BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

BACKGROUND:Due to the lack of blood supply to tendons and the low repair ability of tendon cells,the repair cycle of tendon tissue is long.With the maturity of decellularization technology,decellularized extracellular matrix is receiving increasing attention in the fields of tissue engineering and regenerative medicine.Due to its high activity,low immunogenicity,and ability to support cell attachment,proliferation,and differentiation,decellularized tendon scaffolds are expected to promote tendon repair.OBJECTIVE:To summarize the biological characteristics of decellularized tendon scaffolds,elucidate the mechanism by which decellularized tendon scaffolds promote tendon healing,and explain the application methods and future limitations of decellularized tendon scaffolds in combination with other materials.METHODS:Relevant literature was retrieved from China National Knowledge Infrastructure and PubMed databases using the Chinese search terms"tendon injury,tendon repair,tendon disease,decellularized tendon scaffold"and English search terms"tendon injury,tendon repair,tendinopathy,decellularized tendon scaffold,decellularized tendon scaffolds."By reading and screening relevant literature,77 articles were ultimately included for result analysis.RESULTS AND CONCLUSION:(1)Decellularization technology can be divided into physical treatment,chemical treatment,and biological procedures.(2)Decellularized tendon scaffolds,as a common biomedical material,have certain biocompatibility,biodegradability,and biomechanical properties,which provide a prerequisite and foundation for tendon injury repair.(3)Decellularized tendon scaffolds can alleviate the inflammatory response of tissues,promote the adhesion,proliferation,and differentiation of bone marrow mesenchymal stem cells/tendon derived stem cells,and maintain the biomechanical properties of tissues.(4)Decellularized tendon scaffolds can be used in combination with other materials,such as electrospinning,hydrogel,stem cell implantation,and 3D printing technology.(5)Future research can further investigate its pathogenic mechanism and improve tendon tissue repair by combining other biomaterials with decellularized tendon scaffold applications.

BACKGROUND:Due to the lack of blood supply to tendons and the low repair ability of tendon cells,the repair cycle of tendon tissue is long.With the maturity of decellularization technology,decellularized extracellular matrix is receiving increasing attention in the fields of tissue engineering and regenerative medicine.Due to its high activity,low immunogenicity,and ability to support cell attachment,proliferation,and differentiation,decellularized tendon scaffolds are expected to promote tendon repair.OBJECTIVE:To summarize the biological characteristics of decellularized tendon scaffolds,elucidate the mechanism by which decellularized tendon scaffolds promote tendon healing,and explain the application methods and future limitations of decellularized tendon scaffolds in combination with other materials.METHODS:Relevant literature was retrieved from China National Knowledge Infrastructure and PubMed databases using the Chinese search terms"tendon injury,tendon repair,tendon disease,decellularized tendon scaffold"and English search terms"tendon injury,tendon repair,tendinopathy,decellularized tendon scaffold,decellularized tendon scaffolds."By reading and screening relevant literature,77 articles were ultimately included for result analysis.RESULTS AND CONCLUSION:(1)Decellularization technology can be divided into physical treatment,chemical treatment,and biological procedures.(2)Decellularized tendon scaffolds,as a common biomedical material,have certain biocompatibility,biodegradability,and biomechanical properties,which provide a prerequisite and foundation for tendon injury repair.(3)Decellularized tendon scaffolds can alleviate the inflammatory response of tissues,promote the adhesion,proliferation,and differentiation of bone marrow mesenchymal stem cells/tendon derived stem cells,and maintain the biomechanical properties of tissues.(4)Decellularized tendon scaffolds can be used in combination with other materials,such as electrospinning,hydrogel,stem cell implantation,and 3D printing technology.(5)Future research can further investigate its pathogenic mechanism and improve tendon tissue repair by combining other biomaterials with decellularized tendon scaffold applications.

Objective:To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells.Methods:K562 cells were treated with ginsenoside-Rg5 and imatinib.Cell survival was detected by CCK-8 assay,and IC50 were calculated separately for each drug.Based on the value of IC50 of ginsenoside-Rg5 and imatinib,an appropriate concentration gradient was selected for the combination.The synergistic effect of the two drug was analyzed using the online software synergy finder.The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry.Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy.Results:Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dose-dependent manner(r=-0.991,r=-0.942).The synergy score ZIP＞10 was measured by Synergy Finder online software,indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells.The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96％and 8.13％,respectively,while the rate increased to 21.35％with the combination of two drugs,the apoptosis rate in the combination group was higher than that in the single-drug group(P＜0.05).The proportion of K562 cells in the G0/G1 phase was significantly increased with the combined treatment of two drugs(P＜0.05).The protein expression levels of p-PI3K,p-AKT,p-mTOR in K562 cells treated with the combination were significantly decreased,with noticeable downregulation of BCL-2 and upregulation of BAX,leading to a decreased Bcl-2/BAX ratio,while no significant changes were observed in the non-phosphorylated forms of PI3K,AKT,and mTOR proteins.Conclusion:The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis,and the mechanism may act through PI3K/AKT/mTOR signaling pathways.

Chronic prostatitis is a process of kidney deficiency and blood stasis mixed with various pathological factors involving the essence chamber,which is manifested as kidney deficiency and blood stasis.Based on the concept of the"brain-heart-kidney-es-sence chamber"axis of medication,Xiongji Formula is applied to the treatment of chronic prostatitis,due to its"simultaneous holistic and local action"and effects of tonifying the kidney yang and assisting the systemic yang,acting on the brain,heart and kidney as a whole,and meanwhile activating blood circulation,eliminating blood stasis and restoring the function of the essence chamber.This pa-per discusses the etiology and pathogenesis of chronic prostatitis with kidney deficiency and blood stasis in Chinese medicine,expounds the significance of"brain-heart-kidney-essence chamber"axis of medication,and explores the specific value and clinical application of Xiongji Formula.

Objective To investigate the application value of combining the Demirjian's method with ma-chine learning algorithms for dental age estimation in northern Chinese Han children and adolescents.Methods Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected.The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method.Various machine learning algorithms,including support vector re-gression(SVR),gradient boosting regression(GBR),linear regression(LR),random forest regression(RFR),and decision tree regression(DTR)were employed.Age estimation models were constructed based on total,female,and male samples respectively using these algorithms.The fitting performance of different machine learning algorithms in these three groups was evaluated.Results SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples,while GBR showed the best performance in male samples.The mean absolute error(MAE)of the op-timal age estimation model was 1.246 3,1.281 8 and 1.153 8 years in the total,female and male samples,respectively.The optimal age estimation model exhibited varying levels of accuracy across dif-ferent age ranges,which provided relatively accurate age estimations in individuals under 18 years old.Conclusion The machine learning model developed in this study exhibits good age estimation effi-ciency in northern Chinese Han children and adolescents.However,its performance is not ideal when applied to adult population.To improve the accuracy in age estimation,the other variables can be con-sidered.

Background: Ophiopogon japonicus (L.f) Ker-Gawl. growing in Zhejiang is recognized as the Dao-di medicinal herb for the production of Ophiopogonis Radix. Borneol-7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, a prominent pharmacologically active compound, serves as a marker distinguishing O. japonicus in Zhejiang from those in other geographical areas. It is synthesized from borneol through glycosylation, with terpene synthase (TPS) being the critical enzyme catalyzing the conversion of terpene precursors into borneol. Objective: The aim of the study was to define key genes involved in biosynthesis of borneol in O. japonicus. Methods: The candidate terpene synthase genes were identified from the root and leaf transcriptome data of O. japonicus in Zhejiang and the functions of these enzymes were identified using engineered Escherichia coli. Results: This study developed a rapid expression system for monoterpene and sesquiterpene synthases based on engineered E. coli. Seven terpene synthase genes (OjTPS1 to OjTPS7) were identified in different terpene synthase subfamilies, including 2 from TPS-a, 4 from TPS-b, and 1 from TPS-g. Biochemical analysis using an engineered system E. coli demonstrated that all the 7 terpene synthases produced monoterpenes, and OjTPS3, OjTPS5, and OjTPS6 also yielded sesquiterpenes. Conclusions: These 7 terpene synthases produced 13 monoterpenes and 8 sesquiterpenes. Notably, OjTPS1 produced borneol establishing the groundwork for elucidating the biosynthetic pathways of borneol-7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside and other volatile oil components.

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.
Female ; Animals ; Rats ; Ovary ; Uterus ; Ovarian Follicle ; Lactate Dehydrogenase 5 ; Glycolysis

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.
Male ; Humans ; Adult ; Middle Aged ; Female ; Coronary Artery Disease/complications* ; Cholesterol, HDL ; Cholesterol, LDL ; Prospective Studies ; Myocardial Infarction/etiology* ; Stroke ; Risk Factors