IL-3 has effects on a wide variety of cell types, including immature cells of the immune cells, and mature immune cells such as granulocytes. In the purpose of studying the immunoregulatory function of IL-3 and its potential role in cancer therapy, we established a IL-3-secreting tumor model using gene transfection to deliver locally IL-3 to tumor site. First, we constructed IL-3 expression vector BMGNeo-mIL-3, then transfected it into B16 murine melanoma cells. By G418 resistant screening and limiting dilution, we obtained a transfectant that expressed high levels of IL-3 (806U / ml) . The IL-3 expression of the transfectant was confirmed by Northern blot analyses. Although the wild-type B16 cells and the B16-Neo cells transfected with BMGNeo did not express IL-3, the IL-3 expression in B16 cells had no obvious effect on the in vitro proliferation of the transfectant. These results showed we had successfully established a IL-3-secreting tumor cell clone which would enable us to further study its in vivo tumorigenicity and immune function.

AIM: To identify the non-steroid transcription factors upregulating the expression of L-plastin in hormone-independent prostate cancer, and partly elucidate the mechanism of hormone-refractory prostate cancer. METHODS: TF SEARCH software was used to analysis the possible binding sites of transcription factors in the 3’ end of L-plastin promoter that had been identified as important part of regulation response elements. Gel shift assay and supershift assay were used to confirm the transcription factors binding the speculated response elements. PCR site-mutagenesis technique was performed to delete the binding site of transcription factor and luciferase activity assay was carried out after deletion of the binding site. RESULTS: SP-1 respond element GGTGGGGCGGGGA located at -54- -41 of L-plastin promoter was identified with the TF SEARCH software. Gel shift assay and supershift assay confirmed that SP-1 was the transcription factor binding to GGTGGGGCGGGGA. Mutant deleted the SP-1 binding-site had low-luciferase activity than that of the naive. CONCLUSION: SP-1 plays an important role in the up-regulation of L-plastin expression in hormone-independent prostate cancer.

Objective:To explore the inhibitory effect of dihydroartemisinin (DHA ) on the growth of neuroblastoma cells,and to clarify the anti-tumor mechanism of DHA.Methods:The experiment was divided into blank control group and DHA groups (the final concentrations of DHA were 0.05, 0.50, 5.00 and 50.00μmol·L-1 ).The proliferation rates of neuroblastoma SH-SY5Y cells after treated with DHA were examined by MTT assay;the changes of cell cycle of SH-SY5Y cells after treated with DHA were examined by flow cytometry;the expression levels of cyclin D1 and caspase-3 proteins were detected by ELISA and Western blotting methods.Results:The proliferation of SH-SY5Y cells 24,48,and 72 h after treated with different concentrations of DHA were inhibited.Compared with blank control group,the proliferation rates of SH-SY5Y cells in 0.50,5.00 and 50.00μmol·L-1 DHA groups were significantly decreased (P<0.05 or P<0.01).The density of cells was decreased with the increasing of DHA concentration.Compared with blank control group,the percentage of SH-SY5Y cells at SubG1 phase in 50.00μmol·L-1 DHA group was increased (P<0.05),and the percentage of cells at G0/G1 phase was increased first then was decreased;otherwise, the percentages of cells at S and G2/M phase were decreased.Compared with blank control group,the expression level of cyclin D1 protein in 50.00μmol·L-1 DHA group was decreased (P<0.05),but the expression level of caspase-3 protein in 50.00μmol· L-1 DHA group was increased (P<0.05).Conclusion:DHA could inhibit the proliferation through arresting the cell cycle and inducing the apoptosis of neuroblastoma cells.

Objective To present our initial experience in laparoscopic radical prostatectomy performed through an umbilical incision using a home-made multichannel port. Methods From August 2009 to March 2010, we performed single-port laparoscopic radical prostatectomy in 11 patients with localized prostate cancer. A home-made multichannel port was inserted extraperitoneally through a 3-cm umbilical incision. The single port extraperitoneal procedures included obturator fossa lymphadenectomy, radical prostatectomy and urethro-vesical anastomosis, while the urethro-vesical anastomosis was performed by a slip-knot running suture technique. Data were collected and analyzed prospectively. Results All cases were completed successfully, without conversion to a standard laparoscopic approach or open surgery except adding an additional port in one case. The average operative time was 256 minutes (range195-315), and the mean blood loss was 90 ml (range 20- 180), without any blood transfusion. The postoperative hospital stay was 15.4 days (range13- 24), and the Foley catheter was removed 12 days after surgery. No intraoperative complications occurred. One patient developed a vesico-rethralanastomosis leakage, 2 had lymphatic leakage and 1 had urinary tract infection,all of the cases were managed successfully with conservative treatment. Histopathological results showed negative surgical margine and negative lymph node dissection. All patients had no biochemical relapse after an average follow-up of 7 months. Conclusions Single-port laparoscopic radical prosta tectomy is feasible, cosmetic and minimally invasive with a low complication rate and good short-term outcome. Additional investigation is needed to evaluate the long-term safety and oncologic adequacy of this new approach.

Objective:Objectives To investigate the predictive value of color Doppler flow imaging (CDFI) for the proteinuria following pyeloplasty for congenital ureteropelvic junction obstruction (UPJO) in children.Methods:We identified a series of 206 children with a mean age of (20.0±28.8) months (1-132 months), consisted of 171 males and 35 females, diagnosed with congenital UPJO accepted pyeloplasty from January 2014 to September 2018, the preoperative mean urinary Albumin/Creatinine Ratio (ACR) was (17.3±160.1) mg/mmol and the mean β2-microglobulin/Creatinine Ratio (β2-MG/Cr) was (135.6±383.8) μg/mmol, ultrasound showed a mean renal pelvis dilatation of (3.1±1.5) cm and a mean cortical thickness of (0.3±0.1) cm, and classified as grade Ⅰ-Ⅴ according to the blood flow distribution in renal by CDFI, these children were divided into three groups of increased, decreased and unchanged blood flow according to the postoperative CDFI within 1 week, the postoperative urinary protein and renal function indexes within 1 week and 2 years were retrospectively analysed among groups.Results:Within 1 week postoperatively, an increased, decreased and unchanged blood flow occurred in 113 (54.9%), 31(15.0%), 62(30.1%) children, respectively. Urinary ACR in above mentioned groups was (112.3±400.7), (16.1±29.3), (32.7±48.4) mg/mmol, β2-MG/Cr was (887.4±6061.0), (50.2±62.7), (51.9±57.8)μg/mmol, there were significant differences among groups ( P<0.01). Contralateral hydronephrosis occurred in 21(18.6%), 4(12.9%), 8(12.9%) children, urinary N-Acetyl-β-D-glucosaminidase (NAG) was (7.5±5.2), (7.0±5.4)、(5.7±4.5) U/L, these indexes showed no significant differences among groups. There was a positive correlation between the increased blood flow level and the decreased renal pelvis dilatation (Spearman’s correlation coefficient 0.2, P<0.01), ACR (Spearman’s correlation coefficient 0.4, P<0.01) and β2-MG/Cr (Spearman’s correlation coefficient 0.3, P<0.01). After a follow up of 2 years, 67 children were diagnosed with proteinuria in this series, 51 cases of them with an increased blood flow, which had significantly higher percentage than children with a decreased (4 cases, 12.9%) or unchanged blood flow (12 cases, 19.3%). Logistic multivariate analysis indicated that early postoperative (within 1 week) increased blood flow ( OR=1.9, 95% CI 1.5-2.6), contralateral hydronephrosis ( OR=2.2, 95% CI 1.1-4.8) and urinary NAG ( OR=1.1, 95% CI 1.0-1.1) were predictive of proteinuria, the increased blood flow was independent predictor of proteinuria (Ⅰ level increased: OR=1.9, 95% CI 1.5-2.6). Conclusions:The CDFI reveals good predictive value for the postoperative proteinuria, an early marked increased blood flow postoperatively indicated risk of proteinuria in the long term.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

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