基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

肾周脂肪梅奥粘连概率评分系统在肾癌后腹腔镜肾部分切除术中的应用

目的探讨肾周脂肪梅奥粘连概率评分系统（MAP）在肾癌后腹腔镜肾部分切除术中的临床应用价值。 方法回顾性分析2015年1月至2020年6月徐州医科大学附属淮安医院泌尿外科收治的行后腹腔镜肾部分切除术的153例肾癌患者的临床病例资料。依据MAP评分系统将其分为低度复杂组、中度复杂组和高度复杂组三组。比较各组间的手术时间、术中出血量、术中及术后并发症、术中热缺血时间、术后住院时间及术后血肌酐变化情况。 结果在153例患者中，低度复杂组68例，中度复杂组58例和高度复杂组27例。三组患者在年龄、性别、术前血肌酐水平、肿瘤最大径、肿瘤位置、BMI、RENAL评分等方面差异无统计学意义（P>0.05）。随着复杂程度的提高，手术时间、术中出血量也在不断增加（P<0.05）；而术中热缺血时间、术后住院时间及术后血肌酐水平无明显变化（P>0.05）。在术中并发症方面，随着复杂程度的提高，术中并发症的发生率也在增加（P<0.05），且高度复杂组的术后并发症发生风险是低度复杂组的13.895倍（P=0.002)，MAP评分系统预测术中并发症发生的精度较高（AUC=0.757，P=0.002）。但是术后并发症各组比较差异无统计学意义（P>0.05）。 结论MAP评分系统在肾癌后腹腔镜肾部分切除术中，对预估手术难度及术中并发症发生风险有较好的临床应用价值。     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

腹腔镜低位直肠癌根治术中应用盆腔腹膜关闭技术的疗效研究

目的:探讨盆腔腹膜关闭技术在腹腔镜低位直肠癌根治术应用的疗效。方法:回顾性分析2012年1月至2016年5月我院54例腹腔镜低位直肠癌根治术中行盆底腹膜关闭患者和57例未行盆底腹膜关闭患者的临床资料。结果:盆腔腹膜关闭组与盆腔腹膜未关闭组在手术时间、术中出血量、肛门排气时间、术后进食时间以及盆腔引流管拔除时间等方面差异均无统计学意义(P>0.05)。盆腔腹膜关闭组中8例患者发生短期并发症;6例患者发生中期并发症;14例患者发生远期并发症,均为肠梗阻。盆腔腹膜未关闭组中31例患者发生短期并发症,28例患者发生中期并发症,36例患者发生远期并发症。所有患者均治疗好转。Coxs回归模型分析提示,盆腔腹膜是否关闭是腹腔镜低位直肠癌根治术患者术后生存的独立指标。结论:腹腔镜Miles术中行盆底腹膜关闭安全可行,具有临床实用价值。     

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI)

IntroductionThe PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.Materials and methodsCRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.ResultsThe survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.ConclusionThe PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.     

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

BackgroundMajor depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.MethodsMDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.ResultsMDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.ConclusionWithin MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.Registration of clinical trialsThe ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, “Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders.”     

改进Seldinger法经皮穿刺腹膜透析置管术在终末期肾病患者中的应用

目的:探讨改进Seldinger法经皮穿刺腹膜透析置管术在终末期肾病患者中的应用效果。方法:选取2019年12月~2020年12月于本院进行腹膜透析置管术的终末期肾病患者61例,随机分为观察组(31例)和对照组(30例),对照组患者采用常规开腹手术置管,观察组采用改进Seldinger法置管,比较两组患者完成置管手术的相关指标(手术时间、术后排气时间、切口长度、住院时间),术后3d、1个月患者并发症发生情况。结果:较对照组,观察组手术时间、术后排气时间均更短,腹部切口长度更短(P<0.05),两组患者住院时间比较(P>0.05),观察组穿刺成功率明显高于对照组(100.00%,80.00%,χ²=6.88,P=0.01)。较对照组,观察组患者术后3d并发症发生率明显低于对照组(22.58%,50.00%,χ²=4.97,P=0.03),观察组患者术后1个月并发症发生率明显低于对照组(19.35%,53.33%,χ²=7.05,P=0.01)。结论:对终末期肾病患者运用改进Seldinger法经皮穿刺腹膜透析置管术进行置管可有效缩短手术时间和术后排气时间,创口较小,患者术后早期、远期并发症较少,临床应用效果较好。     

E‐cadherin and p120ctn protein expression are lost in hidradenitis suppurativa lesions

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease affecting the pilosebaceous units in the axilla, groin and buttocks. While the pathogenesis of HS is not clear, mechanical stress exacerbates HS. In this study, we aimed to determine whether intracellular adhesive junctions may be aberrant in HS patient skin. Strikingly, we observed loss of E‐cadherin and p120ctn protein expression, two key adherens junction proteins, in ~85% of HS severe skin lesions. Moreover, loss of protein expression was apparent in non‐lesional skin from HS patients and the degree of loss positively correlated with HS Hurley Stage of disease. E‐cadherin expression was unaltered in other inflammatory skin conditions including chronic wound epithelium, atopic dermatitis, and acne vulgaris compared with healthy skin suggesting that its loss may be uniquely relevant to HS pathogenesis. A complete loss of α‐catenin, β‐catenin and ZO‐1 was not observed; however, some cytoplasmic staining of the catenins was noted in HS epithelium. We also demonstrated diminished desmosome size in HS lesional skin. Overall, our data suggested that loss of adherens junction proteins and diminished desmosome size in HS skin contributes to the skin's inability to withstand mechanical stress and provides rationale as to why mechanical stress exacerbates HS symptoms.