Osteoporosis is a common bone metabolic disease， which is mainly characterized by the decrease in the number of bone trabeculae and the destruction of bone tissue microstructure， leading to increased bone fragility and fracture risks. This disease is common in postmenopausal women， elderly men， diabetes patients， and obese people. Due to the lack of awareness to prevent bone losses and the limitations of bone mass measurement methods， osteoporosis is only concerned when there are serious complications， which imposes a heavy burden on both patients and medical resources. Oxidative stress refers to the excessive production of highly active molecules such as reactive oxygen species and reactive nitrogen in the body subjected to harmful stimuli， leading to the imbalance between the oxidative and antioxidant systems and causing oxidative damage. Studies have shown that oxidative stress can increase the generation and activity of osteoclasts and inhibit the differentiation of osteoblasts， thus playing a role in the occurrence and development of osteoporosis. Traditional Chinese medicine （TCM） is considered an effective antioxidant that can alleviate oxidative stress-induced osteoporosis by regulating a variety of signaling pathways. Studies have shown that TCM can alleviate oxidative stress and promote bone angiogenesis and osteogenesis by regulating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor-kappa B， and nuclear factor erythroid 2-related factor （Nrf2） signaling pathways. TCM alleviates oxidative stress and promotes osteogenesis by regulating the Nrf2， PI3K/Akt/mammalian target of rapamycin， and secreted glycoprotein Wnt/β-catenin signaling pathways. In addition， TCM regulates NF-κB， mitogen-activated protein kinase， and receptor activator of nuclear factor kappa B （RANK）/RANK ligand/osteoprotegerin signaling pathway to alleviate excessive bone resorption induced by oxidative stress. This paper systematically summarizes the literature on the prevention and treatment of osteoporosis by TCM or its active ingredients via the above-mentioned signaling pathways to reduce oxidative stress in recent years. It briefs the possible molecular mechanisms of oxidative stress regulation-related signaling pathways to cause osteoporosis. In addition， this paper discusses the effects and mechanisms of TCM on bone angiogenesis， osteogenesis， and bone resorption by reducing oxidative stress through the regulation of related signaling pathways， aiming to provide a theoretical basis for the research and clinical treatment of osteoporosis.

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

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVES: To investigate the ethnic origin of Chuanqing people, one of the largest unidentified ethnic groups in Guizhou, China, and analyze its genetic relationships with surrounding populations. METHODS: Based on a self-developed microhaplotype system, we conducted genotyping and analyzed the genetic distribution of microhaplotype loci and their forensic applicability in Chuanqing population in Guizhou Province. Using the microhaplotype data from different intercontinental populations and previously reported data from Han population living in Guizhou Province, we systematically investigated the genetic background of Chuanqing people through population genetic approaches, including genetic distance estimation, principal component analysis, and phylogenetic tree construction. RESULTS: Among the studied population, the number of haplotype per microhaplotype ranged from 6 to 25. The average expected heterozygosity (He), observed heterozygosity (Ho), power of discrimination (PD), and probability of exclusion (PE) were 0.8291, 0.8301, 0.9387, and 0.6593, respectively. The cumulative power of discrimination (CPD) and cumulative probability of exclusion (CPE) for these 33 loci were 1-2.62×10^-41 and 1-7.64×10^-17, respectively. Population genetic analyses revealed that the Chuanqing population had close genetic relationships with the East Asian populations, especially the local Guizhou Han population, Beijing Han population and the Han populations living in southern China. CONCLUSIONS The 33 microhaplotypes exhibit high levels of genetic diversity in the Guizhou Chuanqing population, highlighting their potentials for both forensic identification and parentage testing. The Han populations might have contributed a significant amount of genetic material to the Chuanqing population during the formation and development of the latter.
Humans ; China/ethnology* ; Ethnicity/genetics* ; Forensic Genetics/methods* ; Genetics, Population ; Genotype ; Haplotypes ; Phylogeny ; East Asian People/genetics*

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Objective To establish a renal cell co-culture system to simulate the renal barrier system,and to test its responsiveness to different glucose concentrations,and to investigate the regulatory effect of miR-29b-3p on osteopontin(OPN)/transforming growth factor β(TGF-β)pathway and the changes of this pathway under high glucose condition.Methods The three-cell co-culture system consisting of human renal podocytes,human glomerular mesangial cells and human renal tubular epithelial cells was established to test the cell viability and glucose consumption value at glucose concentrations of 5,8,12 and 16 mmol/L.The content of TGF-β and OPN in cell supernatant was measured.The recombinant plasmid and siRNA of OPN were transfected,and the expressions of TGF-β and OPN were detected by Q-PCR and Western blot.Results The mRNA expressions of OPN,TGF-β and miR-29b were significantly increased at 12 mmol/L glucose conditions.Western blot results showed that the protein expression of OPN increased in high glucose conditions,while the protein expression of TGF-β did not change significantly.After adding miR-29b-3p activator,the mRNA levels of OPN and TGF-β in the cell supernatant were significantly increased.After adding miR-29b-3p inhibitor,the mRNA levels of OPN and TGF-β in the cell supernatant were significantly decreased.Western blot results showed that compared with 5 mmol/L glucose,the protein expressions of OPN and TGF-β were increased by miR-29b-3p activator,and the protein expressions of OPN and TGF-β were decreased by miR-29b-3p inhibitor.After transfection with OPN recombinant plasmid,the content of TGF-β in the cell supernatant was significantly increased,and the mRNA expressions of OPN and TGF-β in the cells were significantly increased.After transfection with OPN siRNA,the content of TGF-β in the cell supernatant was decreased,and the expression of OPN mRNA in the cells was significantly decreased,but the expression of TGF-β mRNA was not significantly increased.Conclusion The renal cell co-culture system can mimic the complex renal environment in vivo.When induced by high glucose,cell proliferation is inhibited,glucose consumption is increased,and the content of TGF-β in the cell supernatant is increased,and miR-29b-3p has a regulatory effect on OPN/TGF-β signaling pathway in the co-culture system.

Background::Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening.Methods::We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial.Results::This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios.Conclusion::This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Objective To observe the therapeutic effect and mechanism of Baoyuan Decoction for chronic heart failure model rat.Methods SD rats were randomly divided into blank group,model group,Baoyuan Decoction group,Captopril group,Baoyuan Decoction+CCT020312[protein kinase R-like endoplasmic reticulum kinase(PERK)activator]group,15 rats in each group.Except for the blank group,the rats in the other groups were induced by Adriamycin to construct a chronic heart failure model.After corresponding drug intervention,cardiac function indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),brain natriuretic peptide(BNP),cardiac troponin I(cTnI)],inflammation-related factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)],oxidative stress factors[malondialdehyde(MDA),superoxide dismutase(SOD)]were detected in each group.Changes in apoptosis-related indicators[B-cell lymphoma 2(Bcl-2),B-cell lymphoma 2-associated X protein(Bax),Caspase-3]and PERK/transcription activator 4(ATF4)signaling pathway-related proteins glucose-regulated protein 78(GRP78),PERK,ATF4,C/EBP homologous protein(CHOP)levels.Results Compared with the blank group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in the model group were significantly increased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly decreased(all P＜0.05).Compared with the model group and Baoyuan Decoction+CCT020312 group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in Baoyuan Decoction group and Captopril group were significantly decreased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly increased(all P＜0.05).Compared with the Captopril group,there was no significant change in the above indexes(except CHOP protein expression level)in the Baoyuan Decoction group(P＞0.05).Conclusion Baoyuan Decoction can delay the progression of chronic heart failure rats,and its mechanism may be related to inhibiting the PERK/ATF4 signaling pathway to alleviate cardiomyocyte apoptosis,further reducing the degree of inflammatory response and oxidative stress,thereby promoting the repair of cardiac function and myocardial injury.