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:To analyze the diagnostic value of transvaginal two-dimensional ultrasound and three-dimensional ultrasound volume imaging (3DVI) technology for intrauterine adhesions.Methods:A total of 120 suspected patients with intrauterine adhesions admitted to Beijing Tongzhou District Maternal and Child Health Hospital from July 2022 to June 2023 were selected as the research subjects. All patients underwent transvaginal two-dimensional ultrasound and 3DVI technology examination, and the diagnostic value of vaginal two-dimensional ultrasound and 3DVI technology single examination and combined examination was compared based on the results of hysteroscopy examination as the gold standard; Comparison of ultrasound parameters between the intrauterine adhesions group and the non intrauterine adhesions group, as well as patients with different degrees of intrauterine adhesions [endometrial thickness (ED), endometrial volume (EV), vascular index (VI), blood flow index (FI), vascular comprehensive index (VFI)].Results:Among 120 suspected patients with intrauterine adhesions, 104 cases were positive in hysteroscopy examination, with a positive rate of 86.67%. Among them, 50 cases were mild, 36 cases were moderate, and 18 cases were severe. 76 cases were positive in vaginal two-dimensional ultrasound examination, with a positive rate of 63.33%; 79 cases were positive for 3DVI technology examination, with a positive rate of 65.83%; The combined examination results of vaginal two-dimensional ultrasound and 3DVI technology were positive in 87 cases, with a positive rate of 72.50%. The sensitivity, specificity, positive predictive value, and negative predictive value of vaginal two-dimensional ultrasound examination were 68.27%, 68.75%, 93.42%, and 25.00%, respectively. The 3DVI technique examination was 73.08%, 81.25%, 96.20%, and 31.71%, respectively. The combined examination was 83.65%, 100.00%, 100.00%, and 48.48%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the combined examination were all higher than those of vaginal two-dimensional ultrasound examination (all P<0.05). 104 cases in the intrauterine adhesions group and 16 cases in the non intrauterine adhesions group; The ED, EV, VI, FI, and VFI of the intrauterine adhesions group were lower than those of the non intrauterine adhesions group (all P<0.05). The differences in ED, EV, and VI among patients with different degrees of intrauterine adhesions were statistically significant (all P<0.05); The ED, EV, and VI in the moderate group were lower than those in the mild group (all P<0.05), while the ED, EV, and VI in the severe group were lower than those in the mild and moderate groups (all P<0.05), and the FI was lower than those in the mild group ( P<0.05). Conclusions:Transvaginal two-dimensional ultrasound combined with 3DVI technology has high diagnostic value for intrauterine adhesions and can be used to evaluate the degree of intrauterine adhesions.

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.

Objective:To explore the clinicopathological characteristics and the related influencing factors of efficacy and prognosis of elderly patients with malignant mesothelioma(MM)in Chinese population.Methods:We retrospectively analyzed the clinical data of 115 patients aged 65 years and above who were diagnosed with MM in Beijing Hospital, Peking University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences between November 2007 and July 2024, and the patients were grouped according to age(≥75 years in the older group and <75 years in the younger group), histological types and therapy regimens.Kaplan-Meier curve and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The positive expression rate of Calretinin in the Chinese elderly population with MM was consistent with previous reports, while the positive rates of Cytokeratin 5/6(CK5/6), WT-1, and D2-40 were much lower.The overall response ratio(ORR)for first-line treatment was 17.3%(9/52), and the disease control rate(DCR)was 92.3%(48/52).The ORR for second-line treatment was 7.7%(1/13)and the DCR was 76.9%(10/13).The ORR and DCR were higher in the first-line immunotherapy group than in the chemotherapy group, 50.0% vs.14.6%( P=0.134)and 100.0% vs.91.6%( P=1.000), respectively.The ORR in the second-line immunotherapy group was higher than that in the chemotherapy group, 25.0% vs.0, respectively, and the DCR were both 75.0% in two groups.The median progression free survival(mPFS)was 9.2 months and median overall survival(mOS)was 19.0 months for patients receiving first-line treatment, and the mPFS was 3.3 months and mOS was 11.0 months for second-line therapy.The first-line immunotherapy provided more shorter mPFS(1.6 months vs.9.2 months, P=0.081)and longer mOS(not reached vs.18.1 months, P=0.147)than the chemotherapy group.The younger group had prolonged mPFS(9.7 months vs.7.2 months, P=0.305)while shorter mOS(18.1 months vs.23.9 months, P=0.289)compared with the older group, and none of them reached statistical differences.Both mPFS and mOS were prolonged in the epithelioid subtype compared with the non-epithelioid subtypes, 10.4 months vs.1.6 months( P<0.001)and 20.3 months vs.4.6 months( P=0.803), respectively.Both mPFS(7.1 months vs.4.7 months, P=0.583)and mOS(18.3 months vs.6.3 months, P=0.134)were prolonged in the second-line chemotherapy group compared with the immunotherapy group.The Cox regression analysis showed that gender, Eastern Cooperative Oncology Group, Performance Status(ECOG PS)and positive CK5/6 were both the independent predictors for the first-line PFS.Histological type was an independent prognostic factor for the first-line OS. Conclusions:MM in the Chinese elderly population exhibits unique clinicopathologic characteristics.The immunotherapy improves ORR, DCR and prolongs mOS in first-line use, and improves ORR in second-line.First-line treatment improves mPFS in the younger group compared with the older group.Multivariate Cox regression demonstrates that gender, ECOG PS and CK5/6 expression are both predictors of efficacy, and histological type is an independent prognostic factor for survival of the Chinese elderly population with MM.

Islelet transplantation (IT) is an ideal treatment for type 1 diabetes. However, a large number of transplanted islet cells become lost due to immune responses and other reasons, resulting in a poor long-term efficacy of IT. Islet encapsulation is wrapping islet cells with semi-permeable materials for protecting insulin secretion function by islet cells, reducing islet cell apoptosis and minimizing immune responses. Nanotechnology enables a nanoscale control of encapsulated materials. A better "isolation" of islet cells and external environment is essential for prolonging the survival time of islet cells. This review summarized the advantages and disadvantages of different nanotechnologies in encapsulating IT for the goals of prolonging the survival of islet cells, improving insulin secretion and boosting the efficacy of IT.

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

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.

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a peripheral retinal disease characterized by subretinal hemorrhage and/or subretinal pigment epithelial hemorrhage or exudation. It is often misdiagnosed as age-related macular degeneration, polypoidal chorioretinopathy or choroidal melanoma. With the development of multimodal imaging, PEHCR has different features under different examinations, such as B-scan ultrasound, fluorescein fundus angiography, optical coherence tomography and so on, which contributes to differention from other diseases. Clinical treatments for the disease include intravitreal injection of retinal photocoagulation therapy, anti-vascular endothelial growth factor, pars plana vitrectomyand so on, but there is still no universal consensus. In order to gain a deeper understanding of the clinical features, treatment options and prognosis of PEHCR, minimize missed diagnoses and misdiagnoses, and improve treatment efficiency, further research is required.

Objective:To translate the Treatment Burden Questionnaire (TBQ) into Chinese, and test its reliability and validity.Methods:The original questionnaire was translated, synthesized and back-translated according to the Brislin model. From March to July 2021, convenience sampling was used to select 240 elderly people from the 6 designated nursing homes for the aged of Qingdao Municipal Medical Insurance Bureau as the research object to conduct a questionnaire survey. The content validity index ( CVI) and construct validity were used to evaluate the validity of the scale, and the construct validity was evaluated by exploratory factor analysis. Cronbach's alpha coefficient and test-retest reliability were used to test the reliability of the scale. Results:A total of 240 questionnaires were distributed in this study, and 220 valid questionnaires were recovered. The Chinese version of TBQ included 15 items. A total of three common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 58.15%. The item-level CVI of the Chinese version of the TBQ was from 0.80 to 1.00, and the scale-level CVI was 0.91. The Cronbach's α of the total scale was 0.71, and the test-retest reliability coefficient was 0.77. Conclusions:The Chinese version of the TBQ has good reliability and validity, and can be used to assess the treatment burden in the elderly under the Chinese cultural background.