Objective To investigate the effects of silymarin on expressions of nuclear factor kappa B(NF-?B) and intercellular adhesion molecule-1(ICAM-1) in the kidneys of rats with unilateral ureteral obstruction(UUO)-induced renal fibrosis.Methods Seventy-two male Sprague-Dawley rats were randomly divided into 3 groups: sham-operated group(n=24),operated group(n=24) and silymarin treated group(n=24).Renal tubulointerstitial fibrosis model was established via UUO.Silymarin was given by gavage with 30 mg/(kg?d) in silymarin treated group,and the same volume normal saline was given by gavage in operated group and sham-operated group.In each group,8 rats were killed at 7,14 and 21 d after operation.Histological changes were observed in tubulointerstitial injury under microscope.The expressions of NF-?B and ICAM-1 in renal tissue were determined with immunohistochemical method.Results Tubuloin-terstitial injury scores in operated group at 7,14 and 21 d were 1.168?0.108,1.776?0.064 and 2.301?0.157,respectively,and Tubulointerstitial injury scores in the treated group at 7,14 and 21 d were 1.043?0.114,1.677?0.083 and 2.084?0.201,respectively.Tubulointerstitial injury scores in silymarin treated group were significantly lower than those in operated group(Pa

Fifty-six patients with Graves' ophthalmopathy(GO)were treated with antithyroid drug and oral prednisone for three months,TSH receptor antibody(TRAb)level was reduced,GO activity and severity of some patients were ameliorated but still positively associated with TRAb.It suggests that TRAb not only triggers off GO but also plays a possible role in the maintenance of the autoimmune process in GO.

The anti-apoptotic members of Bcl-2 family proteins, Bcl-2 and Mcl-1, are considered therapeutic targets of various cancers. In this article, we developed four hydrophobic tag (HyT)-based protein degraders of Bcl-2/Mcl-1, based on a Bcl-2/Mcl-1 dual inhibitor S1-6, and tested their capability in Bcl-2/Mcl-1 degradation and apoptotic induction in MCF-7 cells. Interestingly, different linkers in the HyT degraders led to selective Bcl-2/Mcl-1 degradation, though the degraders S1-D1-S1-D4 maintained the pan-Bcl-2 family binding capacity. Among them, S1-D2 and S1-D4, two compounds bearing a hydrophobic linker or a PEG linker, were observed to potently and selectively induce the ubiquitination and proteasomal degradation of Bcl-2 and Mcl-1 in living cells, with a degradation rate of more than 80% or 60%, respectively. Moreover, the HyT-based degraders showed increased lethality of cancer cells compared to the parent inhibitor S1-6, demonstrating that the advantage of degraders to the occupancy-based inhibitors.

Apoptosis ; drug effects ; Cell Division ; drug effects ; Esophageal Neoplasms ; pathology ; Humans ; Selenomethionine ; pharmacology ; Tumor Cells, Cultured

The two-dimensional model of cell culture is an important method in the study of testicular development and spermatogenesis but can not effectively mimic and regulate the testicular microenvironment and the whole process of spermatogenesis due to the lack of relevant cell factors and the disruption of a three-dimensional spatial structure. In the past 20 years, the development and optimization of the in vitro model such as testis organotypic culture and in vivo model such as testis transplantation achieved a transformation from two- to three-dimension. The maintenance and optimization of the testicular niche structure could mimic the testicular microenvironment and cell types including Leydig, Sertoli and germ cells, which showed similar biological behaviors to those in vivo. Besides, the cell suspension or tissue fragment floats in the gas-liquid interface so that the development of somatic and germ cells is well maintained in vitro whilst the feedback linkage between grafted testis tissue and hypothalamus-pituitary of the host rebuilt in the in vitro model provides an endocrinological basis for spermatogenesis, which serves as an effective methodology to better understand the organogenesis and development of the testis as well as testicular function regulation, advancing the concept of treatment of male infertility. Al- though each of the methods may have its limitations, the progress in the processing, freezing, thawing, and transplantation of cells and tissues will surely promote their clinical application and present their value in translational medicine.
Cell Culture Techniques ; Germ Cells ; physiology ; Humans ; Infertility, Male ; therapy ; Male ; Spermatogenesis ; physiology ; Testis ; growth & development

The crude toxin was extracted from hypha and culture solution of Phyllosticta commelimecola through three different polarity solvent: benzinum, puncificatum ethyl acetate and chloroform. The result indicated that the toxin secreted by Phyllosticta commelimecola not only was in hypha but also in culture solution and the extracting effect of ethyl acetate was the best. The soybean median and PSK media can be respectively used as solid and liquid culture media to produce toxin and grow mycelium. The optimal cultural conditions for producing toxin were temperature 32℃,cultured period 14d, cultured ways shaking of 150r/min.

Objective To study the effects of angiotensin converting enzyme inhibitor benazepri1 on apoptosis and the expression of Fas and FasL in the kidney of rats with adriamycin-indued nephritic glomeruosclerosis.Methods After uninephrectomy and the injection of adriamycin induced rats model with glomerulosclerosis, benazapril(6 mg/kg) was delivered daily by gavage to the rats in therapeutic groups for 12 weeks.Apoptosis was examined by means of terminal-deoxynucleotidyl trans ferase mediated d-UTP nick end label ling(TUNEL) and immunohistochemistry was utlized to detect the expression of Fas and FasL.Software of pathological analysis quantitated the level of Fas and FasL.Results Compared with those of the control group, the kidney of model group had moresevere glomerulosclerosis, much more apoptotic cells and higher level of exprssion of Fas and FasL. The degree of glomeruloscleroais, the nuxner of apoptotic cells and the level of expression of Fas and FasL were ameliofated by benazepril treatment.Conclusion Benazepril may suppress the excessive apoptosis of kidney cell by lowering the expression of the protin correlatng apoptosis Fas and FasL,so as to postpone the process of glomeruosclerosis.

Objective To investigate the MRI and echocardiography manifestations of noncompaction of ventricular myocardium(NVM)and assess the role of MRI in the diagnosis of NVM by comparing it with echocardiography.Methods Fourteen cases of NVM diagnosed by echocardiography were examined with MRI,including scanning of black-blood sequences,double inversion recovery fast spin echo (DIRFSE)and triple inversion recovery fast spin echo(TIRFSE),and white blood sequence:fast imaging employ steady state acquisition(FIESTA).Scanning plane includes short axis view,four-chamber view and long axis view.Results Both MRI and echocardiography displayed involvement of left ventricles in thirteen cases and involvement of double ventricles in one case.Apexes of heart and the intermedius are commonly affected.MRI showed 54 segments and echocardiography showed 53 segments affected,and there is no significant difference between the capability of MRI and echocardiography(P=1.000).The affected myocardium consisted of two layers:subendoeardial noncompacted myocardium and epicardial compacted myocardium,and the ratio measurement of N/C by MRI was 3.37?0.89 and it was 3.19?0.82 by echocardiography.Noncompacted myocardium was characterized by prominent and excessive myocardial trabeculations and deep intratrabecular recesses,in which the blood flow was communicated with the ventricle.One case was complicated with ventricular aneurysm,and coronary arteriography was performed with unremarkable findings.One case underwent heart transplantation because of progressive heart failure, Gross findings demonstrated prominent muscular trabeculations with deep intratrabecular recesses,which coincided well with MRI findings.Conclusion The MRI manifestation of NVM is characteristic,and MRI with multiple series and planes is helpful in the diagnose of NVM.Compared with echoeardiography,MRI could display the pathological cardiac muscle more clearly,because of its high soft-tissue resolution and spatial resolution.

Objective: To study the chemical constituents from the stems of Uncaria scandens. Methods: The compounds were isolated and purified by silica gel column chromatography, Sephadex LH-20, RP18, and HPLC. The structures were identified by spectroscopic methods and physicochemical properties. The contents of rhynchophylline and isorhynchophylline were detected by HPLC method. Results: Seventeen compounds were isolated and identified from 95% ethanol extract of the stems of U. scandens and characterized as 5α-carboxystrictosidine (1), 3β-isodihydrocadambine (2), strictosamide (3), 3α-dihydrocadambine (4), mitraphylline (5), uncarine F (6), 3β-isodihydrocadambine 4-oxide (7), isodihydrocdambine (8), nauclefine (9), cadambine (10), calyxamine B (11), methyl chlorogenate (12), 3,4,5-trimethoxyphenol (13), α-tocopherylquinone (14), quinovic acid (15), methyl caffeate (16), and hyperoside (17). The contents of rhynchophylline and isorhynchophylline from U. scandens were 0.72 and 0.38 μg/g. Conclusion: Compounds 7-9 and 11-14 are isolated from Uncaria genus for the first time. Compounds 1-6 and 16, 17 are isolated from U.scandens for the first time. The contents of rhynchophylline and isorhynchophylline is low and the reasonable use of them as U. scandens in some areas needs to be further verified.

Abstract: Objective　To understand the situation of drug-resistant tuberculosis screening and epidemiological characteristics of multi-drug resistant tuberculosis (MDR-TB) and pre-extensively drug resistant tuberculosis (pre-XDR-TB) in Changsha, in order to provide a scientific basis for improving the quality of drug-resistant tuberculosis prevention and control in the city. Methods　Demographic information and drug susceptibility date of etiologically positive pulmonary tuberculosis patients in Changsha from 2018 to 2021 were collected, the successful rate of resistance screening, incidence and tendency in MDR-TB and pre-XDR-TB in patients included in this study were statistically analyzed accordingly. 　　Results From 2018 to 2021, the successful screening rates were 86.2%, 87.7%, 81.9% and 71.5% for MDR-TB and 82.2%, 84.8%, 76.9% and 68.2% for pre-XDR-TB, respectively. In each year, MDR-TB patients identified accounted for 7.6% (101/1 222), 6.5%(124/1 774), 6.6%(110/1 555) and 6.3%(99/1 478), and pre-XDR-TB patients identified accounted for 3.6%(46/1 219), 3.8%(69/1 766), 4.4%(69/1 495) and 4.6%(69/1 436), correspondingly. The incidence of MDR-TB showed a slowly downward trend, while the incidence of pre-MDR-TB showed a slowly upward trend, with neither decreasing nor increasing trends being statistically significant (（χ2=1.947，0.806，P>0.050). The incidence of MDR-TB in the retreatment failure population was 66.6% (2/3), and the others, failure initial treatment and recrudescence populations were 23.5% (19/81), 16.7% (2/12) and 15.2% (70/461), respectively. Similar to the incidence above, the incidence of pre-XDR-TB was 16.7% (2/12) among patients who failed in initial treatment, and 12.2% (9/74), 9.8% (43/439), and 4.5% (2/44) among the others, recrudescence and returned patients, respectively. The incidence rates of MDR-TB and pre-XDR-TB in different populations were significantly different (χ2=117.600，59.030，P<0.05). Conclusions There are still areas for improvement in tuberculosis drug resistance surveillance system in Changsha. On the premise of paying attention to patients in retreatment failure, other, initial treatment failure and relapse patients, high sensitivity molecular drug susceptibility testing, and scientifically efficient screening strategies must be explored.