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

In recent years，with the change in lifestyle and social environment and the increase in pressure in both life and work，male fertility has decreased significantly in China，and the incidence of male infertility has increased year by year，which has brought great challenges to andrologists. Traditional Chinese medicine （TCM） has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility，the China Association of Chinese Medicine （CACM） invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia，abnormal semen liquefaction，varicocele，immune infertility，improving success ratio of assisted reproductive technology，and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages，characteristics，disadvantages，diseases responding specifically，and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility，western medicine cannot achieve a good curative effect，while TCM，taking the holistic view as the core，specializes in improving functional diseases and can correspond to multiple targets and factors，with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists，increase mutual learning and communication between TCM and western physicians，provide patients with excellent and personalized treatment plans in clinical practice，and improve the curative effect of male infertility and fertility of males in China.

Objective:To investigate the risk factors and their warning value for the occurrence of sepsis in patients with severe multiple trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 patients with severe multiple trauma admitted to Yuyao People′s Hospital from July 2019 to October 2021. There were 71 males and 21 females, with the age range of 36-55 years [(45.5±13.6)years]. The injury severity score (ISS) was 20-29 points [(25.3±6.4)points]. The patients were divided into sepsis group ( n=32) and non-sepsis group ( n=60) according to whether sepsis occurred during hospitalization. Data were recorded for the two groups, including gender, age, basic diseases, cause of injury, number of injury sites, ISS, post-injury complications, and levels of aryl hydrocarbon receptor (AHR), C-reactive protein (CRP) and procalcitonin (PCT) at 1, 3 and 5 days after injury. The above data were analyzed to identify their correlation with the occurrence of sepsis in patients with severe multiple trauma by univariate analysis. The independent risk factors for sepsis in patients with severe multiple trauma were determined by multivariate Logistic regression analysis. The warning value of the single or combined risk factors for the occurrence of sepsis in patients with severe multiple trauma was evaluated by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results:By univariate analysis, it was demonstrated that the occurrence of sepsis was correlated with ISS, level of AHR at day 1 after injury, level of CRP at day 3 after injury and level of PCT at day 3 after injury ( P<0.05 or 0.01), but not with age, sex, basic diseases, level of AHR at 3, 5 days after injury, level of PCT at 1, 5 days after injury and level of CRP at 1, 5 days after injury (all P>0.05). By multivariate Logistic regression analysis, higher ISS ( OR=1.12, 95% CI 1.01, 1.24, P<0.05), level of AHR at day 1 after injury ( OR=1.30, 95% CI 1.10, 1.52, P<0.01) and level of PCT at day 3 after injury ( OR=1.81, 95% CI 1.08, 3.03, P<0.05) were found to be strongly correlated with the occurrence of sepsis. ROC curve analysis showed that higher ISS (AUC=0.69, 95% CI 0.57, 0.76) and level of AHR at day 1 after injury (AUC=0.79, 95% CI 0.68, 0.90) had warning value for the occurrence of sepsis, and the warning efficiency of combined panel was much better (AUC=0.86, 95% CI 0.77, 0.95). Conclusions:Higher ISS, level of AHR at day 1 after injury and level of PCT at day 3 after injury are independent risk factors for the occurrence of sepsis in patients with severe multiple trauma. ISS, AHR and combination of both exhibit good warning value for the occurrence of sepsis in patients with severe multiple trauma.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in men. In recent years, it has become younger, which seriously affects the patients＇quality of life. A deep understanding of the pathogenesis of CP/CPPS will help the choice of treatment. Its pathogenesis is not only related to immune factors, but also related to local microcirculation disorders of the prostate, endocrine hormone imbalance, adjacent gut microbes and compression of lumbar intervertebral disc, but it has not been fully elucidated. Therefore, this article aims to review the pathogenesis of CP/CPPS and provide directions for its diagnosis and treatment.

Objective:To observe the effect of interleukin-6 (IL-6) on the phenotype and function of human umbilical vein endothelial cells (HUVECs) and explore the role of IL-6 in the process of endothelial-to-mesenchymal transition (EndMT).Methods:The experimental research method was used. Fresh umbilical cord discarded after normal maternal delivery was collected. On the second day of the primary cell isolation and cultivation, the cell morphology was observed under inverted phase contrast microscope. HUVECs of the 4th passage were identified by immunofluorescence method, and 2 batches of HUVECs ofthe 3rd to 5th passages were used for the subsequent experiments. The first batch of cells were divided into 6 groups according to the random number table (the same below): blank control group, 5 ng/mL IL-6 group, 10 ng/mL IL-6 group, 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group. The second batch of cells were divided into 4 groups: blank control group, 10 ng/mL IL-6 group, 25 ng/mL IL-6 group,and 50 ng/mL IL-6 group; the cells in blank control group was cultured with complete culture medium only, while the cells in the other groups were added with IL-6 of the corresponding final mass concentrations.Cells from the 1st batch were cultured for 72 hours after grouping, the morphology of HUVECS in the 6 groups was observed under inverted phase contrast microscope. At 72 h after grouping culture, the positive expressions of coagulation factor Ⅷ and α vascular smooth muscle actin (α-SMA) in HUVECs in the 6 groups were detected by immunofluorescence method, and the ratio of the number of double positive cells to the number of coagulation factor Ⅷ positive cells (the ratio of double positive cells for short) was calculated, with 6 samples per group; mRNA expression levels of vascular endothelial cadherin and α-SMA of HUVECs in 6 groups were detected by reverse transcription-polymerase chain reaction, with 3 samples per group.Cells from the 2nd batch were cultured 72 hours after grouping, the protein expression levels of vascular endothelial cadherin, α-SMA, and type Ⅰ collagen in the 4 groups were detected by Western blotting, with 3 samples per group. Data were statistically analyzed with one-way analysis of variance and Bonferroni correction.Results:On the 2nd day after isolation and cultivation, the primary cells were in short spindle shape or polygon, cells of the 4th passage were identified as HUVECs by immunofluorescence method. At 72 hours of culture after grouping, the cells from the 1st batch in the 6 groups changed to long spindle shape morphologically along with the increase of IL-6 concentration, the intercellular connections decreased or disappeared with the gap between cells becoming larger. At 72 h after grouping culture, compared with that inblank control group, the ratio of double positive cells in 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group were significantly increased ( P<0.01); compared with that in 5 ng/mL IL-6 group, the ratio of double positive cells in 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group were significantly increased ( P<0.01); compared with that in 10 ng/mL IL-6 group, the ratio of double positive cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly increased ( P<0.01); the ratio of double positive cells in 100 ng/mL IL-6 group was significantly increased compared with those in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the mRNA expression levels of vascular endothelial cadherin of cells in 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group were significantly decreased ( P<0.01 or P<0.05); compared with that in 5 ng/mL IL-6 group, the mRNA expression levels of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly decreased ( P<0.01); compared with that in 10 ng/mL IL-6 group, the mRNA expression levels of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly decreased ( P<0.01); compared with that in 25 ng/mL IL-6 group, the mRNA expression levels of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly decreased ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the mRNA expression levels of α-SMA of cells in 5 ng/mL IL-6 group, 10 ng/mL IL-6 group, 25 ng/mL IL-6 group, 50 ng/mL IL-6, group, and 100 ng/mL IL-6 group were significantly increased ( P<0.05 or P<0.01). Cells from the 2nd batch were cultured for 72 hours after grouping. Compared with 1.391±0.026 in blank control group, the protein expressions of vascular endothelial cadherin of cells in 10 ng/mL IL-6 group (1.185±0.063), in 25 ng/mL IL-6 group (0.717±0.078), and in 50 ng/mL IL-6 group (0.239±0.064) were significantly decreased ( P<0.05); compared with that in 10 ng/mL IL-6 group, the protein expressions of vascular endothelial cadherin of cells in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group were significantly decreased ( P<0.01); compared with that in 25 ng/mL IL-6 group, the protein expression of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group was significantly decreased ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the protein expression levels of α-SMA of cells in 10 ng/mL IL-6 group, 25 ng/mL IL-6 group, and 50 ng/mL IL-6 group were significantly increased ( P<0.01); compared with that in 10 ng/mL IL-6 group, the protein expression levels of α-SMA of cells in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group were significantly increased ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the protein expressions of type Ⅰ collagen of cells in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group were significantly increased ( P<0.05). Conclusions:After IL-6 treatment, the phenotype and function of HUVECS showed the characteristics of mesenchymal cells in a concentration-dependent manner. The inflammatory factor can promote the process of EndMT, and become one of the important factors regulating the mechanism of tissue fibrosis.

Objective To investigate the characteristics of pulmonary function and pathological changes in rats with acute lung injury (ALI) and provide experimental basis for further study on the mechanism of ALI.Methods Twenty five male SD rats were randomly divided into the control group (n =5) and acute lung injury (ALI) group (n =20).Lipopolysaccharide (LPS) (4.5 mg/kg) were injected into the ALI group rats to establish the ALI rat model.The rats in control group were given 150 μl isotonic saline.At 12,24,48,and 72 hours after injury,lung function of the rats were tested by Buxco small animal lung function test system,including the dynamic lung compliance (Cdyn),forced vital capacity (FVC),functional residual gas (FRC),quasi static compliance (Cchord),100th millisecond expiratory volume (FEV100),and airway resistance (RI).In addition,the bronchoalveolar lavage fluid (BALF) was collected for detection of protein level and tumor necrosis factor (TNF-alpha)concentration.At the same time,the changes of lung tissues were recorded,and the pathological changes were observed by HE staining.Results Compared with the control group,Cdyn,FVC,FRC,and FEV100 in ALI group were significantly decreased at each time point after injury (P ＜0.05 or ＜0.01),while the airway resistance (R1) in ALI group was significantly increased at 24 and 48 hours after injury (P ＜ 0.01).There was no significant difference in quasi static compliance (Cchord) between two groups (P ＞ 0.05).The protein level and TNF-alpha concentration of BALF in ALI group were increased significantly (P ＜0.05 or ＜0.01) 12-72 hours after injury (P ＜ 0.01).Compared with the control group,the whole lung was dark red in ALI group 12 hours after injury,and the most serious bleeding occurred in the pulmonary hilum area with single or multiple hemorrhagic foci of different sizes.Multiple punctate and focal bleeding of different sizes were seen on the lung surface,which were radially distributed around the pulmonary hilum.The color of lung tissue was gradually restored to normal at 72 hours after injury.Under the light microscope,pulmonary interstitial edema,inflammatory cell infiltration,pulmonary vascular congestion and focal pulmonary hemorrhage were observed 12 h after injury,showing typical ALl pathological changes.The pathological changes were the most significant at 24 hours and reduced obviously at 72 hours.Conclusions A single intratracheal injection of LPS can induce typical ALI pathological changes.There is a similar trend between the pulmonary function indexes,lung pathology characteristics,and the protein level of BALF and proinflammatory cytokine level,suggesting that the pulmonary function test parameters can provide reference for evaluation of ALI.

Objective To evaluate the changing trend of serum thyrotropin (TSH) levels for hemithyroidectomy patients,and to discuss the necessity and strategy of TSH suppression for low-risk differentiated thyroid carcinoma(DTC). Methods One hundred and twenty-seven patients with benign thyroid nodules undergoing hemithyroidectomy between January 2013 and June 2014 were retrospectively studied. Serum thyroid hormones levels FT3,FT4,TSH,thyroid peroxidase antibody(TPOAb),and thyroglobulin antibody(TGAb)were detected at 1 month after surgery for all patients and at 3 month for 54 patients. Results (1)Mean TSH level at 1 month after surgery was significantly higher than preoperative TSH level(2.45 mIU/L vs 2.20 mIU/L,n=127,P<0.01). The mean TSH level at 3 month after operation was significantly higher than preoperative ones(2.46 mIU/L vs 2.35 mIU/L,n=54, P<0.05). (2)TSH<2. 0 mIU/L was found in 52 patients(40. 9%) and TSH>4. 94 mIU/L in 18 patients (14.17%) at 1 month after operation. TSH<2.0 mIU/L was found in 28 patients(51.85%)and TSH>4.94 mIU/L in 8 patients(14.81%) at 3 month after operation. (3)A preoperative TSH≥2.0 mIU/L and the coexistence of Hashimoto's thyroiditis were found to be independent risk factors for the TSH levels higher than 2.0 mIU/L. Among the patients with TSH≥2. 0 mIU/L at 1 month, 13 exhibited spontaneous recovery at 3 month, coexistence of Hashimoto's thyroiditis was related to this phenomenon. Among the patients with TSH<2.0 mIU/L at 1 month,TSH levels were elevated over 2. 0 mIU/L in 7 patients by 3 month comparing to that by 1 month. Coexistence of Hashimoto's thyroiditis was independent risk factor for the TSH elevation. Conclusion TSH suppression may still be performed to patients with low risk DTC after operation especially to whom the preoperative TSH≥2.0 mIU/L and the coexistence of Hashimoto's thyroiditis. Suppression therapy should be carefully considered with close follow-up.

Female ; Humans ; Lymphoma ; diagnosis ; Pregnancy ; Pregnancy Complications, Neoplastic ; diagnosis

Objective To investigate the effects of PTD4-GFP-Apoptin protein on proliferation inhibition and apoptosis-inducing of different types of leukemia cells. Methods Genetic engineering was used to restructure a carrier containing PTD4-GFP-Apoptin gene, and MTT was applied to detect the expressed PTD4-GFP-Apoptin fusion protein and its effect on the leukemia cell proliferation. Flow cytometry (FCM) was used to detect the effects on cell apoptosis. Results MTT cell proliferation inhibitory experiment showed that PTD4-GFP-Apoptin had different degree of proliferation inhibition on different types of leukemia cells;furthermore, the inhibitory effect presented positive correlation with time and concentration. FCM showed that PTD4-GFP-Apoptin had apoptosis-inducing effect on HL-60 cells, and the apoptotic rate had significant difference compared with the control group (P <0.05). Conclusions PTD4 can carry large proteins to penetrate the cell membrane, and PTD4-GFP-Apoptin may produce the inhibiting proliferation in vitro for a variety of leukemia cells. Apoptin can induce tumor cell apoptosis without affecting normal cells, which might become a new agent for the clinical treatment of leukemia.

Objective To evaluate the clinical and pathological characteristics and risk factors of the prognosis of Cardia cancer.Methods Clinical data of 52 cases of cardiac cancer patients who were treated by surgery and follow-up data were collected from June 2009 to August 2011.Factors influencing the prognosis of the patients were analyzed by univariate and multivariate analysis.Results The survival rates in 1,2,3years were 73％,54％,46％.Single factor analysis showed that there was a significant correlation between T stage,N stage,TNM stage,classification Siewert,MSLN and venous invasion.Stepwise Cox proportional hazard model showed that T stage,N stage and MSLN were independent risk factors.Peritoneal and liver were the main way of recurrence and metastasis.Peritoneal metastasis was related to T stage and lymph node invasion,while the liver metastasis was related to MSLN.The survival curves of patients with Kaplan-Meier showed that the survival period of patients with liver metastasis and peritoneal metastasis was significantly shortened.Conclusion Standardization of lymph node cleaning is a key factor affecting prognosis,D2 surgery should be an operation standard in cardia cancer.