ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Repeated transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation techniques. In order to investigate the effects of rTMS on the excitability of different types of neurons, this study is conducted to investigate the effects of rTMS on the cognitive function of mice and the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons from the perspective of electrophysiology. In this study, mice were randomly divided into glutaminergic control group, glutaminergic magnetic stimulation group, gamma-aminobutyric acid energy control group, and gamma-aminobutyric acid magnetic stimulation group. The four groups of mice were injected with adeno-associated virus to label two types of neurons and were implanted optical fiber. The stimulation groups received 14 days of stimulation and the control groups received 14 days of pseudo-stimulation. The fluorescence intensity of calcium ions in mice was recorded by optical fiber system. Behavioral experiments were conducted to explore the changes of cognitive function in mice. The patch-clamp system was used to detect the changes of neuronal action potential characteristics. The results showed that rTMS significantly improved the cognitive function of mice, increased the amplitude of calcium fluorescence of glutamergic neurons and gamma-aminobutyric neurons in the hippocampus, and enhanced the action potential related indexes of glutamergic neurons and gamma-aminobutyric neurons. The results suggest that rTMS can improve the cognitive ability of mice by enhancing the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons.
Animals ; Mice ; Hippocampus/cytology* ; Transcranial Magnetic Stimulation ; Neurons/physiology* ; Male ; Cognition/physiology* ; gamma-Aminobutyric Acid/metabolism* ; Action Potentials/physiology*

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the effect of donor blood lipid levels and the degree of fat deposition on the pancreatic surface on the outcome of islet isolation.Method:A retrospective analysis was conducted on 171 cases of islet isolation data from organ donors between May 2015 and December 2024. According to the percentage of fat deposition area on the surface of the pancreatic capsule after trimming, the samples were divided into three groups: mild surface fat group (<30%, 60 cases) , moderate surface fat group (30%–70%, 55 cases) , and severe surface fat group (>70%, 56 cases). The modified Ricordi method was used to digest pancreatic tissue, and islets were purified by continuous density gradient centrifugation. The digestion efficiency, digestion time, islet yield (islet equivalent/quantity) , purity, score, and size were analyzed and compared among groups. One-way ANOVA was used for inter-group comparisons, and Pearson correlation analysis and multiple linear regression analysis were used to explore the relationship between blood lipid levels and islet isolation parameters.Result:The severe surface fat group had significantly higher pre-purification and post-purification islet equivalents, islet number, amount of digested pancreatic tissue, donor triglyceride levels, and low density lipoprotein (LDL) levels than the other groups (all P<0. 05) . Correlation analysis showed that LDL level was positively correlated with pre-purification islet equivalents (62 cases, r=0. 298, P=0. 019) and islet number (58 cases, r=0. 285, P=0. 030) . Donor high density lipoprotein (HDL) level was negatively correlated with post-purification islet equivalents (54 cases, r= – 0. 282, P=0. 039) ; donor triglyceride level was positively correlated with the amount of digested tissue (56 cases, r=0. 268, P=0. 046) and negatively correlated with purity (51 cases, r= - 0. 297, P=0. 035) ; donor very low density lipoprotein (VLDL) level was positively correlated with the amount of digested tissue (67 cases, r=0. 337, P=0. 005) and negatively correlated with purity (61 cases, r=- 0. 348 , P=0. 006) ; donor total cholesterol level was negatively correlated with pancreatic digestion efficiency (34 cases, r= - 0. 370, P=0. 032) , and the above differences were all statistically significant. Conclusion:Pancreata with heavier surface fat deposition can yield a higher number of islets. Meanwhile, donor blood lipid levels are correlated with islet isolation outcomes and can serve as important indicators for donor pancreas selection.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.

Objective To explore the short-term prognosis and risk factors for in-hospital mortality in patients with fulminant myocarditis induced refractory cardiogenic shock(FM-RCS)receiving veno-arterial extracorporeal membrane oxygenation(VA-ECMO)treatment,and to construct an early prognosis prediction model using relevant indicators.Methods A total of 61 FM-RCS patients treatment by VA-ECMO in the department of intensive care unit of the Second Affiliated Hospital of Zhengzhou University from January 2017 to February 2024,excluding 15 cases with age less than 18 years and 3 cases with ECMO treatment duration less than 24 hours,a total of 43 patients were finally included.Participants were stratified into survival(n=19)and mortality(n=24)groups according to discharge outcomes.Demographic data,chronic disease history,early laboratory indicators,left ventricular function indicators,and basic reference values of hemodynamics were systematically compared between the two groups.Variable selection was performed using LASSO regression,followed by multivariate COX regression analysis to screen independent risk factors for in-hospital mortality in ECMO-treatment FM-RCS patients.A nomogram prediction model was subsequently developed using R software and validated through calibration curves,concordance index(C-index),and receiver operator characteristic curve(ROC curve)analysis.Results The overall survival rate of the 43 enrolled patients was 44.2%,with 19 cases in the survival group and 24 cases in the mortality group.In early laboratory indicators,the survival group exhibited significantly lower levels of initial lactic acid(Lac),24-hour Lac(Lac 24 h),24-hour MB isoenzyme of creatine kinase(CK-MB 24 h),24-hour cardiac troponin T(cTnT 24 h),24-hour total bilirubin(TBil 24 h),24-hour serum creatinine(SCr 24 h),and lactate albumin ratio(LAR)compared to the mortality group[initial Lac(mmol/L):2.7(1.3,7.6)vs.9.2(5.9,14.0),Lac 24 h(mmol/L):2.4(2.0,3.6)vs.5.4(3.3,9.2),CK-MB 24 h(U/L):58.0(28.0,115.0)vs.167.7(68.5,280.3),cTnT 24 h(μg/L):0.53(0.37,2.41)vs.3.92(3.10,8.86),TBil 24h(μmol/L):18.3(9.9,37.8)vs.40.2(24.6,67.0),SCr 24 h(μmol/L):90.63±42.49 vs.177.76±70.76,LAR:0.09(0.04,0.23)vs.0.31(0.20,0.38),all P<0.05],serum albumin(Alb)levels were significantly higher in the survival group[g/L:36.0(31.9,39.2)vs.31.7(26.4,34.4),P<0.05].The mortality group had a higher incidence of malignant arrhythmias[66.7%(16/24)vs.31.6%(6/19),P<0.05].The LASSO regression model identified four non-zero coefficient variables-Lac 24 h,CK-MB 24 h,cTnT 24 h,and SCr 24 h-which were included in the subsequent multivariate COX regression analysis.The results demonstrated that Lac 24 h[hazard ratio(HR)and 95%confidence interval(95%CI)was 1.186(1.074-1.310),P<0.001]and cTnT 24 h(HR=1.230,95%CIwas 1.078-1.404,P=0.002)were independent risk factors for in-hospital mortality in VA-ECMO treatment FM-RCS patients.A predictive model constructed using these two indicators showed a C-index of 0.812,area under the curve(AUC)=0.941,with 91.7%sensitivity and 94.7%specificity.Furthermore,compared to the survival group,the mortality group exhibited significantly higher incidences of acute kidney injury[91.7%(22/24)vs.36.8%(7/19)]and hypoxic-ischemic encephalopathy[62.5%(15/24)vs.10.5%(2/19),both P<0.05].The mortality group also required greater transfusion volumes[mL:3 800(1 420,8 515)vs.1 200(400,3 020),P<0.05],but had shorter total hospitalization durations[days:7(3,13)vs.23(20,44),P<0.05].Conclusion For FM-RCS patients receiving VA-ECMO treatment,Lac 24 h and cTnT 24 h after ECMO initiation are independent predictors of in-hospital mortality.Clinicians should be vigilant about poor prognosis in FM-RCS patients with high Lac 24 h hours(>2.5 mmol/L)and cTnT 24 hours(>3.01 μg/L)after ECMO treatment.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:With the aging of the population and the increase of medical treatment in different places,chaperone services are gradually emerging,but there are problems such as insufficient training of patient navigators and lack of rules and regulations in the industry.It is necessary to strengthen supervision and standardized management to improve service quality.To explore the current situation and risks of the chaperone service industry from the perspective of patient navigators and doctors,and to provide suggestions for policy formulation.Methods:The Theory of Planned Behavior(TPB)and Knowledge-Attitude-Practice(KAP)models were developed to outline the interview.A total of 22 doctors and patient navigators were selected from 5 large Grade Three hospitals and 20 online consultation platforms in Shanghai for semi-structured interviews.The data were analyzed using"7 Steps of Data Analysis in Colaizzi Phenomenology Research".Results:The chaperone service industry faces risks such as lack of professional norms,vague definition of legal responsibilities,insufficient professional competence among practitioners,and regulatory gaps.Conclusions:We should further establish a unified industry standard and certification system,strengthen the training of patient navigators,improve the supervision of online platforms,and effectively protect the rights and interests of doctors,so as to better promote the development of the industry and provide quality services for patients and doctors.