OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

Objective: To understand the hydration status and related factors of rural boarding primary school students, so as to provide a scientific basis for drinking water health intervention for primary school students. Methods: In November 2023, a convenience sampling approach was employed to conduct a hydration status survey among 144 boarding students in grades 5 and 6 of a rural primary school in Guangxi. The Duplicate meal method and weighing method were utilized to measure the food derived water intake over three consecutive days. Urine osmolarity of students was measured on site for three days, and a simple physical examination was also carried out. A self administered questionnaire was used to investigate students drinking water literacy, daily water intake, and physical activity levels. Meanwhile, a drinking water literacy survey was conducted among 21 substitute teachers and 144 parents of the boarding students in grades 5 and 6. Logistic regression was used to identify factors associated with students hydration status. Results: The median daily total water intake of students was 2 043.55 mL, and 54.86% of the students did not reach the recommended Adequate Intake (AI). The median food derived water intake was 1 149.24 mL, accounting for 53.94% of the total water intake. Univariate analysis revealed that the daily drinking frequency, daily water intake, and food derived water intake of students were related factors of hydration status ( β =-1.60, -1.01, -0.00, all P <0.05). Multivariate Logistic regression analysis showed that primary school students with a daily drinking frequency of ≥7 times were more likely to maintain an adequate hydration status ( OR =0.28, 95% CI =0.09-0.93, P ＜0.05). Conclusions The water intake from food is the main source of water in the body for boarding primary school students in a certain rural school in Guangxi. Primary school students should increase their water intake frequency appropriately to maintain an adequate hydration status.

Objective To investigate the predictive value of the red cell distribution width/platelet count ratio(RPR)for lower extremity deep vein thrombosis(DVT)after transurethral resection of the prostate(TURP).Methods A total of 104 benign prostatic hyperplasia(BPH)patients who underwent TURP in the hospital from January 2022 to December 2024 were selected as the study subjects.Patients who developed postoperative lower extremity DVT were assigned to the DVT group(n=25),while those without DVT were assigned to the non-DVT group(n=79).Red cell distribution width(RDW),platelet count(PLT)and RPR at admission were compared between the two groups.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of RDW,PLT,and RPR for lower extremity DVT after TURP.Multivariate Logistic stepwise regression analysis was performed to explore influencing factors for lower extremity DVT after TURP.Results RDW and RPR in the DVT group were significantly higher than those in the non-DVT group(P<0.05),while PLT was significantly lower(P<0.05).ROC curve analysis showed that the area un-der the curve(AUC)of RDW,PLT,and RPR for predicting postoperative lower extremity DVT in BPH pa-tients were 0.749(95%CI:0.704-0.799),0.822(95%CI:0.777-0.872),and 0.913(95%CI:0.868-0.963),with cut off values of 16.64%,219.15×109/L,and 0.07,respectively.The AUC of RPR was signifi-cantly higher than that of RDW or PLT alone(Z=9.805,P<0.001,Z=11.491,P<0.001).The DVT group had higher levels of D-dimer,fibrinogen,intraoperative blood loss,and a higher proportion of patients with a history of cerebral infarction compared to the non-DVT group(P<0.05).Multivariate Logistic stepwise re-gression analysis showed that D-dimer(OR=2.280,95%CI:1.274-4.080),fibrinogen(OR=2.479,95%CI:1.220-5.041),and RPR(OR=3.885,95%CI:1.964-7.684)were independent risk factors for postop-erative lower extremity DVT(P<0.05).Conclusion The elevation of RPR is closely related to the risk of postoperative lower extremity DVT in patients with BPH,and this indicator is expected to become an impor-tant reference for predicting the risk of lower extremity DVT.

Objective:To investigate relationship between IL-17/IL-23 immunoinflammatory axis and chronic heart failure(CHF)and clinical prognosis.Methods:A total of 112 patients with CHF in Chengde Central Hospital from January 2020 to Septem-ber 2021 were selected as observation group,and another 112 patients admitted to same period for healthy physical examination were selected as control group.Serum IL-17 and IL-23 levels of two groups were compared,relationship between serum IL-17 and IL-23 levels and degree of disease were analyzed;clinical data,serum IL-17 and IL-23 levels of patients with different prognosis were compared,relationship between serum IL-17 and IL-23 levels and clinical prognosis of CHF patients were analyzed.Predictive value of serum IL-17 and IL-23 levels on clinical prognosis of CHF patients was evaluated,and predictive value of each prediction scheme was compared.Results:Serum IL-17 and IL-23 levels were higher in observation group than control group(P<0.05);serum IL-17 and IL-23 levels of CHF patients were positively correlated with NYHA classification(P<0.05).Serum IL-17 and IL-23 levels were higher in patients with poor prognosis than in those with good prognosis(P<0.05).Serum IL-17 and IL-23 were independently associated with clinical prognosis of CHF patients,and the higher the serum IL-17 and IL-23 levels,the greater risk of poor clinical prognosis of CHF patients.AUC of serum IL-17 and IL-23 levels for predicting clinical prognosis of CHF patients were 0.787 and 0.726,respectively,and combined predicted AUC was 0.918(P<0.001);combined predicted AUC of serum IL-17 and IL-23 was significantly higher than single index(P<0.05).Conclusion:IL-17 and IL-23 levels in IL-17/IL-23 immunoinflammatory axis of CHF patients are significantly elevated and involve in disease occurence and development,whose clinical detection can help predict clinical prognosis of CHF.

Cardiovascular disease morbidity and mortality are increasing year by year,and cardiac rehabilitation,as an emerging branch of rehabilitation medicine,is gradually gaining attention.Through combing relevant literature,this paper summarizes and analyzes the theoretical basis and clinical research of acupuncture and moxibustion therapy applied to cardiac rehabilitation based on the systematic and comprehensive discussion of the development,current clinical application and clinical implementation status of cardiac rehabilitation,aiming to provide some reference for the clinical application of acupuncture and moxibustion therapy in cardiac rehabilitation.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

Objective Based on the"preventive treatment of disease"theory and real-world data,this study aimed to evaluate the clinical efficacy of Yangyin Shugan Formula in patients with ovarian dysfunction characterized by the syndrome of kidney deficiency and liver depression at different stages and to provide evidence for optimizing the timing of traditional Chinese medicine(TCM)in premature ovarian insufficiency(POI)management.Methods Ovarian dysfunction patients under 40 years old characterized by syndrome of kidney deficiency and liver depression,registered in the outpatient electronic medical records of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to December 2023,were stratified into three groups:subclinical POI,POI,and premature ovarian failure(POF)groups.The therapeutic outcomes of the three groups of patients were compared,including TCM syndrome total response rates,menstrual total response rates/normalization(cured)rates,base follicle-stimulating hormone(FSH)total response rate/normalization rates and anti-Müllerian hormone(AMH)levels.Results A total of 307 patients meeting the research criteria were included(97 cases in subclinical POI group,112 cases in POI group,and 98 cases in POF group).The TCM syndrome total response rates ranked as subclinical POI group(98.97%,96/97)>POI group(95.54%,107/112)>POF group(83.67%,82/98),with the POF group was lower than that of the subclinical POI and POI groups(P<0.017);while the difference of the subclinical POI group with the POI group was not significant.Menstrual total response rates ranked as subclinical POI group(97.22%,70/72)>POI group(72.32%,81/112)>POF group(51.02%,50/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017);normalization rates ranked as subclinical POI group(90.28%,65/72)>POI group(54.46%,61/112)>POF group(26.53%,26/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017).FSH total response rates ranked as subclinical POI group(89.69%,87/97)>POI group(81.25%,91/112)>POF group(60.20%,59/98),while POF group was lower than that of the other two groups(P<0.017),and the difference of the subclinical POI group with the POI group was not significant.Normalization FSH rates ranked as subclinical POI group(71.13%,69/97)>POI group(53.57%,60/112)>POF group(16.33%,16/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017).Compared with before treatment,the FSH levels in all three groups decreased after treatment(P<0.01).The reduction of FSH in the POF and POI groups were better than that in the subclinical P OI group(P<0.017).No significant difference was observed in the reduction of FSH between the POI and POF groups.Post-treatment AMH elevation observed in the subclinical POI and POI groups(P<0.01).Conclusion Yangyin Shugan Formula improves the menstrual conditions and TCM syndromes across all the stages.It also improves elevated FSH levels across all the stages and has a specific effect on normalizing FSH and menstruation.Yangyin Shugan Formula increases the AMH levels of patients with subclinical POI and POI,highlighting the applicability of TCM in staged preventive management.

Dendrobium is the largest genus of the Orchidaceae family.The fresh and dried stems of many species of this genus have been used as Shihu(Dendrobii Caulis)in traditional Chinese medicine,it is known as the foremost of the"Nine Great Herbs of China".Ancient texts highlight its uses for"strengthening yin,enhancing essence,nourishing the five viscera,alleviating fatigue,and dispelling skin heat and prickly heat".Modern research confirms that the polysaccharides and alkaloids it contains have antiviral ef-fects,it can apply in treating immunodeficiency caused by viral infections clinically.While studies are gradually uncovering the antivi-ral mechanisms and material basis of Dendrobium,the lack of systematic analysis and organization has hindered its resource develop-ment.The paper employed CiteSpace software for bibliometric analysis of Chinese and English literature on Dendrobium.It reviewed the herbalism,material basis,and mechanisms of its antiviral properties building upon the systematic review of ancient materia medica and modern literature.Results indicate that Dendrobium can boost vital energy and resist pathogens,showing great potential in antiviral drug development.

Objective:To analyze the equity of elderly care institution resource allocation in Northeast China and its influencing factors,and provide certain reference for the further development of elderly care care in Northeast China.Methods:The total amount of nursing institution resource allocation and the per capita old and above per 1 000 km2 were summarized by using general descriptive analysis.The Lorenz curve,Gini coefficient,and Theil index were calculated to evaluate the equity of nursing institution resource allocation.Results:Jilin Province did not have an advantage in the total allocation of elderly care insitution resources in Northeast China.In terms of resource allocation per 1 000 km2,Heilongjiang Province still has considerable room for improvement.The overall arc of the Lorenz curve for allocating resources by geographical area has become smaller year by year,while the overall arc of the Lorenz curve for allocating resources by population has become larger year by year.Conclusion:The equity of allocating institution home resources by population has generally weakened over the years,while the equity of allocating elderly care institution resources by geographical area has generally strengthened over the years.The development pressure of nursing care in Liaoning Province is relatively large,and efforts should be made to enhance the fairness of nursing home resource allocation.