骨形态发生蛋白2及碱性成纤维生长因子2对大鼠骨髓间充质干细胞膜片增殖和成骨分化的影响

文题释义： 细胞膜片技术：是在体外接种培养高密度的细胞，使其相互融合生长至100%而形成的透明致密膜状物。该技术不需要胰酶消化即可收集细胞，因此保留了大量的胞外基质、细胞间连接以及细胞-基质连接等结构。目前细胞膜片技术已成为组织工程领域的研究热点，已被推广应用于牙周膜、角膜、心脏、软骨、食管等多种组织器官修复。 成骨细胞：主要由内外骨膜和间充质始祖细胞分化而来，在复杂的骨形成过程中发挥着主要的功能，承担着骨基质的合成、分泌和矿化。骨髓间充质干细胞具有多向分化潜能，能定向分化为成骨细胞，其成骨分化过程可受多种因素的影响，如细胞因子的调控、遗传因素和激素水平等。背景：现阶段骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖、成骨分化的影响和作用机制还尚未可知，如何将生长因子与组织工程细胞膜片技术相整合，最终将其用于骨缺损修复具有重要意义。 目的：探讨单独及联合应用骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖和成骨分化的影响。 方法：体外分离培养鉴定SD大鼠骨髓间充质干细胞并构建细胞膜片，选用不同质量浓度的骨形态发生蛋白2和碱性成纤维生长因子2单独及联合诱导骨髓间充质干细胞膜片，CCK-8法结合碱性磷酸酶活性检测确定2种因子促进膜片增殖和成骨分化的最佳有效质量浓度；然后对骨髓间充质干细胞膜片进行成骨诱导，通过大体及显微镜观察、Vonkossa染色、茜素红染色、RT-PCR检测相关成骨标志物来评估诱导效果。 结果与结论：单独应用骨形态发生蛋白2可增强骨髓间充质干细胞膜片的碱性磷酸酶活性，最佳质量浓度为100 μg/L(P < 0.001)，单独应用碱性成纤维生长因子2能加速骨髓间充质干细胞膜片的增殖，最佳质量浓度为20 μg/L(P < 0.001)，而联合应用既可以促进膜片增殖又能提高其碱性磷酸酶活性(P < 0.001)；经成骨诱导后，4组膜片在形态学上无明显差异，均能诱导骨髓间充质干细胞膜片的成骨分化，其中联合组钙结节最明显(P < 0.001)，可显著促进膜片晚期成骨分化并抑制其早期成骨分化，具有明显的协同促进作用(P < 0.001)。结果表明，骨形态发生蛋白2和碱性成纤维生长因子2联合应用时具有协同作用，既可以促进骨髓间充质干细胞膜片增殖，又能显著增强其成骨诱导能力。ORCID: 0000-0003-1918-579X(何惠宇) 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程     

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。     

CyclinA1 Promoter Methylation in Self-Sampling Test

Background: Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test.  Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). Materials and Methods: A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled.  Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure  was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Results: Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its  specificity and accuracy were 99.5% and 82.14%, respectively.  The sensitivity of SS-HPV was 70.5%, and its  specificity and accuracy were 39.2% and 43.3%, respectively. Conclusion:  Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling.     

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。     

针灸联合川芎茶调散治疗周围性面神经麻痹(风寒证)

目的:观察川芎茶调散加减方联合针灸治疗周围性面神经麻痹(风寒证)的临床效果。方法:选取2018年2月至2019年2月威海市中医院收治的急性周围性面瘫患者108例作为研究对象,按照随机数字表法分为对照组与观察组,每组54例。对照组给予常规西药治疗,观察组给予川芎茶调散加减方口服联合针灸治疗。比较2组患者主要症状的改善时间、肌电图检查相关指标、面部神经功能分级的变化,测定血清中相关因子水平,比较临床效果。结果:观察组、对照组的有效率92.59%、75.93%,以观察组临床效果更好(P0.05);观察组患者治疗后的闭目、抬眉、鼓颊的改善时间明显短于对照组(P0.05);观察组患者的肌电图结果RI潜伏期低于对照组,CMAP波幅高于对照组,面部神经功能分级改善更明显(P0.05);观察组患者血清中TNF-α、IL-17含量明显低于对照组,GDNF含量显著高于对照组(P0.05)。结论:川芎茶调散加减方联合针灸利于促进患者临床症状的缓解,改善肌电图指标,促进面部神经功能的恢复,推断其起效可能与通过调控血清中TNF-α、GDNF、IL-17等水平以减轻患者神经病变的炎性反应损伤程度有关。     

Neonatal weight loss and gain patterns in caesarean section born infants: integrative systematic review

There is evidence that caesarean section delivery can impact on neonatal weight loss and weight gain patterns in the first 5 days of life. We conducted an integrative systematic review to examine the association of mode of delivery on early neonatal weight loss. Pubmed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpta Medica dataBASE, and Medical Literature Analysis and Retrieval System Online were searched for relevant papers published before June 2019. Reference lists from the relevant papers were then backwards and forwards searched. As neonatal weight loss was reported in different formats, a meta‐analysis could not be carried out. Most studies did not distinguish between elective and emergency caesarean sections or instrumental and nonassisted vaginal deliveries. Seven papers were included. All papers except one found that caesarean section was associated with higher weight loss in the early days of life. Two papers presented data from studies on babies followed up to 1 month. One study found that on day 25, babies born by caesarean section had significantly higher weight gain than those born vaginally, while another found that by day 28, babies born vaginally gained more weight per day (11.9 g/kg/day) than those born by caesarean section (10.9 g/kg/day; p = .02). Overall, infants born by caesarean section lost more weight than those born vaginally, but due to the small number of studies included, more are needed to look at this difference and why it may occur. This discrepancy in weight between the two groups may be corrected over time, but future studies will need larger sample sizes and longer follow‐up periods to examine this.     

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients.