Panvascular diseases represent systemic vascular disorders characterized by atherosclerosis as their core pathological feature. Their incidence rates continue to rise， posing significant challenges for clinical management. Based on Traditional Chinese Medicine （TCM） theory of ''positive deficiency phlegm stasis''， this study delved into the pivotal role of mitochondrial homeostasis dysregulation in the pathogenesis and progression of pan-vascular diseases， along with its intrinsic connection to TCM pathogenesis. Mitochondrial homeostasis dysregulation pervades the entire course of these diseases， with mitochondrial oxidative stress serving as the initiating factor. Excessive reactive oxygen species （ROS） trigger endothelial dysfunction， lipid accumulation， and inflammatory initiation. Additionally， the imbalance between mitochondrial autophagy and apoptosis constitutes a pivotal link in disease progression. Excessive or insufficient autophagy may lead to the accumulation of damaged mitochondria and excessive cellular apoptosis， thereby promoting plaque instability. Furthermore， mitochondrial metabolic reprogramming impairs energy supply and function in vascular wall cells， hindering subsequent vascular repair. These pathological processes constitute the microscopic manifestation of the core pathogenesis， which is characterized by ''the intermingle of phlegm and stasis and the deficiency of healthy Qi''. Specifically， the endogenous phlegm-turbidity drives mitochondrial oxidative stress injuries， the mutual entanglement of phlegm and stasis induces an imbalance between mitochondrial autophagy and apoptosis， while deficiency of healthy Qi propels mitochondrial energy metabolism disorders and reprogramming. In view of this， this study proposed to employ phlegm-resolving and turbidity-clearing methods to mitigate mitochondrial oxidative stress injuries， phlegm-resolving and blood-activating methods to regulate mitochondrial autophagy and apoptosis， and spleen-tonifying and kidney-nourishing methods to modulate mitochondrial metabolic reprogramming. This approach can prevent and treat panvascular diseases by multi-target regulation of mitochondrial homeostasis， providing a theoretical framework and therapeutic strategies for the prevention and treatment of panvascular diseases through integrated Chinese and Western medicine.

OBJECTIVE To compare the efficacy and safety of vedolizumab （VDZ） versus infliximab （IFX） in biologic-naive（Bio-naive） patients with moderate-to-severe active ulcerative colitis （UC）， and to analyze the factors influencing efficacy. METHODS Clinical data were retrospectively collected from Bio-naive patients with moderate-to-severe active UC who received treatment in the Department of Gastroenterology at Shanxi Provincial People’s Hospital from June 2023 to June 2024. Based on the type of biologic agent administered， the patients were divided into the IFX group （41 cases） and the VDZ group （30 cases）. Patients in the two groups received IFX （5 mg/kg） or VDZ （300 mg） for induction and maintenance of remission therapy. The two groups were compared regarding modified Mayo score， serological indicators （hemoglobin， albumin， platelet count， erythrocyte sedimentation rate， C-reactive protein）， combined medication， efficacy-related indexes （clinical response rate/remission rate， and endoscopic response rate/remission rate）， and the occurrence of adverse drug reactions （ADR）. Based on Logistic regression model， univariate and multivariate analyses were conducted to identify potential factors influencing clinical remission at week 14 and endoscopic remission at week 38. RESULTS There were no statistically significant differences in clinical response rate/remission rate， or endoscopic response rate/remission rate between the two groups at weeks 14 and 38 （ P ＞0.05）. However， at week 14 of treatment， the proportion of patients using concomitant corticosteroids in VDZ group was 26.67%， significantly higher than the 7.50% in IFX group （ P ＜0.05）. There was no statistical significance in the overall incidence of ADR between the two groups （ P ＞0.05）； all ADRs in the IFX group were grade 3 and led to treatment discontinuation （6 cases）， whereas ADR in the VDZ group was grade 2 and did not interrupt therapy （1 case）. Univariate and multivariate regression analyses revealed that disease type （relapsing） was significantly associated with clinical remission at week 14 of treatment， and a history of smoking was significantly associated with endoscopic remission at week 38 of treatment （the odds ratios were 0.08 for both， with 95% confidence intervals of 0.01-0.77 and 0.01-0.91 respectively， P ＜0.05）. CONCLUSIONS For Bio-naive patients with moderate-to-severe active UC， VDZ and IFX demonstrate comparable efficacy in inducing and maintaining clinical remission and promoting mucosal healing， as well as overall safety. Although IFX can achieve faster control of inflammation in the early stage of the disease， it causes more severe ADR. Disease type （relapsing） and smoking history are identified as independent negative predictors for short-term clinical remission and long-term endoscopic remission， respectively.

ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules （QDYF） alleviate nasal mucosal remodeling in allergic rhinitis （AR） via the interleukin-33 （IL-33）/growth stimulation expressed gene 2 （ST2）/interleukin-1 receptor accessory protein （IL-1RAP） signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst， according to the previous network pharmacology results， this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways， components， and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently， a rat model of ovalbumin （OVA）-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups： Control， model， low-dose QDYF （QDYF-L， 4.04 g·kg^-1）， medium-dose QDYF （QDYF-M， 8.08 g·kg^-1）， high-dose QDYF （QDYF-H， 16.16 g·kg^-1）， and loratadine （0.9 mg·kg^-1）. After 14 days of intervention， behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin （HE） staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction （CVF）. The expression of E-cadherin （E-cad） in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 （Th2） cytokines interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） as well as helper T cell 1 （Th1） cytokines interleukin-2 （IL-2） and interferon-γ （INF-γ） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of transforming growth factor-beta 1 （TGF-β₁）， IL-33， ST2， and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33， ST2， and IL-1RAP had strong binding ability with the main active ingredients—wogonin， 7-methoxy-2-methylisoflavone， formononetin， naringenin， stigmasterol， and beta-sitosterol of QDYF， with the binding energy < -4.25 kcal⋅mol^-1（1 cal≈4.184 J）. The results of in vivo experiments showed that compared with the control group， the model group exhibited increased behavioral scores （P<0.05）， aggravated pathological damage of nasal mucosa， increased collagen fiber deposition and CVF （P<0.05）， elevated serum levels of IL-4， IL-5， and IL-13， up-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）， down-regulated expression of E-cad， and declined serum levels of IL-2， IFN-γ， and IFN-γ/IL-4 ratio （P<0.05）. Compared with the model group， the QDYF groups and loratadine group showed reduced behavioral scores （P<0.05）， alleviated pathological damage of nasal mucosa， reduced collagen fiber deposition and CVF （P<0.05）， and up-regulated E-cad expression （P<0.05）. Compared with the model group， the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio （P<0.05）， declined serum levels of IL-4， IL-5， and IL-13， and down-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）. In addition， the QDYF-H group exhibited an elevated serum IL-2 level （P<0.05）. The QDYF-M group showed down-regulated protein levels of TGF-β₁， IL-33 and IL-1RAP in the nasal mucosa （P<0.05）. The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa （P<0.05）. ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway， thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.

ObjectiveTo establish a mouse model of hypoxic pulmonary hypertension (HPH) through intermittent hypoxia induction, and to develop a comprehensive and reliable evaluation system for the HPH model, thereby providing experimental evidence for mechanistic studies and translational applications related to this disease. MethodsTwenty-four male specific pathogen-free (SPF) BALB/c mice were randomly divided into a control group and a model group, with 12 mice per group. Mice in the model group were placed in a hypobaric oxygen chamber control system to establish the HPH model, whereas mice in the control group received no intervention. After 28 days of modeling, a comprehensive evaluation of the pathophysiological characteristics of both groups was performed using a general condition scoring scale, echocardiography, hemodynamic measurements, blood gas analysis, hematological tests, organ coefficient determination, histopathological examination, and enzyme-linked immunosorbent assay (ELISA). In addition, correlation analyses were conducted among echocardiographic parameters, the contents of endothelin‑1 (ET‑1) and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) in lung tissue, and other measured indices. ResultsWith prolonged modeling duration time, body weight, water intake, and activity level of mice in the model group were significantly decreased compared with the control group (P<0.05). Echocardiography showed that, compared with the control group, the model group exhibited increased right ventricular dimensions (P<0.01), right ventricular anterior wall thickening (P<0.01), and widened main pulmonary artery diameter (P<0.01), whereas the peak systolic velocity across the pulmonary valve, tricuspid annular plane systolic excursion, and peak systolic velocity of the tricuspid annulus were significantly decreased (P<0.001); tricuspid regurgitation was observed in some model animals. Hemodynamic results revealed that right ventricular systolic pressure was elevated in the model group compared with the control group (P<0.001). Blood gas analysis showed that pH, partial pressure of oxygen, oxygen saturation, actual bicarbonate, and total carbon dioxide were all decreased in the model group compared with the control group (P<0.01). Hematological indices demonstrated that lymphocyte counts (P<0.05) and reticulocyte counts (P<0.001) were decreased in the model group compared with the control group. Compared with the control group, the organ coefficients of heart and lung in the model group were significantly increased (P<0.05 and P<0.001). Pathological examination revealed that the right ventricular hypertrophy index was significantly increased in the model group (P<0.001), with varying degrees of damage to the right ventricle, pulmonary artery, and pulmonary vessels; both the pulmonary artery wall thickness percentage and the pulmonary wall area percentage were significantly elevated (P<0.001). ELISA results showed that the levels of ET‑1 and NT‑proBNP in lung tissues were significantly increased in the model group compared with the control group (P<0.05 and P<0.001, respectively). Correlation analysis indicated that some echocardiographic parameters were highly correlated with multiple indices in the development of HPH (P<0.05). ConclusionEchocardiography can accurately assess a series of hemodynamic changes in HPH, including right ventricular structural, functional impairment, and pulmonary hypertension. Laboratory tests not only help verify whether the model has been successfully established, but also provide deeper insights into the pathogenesis of HPH, evaluate the effects of interventions, and offer scientific evidence for clinical outcomes. Pathological examination can further confirm the alterations in pulmonary vascular remodeling and increased right heart load. This multimodal analysis provides a reliable animal model and evaluation paradigm for both basic and translational research on HPH, and is of great significance for exploring disease mechanisms and developing precision therapeutic strategies.

ObjectiveTo meet the requirements of Good Laboratory Practice (GLP), Sichuan Institute for Drug Control (Sichuan Testing Center of Medical Devices, Sichuan Institute of Musk Deer Breeding) Safety Evaluation Center (hereinafter referred to as the center) conducts a targeted validation study to address the lack of supporting data for the specified validity periods of disinfectants, feed, and bedding during their use in laboratory animal facilities. The study summarizes practical experience in material management and provides a scientific basis for the standardized management of materials in the facility. MethodsUnder the routine operating conditions of the laboratory animal facility at the center, the disinfection efficacy of four commonly used disinfectants was confirmed using the quantitative suspension kill test, with the disinfectants tested on day 0, day 7, and at 1, 2, and 3 months after preparation and after opening; for laboratory animal feed, nutritional components, chemical contaminants, and microbial indicators were tested 7 days after opening; microbial indicators of laboratory animal corncob bedding were tested after storage for 7 days following opening and sterilization. ResultsUnder the GLP management system of our center, the disinfection efficacy log reduction values of prepared 0.04% sodium hypochlorite solution, 0.1% didecyldimethylammonium bromide solution, and 0.2% benzalkonium bromide solution were all ≥5 on days 0 and 7. The log reduction values of opened 75% ethanol were ≥5 on days 0 and 7 and at 1, 2, and 3 months after opening. All disinfectants were therefore qualified and effective. Compared with the factory inspection data, the nutritional components, chemical contaminants, and microbial indicators of SPF-grade rat and mouse maintenance feed, SPF-grade guinea pig growth and reproduction feed, conventional-grade guinea pig growth and reproduction feed, rabbit maintenance feed, and dog maintenance feed showed a slight overall downward trend but no significant differences 7 days after opening. The microbial indicators of specialized corncob bedding for SPF-grade laboratory animals stored for 7 days after opening and conventional-grade corncob bedding stored for 7 days after sterilization showed no significant fluctuations. All indicators still met the relevant requirements of GB/T 14924.2—2001 Laboratory Animals—Hygienic Standard for Formula Feeds and GB 14924.3—2010 Laboratory Animals—Nutrients for Formula Feeds. ConclusionBased on practical experience in managing the center's GLP laboratory animal facility and validation of core quality indicators, the specified validity periods of disinfectants, feed, and bedding meet the quality requirements, providing a practical reference for the standardized management of laboratory animal facilities.

Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.

Objective To evaluate the clinical efficacy of acupuncture combined with Modified Zuojin Granules in treating reflux esophagitis(RE)with liver-stomach disharmony syndrome.Methods A total of 100 patients diagnosed with liver-stomach disharmony syndrome RE were enrolled from October 2022 to October 2024 at Zigong First People's Hospital.The patients were randomly assigned to the observation group and the control group,with 50 cases in each group.The control group was treated with Modified Zuojin Granules,while the observation group was given acupuncture plus Modified Zuojin Granules,both group were treated for 4 weeks.The changes in the traditional Chinese medicine(TCM)syndrome scores,24-hour esophageal acid reflux parameters(frequency and longest duration),serum gastrointestinal hormones[gastrin(GAS),motilin(MTL),vasoactive intestinal peptide(VIP)],gut microbiota composition(Lactobacillus,Bifidobacterium,Enterococcus,Enterobacter)were observed.The adverse reactions and safety profiles were evaluated.Results(1)Both groups showed significant improvement in TCM syndrome scores(P＜0.05),with greater improvement in the observation group,and the differences were statistically significant(P＜0.05).(2)After treatment,both groups of patients showed significant improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration(P＜0.05).The observation group demonstrated significantly better improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration compared to the control group,with statistically significant differences(P＜0.05).(3)After treatment,the serum levels of GAS,MTL,and VIP in both groups of patients were significantly improved(P＜0.05).The observation group showed significantly better improvement in serum GAS,MTL,and VIP levels compared to the control group,with statistically significant differences(P＜0.05).(4)After treatment,the levels of Lactobacilli and Bifidobacteria in both groups increased significantly compared to before treatment(P＜0.05),while the levels of Enterococci and Enterobacteria were significantly decreased(P＜0.05).The improvement in intestinal microbiota levels was more pronounced in the observation group,with statistically significant differences(P＜0.05).(5)The overall efficacy rate was 96.00％(48/50)in the observation group and 80.00％(40/50)in the control group.The observation group demonstrated superior efficacy compared to the control group,with statistically significant differences(P＜0.05).(6)The incidence of adverse reactions in the observation group was 8.00％(4/50),while that in the control group was 12.00％(6/50).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The combined therapy significantly improves clinical symptoms,modulates gastrointestinal hormones and gut microbiota,demonstrating excellent efficacy and safety for liver-stomach disharmony syndrome RE.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To explore the consistency of claudin 18.2 immunohistochemistry (IHC) using 4 different clone antibodies in gastric adenocarcinoma.Methods:A total of 226 gastric adenocarcinomas diagnosed and treated at the Drum Tower Hospital Affiliated to Nanjing University Medical College between January 2022 to March 2023 were included in this study. The cohort consisted of 165 males and 61 females, with a mean age of (61.3±12.1) years. Tumor tissues from radical resection specimens were collected for tissue microarrays. IHC detection of claudin 18.2 was performed using the EnVision method, utilizing 4 clones of antibody: OTIR157B5, 43-14A, EPR19202 and D313D22. The results were interpreted based on both the intensity of staining on tumor cell membranes and the percentage of positive tumor cells relative to the total tumor cells.Results:The positive cutoff value was set as moderately to strongly linear membrane staining in ≥75% of all viable invasive tumor cells, and clone OTIR157B5 demonstrated the highest positive expression rate at 52.2% (118/226). Additionally, the clones OTIR157B5, 43-14A, and EPR19202 were consistently and strongly positive, with all agreement rates of Cohen κ exceeding 0.8. In gastric adenocarcinoma and its three Lauren subtypes, OTIR157B5 exhibited clear membranous localization.Conclusions:Clone OTIR157B5 of claudin 18.2 antibody shows the highest rate of moderately to strongly linear membrane-positive staining, accounting for ≥75% of all viable invasive tumor cells, and clones 43-14A and EPR19202 show strong consistency and high sensitivity.