Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To investigate the effects of soybean isoflavones(SIF)on immune function of rats with ulcerative colitis(UC)by regulating high-mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signal pathway.Methods:Sixty SD rats were randomly grouped into Model group,low dose SIF group(SIF-L group,300 mg/kg SIF),high dose SIF group(SIF-H group,450 mg/kg SIF),high dose SIF+HMGB1 inhibitor glycyrrhizic acid group(SIF-H+glycyrrhizic acid group,450 mg/kg SIF+30 mg/kg glycyrrhizic acid)and Control group,with 12 rats in each group.The UC rat model was established by TNBS/ethanol combined enema.Body weight changes of rats in each group were measured,and disease activity index(DAI)was determined in each group.Histopathological changes of colon were observed by HE staining;levels of superoxide dismutase(SOD)and malondial-dehyde(MDA)in colon tissue of rats were measured by colorimetry;serum levels of IL-1β,TNF-α and IL-4 were determined by ELISA;flow cytometry was used to determine the percentages of CD3+T,CD4+T and CD8+T lymphocytes in peripheral blood mononuclear cells;levels of serum IgA and IgG were measured by automatic specific protein analyzer;expressions of HMGB1 and RAGE in colon tissues were determined by Western blot and immunohistochemistry.Results:Compared with Control group,levels of DAI,serum TNF-α,IL-1β,IgA,IgG,MDA in colon tissue,HMGB1 and RAGE protein expressions in colon tissue of Model group were obviously higher(P<0.05),while SOD level,IL-4,CD3+T,CD4+T and CD8+T lymphocyte percentages,CD4+/CD8+T were obviously lower(P<0.05),the mucosa of colon tissue was damaged.Compared with Model group,changes of relevant indexes in SIF-H group were contrary to the above(P<0.05),and the damage of colon tissue was alleviated.Conclusion:SIF may enhance the immune function of UC rats by inhibiting HMGB1/RAGE signal pathway.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To investigate the effects of soybean isoflavones(SIF)on immune function of rats with ulcerative colitis(UC)by regulating high-mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signal pathway.Methods:Sixty SD rats were randomly grouped into Model group,low dose SIF group(SIF-L group,300 mg/kg SIF),high dose SIF group(SIF-H group,450 mg/kg SIF),high dose SIF+HMGB1 inhibitor glycyrrhizic acid group(SIF-H+glycyrrhizic acid group,450 mg/kg SIF+30 mg/kg glycyrrhizic acid)and Control group,with 12 rats in each group.The UC rat model was established by TNBS/ethanol combined enema.Body weight changes of rats in each group were measured,and disease activity index(DAI)was determined in each group.Histopathological changes of colon were observed by HE staining;levels of superoxide dismutase(SOD)and malondial-dehyde(MDA)in colon tissue of rats were measured by colorimetry;serum levels of IL-1β,TNF-α and IL-4 were determined by ELISA;flow cytometry was used to determine the percentages of CD3+T,CD4+T and CD8+T lymphocytes in peripheral blood mononuclear cells;levels of serum IgA and IgG were measured by automatic specific protein analyzer;expressions of HMGB1 and RAGE in colon tissues were determined by Western blot and immunohistochemistry.Results:Compared with Control group,levels of DAI,serum TNF-α,IL-1β,IgA,IgG,MDA in colon tissue,HMGB1 and RAGE protein expressions in colon tissue of Model group were obviously higher(P<0.05),while SOD level,IL-4,CD3+T,CD4+T and CD8+T lymphocyte percentages,CD4+/CD8+T were obviously lower(P<0.05),the mucosa of colon tissue was damaged.Compared with Model group,changes of relevant indexes in SIF-H group were contrary to the above(P<0.05),and the damage of colon tissue was alleviated.Conclusion:SIF may enhance the immune function of UC rats by inhibiting HMGB1/RAGE signal pathway.

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 changes in the bladder morphological structure and function and the expression of transforming growth factor-beta1 (TGF-β1) pathway-related proteins in the bilateral spinal nerve amputated neurogenic bladder(NB) rat.Methods:A total of 64 female SD rats were included, and 32 of them underwent bilateral spinal nerve L6+ S1 amputation to construct the NB model and the others were used as sham operation controls.Rats in both NB and control groups received bladder cystometry 3, 6, 12, 24 weeks after corresponding operation.Collagen fibers in their bladder tissues were detected by Masson staining and Sirius scarlet staining.TGF-β1, Smad2 and Smad6 proteins were checked by immunohistochemical staining.TGF-β1 receptor Ⅰ protein was measured by Western blot.Results:Bladders in the NB group were instable, with bladder leak point pressure(BLPP) and underactive voiding pressures.The basal pressure [(22.10±2.51), (18.20±1.52), (31.20±2.82), (41.10±3.41) cmH 2O(1 cmH 2O=0.098 kPa)] and bladder volume [(22.30±1.72), (49.10±5.54), (30.30±2.68), (13.50±1.52) mL] of the NB rats at 3, 6, 12 and 24 weeks were significantly higher than those of the sham operation controls[(3.51±0.45) cmH 2O and (0.52±0.04) mL], and the difference were significant(all P<0.05). The bladder size and thickness in the NB group firstly increased (3, 6 weeks) and then decreased (12, 24 weeks), but the bladder weight increased continuously.Masson staining showed disordered fibrous connective tissues, disintegrated layered bla-dder wall, hypertrophied smooth muscle tissues and deposited intramuscular collagen on the nerve-amputated bladder wall.Sirius scarlet staining suggested that 24 weeks after nerve amputation, collagen Ⅲ increased greatly, and the ratio of type Ⅲ/Ⅰ collagen fibers (3.14±0.71) was significantly higher than that in the sham group (0.88±0.21) ( t= 7.48, P<0.01). According to the immunohistochemical staining results, the expressions of TGF-1β and Smad2 increased while the pathway inhibitory protein Smad6 decreased with time in the NB group.Western blot showed that the expression of TGF-β1 receptor Ⅰ in the amputated bladder was 1.3 and 1.6 folds higher than that in the sham group 12 weeks and 24 weeks after operation( t=6.06, 14.45, all P<0.01). Conclusions:In NB rats with bilateral spinal nerve amputated, bladder contraction becomes paralysis, intravesical pressure increases, bladder normal structure disintegrates and the fibrosis pathway TGF-β1/Smads is activated.Therefore, the key step of development of pediatric NB is bladder fibrosis, which should be prevented as early as possibly in the clinical practice.

To investigate the feasibility and clinical efficacy of free graft of vascularized iliac bone flap based on deep iliac circumflex vessels for the treatment of osteonecrosis of femoral head (ONFH). Methods Twelve cases of ONFH(13 hips) received free graft of vascularized iliac bone flap based on deep iliac circumflex ves-sels from April, 2016 to July, 2017.The average Harris score was (74.7±6.9) in the second stage and (68.6±9.2) in the third stage. After debriding the necrosis bone of the femoral head, the contralateral vascularized iliac bone flap had been harvested, and then implanted into the femoral head. The deep iliac circumflex artery and its accompanying vein were anastomosed with the transverse branch (or ascending branch) of the lateral circumflex femoral artery and con-comitant vein respectively. The herringbone brace was used for hip fixation for 3 weeks after operation. X-ray exami-nation (1, 3, 6, 9 and 12 months after operation, respectively) and Harris hip score (6 and 12 months after operation, respectively) were performed to evaluate the recovery results of the femoral head. Scores were recorded and analyzed by paired t-test.The difference was considered to statistically significant if P＜0.05. Results The patients were fol-lowed-up for 15(12-20)months. The iliac bone flap of 12 patients (13 hips) healed well. There was no necrosis and collapse in 12 hips, except 1 femoral head collapsed slightly because of weight loading too early. The average Harris score was (91.6±4.5) of the second stage and (84.8±6.1) of the third stage. Compared with scores before the operation, the difference was statistically significant (P＜0.05). Conclusion Free vascularized iliac bone grafting based on deep iliac circumflex vessels is an ideal treatment for ONFH head in middle and advanced stage.