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 investigate the short- to medium-term therapeutic effects of a new internal fixation device,intraosseous internal fixation(IO-FIX),in the foot-ankle arthrodesis.Methods From August 2016 to December 2018,32 patients(40 feet) underwent foot-ankle arthrodesis with IO-FIX at Department of Orthopaedic Surgery,The Ninth Peopled Hospital of Shanghai.They were 6 males and 26 females,aged from 23 to 83 years(61.7±15.1 years).There were 28 cases(36 feet) of hallux valgus,2 cases(2 feet) of ankle arthritis,one case(1 foot) of ankle rheumatoid arthritis and one case(1 foot) of naviculocuneiform arthrosis.The therapeutic effects were assessed in terms of imaging evaluation,American Orthopaedic Foot and Ankle Society(AOFAS) score,fusion rate and full weight-bearing time.Results The follow-up ranged from 3.0 to 31.3 months(mean,12.6 months).The total fusion rate was 95.0%(38/40);the total AOFAS score increased significantly from preoperative 41.9±9.5 to postoperative 86.9±4.7(P<0.05).The 28 patients(36 feet) with hallux valgus achieved a successful fusion rate of 97.2%(35/36) and full weight-bearing at 8 weeks after operation.Their fusion time ranged from 45 to 64 days(57.1 days).Their metatarsophalangeal angle was decreased significantly from 52.10±13.50 preoperatively to 13.40±4.90 postoperatively and their 1-2 intermetatarsal angle significantly from 14.5°±2.4°to 8.90±2.4°(P<0.05).Their AOFAS ankle-hindfoot score was improved significantly from 41.8±9.9 to 87.0±4.8(P<0.05).All the 3 cases of ankle arthrodesis achieved good bone union and full weight-bearing within 12 weeks and their AOFAS ankle-hindfoot score was improved significantly from preoperative 43.4±3.5 to 86.3±3.5 at the final follow-up.Conclusion In foot-ankle joint arthrodesis,due to advantages of stable fixation,zero profile,limited soft tissue irritation,reinforced bone bridge and easy reproducibility,10-FIX can lead to satisfactory short- to mid-term therapeutic effects.

Objective To evaluate the validity and security of our self-designed bone marrow stem cell Screen-Enrich-Combine(-Biomaterials) Circulating System(SECCS) for bone non-union of limbs. Methods From May 2013 to December 2015, 24 patients with limb non-union were treated at our de-partment. They were aged from 20 to 65 years (mean, 42.8 years). Their non-union involved femur in 17 cases, tibia in 4, radius in one, humerus in one and fibula in one. In surgery, 80 mL bone marrow blood was aspirated from the anterior superior iliac spine for rapid preparation of bone substitute(β-TCP)composite with bone marrow stem cells by SECCS which was then implanted at the non-union locations. The bone marrow blood was collected before and after enrichment for stem cell counts. The bone union, clinical union time and related com-plications were evaluated by follow-up X-rays at 1, 3, 6 and 9 months after surgery. Results Each collection of bone marrow blood took 13.5 minutes on average. The enrichment rate of stem cells was 81.2%. 11,751 ± 1,011 stem cells were implanted per patient on average. All the patients were followed up for 9 to 48 months (mean, 19.2 months). Twenty-two patients acquired clinical union 9 months after operation and the other 2 suffered from malunion due to insufficient bone implant, yielding a union rate of 91.6% and an average union time of 6.5 months. No graft infection or internal fixation failure occurred and no severe complications hap-pened at the donor or implant sites.Conclusion The bioactive bone substitute manufactured by our self-designed SECCS can be used as a novel therapy for limb non-union, and this device is moreover charac-terized with convenience, limited invasion and satisfactory osteogenesis so that complications of autologous bone transplantation can be avoided.

Objective To introduce a new method for preparation of bioactive β-tricalcium phosphate (β-TCP) by rapid stem cell screen-and-enrich-and-combine circulating system (SECCS) and evaluate its efficacy in the treatment of fresh fractures and bone defects.Methods Twenty-two patients with fresh fracture and bone defects were treated with SECCS from July 2013 to April 2016.They were 16 males and 6 females with an average age of 52.2 years (from 27 to 81 years).There were 15 tibial plateau fractures and 7 calcaneal fractures.The average size of bone defects was 12.5 mL.Bioactive β-TCP was prepared by SECCS intraoperatively and implanted back immediately into the bone defects.Radiographic examination,Lysholm knee scoring and Maryland foot scoring were used for assessment of curative efficacy.Results The 22 patients were followed up for an average of 25.7 months (from 12 to 46 months).By SECCS,the enrichment efficiency of bone marrow stromal cells (BMSCs) reached up to 82.4％ and the cell viability was not affected.The tibial plateau fractures were re-transplanted with 13,381.3 BMSCs on average and healed after an average of 8.9 weeks (from 6 to 15 weeks).The Lysholm knee scores at one year postoperatively averaged 93.6 points (from 84 to 100 points),yielding 10 excellent cases,4 good cases and one fair case.The calcaneal fractures were implanted back with 16,677.7 BMSCs on average and healed after an average of 9.4 weeks (from 8 to 13 weeks).The average Maryland foot score at one year after operation was 93.6 points (from 85 to 98 points),yielding 6 excellent cases and one good case.Conclusion Bioactive materials prepared by SECCS are good bone grafts for fresh fractures and bone defects.

Objective To investigate the effect of acupuncture on cholinergic anti-inflammatory pathway in the hippocampus of aged rats during global cerebral ischemia-reperfusion ( I∕R ) . Methods Ninety-six clean-grade healthy male Sprague-Dawley rats, aged 17-22 months, weighing 440-580 g, were divided into 3 groups ( n=32 each) using a random number table method: sham operation group ( group S), global cerebral I∕R group (group I∕R) and acupuncture group (group AP). Global cerebral I∕R was induced by 4-vessel occlusion method described by Pulsinelli in group I∕R and group AP. Baihui and Feng-chi were stimulated for 14 consecutive days before ischemia in group AP. Four rats were sacrificed at 1, 3, 5 and 7 days of reperfusion, and brains were removed for determination of neuronal apoptosis by TUNEL. Four rats were sacrificed at 1, 3, 5 and 7 days of reperfusion, and brains were removed for determination of the expression of α7 nicotinic acetylcholine receptor (α7nAChR), choline acetyltransferase (ChAT), tumor necrosis factor-α ( TNF-α) and interleukin-1β ( IL-1β) in the hippocampal CA1 region by Western blot. The apoptosis rate was calculated. Results Compared with group S, the apoptosis rate of hippocam-pal neurons was significantly increased, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point of reperfusion in I∕R and AP groups ( P<0. 05) . Compared with group I∕R, the apoptosis rate of hippocampal neurons was significantly decreased, the expression of α7nAChR and ChAT was up-regulated, and the expression of TNF-α and IL-1β was down-regulated at each time point ofreperfusion in group AP (P<0. 05). Conclusion The mechanism by which acupuncture mitigates global cerebral I∕R injury may be related to activating cholinergic anti-inflammatory pathway in the hippocampus of aged rats.

Objective To evaluate the efficiency of our self-designed enriched filtrator of stem cells in screening and collecting enriched human bone marrow stem cells (BMSCs) for rapid construction of bioactive materials.Methods Bone marrow blood from 32 patients was circulated in our self-designed enriched filtratorand filtered through beta-tricalcium phosphate(β-TCP).The numbers of BMSCs were counted pre-and post-filtration to assess the enrichment efficiency.The numbers of nucleated cells,red blood cells and platelets were compared pre-and post-filtration to assess the effects of the enriched filtrator of stem cells on blood cells.Bacteriological examinations were performed to test the safety of the device.Scanning electron microscopy was carried out to observe the adhesion of BMSCs on β-TCP.Results There was a significant difference between the pre-fihration colony number of BMSCs cultured (232.8 ± 128.6/mL) and the post-filtration one (37.8 ± 34.9/mL) (t =10.743,P ＜ 0.001).The efficiency of BMSCs enrichment of the device was 85.6％ ±8.4％ (from 63.8％ to 97.1％).There were no significant differences between pre-filtration and post-filtration in the numbers of nucleated cells [(16.8 ± 5.4) × 109/mL versus (16.3 ±5.0) ×l09/mL],red blood cells [(3.9±0.6) ×1012/mL versus (3.8±0.6) ×1012/mL] and platelets [(120.4 ± 54.6) × 109/mL versus (123.0 ± 51.8) × 109/mL] (P ＞ 0.05).All the bacteriological examinations of the bone marrow samples were negative.After in vitro osteogenic induction culture,formation of numerous BMSCs colonies was observed on the β-TCP by scanning electron microscopy.Conclusion Since our self-designed enriched filtrator can efficiently collect enriched BMSCs and combine them with β-TCP simultaneously,the device is capable of rapid and safe construction of bioactive materials.

OBJECTIVETo evaluate the alterations in renal function after radical nephrectomy (RN) and partial nephrectomy (PN) for renal cell carcinoma (RCC) and to determine the risk factors for the onset of postoperative renal function impairment.

METHODSWe assessed the renal function of 429 T1a RCC patients by investigating the time-dependent changes of the estimated glomerular filtration rate (eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR < 60 ml · min⁻¹ · 1.73 m⁻² function, and to evaluate the prognosis for the two groups.

RESULTSThe mean eGFR values (ml · min⁻¹ · 1.73 m⁻²) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51.4 ± 12.6, 52.1 ± 17.8, 53.2 ± 19.5, 54.6 ± 20.2, 53.8 ± 16.6, 52.7 ± 22.3 and 51.5 ± 18.4 in the RN group and 69.6 ± 18.3, 70.3 ± 19.5, 71.5 ± 21.4, 76.2 ± 22.8, 75.4 ± 19.7, 74.3 ± 16.3 and 73.1 ± 23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group (P < 0.05). Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction.

CONCLUSIONSRenal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR < 60 ml · min⁻¹ · 1.73 m⁻² impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.

Age Factors ; Carcinoma, Renal Cell ; pathology ; physiopathology ; surgery ; Glomerular Filtration Rate ; Humans ; Kidney Neoplasms ; pathology ; physiopathology ; surgery ; Nephrectomy ; adverse effects ; methods ; Postoperative Complications ; physiopathology ; Postoperative Period ; Renal Insufficiency, Chronic ; etiology ; physiopathology ; Risk Factors

Background and purpose:Laparoscopic retroperitoneal adrenalectomy makes access to the adrenal glands easier and less invasive than open surgery. The aim of this study was to evaluate the clinical efifcacy of laparoscopic retroperitoneal adrenalectomy.Methods:A total of 130 patients who underwent retroperitoneal adrenalectomy for adrenal mass from Jan. 2007 to Dec. 2012 in Fudan University Shanghai Cancer Center were retrospectively assessed. Their clinicopathological factors, perioperative complications and short-term prognostic data were retrieved from the medical records.Results:One hundred and twenty-seven of 130 patients underwent retroperitoneal adrenalectomy successfully, and 3 patients were converted to open surgery due to severe bleeding. Among 130 patients, 63 were male and 67 were female, with the mean age 50.0 years. The pathological results of the 130 patients indicated adrenocortical adenoma in 68, pheochromocytoma in 15, medullary lipoma in 13, adrenal cysts in 10 , ganglioneuroma in 7, metastatic cancer in 5, adrenal hyperplasia in 4, schwannoma in 3, lymphangioma in 2, adrenal hematoma in 1, adrenal cortical carcinoma in 1, adrenal angiosarcoma in 1 and the deputy spleen in 1 (one patient suffering from both pheochromocytoma and ganglioneuroma). The maximum diameters were ranging from 0.5 to 9.0 cm, and mean diameter was 3.48 cm. The average blood loss in surgery was 62.73 mL. Mean length of stay in hospital was 7 d. GradeⅠ complications occurred in 5 patients, including 2 of fever, 1 of food allergy, 1 of drug allergy and 1 of hypokalemia.Conclusion: Retroperitoneal adrenalectomy should be considered as the procedure of choice for the resection of most adrenal tumors in skilled centers with the advantages of minimal invasion, increased safety and faster recovery.

Objective To evaluate the alterations in renal function after radical nephrectomy ( RN) and partial nephrectomy ( PN) for renal cell carcinoma ( RCC) and to determine the risk factors for the onset of postoperative renal function impairment. Methods We assessed the renal function of 429 T1a RCC patients by investigating the time?dependent changes of the estimated glomerular filtration rate ( eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR<60 ml·min-1 ·1.73 m-2 function, and to evaluate the prognosis for the two groups. Results The mean eGFR values ( ml·min-1 ·1.73 m-2 ) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51. 4 ± 12. 6, 52. 1 ± 17. 8, 53. 2 ± 19. 5, 54. 6 ± 20. 2, 53. 8 ± 16. 6, 52.7±22.3 and 51.5±18.4 in the RN group and 69.6±18.3, 70.3±19.5, 71.5±21.4, 76.2±22.8, 75.4± 19.7, 74.3±16.3 and 73.1±23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group ( P<0.05) . Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction. Conclusions Renal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR<60 ml· min-1 ·1.73 m-2 impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.

Objective To evaluate the alterations in renal function after radical nephrectomy ( RN) and partial nephrectomy ( PN) for renal cell carcinoma ( RCC) and to determine the risk factors for the onset of postoperative renal function impairment. Methods We assessed the renal function of 429 T1a RCC patients by investigating the time?dependent changes of the estimated glomerular filtration rate ( eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR<60 ml·min-1 ·1.73 m-2 function, and to evaluate the prognosis for the two groups. Results The mean eGFR values ( ml·min-1 ·1.73 m-2 ) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51. 4 ± 12. 6, 52. 1 ± 17. 8, 53. 2 ± 19. 5, 54. 6 ± 20. 2, 53. 8 ± 16. 6, 52.7±22.3 and 51.5±18.4 in the RN group and 69.6±18.3, 70.3±19.5, 71.5±21.4, 76.2±22.8, 75.4± 19.7, 74.3±16.3 and 73.1±23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group ( P<0.05) . Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction. Conclusions Renal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR<60 ml· min-1 ·1.73 m-2 impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.