ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Ischemic stroke accounts for approximately 80% of all stroke cases worldwide and remains a leading cause of long‑term neurological disability and mortality. Intravenous thrombolysis and endovascular thrombectomy constitute the mainstay of acute reperfusion therapies, yet their clinical utility is severely constrained by narrow therapeutic time windows. Even when large‑vessel recanalization is successfully achieved, a considerable proportion of patients still suffer poor functional outcomes due to futile reperfusion and ischemia‑reperfusion injury. Historically, preclinical studies have largely focused on direct neuronal protection against calcium overload, oxidative stress and ferroptosis. Unfortunately, most promising neuroprotective agents that exhibited robust benefits in rodent models have failed to demonstrate satisfactory efficacy in phase‑Ⅱ and phase‑Ⅲ clinical trials. One critical contributor to such translational failure is the disregard for the pathological disturbance within the cerebral vascular microenvironment. Instead of merely regarding neuronal death as an autonomous cellular event, accumulating evidence indicates that sequential biochemical disruption of perivascular microenvironment acts as an initiating amplifier that propagates damage toward brain parenchyma after ischemic insult. The cerebral vascular microenvironment centers on brain microvessels and comprises endothelial cells, endothelial glycocalyx, basement membrane, pericytes, astrocytic end‑feet, perivascular microglia, as well as interstitial ions, inflammatory mediators, reactive oxygen species and extracellular matrix components. Distinct from the concept of neurovascular unit which emphasizes functional coupling between neurons, glia and vessels, the vascular microenvironment highlights dynamic biochemical homeostasis in perivascular interstitial space. Following cerebral ischemia, injured brain tissue can be spatially divided into the irreversibly damaged infarct core, metabolically‑stressed ischemic penumbra and mildly‑affected peripheral regions. These three zones lack rigid anatomical boundaries and evolve dynamically depending on reperfusion timing, presenting divergent features in blood perfusion, blood‑brain barrier integrity, cellular viability and immune‑inflammatory profiles. Four interrelated pathological cascades jointly disrupt microenvironmental homeostasis: calcium‑overload‑triggered cytotoxic cascades; blood‑brain barrier breakdown resulting from glycocalyx shedding, tight‑junction dissociation and matrix metalloproteinase‑driven basement‑membrane degradation; inflammatory‑immune dysregulation dominated by microglial phenotypic reprogramming; and mutual crosstalk between coagulation disturbance and neuroinflammation that exacerbates secondary brain injury. Multiple molecular layers orchestrate these pathological alterations. Excessive activation of HIF‑1α, NF‑κB and MAPK/ERK signaling pathways promotes barrier leakage, pro‑inflammatory factor secretion and extracellular‑matrix remodeling. Epigenetic modulation mediated by non‑coding RNAs including miRNAs and lncRNAs reshapes vascular microenvironment via three major patterns: modulating endothelial‑pericyte barrier integrity, switching microglia‑astrocyte inflammatory phenotypes, and driving metabolic reprogramming among multiple cell populations within microdomains. In addition, metabolic shift toward glycolysis among endothelial cells, microglia, astrocytes and compromised neurons establishes self‑amplifying vicious cycles of energy depletion and oxidative stress in perivascular niches. Targeted theranostic approaches oriented toward vascular microenvironment bring new opportunities for precision medicine of ischemic stroke. Magnetic nanoprobes and near‑infrared fluorescent probes respond to elevated reactive oxygen species, pH shift and inflammatory signals, enabling in situ visualization of pathological signatures of microenvironment and risk evaluation of hemorrhagic transformation. Function‑tailored nanodelivery systems exert multi‑modal protective effects: reactive oxygen species‑responsive polymeric micelles deliver calcium chelators to block calcium‑overload‑initiated injury cascades; nanozymes scavenge reactive oxygen/nitrogen species and revert microglial pro‑inflammatory polarization; biomimetic membrane‑coated nanoparticles accumulate at micro‑thrombosis sites to break thrombo‑inflammatory loops and mitigate no‑reflow phenomenon; ferroptosis‑inhibitor‑loaded nanocarriers eliminate excessive labile iron within perivascular toxic microdomains. During subacute and recovery phases, spatiotemporally controlled release of angiogenic factors by nanocarriers facilitates maturation of newly‑formed microvessels rather than blind vascular sprouting, which helps reconstruct intact blood‑brain barrier and restore microenvironmental homeostasis. Nevertheless, substantial translational bottlenecks still impede clinical transformation of these nanomedicines, including potential biosafety risks caused by in vivo material accumulation, protein‑corona‑induced impairment of targeting capacity, intrinsic blood brain barrier transport obstacles, lack of unified quality‑control criteria for large‑scale manufacture, reliance on high‑end clinical imaging instruments, and prominent interspecies discrepancies between experimental animals and human patients. On the basis of summarizing spatiotemporal pathological characteristics, multi‑level regulatory mechanisms and cutting‑edge microenvironment‑oriented diagnostic and interventional strategies, the present review advocates a conceptual shift from isolated neuronal protection to comprehensive reconstruction of perivascular vascular microenvironment homeostasis. Such perspective provides theoretical foundations for expanding therapeutic time windows and inspires future development of novel therapeutic modalities for ischemic stroke.

Objective: To investigate the role of murine double minute 2(MDM2) in dihydroartemisinin′s(DHA) inhibition of lung adenocarcinoma cell proliferation and migration. Methods: CCK8 assay was used to detect the inhibitory effect of gradient concentrations of DHA(0, 5, 10, 25, 50 and 100 μmol/L) and time gradients(0, 24, 48, and 72 h) on the proliferation of lung adenocarcinoma A549 and PC9 cells, and the half maximal inhibitory concentrate(IC50) were calculated respectively. Colony formation and scratch assays were used to detect the inhibitory effects of DHA on colony formation and migration of A549 and PC9 cells. Western blot was used to detect the inhibitory effects of DHA on MDM2 expression and epithelial-mesenchymal transition(EMT)-related proteins E-cadherin and N-cadherin. The promoting effects of MDM2 on proliferation, migration and EMT of lung adenocarcinoma cells were verified by small interfering RNA-mediated knockdown of MDM2(si-MDM2). The reversal effects of MDM2 overexpression on DHA′s inhibition on the proliferation and migration of A549 and PC9 cells were observed. Results: DHA inhibited the proliferation of A549 and PC9 cells in a dose⁃ and time⁃dependent manner,with IC50 values of 30. 57 and 78. 61 μmol/L , respectively. Compared with the Control group , A549 and PC9 cells had significantly decreased colony formation (both P < 0. 01) and migration (both P < 0. 01) upon treatment with DHA. Moreover, DHA significantly inhibited the protein expression levels of MDM2 and N ⁃cadherin in A549 and PC9 cells , and upregulated the expression of E ⁃cadherin protein (both P < 0. 05) . Compared with si⁃Control ,si⁃MDM2 significantly inhibited the protein levels of MDM2 and N ⁃cadherin in A549 and PC9 cells , and upregulat⁃(both P < 0. 01) of both cells. After overexpression of MDM2 in A549 and PC9 cells , the proliferation and migra⁃ tion ability were significantly enhanced (both P < 0. 05) , and the inhibitory effects of DHA were partially reversed by MDM2 overexpression (both P < 0. 05) . Conclusion DHA effectively inhibits the proliferation and migration of lung adenocarcinoma cells , and its mechanism is associated with the suppression of MDM2.

Objective To explore the rehabilitative effects of flash cupping combined with respiratory training in patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis"). Methods A total of 94 patients with pneumoconiosis were selected as the study subjects by the convenient sampling method. Participants were divided into treatment group and control group based on pneumoconiosis stage using the stratified block randomization method, with 47 cases in each group. The patients in the control group received routine symptomatic treatment, and the patients in the treatment group received flash cupping therapy combined with respiratory training in addition to the routine treatment for six weeks. Diaphragmatic displacement (DD), 6-minutes walking distance (6MWD), metabolic equivalents of task (MET), predicted percentage of forced vital capacity (FVC%), predicted percentage of forced expiratory volume in one second (FEV₁%), Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score, and the modified British Medical Research Council Respiratory Questionnaire (mMRC) were assessed before treatment, after six weeks of treatment, and three months after completion of treatment. Results Before treatment, no significant differences were observed in patients between the two groups in DD, 6MWD, MET, FVC%, FEV₁%, CAT score, or mMRC grade (all P>0.05). DD, 6MWD, and MET of patients in the treatment group were higher than those before treatment in the same group and those of the control group at the corresponding time points after six weeks of treatment (all P<0.05). In addition, the CAT score of patients in the treatment group was lower than that before treatment (P<0.05). At three months after treatment, 6MWD and MET of patients in the treatment group were higher than those before treatment and those of the control group at the same time points (all P<0.05). There were no significant differences in FVC%, FEV₁% and mMRC grade of patients between the two groups (all P>0.05). Conclusion Flash cupping combined with respiratory training can improve the diaphragmatic function, exercise endurance and quality of life of patients with pneumoconiosis, and has improved exercise endurance, which can be used as a useful supplementary treatment in the pulmonary rehabilitation of pneumoconiosis.

Objective:To explore the effect of Sugammadex sodium on muscle relaxant recovery and coagulation function after modified radical mastectomy for breast cancer.Methods:A total of 110 patients who underwent modified radical mastectomy in Shanxi Cancer Hospital from May. 2022 to May. 2024 were chosen and separated into two groups according to random number table method, with 55 cases in each group, receiving the same anesthesia scheme. Muscle relaxant was monitored by train-of-four stimulation (TOF) . After surgery, when the TOF count was ≥2, the study group was given Sugammadex sodium, and the control group was given neostigmine + atropine. Operation-related indexes and adverse reactions were recorded; The muscle relaxant residue was analyzed at 5, 15 and 30min after injection of muscle relaxant antagonists; Blood clot formation time (K value) , blood clot formation rate (Angle) , maximum blood clot intensity (MA value) and blood clot reaction time (R value) of the two groups were compared before (T1) and 5min (T2) , 15min (T3) and 30min (T4) after injection.Results:The extubation time and the first extubation time in the study group were shorter [ (4.10±1.05) min, (22.95±2.24) h vs. (13.28±2.96) min, (29.83±3.06) h] ( t=21.68, 13.46, all P < 0.05) . The muscle relaxation residual rates in the study group at 5min and 15min were lower [12.73% (7/55) , 0.00% (0/55) vs. 100.00% (55/55) , 63.64% (35/55) ] ( χ2=85.16, 51.33, P < 0.05) . There were no differences in K value, Angle value, MA value and R value between the two groups at T1, T2, T3 and T4 ( t K=0.17, 0.44, 0.14, 0.13, t Angle=0.93, 1.29, 1.04, 1.00, t MA=1.17, 1.72, 0.87, 1.03, t R=0.36, 0.08, 0.09, 0.37, all P > 0.05) . The incidence rates of postoperative nausea, vomiting and respiratory depression in the study group were lower [5.45% (3/55) , 7.27% (4/55) , 0.00% (0/55) vs. 18.18% (10/55) , 21.82% (12/55) , 10.91% (6/55) ] ( χ2/ Fisher=4.27, 4.68, -, all P < 0.05) . Conclusion:Sugammadex sodium can promote the recovery of muscle relaxant in patients after modified radical mastectomy for breast cancer, and has little effect on coagulation function, which can reduce the occurrence of postoperative adverse reactions.

Objective:To study the effects of remimazolam on stress response index, T lymphocyte subsets and postoperative delirium in patients undergoing modified radical mastectomy.Methods:A total of 120 patients with breast cancer who underwent modified radical mastectomy in our hospital from Aug. 2024 to Dec. 2024 were separated into the control group (n=60, anesthetic induction and maintenance with Propofol) and the observation group (n=60, anesthetic induction and maintenance with remimazolam) according to random number table method, and the other anesthetic drugs were the same. The operation time, anesthesia recovery time, postoperative delirium and cognitive dysfunction of the two groups were observed, and the changes of stress response indexes and T lymphocyte subsets indexes at different time points were compared, and the adverse reactions after anesthesia were counted.Results:The incidence of postoperative delirium and cognitive dysfunction in the observation group was lower than that in the control group ( x2=4.62, 5.18, P < 0.05), and there was no statistically significant difference in operation time or anesthesia recovery time between the two groups ( t=0.43, 1.71, P > 0.05). The observation group had lower serum cortisol (Cor), norepinephrine (NE) and epinephrine (E) levels 30 min after anesthesia induction (T 1) and immediately after surgery (T 2) ( t=5.53, 6.71, 9.33, 6.74, 7.26, 8.77, P < 0.05), while the comparison of those indexes before surgery (T 0) and 12 h after surgery (T 3) showed no statistically significant difference ( t=1.19, 1.85, 0.90, 1.55, 1.64, 1.81, P > 0.05). The levels of CD3 +T, CD4 +T and CD4 +/CD8 + in the observation group were higher than those in the control group at T 1, T 2 and T 3 ( t=2.21, 4.94, 4.77, 4.44, 6.24, 7.07, 2.11, 2.56, 2.15, P < 0.05), and there was no statistically significant difference in those indexes between the two groups at T 0 ( t=0.76, 0.79, 1.51, P > 0.05). The incidence of adverse reactions after anesthesia showed no statistically significant difference between the two groups [25.00% (15/60) and 33.33% (20/60) ] ( χ2=1.008, P > 0.05) . Conclusion:The induction and maintenance of remimazolam anesthesia can effectively reduce the incidence of postoperative delirium and cognitive dysfunction in patients with modified radical mastectomy, relieve the body stress response of patients, and effectively reduce the influence of anesthesia on T lymphocytes.

Objectives:To explore the feasibility of zero-ray radiofrequency catheter ablation for paroxymal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.Methods:This is a single-center prospective observational study.A total of 12 patients with paroxysmal atrial fibrillation who underwent radiofrequency catheter ablation in Fuwai Hospital,Chinese Academy of Medical Sciences from June 1,2024 to September 30,2024 were included.All patients underwent successful percutaneous puncture,atrial septal puncture under the guidance of transthoracic echocardiography,and all patients underwent left atrial modeling and discharge ablation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.The disappearance of pulmonary vein potential was confirmed after the ablation operation and as the ablation endpoint and successful ablation marker.The operation results and 1-month and 3-month follow-up results of the patients were observed.Results:There were 12 patients with paroxysmal atrial fibrillation,9 males and 3 females,aged(56.8±11.2)years,with a history of paroxysmal atrial fibrillation(4.2±2.3)years.The mean left atrial diameter was(36.5±2.5)mm,the left ventricular end-diastolic diameter was(47.8±4.1)mm,and the left ventricular ejection fraction was 55%-65%.The mean overall operation time was(102.25±14.51)min,the ultrasound operation time was(29.58±6.23)min,and the catheter operation time was(33.08±4.10)min.All patients completed circumferential pulmonary vein isolation without intraoperative complications.The hospitalization time was 2-6 days.At the 1-month follow-up after ablation,all patients showed sinus rhythm on 24-hour ambulatory electrocardiogram,and 2 patients had occasional atrial premature contractions without recurrence of atrial fibrillation.At the 3-month follow-up,two patients had occasional premature atrial contractions,and no recurrence of atrial fibrillation was recorded on the electrocardiogram of all patients.Conclusions:It is feasible to complete radiofrequency catheter ablation of paroxysmal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.

Historically,with the decentralisation of county-level medical service price management,inconsistencies in large urban county medical service prices have arisen,facing a serious challenge to the allocation of regional medical resources and the fairness of patients' access to healthcare.There is therefore an urgent need to integrate and standardise county medical service prices.It provides a comprehensive overview of the integration process of county medical service prices in Zhengzhou,focusing on the establishment of integration principles,the determination of programme parameters,the initial integration phase,and the refinement of measurement mechanisms.It also puts forward a series of recommendations and strategies for enhancement,including the further rationalisation of the ratio-price relationship among items,the gradual promotion of price adjustment,and the establishment of a continuous dynamic monitoring mechanism.It also puts forward suggestions and strategies for improvement in terms of further rationalising the price relationship between items and gradually promoting price adjustment,and establishing a continuous dynamic monitoring mechanism.

Objective To investigate the changes of serum cathepsin L(CTSL)in patients with acute exacerbation of chronic heart failure(CHF)and its relationship with lipid metabolism and severity of the disease.Methods A prospective study was conducted on 186 elderly patients with acute exacerbation of CHF admitted to our hospital from February 2021 to October 2024.Their serum levels of CTSL and lipid metabolism indicators were measured at admission.According to the quartile of CTSL,they were divided into groups A(CTSL≤3.31 μg/L,47 cases),B(3.31μg/L＜CTSL≤3.70 μg/L,46 cases),C(3.70 μg/L＜CTSL＜4.41 μg/L,47 cases),and D(CTSL≥4.41 μg/L,46 cases).The general clinical data,blood lipid metabolism and severity of disease were compared among the four groups.Pearson correlation analysis was used to analyze the correlation between CTSL and blood lipid metabolism indicators,and ordinal regression model and restricted cubic spline analysis was employed to examine the relationship between serum CTSL and the se-verity of acute exacerbation of CHF.Results There were significant differences in total cholester-ol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipopro-tein cholesterol(LDL-C)among the four groups of patients(P＜0.05,P＜0.01).Pearson correla-tion analysis showed that serum CTSL level was positively correlated with TC,TG and LDL-C levels(r=0.203,P=0.005;r=0.178,P=0.015;r=0.184,P=0.012),and negatively with HDLC(r=—0.344,P=0.000).Ordinal regression analysis indicated that serum CTSL level was an inde-pendent risk factor affecting the severity of CHF in patients with acute exacerbation(P＜0.05).Restricted cubic spline analysis revealed that serum CTSL level was in a linear relationship with the severity of acute exacerbation of CHF(x2=3.140,P=0.371).When serum CTSL＞3.73μg/L,the severity of the condition was increased significantly.Conclusion Serum CTSL level is closely associated with lipid metabolism in elderly patients with acute exacerbation of CHF,and is an independent risk factor for the severity of disease.

AIM To prepare the borneol-menthol eutectic mixture-loaded nanoemulsion gel of tetramethylpyrazine.METHODS The equilibrium solubilities of tetramethylpyrazine in different oil phases,emulsifiers and co-emulsifiers were determined,after which compatibility experiment was performed,and pseudo-ternary phase diagram was drawn.With Km value,oil phase proportion and water phase consumption as influencing factors,particle size,PDI and saturated drug loading as evaluation indices,the formulation was optimized by central composite design-response surface method.The drug-loaded nanoemulsion was dispersed into carbomer 940 gel matrix to prepare nanoemulsion gel,then the physicochemical properties,in vitro drug release and transdermal absorption properties were investigated.RESULTS The optimal formulation was determined to be 3.31∶6.16∶1.56∶88.97 for eutectic mixture-EL-40-1,2-propylene glycol-water ratio,the particle size,PDI and saturated drug loading were 37.85 nm,23.04 and 5.82 mg/g,respectively.The obtained white,semi-solid nanoemulsion gel demonstrated the average pH value and viscosity of 6.68±0.07 and(289.69±1.06)mPa·s,respectively,whose in vitro drug release accorded with Higuchi equation,and the accumulative permeability per unit area was(2 048.23±55.6)μg/cm2 within 24 h,which were 3.72 and 1.21 times higher than those of hydrogel and aqueous solution,respectively.CONCLUSION The borneol-menthol eutectic mixture-loaded nanoemulsion gel of tetramethylpyrazine meets preparation requirements,thus can achieve the effective transdermal delivery of raw medicine.