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, more and more studies have shown that myeloid-derived suppressor cells (MDSCs) participate in the development and progression of various chronic liver diseases including chronic viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver diseases, and liver cancer. As a type of cells derived from bone marrow progenitor cells and immature myeloid cells, MDSCs play an important role in the development, progression, and repair of liver diseases by regulating inflammatory response and the differentiation and function of immune cells. This article reviews the research advances in the association between MDSCs and various liver diseases, in order to provide new thoughts for the clinical diagnosis, prognosis, and treatment of chronic liver diseases.

Objective To evaluate the effects of dexmedetomidine combined with lidocaine on postopera-tive cytokine response after abdominal hysterectomy. Methods We enrolled 80 women with American Society of Anesthesiologists(ASA)physical statusⅠandⅡ,aged 35-68,and scheduled for elective abdominal hysterectomy under general anesthesia.The patients were randomly assigned into CON group,LIDO group,DEX group and LI-DO + DEX group(n=25 in each group). The four groups received an Ⅳ bolus infusion of normal saline,lido-caine,dexmedetomidine,and lidocaine combined with dexmedetomidine respectively,over 10 minutes before in-duction of anesthesia,followed by a continuous IV infusion of normal saline,lidocaine,dexmedetomidine,and li-docaine combined with dexmedetomidine until abdominal wound closure,respectively.Interleukin-6 and tumor ne-crosis factor-α levels in serum were measured before administration of drugs(T1),at the end of surgery(T2),post-operative 2 hour(T3)and postoperative 24 hour(T4). Results Interleukin-6 and tumor necrosis factor-α level in serum were higher at T2,T3and T4in the four groups. Compared to those in CON group,interleukin-6 and tumor necrosis factor-α levels in DEX and DEX+LIDO group were significantly decreased at T2,T3and T4(P<0.05). Interleukin-6 and tumor necrosis factor-α level in serum in LIDO group were also decreased at T2,T3and T4,but there was no significant difference between CON group and LIDO group(P > 0.05). Compared to that in LIDO group,tumor necrosis factor-α level in serum in DEX group was significantly decreased at T3and T4;interleukin-6 level in serum in DEX group was significantly decreased at T2,T3and T4(P<0.05).Interleukin-6 and tumor ne-crosis factor-α levels in serum in DEX+LIDO group were the lowest compared to those in other three groups at T2,T3and T4(P < 0.05). Recovery time and extubation time were significantly prolonged between DEX group and DEX + LIDO group(P < 0.05). Conclusions Dexmedetomidine combined with lidocaine infusion significantly decrease postoperative cytokine response and this may be attributed to the anti-inflammation effects of dexmedetomi-dine and lidocaine.

Objective The aim of this study was to evaluate the value of serum exosomal miRNAs,originating from tumor tissue cells,could be used as noninvasive biomarker for distinguishing clear cell renal cell carcinoma (ccRCC).Methods 30 pairs of tissue samples and the corresponding serum samples were collected from 20 ccRCC male patients and 10 female ccRCC patients,operated in our department from June 2015 to June 2016.Their age ranged from 45 to 70 years old,mean 57 years old.Based on the miRNA microarray analysis of ccRCCs miRNA expression profiles,we picked up four miRNAs,including miR-210,miR-224,miR-452,and miR-34a,to confirm our hypothesis.Then the expression quantity of these four miRNAs in tissues,serums and serum exosomes were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR).Sensitivity,specificity and area under curve (AUC) for serum miRNA levels were determined using receiver operator characteristic (ROC) analysis.Results Expression of miR-210,miR-224,and miR-452 were higher in tumor tissues compared to those in adjacent noncancerous tissues (P＜0.05),increasing by 20.51-fold,54.08-fold and 2.48-fold respectively.But only miR-210 was significantly higher in ccRCC patients compared to healthy controls (HCs) in serum and serum exosome (P ＜0.05),increasing by 2.45-fold and 2.32-fold respectively.ROC curve analysis indicated that the serum exosomal miR-210 level might serve as a useful biomarker for differentiating patients with ccRCC from those with HCs;the AUC was 0.8789 (95％ CI 0.7803-0.9775) and the sensitivity and specificity was 92.1％ and 80.0％,respectively.Conclusion The detection of miR-210 in the serum exosome is useful for early diagnosis of clear cell renal cell carcinoma.

Objective Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China,so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking.This study aimed to analyze the direct,indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China.Methods The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study.All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases.The direct expenditure included direct medical cost and direct non-medical cost.The indirect expenditure,including work loss of patients and caregivers,were calculated by using human capital method for urban and rural populations in 12 areas.The intangible expenditure were reflected by willing to pay and stochastic tournament.The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis.Results A total of 27 hospitals in 12 areas were included in the survey.A total of 4 718 cases were surveyed,the overall response rate was 77.7％.The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case,in which the highest proportion (61.2％)was medicine fees [10 365.10 yuan (RMB)].The average direct expenditure and indirect expenditure were consistent with the severity of illness,which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively,with the ratio of 3.85:1.The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)].It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures.Among the average indirect expenditure,the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)],The total direct and indirect expenditure was highest for liver transplantation,followed by severe hepatitis,hepatocellular carcinoma and decompensated cirrhosis,acute hepatitis B,compensated cirrhosis and chronic hepatitis B.The influencing factors for both direct and indirect expenditure were high hospital level,severity of hepatitis B,living in urban area,antiviral therapy,long hospitalization and monthly income of family.For average 3.74 outpatient visits and 1.51 hospitalization,the average annual direct,indirect and intangible expenditure for HB-related diseases were 30 135.30,6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)],accounting for 37.3％,7.7％ and 55.0％,respectively.Of the annual direct medical expenditure [28 402.80 yuan (RMB)],which were much higher than non-medical expenditure [1 732.50 yuan (RMB)],hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)].The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB),respectively.Of the annual intangible expenditure,the highest was that for/primary hepatocellular carcinoma,followed by cirrhosis,chronic hepatitis B,severe hepatitis B,liver transplantation and acute hepatitis B.Conclusions A heavy economic burden has been caused by HB-related diseases in China,and patients are more likely to rely on medical service rather than non-medical service.It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits.The influence of HB related diseases on mental health of the people can be reflected by an economics term,intangible expenditure.

Objective To observe the effects of enriched environment on cognitive function in mice with sepsis-associated encephalopathy and to study the neuron PAS domain protein 4 (NPAS4)/brain deprive neurotrophic factor (BDNF)related mechanisms.Methods Sixty adult male mice were divided randomly into three groups:sham operation with standard environment group (group SS,n =12),cecal ligation and puncture with standard environment group (group CS,n =24),cecal ligation and puncture with enriched environment group (group CE,n =24).All mice were reared in standard environment or enriched environment for 28 days.The fear condition test was conducted on day 29 af-ter operation in mice.The change of NPAS4 and BDNF,the density of dendritic spine were detected by western blot or golgi staining.Results Compared with group SS,the context freezing time, NPAS4 and BDNF expression and the density of dendritic spine in hippocampus decreased significantly in group CS (P < 0.05).Compared with group CS,the context freezing time,NPAS4 and BDNF expression and the density of dendritic spine in hippocampus increased significantly in group CE (P <0.05).No significant difference was observed in the conditional freezing time among three groups.Conclusion Enriched environment can obviously improve cognitive function impairment induced by sepsis-associated encephalopathy,which may be related with up-regulated expression of NPAS4/BDNF,and promoted synaptic plasticity.

Objective To evaluate the clinical efficacy and safety of integrated traditional Chinese and Western medicine in treating active rheumatoid arthritis (aRA).Methods A prospective randomized controlled study was carried out. Totally 148 aRA patients were divided into the control group and the treatment group, 74 cases in each group. Control group was treated with MTX (methotrexate) and LEF (leflunomide), while the treatment group took traditional Chinese medicine based on syndrome differentiation, on the basis of treatment with MTX and LEF. The therapeutic course for all was 3 months. Efficacy indexes, like clinical symptoms and signs, ESR, TCM syndrome integrals, DAS 28 score, and safety indexes were observed.Results This study finally completed 136 cases, including 69 cases in the treatment group and 67 cases in the control group. In the two groups, significant improvement of clinical signs and symptoms, ESR, DAS28, and TCM syndrome integrals after treatment were shown, with statistical significance (P<0.01). Better effects were obtained in the treatment group in lessening tender joint numbers and swollen joint numbers, DAS28, and TCM syndrome integrals (P<0.01). The total effective rate of the TCM syndrome efficacy was 86.96% (60/69) in the treatment group, and 76.12% (51/67) in the control group, without statistical significance (P>0.05). The significant efficiency of the treatment group was 11.59% (8/69), and the control group was 5.97% (4/67), with statistical significance (P<0.05). Adverse reactions occurred fewer in the treatment group than in the control group (P<0.01).Conclusion Compared with single traditional Chinese medicine, integrated traditional Chinese and Western medicine for treating aRA can better improve DAS28 and TCM syndrome integrals, and reduce the incidence of adverse reactions.

Objective To compare the clinical outcomes of long and short InterTan intramedullary nailing of senior intertrochanteric hip fracture in conjunction with early total care (ETC).Methods In this prospective study, records of 30 elder patients with intertrochanteric fracture hospitalized between January 2011 and September 2013 were included.Using the concept of ETC, the patients were treated with long (long-nail group, n =15) and short InterTan intramedullary nails (shortnail group, n =15) within 72 hours postinjury.The two groups were compared for operation time, intraoperative blood loss, fracture healing time, Harris hip score, time to pre-injury mobilization and hardware failure rate.Results Operation time was (77.25 ± 7.38) minutes in long-nail group versus (72.10 ± 6.90) minutes in short-nail group (P ＜ 0.01).Time to pre-injury mobilization was (7.45 ± 1.61) months in long-nail group versus (8.57 ± 2.18) months in short-nail group (P ＜ 0.05).There were no significant differences between long-and short-nail groups regarding the blood loss [(180.75 ± 38.26)ml vs (178.62 ± 34.79)ml], fracture healing time [(4.82 ± 1.12)months vs (4.76 ± 1.04) months], and Harris hip score [(83.75 ± 1.71) points vs (82.57 ± 2.18) points] (P ＞ 0.05).Conclusions Either long or short InterTan intramedullary nailing combined with ETC is effective in treatment of intertrochanteric hip fracture in the elderly.However patients treated with long nails return to pre-injury mobilization relatively earlier.Long InterTan intramedullary nail system is better for the patients combined with serious osteoporosis.

Objective:To study the anti-human respiratory syncytial virus ( RSV) activity of natural curcuminoids in Curcuma lon-ga in vitro. Methods:The anti-RSV activity of ethyl acetate part of 95% ethanol extracts of Curcuma longa and natural curcuminoids in Curcuma longa in vitro were detected by cytopathic inhibition method. Results:Bisdemethoxycurcumin exhibited anti-RSV activity with IC50 of 12. 5 μg·ml-1 and SI of 1. Conclusion:Natural curcuminoids in Curcuma longa exhibit anti-RSV activity.

Objective To investigate the distribution of arterial stenosis in patients with ischemic cerebrovas-cular disease and its risk factors .Methods 224 patients with ischemic cerebrovascular disease were divided into four groups according to DSA results .Patients showed no stenosis or mild stenosis were selected as control group ( 43 ca-ses),the other patients were divided into pure extracranial stenosis group (41 cases),simple intracranial stenosis group (93 cases) and extracranial stenosis group (47 cases).The results of laboratory test were analyzed .The ques-tionnaire was designed and the indicators including name ,age,long-term smoking,drinking,hypertension and diabetes were collected .Results Of all the subjects , there were 181 cases with artery stenosis .Single factor results showed that gender,age,long-term smoking,long-term drinking,hypertension,diabetes,high homocysteine,high level of lyso-phosphatidic acid were the independent risk factors of cerebral artery stenosis (χ2/t =8.744, 5.562, 10.736, 11.032,9.812,10.002,9.083,2.576,all P<0.05).Multivariate analysis showed that high homocysteine ,long-term smoking and drinking were the risk factors of simple intracranial artery stenosis .High homocysteine and high fibrino-gen were risk factors of simple extracranial stenosis .Age,hypertension,long-term smoking and drinking ,high homocys-teine and fibrinogen were risk factors of intracranial and extracranial stenosis .Conclusion In patients with ischemic cerebrovascular diseases ,the simple intracranial artery stenosis is most common .The incidence of cerebral artery ste-nosis has age characteristic ,with the increase of age ,the incidence rate of intracranial and extracranial artery stenosis is rising.High homocysteine,long-term smoking and drinking,hypertension,diabetes,high lysophosphatidic acid are independent risk factors of cerebral artery stenosis .