BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

Objective To investigate the application value of the MHSeqTyper47 kit in kinship identification.Methods Multiplexed amplification and library preparation were performed for DNA samples from 113 related individuals by using the MHSeqTyper47 kit.The libraries were sequenced on a MiSeq FGx sequencer,and the data were analyzed using MHTyper for microhaplotype genotyping.The kinship indexes were calculated to evaluate the application efficiency of this kit in kinship identification and compared with those of the GlobalFilerTM kit.Results For the MHSeqTyper47 kit,the CPI values in trio identification were 1.43× 1011～6.15×1018.The CPI values in duo identification were 1.02× 105～1.53× 1013.The CFSI values in full sibling identification were 7.73×101～2.59×1016.Trios,duos and full siblings could be completely distinguished from unrelated pairs.The combined efficiency of these two kits in 2nd-degree kinship identification was 0.466 2.Conclusion The application value of MHSeqTyper47 kit is relatively higher in the identification of lst-degree kinships.If jointly used with the GlobalFilerrM kit,2nd-degree kinship identification could be achieved in some cases.

Vertebrobasilar dolichoectasia is a rare and challenging disorder. Vertebrobasilar dolichoectasia is closely related to enzyme action and hemodynamic changes, and is characterized by ischemic stroke, neurological compression symptoms, hydrocephalus, and other clinical symptoms. With development of interventional techniques and materials in recent years, endovascular treatment of vertebrobasilar dolichoectasia has become the focus. This article summarizes the current endovascular treatment of vertebrobasilar dolichoectasia, aiming to provide references for clinicians.

Objective:To explore the current status of lipid-lowering therapy, the distribution of low-density lipoprotein cholesterol (LDL-C) levels and the risk assessment of cardiovascular events recurrence in patients with coronary heart disease (CHD) complicated by hypertension.Methods:This was a cross-sectional study. Patients with CHD combined with hypertension were hospitalized in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from August 5, 2008 to July 22, 2018 were included, and were divided into standard group and substandard group according to whether LDL-C reached the standard. Study data were obtained from inpatient coronary angiography records and electronic medical records database of Department of Cardiology, General Hospital of Chinese People′s Liberation Army, who used data from the first diagnosis of CHD. Clinical data of the selected patients were collected. Multivariate logistic regression model was used to analyze the associated factors of whether LDL-C reached the standard in CHD patients with hypertension.Results:A total of 18 800 patients were selected from 31 provinces/autonomous regions/municipalities directly under the central government in China, with Beijing accounting for the largest proportion (5 692 patients (30.28%)), followed by Hebei (3 621 patients (19.26%)), Henan (1 837 patients (9.77%)), and Shandong (1 618 patients (8.61%)). Among the selected patients, 1 493 had LDL-C<1.4 mmol/L (standard group), and 17 307 had LDL-C≥1.4 mmol/L (substandard group). Only 1 493 patients (7.94%) had LDL-C<1.4 mmol/L. There were 4 518 patients (24.03%), 4 366 patients (23.22%), 6 924 patients (36.83%) and 1 499 patients (7.97%) with LDL-C for 1.4-<2.0, 2.0-<2.5, 2.5-<3.8 and≥3.8 mmol/L levels, respectively. 17 855 patients (95.15%) were treated with statins, but only 1 334 patients (7.10%) were treated with statins and ezetimibe. Of the selected patients, 4 986 patients (26.52%) were at low risk, 6 515 patients (34.65%) were at intermediate risk, and 7 299 patients (38.82%) were at high risk. The combined lipid-lowering treatment rates of statin and ezetimibe in the middle-and high-risk patients were 7.43% (484/6 515) and 7.48% (546/7 299), respectively. The results of multivariate logistic regression analysis showed that increasing age, male, diabetes mellitus, stroke, and history of percutaneous coronary intervention (PCI) were positively associated with LDL-C standards in patients with CHD and hypertension, whereas obesity and acute myocardial infarction (AMI) were negatively associated with LDL-C standards (all P<0.01). Conclusions:The rate of achieving the standard LDL-C in patients with CHD combined with hypertension was low in China. Although the majority of patients had received moderate-intensity statin therapy, the proportion of statin-treated patients combined with ezetimibe was extremely low. The proportion of high-risk patients with recurrent cardiovascular events was higher in patients with CHD and hypertension in China, whereas the proportion of such patients receiving statin combined with ezetimibe lipid-lowering therapy was lower. This study also found that increasing age, male, diabetes mellitus, stroke, and history of PCI were positively associated with LDL-C standards, while obesity and AMI were negatively associated with LDL-C standards in patients with CHD and hypertension.

Objective:To investigate the short-term efficacy and safety of Donafenib as postoperative adjuvant therapy for patients with high risk of recurrence after radical resection of hepatocellular carcinoma (HCC).Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinicopathological data of 157 HCC patients with high risk of recurrence after radical resection who were admitted to 6 medical centers, including The First Affiliated Hospital of Nanjing Medical University et al, from June 2021 to February 2023 were collected. There were 128 males and 29 females, aged (59±10)years. Of 157 patients, 101 cases undergoing Donafenib as postoperative adjuvant therapy were divided into the the Donafenib group, and 56 cases under-going no systemic postoperative adjuvant therapy were divided into the control group. Observation indicators: (1) PSM and comparison of general data of patients between the two groups after matching; (2) postoperative treatment; (3) follow-up and survival of patients; (4) analysis of risk factors affecting recurrence-free survival of patients. PSM was done based on the principle of optimal perfect matching, with the clamp value of 0.5, and the Donafenib group and the control group were matched at a ratio of 1.25∶1. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and/or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Kruskal-Wallis H test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and the Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) PSM and comparison of general data of patients between the two groups after matching. Of 157 patients, 126 cases were successfully matched, including 70 cases in the Donafenib group and 56 cases in the control group, respectively. The elimination of tumor number confounding bias ensured comparability between the two groups after PSM. (2) Postoperative treatment. After PSM, of 70 patients in the Donafenib group, there were 23 cases receiving Donafenib monotherapy, 26 cases combined with transcatheter arterial chemoembolization (TACE), 14 cases combined with immunotherapy, and 7 cases combined with TACE+immunotherapy. Of 56 patients in the control group, there were 37 cases receiving postoperative follow-up alone and 19 cases combined with TACE. (3) Follow-up and survival of patients. All 157 patients were followed up, and the follow-up time of the 101 patients in Donafenib group and the 56 patients in control group were 10.1(range, 6.3-14.6)months and 22.2(range, 15.1-25.5)months, respectively. During the follow-up period, 70 patients in the Donafenib group experienced treatment-related adverse reactions, inclu-ding 8 cases of grade 3 adverse reactions, 23 cases of grade 2 and 39 cases of grade 1 adverse reactions, respectively. After PSM, the postoperative 12-, 18-month recurrence-free survival rates were 83.7%, 83.7% in the 70 patients of Donafenib group and 67.8%, 58.9% in the 56 patients of control group, respectively, showing a significant difference in the postoperative recurrence-free survival time between the two groups ( hazard ratio=0.395, 95% confidence interval as 0.176-0.888, P<0.05). (4) Analysis of risk factors affecting recurrence free survival of patients. Results of multivariate ana-lysis showed that microvascular invasion, vascular thrombus, clinical stage as ⅢA were independent risk factors affecting recurrence-free survival in patients with high risk of recurrence after radical resection of HCC ( hazard ratio=2.181, 2.612, 2.612, 95% confidence interval as 1.028-4.629, 1.128-6.047, 1.128-6.047, P<0.05), Donafenib as postoperative adjuvant therapy was an independent protective factor affecting recurrence-free survival in patients with high risk of recurrence after radical resection of HCC ( hazard ratio=0.457, 95% confidence interval as 0.227-0.920, P<0.05). Results of further analysis showed that after PSM, there were significant differences in the postoperative recurrence-free survival time in patients with different clinical factors, including male, age ≥60 years, tumor diameter >5 cm, positive microvascular invasion, positive hepatitis B virus infection, alpha fetoprotein <200 μg/L, between the Donafenib group and the control group ( hazard ratio=0.283, 0.202, 0.174, 0.345, 0.273, 0.180, 95% confidence interval as 0.114-0.707, 0.044-0.937, 0.038-0.794, 0.128-0.929, 0.091-0.819, 0.052-0.620, P<0.05). Conclusion:Donafenib as postoperative adjuvant therapy can effectively reduce the short-term recurrence rate in patients with high risk of recurrence after radical resection of HCC, with good safety and tolerance.

Background::The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF.Methods::This cross-sectional study was conducted in Chinese People’s Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD.Results::The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28 % (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2DS 2-VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P < 0.01), but remained at a relatively low level. Conclusions::AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

Alzheimer Disease/genetics* ; Animals ; Apolipoprotein E4/metabolism* ; Gene-Environment Interaction ; Hippocampus/metabolism* ; Male ; Noise/adverse effects* ; Rats

Objective:To analyze the distribution and clinical significance of cytochrome P 450 2C19 (CYP2C19) gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan. Methods:The data of 245 patients with cardiovascular and cerebrovascular diseases who received treatment in Southern Central Hospital of Yunnan Province between May 2019 and June 2020 were retrospectively analyzed. The distribution of CYP2C19 gene and its relationship with nationality, age, sex, blood lipids, hypertension, and diabetes were analyzed and compared between southern Yunnan and other regions.Results:The proportions of seven phenotypes of CYP2C19 gene *1/*17, *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, *3/*3 in 245 patients were 2.86%, 38.37%, 39.18%, 5.31%, 9.39%, 4.08% and 0.82%, respectively. The proportions of individuals with superfast/ultrafast metabolism, fast metabolism, intermediate metabolism, and slow metabolism in 245 patients were 2.86%, 38.37%, 44.49%, and 14.29%, respectively. The frequency of polymorphisms in the CYP2C19 gene was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), which was constant and representative. The Fisher test showed that the CYP2C19 gene distribution of patients with cardiovascular and cerebrovascular diseases in southern Yunnan was not greatly correlated with nationality, age, sex, underlying disease, blood lipids, and the types of cardiovascular and cerebrovascular diseases (all P > 0.05). There was a significant difference in CYP2C19 gene distribution in patients from southern Yunnan versus Dongguan, Jiangxi, Fujian, northern Sichuan, Chifeng, Xiamen, Shaanxi, and Kunming ( P < 0.001, < 0.001, 0.045, 0.008, 0.001, 0.005, < 0.001, 0.016). Conclusion:The distribution of CYP2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan is not obviously correlated with nationality, age, sex, underlying diseases, blood lipids, and the types of cardiovascular and cerebrovascular diseases. CYP2C19 gene distribution is related to regional distribution, which can guide personalized medication in different regions.

OBJECTIVE To explore the the reg ulation of intestinal flora and effects of Qingjie huagong decoction on intestinal mucosal barrier in severe acute pancreatitis （SAP）mode rats . METHODS SAP rat model was induced by intraperitoneal injection of caerulein and lipopolysaccharide.The survival state of rats in each group were observed.The levels of serum amylase ，interleukin 10（IL-10），IL-18 and IL- 1β in serum were all detected. The pathological changes of pancreatic and small intestinal tissue were observed. The expressions of Occludin，ZO-1 and HMGB1 were detected in small intestinal tissue of rats. The structure and relative abundance of intestinal microflora in rats were detected by 16S rRNA high throughput sequencing. RESULTS After the intervention of Qingjie huagong decoction ，abdominal distension symptoms of SAP model rats were significantly relieved ，and their mental state recovered better ；the levels of serum amylase and IL- 18 in serum were decreased significantly （P＜0.05），while the level of IL- 10 was increased significantly （P＜0.05）. The necrotic area of pancreatic tissue and the infiltration of inflammatory cells were reduced ， the degree of intestinal epithelial cell structural disorder was alleviated ，and the shedding of intestinal mucosal epithelium was reduced.The protein expression of HMGB 1 in small intestinal tissue was decreased significantly （P＜0.05），and the protein expression of Occludin and ZO- 1 were increased significantly . Results of 16S rRNA high throughput sequencing showed that Qingjie huagong decoction could increased the relative abundance of probiotics such as Bacteroidea and Lactobacillus in rat intestine ，reduced the colonization of harmful bacteria such as Firmicutes. CONCLUSIONS Qingjie huagong decoction can improve the intestinal barrier by up-regulating the expression of Occludin and ZO- 1 in small intestinal tissue and down-regulating the protein expression of HMGB 1. It can also adjust the relative abundances of different flora to protect the intestinal tract.

One-sixth of the currently known natural products contain α, β-unsaturated carbonyl groups. Our previous studies reported a rare C-sulfonate metabolic pathway. Sulfonate groups were linked to the β-carbon of α, β-unsaturated carbonyl-based natural compounds through this pathway. However, the mechanism of this type of metabolism is still not fully understood, especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition. In this work, the enzyme-mediated and non-enzymatic pathways were studied. First, the sulfite content in rat intestine was determined by LC-MS/MS. The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383 μg·g