Combination of CRAFITY score with Alpha-fetoprotein response predicts a favorable outcome of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients.     

河南汉族人群DYS713和DYS720基因位点遗传多态性检测

目的:分析DYS713和DYS720基因位点在河南汉族群体中的遗传多态性分布.方法:应用PCR-聚丙烯酰胺凝胶电泳及银染显带技术,对203名河南汉族无血缘关系男性个体的Y染色体短串联重复序列基因DYS713和DYS720位点进行分型检测,计算其基因多样性(GD)和个体识别力(DP).结果:DYS713和DYS720基因...     

钢板前置内固定治疗锁骨骨折的疗效

目的评价钢板前置内固定治疗锁骨中段骨折的临床疗效。方法 2006年9月—2010年8月,采用切开复位钢板前置内固定术治疗53例锁骨中段移位骨折患者,其中Robinson 2A2型27例、2B1型23例、2B2型3例。分别于术后第3、6周和术后第3、6、12、18个月拍摄锁骨X线片观察骨折愈合情况,以Constant标准评价患侧肩关节功能。结果所有患者术后均获随访,平均随访时间为(13.4±2.2)个月。锁骨X线片显示骨折均骨性愈合,平均愈合时间为(3.6±0.7)个月。52例患者行肩关节功能的Constant评分,疗效评价为优34例、良16例、可2例,总体优良率为96.2%(50/52)。结论钢板前置内固定是治疗锁骨中段移位骨折的一种有效方法。     

Effect of goal-directed fluid therapy on renal function in critically ill patients: a systematic review and meta-analysis

ObjectiveTo evaluate whether goal-directed fluid therapy (GDFT) reduces the risk of renal injury in critical illness.MethodsMEDLINE via PubMed, EMBASE, CENTRAL and CBM was searched from inception to 13 March 2022, for studies comparing the effect of GDFT with usual care on renal function in critically ill patients. GDFT was defined as a protocolized intervention based on hemodynamic and/or oxygen delivery parameters. A fixed or random effects model was applied to calculate the pooled odds ratio (OR) based on heterogeneity through the included studies.ResultsA total of 28 studies with 9,019 patients were included. The pooled data showed that compared with usual care, GDFT reduced the incidence of acute kidney injury (AKI) in critical illness (OR 0.62, 95% confidence interval (CI) 0.47 to 0.80, p< 0.001). Sensitivity analysis with only low risk of bias studies showed the same result. Subgroup analyses found that GDFT was associated with a lower AKI incidence in both postoperative and medical patients. The reduction was significant in GDFT aimed at dynamic indicators. However, no significant difference was found between groups in RRT support (OR 0.88, 95% CI 0.74 to 1.05, p= 0.17). GDFT tended to increase fluid administration within the first 6 h, decrease fluid administration after 24 h, and was associated with more vasopressor requirements.ConclusionsThis meta-analysis suggests that GDFT aimed at dynamic indicators may be an effective way to prevent AKI in critical illness. This may indicate a benefit from early adequate fluid resuscitation and the combined effect of vasopressors.     

三维适形放疗联合深部热疗对局部晚期非小细胞肺癌的疗效研究

目的：探讨三维适形放疗联合深部热疗对局部晚期非小细胞肺癌的疗效及预后影响。方法选取2012年6月—2014年6月该院收治的111例局部晚期NSCLC患者为研究对象,采用随机抽样法分成联合组（A 组,n=56）和对照组（B 组,n=55）两组。 B 组给予单纯三维适形放疗方案,A 组则在上述基础上联合深部热疗方案进行治疗。比对近期治疗效果及不良反应发生情况,行为期一年随访,记录患者KPS 评分结果差异。结果①治疗后A组近期治疗有效率为62.5%,随访期内生存45例,死亡11例,生存率为80.4%,B 组近期治疗总有效率为38.2%,随访期生存率为54.6%,两组就近期疗效及随访生存率对比而言差异有统计学意义（P＜0.05）;②治疗后,A组KPS评分增高45例,稳定8例,降低3例,生存质量改善率为80.4%,明显高于B组的54.6%,差异有统计学意义（P＜0.05）;③治疗后,A组白细胞降低率为37.5%,放射性肺炎发生率为30.4%,放射性食管炎发生率为17.9%,皮肤反应发生率为16.1%,均同B组对比差异无统计学意义（P>0.05）。结论对局部晚期NSCLC 患者予以三维适形放疗联合深部热疗方案,临床疗效显著,可有效改善患者生活质量,值得推广使用。     

合并高血压的前列腺增生组织中α1受体亚型含量的变化

目的 探讨合并高血压的前列腺增生组织中α1受体亚型含量的变化.方法 收集经尿道电切除的增生前列腺新鲜标本共47例,分为单纯BPH组23例和合并高血压(血压控制良好)BPH组24例,RT-PCR法测定前列腺组织中的α1受体亚型mRNA的表达.结果 α1A、α1B、α1D 3种α1受体亚型mRNA在47例BPH组织中的相对表达量分别为0.95±0.22、0.97±0.16、1.00±0.28 (P＞ 0.05),表达比例为32.4％∶33.1％∶34.5％,3种亚型的表达没有差别.α1受体总mRNA和α1B受体亚型mRNA的相对表达量在合并高血压BPH组与单纯BPH组无差别,但α1A和α1D受体亚型mRNA的相对表达量却发生了变化.在合并高血压BPH组中,3种受体亚型mRNA的相对表达量分别为1.06±0.16、0.95±0.14、0.84±0.17(P＜0.05),表达比例为37.1％∶33.4％∶29.5％,以α1A亚型的表达占优,且高于单纯BPH组(P＜0.05).在单纯BPH组中,3种受体亚型mRNA的相对表达量分别为0.83±0.22、0.98±0.18、1.19±0.27 (P＜ 0.05),表达比例为27.7％∶32.7％∶39.4％,以α1D亚型的表达占优,且高于合并高血压BPH组(P＜0.05).结论 相对于单纯BPH组,合并高血压BPH组的α1A型受体mRNA的表达显著增加,重点阻滞α1A型受体亚型的功能可能更有利于高血压合并BPH患者的临床治疗.     

Bioaccumulation of PBDE congener 2,2′,4,4′-tetrabromodiphenyl ether by Heterosigma akashiwo in response to different nutrient concentrations

Changes in the bioaccumulation of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in the marine alga Heterosigma akashiwo (Raphidophyceae) were examined for different concentrations of nitrate (0, 128, and 512 μmol dm^?3) and phosphate (0, 8, and 32 μmol dm^?3) in the semi-continuous culture with 20% renewal rate. The BDE-47 content per cell and per culture, as well as the accumulated percentage of available BDE-47, presented a significant decreasing trend with the increase in nitrate and phosphate concentrations. The N-0 (4.0 × 10^?6 ng cell^?1) and P-0 (5.8 × 10^?6 ng cell^?1) treatments had significantly higher BDE-47 content per cell than other treatments. In comparison, the difference in BDE-47 per algal culture and accumulated percentage between the nitrate treatments or phosphate treatments was not as obvious as the BDE-47 content per cell. BDE-47 per cell presented significantly negative correlation with nitrate and phosphate concentrations, and the accumulated BDE-47 was in positive correlation with lipid content. log BAF_lip for BDE-47 in H. akashiwo ranged from 6.70 to 7.25. The results of this study indicate that variation in BDE-47 accumulation by H. akashiwo corresponds to the change in cellular lipid content induced by different nitrate and phosphate concentrations.     

TNF-α对大鼠Leydig细胞的作用及机制研究

目的观察TNF-α对睾丸细胞功能的影响并探讨其可能机制。方法通过Percoll不连续密度梯度分离获取大鼠Leydig细胞进行原代培养。HE染色进行细胞形态学观察。Leydig细胞培养48h后在培养液中分别加入不同浓度的大鼠TNF-α,使其终浓度达到0.1、1、10、100ng/ml,分别在培养的第1、2、3、4天取上清,通过放免法测定上清液中睾酮的含量,应用MTT法测定细胞增殖情况,流式细胞术与丫啶橙(AO)染色检测及观察Leydig细胞凋亡情况。结果原代细胞通过提纯后的细胞纯度可达70%~80%。HE染色后可见细胞胞质含量丰富,含有分泌颗粒,胞核圆。TNF-α在0.1~100ng/ml浓度范围内能呈剂量依赖的方式抑制Leydig细胞睾酮的基础分泌。0.1、1、10、100ng/mlTNF-α作用24h后,对Leydig细胞睾酮分泌量的抑制率分别为22.03%、34.98%、52.95%、74.83%。各组Leydig细胞睾酮的分泌量随时间延长呈减少的趋势,但除100ng/ml组外,其他各组各时间点比较差异无统计学意义。高浓度TNF-α(10、100ng/ml)组具有抑制Leydig细胞增殖和促进其凋亡作用,其增殖抑制率分别达到38.35%±4.17%、76.35%±8.65%,而凋亡率分别为13.23%±1.11%、26.43%±5.82%,与对照组比较有统计学意义(P<0.01)。AO染色见高浓度TNF-α(10、100ng/ml)组出现明显的细胞凋亡。结论TNF-α对Leydig细胞睾酮的基础分泌具有抑制作用,在较高浓度时该作用可能与其抑制Leydig细胞增殖并促进细胞凋亡有相关。     

一例染色体复杂易位致胎儿多发畸形的遗传学诊断

目的: 对一例染色体复杂易位致多发畸形胎儿进行遗传学分析和诊断。方法: 对一例多发畸形胎儿行G显带染色体核型分析、单核苷酸多态性微阵列（SNP array）及荧光原位杂交（FISH）检测。胎儿父母行外周血染色体核型分析及FISH检测。结果: 胎儿的羊水染色体核型为46,XN,t（12;13）（q22;q32）。SNP array显示胎儿存在1q42.13q44重复（20 192 kb）及15q26.1q26.3缺失（13 293 kb）,核型分析与基因芯片结果不一致。FISH验证了SNP array的结果。母亲外周血FISH结果确认为隐匿性46,XX,t（1;15）（q42.1;q26.1）携带者,而胎儿遗传了其中一条衍生的15号染色体der（15）t（1;15）（q42.1;q26.1）。即胎儿遗传了父亲的t（12;13）（q22;q32）平衡易位及母亲的隐匿性平衡易位形成的衍生15号染色体。结论: 1q42.13q44重复和15q26.1q26.3缺失是导致本例胎儿畸形的遗传学病因,产前诊断时多种遗传学技术联合应用可为临床提供准确的诊断。