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.     

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.”     

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.     

针灸联合西药对中重度间歇性过敏性鼻炎患者T淋巴细胞亚群、IL-4、IL-10、VACM-1水平的影响

目的观察针灸联合西药对中重度间歇性过敏性鼻炎患者血清T淋巴细胞亚群、炎性因子及血管细胞黏附分子-1(VACM-1)的影响。方法将120例中重度间歇性过敏性鼻炎患者随机分为对照组和治疗组,每组60例。对照组予丙酸氟替卡松鼻喷雾剂、盐酸氮卓斯汀片治疗,治疗组在对照组治疗措施的基础上加用针灸疗法。两组疗程均为28天,观察临床疗效,比较中医证候积分、血清T淋巴细胞亚群、炎性因子[白介素-4(IL-4)、白介素-10(IL-10)]及VACM-1水平的变化情况。结果①治疗组、对照组总有效率分别为95.0%、81.7%,治疗组临床疗效优于对照组(P0.05)。②治疗前与疗程结束后7天组内比较,两组中医证候(鼻塞不通、鼻痒难耐、鼻流清涕、喷嚏频作)较治疗前改善(P0.05);组间疗程结束后7天比较,治疗组中医证候改善情况优于对照组(P0.05)。③治疗前与疗程结束后7天组内比较,两组血清CD3~+、CD4~+水平和CD4~+/CD8~+较治疗前升高(P0.05),血清CD8~+、IL-4、IL-10、VCAM-1水平较治疗前降低(P0.05);组间疗程结束后7天比较,上述指标差异有统计学意义(P0.05)。结论针灸联合西医治疗中重度间歇性过敏性鼻炎疗效满意,可有效缓解患者的临床症状,改善机体免疫状态,减轻炎症反应。     

Contribution to the rheological testing of pharmaceutical semisolids

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice.     

基质金属蛋白酶在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用

目的分析基质金属蛋白酶(MMPs)在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用。方法选取2017年1月-2018年12月在温州市人民医院进行腹腔镜手术的60例子宫内膜异位症患者为观察组,选取同期进行腹腔镜手术的30例非子宫内膜异位症患者为对照组。观察组根据术中盆腔粘连程度分为1组(无或仅有轻度盆腔粘连,子宫内膜异位症Ⅰ~Ⅱ期,24例)和2组(中重度盆腔粘连,子宫内膜异位症Ⅲ~Ⅳ期,36例)。采集3组腹腔液和血清,采用ELISA法检测腹腔液及血清基质金属蛋白酶-2 (MMP-2)、基质金属蛋白酶-3 (MMP-3)、基质金属蛋白酶-7 (MMP-7),血清雌二醇(E2)、黄体生成素(LH)、孕酮(P)、卵泡刺激素(FSH),白细胞介素-6 (IL-6)、白细胞介素-8 (IL-8)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)水平。结果 1组腹腔液MMP-2、MMP-3、MMP-7水平显著高于对照组,差异有统计学意义(均P<0. 05),2组腹腔液MMP-2、MMP-3、MMP-7水平显著高于1组(均P<0. 05)。1组血清FSH、LH水平显著高于对照组(均P<0. 05),2组血清FSH、LH水平显著高于1组(均P <0. 05)。1组血清E2、P水平显著低于对照组(均P<0. 05),2组血清E2、P水平显著低于1组(均P<0. 05)。1组血清IL-6、IL-8、TNF-α水平显著高于对照组(均P<0. 05),2组血清IL-6、IL-8、TNF-α水平显著高于1组(均P<0. 05)。结论子宫内膜异位症患者腹腔液中MMPs水平升高,可能与盆腔粘连的发生及严重程度相关。     

PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland

AIM: To determine whether lectin-like ox-LDL receptor (LOX-1) regulates adhesion molecules expression and neutrophil infiltration in A. fumigatus keratitis of C57BL/6 mice.METHODS: C57BL/6 mice were pretreated with a neutralizing antibody to LOX-1 (5 μg/5 μL) or control nonspecific IgG (5 μg/5 μL), LOX-1 inhibitor Poly-I (2 μg/5 μL) or PBS by subconjunctival injection. Fungal keratitis mouse models of C57BL/6 mice were established by scraping corneal central epithelium, smearing A. fumigatus on the corneal surface and covering the eye with contact lenses. The corneal response to infection was assessed via clinical score. The mRNA levels of the adhesion molecules ICAM-1, VCAM-1, P-selectin and E-selectin were tested in control and infected corneas by RT-PCR. The protein levels of ICAM-1 were evaluated by immunofluorescence (IF) and Western blot. Neutrophils were extracted from the abdominal cavity of C57BL/6 mice followed by pretreatment using antibody to LOX-1 (10 μg/mL) or control nonspecific IgG (10 μg/mL), the Poly-I (4 μg/mL) or PBS. The cells were then stimulated with A. fumigatus and tested mRNA and protein levels of LFA-1 using RT-PCR and Western blot. IF and myeloperoxidase (MPO) assays were used to assess neutrophil infiltration in mice corneas.RESULTS: Pretreatment of LOX-1 antibody or the Poly-I reduced the degree of inflammation of cornea and decreased the clinical fungal keratitis score compared with pretreatment of IgG or PBS. And these pretreatment also displayed an obvious decline in the mRNA levels of ICAM-1, VCAM-1, P-selectin, E-selectin and LFA-1 expression compared with control groups . Furthermore, pretreated with LOX-1 antibody or Poly-I, the protein levels of ICAM-1 and LFA-1 also decreased compared with control groups. Neutrophil infiltration in the cornea was significantly reduced after pretreatment of LOX-1 antibody or Poly-I compared with control groups by IF and MPO assays. CONCLUSION: These data provide evidence that inhibition of LOX-1 can decrease the expression of adhesion molecules and thus reduce neutrophil infiltration in A. fumigatus infected corneas of C57BL/6 mice.