The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To investigate the effect of down-regulating adenosine deaminase acting on RNA-1(AD AR1)on the radiosensitivity of lung adenocarcinoma cells.Methods Lentiviral transfection was used to establish an ADAR1 knockdown cell line based on A549 cells.Then the cells were divided into negative control(shNC)and ADAR1 knockdown(shADAR1)groups,which were followed by a single-dose irradiation of 0 Gy and 6 Gy X-rays.Western blotting and RT-PCR were utilized to detect the expression of AD AR1 at protein and mRNA levels,respectively.CCK-8 assay,wound healing assay and Transwell migration assay were applied to measure cell proliferation and migration abilities.Meanwhile,clone formation assay was performed to detect the effect of down-regulating ADAR1 on the radiosensitivity of A549 cells.Flow cytometry and Western blotting were conducted to detect the expression levels of apoptosis and apoptosis-related proteins Bax and Bcl-2.Immunofluorescence assay and Western blotting were used to detect the expression level of γ-H2AX.Comet assay was performed to detect the level of cellular DNA damage.Twelve female nude mice(4～6 weeks old,weighing 16～18 g)were divided into shNC group,shADAR1 group,shNC+ionizing radiation(IR)group and shADAR1+IR group,with 3 mice in each group.The growth of tumor of different groups was observed with subcutaneous tumorigenesis assay.Results Western blotting and RT-qPCR showed that the protein and mRNA expression of ADAR1 were significantly reduced in A549 shADAR1 cells(P＜0.05).CCK-8 assay,wound healing assay and Transwell migration assay indicated that down-regulation of ADAR 1 inhibited the proliferation and migration abilities of A549 cells,and this inhibition trend became more obvious(P＜0.01)after IR.Cell clone formation assay showed that the clone formation rate of both groups was decreased,with the increase of radiation dose.But the number of formed clones was lower in the shADAR1 group than the shNC group.Flow cytometry and Western blotting displayed that down-regulation of AD AR1 increased the apoptotic rate and Bax expression in A549 cells(P＜0.01)and decreased Bcl-2 expression(P＜0.05),and the apoptotic rate and Bax protein level were further increased in A549 shADAR1 cells after IR(P＜0.01),and the Bcl-2 protein level was further decreased(P＜0.01).The number of γ-H2AX foci and protein level in A549 shADAR1 cells were significantly increased after IR(P＜0.05),and the results of comet assay showed that the DNA damage was more obvious in A549 shADAR1 cells after IR(P＜0.01).Subcutaneous tumorigenesis assay in nude mice showed that the growth of subcutaneous tumour of A549 shADAR1 cells was significantly inhibited after IR(P＜0.01).Conclusion Down-regulation of ADAR1 significantly inhibits the proliferation and migration of A549 cells after IR and promotes apoptosis and DNA damage,and thereby increases the radiosensitivity of lung adenocarcinoma cells.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

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

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Objective:To evaluate the effect of intraoperative cell salvage (ICS) on the number and viability of cancer cells in salvaged autologous blood from the patients undergoing liver cancer surgery.Methods:Twenty patients undergoing open radical primary hepatocellular carcinoma were selected, and blood from the operative field was collected after exposing the liver and treated with ICS. Blood specimens 20 ml from the surgical field (S 1), blood specimens 20 ml before ICS treatment-leukocyte depletion filter (LDF) filtration (S 2) and blood specimens 20 ml after LDF filtration (S 3) were collected and enriched, of which the blood sample 10 ml was used for cancer cell identification and count by immunofluorescence staining, and the remaining blood sample 10 ml was continuously cultured for 3 weeks, and then cell viability was observed by immunofluorescence method. Results:Hepatocellular carcinoma(HCC) cells were identified in 19 S 1 specimens, 18 S 2 specimens, and 16 S 3 specimens, but there was no significant difference in the detection rate among the three specimens ( P>0.05). Compared with S 1 specimens, HCC cell count was significantly reduced in S 2 and S 3 specimens ( P<0.05). There was no significant difference in the HCC cell count between S 3 specimens and S 2 specimens ( P>0.05). After 3 weeks of culture, the results of light microscopy showed that: hepatocellular carcinoma cell clusters were found in S1 specimens, and no hepatocellular carcinoma cell cluster was found in S 2 and S 3 specimens; the results of fluorescence microscopy showed that: 400 and 14 mixed epithelial-mesenchymal HCC cells and 100 and 21 mesenchymal HCC cells were found in S 1 and S 2 specimens, respectively, while no HCC cells were identified in S 3 specimens, among which HCC cells mainly presented as clusters of hepatocellular carcinoma cells in S 1 specimen, while no clusters of hepatocellular carcinoma cells were found in S 2 and S 3 specimens. Conclusions:After treatment with ICS or ICS-LDF, the number and viability of hepatocellular carcinoma cells in salvaged autologous blood are significantly reduced, and hepatocellular carcinoma cells exist as single cells and fail to develop clusters of hepatocellular carcinoma cells; LDF can reduce the risk of hepatocellular carcinoma cell autotransfusion to a certain extent, although it can not effectively filter out hepatocellular carcinoma cells continuously.

Patients with malignant tumour often require massive transfusion. Intraoperative cell salvage(IOCS) was initially limited in cancer surgery by concerns about the possibility of dissemination of tumor cells into circulation. However, as supportive literature concerning IOCS research and application in cancer surgery are increasing, it is necessary to reassess the perioperative application of IOCS in patients with malignancy. This review summarizes the application, risks and value of IOCS during cancer operations.

Objective:To evaluate the effect of social media based behavioral intervention on promoting joint testing of HIV and syphilis in young men who have sex with men (MSM).Methods:After the recruitment, the participants who met the inclusion criteria were randomly divided (1∶1) into two groups, i.e. social media intervention group and control group. The control group was given routine voluntary counseling and testing (VCT) services. The intervention group was also given VCT services, besides; the comprehensive strategies through social media, including regular health education message and testing information sending, were given to them to strengthen the behavioral intervention. Follow up was conducted for the participants for 12 months after the intervention. The number and the proportion of young MSM receiving HIV and syphilis testing, and the reported proportion of the young MSM with sexually transmitted diseases (STD) symptoms between the intervention group and the control group were compared to evaluate the effect of the intervention.Results:A total of 315 young MSM were recruited (158 in the intervention group and 157 in the control group), in whom 248 young MSM completed the follow up. The follow-up rate was 78.7%. There was no significant difference in baseline characteristics between the intervention group and the control group (all P>0.05). The proportion of young MSM receiving more than one joint testing in the intervention group was slightly higher than that in the control group (53.2% vs. 48.4%, rate difference (RD): 4.8%, 95% CI: -7.5%-17.0%, P=0.448) without significant difference. However, in the young MSM who used condoms in the last anal sex, the proportion of those receiving more than one joint testing in the intervention group was higher than that in the control group (63.8% vs. 46.1%, RD: 17.7%, 95% CI: 1.5%-32.6%, P=0.035). In addition, the reported proportion of young MSM with STD symptoms in the intervention group was significantly lower than that in the control group (6.3% vs. 18.0%,RD: -11.7%, 95% CI: -20.6%- -3.0%, P=0.005). Conclusion:Compared with routine VCT, social media based behavioral intervention might promote joint HIV and syphilis testing in the young MSM who used condom in the study. It could significantly reduce the reporting proportion of STD symptoms, suggesting that this method can promote the AIDS and STD prevention related behaviors in young MSM.

Objective:To explore the mediating role of self-control in the relationship between alexithymia and internet addiction.Methods:From August to September 2019, a total of 433 college students were selected from three universities in Jiangxi province by cluster random sampling method. The Chinese internet addiction scale-revised, the twenty-item Toronto alexithymia scale and brief self-control scale were used for questionnaire testing. SPSS 23.0 software was used for descriptive statistics, Pearson correlation analysis and PROCESS V3.5 macro program was used to test the mediating effect.Results:The total scores of alexithymia, internet addiction and self-control were (53.61±9.44), (45.31±9.84) and (41.91±6.09), respectively. Pearson correlation analysis showed that alexithymia was significantly positively correlated with internet addiction ( r=0.47, P<0.01), and significantly negatively correlated with self-control ( r=-0.37, P<0.01). The negative correlation between self-control and internet addiction was significant ( r=-0.46, P<0.01). Multivariate hierarchical regression analysis showed that alexithymia directly predicted internet addiction after controlling the influence of gender. Self-control played a partially mediating role in the relationship between alexithymia and internet addiction (effect size=0.13, 95% CI: 0.082-0.185), the mediating effect accounted for 25% of the total effect. Conclusion:Alexithymia not only directly affects college students′ internet addiction, but also indirectly affects college students′ internet addiction through self-control.

OBJECTIVE: To investigate the IL-7R gene mutation and clinical features of adult patients with acute lymphoblastic leukemia (ALL). METHODS: One hundred sixty-four cases of newly treated adults with ALL from May 2016 to December 2018 were selected. Targeted and specific next-generation sequencing technology was used to detected a total of 16 types of Ph-like ALL mutations, which include IL-7R mutation, and the cilinical features, rate, types and sites of IL-7R were analyzed. RESULTS: IL-7R mutation was determined in 10 cases of 164 adult patients with ALL and the total mutation frequency was 13 times (6.1%). Out of 10 cases 5 cases were male (50%), 5 cases were female (50%). 6 cases of B-ALL ( 60% ) and 4 cases of T-ALL (40%). The mutation site of all cases was located at exon 6, among which 6 cases had replacement mutations, 3 cases had deletion mutations and 4 cases had insertion mutations. In addition, 1 triple and 1 double mutation of IL-7R were found. Besides, six mutation sites were newly identified, including: c.720_724del, c.723_726del, c.721_722insAGTG, c.727_728insTAACGGCCCCCTGCT, c.727_728insATGCAGGGAGCGAA and c.728_729insAAGTGTCA. CONCLUSION Six novel mutation sites and a poor manifestation of IL-7R have been explored in this research. Thus more samples are required to study the effects of IL-7R mutation on ALL treatment.
Adult ; Female ; Humans ; Interleukin-7 Receptor alpha Subunit ; genetics ; Male ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Signal Transduction