人工肝支持系统治疗重型肝炎临床疗效评估

目的 评估人工肝支持系统（ALSS）在治疗重型肝炎的疗效，提出该适应症的标准。方法 ALSS治疗组为92例重型肝炎患者在综合性治疗的基础上加用ALSS疗法，103例重型肝炎患者采用综合性治疗作为对照组，观察与比较两组血清肝脏生化指标和存活率。结果 ALSS治疗组患者经ALSS治疗后血清肝脏生化指标有明显改善；ALSS治疗组存活率（71．7％）明显高于对照组（55．3％），P＜0．05。结论 人工肝是治疗重型肝炎的有效方法。对人工肝治疗重型肝炎的适应症标准提出了几点建议。     

AFP在肝细胞癌及卵黄囊瘤以外恶性肿瘤的临床意义

为探索血清甲胎蛋白（ＡＦＰ）对肝细胞癌（ＨＣＣ）和卵黄囊瘤（ＹＳＴ）以外恶性肿瘤的临床意义，我院自１９８２年以来，对ＨＣＣ和ＹＳＴ以外恶性肿瘤病人进行了ＡＦＰ检测，结果发现阳性（＞２０μｇ／Ｌ）者７４例。其中胃癌４８例（４８／１０２７），结肠直肠癌１１例（１１／８３５），食管癌２例（２／４２１），胰腺癌３例（３／１０４），肺癌６例（６／７３６），卵巢癌１例（１／２８９），胆囊癌２例（２／３１），肾癌１例（１／５７）。２４例胃癌和４例结肠癌病程中发现肝转移者分别为１４例（５８．３％）和３例（７５％）。结合文献与本文病例分析结果表明：ＨＣＣ和ＹＳＴ以外恶性肿瘤，其血清中增高的ＡＦＰ是癌细胞合成和分泌的。因此，ＡＦＰ检测对此类肿瘤有诊断价值，并可作为患者术后疗效监护指标。由于ＡＦＰ有免疫抑制作用，此类肿瘤易发生肝转移而预后不良，属高度恶性肿瘤     

本体感觉神经肌肉促进法对5km越野后肌疲劳的干预作用

目的观察本体感觉神经肌肉促进(PNF)法对新学员5 km越野训练肌疲劳度的影响,为今后制定降低高强度训练后疲劳发生率的措施提供依据。方法选择某军校152名新学员作为观察对象,按班随机分为训练后PNF干预组(A组)、训练前PNF干预组(B组)和正常训练组(C组),前2组分别在5 km越野训练后、训练前针对双下肢、骨盆带肌肉采用PNF法干预。并在训练前,训练后的当天,第3天,第5天分别评定其肌疲劳度并行相关血液生化指标检查。结果3个组新学员训练前疲劳程度分布无统计学意义(P0.05)。训练后当天疲劳程度达3级以上的发生率A组29.2%,B组60.0%,C组83.3%;第3天A组2.1%,B组32.0%,C组44.4%;第5天B组4.0%,C组5.6%。训练后当天、第3天、第5天3组新学员疲劳变化程度的差异均有统计学意义(P0.01),其中A组疲劳程度最轻,B组次之,C组最重。3组之间相关血液生化指标的平均增幅差异在训练当天、训练后第3天和第5天均有统计学意义(P0.05),其平均增幅A组B组C组。相关血液生化指标在训练后的当天和第3天与疲劳的相关关系有统计学意义(P0.05),相关关系为中度正相关(rs0.4)。结论PNF法能有效降低运动后疲劳;训练后立即行PNF干预为最佳时机。     

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma

Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays critical roles in malignant transformation and tumor progression. Previously, we have shown that microRNA-451 (miR-451) inhibits growth, increases chemo- or radiosensitivity and reverses epithelial to mesenchymal transition (EMT) in lung cancer. However, the roles of miR-451 in hepatocelluar carcinoma (HCC) progression and metastasis are still largely unknown. Reduced miR-451 in HCC tissues was observed to be significantly correlated with advanced clinical stage, metastasis and worse disease-free or overall survival. Through gain- and loss-of function experiments, we demonstrated that miR-451 inhibited cell growth, induced G0/G1 arrest and promoted apoptosis in HCC cells. Importantly, miR-451 could inhibit the migration and invasion in vitro, as well as in vivo metastasis of HCC cells through regulating EMT process. Moreover, the oncogene c-Myc was identified as a direct and functional target of miR-451 in HCC cells. Knockdown of c-Myc phenocopied the effects of miR-451 on EMT and metastasis of HCC cells, whereas overexpression of c-Myc partially attenuated the functions of miR-451 restoration. Furthermore, miR-451 downregulation-induced c-Myc overexpression leads to the activation of Erk1/2 signaling, which induces acquisition of EMT phenotype through regulation of GSK-3β/snail/E-cadherin and the increased expression of MMPs family members in HCC cells. Collectively, these data demonstrated that miR-451 is a novel prognostic biomarker for HCC patients and that function as a potential metastasis inhibitor in HCC cells through activation of the Erk1/2 signaling, at least partially by targeting c-Myc. Thus, targeting miR-451/c-Myc/Erk1/2 axis may be a potential strategy for the treatment of metastatic HCC.     

树突状细胞疫苗联合射频消融术治疗结直肠癌肝转移临床疗效

目的:探讨树突状细胞(dendritic cell,DC)疫苗联合射频消融术(radiofrequency ablation,RFA)治疗结直肠癌肝转移(colorectal liver metastases,CRLM)患者的临床疗效.方法:选取2012年8月至2014年8月在解放军第八一医院确诊并行RFA治疗的46例CRLM患者,其中26例进行DC疫苗联合RFA治疗(DC-RFA组),20例单纯进行RFA治疗(RFA组),比较两组患者近期、远期疗效,免疫功能,安全性及生活质量改善情况.结果:(1)DC-RFA组总有效率明显高于对照组(92.31％ vs 70.00％,P＜0.05);DC-RFA组与RFA组治疗后6个月生存率分别为96.15％、90.00％;1、2年生存率DC-RFA组略优于RFA组(P＞0.05);(2)DC-RFA组外周血CD3+、CD4+、CD4+/CD8+百分比明显升高(P＜0.05),CD8+数值降低(P＞0.05);RFA组治疗后外周血CD3+、CD4+及CD4 +/CD8+百分比明显升高(P＜0.05),CD8+数值升高(P＞0.05);(3)DC-RFA组治疗后仅有2例低热,1例过敏反应,对症处理后均恢复正常;(4)DC-RFA组患者生活质量有所提高,尤其是疼痛控制和精神状态方面.结论:DC疫苗联合RFA治疗CRLM患者可提高单纯RFA治疗的效果、延长生存期、提高机体免疫功能,同时可以有效改善患者生活质量,且治疗安全可靠.     

SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating from the liver. These tumors are associated with heterogeneous prognosis, and few treatment targets for PHNETs have been identified. Because the major genetic alterations in PHNET are still largely unknown, we performed whole-exome sequencing of 22 paired tissues from PHNET patients and identified 22 recurring mutations of somatic genes involved in the following activities: epigenetic modification (BPTF, MECP2 and WDR5), cell cycle (TP53, ATM, MED12, DIDO1 and ATAD5) and neural development (UBR4, MEN1, GLUL and GIGYF2). Here, we show that TP53 and the SET domain containing the 1B gene (SETD1B) are the most frequently mutated genes in this set of samples (3/22 subjects, 13.6%). A biological analysis suggests that one of the three SETD1B mutants, A1054del, promotes cell proliferation, migration and invasion compared to wild-type SETD1B. Our work unveils that SETD1B A1054del mutant is functional in PHNET and implicates genes including TP53 in the disease. Our findings thus characterize the mutational landscapes of PHNET and implicate novel gene mutations linked to PHNET pathogenesis and potential therapeutic targets.     

Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B

Aim

The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week‐104 treatment outcome in CHB patients.

Methods

Baseline serum 25‐hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine‐based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104.

Results

The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62–0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization.

Conclusions

Vitamin D insufficiency was highly prevalent in treatment‐naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week‐104 virologic response, but not HBeAg seroconversion or ALT normalization.     

儿童甲状腺乳头状癌的外科治疗

目的 探讨儿童甲状腺乳头状癌的临床特点、外科治疗和预后。方法 回顾性分析我院１９８０－１９９９年收治的１９例儿童甲状腺乳头状癌,并进行随访。结果 本组均行手术治疗。术后随访时间１－１８年,中位随访时间７年。除１例术中颈静脉角处有癌灶残留,术后２年出现颈部淋巴及肺部广泛转移死亡外,其余患儿均生存良好（包括１例１０年间３次手术的患儿）。结论 手术是治疗儿童甲状腺乳头状癌的主要方法。选择适宜的手术方式,避免并发症的发生,直接影响到患儿的预后。即使对有局部复发或颈部淋巴结转移的病例,再次手术仍可获得良好的效果。     

非卵黄囊瘤的AFP阳性卵巢恶性肿瘤4例临床病理观察

目的 探讨非卵黄囊瘤的ＡＦＰ阳性卵巢恶性肿瘤的病理组织形态和临床生物学行为。方法 报道４例非卵黄囊瘤的ＡＦＰ阳性卵巢恶性肿瘤,１例为单纯肝样癌,３例为有梭形细胞成分的内膜样癌（其中１例伴有肝样癌）。结果 肝样癌癌细胞的胞质内含有ＡＦＰ、ＡＡＴ和ＡＣＴ成分,而在内膜样癌癌细胞的胞质内以ｃｙｔｏｋｅｒａｔｉｎ和ＣＥＡ成分为主。由于ＡＦＰ具有免疫抑制作用,病人的预后不好。４例中３例已死亡,平均生存２５个