阿帕替尼单药在标准方案治疗失败晚期结直肠癌患者中的疗效及安全性

目的：探讨阿帕替尼单药在标准治疗方案失败晚期结直肠癌（colorectal cancer，CRC）患者中的疗效和安全性。方法：本研究为前瞻性研究设计，用PASS15 软件计算研究所需的样本量，从2017 年7 月到2018 年8 月入组标准方案治疗失败的晚期CRC患者52 例，给予阿帕替尼起始剂量750 mg或500 mg单药治疗；评估患者的客观缓解率（ORR）和疾病控制率（DCR），随访评价患者的无进展生存期（PFS）和总生存期（OS），并记录治疗过程中出现的不良反应。主要研究终点为PFS，次要研究终点为ORR、DCR、OS和安全性。结果：纳入研究的52 例CRC患者中45 例可以评价疗效及安全性，其均为既往接受过至少2 次系统性化疗的晚期CRC患者。疗效：完全缓解0 例、部分缓解5 例、疾病稳定30 例、疾病进展10 例，ORR为11.11%、DCR为77.78%；预后：45 例患者的中位PFS 为3.95 个月（95% CI=3.16~4.74），中位OS为10.3 个月（95% CI=5.70~14.90）；3 级以上不良反应：手足综合征6 例（13.33%），高血压5 例（11.11%），蛋白尿5 例（6.67%），转氨酶升高4 例（8.89%），腹泻3 例（6.67%），疲劳2 例（4.44%），出血1例（2.22%）。结论：阿帕替尼单药治疗标准方案失败的晚期CRC患者具有潜在的临床获益，安全性事件总体可控。     

A novel cysteine-sparing G73A mutation of NOTCH3 in a Chinese CADASIL family

neurogenetics - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disease leading to stroke and vascular dementia....     

Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.     

归脾丸加减对围绝经期功血患者免疫功能的影响

目的:探究归脾丸加减对围绝经期功血患者免疫功能、白细胞介素2(IL-2)、可溶性白细胞介素-2受体(sIL-2R)的影响。方法:选取2019年3月至2018年6月山东省济南市中西医结合医院收治的符合纳入条件的围绝经期功血患者118例作为研究对象,按照就诊顺序编号随机分为对照组和观察组,每组59例。对照组常规西医治疗,观察组加用归脾丸加减治疗,均治疗3个月。观察2组治疗前、完成治疗后T淋巴细胞亚群、IL-2、sIL-2R、凝血功能、子宫内膜厚度、激素水平、症状积分变化;完成治疗后统计治疗过程中的不良反应。结果:1)完成治疗后,2组CD3+、CD4+、CD4+/CD8+、IL-2较治疗前均显著升高,CD8+、sIL-2R则显著下降(P<0.05);完成治疗后观察组CD8+、sIL-2R显著低于于对照组,余均高于对照组(P<0.05)。2)完成治疗后2组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、子宫内膜厚度较治疗前均显著下降(P<0.05),完成治疗后观察组以上指标均显著低于对照组(P<0.05)。3)完成治疗后2组黄体生成素(LH)、促排卵生成素(FSH)、雌二醇(E2)、孕酮(P)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)较治疗前均显著下降(P<0.05),完成治疗后观察组以上指标均显著低于对照组(P<0.05)。4)完成治疗后2组月经周期、阴道出血量、阴道出血天数、神疲乏力积分较治疗前均显著下降(P<0.05),完成治疗后观察组以上指标均显著低于对照组(P<0.05)。5)完成治疗后观察组胃肠道反应、体质量增加、肝功能异常、乳房胀痛发生率均显著低于对照组,2组比较差异有统计学意义(P<0.05)。结论:归脾丸加减能提高围绝经期功血患者免疫功能,抑制IL-2、sIL-2R,改善凝血功能,从而改善症状,提高疗效。     

温室作业对蔬菜种植人员职业性肌肉骨骼疾患的影响

目的 探讨温室作业对蔬菜种植人员职业性肌肉骨骼疾患（WMSDs）的影响。方法 采用流行病学横断面调查方法，选取西北某地区602人作为研究对象，其中温室作业人员（温室组）307人、非温室作业人员（非温室组）295人。通过问卷调查和体格检查，收集研究对象个人基本信息和各部位WMSDs检出信息。采用卡方检验进行组间WMSDs检出率的比较、Logistic回归模型进行多因素分析。结果 温室组WMSDs检出率为84.04%，高于非温室组（60.68%）（χ2=41.265，P＜0.001）。温室组颈部、肩部、下背部、手部和腿部5个部位WMSDs检出率分别为36.2%、29.0%、62.2%、20.2%和51.1%，均显著高于非温室组（24.7%、18.6%、41.4%、12.2%和26.4%）（P＜0.05）。温室组2个部位、3个部位和≥4个部位WMSDs检出率分别为25.1%、16.9%和19.2%，亦显著高于非温室组（18.3%、9.2%和10.2%），但两组间单一部位WMSDs检出率差异无统计学意义。校正性别、年龄等因素后，从事温室作业能增加作业人员WMSDs的风险（OR=3.558，95%CI 2.338～5.414），女性患病风险（OR=4.682，95%CI 2.600～8.433）高于男性（OR=2.667，95%CI 1.421～5.007）。结论 温室作业可增加蔬菜种植人员WMSDs的患病风险，多部位WMSDs尤其值得关注。     

温阳解毒化瘀颗粒对肝衰竭IETM大鼠TLR4 mRNA,TNF-α及肝细胞凋亡的影响

目的:研究Toll样受体4(TLR4) mRNA及其下游炎性因子肿瘤坏死因子-α(TNF-α)与肝衰竭肠源性内毒素血症(IETM)大鼠肝细胞凋亡的关系,并探索温阳解毒化瘀颗粒对内毒素介导的肝细胞凋亡的调控机制。方法:SPF级雄性SD大鼠85只,随机分为正常组,模型组,TLR4单克隆抗体组和温阳解毒化瘀颗粒组(8.925 g·kg^-1)。采用D-半乳糖胺(D-Gal)腹腔注射建立肝衰竭IETM模型,TLR4单克隆抗体组和温阳解毒化瘀颗粒组在造模前5 d给予温阳解毒化瘀颗粒溶液灌胃,正常组、模型组以等容积蒸馏水代替,直至处死。各组分别在24,48,72 h随机处死大鼠并采集标本。检测24,48,72 h各组时间点血清丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)水平,苏木素-伊红(HE)染色观察肝组织病理变化,实时荧光定量聚合酶链式反应(Real-time PCR)检测肝组织TLR4 mRNA表达,酶联免疫吸附测定法(ELISA)检测肝组织TNF-α表达,流式细胞仪检测肝细胞凋亡率。结果:与正常组比较,模型组ALT,AST升高,肝组织病理损伤程度明显加重,TLR4mRNA,TNF-α表达均增高(P<0.05,P<0.01),肝细胞凋亡率明显上升(P<0.05,P<0.01);与模型组比较,温阳解毒化瘀颗粒组ALT,AST显著降低(P<0.01),肝组织病理损伤程度明显减轻(P<0.05),TLR4 mRNA,TNF-α表达显著下降(P<0.01),肝细胞凋亡率亦显著降低(P<0.01)。结论:TLR4 mRNA,TNF-α在肝衰竭时与肝细胞凋亡呈正相关,温阳解毒化瘀颗粒能够改善肝衰竭IETM大鼠肝功能,减轻肝细胞损伤,减少肝细胞凋亡,其机制可能与其下调肝脏TLR4 mRNA表达,抑制TNF-α释放,降低肝细胞凋亡率有关。     

Stability and change in family psychosocial risk over 6 months in pediatric cancer and its association with medical and psychosocial healthcare utilization

Purpose: Family psychosocial risk in pediatric oncology can be assessed using the Psychosocial Assessment Tool (PAT), a brief parent report screener based on the Pediatric Psychosocial Preventative Health Model (PPPHM; universal, targeted, and clinical). However, little is known about risk over the course of treatment and its association with medical and psychosocial healthcare utilization. Methods: Primary caregivers of children with cancer participated in this prospective multisite investigation, completing the PAT at diagnosis (T1; n = 396) and 6 months later (T2; n = 304). Healthcare utilization data were extracted from electronic health records. Results: The distribution of PPPHM risk levels at T1 and T2 was highly consistent for the samples. Two‐thirds of families remained at the same level of risk, 18% decreased and 16% increased risk level. Risk was not related to sociodemographic or treatment variables. The PAT risk score correlated with psychosocial contacts over the 6‐month period. Conclusions: Although the majority of families reported universal (low) risk on the PAT and were stable in their risk level over 6 months, reassessing risk is helpful in identifying those families who report higher level of risk during treatment than at diagnosis. PAT scores were related to psychosocial services that are provided to most but not all families and could be tailored more specifically to match risk and delivery of evidence‐based care.     

神经内镜辅助下经鼻蝶入路治疗鞍区肿瘤

目的探讨神经内镜辅助下经鼻蝶入路切除鞍区肿瘤的方法和优势。方法回顾性分析30例鞍区肿瘤病人的临床资料,垂体腺瘤26例(其中无功能垂体腺瘤6例、泌乳素瘤16例、垂体生长激素腺瘤4例),拉克囊肿1例,胆脂瘤1例,脑膜瘤1例,颅咽管瘤1例。采用神经内镜辅助下经鼻蝶入路手术切除肿瘤。结果肿瘤全切27例,部分切除3例。术后3例发生脑脊液鼻漏,经腰大池持续引流后痊愈。无死亡病例。随访3~6个月,病人恢复良好。结论在神经内镜辅助下经鼻蝶入路治疗鞍区肿瘤,较单纯的显微镜手术治疗创伤更小,肿瘤全切率更高。