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.

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.

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

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP). METHODS: With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals. RESULTS: Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals. CONCLUSION The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.
Brain/abnormalities* ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Female ; Humans ; Interferon Regulatory Factors/genetics* ; Mutation, Missense ; Pedigree ; Whole Exome Sequencing

Objective: To investigate the ultrasonic features of fetal isolated coronary artery fistula (CAF). Methods: A total of 13 cases of fetal isolated CAF from December 2011 to March 2018 were retrospectively analyzed. Data of echocardiography and follow-up were collected.All cases were divided into retrograde group and no retrograde group based on the presence of diastolic retrograde flow in aortic arch. The inner diameters of affected coronary arteries (CA) and aortic annulus (AO) were measured, and the CA to AO ratios (CA/AO) were then calculated.Correlations between CA, CA/AO and the presence of retrograde flow were analyzed. Adverse birth outcomes including abortion, enlarged cardiac cavity, pulmonary hypertension were recorded at follow-up. Correlation between diastolic retrograde flow in aortic arch and the rate of adverse birth outcomes was analyzed. Results: ①Thirteen cases of fetal CAF were characterized by the varying degrees of dilation of affected coronary arteries. Thirteen cases were presented with abnormal blood flow in the large arteries or cardiac cavities: biphasic continuous flow pattern in atrio-coronary fistula and biphasic bidirectional continuous flow pattern with a diastolic dominant flow in coronary artery to ventricle fistula. Seven cases were presented with retrograde holodiastolic flow in aortic arch. ②The CA/AO ratios of retrograde group was higher than in no retrograde group [(0.63±0.24)mm vs (0.39±0.09)mm, P=0.047], there was no significant difference of CA between the two groups [(3.00±1.25)mm vs (2.03±0.62)mm, P=0.115]. ③The rate of adverse birth outcomes in retrograde group was higher than in no retrograde group (80% vs 20%, χ²=4.80, P=0.028). Conclusions Fetal isolated CAF has distinct ultrasonic features. Abnormal CA/AO ratio and diastolic retrograde flow in aortic arch are significant ultrasonic features and has prognostic values.

Objective To investigate the ultrasonic features of fetal isolated coronary artery fistula ( CAF) . Methods A total of 13 cases of fetal isolated CAF from December 2011 to M arch 2018 were retrospectively analyzed . Data of echocardiography and follow‐up were collected .All cases were divided into retrograde group and no retrograde group based on the presence of diastolic retrograde flow in aortic arch . T he inner diameters of affected coronary arteries ( CA ) and aortic annulus ( AO ) were measured ,and the CA to AO ratios ( CA/AO ) were then calculated .Correlations between CA ,CA/AO and the presence of retrograde flow were analyzed . Adverse birth outcomes including abortion , enlarged cardiac cavity , pulmonary hypertension were recorded at follow‐up . Correlation between diastolic retrograde flow in aortic arch and the rate of adverse birth outcomes was analyzed . Results ① T hirteen cases of fetal CAF were characterized by the varying degrees of dilation of affected coronary arteries . T hirteen cases were presented with abnormal blood flow in the large arteries or cardiac cavities :biphasic continuous flow pattern in atrio‐ coronary fistula and biphasic bidirectional continuous flow pattern with a diastolic dominant flow in coronary artery to ventricle fistula . Seven cases were presented with retrograde holodiastolic flow in aortic arch . ②T he CA/AO ratios of retrograde group was higher than in no retrograde group [ ( 0 .63 ± 0 .24 ) mm vs ( 0 .39 ± 0 .09) mm , P ＝0 .047] ,there was no significant difference of CA between the two groups [ ( 3 .00 ± 1 .25) mm vs ( 2 .03 ± 0 .62) mm , P ＝0 .115] . ③T he rate of adverse birth outcomes in retrograde group was higher than in no retrograde group ( 80% vs 20% ,χ2 ＝4 .80 , P ＝0 .028) . Conclusions Fetal isolated CAF has distinct ultrasonic features . Abnormal CA/AO ratio and diastolic retrograde flow in aortic arch are significant ultrasonic features and has prognostic values .

Objective To explore the impact of breast conservation surgery and modified radical mastectomy combined with intensity modulated radiation therapy respectively on the living quality and sexual life for patients with early-stage breast cancer.Methods From January 2011 to December 2016, 89 patients with breast cancer were admitted and divided into two groups according to different surgical methods.Patients in the conservation group (n=24) received breast conservation surgery combined with intensity modulated radiation therapy, while patients in the modified radical group (n=65) received breast radical surgery combined with intensity modulated radiation therapy.The quality of life and sexual satisfaction of patients were measured by questionnaire investigation.And the data were calculated by SPSS 16.0.Results Different surgical methods combined with radiotherapy affectted the score of living quality a lot.The average score was (87.500±7.940) points in the conservation group, while it was (65.350±8.490) points in the modified radical group, the difference was statistically significant (P<0.01).At the same time,the degree of self acceptance and sexual satisfaction in the conservation group after surgery was better than that in the modified radical group,and the difference was statistically significant (P<0.01).Conclusion Breast conservation surgery combined with intensity modulated radiation therapy for breast cancer patients could receive better quality of life and sexual satisfaction compared with modified radical mastectomy combined with intensity modulated radiation therapy.

Objective To explore skeletal‐related events (SREs) clinical factors and analysis prognosis factors on patients with non‐small cell lung cancer(NSCLC) with bone metastases .Methods We collected clinical data of pathology confirmed 383 patients with non‐small cell lung cancer between April 2007 and January 2007 in the third affiliated hospital of the third military medical uni‐versity .It was used to screening for Emission Computed Tomography (ECT ) for bone metastases .And then it was need to con‐firmed for CT ,MRI or PET‐CT or pathology .Statistics in patients between clinical features and the SREs prediction factor with Univariate and Multivariate .And Kaplan‐Meier method analysis of survival in the non‐small cell lung cancer patients with bone me‐tastases .Results Out of 383 patients with bone metastases ,178 patients with SREs .The incidence was 46 .5% .Univariate analysis showed that women ,adenocarcinoma ,never smoking history ,single bone metastases ,bisphosphonate therapy ,targeted therapy in patients with bone metastases are less likely to have SREs ,it was considered statistically significant (P<0 .05) .Multivariate analy‐sis showed multiple bone metastases and no bisphosphonate therapy is independent risk factors for SREs .Median survival time was 14 .5 months in non‐small cell lung cancer patients with bone metastases ,1 year survival rate was 46 .5% ,2 years survival rate was 15 .9% .The survival analysis shows that more bisphosphonate treatment and bisphosphonate with EGFR‐TKI therapy on the prog‐nosis of patients with statistically significance (P<0 .05) .Conclusion It was likely to occur SREs in NSCLC patients with bone metastases .No bisphosphonate and multiple bone metastases are independent risk factors for SREs .Bisphosphonate treatment may prevent or reduce occur SREs for NSCLC patients with bone metastases ,and it may prolong survival ,it speculated that bisphospho‐nate may have resistant NSCLC cell activity .

Objective To investigate the short-term efficacy and the influencing factorof zoledroniacid combined with ra-diotherapy and single radiotherapy in the treatmenof bone metastasiin non-small cell lung cance(NSCL) .MethodTotally 117 NSCLpatientwith bone metastase(153 lesions) receiving the bone lesion radiotherapy in the TumoCenteof ouhospital from 2009 to 2013 were selected and treated by zoledroniacid combined with radiotherapy (combined therapy group ,n=54) and the single radiotherapy (single radiotherapy group ,n=63) .The bone pain relief and influence factorwere analyzed .ResultThe effective ratein the single radiotherapy group and the combined radiotherapy group were 69 .74% and 92 .21% respectively (χ2 =13 .75 ,P＜0 .01);the multivariate Logistiregression analysishowed thathe bone pain relief wacorrelated with the treatmenmode ,moreovethe bone pain relief rate in the combined therapy group wasignificantly highethan thain the single therapy group (OR=4 .60 ,95% CI:1 .23-17 .20 ,P=0 .02) .In the subgroup analysiof treatmenmode,the patientwith osteolytile-sions(OR=26 .59 ,95% CI:3 .29-215 .12 ,P=0 .00) had betteeffec.The combined therapy group had more superiority in the as-pecof non-skeletal related eventoccurrence (OR=4 .40 ,95% CI:1 .49 -12 .99 ,P=0 .01) .Conclusion Radiotherapy combined with zoledroniacid habettecurative effeccompared with single radiotherapy in the NSCLC patientwith bone metastasi.

Objective To observe the clinical effect of patients in the department of neurosurgeryoperation combined with autologous blood transfusion. Methods A retrospective analysis of 113 cases of operation patients in department of neurosurgery. All the patients were under general anesthesia using autologous blood transfusion. Thepreoperative , the first dayand the third day postoperative blood routine indexes , coagulation function examination and the electrolyte were analyzed. Resuits Theblood transfusion volume was (262.53 ± 163.41)mL. Hemoglobin , hematocrit and platelet count after 1 days and 3 days after operation were significantly lower than preoperative. The potassium ionsthat first day postoperation was significantly higher than preoperation , postoperative 1 day and the 3 day after the operation of sodium ions and chloride ions were significantly increased. Conclusion Patients in the department of neurosurgery of autologous blood transfusion is safe and effective, which can save the blood and reduce the risk of allogeneic blood transfusion.