10 and Foxp3 expression, reduce the IL-17 and ROR-γt expression and adjust Treg/Th17 immune balance; effect of 0.1 mg/mL FSN +0.1 mg/mL MTX is the most obvious.

Objective:To study the correlation between deposition of C4d along peritubular capillaries (PTC) and interstitial eosinophilic infiltration in renal allografts.Methods:Deposition of C4d in kidneys was assayed by indirect immunoflourescence of the renal allograft biopsies.Twenty-six patients were demonstrated strongly diffuse staining of PTC,who were defined as C4d+ group,while the biopsies of thirty patients with acute rejection exhibited negative for PTC C4d staining served as the controls,who were defined as C4d-group.Eosinophils were counted under microscope.Results:The C4d+group was demonstrated significantly greater interstitial eosinophilic infiltration than did the C4d-group(P

Objective To explore the correlation of the indoor carbon monoxide concentration and chronic diseases by monitoring the indoor carbon monoxide concentration timely.Methods Collected the data of non-traumatic patients(n=80)from July 201 1 to January 2014,and assigned them into the experiment group with carbon monoxide concentration measured and the control group without measured.All the subjects were further divided into one group with complaint of carbon monoxide poisoning and the other one without.For patients exposed to high concentration of carbon monoxide,carboxyhemoglobin was also measured and APACHEⅡ was scaled,and the relationship between them was analyzed.The confirmation and misdiagnosis rate of carbon monoxide poison-ing were calculated.For the patients with acute exacerbation of chronic diseases like chronic cardiac failure,chronic obstructive pul-monary disease,cerebral infarction induced by carbon monoxide poisoning,BNP,CAT and NIHSS were documented on admission and during follow-up with removal of carbon monoxide exposure and compared respectively.Results The relationship between blood carboxyhemoglobin,APACHEⅡ scores on admission and indoor carbon monoxide concentration was linear,and obviously positive.Between the experiment group(n=40)and the control group(n=40),there was significant difference(P <0.05)in confirma-tion rate and misdiagnosis rate with 80.00% vs.55.00% and 6.25% vs.81.80% respectively.For the 54 patients with carbon monoxide poisoning diagnosed,the changes between before and after removal of carbon monoxide exposure of the CAT scores of chronic obstructive pulmonary disease and NIHSS score of CI disease and myoglobin,troponin I,creatine kinase isoenzyme,BNP for chronic cardiac failure were significantly different(P <0.01).Conclusion The indoor carbon monoxide concentration may indicate the severity of carbon monoxide poi-soning,which could increase the confirmation rate of carbon monoxide poisoning,and reduce the misdiagnosis rate.It is helpful to identify carbon monoxide exposure,the common inducing factor,so as to improve the patients′clinical symptoms.

Objective To evaluate the efficacy of laparoscopic adrenalectomy and open adrenalectomy in treating recurrent Cushing′s disease. Methods Forty-three patients (29 females and 14 males) with recurrent Cushing′s disease treated with laparoscopic adrenalectomy (LA, n=32) or open (OA, n=11) adrenalectomy from 2000 to 2008 were retrospectively analyzed. Patients completed the follow-up survey including a 36 item short-form (SF-36) health survey. Results All 43 patients achieved successful adrenalectomies without intraoperative complication. The duration of the LA was significantly shorter than that for the OA. Intraoperative blood loss was low in both groups. Median length of hospital stay was shorter in the laparoscopic adrenalectomy group, P<0.05. The median follow-up was 48.5 mon. Of the 34 (79.1%) patients available for follow-up, 22 (64.7%) had an adrenocorticotropic hormone levels >200 ng/ml and six (27.3%) had clinical Nelson syndrome. Thirty-four patients who completed the SF-36 survey reported that they felt their health status had changed from good to excellent after adrenalectomy. However, except for social activity, they showed significantly lower SF-36 scores compared with the general population, P<0.05. No statistical difference was found in SF-36 scores between the laparoscopic and open groups. Conclusions Adrenalectomy is safe and an effective option in the treatment of recurrent Cushing′s disease. It can help patients to improve both survival rate and quality of life.

Objective To investigate the inhibition effects of an hTERT-promoter-dependent oncolytic adenovirus Ad-VT that expresses apoptin on human prostatic carcinoma cell PC-3. Methods MTT assay was used to measure viability of PC-3 cell which was infected by recombinant adenovirus.The viability was measured at time points of 12,24,36,48,60,72,84 and 96 h after infection.AO/EB staining,DAPI staining,Annexin V assay were used to investigate the lethal effect and style of Ad-VT on PC-3 cell in vitro.The Caspases were measured by whole cell extraction of PC-3 cells 48hrs after infection. Results Ad-VT,Ad-VP3 and Ad-GT inhibited the proliferation of PC-3 cell in vitro.Ad-VT and Ad-GT were more effective than Ad-VP3 on cell growth,P ＜ 0.05.At 48,72,96 h time points,the inhibition effect of Ad-VT on PC-3 cell exhibited a dose related manner.When infection at MOI 100,the inhibition effect of Ad-VT on PC-3 cells exhibited time related manner.The AO/EB staining,DAPI staining,Annexin V assay,Annexin V assays and Caspase assays showed that Ad-VT inhibited the proliferation of PC-3 cells by inducing apoptosis of prostate cancer cells,Loss of cytoplasmic membrane integrity. Conclusions The hTERT-promoterdependent oncolytic adenovirus Ad-VT could effectively suppress prostate cancer cells PC-3 growth.

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.
Humans ; Cell Cycle/physiology* ; Cell Division ; Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism*

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone