Cardiovascular System/pathology* ; Constriction, Pathologic/genetics* ; Point Mutation ; Neurofibromin 1/genetics* ; Animals ; Mice

BACKGROUNDIn qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. The aim of this study was to evaluate the value of intraductal ultrasonography (IDUS), endoscopic brush cytology and K-ras, P53 gene mutation in the early diagnosis of malignant biliary stricture.

METHODSFrom February 2012 to February 2013, 84 patients with suspected malignant biliary stricture were performed IDUS firstly, then endoscopic brush cytology and finally K-ras, P53 gene mutation detection, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of all above ways were evaluated and compared.

RESULTSOf 84 patients, 52 cases were ultimately diagnosed malignant biliary stenosis; of which, 9 cases had no recurrence or metastasis to other organs after radical operation during the follow-up period. IDUS combined with brush cytology and K-ras + P53 gene mutation detection had obvious advantage in the sensitivity, accuracy and negative predictive value than any other joint detection and single detection (the advantage was more significant compared with IDUS + brush cytology or any single detection P < 0.01). There were obvious statistical significance in the sensitivity and accuracy between IDUS + brush cytology + P53 or IDUS + brush cytology + K-ras and IDUS + brush cytology or IDUS (P < 0.05). There was no statistical significance in the sensitivity, specificity, positive predictive value, negative predictive value and accuracy between IDUS + brush cytology + P53 and IDUS + brush cytology + K-ras (P > 0.05).

CONCLUSIONSIDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.

Aged ; Aged, 80 and over ; Bile Duct Diseases ; diagnosis ; genetics ; Bile Duct Neoplasms ; diagnosis ; genetics ; Bile Ducts ; pathology ; Constriction, Pathologic ; diagnosis ; genetics ; Female ; Genes, p53 ; genetics ; Genes, ras ; genetics ; Humans ; Male ; Middle Aged ; Mutation

Humans ; Nerve Tissue Proteins ; Epithelial-Mesenchymal Transition/genetics* ; Constriction, Pathologic ; Receptors, Immunologic ; Epithelial Cells/metabolism* ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism*

OBJECTIVE: To observe the effect of acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6) + "Yuji" (LU 10) for the airway remodeling in asthma rats based on the transforming growth factor-β1 (TGF-β1)/ Smad family member 3 (Smad3) signaling pathway; and explore the efficacy difference between the two acupoint combinations. METHODS: Forty SPF male SD rats, aged 4 weeks, were randomly divided into a blank group (n = 10) and a modeling group (n = 30). The ovalbumin (OVA) sensitization method was used to establish asthma model in the modeling group. After successful model preparation, the rats of the modeling group were randomized into a model group, an acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) (AAF) group, and acupuncture at "Kongzui" (LU 6)+"Yuji" (LU 10) (AAK) group, with 10 rats in each one. Starting from day 15 of the experiment, 5 min after motivating, acupuncture was applied to "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6)+"Yuji" (LU 10) in the AAF group and the AAK group respectively. The intervention was delivered for 30 min each time, once daily, lasting 3 weeks consecutively. Using lung function detector, the airway resistance (RL) and dynamic compliance (Cdyn) of the lungs were detected. The histomorphology of lung tissues was detected with HE staining and Masson staining, and the mRNA and protein expression of TGF-β1 and Smad3 in lung tissues was detected with the real-time PCR and Western blot methods. RESULTS: Compared with the blank group, RL was increased and Cdyn was decreased in the rats of the model group (P<0.01); and RL was reduced and Cdyn was increased in the AAF group and the AAK group when compared with those in the model group (P<0.01, P<0.05). The rats of the model group had bronchial lumen stenosis, inflammatory cell infiltration, collagen fibre hyperplasia and thickened smooth muscle in the lung tissues when compared with those in the blank group; and in comparison with the model group, all of the above morphological changes were attenuated in the AAF group and the AAK group. Besides, these morphological changes of the lung tissues were more alleviated in the AAF group when compared with those in the AAK group. In comparison with the blank group, the mRNA and protein expression of TGF-β1 and Smad3 of the lung tissues was increased in the model group (P<0.01), and it was reduced in the AAF group and the AAK group when compared with that in the model group (P<0.05, P<0.01). The mRNA expression of TGF-β1 and Smad3 was lower in the AAF group when compared with that in the AAK group (P<0.05). CONCLUSION Acupuncture at either "Feishu" (BL 13)+"Dingchuan" (EX-B 1) or "Kongzui" (LU 6)+"Yuji" (LU 10) reduces the airway remodeling in the rats with asthma, which may be related to the down-regulation of mRNA and protein expression of TGF-β1 and Smad3. The better efficacy is obtained with acupuncture at "Feishu" (BL 13)+"Dingchuan" (EX-B 1).
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/genetics* ; Airway Remodeling ; Acupuncture Therapy ; Signal Transduction ; Asthma/therapy* ; Constriction, Pathologic ; Anti-Asthmatic Agents

Moyamoya disease is characterized by bilateral stenosis or occlusion of distal internal carotid artery (ICA) bifurcation including its proximal branches and abnormal vascular network (moyamoya vessel, MMV) in the vicinity of the arterial occlusions. It is the most common pediatric cerebrovascular disease in Eastern Asia, particularly in Korea and Japan. The etiology is still unknown, but much about the pathology from autopsies, factors involved in its pathogenesis, and its genetics have been studied and reported. It may cause ischemic attacks or cerebral infarctions in children and cerebral hemorrhage in adults. Because of its aggressive clinical course in very young children, the need for early detection and treatment has been recognized. Magnetic resonance imaging (MRI)/MR angiography (MRA), cerebral hemodynamic studies, and cerebral angiography are used for the diagnosis. The treatment basically focuses on prevention of further ischemia and infarction through revascularization. Technically, direct and indirect bypass methods are used. The treatment strategy needs to be individualized in each patient. Outcomes of revascularization procedures are excellent in preventing transient ischemic attacks (TIAs) in most patients.
Adult ; Angiography ; Autopsy ; Carotid Artery, Internal ; Cerebral Angiography ; Cerebral Hemorrhage ; Cerebral Infarction ; Child ; Constriction, Pathologic ; Diagnosis ; Far East ; Genetics ; Hemodynamics ; Humans ; Infarction ; Ischemia ; Ischemic Attack, Transient ; Japan ; Korea ; Magnetic Resonance Imaging ; Moyamoya Disease* ; Pathology

Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ²=11.292,P=0.001)and anal stenosis(χ²=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).
Adolescent ; Adult ; Ainhum ; Blister ; Carcinoma, Squamous Cell ; Child ; Constriction, Pathologic ; Deglutition Disorders/complications* ; Epidermolysis Bullosa ; Female ; Humans ; Inflammation ; Keratoderma, Palmoplantar/complications* ; Male ; Membrane Proteins ; Mutation ; Neoplasm Proteins/genetics* ; Periodontal Diseases ; Photosensitivity Disorders ; Urethral Stricture/complications* ; Young Adult

OBJECTIVETo observe the effects of repeated electroacupuncture (EA) of Zusanli (ST36)- Yanglingquan (GB34) on hypothalamic acetylcholinesterase (AchE) and vesicular acetylcholine (ACh) transporter (VAChT) activities and choline acetyltransferase (ChAT) mRNA and muscarinic M1 receptor (M1R) mRNA expression in chronic constrictive injury (CCI) and/or ovariectomy (OVX) rats so as to reveal its underlying mechanism in cumulative analgesia.

METHODSA total of 103 female Wistar rats were randomly divided into normal control (n =15), CCI (n =15), CCI+EA2d (n =15), CCI+EA2W (n =15), OVX+CCI =13), OVX+CCI+EA2d (n =15), and OVX+CCI+EA2W groups (n =15). CCI model was established by ligature of the unilateral sciatic nerve with surgical suture. Memory impairment model was established by removal of the bilateral ovaries. Morris water test was conducted to evaluate the OVX rats' memory learning ability, and the thermal pain threshold (PT) of the bilateral paws was detected the next morning after EA. EA (2/15 Hz, 1 mA) was applied to bilateral ST36-GB34 for 30 min, once daily for 2 days or 2 weeks, respectively. Hypothalamic AChE activity was detected by histochemistry, VAChT immunoactivity was determined by immunohistochemistry, and ChAT mRNA and M1R mRNA expressions were assayed by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSIn comparison with the normal control group, the AChE activity in hypothalamic arcuate nucleus (ARC) and supraoptic nucleus (SON) regions of CCI group, AChE activity in paraventricular nucleus (PVN), ARC, and SON regions of OVX+CCI group, and hypothalamic muscarinic M1R mRNA expression levels in both CCI and OVX+CCI groups were down-regulated significantly (P <0.05). Compared with the CCI group, the AChE activities in hypothalamic ARC and SON regions of CCI+EA2d and CCI+EA2W groups and PVN region of CCI+EA2W group and hypothalamic ChAT mRNA and M1R mRNA expression levels in CCI+EA2W group were up-regulated considerably (P <0.05). In comparison with the OVX+CCI group, the AChE activities in PVN, ARC, and SON regions and the expressions of hypothalamic ChAT mRNA and VAChT in ARC region of OVX+CCI+EA2W group were up-regulated remarkably (P <0.05). The effects in rats of CCI+EA2W group were evidently superior to those of OVX+CCI+EA2d group in up-regulating AChE activities in PVN, ARC, and SON regions, VAChT immunoactivity in ARC region, and expression levels of hypothalamic ChAT mRNA and M1R mRNA (P <0.05). Similar situations were found in OVX+CCI rats after EA2W. It suggested a cumulative effect after repeated EA of ST36-GB34. Comparison between CCI+EA2W and OVX+CCI+EA2W groups showed that the effects in rats of the former group were evidently better than those of the latter group in up-regulating AChE activity in ARC and SON regions and the expressions of hypothalamic ChAT mRNA and M1 mRNA (P <0.05), suggesting a reduction of EA2W effects after OVX.

CONCLUSIONRepeated EA can significantly up-regulate AChE and VAChT activities and ChAT mRNA and M1R mRNA expressions in the hypothalamus of CCI and OVX+CCI rats, which may contribute to the cumulative analgesic effects of repeated EA and be closely related to the animals' neuromemory ability.

Acetylcholinesterase ; genetics ; metabolism ; Acupuncture Analgesia ; Animals ; Choline O-Acetyltransferase ; genetics ; metabolism ; Cholinergic Agents ; metabolism ; Chronic Pain ; enzymology ; metabolism ; pathology ; Constriction, Pathologic ; Electroacupuncture ; Female ; Gene Expression Regulation ; Hypothalamus ; enzymology ; metabolism ; pathology ; Neuralgia ; enzymology ; metabolism ; pathology ; Ovariectomy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Receptor, Muscarinic M1 ; genetics ; metabolism ; Vesicular Acetylcholine Transport Proteins ; genetics ; metabolism

Moyamoya disease is characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, recent genome-wide and locus-specific association studies identified RNF213 as an important susceptibility gene of moyamoya disease among East Asian population. A polymorphism in c.14576G>A in RNF213 was identified in 95% of familial patients with moyamoya disease and 79% of sporadic cases, and patients having this polymorphism were found to have significantly earlier disease onset and a more severe form of moyamoya disease, such as the presentation of cerebral infarction and posterior cerebral artery stenosis. The exact mechanism by which the RNF213 abnormality relates to moyamoya disease remains unknown, while recent reports using genetically engineered mice lacking RNF213 by homologous recombination provide new insight for the pathogenesis of this rare entity. Regarding biomarkers of moyamoya disease, moyamoya disease is characterized by an increased expression of angiogenic factors and pro-inflammatory molecules such as vascular endothelial growth factors and matrix metalloproteinase-9, which may partly explain its clinical manifestations of the pathologic angiogenesis, spontaneous hemorrhage, and higher incidence of cerebral hyperperfusion after revascularization surgery. More recently, blockade of these pro-inflammatory molecules during perioperative period is attempted to reduce the potential risk of surgical complication including cerebral hyperperfusion syndrome. In this review article, we focus on the genetics and biomarkers of moyamoya disease, and sought to discuss their clinical implication.
Angiogenesis Inducing Agents ; Animals ; Asian Continental Ancestry Group ; Biomarkers* ; Brain ; Carotid Artery, Internal ; Cerebral Infarction ; Constriction, Pathologic ; Genetics* ; Hemorrhage ; Homologous Recombination ; Humans ; Incidence ; Matrix Metalloproteinase 9 ; Mice ; Moyamoya Disease* ; Neovascularization, Pathologic ; Perioperative Period ; Posterior Cerebral Artery ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

The establishment of a polarized cellular morphology is essential for a variety of processes including neural tube morphogenesis and the development of the brain. Cdc42 is a Ras-related GTPase that plays an essential role in controlling cell polarity through the regulation of the actin and microtubule cytoskeleton architecture. Previous studies have shown that Cdc42 plays an indispensable role in telencephalon development in earlier embryo developmental stage (before E12.5). However, the functions of Cdc42 in other parts of brain in later embryo developmental stage or in adult brain remain unclear. Thus, in order to address the role of Cdc42 in the whole brain in later embryo developmental stage or in adulthood, we used Cre/loxP technology to generate two lines of tissue-specific Cdc42-knock-out mice. Inactivation of Cdc42 was achieved in neuroepithelial cells by crossing Cdc42/ flox mice with Nestin-Cre mice and resulted in hydrocephalus, causing death to occur within the postnatal stage. Histological analyses of the brains from these mice showed that ependymal cell differentiation was disrupted, resulting in aqueductal stenosis. Deletion of Cdc42 in the cerebral cortex also induced obvious defects in interkinetic nuclear migration and hypoplasia. To further explore the role of Cdc42 in adult mice brain, we examined the effects of knocking-out Cdc42 in radial glial cells by crossing Cdc42/flox mice with human glial fibrillary acidic protein (GFAP)-Cre mice. Inactivation of Cdc42 in radial glial cells resulted in hydrocephalus and ependymal cell denudation. Taken together, these results highlight the importance of Cdc42 for ependymal cell differentiation and maintaining, and suggest that these functions likely contribute to the essential roles played by Cdc42 in the development of the brain.
Animals ; Brain ; metabolism ; pathology ; Cell Differentiation ; Cell Polarity ; Cerebral Cortex ; cytology ; metabolism ; Constriction, Pathologic ; Embryo, Mammalian ; metabolism ; Embryonic Development ; Ependyma ; cytology ; metabolism ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Humans ; Hydrocephalus ; metabolism ; pathology ; Integrases ; genetics ; metabolism ; Mice ; Mice, Knockout ; cdc42 GTP-Binding Protein ; genetics ; metabolism

OBJECTIVETo explore the molecular biological mechanism for tanshinone II A reversing left ventricular hypertrophy, it would be studying the effect of tashinone on the endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC) in the hypertrophic cadiocyte of rats suffered abdominal aorta constriction.

METHODSD rats were operated with abdominal aorta constriction and 8 rats were done with sham surgery. After 4 weeks, all rats were divided into 4 groups: myocardial hypertrophy group, low dose tanshinone II A group (10 mg x kg(-1) x d(-1)), high dose tanshinone II A group (20 mg x kg(-1) x d(-1)) and valsartan group (10 mg x kg(-1) d(-1) intragastric administration). 8 weeks later, the rats were used to measure the left ventricular mass index (LVMI) with the tissue of left ventricle and myocardial fiber dimension (MFD) by pathological section and HE stain, to detect the nitric oxide content by nitrate reductase, to detect the genic expression of eNOS by RT-PCR and to detect the activity of protein kinase C (PKC) by Western blotting.

RESULT1) The blood pressure in group myocardial hypertrophy [(186 +/- 13) mmHg] and tansginone II A [low and high dose (188 +/- 11,187 +/- 14) mmHg] was obviously higher than that in group sham surgery and valsartan group [vs (117 +/- 8, 136 +/- 15) mmHg, P < 0.01]. But there was no difference between group myocardial hypertrophy and group tanshinone II A (low and high dose). 2) The LVMI and MFD were obviously higher in group tanshinone II A low and high dose) and group valsartan than those in group sham surgery (P < 0.05), and lower than those in group myocardial hypertrophy (P < 0.01). 3) The NO level was obviously higher in group tanshinone II A (low and high dose) and group valsartan than that in group myocardial hypertrophy (12.78 +/- 1.66, 11.95 +/- 1.39, 12.26 +/- 2.08 vs 5.83 +/- 1.06) micromol x L(-1), (P < 0.01 ), and lower than that in group sham surgery (vs 19.35 +/- 1.47) micromol x L(-1), (P < 0.05). 4) The expressive level of eNOS mRNA and protein in myocardial hypertrophy group was less than that in other groups (P < 0.01). And valsartan group was less than tanshinone II A groups and sham surgery group (P < 0.05), but there were no difference among the two tanshinone II A groups and sham surgery group. 5) The level of PKC protein in group myocardial hypertrophy was obviously higher than that in all the other groups (1.291 +/- 0.117 vs 0.563 +/- 0.094, 0.605 +/- 0.051, 0.519 +/- 0.062, 0.827 +/- 0.086, P < 0.01), and the level in group valsartan was higher than that in group sham operation and group tanshinone II A (low and high dose).

CONCLUSIONNO/NOS system in local myocardium has close relationship with the pathological process for myocardial hypertrophy. Tanshinone II A can produce the pharmacological action to reverse myocardial hypertrophy by inhibiting the activity of PKC and promoting the genic expression of eNOS in local myocardium and the production of endogenous NO.

Animals ; Aorta, Abdominal ; pathology ; Benzofurans ; pharmacology ; Blood Pressure ; drug effects ; Cardiomyopathy, Hypertrophic ; complications ; enzymology ; physiopathology ; Constriction, Pathologic ; complications ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; drug effects ; enzymology ; Female ; Gene Expression Regulation, Enzymologic ; drug effects ; Heart Ventricles ; drug effects ; metabolism ; pathology ; physiopathology ; Male ; Myocytes, Cardiac ; drug effects ; enzymology ; pathology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; genetics ; metabolism ; Protein Kinase C ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats