OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective: To investigate the Alzheimer's disease (AD) influencing factors among the elderly, so as to provide a basis for early prevention and intervention. Methods: From March to June 2024, participants aged 60 years and above from a sub-district in Haishu District, Ningbo City, Zhejiang Province were selected using a convenience sampling method. Data on demographics, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were evaluated using the short-form Geriatric Depression Scale. The Chinese Mini-Mental State Examination (MMSE) was used for the initial screening of AD, and individuals who screened positive were further diagnosed by psychiatrists. Factors affecting AD among the elderly were analyzed using a multivariable logistic regression model. Results: A total of 3 644 individuals were surveyed, comprising 1 526 males (41.88%) and 2 118 females (58.12%). The mean age was (71.85±7.44) years. AD was detected in 200 cases, with a detection rate of 5.49%. Multivariable logistic regression analysis showed that individuals aged ≥65 years (65-<70 years, OR=3.012, 95%CI: 1.007-9.012; 70-<75 years, OR=3.131, 95%CI: 1.059-9.260; 75-<80 years, OR=5.779, 95%CI: 1.989-16.784; ≥80 years, OR=16.810, 95%CI: 5.926-47.685), those who were unmarried, divorced, or widowed (OR=1.973, 95%CI: 1.383-2.815), those with hearing loss (OR=1.573, 95%CI: 1.128-2.193), those with diabetes mellitus (OR=1.958, 95%CI: 1.362-2.814), and those with depressive symptoms (OR=4.143, 95%CI: 2.997-5.728) had a higher risk of AD. Conversely, individuals with an educational level of primary school or above (primary school, OR=0.579, 95%CI: 0.401-0.835; junior high school or above, OR=0.438, 95%CI: 0.259-0.741), and those who engaged in regular physical exercise (OR=0.414, 95%CI: 0.264-0.649) had a lower risk of AD. Conclusions The detection rate of AD was relatively high among the elderly in Haishu District. AD among the elderly was related to age, educational level, marital status, physical exercise, hearing loss, diabetes mellitus, and depressive symptoms.

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

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*

The bacterial CBASS(cyclic-oligonucleotide-based anti-phage signaling system) represents a novel innate immune defense mechanism mediated by cyclic nucleotides.The system employs cGAS/DncV-like nucleotidyltransferases (CD-NTases) to recognize exogenous nucleic acids, catalyzing the production of second messenger molecules such as cyclic GMP-AMP (cGAMP) to activate effector proteins (e.g., nucleases), thereby triggering "cell suicide" to combat phage infection. The molecular mechanisms and evolutionary features of CBASS not only uncover the diversity of bacterial immune defenses but also provide critical insights into the conservation of prokaryotic-eukaryotic immune pathways. Notably, the bacterial CBASS system exhibits profound homology with the eukaryotic cGAS-STING (Cyclic GMP-AMP Synthase—Stimulator of Interferon Genes) pathway across multiple dimensions, including the catalytic domains of CD-NTase/cGAS and cyclic nucleotide signaling mechanisms. This finding supports the hypothesis that eukaryotic innate immunity may have originated from prokaryotic horizontal gene transfer and highlights an evolutionary shift in defense strategies from bacterial "population lysis" to "individual inflammatory activation" in higher organisms.This review systematically synthesizes the functional architecture and mechanisms of the CBASS system, with a deep exploration of its evolutionary connections to the eukaryotic cGAS-STING pathway. The insights gained herein offer fresh perspectives for understanding the origin and evolution of the innate immune system, and for driving advancements in biotechnological research and development.

Objective To analyze the correlations of the expressions of miR-4500 and nerve growth factor(NGF)in breast cancer patients with preoperative magnetic resonance(MR)signs.Methods A total of 105 patients with breast cancer admitted to our hospital were selected,the mRNA expression levels of miR-4500 and NGF in breast cancer tissues and adjacent tissues of patients were detected by qRT-PCR,and the positive expression rates of NGF in breast cancer tissues and adjacent tissues were determined by immunohistochemistry method.The correlations of the expressions of miR-4500 and NGF in breast cancer tissues with clinicopathological features and MR signs of patients were analyzed.The targeting relationship between miR-4500 and NGF was predicted by the bioinformatics website,and the correla-tion between the expressions of the two was analyzed.Results Compared with the adjacent tissues,the expression level of miR-4500 in breast cancer tissue decreased(P<0.05),while the level of NGF mRNA and the positive expression rate of NGF increased(P<0.05).There was no significant difference in age,pathological type,tumor classification,parenchymal background,apparent diffusion coefficient or enhancement curve among different expressions of miR-4500 and NGF(P>0.05).The histological grade,lymph node metastasis,tumor diameter,tumor morphology,ring-like enhancement,and peritu-moral brain edema were related to the expressions of miR-4500 and NGF(P<0.05).The bioinformatics website prediction showed that miR-4500 and NGF had binding sites,and the expressions of miR-4500 and NGF mRNA in breast cancer tissues were negatively correlated(r=-0.576,P<0.05).Conclusion The expression of miR-4500 in breast cancer tissue is low,and the expression of NGF is high,which are correlated with the preoperative MR signs in patients,providing a molecu-lar basis for MR signs.

"State-target medicine" is a traditional Chinese medicine （TCM） diagnosis and treatment theoretical system proposed by Academician Tong Xiaolin based on the current development of modern medicine. The active stage of gastric ulcer， as a precancerous state of gastric cancer， has a great impact on people's health. Prof. ZHOU Xuewen， a master of TCM， innovatively put forward the theory of "toxicity-heat" etiology for the active stage of gastric ulcer， which plays an important guiding role in clinical diagnosis and treatment. The article took the theoretical system of "state-target medicine" as the framework to explain the rationale， method， formula， and medicine of Prof. ZHOU Xuewen， who applied the Xiaoyong Kuidekang based on the "toxicity-heat" theory to treat the gastric ulcer in the active stage. The Chinese medical name of gastric ulcer， "gastric carbuncle"， was established， and it was believed that gastric ulcer is born due to "toxicity" and is based on "toxicity and heat". In the course of the disease， "toxicity"， "heat"， "deficiency"， and "stasis" coexisted， and its pathogenesis was divided into three phases， namely， toxicity-heat accumulation phase， toxicity-heat affecting the health phase， and weakened body resistance and strengthened toxicity phase. According to the positioning of gastric ulcer as an "internal carbuncle"， Prof. ZHOU Xuewen proposed the treatment of gastric ulcer in the active stage with "carbuncle theory" and introduced the surgical methods of "elimination"， "support"， and "tonifying" into the treatment of gastric ulcer in the active stage. Prof. ZHOU Xuewen took "clearing heat and removing toxins， eliminating carbuncle and generating muscle" as the basic treatment of the disease. For different stages of the disease， Prof. ZHOU Xuewen emphasized the use of the methods of clearing heat and removing toxins， supporting rot and muscle growth， and strengthening the spleen and harmonizing the stomach and created the representative formula for the treatment of gastric ulcer in the active stage with "carbuncle theory"， namely "Xiaoyong Kuidekang"， which could regulate state and targets.

italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.