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简介：AbstractBackground:Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia.Methods:Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein.Results:DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P < 0.05). In response to hyperthermia, F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia (WT cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.34 ± 0.02 vs. 0.24 ± 0.01, 0.31 ± 0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ± 0.01 vs. 0.30 ± 0.01, 0.51 ± 0.02, P < 0.001, P < 0.01). WT cells restored to baseline levels observed in the unheated condition, while DnaJA4-KO cells exceeded baseline levels in the recovery. As the upstream factors of F-actin, a similar profile in rho-associated serine/threonine kinase 1 (ROCK 1) and RhoA expressions was observed after hyperthermia. While E-cadherin expression was decreased in response to hyperthermia, it was increased in DnaJA4-KO cells compared with WT cells.Conclusions:Hyperthermia affects the expression levels of F-actin in HaCaT cells. DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia. DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.

简介：摘要放疗是肿瘤治疗三大手段之一，近年来伴随着免疫治疗的飞速发展，放疗联合免疫治疗的理论与实践方式也愈发得到关注。人细胞毒性T细胞抗原4(CTLA-4)抑制剂是免疫治疗的重要药物之一，在黑色素瘤、肺癌等癌种的治疗中都显示出巨大的应用潜力，因而其与放疗联用的机制与方式也成为目前关注的重点。本文梳理了近年来CTLA-4单抗与放疗联用的基础与临床研究实践，为下一步开展相关研究提供参考。

简介：摘要目的探讨T4期前列腺癌患者手术治疗的疗效。方法回顾性分析2013年7月至2019年12月同济大学附属第十人民医院手术治疗的18例T4期前列腺癌患者的临床资料。平均年龄68.3(53~81)岁。其中去势抵抗性前列腺癌(CRPC)10例，均有不同程度膀胱血块填塞和(或)下尿路梗阻症状；激素敏感性前列腺癌(HSPC)8例，其中5例出现严重血尿且局部症状严重、生活质量低，3例肿瘤单纯侵犯膀胱颈。18例术前Gleason评分中位值8(7~10)分；临床分期T4N0M0期10例，T4NxM0期2例，T4N1M0期6例。所有患者术前卡氏评分(KPS)均≥80分，平均84(80~90)分。术前生活质量评分(QOL)平均28(21~32)分。18例中2例因肿瘤侵犯直肠行全盆腔脏器切除术(CRPC和HSPC各1例)；7例因肿瘤侵犯输尿管开口行根治性膀胱前列腺切除术(CRPC 5例，HSPC 2例)；9例肿瘤侵犯膀胱颈行保留膀胱的根治性前列腺切除术(CRPC 4例，HSPC 5例)，其中4例HSPC行扩大淋巴结清扫。结果本组18例手术均顺利完成，平均手术时间256(219~310)min。术中出血量中位值300(250~350)ml，其中4例(CRPC 3例，HSPC 1例)术后输血治疗。术后平均住院时间21(11~37)d。18例均获随访，中位随访时间23.8(13~58)个月，无围手术期死亡病例。18例术后3个月QOL平均37(25~45)分；9例保留膀胱患者无真性尿失禁或膀胱出口狭窄，术后3个月平均最大尿流率23(19~25)ml/s。10例CRPC中2例分别于术后8、15个月死亡；7例于术后9~15个月PSA复发，行多西他赛或阿比特龙治疗；1例行全盆腔脏器切除术患者随访58个月，末次随访PSA 0.003 ng/ml，未见远处转移。8例HSPC术后予内分泌治疗，PSA均<0.2 ng/ml。结论对于手术经验丰富的医生，采用手术治疗T4期前列腺癌患者安全、可行，围手术期无明显并发症，无死亡病例；短期内可明显改善CRPC患者的症状，提高生活质量，远期获益需进一步大样本研究评估；对于HSPC患者不仅可改善临床症状，提高患者生活质量，且可能长期获益。

简介：摘要报道1例以水肿、多浆膜腔积液为首发表现的患者诊治经过。从最初发现的低白蛋白血症的鉴别诊断入手，通过相关检查，明确了患者存在经肠道丢失蛋白的情况；进一步追查病因，在发现肠道占位的同时，经包含肠道组织活检在内的多种检查方法，最终排除了恶性肿瘤，证实是1例少见的以蛋白丢失性肠病起病的IgG4相关性疾病。

简介：摘要遗传性痉挛性截瘫(hereditary spastic paraplegia, HSP)是一组缓慢进展的以双下肢肌张力增高、痉挛步态和肌无力为主要特征的单基因神经系统退行性遗传病，具有高度的临床和遗传异质性。该病发病率低，基因检测为诊断的金标准，迄今为止已报道了70多个致病基因和80多个致病基因相关位点。在所有HSP类型中，以SPAST基因突变所致的遗传性痉挛性截瘫4型(hereditary spastic paraplegia type 4，SPG4)最常见。随着医疗水平的不断提高，人们对SPG4的发病机制、临床特征和诊治等方面的研究日渐深入，现综述如下。

简介：AbstractBackground:The chaperonin containing t-complex (CCT) proteins play an important role in cell cycle-related protein degradation in yeast and mammals. The role of the chaperonin containing t-complex 4 (CCT4), one subtype of CCT proteins, in the progress of hepatocellular carcinoma (HCC) was not fully elucidated. Here, we aimed to explore the mechanisms of CCT4 in HCC.Methods:In this study, we used the UALCAN platform to analyze the relationship between CCT4 and HCC, and the association of CCT4 with the overall survival (OS) of HCC patients was also analyzed. CCT4 expression in HCC tumor tissues and normal tissues was also determined by western blot (WB) assay. Lentivirus vector was used to knock down the CCT4 expression, and quantitative polymerase chain reaction and WB were used to determine the level of CCT4 in HCC cell lines. Cell counting kit-8 (CCK-8) and 5-ethynyl-2＇-deoxyuridine (EdU) assays were used to detect the cell proliferation, and flow cytometry (FCM) was performed to evaluate the effect of CCT4 on the apoptosis of HCC cells. Co-immunoprecipitation (co-IP) assay and WB were used to explore the mechanisms of CCT4 regulating the growth of HCC. Data were calculated from at least three replicate experiments and expressed as mean ± standard deviation. Student’s t test, paired t test, and Kaplan-Meier analysis were used to compare across different groups.Results:We found CCT4 was upregulated in HCC tissues compared with normal tissues, and its high expression was associated with poor prognosis (P < 0.001). CCT4 was significantly increased in HCC tumor tissues compared with normal tissues (0.98 ± 0.12 vs. 0.23 ± 0.05, t = 7.73, P < 0.001). After being transfected with CCT4 short-hairpin RNA (shRNA), CCT4 was decreased in mRNA level and protein level in both Huh7 (mRNA level: 0.41 ± 0.07 vs. 1.01 ± 0.11, t = 8.09, P = 0.001; protein level: 0.61 ± 0.03 vs. 0.93 ± 0.07, t = 7.19, P = 0.002) and Hep3b cells (mRNA level: 0.55 ± 0.11 vs. 1.04 ± 0.15, t = 4.51, P = 0.011; protein level: 0.64 ± 0.10 vs. 0.95 ± 0.08, t = 4.32, P = 0.012). CCK8 assay indicated that CCT4 knockdown inhibited cell proliferation in both Huh7 (OD value of 3 days: 0.60 ± 0.14 vs. 0.97 ± 0.16, t = 3.13, P = 0.036; OD value of 4 days: 1.03 ± 0.07 vs. 1.50 ± 0.12, t = 5.97, P = 0.004) and Hep3b (OD value of 3 days: 0.69 ± 0.14 vs. 1.10 ± 0.11, t = 3.91, P = 0.017; OD value of 4 days: 1.12 ± 0.12 vs. 1.48 ± 0.13, t = 3.55, P = 0.024) cells. EdU assay showed that CCT4 knockdown inhibited the cell proliferation in both Huh7 (EdU positive rate: [31.25 ± 3.41]% vs. [58.72 ± 3.78]%, t = 9.34, P = 0.001) and Hep3b cells (EdU positive rate: [44.13 ± 7.02]% vs. [61.79 ± 3.96]%, t = 3.79, P = 0.019). FCM assay suggested that CCT4 knockdown induced apoptosis in HCC cells (apoptosis rate of Huh7: [9.10 ± 0.80]% vs. [3.66 ± 0.64]%, t = -9.18, P = 0.001; apoptosis rate of Hep3b: [6.69 ± 0.72]% vs. [4.20 ± 0.86]%, t = -3.84, P = 0.018). We also found that CCT4 could regulate anaphase-promoting complex (APC)Cdc20 activity via interacting with Cdc20. Furthermore, CCT4 knockdown induced securin (0.65 ± 0.06 vs. 0.44 ± 0.05, t = -4.69, P = 0.009) and B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (Bim; 0.96 ± 0.06 vs. 0.61 ± 0.09, t = -5.65, P = 0.005) accumulation. The upregulation of securin inhibited cell growth by downregulating cyclin D1 (0.65 ± 0.05 vs. 1.04 ± 0.07, t = 8.12, P = 0.001), and the accumulation of Bim inhibited Bcl-2 (0.77 ± 0.04 vs. 0.87 ± 0.04, t = 3.00, P = 0.040) and activated caspase 9 (caspase 9: 0.77 ± 0.04 vs. 0.84 ± 0.05, t = 1.81, P = 0.145; cleaved caspase 9: 0.64 ± 0.06 vs. 0.16 ± 0.07, t = 1.81, P = 0.001), which led to elevated apoptosis.Conclusions:Overall, these results showed that CCT4 played an important role in HCC pathogenesis through, at least partly, interacting with Cdc20.

简介：摘要目的探讨"4C"延续护理模式对产妇产褥期的生活质量与母乳喂养自我效能的影响。方法采用便利抽样法，选择2019年2—12月某三级医院产科住院的136名产妇为研究对象。按照随机数字表随机分为对照组和干预组，每组68名。对照组采用常规护理方法，干预组在对照组的基础上应用"4C"延续护理模式进行干预。采用简明健康调查量表、母乳喂养自信心量表比较两组产妇干预前后的生活质量与母乳喂养自我效能。本研究共发放问卷136份，回收有效问卷126份，有效回收率为92.65%。结果干预组产妇干预后的简明健康调查量表、母乳喂养自信心量表评分均高于对照组，差异有统计学意义（P<0.05）。结论"4C"延续护理模式能提高产妇产褥期的生活质量，提高其母乳喂养自我效能。

简介：摘要报道1例以水肿、多浆膜腔积液为首发表现的患者诊治经过。从最初发现的低白蛋白血症的鉴别诊断入手，通过相关检查，明确了患者存在经肠道丢失蛋白的情况；进一步追查病因，在发现肠道占位的同时，经包含肠道组织活检在内的多种检查方法，最终排除了恶性肿瘤，证实是1例少见的以蛋白丢失性肠病起病的IgG4相关性疾病。

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简介：摘要目的探讨SMARCA4缺失肠癌的临床病理学及分子特征。方法收集2例SMARCA4缺失肠癌患者的临床资料，对其进行组织学观察、免疫组织化学染色及二代测序，并结合文献进行讨论。结果2例患者均为男性，年龄65岁和69岁。肿瘤位于升结肠和回肠，最大径5 cm和2.5 cm。镜下观察：例1上皮样肿瘤细胞具有黏附性，呈条索状、巢状及实性生长，局灶出现腺腔结构及黏液样基质。例2肿瘤细胞缺乏黏附性，弥漫成片分布，部分肿瘤细胞呈横纹肌样特征，部分呈梭形细胞形态。免疫组织化学例1肿瘤细胞弥漫强表达广谱细胞角蛋白和上皮细胞膜抗原；例2肿瘤细胞弥漫强表达波形蛋白，部分呈核旁球状染色。2例肿瘤细胞SMARCA4完全核缺失表达。二代测序例1检测到BRAF V600E基因突变和TP53基因突变，例2检测到SMARCA4基因突变。结论SMARCA4缺失肠癌是肠癌的一组特殊亚群，具有独特的临床病理及分子特征，临床过程呈现高度侵袭性。

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简介：摘要目的探讨不同期别矽肺患者肺泡巨噬细胞（alveolar macrophages，AMs）过氧化物还原酶4（PRDX4）表达的差异。方法于2017年6月至2018年6月，采用随机抽样方法选取中国煤矿工人北戴河疗养院尘肺科就诊的12名矽肺患者作为研究对象，分为肺内粉尘沉着症组、矽肺壹期组、矽肺贰期组、矽肺叁期组共4组，每组3人。取其肺灌洗液经过滤、离心得到AMs，提取胞内蛋白，以蛋白免疫印迹（Western blotting）方法对PRDX4进行检测，结果进行统计学分析。结果肺内粉尘沉着症组、矽肺壹期组、矽肺贰期组、矽肺叁期组患者的AMs中PRDX4均有表达；4组患者AMs中PRDX4蛋白平均相对表达量分别为0.258±0.026、0.214±0.012、0.180±0.004、0.165±0.008，差异有统计学意义（P<0.05）；肺内粉尘沉着症组表达水平最高，矽肺叁期组最低。结论氧化应激损伤与矽肺的发生发展关系密切，PRDX4在不同期别矽肺患者AMs中存在差异表达，应对氧化应激指标监测，以便预测矽肺发病和评估预后。

简介：摘要IgG4相关性疾病（IgG4-RD）是一种较罕见的由免疫介导的慢性炎症伴纤维化疾病，可累及全身多个器官和系统，临床表现复杂多样。由于对该病认识时间较短，我国IgG4-RD的整体诊治水平参差不齐，国内亦无相关专家共识或诊治指南。为进一步提高各专业医生对IgG4-RD的认识和规范诊治水平，由中国罕见病联盟与中华医学会风湿病学分会联合组织专家组，在总结国内外经验和研究结果的基础上，制定了本共识，旨在统一我国临床医生对该病的诊治认识，减少漏诊和误诊，改善患者预后。

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简介：【摘要】目的 探究4A模式管理在门诊药房质量安全管理中的应用价值。方法 分析实施前（2020年1月-6月）和实施后（2020年7月-12月）门诊药房的近似错误和调剂差错发生情况、药师专业技能和患者取药满意度评分、药师工作自我满意度的差异。结果 实施4A模式管理后，门诊药房的近似错误发生率和药品调配差错率显著小于实施前（P＜0.05），药师专业技能评分、患者取药满意度评分和药师工作自我满意度均显著高于实施前（P＜0.05）。结论 4A模式管理在门诊药房的运用，可有效降低门诊药房的近似错误发生率和药品调配差错率，提升药师的专业技能水平，提高患者取药满意度和药师自我工作满意度，值得推广应用。