Objective lo analyze the difference of peri-coronary tat attenuation index(pr Al)on different grades of hypertension(HT),and to explore the value of pFAI in evaluating the risk of HT patients.Methods Retrospective data on hospitalized patients who underwent coronary computed tomography angiography(CCTA)examination for chest pain were collected.A total of 415 clini-cally confirmed HT patients were selected as observation group(including 132 patients in grade 1 HT group,137 patients in grade 2 HT group,146 patients in grade 3 HT group),and 187 non-hypertension patients during the same period as control group.The differ-ence of fat attenuation index(FAI)in three main coronary arteries[left anterior descending artery(LAD),left circumflex artery(LCX),right coronary artery(RCA)]was compared,and the correlation between pF AI and HT patients was analyzed.Results RCA-FAI(-78.86 HU±7.66 HU)and LAD-FAI(-80.62 HU±7.50 HU)were higher in HT group than those in control group(-84.46 HU± 8.00 HU,-83.43 HU±7.51 HU,P＜0.05).pFAI value was higher in grade 3 HT group than that in grade 1 HT group and grade 2 HT group(P＜0.05),while there were no differences between grade 1 HT group and grade 2 HT group(P＞0.05).After adjusting the influence of traditional risk factors and coronaryartery disease,RCA-FAI had relatively closer relationship with HT grades(r=0.47,P＜0.001).Conclusion LAD-FAI,RCA-FAI in the HT group are higher than those in control group and RCA-FAI has relatively closer relationship with HT grades,suggesting that RCA-FAI may be an imaging indicator to evaluate the pro-gression of HT and predict the risk of HT.

BACKGROUND:Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose,infection and inflammation.It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors,and has great application prospect in bone tissue engineering. OBJECTIVE:To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine,especially its osteogenic potential under high glucose,infection and inflammation conditions,and its biological safety,so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS:PubMed,WanFang,and CNKI were searched for relevant literature using the keywords of"berberine,bone defects,bone repair,bone regeneration,osteoinductive,osteoporosis,osteoblast,osteoclast,bone tissue engineering,bone,high glucose,diabetes,inflam*,infect*"in English and Chinese,respectively.A total of 105 literatures were selected for review. RESULTS AND CONCLUSION:Berberine can be used to treat multiple diseases including bone diseases,and it has the ability to promote bone regeneration.This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies.Studies have shown that it can play a role in bone repair by promoting osteogenesis,inhibiting osteoclast formation and activity,and preventing osteoporosis.It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin,PI3K/AKT,EGFR/MEK/p38MAPK,cAMP/PKA/CREB,ERK and other signaling pathways.Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose,infection and inflammation,which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site.Berberine also has the advantages of low toxicity,low price,easy access(currently it can be synthesized),which is a relatively ideal bone induction potential drug.In recent years,the application of berberine in the treatment of bone defect tends to be localized,mainly through the combination with bone tissue engineering technology to improve bioavailability,and has shown good bone repair effect and excellent biological safety in animal experiments.In addition,preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes,local infection and inflammation.In the future,more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine,and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength,efficacy and biological safety.

Objective This article aims to investigate the association between hypertension and the risk of GSD by conducting a national multicenter study,a systematic review,and a meta-analysis.Methods The study was conducted in three stages.In the first stage,subjects were recruited for health examination in four hospitals in Chengdu,Tianjin,Beijing,and Chongqing,China,from 2015 to 2020,and the multivariate logistic regression analysis was used to investigate the association between hypertension and the risk of GSD in each center.In the second stage,Embase,PubMed,Wanfang Data,VIP,and CNKI databases were searched for related studies published up to May 2021,and a meta-analysis was conducted to further verify such association.In the third stage,the random effects model was used for pooled analysis of the results of the multicenter cross-sectional study and the findings of previous literature.Results A total of 633 948 participants were enrolled in the cross-sectional study,and the prevalence rate of GSD was 7.844%.The multivariate logistic regression analysis showed that hypertension was positively associated with the risk of GSD(P＜0.05).Subgroup analysis showed that there was no significant difference in the association between hypertension and GSD between individuals with different sexes,ages,and subtypes of GSD.A total of 80 articles were included in the systematic review and the meta-analysis,and the results showed that the risk of GSD was increased by 1.022 times for every 10 mmHg increase in diastolic pressure and 1.014 times for every 10 mmHg increase in systolic pressure.Conclusion Hypertension significantly increases the risk of GSD,and the findings of this study will provide a basis for the etiology of GSD and the identification of high-risk groups.

Based on the characteristics of postoperative gynaecological diseases， Lingnan LUO's Gynaecology has summarized the idea of "eliminating abdominal mass to help pregnancy"， and applied the elimination method in the postoperative gynaecological treatment to promote rehabilitation， prevent recurrence， and regulate menstruation in a sequential manner， which is divided into three phases of diagnosis and treatment. The first stage of postoperative rehabilitation （2 weeks after surgery） is based on the pathogenesis of profuse deficiency， profuse stasis， and easy to retain pathogens， and the treatment should focus on tonifying the positive qi and eliminating abdominal mass at the same time， commonly used in modified Sijunzi Dcoction （四君子汤） and Shenghua Dcoction （生化汤）. In the second stage of postoperative rehabilitation （2 weeks to 2-3 months after surgery）， the pathogenesis is mainly kidney deficiency and blood stasis， which should be treated by tonifying kidney and supplement essence， eliminate blood stasis and eliminate abdominal mass， and commonly use the Guishen Pill （归肾丸） with herbs that invigorating blood， dissolving stasis， and clearing the collaterals. Postoperative sequential menstrual regulation and fertility promotion stage （after the end of the postoperative rehabilitation stage， the normal anatomy of the uterine cavity and pelvis is basically restored） adopts cyclic sequential therapy， according to the characteristics of the pathogenesis of the different periods of menstruation in phases， always tonifying kidney and regulating menstruation， eliminating abdominal mass， and attaches importance to the application of four methods of eliminating abdominal mass， including invigorating blood and dissolving stasis， moving qi to resolve constraint， dissolving phlegm and dispelling dampness， resolving accumulation and removing stagnation.

Objective To systematically evaluate the efficacy of traditional Chinese medicine(TCM)in the treatment of recurrent spontaneous abortion and their regulatory effects of levels of peripheral blood Th17 cells and Treg cells.Methods Computer retrieval of CNKI,WanFang,VIP,SinoMed,FMRS,PubMed,Cochrane Library,Embase,Web of science and other databases were carried out.RCTS related to the regulation of Th17 and Treg cells by TCM in the treatment of recurrent spontaneous abortion,published from the establishment of the database to June 2023 were screened.Two reviewers evaluated the quality of the literature according to the Cochrane handbook.RevMan5.4 software was used for Meta-Analysis.Results A total of 10 studies that involved 1 052 patients were included.The Meta-Analysis results showed that compared to the control group,the effective rate[RR=1.20,95%CI(1.11,1.30),P＜0.000 01],live birth rate[RR=1.32,95%CI(1.16,1.50),P＜0.000 01]and the reduction of adverse drug reactions[RR=0.34,95%CI(0.14,0.83),P=0.02]were significantly improved by the intervention of TCM.After treatment with TCM,the expression of Th17 cells was decreased[MD=-0.71,95%CI(-1.01,-0.41),P＜0.000 01],and the expression of Treg cells was increased[SMD=1.21,95%CI(0.80,1.62),P＜0.000 01].The ratio of Th17/Treg cells was decreased[SMD=-2.62,95%CI(-4.09,-1.14),P=0.000 5].Conclusion TCM used for post-pregnancy or before and after pregnancy can significantly improve the clinical symptoms and live birth rate of patients with recurrent spontaneous abortion,wihch showed high safety.Moreover,TCM can reduce the expression of Th17 cells,up-regulate the expression of Treg cells and regulate the immune balance of Th17/Treg cells,which is conducive to embryonic development after pregnancy.

Electrocardiogram (ECG) signal is an important basis for the diagnosis of arrhythmia and myocardial infarction. In order to further improve the classification effect of arrhythmia and myocardial infarction, an ECG classification algorithm based on Convolutional vision Transformer (CvT) and multimodal image fusion was proposed. Through Gramian summation angular field (GASF), Gramian difference angular field (GADF) and recurrence plot (RP), the one-dimensional ECG signal was converted into three different modes of two-dimensional images, and fused into a multimodal fusion image containing more features. The CvT-13 model could take into account local and global information when processing the fused image, thus effectively improving the classification performance. On the MIT-BIH arrhythmia dataset and the PTB myocardial infarction dataset, the algorithm achieved a combined accuracy of 99.9% for the classification of five arrhythmias and 99.8% for the classification of myocardial infarction. The experiments show that the high-precision computer-assisted intelligent classification method is superior and can effectively improve the diagnostic efficiency of arrhythmia as well as myocardial infarction and other cardiac diseases.
Humans ; Electrocardiography ; Heart Diseases ; Myocardial Infarction/diagnostic imaging* ; Algorithms ; Electric Power Supplies

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8⁺ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Objective:To investigate the impact of cleavage factor Im25(CFIm25)on VSMCs-specific knockdown in the context of hyperlipidemia.Methods:Mice models were constructed with specific knockout of CFIm25 in VSMCs(CFIm25f/+ TaglnCre)and control mice(TaglnCre).The mice were fed a normal diet or high-fat diet(HFD)for 18 weeks and their body weight changes were monitored.ELISA was used to measure serum total cholesterol(TC), triacylglycerol(TG), high-density lipoprotein(HDL-C)and low-density lipoprotein(LDL-C)levels.The extent of aortic lipid deposition in mice was assessed by oil red O staining.Results:During the feeding of a high-fat diet, CFIm25f/+ TaglnCre mice showed a significant increase in body weight compared to the control group[Male(1.01±0.06)g and(0.87±0.31)g, t=7.53, P<0.05; Female: (0.64±0.02)g and(0.35±0.04)g, t=9.68, P<0.05].After 18 weeks of high-fat diet feeding, CFIm25f/+ TaglnCre mice had significantly higher levels of TC[(6.80±0.35)mmol/L and(3.76±0.87)mmol/L, t=5.63, P=0.004], TG[(0.97±0.21)mmol/L and(0.42±0.10)mmol/L, t=4.08, P=0.015], and LDL-C[(5.20±0.30)mmol/L and(2.00±0.98)mmol/L, t=5.40, P=0.006]compared to the TaglnCre group.Specifically, TC levels increased by 80.72%, TG increased by 132.79%, and LDL-C increased by 160.32%.There was a significant increase in aorta lipid deposition and atherosclerotic plaque area in CFIm25f/+ TaglnCre mice( P<0.05). Conclusions:The research indicated that VSMCs-specific CFIm25 knockdown in mice further worsened hyperlipidemia and atherosclerotic lesions.

Objective To investigate the effects of cyclic stretch on migration of MC3T3-E1 cells and its related mechanism. Methods The strain loading system was used to stretch MC3T3-E1 cells cultured in vitro with 15% amplitude, to simulate the mechanical condition in vivo. The wound healing assay was used to detect the migration of MC3T3-E1 cells. Western blotting was used to test Runx2 expression. RNA interfering was used to decrease Runx2 expression. Results Cyclic mechanical stretch with 15% amplitude, 1.25 Hz frequency and lasting for 24 hours could promote the migration of MC3T3-E1 cells and increase the expression level of Runx2. Runx2 interference inhibited the migration of MC3T3-E1 cells in static culture condition. Interference with Runx2 expression in MC3T3-E1 cells could partially reduce the positive effect of cyclic mechanical stretch on cell migration. Conclusions Cyclic stretch can promote the migration of MC3T3-E1 cells, and Runx2 may play an important role in this process. This study provides experimental basis for finding innovative clinical treatment method to promote fracture healing.