Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Objective: Randomized controlled trials (RCTs) of Chinese patent medicines and classic traditional Chinese medicine prescriptions were systematically reviewed from both Chinese and English journals published in 2023. A preliminary summary and evaluation were conducted on the generation and translation of clinical evidence for these treatments. This analysis aims to inform future research on clinical efficacy evaluation and guide the rational application of evidence. Methods: RCTs of Chinese patent medicines and classic traditional Chinese prescriptions published in 2023 were comprehensively retrieved from the Artificial Intelligence Clinical Evidence Database for Chinese Patent Medicine (AICED-CPM), with supplementary searches conducted in China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (SinoMed), Cochrane Library, PubMed, Embase, and Web of Science. The study characteristics and methodological quality of these RCTs were systematically analyzed and evaluated. Results: A total of 1 443 RCTs of Chinese patent medicines were included, comprising 1 399 Chinese articles and 44 English articles. Additionally, 334 RCTs of classic traditional Chinese medicine prescriptions were found, with 331 published in Chinese and 3 in English. 196 567 participants were included, covering 585 types of Chinese patent medicines (487 oral, 61 injectable, and 37 topical) and 179 classic traditional Chinese medicine prescriptions. The involved studies encompassed 22 types of diseases, with research primarily focusing on diseases of the circulatory system, the respiratory system, and the genitourinary system. The sample sizes ranged from 18 to 3 777 participants, and most studies were conducted at a single center. Methodologically, the implementation of allocation concealment and blinding remained insufficiently emphasized. Conclusion Overall, compared with 2022, both the number of RCT publications and their methodological quality have improved in 2023, with heightened attention to research on diseases of the genitourinary system. However, quality control and standardized management in the design and implementation processes still require enhancement to produce more high-quality clinical evidence and accelerate the translation and application of this evidence.

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Objective:To employ qualitative research methods to evaluate the sustainability of the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) interventions and their influencing factors.Method:In September 2023, interviewees meeting the inclusion criteria were recruited through purposive sampling in Jinan, Shandong Province. A semi-structured interview guide was designed based on the CFIR and RE-AIM frameworks. Personal in-depth interviews and focus group discussions were conducted to gather insights on the feasibility, effectiveness, and sustainability of the project interventions from various stakeholders, including representatives from the government, food manufacturers, restaurants, academia, and residents.Results:A total of 15 individuals participated in in-depth interviews, involving six representatives from food manufacturers, four from restaurants, three from the government, and two from academia. There were four focus group discussions with 30 residents. The study found that at the individual resident level, health awareness and the availability of sodium reduction tools in the market could affect their salt reduction practices. For food manufacturers and restaurants, consumers′ preferences, technical challenges in reformulation, and government support were key factors determining the smooth progress of their salt reduction efforts. At the governmental level, multi-sectional coordination, chronic disease management demonstration areas, and the impact of the pandemic were the main factors influencing the implementation of sodium reduction interventions.Conclusion:Future endeavours should strengthen long-term management and optimise the complex influencing factors associated with intervention measures. This will be essential in sustaining and expanding the positive health outcomes achieved through the Shandong population sodium reduction strategy.

Objective·To investigate the safety and feasibility of early goal-directed mobilization in the recovery of gastrointestinal function after pancreaticoduodenectomy.Methods·The non-contemporaneous controlled studies were conducted.Subjects who underwent pancreaticoduodenectomy were included.From Sep 2022 to May 2023,forty patients were selected as the control group,and forty patients were selected from June 2023 to February 2024 as the experimental group.The general clinical data of the two groups were collected.The control group was treated with the nursing routine after pancreaticoduodenectomy,and there were no specific requirements for the time and goal of early activity.The experimental group had daily activity goals established for early mobilization,which were performed by the patients and their families,while the rest of their care was identical to that of the control group.The main index of effectiveness evaluation was the time of first flatus and first defecation,and the secondary indexes included the time of first getting out of bed,the time of oral drinking,the time of the gastric tube removal,and the postoperative levels of K+,Na+,and Cl-on the 3rd day of the postoperative period.Safety evaluations included chyle leak,postoperative pancreatic fistula,biliary leak and delayed gastric emptying,postoperative hemorrhage,unplanned reoperation,unplanned extubation,falls and death.Results·There was no statistically significant difference in the general clinical data of the patients in the 2 groups.After the implementation of early goal-directed mobilization,the time of first flatus was advanced from(3.95±1.68)d to(2.88±0.91)d(t=-3.560,P=0.001),and the time of first defecation was advanced from(4.90±1.61)d to(3.80±1.30)d(t=-3.352,P=0.001).The time of first getting out of bed was advanced from(5.18±1.77)d to(2.30±0.88)d(t=-9.205,P＜0.001),and the time of oral drinking was advanced from(4.10±1.89)d to(2.73±1.20)d(t=-3.883,P＜0.001).Significant differences were also observed in postoperative day 3 Na+(t=-2.745,P=0.008)and Cl-(t=-2.033,P=0.045)levels.Conclusion·Early goal-directed activity programs are safe and effective in promoting the recovery of gastrointestinal function after pancreaticoduodenectomy.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.