This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

Objective:To understand the occupational stress and mental health status of hospital infection prevention and control practitioner (HIPCPs) in medical institutions, and analyze their main influencing factors.Methods:In November 2021, 550 nosocomial infection managers in Tianjin were randomly selected to conduct a questionnaire survey using the Concise Occupational Stress Questionnaire, Depression Screening Scale (PHQ-9) and Self-Rating Anxiety Scale (SAS). 497 valid questionnaires were obtained, and the total recovery efficiency was 90.36%. Single factor analysis and multivariate logistic regression method were used to analyze the main influencing factors of occupational stress and mental health status of psychiatric managers.Results:The detection rate of anxiety and depression among 497 HIPCPs was 22.73% (113/497) and 58.95% (293/497), respectively. Gender and major were the influencing factors of depression ( P=0.000, 0.001). Average working hours>52 hours per week and night shift days>1 days per week were the influencing factors of anxiety ( P=0.035, 0.014). Average working hours>52 h per week, night shift days >1 d per week and different majors were the influencing factors of occupational stress ( P=0.000, 0.025, 0.010). Multivariate logistic regression results showed that the risk of anxiety in those who worked more than 52 hours per week was 1.753 times that of those who worked less than 52 hours per week ( P=0.038), and the risk of depression in women was 3.071 times that of men ( P=0.006) . Conclusion:Working hours are an important influencing factor for occupational stress and anxiety among HIPCPs. In order to reduce the occurrence of occupational stress and mental health problems, it is necessary to strengthen psychological counseling for HIPCPs and balance work and rest.

Objective To evaluate the effect of preoperative visits using virtual reality(VR)tech-nology on alleviating perioperative anxiety in children undergoing adenotonsillectomy for obstructive sleep ap-nea syndrome(OSAS).Methods Sixty children with OSAS scheduled for elective adenotonsillectomy were selected,including 32 males and 28 females,aged 6 to 12 years,ASA physical status Ⅰ or Ⅱ.The chil-dren were randomly divided into two groups using random number table:control group and VR group,30 children in each group.The control group received routine education and preoperative visits,while the VR group used VR smart glasses to play videos of three-dimensional scenes of the operating room in addition to routine visits.The modified Yale preoperative anxiety scale-short form(m-YPAS-SF)was used to assess perioperative anxiety levels.The heart rates(HR)of the children on the day before surgery,upon entering the preparation room,and immediately after anesthesia induction,and the induction compliance checklist(ICC)was used to evaluate anesthesia induction compliance,as well as the duration of stay in the recovery room and the length of hospital stay were recorded.Results Compared with control group,the m-YPAS-SF scores in VR group were significantly lower(P＜0.05),the HR was significantly lower upon entering the preparation room and immediately after anesthesia induction(P＜0.05),and the ICC scores were signifi-cantly lower(P＜0.05),recovery room stay duration and length of hospital stay were significantly short-ened(P＜0.05).Conclusion Preoperative visits using VR can effectively alleviate perioperative anxiety in children with OSAS undergoing adenotonsillectomy which can improve anesthesia compliance and reduce the length of hospital stay.

Objective:To investigate the influence of Kruppel-like factor 16 (KLF16) on the proliferation and migration of pancreatic cancer cells.Methods:Immunohistochemical images of KLF16 were collected from 171 pancreatic cancer tissues and their matched paracarcinoma normal pancreas tissues and 8 pancreatic cancer tissues only in GEPIA database. The expression of KLF16 protein was detected by immunohistochemical imaging software. The protein and mRNA expressions of pancreatic cancer cell lines AsPC-1 and MIA PaCa-2 KLF16 were detected by Western blot and quantitative fluorescence PCR. By knockdown or exogenous overexpression of KLF16, the two cells were divided into blank control group (NC group), negative control group (siRNA-NC group), downexpression KLF16 group (siKLF16 group), overexpression control group (OE-NC group) and ovexpression KLF16-OE group (KLF16-OE group). CCK-8 assay, colony formation assay and transwell chamber were used to detect cell proliferation and migration.Results:The KLF16 protein expression level (4.02±1.26 vs 1.73±1.07) and positive expression rate (91.6% vs 13.5%) in pancreatic cancer tissues were significantly higher than those in paracancer normal pancreas tissues, with statistical significance ( P<0.05). After downregulating KLF16 expression and culturing for 24, 48, 72, and 96 hours, the A450 values of both AsPC-1 (0.19±0.02 vs 0.23±0.03, 0.24±0.06 vs 0.36±0.06, 0.45±0.09 vs 0.78±0.10, 0.69±0.04 vs 0.88±0.07) and MIA PaCa-2 cells (0.20±0.03 vs 0.22±0.02, 0.29±0.05 vs 0.31±0.04, 0.47±0.06 vs 0.78±0.10, 0.71±0.02 vs 0.90±0.07) and colony counts [(36±4.32) per well vs (118.51±10.01) per well, (13.6±2.62) per well vs (83.1±9.11) per well], and the number of migrated cells [(16.67±2.05) vs (46.67±5.91), (19.67±1.69) vs (55±4.89)] all decreased significantly. However, after up-regulating the expression of KLF16 and culturing for 24, 48, 72 and 96 h, the A450 value of both AsPC-1 (0.21±0.05 vs 0.20±0.04, 0.48±0.03 vs 0.31±0.04, 0.91±0.09 vs 0.72±0.03, 1.28±0.10 vs 1.05±0.02) and MIA PaCa-2 cells (0.20±0.01 vs 0.19±0.05, 0.44±0.03 vs 0.30±0.04, 0.89±0.06 vs 0.72±0.03, 1.19±0.05 vs 1.01±0.10), and the number of cell colonies [(189±6.37)/per hole vs (108±9.62)/ per hole, (141±12.56)/ per hole vs (80.69±10.32)/ per hole]], migration cell numbers [(79±4.89) per hole vs (50.33±4.11) per hole, (79.66±3.85) per hole vs (51±4.08) per hole] all increased significantly. Conclusions:KLF16 is highly expressed in pancreatic cancer. The up-regulated expression of KLF16 in pancreatic cancer cell lines can promote the proliferation and migration of pancreatic cancer cells.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.