ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

OBJECTIVE To evaluate the effectiveness and safety of warfarin anticoagulation therapy guided by gene test in patients undergoing left ventricular assist device （LVAD） implantation， and to analyze the influencing factors of warfarin anticoagulation efficacy. METHODS Patients who underwent LVAD implantation at the Heart and Vascular Center of Northern Jiangsu People’s Hospital from January 2023 to October 2024 and required warfarin anticoagulant therapy were selected as the study subjects. They were divided into genetic testing group （n＝51） and empirical treatment group （n＝17） based on whether they underwent CYP2C9 and VKORC1 gene test. The gene test group was given warfarin based on the predicted dose calculated by gene test， while the empirical treatment group was given warfarin by clinical doctors based on international normalized ratio （INR） experience， all patients were given warfarin once a day. Follow-up observation was conducted for 6 months to compare the effectiveness [time in therapeutic range（TTR）， the time required to reach INR for the first time， the incidence of embolic events， the incidence of INR＜1.5 events] and safety （the incidence of major and minor bleeding events，the incidence of INR＞3.5 events） of warfarin treatment between two groups of patients. According to whether the patient’s TTR was ≥60%， they were divided into TTR≥60% group （n＝20） and TTR＜60% group （n＝48）. Univariate and multivariate binary Logistic regression analysis were used to determine the factors affecting the anticoagulant effect of warfarin in patients. RESULTS The TTR of patients in the gene test group was significantly higher than that in the empirical treatment group （P＜0.05）. The incidence of INR＜1.5 events in the gene test group was significantly lower than in the empirical treatment group （P＜0.05）. The incidence of minor bleeding events and INR＞3.5 events in the gene test group were lower than in the empirical treatment group， but the difference was not statistically significant （P＞0.05）. The results of multivariate binary Logistic regression analysis showed that gene test was an independent protective factor for warfarin anticoagulant therapy [odds ratio （OR）＝10.842， 95% confidence interval （CI）： 1.211-27.037， P＝0.033]， and the combination of statins was an independent risk factor for warfarin anticoagulant therapy [OR＝0.196， 95%CI： 0.045-0.861， P＝0.031]. CONCLUSIONS Under the guidance of gene test， warfarin anticoagulation therapy for LVAD patients after implantation can improve TTR， shorten the anticoagulation target time， and has good safety； meanwhile， it should be noted that the combination of statins may enhance the anticoagulant effect of warfarin， thereby increasing the risk of bleeding in patients.

Objective The ketogenic diet(KD)is a dietary intervention with potential therapeu-tic effects on polycystic ovary syndrome(PCOS),yet the existing evidence remains controversial.Fur-thermore,there is a lack of evidence-based medicine data for a comprehensive assessment of the safety of KD in the treatment of PCOS.This study aims to systematically evaluate,through a meta-analysis,the effects of KD on body composition,metabolic indicators,and reproductive hormone levels in over-weight/obese patients with PCOS,and to explore its safety and clinical applicability.Methods This study systematically searched PubMed,Web of Science,Embase,Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang Database,and VIP Database.Randomized controlled trials(RCT)on KD for the treatment of PCOS were included,with the search time frame spanning from the establishment of each database to May 31,2025.Two researchers independently screened and extracted data according to inclusion and exclusion criteria,and assessed the quality of the in-cluded literature using the Cochrane Handbook.The Q-test and inconsistency index(I2)were used to evaluate the heterogeneity of the results.Based on the level of heterogeneity,a fixed-effects model or a random-effects model was selected for data pooling.Sensitivity analysis was employed to explore the robustness of the results.Results A total of 7 RCT studies involving 495 overweight/obese subjects were included in this study.Body composition analysis revealed that,compared with the control group,KD significantly reduced body mass index,body weight,waist circumference,waist-to-hip ra-tio,total fat mass,and visceral fat area in overweight/obese patients with PCOS(P＜0.05),but had no significant effect on fat-free mass.Analysis of glucose and lipid metabolism indicated that KD sig-nificantly decreased fasting blood glucose,fasting insulin,insulin resistance index,and triglycerides(P＜0.05),but had no significant impacts on total cholesterol,low-density lipoprotein cholesterol,or high-density lipoprotein cholesterol.Reproductive hormone analysis showed that KD significantly reduced luteinizing hormone,the ratio of luteinizing hormone to follicle-stimulating hormone,and total testosterone levels,while significantly increased sex hormone-binding globulin levels(P＜0.05),but had no significant effect on follicle-stimulating hormone.Sensitivity analysis suggested that the results were relatively robust.In terms of safety,no serious adverse reactions were observed during the KD intervention;however,further verification through high-quality RCTs with larger sample sizes and long-term interventions is still required.Conclusion KD can effectively improve body composition,glucose metabolism,lipid metabolism indicators,and reproductive hormone levels in overweight/obese patients with PCOS.This study confirms that KD significantly increase sex hormone-binding globulin level and reduce visceral fat area.It is found that KD has a more pronounced effect on impro-ving triglycerides compared to its effects on low-density lipoprotein cholesterol and high-density lipo-protein cholesterol.The current evidence does not indicate significant safety risks associated with KD,but relevant conclusions still require further confirmation with more high-quality evidence.

Objective:To explore the impact of home enteral nutrition (HEN) on the treatment strategy of patients with high position intestinal fistula.Methods:The clinical and follow-up data of 36 patients with high position intestinal fistula requiring HEN treated in Beijing Tsinghua Changgung Hospital from Jan 2021 to Sep 2023 was retrospectively analyzed.Results:Among the 36 cases, 2 had indwelling nasogastric tubes, 12 had indwelling nasojejunal nutritional tubes, and 22 had percutaneous jejunostomy. The incidence of HEN-related complications in patients was 13.9%, and there were no serious catheter complications.During HEN, high position intestinal fistula healed in 19 cases (52.8%), returned to the hospital for the next stage of intestinal fistula treatment in 11 cases (30.6%), needed to return to the hospital for nutritional support in 1 case (2.8%), and intestinal fistula aggravated to terminate HEN in 2 cases (5.6%).Conclusion:Under the management of professional team, HEN via nasogastric/jejunal nutritional tube or percutaneous jejunostomy is safe and feasible in patients with high intestinal fistula.

Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P＞0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.

Objective:To investigate the current situation and influence factors of prehospital thrombolysis treatment for ST segment elevation myocardial infarction (STEMI) in China, to analyze the main factors affecting prehospital thrombolysis implementation, and optimize the pre-hospital thrombolysis strategy for STEMI to reduce mortality.Methods:A multicenter cross-sectional survey was conducted. 21 cities from six major geographical regions in China were selected by using convenient sampling method. An anonymous online electronic questionnaire was used to investigate the current situation and influence factors of prehospital emergency physicians and grassroots physicians implementing prehospital thrombolysis treatment for STEMI patients. Chi-square test was used to analyze the differences in count data between groups, and multivariate logistic regression was used to analyze the factors affecting prehospital thrombolysis in STEMI.Results:A total of 5 163 prehospital emergency physicians and physicians from grassroots township health centers/community health service centers or village clinics participated in this survey. Among them, 3208 (62.13%) have never implemtent thrombolysis, and 1 955 (37.87%) have did it before. The results of the multivariate logistic regression analysis indicated that physicians with 5-10 years of experience ( OR=1.41, 95% CI: 1.18-1.69, P<0.01), 11-20 years of experience ( OR=1.25, 95% CI: 1.03-1.52, P=0.02), those working in village clinics ( OR=1.30, 95% CI: 1.05-1.61, P=0.02), those in pre-hospital emergency medical institutions/departments ( OR=3.19, 95% CI: 2.80-3.64, P<0.01), those whose units are equipped with remote ECG transmission capabilities ( OR=1.72, 95% CI: 1.50-1.96, P<0.01), or ECG AI-assisted diagnostic tools ( OR=1.31, 95% CI: 1.15-1.49, P<0.01), and those who believe that thrombolysis is highly effective and should be widely adopted ( OR=2.55, 95% CI: 2.09-3.12, P<0.01) or consider it somewhat effective but warranting caution ( OR=2.11, 95% CI: 1.73-2.59, P<0.001), were more likely to make pre-hospital thrombolysis decisions for STEMI patients. To improve the current situation of pre-hospital thrombolysis for STEMI, the top four measures prioritized by pre-hospital emergency and grassroots physicians were enhancing the rescue capabilities of primary care doctors (92.22%), strengthening guidance from higherlevel hospitals (84.99%), increasing support for information technology (83.37%), and improving public health education (74.75%). Conclusions:The implementation rate of prehospital thrombolysis for STEMI in China still needs to be improved. Optimizing the prehospital thrombolysis strategy for STEMI, strengthening the allocation of basic medical resources and information technology support, and improving the referral mechanism are conducive to the implementation of prehospital thrombolysis for STEMI.

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Objective:To investigate the correlation between inositol level and glycolipid metabolism in gravidas with gestational diabetes mellitus (GDM).Methods:A cross-sectional study was conducted on 80 GDM cases undergoing routine examination at Fujian Provincial Maternity and Children's Hospital from November 2018 to August 2019, who were selected as GDM groups. Another 50 women with uncomplicated pregnancies during the same period were selected as the control group. Blood and urine inositol level and serum glycolipid profiles were compared between the two groups, and their association was analyzed. Independent or paired-sample t test, Mann-Whitney test, Chi-square (or Fisher's exact) test, and Pearson correlation test were performed for statistical analysis. Results:The serum inositol concentration and high-density lipoprotein (HDL) cholesterol in the GDM group were significantly lower [322.1 ng/ml (279.1-364.1 ng/ml) vs 403.8 ng/ml (391.8-425.3 ng/ml), Z=-7.879; 1.8 mmol/L (1.5-2.0 mmol/L) vs 2.0 mmol/L (1.7-2.2 mmol/L), Z=-2.419; both P<0.05], while the concentration of urine inositol, lipoprotein-a (lipo-a), 0 h-, 1 h-, 2 h-oral glucose tolerance test (OGTT) glucose, fasting insulin, and glycosylated hemoglobin (HbA1c) were significantly higher when comparing to the control group [192.2 ng/ml (171.0-219.9 ng/ml) vs 143.8 ng/ml (121.1-158.6 ng/ml), Z=-6.834; 253.2 mg/L (65.0-349.0 mg/L) vs 148.5 mg/L(46.5-159.3 mg/L), Z=-0.187; 5.0 mmol/L (5.1-5.6 mmol/L) vs 4.4 mmol/L (4.2-4.6 mmol/L), Z=-5.547; 10.0 mmol/L (9.1-11.3 mmol/L) vs 7.8 mmol/L (7.0-8.4 mmol/L), Z=-6.987; 8.6 mmol/L(7.6-9.4 mmol/L) and 6.6 mmol/L (5.7-7.1 mmol/L), Z=-7.100; 18.2 mU/L(10.6-25.9 mU/L) vs 11.0 mU/L (6.3-12.7 mU/L), Z=-4.537; 5.4%(4.5%-5.5%) vs 5.1%(4.9%-5.4%), Z=-3.468; all P<0.05]. (2) Serum inositol concentration was negatively correlated with fasting insulin and 0 h-, 1 h-, 2 h- OGTT glucose level ( r=-0.386, -0.416, -0.350 and -0.407, respectively); urinary inositol concentration was positively correlated with 0 h-, 1 h-, 2 h-OGTT glucose levels ( r=0.402, 0.389 and 0.429, respectively) (all P<0.05). Conclusions:Serum inositol concentration was decreased, and urinary inositol excretion was increased in women with GDM. Measurement of changes in inositol levels during the second trimester may be helpful to assess the metabolic status of pregnant women.