二次电切在降低非肌层浸润性膀胱癌初次电切术后复发率中的临床价值

目的探讨经尿道膀胱肿瘤二次电切术（Re-TURBT）在降低T_a和T₁期非肌层浸润性膀胱癌（NMIBC）电切术后肿瘤复发率的临床价值。 方法回顾性分析2015年2月至2018年11月我院86例诊断为T_a和T₁期的NMIBC患者。患者接受单次经尿道膀胱肿瘤电切术为对照组（40例）,接受二次经尿道膀胱肿瘤切除术为观察组（46例）,两组患者首次电切术中均联合了吉西他滨即刻膀胱灌注化疗。统计观察组二次电切的阳性率及肿瘤分期分级变化情况,同时比较两组患者术后2年内的肿瘤复发及进展情况。 结果两组患者年龄、性别、吸烟史、肿瘤最大径、肿瘤个数、首次电切病理分期比较差异无统计学意义（P>0.05）。观察组二次电切术后的病理结果显示,11例（23.91%）检出残余癌,5例出现临床分期升级,4例病理分级升级。观察组术后2年总复发率低于对照组（P<0.05）。两组术后2年总进展率差异无统计学意义（P>0.05）。 结论Re-TURBT可明显降低T_a和T₁期NMIBC电切术后肿瘤复发率,同时可获得更准确的肿瘤分期,具有一定的临床价值。     

Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength

The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild‐type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild‐type mice. A micro‐CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone‐formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU‐positive osteoblastic cell numbers were increased, TUNEL‐positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three‐point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild‐type mice. The frequency of TUNEL‐positive primary osteoblasts was lower in BCLXL transgenic mice than in wild‐type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. © 2016 American Society for Bone and Mineral Research.     

Impact of synthetic ghrelin administration for patients with severe body weight reduction more than 1 year after gastrectomy: a phase II clinical trial

Purpose

Ghrelin is mainly secreted from the stomach and plays a role in appetite, weight gain, and the promotion of a positive energy balance. The levels of ghrelin decrease immediately after gastrectomy. We herein investigated the effect of the administration of synthetic ghrelin to treat postoperative severe weight loss in a prospective, one-arm clinical trial to develop new strategies for weight gain.

Methods

Ten patients (four distal gastrectomy and six total gastrectomy) received ghrelin treatment. Eligibility criteria included patients who underwent gastrectomy more than 1 year previously and 15 % body weight loss from the preoperative weight or a body mass index under 19. Synthetic human ghrelin (3 μg/kg) was administered to the patients twice a day for 1 week. Oral intake of calories, appetite [evaluated using the visual analog scale (VAS)], and body weight before and during administration of ghrelin were compared.

Results

There was a significant difference in the oral food intake before and during treatment (before treatment: 1236 ± 409 kcal vs. during treatment: 1398 ± 365 kcal, p = 0.039), and the VAS for appetite significantly improved with each day of ghrelin administration (p < 0.05). Significant amounts of body weight were gained (39.5 ± 6.8 vs. 40.1 ± 6.9, p = 0.037).

Conclusions

The administration of synthetic ghrelin improved the food intake and was effective for treating appetite loss and body weight loss. Synthetic ghrelin may be a promising new therapy for severe body weight loss following gastrectomy.

     

Comparison of differences in development potentials between frozen-thawed D5 and D6 blastocysts and their relationship with pregnancy outcomes

Purpose

Whether there are differences in the pregnancy outcomes of blastocysts cryopreserved during different developmental stages remains under debate because the results among studies are inconsistent. We analyzed blastocyst quality and pregnancy outcomes by considering blastocyst euploidy and investigated the differences in the development potential between blastocysts of different developmental stages (frozen-thawed day 5 [D5] and day 6 [D6] cycles) and their relationship with clinical pregnancy outcomes.

Methods

In total, 1374 D5 and 255 D6 frozen-thawed blastocyst transfer cycles were retrospectively analyzed. Additionally, the chromosome euploidy and clinical pregnancy rates of 237 blastocysts from 50 pre-implantation genetic diagnosis (PGS) cycles were statistically analyzed. The corresponding euploidy rate and pregnancy outcomes of the D5 and D6 blastocyst transfers were also compared.

Results

The clinical pregnancy rate (47.2 vs 40.0 %; P?=?0.04) and implantation rate (34.2 vs 28.8 %; P?=?0.03) of the D5 blastocysts were higher than were those of the D6 blastocysts. However, the clinical pregnancy rate (52.4 vs 52.6 %; P?=?0.97) and implantation rate (38.9 vs 35.6 %; P?=?0.39) of the high-quality D5 blastocysts did not significantly differ from those of the high-quality D6 blastocysts. Analysis of blastocyst euploidy in 237 blastocysts examined in 50 PGS cycles showed that the euploidy rates of the D5 and D6 blastocysts were both 48.1 % (P?=?0.99). The clinical pregnancy rate of the D5 blastocysts (48.5 vs 17.6 %; P?=?0.03) was higher than that of the D6 blastocysts. The euploidy rates (55.2 vs 55.3 %; P?=?0.99) and clinical pregnancy rates (60.0 vs 42.9 %; P?=?0.77) of the high-quality D5 and D6 blastocysts did not differ. The euploidy rate (55.3 vs 41.5 %, P?=?0.03) and clinical pregnancy rate (54.5 vs 25.0 %, P?=?0.03) of the high-quality blastocysts were higher than were those of the poor-quality blastocysts.

Conclusions

The euploidy rates between the D5 and D6 blastocysts did not differ. High-quality D6 blastocysts in frozen-thawed cycles had similar developmental potential and pregnancy outcomes compared to those of high-quality D5 blastocysts. The quality of the blastocysts was an important factor that affected the pregnancy outcomes of the frozen-thawed cycles.

     

Preimplantation genetic diagnosis/screening by comprehensive molecular testing

Although embryo screening by preimplantation genetic diagnosis (PGD) has become the standard technique for the treatment of recurrent pregnancy loss in couples with a balanced gross chromosomal rearrangement, the implantation and pregnancy rates of PGD using conventional fluorescence in situ hybridization (FISH) remain suboptimal. Comprehensive molecular testing, such as array comparative genomic hybridization and next‐generation sequencing, can improve these rates, but amplification bias in the whole genome amplification method remains an obstacle to accurate diagnosis. Recent advances in amplification procedures combined with improvements in the microarray platform and analytical method have overcome the amplification bias, and the data accuracy of the comprehensive PGD method has reached the level of clinical laboratory testing. Currently, comprehensive PGD is also applied to recurrent pregnancy loss due to recurrent fetal aneuploidy or infertility with recurrent implantation failure, known as preimplantation genetic screening. However, there are still numerous problems to be solved, including misdiagnosis due to somatic mosaicism, cell cycle‐related background noise, and difficulty in diagnosis of polyploidy. The technology for comprehensive PGD also requires further improvement.