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

Volatile oil microemulsion gel of traditional Chinese medicine has the dual characteristics of microemulsion and gel， which can improve the solubility and stability of drugs， promote drug absorption and achieve long-term sustained release effect. In recent years， it has been widely used in clinical diseases such as internal medicine， gynecology and pediatrics. In this paper， the characteristics， prescription design， molding process and quality evaluation of volatile oil microemulsion gel of traditional Chinese medicine were reviewed by searching relevant literature. The results showed that the volatile oil microemulsion gel had the characteristics of improving the stability of the drug， increasing the transdermal penetration of the drug， strong adhesion， easy to wash， convenient preparation， etc. The prescription design consists of oil phase， surfactant， cosurfactant and gel matrix. The molding process includes the molding process of microemulsion and the molding process of gel， and the formation of microemulsion mainly uses the pseudo-ternary phase diagram method. The quality evaluation can be divided into 2 parts： volatile oil of traditional Chinese medicine and microemulsion gel. The quality evaluation of volatile oil can be studied qualitatively and quantitatively. Microemulsion gel should meet the relevant requirements and be tested for in vitro release and transdermal absorption.

Objective:To evaluate the outcomes of aortic root repair in acute type A aortic dissection (ATAAD) with aortic sinus involvement.Methods:The clinical data of patients with ATAAD involving the aortic sinus and an aortic root diameter of ≤45 mm who were treated from January 1, 2015, to December 31, 2016, were collected. Patients were divided into group A (involvement of one aortic sinus or part of one aortic sinus) and group B (involvement of more than one aortic sinus). The effectiveness of aortic root repair in ATAAD with sinus involvement was analyzed by comparing the preoperative imaging characteristics and postoperative results between the two groups.Results:The study cohort comprised 155 patients, including 100 patients in group A and 55 in group B. There were no differences between the two groups in baseline characteristics, aortic root diameter, 30-day mortality, and complication rates. During an average follow-up of(49.1±14.6) months, there was no difference between the two groups in the survival rate (92.0% vs. 89.5%, P=0.61). The aortic root diameter at follow-up showed no progressive expansion compared with preoperatively in either of the two groups[(38.1±3.6) mm vs. (37.9±3.5)mm, P=0.92, A; (38.4±4.1) mm vs. (38.3±3.6) mm, P=0.74, B]; furthermore, there was no difference between the two groups in aggravation of aortic regurgitation. Conclusion:Aortic root repair achieves satisfactory medium-term outcomes in ATAAD with more than one aortic sinus involved, but the long-term outcomes need to be evaluated.

OBJECTIVE To study the effects of the compatibility of Schisandra chinensis on Psoralea corylifolia -induced oxidative damage and endoplasmic reticulum stress in L 02 hepatocytes，and to provide reference for clinical use of the compatibility attenuation of P. corylifolia -S. chinensis . METHODS L02 cells were divided into blank control group ，P. corylifolia model group （1 200 μg/mL P. corylifolia ，calculated by crude drug ），P. corylifolia -S. chinensis low-dose，medium-dose and high-dose groups （1 200 μg/mL P. corylifolia combined with 600，1 200，2 400 μg/mL S. chinensis ，respectively，calculated by crude drug ）. After the cells in each group were cultured in culture medium or drug solution for 48 hours，the levels of aspartate aminotransferase（AST）and alanine aminotransferase （ALT）were detected ；the levels of glutathione （GSH），superoxide dismutase （SOD）and malondialdehyde （MDA）in cell culture medium were detected ；reactive oxygen species （ROS）level and mitochondrial membrane potential in cells were detected ；mRNA and protein expressions of glucose-regulated protein 78（GRP-78）and protein kinase R-like endoplasmic reticulum kinase （PERK）were detected. RESULTS Compared with blank control group ，the levels of AST，ALT，MDA and ROS ，mRNA and protein expressions of GRP- 78 and PERK were increased significantly in P. corylifolia model group （P＜0.05 or P＜0.01）；while GSH and SOD levels ，mitochondrial membrane potential were decreased significantly （P＜0.05 or P＜0.01）. Compared with P. corylifolia model group ，above indexes of P. corylifolia -S. chinensis low-dose， medium-dose and high-dose groups were all improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS The compatibility of P. corylifolia -S. chinensis can alleviate P. corylifolia -induced oxidative damage and endoplasmic reticulum stress of L 02 cells.

Objective:To investigate the long term outcome of artificial urinary sphincter implantation for patients with stress urinary incontinence.Methods:The data of 46 patients who underwent artificial urethral sphincter implantation in China Rehabilitation Research Center from April 2002 to April 2022 were retrospectively analyzed.The patients’ age ranged from 19-80 years old (median 45.6 years). There were 45 males and 1 female. The history of illness was 8 months to 33 years. The patients category were urethral injuries associated urinary incontinence ( n=24), neurogenic urinary incontinence ( n=9) and post-prostatectomy incontinence ( n=13). Preoperative daily pad usage was 3.5±1.0. The impact of incontinence on the quality of life (QOL)measured by the visual analogue scale (VAS)was 7.1±1.2. All 46 patients underwent artificial urethral sphincter implantation, of which 20 patients were treated with anticholinergic drugs (5 cases) or urinary tract related surgery (urethral stenosis incision in 2 cases, sphincterectomy in 3 cases, urethral dilation in 5 cases, urethral calculus lithotripsy in 1 case, and augmentation cystoplasty in 4 cases) before artificial urethral sphincter implantation. Of the 45 male patients, 25 patients had the transperineal approach and 20 had the trans-scrotal approach. The female case had a trans-retropubic approach. Different cuffs size was used based on individual circumference of bulbar urethra (45 male cases: 4.5cm in 16 cases, 4.0cm in 29 cases; one female case: 8.0cm). Long-term surgical efficacy was evaluated. Assessments included postoperative urinary continence (socially continent: one pad per day or less; complete dry: wearing no pads), artificial urinary sphincter status and complications. The influences of patients of different etiologies, surgical approaches and cuff size on surgical results were compared. Results:The mean follow-up time was 7.1 years ranged from 6 months to 19 years. At the latest visit, 32 patients (69.6%) maintained the primary functional artificial urinary sphincter. Three patients (6.5%) had artificial urinary sphincter revisions and maintained continence with the new device. 11 patients (23.9%) removed the artificial urinary sphincter because of post-complications. Thirty-five patients were socially continent, of which 16 patients were totally dry, leading to the overall social continent rate as 76.1%(35/46). There was a significant reduction in pad usage to 1.2±0.6 diapers per day ( P<0.001). The impact of incontinence on the QOL measured by the VAS dropped to 2.6±1.9 ( P<0.001). The complication rate was 32.6%(15/46), including infections ( n=4), erosions ( n=5), mechanical failure ( n=3), dysurie ( n=2) and urethral atrophy ( n=1). There were no significant differences in social continent rate between patients with different etiologies[75.0%(18/24)vs. 66.7%(6/9) vs. 84.6%(11/13)], perioperative complications [37.5%(9/24)vs. 33.3%(3/9) vs. 23.1%(3/13)] and device re-intervention rate[37.5%(9/24) vs. 33.3%(3/9)vs. 15.4%(2/13)]. There were no statistically significant differences in postoperative complete dry rate [32%(8/25)vs. 40%(8/20), P=0.76] and postoperative device failure free rate [60%(15/25)vs. 80%(16/20), P=0.20] between trans-perineal group and trans-scrotal group. There was no statistically significant difference in postoperative social continent rate between 4.5cm cuff and 4.0 cuff[75%(12/16) vs. 65.5%(19/29), P=0.74]. Conclusions:Artificial urethral sphincter implantation is an effective treatment for stress urinary incontinence due to intrinsic sphincter deficiency. There was no difference in the continent rate and complication rate between patients of different etiologies, different surgical approaches and cuff size selection.

Traumatic craniocerebral injury has been paid close attention by neurosurgeons at home and abroad due to its high morbidity and mortality.Cerebral contusion and intracranial hematoma caused by various injury mechanisms are the main causes of increased intracranial pressure in the acute stage of traumatic brain injury.As a classic surgical method,standard decompressive craniotomy,often together with intracranial hematoma evacuation,brain debridement and internal decompression,has become the main surgical treatment in the acute stage of traumatic brain injury,saving the lives of many patients with severe cerebral injury,the importance of this procedure is irreplaceable.In long-term clinical practice,through the unremitting efforts of first-line neurosurgeons and neuroscientists,a large number of studies have been conducted on the relationship between the details,norms and prognosis of craniotomy,so as to better regulate the treatment of traumatic brain injury and reduce the death and disability rate of patients with severe brain injury.This article systematically reviews and analyzes the pathophysiological mechanism of intracranial hypertension and the mechanism,development history,surgical methods,indications and contraindications,prognosis and prospects of the intracranial hypertension.Through this article,the author hope to have some guidance and suggestions for future clinical work.

Objective To clarify the relationship between intracranial pressure monitoring and prognosis of patients with traumatic brain injury after decompressive craniectomy.Methods From December 2015 to December 2017,48 head-injured patients in Affiliated Suzhou Hospital of Nanjing Medical University were enrolled,who were underwent decompressive craniectomy in this retrospective study.The patients were subdivided into 2 groups based on whether postoperative was monitored (n =19) or not (n =29).The prognosis was evaluated by Glasgow Outcome Scale score,with 1 point of prognosis death,2 to 3 points of poor prognosis,and 4 to 5 points of good prognosis.Count data were expressed as a percentage (％).Count data were expressed as percentage (％).The chi-square test was used to compare the difference in the rate of good prognosis and mortality between the two groups.Results The mortality of monitoring group (10.5％) was significantly lower than that of control group (37.9％) (x2 =4.365 5,P =0.036 7) during hospitalization,The rate of good prognosis in the monitoring group (68.4％) and the control group (44.8％) was not statistically significant (x2 =2.573 8,P =0.108 6).Condusion The study showed that continuous monitoring in patients with severe craniocerebral injury could reduce the mortality of patients during hospitalization,but had no significant effect on the improvement of prognosis.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.

Objective Transient brain function inhibition is a common symptom after mild brain injury,but some patients show persistent post-concussional syndrome (PCS).The aims of this study are to assess functional and causal connectivity of attention and default mode network using resting-state functional MR imaging (fMRI) to investigate the abnormal connectivity and its significance in PCS patients.Methods Resting-state fMRI data were collected from 23 PCS patients with attention disorders,admitted to our hospital from November 2015 to October 2016 and 21 age-,gender,and education-matched healthy controls recruited at the same period.The fMRI data were analyzed by group independent component analysis (ICA) toolbox to attention networks and default mode network (DMN).The components of the selected networks were compared in PCS and healthy controls to explore the changes of functional connectivity (FC).Granger causality analysis (GCA) was performed by taking the above significant brain areas as regions of interest (ROIs) to calculate bivariate coefficient of each pair of ROIs.Comparisons were performed to find the significant different causal connectivity of the two groups.Results In attention networks,the FC value of left frontal eye field (FEF),bilateral intraparietal sulcus (IPS),bilateral ventral prefrontal cortex (vPFC) and bilateral temporo-parietal junction (TPJ) was decreased.In DMN,the FC value of bilateral medial prefrontal cortex (mPFC) was reduced and bilateral precuneus (PCUN) was enhanced.Correlating GCA value,it was increased significantly from left FEF to left PCUN and IPS,while it was reduced from left PCUN and IPS to left FEF;and it was decreased from left IPS to left vPFC and increased from left TPJ to left PCUN.Conclusion The attention networks are restrained in resting state,which may influence the attention function in PCS patients;and the causal connection is altered in the above ROIs,and these changes may be related to inhibition of activation of default network to compensate for the loss of attention function by antagonistic effects in PCS patients.

ObjectiveTo explore the changes of degree attribute values and its significance of post-concussion syndrome (PCS) patients with tinnitus by the brain network research method based on graph theory.Methods34 PCS patients were chosen,including 17 PCS patients with bilateral tinnitus (PCS tinnitus group) and 17 PCS patients without tinnitus (PCS non-tinnitus group).Meanwhile,17 healthy individuals with the matched age,gender and educational background were recruited as the control.Degree attribute values of PCS patients with tinnitus were figured out with the brain network research method based on graph theory.Results(1)The degree attribute values of PCS patients without tinnitus at left orbital middle frontal gyrus (3.13±1.07),left thalamus (2.51±1.03),left superior temporal gyrus (3.67±1.31),right anterior cingulate cortex (3.13±1.25),right posterior cingulate cortex (2.13±1.08) and right supramarginal gyrus (4.46±1.35) were reduced compared with the control group (4.41±1.47,3.71±1.08,5.27±2.13,5.51±0.67,5.63±2.16 and 5.64±1.30) (P<0.05).The degree attribute values of PCS patients without tinnitus at left posterior cingulate cortex (5.87±1.06) and left gyrus lingualis (4.67±1.48) increased compared with the control group (4.41±1.46,3.21±1.27) (P<0.05).(2) The degree attribute values of PCS patients with tinnitus at left posterior cingulate cortex (3.37±1.54),left parahippocampal gyrus (3.41±1.62),left amygdala (2.25±1.43),left angular gyrus (4.17±1.02),left superior temporal gyrus (3.25±1.02),right thalamus (2.35±1.34),right Heschl gyri (3.97±1.62),right superior temporal gyrus (3.26±1.22),right cuneus (3.18±1.32) and right lingular lobe (3.26±1.42) were decreased,compared with the control group (4.41±1.46,5.27±2.13,3.71±1.08,5.63±2.61,5.64±1.30,3.43±1.33,5.63±2.16,5.13±1.64,5.51±0.67,4.24±0.63) (P<0.05).The degree attribute values of PCS patients with tinnitus at right posterior cingulate cortex (5.76±1.83),left MPFC (6.08±1.62) and right precuneus (6.08±1.06) were increased,compared with the control group (4.47±1.26,4.41±1.47,4.81±0.62) (P<0.05).(3)The degree attribute values of PCS patients with tinnitus at left MPFC,left amygdale,left parahippocampal gyrus,right Heschl gyri,right superior temporal gyrus,right cuneus and right lingular lobe were decreased,compared with PCS patients without tinnitus (P<0.05).The degree attribute values of PCS patients with tinnitus at right posterior cingulate cortex and left insular lobe increased,compared with PCS patients without tinnitus (P<0.05).ConclusionsPCS patients with tinnitus present the alteration of degree attribute in related brain network structure.The alteration in degree attribute of relevant brain zones in auditory system,limbic system and default network system may be important factors which result in tinnitus of PCS patients.