Objective: To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway. Methods : 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . Results: Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) . Conclusion Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.

Cerebral ischemia-reperfusion injury （CIRI） has a very high incidence， disability， and mortality rates， which seriously affects human life and health. In recent years， modern medicine has made some progress in the diagnosis and treatment of CIRI， but there are still problems such as difficulties in postoperative rehabilitation and adverse drug reactions， and new therapeutic drugs for CIRI are urgently needed. As an important class of active ingredients in traditional Chinese medicine， flavonoids can play antioxidant， apoptosis inhibition， anti-inflammatory， and other pharmacological effects to improve brain tissue damage， which is important for improving the quality of life of CIRI patients and slowing down the aging of the social population. Numerous studies have found that flavonoids in traditional Chinese medicine can regulate cell surface receptors Toll-like receptor 4/nuclear factor-kappaB （TLR4/NF-κB）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， adenylate-activated protein kinase/mammalian target of rapamycin protein （AMPK/mTOR）， Ras homologous gene family member A/Rho-associated coiled-coil protein kinase （RhoA/ROCK）， nuclear factor E₂-associated factor 2/Kelch-like epoxychloropropane-associated protein-1/haemoglobin oxygenase 1 （Nrf2/Keap1/ HO-1）， Notch， and other signaling pathways， so as to regulate the transcription and expression of related proteins after CIRI， alleviate brain tissue injury， and improve CIRI. This paper analyzed the relevant literature in China and abroad in recent years， reviewed the mechanism of action and related pathways of flavonoids in traditional Chinese medicine to improve CIRI， and explored the new therapeutic direction of CIRI at the metabolic level， with a view to providing a basis for the further development and application of flavonoids in traditional Chinese medicine.

Objective:To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies(ACA)receiving in vitro fertilization(IVF)-embryo transfer(ET)and natural conception.Methods:A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody(ANA)spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023.Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching.Embryo outcomes of IVF were compared between the two groups,and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching.The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.Results:The ACA-positive patients accounted for 0.86%of all IVF patients(34/3955)and 2.51%of total ANA-positive IVF patients.Regardless of whether patients received conventional IVF(c-IVF)or intracytoplasmic sperm injection(ICSI),the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group(both P＜0.01).Moreover,the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos(both P＜0.05).In 5 cases of ACA-positive patients who underwent ICSI cycles,the two pronucleus(2PN)rate did not increase compared to c-IVF cycles(P＞0.05),and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos(both P＜0.05).After 1-2 months of immuno-suppressant treatment,12 ACA-positive patients underwent c-IVF/ICSI again,and there were no changes in egg retrieval and fertilization before and after medication(both P＞0.05),but there was an improvement in the 2PN embryo cleavage rate(P＜0.05).The number of embryos transferred was similar between the ACA-positive and negative groups,but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group(both P＜0.05),with no significant differences in the miscarriage rate between the two groups(P＞0.05).Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure,resulting in a total of 7 cases of clinical pregnancy.Conclusions:Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes,with no improvement observed with ICSI and immunosuppressant use.However,ACA-positive patients may still achieve natural pregnancy.

Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.

Objective:To predict the Ki-67 expression grading in patients with mass breast cancer based on multimodal ultrasound features to aid clinical diagnosis and treatment.Methods:Ninety-three female patients (93 masses in total) with breast cancers confirmed by pathological examination were retrospectively included in the Second Affiliated Hospital of Harbin Medical University from September 2017 to September 2020. According to the immunohistochemical results, the patients were divided into Ki-67 high expression group (55 cases) and Ki-67 low expression group (38 cases). The qualitative and quantitative features from two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) images of all breast masses were retrospectively analyzed, differential features were analyzed based on logistic regression algorithm. ROC curves and Kappa test were used for the evaluation of diagnosis.Results:The univariate analysis revealed statistically significant differences between the two groups for conventional ultrasound features (size, shape, margins), SWE features (stiff rim sign, Eratio), and CEUS features (perfusion defect, IMAX) (all P<0.05). In the multiple logistic regression analysis, the margins, stiff rim sign, and perfusion defect were the independent factors for predicting the Ki-67 expression (all P<0.05). The performance of the predictive model was 0.882 (95%confidence interval of 0.798-0.940, P<0.05) with the sensitivity of 0.818 and specificity of 0.790. Conclusions:A preliminary analysis of the relationship between multi-modal ultrasound features and Ki-67 expression grading in mass breast cancers was performed based on logistic regression algorithm to provide more imaging information for clinical treatment and prognosis assessment.

Objective To explore the temporal and spatial distribution characteristics of air pollutants PM_2.5, PM₁₀, SO₂, CO, and NO₂, and their effects on acute cerebrovascular diseases in Jining City. Methods The data of patients with acute cerebrovascular disease treated in a 3A hospital in Jining from October 1, 2017, to November 31, 2019, were retrospectively collected. Combined with the air pollution data of 29 air quality monitoring stations in Jining City, the Kriging interpolation model was used to analyze the overall situation of air pollution in Jining. On this basis, the relationship between air pollution and acute cerebrovascular diseases in Jining City was analyzed. Results In Jining City, the incidence of acute cerebrovascular disease in male was higher than that in female, and the incidence in rural areas was significantly higher than that in urban areas. The spatial distribution showed a trend of gradual accumulation from southeast to northwest. The daily average concentrations of PM2.5 and PM10 were higher in winter and spring than in summer and autumn. The results of Kriging interpolation analysis showed that the concentrations of these air pollutants formed aggregation points in varying degrees. The spatial distribution of acute cerebrovascular disease patients in Jining City was highly consistent with the spatial distribution of air pollutant concentrations. Spearman correlation analysis showed that CO, SO₂, and NO₂ were positively correlated with the incidence of acute cerebrovascular disease, while the correlation between PM_2.5 and PM₁₀ and the incidence of acute cerebrovascular disease was not significant. Conclusion Some air pollutants such as CO, SO₂, and NO₂ have a positive correlation with the incidence of acute cerebrovascular disease, and the prevalence has a certain population and regional distribution. In the future work of cerebrovascular disease prevention, personal protection should be done according to local conditions and living environment of specific people.

Objective:To investigate the predictive value of the ischemic stroke predictive risk score (iScore) and serum homocysteine (Hcy) for early neurological deterioration (END) in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke admitted to the Affiliated Hospital of Jining Medical University from July 2018 to June 2020 were enrolled retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after admission increased by ≥2 from the baseline. Multivariate logistic regression analysis was used to determine the independent correlations of iScore and serum Hcy level with END, and then the receiver operating characteristics (ROC) curve was used to evaluate the individual and combined predictive values of iScore and serum Hcy for END. Results:A total of 398 patients with acute ischemic stroke were enrolled, including 241 (60.6%) males, aged 65.02±12.17 years. The baseline NIHSS score was 12.15±5.67 and iScore was 124.58±37.51, and 103 patients (25.9%) developed END. Univariate analysis showed that there were significant differences in atrial fibrillation, fasting blood glucose, serum Hcy, stroke etiology type (large artery atherosclerosis and small artery occlusion), baseline NIHSS score and iScore between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for age, atrial fibrillation, fasting blood glucose, and stroke etiology type, the iScore (odds ratio [ OR] 1.016, 95% confidence interval [ CI] 1.009-1.040; P=0.004), serum Hcy ( OR 1.191, 95% CI 1.075-1.588; P<0.001) and baseline NIHSS score ( OR 1.289, 95% CI 1.101-1.613; P=0.023) had significant independent correlation with END. ROC curve analysis showed that the area under the curve of iScore combined with serum Hcy for predicting END was 0.859 (95% CI 0.820-0.898; P<0.001), which was significantly higher than that of iScore or serum Hcy alone ( P<0.001). The sensitivity and specificity of combined prediction were 81.55% and 85.76%, respectively. Conclusion:The iScore combined with serum Hcy has higher predictive value for END in patients with acute ischemic stroke.

We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (

Fournier gangrene is a relatively rare clinical critical disease, and its clinical symptoms are not specific and easily unrecognized by some clinicians. It has the features of acute onset, quick development, severe illness, and often accompanied by infection shock which is seriously life-threatening. It is difficult in treatment with high medical costs and long length of hospitalization, which increases pain for patients and relatives and brings heavy economic and psychological burden on patients, society, and medical workers. By reviewing the literature home and abroad and combined with clinical practice, I summarize the researches on concept, epidemiology, clinical manifestation, diagnosis and treatment of Fournier gangrene, in order to provide reference for vast number of clinical workers.