高血压合并主动脉夹层患者高血压特征及院前降压治疗

Objective: To summarize hypertension characteristics and pre hospital antihypertensive therapy in patients with hypertension and aortic dissection, to explore the measures of prevention and control. Methods:  683 patients with hypertension complicated with aortic dissection patients (AD group), 8974 patients with hypertension (hypertension group), during the five years from October 2009 to October 2014, were analyzed retrospectively according to the hospital medical records data combined with outpatient clinical data.Retrospective analysis of hypertension characteristics and pre hospital antihypertensive therapy from the two groups of patients when first diagnosed was conducted. Results: The two groups ratio of diabetes, coronary heart disease, hyperlipidemia, renal insufficiency, have no statistical difference. Most patients in AD group have over 10 years’ history of hypertension (P <0.05).The incidence of aortic dissection in men of AD group is higher than the hypertensive group（P <0.05）. The ratio of 40～60 years in AD group is more than that in hypertensive group (P <0.05). The ratio of stage 3 hypertension in AD group is more than that in hypertension group (P < 0.05).The ratio of no antihypertensive treatment in patients in the AD group is more than that in hypertension group (P < 0.05).The average age of onset in AD group was lower than that in hypertension group (P<0.05). The ratio of patients in the AD group treated with ARB or ACEI antihypertensive was lower than that in hypertension group (P<0.05). Conclusion:  Hypertension complicated with aortic dissection is mostly accompanied by more than 10 years’ history of hypertension in most male patients of 40～60 age group, with grade 3 hypertension. Most did not receive antihypertensive treatment, the average age of onset is low, using ARB or ACEI for the treatment of patients is less.目的： 总结高血压合并主动脉夹层（aortic dissection,AD）患者入院时高血压特征及院前降压治疗，探讨防治措施。方法：根据住院病历资料结合门诊高血压微机管理病例资料分析2009年10月至２014年10月5年期间存活的683例高血压合并主动脉夹层患者（AD组），高血压病患者8974例（高血压组），对二组患者首诊时的高血压特征及院前降压治疗情况进行回顾性分析。结果：两组糖尿病、冠心病、高脂血症、肾功能不全比例无统计学差异。AD组多有10年以上的高血压病史（Ｐ＜0.0５）。AD组男性主动脉夹层发生率多于高血压组（Ｐ＜0.0５）。AD组40-60岁比例多于高血压组（Ｐ＜0.0５）。AD组高血压3级多于高血压组（Ｐ＜0.0５）。AD组未降压治疗者比例多于高血压组（Ｐ＜0.0５）。AD组发病平均年龄低于高血压病组（Ｐ＜0.0５）。AD组采用ARB或ACEI降压治疗者少于高血压组（Ｐ＜0.0５）。结论：高血压合并主动脉夹层多有10年以上高血压病史，男性患者多，在40-60岁年龄段多，3级高血压多，未接受降压治疗者多，发病平均年龄低，采用ARB或ACEI治疗者少

Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine

In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer

Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration

The thromboxane A2 receptor (TP) has been implicated in restenosis after vascular injury, which induces vascular smooth muscle cell (VSMC) migration and proliferation. However, the mechanism for this process is largely unknown. In this study, we report that TP signaling induces VSMC migration and proliferation through activating YAP/TAZ, two major downstream effectors of the Hippo signaling pathway. The TP-specific agonists [1S-[1α,2α(Z),3β(1E,3S*),4 α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP) and 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619) induce YAP/TAZ activation in multiple cell lines, including VSMCs. YAP/TAZ activation induced by I-BOP is blocked by knockout of the receptor TP or knockdown of the downstream G proteins Gα12/13. Moreover, Rho inhibition or actin cytoskeleton disruption prevents I-BOP-induced YAP/TAZ activation. Importantly, TP activation promotes DNA synthesis and cell migration in VSMCs in a manner dependent on YAP/TAZ. Taken together, thromboxane A2 signaling activates YAP/TAZ to promote VSMC migration and proliferation, indicating YAP/TAZ as potential therapeutic targets for cardiovascular diseases

Different physiological roles of insulin receptors in mediating nutrient metabolism in zebrafish

Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia. results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a (insra) and b (insrb) caused beta-cell hyperplasia and lethality from 5 to 16 days postfertilization (dpf) (Yang BY, Zhai G, Gong YL, Su JZ, Han D, Yin Z, Xie SQ. Sci Bull (Beijing) 62: 486-492, 2017). In this study, we characterized the physiological roles of Insra and Insrb. in somatic growth and fueling metabolism, respectively. A high-carbohydrate diet was provided for insulin receptor knockout zebrafish from 60 to 120 dpf to investigate phenotype inducement and amplification. We observed hyperglycemia in both insra-/- fish and insrb-/- fish. Impaired growth hormone signaling, increased visceral adiposity, and fatty liver were detected in insrb-/- fish, which are phenotypes similar to the lipodystrophy observed in mammals. More importantly, significantly diminished protein levels of P-PPAR alpha, P-STATS, and IGF-1 were also observed in insrb-/- fish. In insra-/- fish, we observed increased protein content and decreased lipid content of the whole body. Taken together, although Insra and Insrb show overlapping roles in mediating glucose metabolism through the insulin-signaling pathway, Insrb is more prone to promoting lipid catabolism and protein synthesis through activation of the growth hormone-signaling pathway, whereas Insra primarily acts to promote lipid synthesis via glucose utilization.</p

Inhibition of the prolyl isomerase Pin1 enhances the ability of sorafenib to induce cell death and inhibit tumor growth in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis. However, the role of Pin1 in the efficacy of sorafenib against HCC is unknown. Here we found that sorafenib down-regulated Pin1 mRNA and protein expression, likely through inhibition of Pin1 transcription by the Rb/E2F pathway. Importantly, Pin1 knockdown potently enhanced the ability of sorafenib to induce cell death in HCC, which was further supported by the findings that Pin1 knockdown led to stabilization of Fbxw7 and destabilization of Mcl-1. Furthermore, all-trans retinoic acid (ATRA), a known anticancer drug that inhibits and ultimately induces degradation of active Pin1 in cancer cells, also potently sensitized HCC cells to sorafenib-induced cell death at least in part through a caspase-dependent manner. Moreover, ATRA also synergistically enhanced the ability of sorafenib to reduce Pin1 and inhibit tumor growth of HCC in mouse xenograft models. Collectively, these results not only demonstrate that Pin1 down-regulation is a key event underlying the anti-tumor effects of sorafenib, but also uncover that Pin1 inhibitors offer a novel approach to enhance the therapeutic efficacy of sorafenib against HCC

Atropine Premedication Facilitates Ultrasound-Guided Reduction by Saline Enema in Children With Intussusception

Background and Objective: Intussusception is the most frequent pediatric abdominal emergency. Intestinal spasm, ischemia, necrosis and even death may occur without prompt diagnosis and treatment. The ultrasound-guided reduction by saline enema is a preferred non-surgical procedure for intussusception. Muscular relaxants can relieve the intestinal spasm and edema by relaxing the intestinal smooth muscle, which may facilitate the treatment of intussusception. However, controversy persists on whether muscular relaxants are effective in the procedure. Therefore, the purpose of our study was to assess the efficacy of atropine known as a muscular relaxant in ultrasound-guided reduction by saline enema in children with intussusception.Methods: All patients with intussusception diagnosed and treated in our department from July 2016 to February 2018 were included. Four hundred and thirty-seven children were enrolled and randomly divided into two groups: an atropine group and a control group. Intramuscular atropine at a dose of 0.02 mg per kilogram of body weight was administrated 15 min before ultrasound-guided reduction by saline enema in the atropine group. In the control group, the ultrasound-guided reduction was performed without using any muscular relaxants. The success rate, duration of the reduction, volume of saline, maximum intra-rectal pressure and complications were recorded and compared between the two groups.Results: The success rate was 95.9% (212 out of 221) and 94.9% (205 out of 216) in the atropine group and the control group, respectively. No significant difference was observed in the success rate between the two groups (P &gt; 0.05). The duration of reduction was significantly lower in the atropine group than in the control group (P &lt; 0.01). The volume of saline was also significantly lower in the atropine group than in the control group (P &lt; 0.05). The maximum intra-rectal pressure showed no difference between the two groups (P &gt; 0.05).Conclusion: Atropine premedication can facilitate ultrasound-guided reduction by saline enema in children with intussusception, by reducing the duration of reduction and the volume of saline in the procedure

Estrogen regulates Hippo signaling via GPER in breast cancer

The G protein–coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis

Virulence Determinants Are Required for Brain Abscess Formation Through Staphylococcus aureus Infection and Are Potential Targets of Antivirulence Factor Therapy

Bacterial brain abscesses (BAs) are difficult to treat with conventional antibiotics. Thus, the development of alternative therapeutic strategies for BAs is of high priority. Identifying the virulence determinants that contribute to BA formation induced by Staphylococcus aureus would improve the effectiveness of interventions for this disease. In this study, RT-qPCR was performed to compare the expression levels of 42 putative virulence determinants of S. aureus strains Newman and XQ during murine BA formation, ear colonization, and bacteremia. The alterations in the expression levels of 23 genes were further confirmed through specific TaqMan RT-qPCR. Eleven S. aureus genes that persistently upregulated expression levels during BA infection were identified, and their functions in BA formation were confirmed through isogenic mutant experiments. Bacterial loads and BA volumes in mice infected with isdA, isdC, lgt, hla, or spa deletion mutants and the hla/spa double mutant strain were lower than those in mice infected with the wild-type Newman strain. The therapeutic application of monoclonal antibodies against Hla and SpA decreased bacterial loads and BA volume in mice infected with Newman. This study provides insights into the virulence determinants that contribute to staphylococcal BA formation and a paradigm for antivirulence factor therapy against S. aureus infections

Original Article Unclassified renal cell carcinoma: a clinicopathological, comparative genomic hybridization, and whole-genome exon sequencing study

Abstract: Unclassified renal cell carcinoma (URCC) is a rare variant of RCC, accounting for only 3-5% of all cases. Studies on the molecular genetics of URCC are limited, and hence, we report on 2 cases of URCC analyzed using comparative genome hybridization (CGH) and the genome-wide human exon GeneChip technique to identify the genomic alterations of URCC. Both URCC patients (mean age, 72 years) presented at an advanced stage and died within 30 months post-surgery. Histologically, the URCCs were composed of undifferentiated, multinucleated, giant cells with eosinophilic cytoplasm. Immunostaining revealed that both URCC cases had strong p53 protein expression and partial expression of cluster of differentiation-10 and cytokeratin. The CGH profiles showed chromosomal imbalances in both URCC cases: gains were observed in chromosomes 1p11-12, 1q12-13, 2q20-23, 3q22-23, 8p12, and 16q11-15, whereas losses were detected on chromosomes 1q22-23, 3p12-22, 5p30-ter, 6p, 11q, 16q18-22, 17p12-14, and 20p. Compared with 18 normal renal tissues, 40 mutated genes were detected in the URCC tissues, including 32 missense and 8 silent mutations. Functional enrichment analysis revealed that the missense mutation genes were involved in 11 different biological processes and pathways, including cell cycle regulation, lipid localization and transport, neuropeptide signaling, organic ether metabolism, and ATP-binding cassette transporter signaling. Our findings indicate that URCC may be a highly aggressive cancer, and the genetic alterations identified herein may provide clues regarding the tumorigenesis of URCC and serve as a basis for the development of targeted therapies against URCC in the future

3-(3-Pyridylmethylidene)-2-indolinone Reduces the Severity of Colonic Injury in a Murine Model of Experimental Colitis

Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response