This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To understand the current status of traditional Chinese medicine(TCM)systematic reviews/Meta-analysis over the past 10 years.Methods Cochrane Database of Systematic Reviews,PubMed,Web of Knowledge,CNKI,SinoMed,WanFang Data,VIP databases,as well as the Cochrane Register and PROSPERO registration platform were searched to collect TCM-related systematic reviews/Meta-analysis published between January 2015 and December 2024.Literature was screened,and standardization of institutions,countries,and journals was performed.Data cleaning was conducted,and trends in publication years,high-frequency diseases,journals,institutions,and highly cited papers were analyzed.Results A total of 11,174 papers were included,involving approximately 56,656 authors from 1,422 institutions across 44 countries,covering 1,300 journals and 1,070 diseases.The top five institutions in terms of publications were Beijing University of Chinese Medicine(954 papers),Guangzhou University of Chinese Medicine(928 papers),China Academy of Chinese Medical Sciences(537 papers),Tianjin University of Chinese Medicine(460 papers),and Chengdu University of Chinese Medicine(393 papers).Foreign institutions with the highest publication volumes were concentrated in South Korea,Iran,and Australia.The most frequently published Chinese journal was Zhongyi Clinical Research with 332 papers,while the most published English journal was Evidence-Based Complementary and Alternative Medicine with 311 papers.There were 282 single-author papers involving 271 authors,and the most cited paper was referenced 323 times,The three most frequently studied diseases were diabetes(267 papers,2.39％),angina pectoris(214 papers,1.92％),and osteoarthritis(210 papers,1.88％).Non-pharmacological interventions such as acupuncture(1,265 papers,11.32％),auricular therapy(101 papers,0.90％),and Tai Chi(98 papers,0.88％)were most frequently reported.In pharmacological interventions,studies on Tripterygium wilfordii tablets(76 papers,0.68％)and Danhong injection(54 papers,0.48％)were more common.Conclusion The systematic reviews/Meta-analysis method is widely used in the field of TCM,and the field continues to grow.Active academic teams,institutions,and journals have emerged.Over the past decade,there has been a considerable body of evidence in Chinese systematic reviews on TCM for chronic diseases such as diabetes,angina pectoris,and osteoarthritis.In English-language studies,non-pharmacological therapies like acupuncture have been more widely reported,and some high-impact studies have emerged.However,challenges remain,such as issues with research transparency and methodological standardization.Future efforts should focus on establishing transparent systems and quality control mechanisms to further enhance the reliability,accuracy,and dissemination of TCM evidence-based research.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective:To establish reference values for clot waveform analysis (CWA) and analyze their diagnostic efficacy in distinguishing acquired hemophilia A (AHA) and lupus anticoagulant (LA)-positive patients.Methods:Case-Control Study. A total of 391 healthy individuals(260 males and 131 females) with a mean age of 45.53±14.85 years were enrolled at Nanyang central Hospital between January 6, 2023 and October 10, 2024. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were measured to establish reference ranges for the CWA parameters, including maximal reaction velocity (Min1), maximal reaction acceleration (Min2), and maximal reaction deceleration (Max2). A total of 158 definitively diagnosed AHA and LA-positive patients (mean age:42.46±14.83 years), including 34 AHA patients and 124 LA-positive patients, were recruited. The Mann Whitney U test was used to analyze the differences in the CWA parameters between the two groups. The diagnostic efficacy of CWA parameters in distinguishing AHA and LA-positive patients was evaluated using the area under the receiver operating characteristic(ROC) curve AUC and the cut-off values were calculated. Results:The reference values for PT-Min1, APTT-Min1, APTT-Min2, APTT-Max2, TT-Min1, TT-Min2, TT-Max2 were 203.41-516.89, 144.63-324.03, 526.46-1 190.03, -404.96±157.22, 159.17±60.34, 272.29-686.99, and -289.47--113.76, respectively. Compared with the CWA parameters in AHA patients, APTT-Max2 was significantly lower in LA-positive patients [-422.74(-577.50, -239.22) vs. -68.87(-92.85,30.28), Z=-7.43, P<0.01], while PT-Min1, APTT-Min1, APTT-Min2, TT-Min1, TT-Min2 were significantly elevated [287.01(188.03, 382.50) vs. 107.45(90.20, 151.39), 972.88(601.20, 1 351.19) vs. 229.10(118.38, 371.67), Z=6.68, 6.69, all P<0.01]. ROC analysis demonstrated the APTT-CWA parameter exhibited high diagnostic efficacy in patients with AHA (AUC>0.900 for both).Additionally, APTT-Min1 and APTT-Max2 were found to be useful in distinguishing between AHA patients and those with LA-positive status accompanied by APTT prolongation (AUC=0.660, 0.700, respectively). Conclusions:Reference values for CWA parameters were successfully established. The APTT-CWA is useful for differentiating between AHA and LA-positive patients and APTT-Max2 demonstrated a good diagnostic value in differentiating AHA patients from those with LA-positive status accompanied by APTT prolongation.

This study established a high performance liquid chromatography(HPLC) fingerprint of Chuanxiong Rhizoma from different producing areas and screened its potential differential components for producing areas by chemometrics. Furthermore, the content of the above differential components in Chuanxiong Rhizoma from different producing areas was measured and compared. Then, the geoherbalism markers(geo-markers) that can be used to distinguish Dao-di and non-Dao-di Chuanxiong Rhizoma were excavated by chemometrics. In fingerprint studies, a total of 27 common peaks were determined, and the fingerprint similarity for 37 batches of Chuanxiong Rhizoma samples from different producing areas was above 0.968. The orthogonal partial least squares-discriminant analysis(OPLS-DA) was capable of distinguishing Chuanxiong Rhizoma from Sichuan and from three other provinces, as well as Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. Meanwhile, 14 potential differential components in Chuanxiong Rhizoma from different provinces and 16 potential differential components in Chuanxiong Rhizoma from different producing areas in Sichuan were screened by the variable importance in projection(VIP) analysis under OPLS-DA. The reference standards were used to identify 10 potential differential components in the common peaks, and subsequent content determination verified that the content of the above 10 potential differential components was different among different producing areas. Then, the OPLS-DA and VIP analysis were performed with the content of the 10 potential differential components as variables. The results showed that Z-ligustilide, chlorogenic acid, and the ratio of butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Chuanxiong Rhizoma from Sichuan and Chuanxiong Rhizoma from Shaanxi, Hebei, and Jiangxi, while Z-ligustilide, n-butylphthalide, and the ratios of Z-ligustilide/senkyunolide A and butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. This study elucidated the differences in material basis of Dao-di and non-Dao-di Chuanxiong Rhizoma based on fingerprinting and content determination combined with chemometrics, which provides a reference for the study of material basis of Dao-di traditional Chinese medicine.
Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Chemometrics/methods* ; Quality Control

Objective:To investigate the prevalence of chronic endometritis(CE)in patients with repeated implantation failure(RIF),and the correlation between diagnostic indexes of CE and classification of peripheral blood immune cells.Methods:A total of 64 patients with RIF who visited Outpatient of Hebei Reproductive Health Hospital from January 2020 to December 2021 were retrospec-tively analyzed.General information of patients,results of hysteroscopy and endometrial immunohistochemistry in the mid luteal phase,the number and percentage of NK cells,Th1 cells,Th2 cells,Th17 cells and Treg cells in peripheral blood,and Th1/Th2,Th17/Treg were collected,and the pregnancy outcome of retransplantation was followed up.To evaluate the consistency of hysteroscopy and endometrial immunohistochemistry CD138 in diagnosis of CE in RIF patients,to analyze whether chronic inflammation of endome-trium was related to classification of peripheral blood immune cells,and to analyze the pregnancy outcome of patients with RIF diag-nosed with CE after retransplantation.Results:Prevalence of CE in RIF patients detected by hysteroscopy was 53.12%,which was sig-nificantly higher than that detected by endometrial immunohistochemistry CD138(25.00%,P<0.05).There was no significant differ-ence in the number and percentage of immune cells in peripheral blood between CE and non CE patients.After antibiotic treatment,the 12-week continuous pregnancy rate and live birth rate in the CD138 positive group were higher than those in negative group,with a statistically significant difference(P<0.05).Conclusion:The combination of hysteroscopy and endometrial CD138 immunohistochem-istry at the right time for RIF patients is beneficial to improve their pregnancy rate and pregnancy outcome.The infiltration of endome-trial plasma cells does not affect the classification of peripheral blood immune cells.

Objective To understand the current status of traditional Chinese medicine(TCM)systematic reviews/Meta-analysis over the past 10 years.Methods Cochrane Database of Systematic Reviews,PubMed,Web of Knowledge,CNKI,SinoMed,WanFang Data,VIP databases,as well as the Cochrane Register and PROSPERO registration platform were searched to collect TCM-related systematic reviews/Meta-analysis published between January 2015 and December 2024.Literature was screened,and standardization of institutions,countries,and journals was performed.Data cleaning was conducted,and trends in publication years,high-frequency diseases,journals,institutions,and highly cited papers were analyzed.Results A total of 11,174 papers were included,involving approximately 56,656 authors from 1,422 institutions across 44 countries,covering 1,300 journals and 1,070 diseases.The top five institutions in terms of publications were Beijing University of Chinese Medicine(954 papers),Guangzhou University of Chinese Medicine(928 papers),China Academy of Chinese Medical Sciences(537 papers),Tianjin University of Chinese Medicine(460 papers),and Chengdu University of Chinese Medicine(393 papers).Foreign institutions with the highest publication volumes were concentrated in South Korea,Iran,and Australia.The most frequently published Chinese journal was Zhongyi Clinical Research with 332 papers,while the most published English journal was Evidence-Based Complementary and Alternative Medicine with 311 papers.There were 282 single-author papers involving 271 authors,and the most cited paper was referenced 323 times,The three most frequently studied diseases were diabetes(267 papers,2.39％),angina pectoris(214 papers,1.92％),and osteoarthritis(210 papers,1.88％).Non-pharmacological interventions such as acupuncture(1,265 papers,11.32％),auricular therapy(101 papers,0.90％),and Tai Chi(98 papers,0.88％)were most frequently reported.In pharmacological interventions,studies on Tripterygium wilfordii tablets(76 papers,0.68％)and Danhong injection(54 papers,0.48％)were more common.Conclusion The systematic reviews/Meta-analysis method is widely used in the field of TCM,and the field continues to grow.Active academic teams,institutions,and journals have emerged.Over the past decade,there has been a considerable body of evidence in Chinese systematic reviews on TCM for chronic diseases such as diabetes,angina pectoris,and osteoarthritis.In English-language studies,non-pharmacological therapies like acupuncture have been more widely reported,and some high-impact studies have emerged.However,challenges remain,such as issues with research transparency and methodological standardization.Future efforts should focus on establishing transparent systems and quality control mechanisms to further enhance the reliability,accuracy,and dissemination of TCM evidence-based research.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.