatal integrated management group) and a control group (postnatally diagnosed group). The perioperative data of the two groups were compared to analyze the surgical outcomes and the advantages of prenatal and postnatal integrated treatment.Results:All 75 patients successfully completed surgery. Preoperatively, 56 cases (74.66%) presented with varying degrees of tracheal stenosis. Except for 1 case that died after abandoning treatment and 1 case that underwent tracheal surgery due to repeated failed ventilator weaning, all other patients were successfully discharged from the hospital. The overall mortality rate was 1.33%, and the rate of tracheal surgery was 1.35%. The age and weight at surgery in the observation group were lower than those in the control group ( P<0.05), and the proportion of preoperative hospitalization history was lower in the observation group ( P<0.05). No significant differences were observed between the two groups in terms of tracheal compression and stenosis, postoperative monitoring time, operation time, ventilator time, and risk of postoperative complications ( P>0.05). Conclusion:Tracheal stenosis is a common complication in children with vascular rings. Early surgical intervention is recommended for complete vascular rings and pulmonary artery slings (as an incomplete ring). Timely prenatal diagnosis of vascular ring anomalies combined with the implementation of an integrated prenatal-postnatal management strategy can significantly reduce the risk of preoperative hospitalization due to related symptoms and may lower the risk of subsequent tracheal surgery, potentially improving long-term prognosis.

The development of 5G remote robot-assisted gastrointestinal surgery is an important breakthrough in remote surgery in the field of four-level surgery. This paper will review the development history of 5G remote robot assisted gastrointestinal surgery, and share the Gansu province people′s hospital in 5G remote robot assisted gastrointestinal surgery about preoperative preparation, network and equipment connection,“3+2” Trocar layout, safety emergency treatment mechanism of exploratory experience, for 5G remote robot assisted gastrointestinal surgery, and the status and prospect of 5G remote robot assisted gastrointestinal surgery.

ObjectiveTo identify the active components in Maimendong decoction (MMDD) against pulmonary fibrosis (PF) and validate their molecular effects in vitro, while focusing on the role of methylophiopogonanone B in regulating fibrosis.MethodsData on MMDD components and targets were gathered from databases including BATMAN-TCM and PubMed, whereas the PF gene data were sourced from GeneCards, OMIM, and TTD. Shared targets were determined using the STRING database, and molecular docking was used to analyze the essential molecules associated with fibrosis. To simulate PF conditions, human embryonic lung fibroblasts (HPF) and A549 cells were exposed to transforming growth factor-β1 (TGF-β1). Various assays were used to determine the effects of MMDD and methylophiopogonanone B on signaling pathways, apoptosis, and epithelial–mesenchymal transition.ResultsWe identified 11 active components from MMDD extracts that targeted 511 shared proteins associated with PF, revealing 10 key targets in network analysis. Gene ontology analysis indicated that processes and pathways such as apoptosis regulation and PI3K/Akt signaling were involved. In vitro experiments revealed that MMDD downregulated the expression of α-smooth muscle actin (α-SMA), collagen type I (COL-I), and collagen type III and regulated Bcl-2/Bax signaling pathways to promote apoptosis. The flow cytometry apoptosis assay revealed that MMDD promoted the TGF-β1-induced apoptosis of myofibroblasts. The primary active ingredient in MMDD, methylophiopogonanone B, reduced α-SMA, COL-I, and PI3K/Akt/mTOR-related protein levels in TGF-β1-treated HPF cells, decreased Bcl-2 and cleaved caspase 3, and increased Bax. Moreover, methylophiopogonanone B increased E-cadherin levels and reduced α-SMA, fibronectin, N-cadherin, vimentin, and snail in TGF-β1-treated A549 cells.ConclusionMethylophiopogonanone B demonstrated the potential to treat PF by inducing myofibroblast apoptosis and inhibiting EMT. However, despite encouraging initial results, further clinical research is warranted to verify the safety and efficacy of methylophiopogonanone B in the management of PF