AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.
Humans ; Adult ; Middle Aged ; Aged ; Female ; Neoplasms, Fibroepithelial/pathology* ; Phyllodes Tumor/genetics* ; Stromal Cells ; Fibroadenoma/pathology* ; Breast Neoplasms/pathology* ; Mutation ; Telomerase/genetics*

Lattice degeneration of the retina(LD)is a peripheral vitreoretinal lesion characterized by atrophic retinal lesions and vitreous liquefaction in the equatorial region of the fundus. The progress of the disease is slow and the pathogenesis is not clear, which may be the result of multiple factors, among which the increase of ocular axis is one of the main risk factors. With the increase of myopia incidence, the prevalence of LD is on the rise. In recent years,it has become possible to quickly examine peripheral retina with the development of ultra-wide field fundus imaging technology. At present, retinal photocoagulation is the main prevention and treatment method for LD, but the need for preventive treatment is still unclear. This article reviews the epidemiology, pathogenesis, influencing factors and treatment of LD, hoping to provide ideas for further research and treatment of myopia-related LD.

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.

OBJECTIVE: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing. RESULTS: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors. CONCLUSION Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

Objective: To evaluate the efficiency of left cardiac sympathetic denervation (LCSD) in inherited arrhythmia patients with adrenergic activity-induced malignant ventricular arrhythmia, and observe exercise-stress test features before and after LCSD. Methods: This retrospective observational study included catecholaminergic polymorphic ventricular tachycardia(CPVT) and long QT syndromes(LQTS) patients who underwent video-assisted LCSD at Beijing Tsinghua Changgung Hospital and Peking University People's Hospital from September 2006 to May 2020. The indications for LCSD surgery were intolerant or refractory to beta-blocker medication. Clinical and exercise-stress tests data of included patients were collected before and 1 month after LCSD. Heart rate, exercise tolerance, atrial and ventricular arrhythmia, QTc interval and predictors for sudden cardiac death were analyzed. Patents were regularly followed up at 1, 3, 6, and 12 months after LCSD and then once every year thereafter. Cardiac events and medication adjustment records were collected. Results: Five patients (2 CPVT, 1 LQT1, and 2 LQT2)were included in the study. All patients experienced syncope as first symptom at the median age of 12(10, 16)years, and underwent LCSD at the median age of 21(16, 26)years, Baseline heart rate was similar before and after LCSD ((65.6±6.5) beats/min vs. (68.0±11.1) beats/min, P=0.57); while maximum workload tended to be lower after LCSD ((12.1±2.8) metabolic equivalents (METS) before surgery vs. (10.5±2.4) METS after surgery, P=0.07). Incidence of atrial and ventricular arrhythmia were significantly reduced post LCSD, and the ventricular arrhythmia score was decreased after LCSD in CPVT patients (4 points before LCSD vs. 3 points after LCSD in case 1;5 points before LCSD vs. 3 points after LCSD in case 2). QTc interval was shortened significantly in three LQTs patients (QTc interval at baseline heart rate: (546.6±72.3) ms before surgery vs. (493±61.1) ms after LCSD, P=0.047; QTc interval at maximal exercise heart rate: (516.3±73.7) ms before surgery vs. (486.7±64.2)ms after LCSD, P=0.035). Additionally, sudden cardiac death risk indicator ΔHRR1 (heart rate decreasing value within the first 1 min during recovery phase) decreased from (51.5±21.1) beats/min before surgery to (32.0±13.9) beats/min after surgery (P=0.035). During a median follow-up of 1(1, 4) year, all five patients were on low dosage of propranolol (37.0±21.7) mg/d. Cardiac events free survival was achieved in four out of 5 patients (80%) after sympathectomy, while 1 case suffered from sudden cardiac death after emotional stress. Conclusion: LCSD surgery can be safely and effectively performed in most hereditary arrhythmia patients with adrenergic activity-induced life-threatening cardiac events. Exercise stress test results show that LCSD could reduce malignant arrhythmias and improve sudden cardiac death risk indicators without decreasing heart rate.

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

Objective:To explore the type distribution and severity of central nervous system(CNS) complications in severe hand, foot and mouth disease (HFMD) cases prior to the introduction of human enterovirus A group 71 type (EV-A71) vaccine, and provide scientific data for early clinical intervention.Methods:A total of 3 583 laboratory-confirmed severe HFMD cases in Jiangsu province during 2010-2016 were collected and analyzed retrospectively. Related early warning signs of increased HFMD severity were estimated with logistic regression analyses.Results:The severity-fatality rate, severity-pediatric intensive care unit(PICU) admission rate, and sequelae rate were 8.09‰(29/3 583), 11.75% (421/3 583)and 5.30‰(19/3 583). Of them, 39.02% (1 398/3 583) patients suffered from mild CNS involvement, 59.22% (2 122/3 583) patients suffered from severe CNS involvement, 1.76%(63/3 583) suffered from critical CNS involvement. The rates of the cases whose age of onset was 6-11 months, the rates of cases with atypical rash, respiratory-related signs and symptoms (shortness of breath, slowed breathing, dyspnea, etc), neurological-related signs and symptoms [(hand and foot shaking, convulsions, lethargy(sleepiness), etc], circulatory-related system signs and symptoms (faster heart rate, abnormal skin color, arrhythmia, cold limbs), laboratory-related indicators (increased white blood cell count, increased lymphocyte count, increased platelet count, increased C-reactive protein, etc), clinical auxiliary examination [electroencephalogram(EEG), brain CT, chest X-ray)] were highest in the critical CNS involvement group, and the differences were significant ( P<0.05). Multivariate logistic regression analysis showed that with the increase of proportion of convulsions, slowed breathing, vomiting, meningeal irritation and other 7 variables, the severity of CNS complications increased ( P<0.05). Conclusions:The indicators such as easily startled, slow breathing, vomiting, elevated lymphocytes, abnormal EEG and other indicators have important clinical significance for children with severe HFMD to progress to CNS complications of different severity.

Objective:To observe the clinical efficacy of modified Yihuo Qnggan Tuiyi Tang on herpes simplex keratitis with liver meridian and wind-heat，so as to explore its mechanism of action. Method:Totally 130 patients with herpes simplex keratitis with liver meridian and wind-heat were randomly divided into control group and observation group，with 65 cases in each group. The control group was treated with conventional western medicine，while the observation group was treated with modified Yihuo Qinggan Tuiyi Tang in addition to the therapy of the control group for 4 weeks. The clinical efficacy，traditional Chinese medicine（TCM） syndrome score，symptoms and signs，adverse reactions and recurrence rate of the two groups were compared. The levels of serum interferon gamma（IFN-γ），interleukin-6（IL-6），interleukin-8（IL-8） inflammatory factors，malondialdehyde (MDA)，antioxidant activity (TAC)，glutathione peroxidase（GSH-PX）of oxidative stress indexes were detected by enzyme linked immunosorbent assay （ELISA）. The levels of CD4⁺ and CD8⁺ were measured by flow cytometry. The recurrence rate was observed during 1-year follow-up visit. Result:The total effective rate of observation group was better than that of control group (Z=2.161，P<0.05). After treatment，the scores of eye pain，shame，photophobia，tears，vision loss，redness and total eyelid swelling were significantly lower than those of control group (P<0.05). The total effective rate of TCM syndrome in the observation group was better than that of control group (Z=2.540，P<0.05). After treatment，the scores of pain，eyelid redness，conjunctival congestion，corneal punctate pannus，corneal pannus and corneal pannus depth of symptoms and signs in observation group were better than those of control group (P<0.05). The level of serum IFN-γ in observation group was higher than that of control group，and the levels of IL-6 and IL-8 were lower than those of control group (P<0.05). Levels of MDA in the observation group was higher than that of control group (P<0.05). The levels of CD4⁺and CD4⁺/CD8⁺ in observation group were higher than those of control group，and the levels of CD8⁺ were lower than that of control group (P<0.05). The recurrence rate in observation group was significantly lower than that in control group after withdrawal for 6 months and 12 months (P<0.05). Conclusion:In addition to the therapy of routine western medicine， modified Yihuo Qinggan Tuiyi Tang has a good clinical efficacy in treating herpes simplex keratitis with liver meridian and wind-heat，and can reduce the scores of TCM syndromes，alleviate symptoms and signs，and reduce the recurrence rate. Its mechanism may be related to reducing inflammation reaction，and improving oxidative stress index and immune function.