肾素血管紧张素转换酶抑制剂/受体阻滞剂对高血压伴心房颤动患者血清结缔组织和碱性成纤维细胞生长因子的影响

目的探究肾素血管紧张素转换酶抑制剂/受体阻滞剂(ACEI/ARB)治疗是否影响高血压伴心房颤动(AF)患者血清结缔组织生长因子(CTGF)、碱性成纤维细胞生长因子(bFGF)水平。方法回顾分析2010年9月至2012年2月中山大学孙逸仙纪念医院心血管内科收治的高血压病例,将高血压伴AF患者85例以及窦性心律(简称窦律)患者54例按是否接受ACEI/ARB治疗分成窦律对照组26例、治疗组28例以及AF对照组42例和治疗组43例,测定血清中CTGF、bFGF水平。结果 AF对照组血清CTGF、bFGF均显著高于窦律对照组(P均<0.05);窦律对照组与治疗组间血清CTGF、bFGF差异均无统计学意义(P均>0.05);AF治疗组血清CTGF、bFGF均明显低于对照组(P均<0.05)。结论高血压伴AF患者血清CTGF、bFGF均升高,ACEI/ARB治疗可降低其CTGF和bFGF水平。

Transforming growth factor-β and fibrosis

Transforming growth factor-β （TGF-β）, a prototype of multifunctional cytokine, is a key regulator of extracellular matrix （ECM） assembly and remodeling. Specifically, TGF-β isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-β expression in affected organs, and subsequent deregulation of TGF-β functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-β receptors. In particular, Smad proteins, TGF-β receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of type I collagen gene expression and in the development of fibrosis, demonstrated both/n vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes.

Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer

AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging Ⅰ+Ⅱ+Ⅲ (35.7% vs 65.2%, P = 0.0027). CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging Ⅰ+Ⅱ+Ⅲ. Over-expression of CTGF in human GC cells results in an increased aggressive ability.

Observational evidence of the Yellow Sea warm current

The Yellow Sea Warm Current (YSWC) is one of the principal currents in the Yellow Sea in winter. Former examinations on current activity in the Yellow Sea have not observed a stable YSWC because of the positioning of current meters. To further understand the YSWC, a research cruise in the southern Yellow Sea was carried out in the winter of 2006/2007. Five moorings with bottom-mounted acoustic Doppler current profilers (ADCP) were deployed on the western side of the central trough of the Yellow Sea. The existence and distributional features of the YSWC were studied by analyzing three ADCP moorings in the path of the YSWC in conjunction with conductivity-temperature-depth (CTD) data over the observed area in the southern Yellow Sea. The results show the following. (1) The upper layer of the YSWC is strongly influenced by winter cold surge; its direction and speed often vary along a south-north axis when strong cold surges arrive from the north. (2) The YSWC near the bottom layer is a stable northwest flowing current with a speed of 4 to 10 cm/s. By combining the analyses of the CTD data, we speculate that the core of the YSWC may lie near the bottom. (3) On a monthly average timescale, the YSWC is stably oriented with northward flow from the sea surface to the sea floor.

Connective tissue growth factor is overexpressed in human hepatocellular carcinoma and promotes cell invasion and growth

AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients(who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1(TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1(FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci(12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma(60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36(33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2(100 ng/mL) resulted in more of the cells transitioning into S phase(23.85 ± 2.35 vs 10.94 ± 0.23),and induced a significant migratory(4.0-fold) and invasive(5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.CONCLUSION:These data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target.

Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function

AIM： To determine the effect of hammerhead ribozyme targeting connective tissue growth factor （CCN2） on human hepatic stellate cell （HSC） function.METHODS： CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor （TGF）-β1 to the culture medium. Semiquantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen I, while protein levels of each molecule in cell /ysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry.RESULTS： In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen I, and an increase in produced and secreted CCN2 or extracellular collagen I protein levels, pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen I protein. Furthermore, the TGF-β1-induced increase in mRNA or protein for CCN2 or collagen I was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase.CONCLUSION： Endogenous CCN2 is a mediator of basal or TGF-β1-induced collagen I production in human HSCs and regulates entry of the cells into S phase.

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Muscularis mucosae in desmoplastic stroma formation of early invasive rectal adenocarcinoma

The origin of myofibroblasts or myofibroblastic cells in the desmoplastic stroma associated with carcinoma invasion has been controversial. In the early invasive area of a rectal adenocarcinoma reported here, an obvious transition between the muscularis mucosa and the bundles of eosinophilic stromal cells observed in the carcinomatous stroma was demonstrated both in morphology and in their cytoskeletal phenotype, which conceivably suggests that the smooth muscle cells of the muscularis mucosa could convert to the eosinophilic stromal cells, namely myofibroblasts. Moreover, type I procollagen was demonstrated in both protein and mRNA levels in the areas of eosinophilic stromal cells with a lesser degree of differentiated smooth muscle phenotype that showed a transition from the muscularis mucosa, implying that the myofibroblastic cells converted from smooth muscle cells of the muscularis mucosa could be responsible for type I collagen production. These findings suggest that the muscularis mucosae may not be a passive barrier through which colorectal carcinomas infiltrate into the submucosa, but may play an active role in the formation and remodeling of tumor stroma.

Connective tissue growth factor reacts as an IL-6/STAT3-regulated hepatic negative acute phase protein

AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients'sera.The inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) signalling.However,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 phosphorylation.An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.

Change of SPARC expression after chemotherapy in gastric cancer

Objective： The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine （SPARC） expression changes after chemotherapy in gastric cancer （GC） is unclear, qqais study investigated the influence of chemotherapy on SPARC expression in GC. Methods： Immunohistochemistry was used to analyze SPARC expression in 132 GC cases （including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy）. SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. Results： SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPAKC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy; gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. Conclusiou： SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.

Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis

AIM:To determine the utility of connective tissue growth factor(CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus(HBV)-induced chronic liver diseases(CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B(CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1(TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density(IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals(P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues(r = 0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B(r = 0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic(ROC) curves(AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.

Histological Investigation of Pelvic Symphysis in Holstein-Friesian Cattle

Knowledge of the changes in cattle pelvic symphysis during gestation and obstetrics gives valuable information about the age of optimal primary calving of cows. The aim of the study was to investigate the histological changes of pelvic symphysis in Estonian Holstein-Frisian＇s （EHF） of different ages. Eight EHF cows up to five years of their age were divided into three age groups： calved, in-calved and after calved bovines. Material for histological and histochemical investigation was taken from four places： （1） cranial part ofpubic bone; （2） pubo-ischiadic junction; （3） symphyseal eminence; （4） body of the interischiadic bone. In all study-groups, the cranial part of pubic bone consisted of cartilage. In pubo-ischiadic junction of calves connective tissue proper, fibrous and hyaline cartilage were noted. In in-calved cattle with gestation of 4-5 months and in after calved cattle group hyaline cartilage and bone tissue were noted, however in in-calved cattle with gestation of 7.5 months fibrous cartilage and connective tissue proper prevalated. In sympyseal eminence of calves connective cartilage osseous tissue was present. The region of interischiadic tissue proper and cartilage were noted; in other groups besides bone of calves consisted of connective tissue proper and fibrous cartilage, meanwhile in in-calved and after calved EHF＇s in the region hyaline cartilage and osseous tissue prevalated. These preliminary results demonstrate that the main changes in the pelvic symphysis histology, retardation of ossification, of EHF kines occur during the second-half of gestation in the pubo-ischiadic junction.

Study of MR image for involvement of paranasal sinuses in 56 cases with nasopharyngeal carcinoma

Objective： The aim of the study was to study the nuclear magnetic resonance image （MRI） feature for involvement of paranasal sinuses in patients with nasopharyngeal carcinoma （NPC）. Methods： The MRI of 56 patients with NPC and paranasal sinuses infringed were evaluated between December 2003 and August 2004. Results： Among them, 56 （100%） showed breakage in the wall of paranasal sinuses, 29 （51.8%） had thick mucous membrane in sinuses, 36 （64.3%） showed tumour invasion sinuses, 55 （98.2%） connected with primary carcinoma with the lesion, and 14 （25%） stored up fluid in si- nuses. On MRI scan technique, the positive ratios of diagnoses were 66.1%, 76.8%, and 98.2% respectively （P 〈 0.000） in the horizontal section, coronal section and sagittal section. And nearly 60% was in the TlWl and T2Wl, but 100% in strengthen scan. Conclusion： The findings of sinuses wall breakage, thick mucous membrane in sinuses, tumour invasion cavity connective mass, and same enhancement signal in MR image may indicate the paranasal sinuses involved by primary turnout. The sagittal section and enhanced MRI scans are helpful to diagnosis.

Histology of the Body Wall of the Piscine Leech, Cystibranchus mastacembeli （Hirudinea： Piscicolidae）

The histology of the body wall of the fish parasitic leech, Cystibranchus masstacembeli Rahemo, 1989 collected from freshwater eel, Mastacembelus simach was investigated. The body wall found consists of five layers, namely： cuticle, epidermis, dennis, muscle layer and botryoidal tissue. Cuticle is very thin layer, casting was evident in some sections, annulation was also seen in longitudinal sections, some time with sensory structures inside the crypts. Epidermis with hammer-shaped ceils, these cells are broad towards the outer and narrower towards their inner ends. In some sections intensively stained haematoxylin-eosin granules from which neck-like tubes leads with filiform projections outward to open to the exterior by minute apertures. Dermis is thicker than epidermis, with distinct large cells connected by a connective tissue and some muscle fibers, also large vacuoles or empty vesicles were detected which are haemocoelomic capillaries, which along with those situated in the epidermis make a respiratory membrane of this leech. Muscle layer consists of outer circular and inner longitudinal, the later is more abundant and occupies more space than the circular. Botryoidal tissue fills the spaces between body wall and inner intestinal or crop diverticulae, its tissue is composed of more or less rounded cells, more eosinophilic cytoplasm but with dark nuclei, intermingled with small oblique or radial muscle fibers, haemocoelomic spaces were also evident in this layer.

Evaluation of cellular responses associated with subcutaneous implantation of dental porcelain in a rat model

Biocompatibility of dental porcelain is of crucial importance to the long-term success of dental prostheses because of its close contact with oral tissues for extended periods. This investigation was aimed to evaluate cellular responses to locally produced dental porcelain （Universiti Sains Malaysia, Malaysia） after a short-term subcutaneous implantation in a rat model. Locally produced dental porcelains supplied in disc form were implanted subcutaneously into 12 Sprague-Dawley male albino rats, which were sacrificed in groups of 3 at 1, 2, 3 and 4 weeks after implantation. A semi-quantitative histological analysis of the tissue surrounding implanted discs was done under an image analyzer after staining with hematoxyline and eosin. The macrophage was clearly the dominant cell type at the implant surface at the first week after implantation, followed by a gradual decrease as the implantation period increased. On the contrary, fibroblasts and fibrocytes were the dominant cell types in the tissue surrounding the implanted discs at the third and fourth week after implantation with the appearance of mature collagen. From pathological point of view, the disappearance of inflammatory cellular responses and the well matured fibrous connective tissue surrounding the implanted discs indicate a satisfactory in vivo biocompatibility.

Cardiac Complications in Maroteaux-Lamy Syndrome： Case Report

MLS （Maroteaux-Lamy syndrome） or MPS VI （mucopolysaccharidosis VI） is an autosomal recessive pathology in which there is absence or low activity of the enzyme N-Acetylgalactosamine-4-Sulfatase, which hydrolyzes GAGs （glycosaminoglycans） in the body （mainly dermatan sulfate）. Consequently, there occurs lysosomal deposition of GAGs in connective tissue multisystemic. Myocardium and heart valves are frequently affected structures, presenting a direct correlation with the reports of complications and deaths. Case report： RGS, male, 3 years and 2 months, diagnosed with MPS VI from the first month of life, in weekly ERT （enzyme replacement therapy） since 4 months of age （inconstant）. At physical examination： normotensive, with holosystolic heart murmur 3＋/6＋ in mitral focus. Complementary tests： normal electrocardiogram, echocardiogram with pronounced mitral regurgitation, concentric left ventricular hypertrophy of moderate degree and mild aortic insufficiency. Discussion： Mitral valve disease is common in patients with MLS. Conditions such as cardiomyopathy, fibroelastosis, aneurysm and pulmonary hypertension may occur in these patients, indicative of morbidity and mortality. Early and constant ERT may be useful in slowing a progression of heart disease. Conclusions： follow-up with a cardiologist is important to evaluate the progression of cardiac complications in MPS VI. Constant and early ERT provides better prognosis for these patients.

Surgical use of fire needle for connective tissue external hemorrhoids：a case report

Objective： To report a patient with connective tissue external hemorrhoids who showed beneficial efficacy after fire needle was used for cutting off the connective tissue. Methods： Burn the front end of needle on the alcohol lamp until red and cut off the connective tissue external hemorrhoids quickly and accurately. Results： The connective tissue external hemorrhoid was totally removed and the patient showed a complete recovery after one and a half-year follow up. Conclusion： Fire needle can quickly eliminate perianal connective tissue, improve pain and bleeding, promote tissue regeneration and shorten the wound healing time, which may provide us a new idea for the surgical treatment of external hemorrhoids.

苦参碱对AngⅡ诱导的大鼠心肌成纤维细胞的影响及其机制研究

目的：研究苦参碱对血管紧张素Ⅱ（AngⅡ）诱导大鼠心肌成纤维细胞增殖和胶原合成的影响，探讨其抑制纤维化的机制。方法以AngⅡ诱导大鼠心肌成纤维细胞为研究对象，0.25～1.0 mmol/L浓度的Mat作用24 h后，采用四氮唑盐（MTT）法检测Mat对心肌成纤维细胞增殖的影响；羟脯氨酸测定胶原合成量；ELISA 法测定血管紧张素Ⅱ1型受体（AT1-R）、血管紧张素Ⅱ2型受体（AT2-R）、肿瘤坏死因子α（TNF-α）、转化生长因子β1（TGF-β1）和结缔组织生长因子（CTGF）的含量变化。结果 Mat以浓度依赖性方式抑制AngⅡ诱导的心肌成纤维细胞增殖和胶原合成（P＜0.01），并显著抑制AT1-R和CTGF的表达（P＜0.01）。结论 Mat能够显著降低AngⅡ诱导的心肌成纤维细胞中AT1-R和CTGF的含量，从而抑制细胞增殖和胶原合成增加，发挥出抗心肌纤维化的作用。

金雀异黄素通过抑制NF—κB信号通路延缓甲状旁腺素诱导的肾间质纤维化

目的 探讨金雀异黄素（Gen）对甲状旁腺素（PTH）引起的人近曲小管上皮细胞分泌结缔组织生长因子（CTGF）的调控作用.方法 应用实时定量PCR、Western印迹、报告基因等技术,观察Gen对PTH诱导人近端肾小管上皮细胞系HK-2细胞CTGF表达的影响.采用凝胶迁移实验（EMSA）技术检测PTH刺激HK-2细胞后NF-κB的DNA结合能力;使用信号通路抑制剂阻断信号通路以明确Gen发挥作用的机制.结果 HK-2细胞有基础量的CTGF mRNA和蛋白表达,PTH刺激后其表达量显著增加（均P＜0.05）,Gen能下调PTH诱导的HK-2细胞CTGF表达.10-10 mol/L PTH作用12 h后,荧光素酶活性较对照组显著升高（1.89±0.08比0.99±0.03,P＜0.01）.正常情况下,胞核内NF-κB处于无活性状态,PTH刺激HK-2细胞后NF-κB的DNA结合能力明显增强,10-10 mol/L PTH作用30 min时NF-κB活性达到高峰.NF-κB通路抑制剂PDTC预处理HK-2细胞后,PTH诱导细胞CTGF表达较PTH组明显下降（P＜0.01）.Gen抑制PTH所致的HK-2细胞NF-κB活化.结论 Gen通过阻断NF-κB信号通路抑制PTH诱导的HK-2细胞CTGF表达从而延缓肾间质纤维化.

阴唇变小了是什么原因

Q:我今年28岁,大概是一个星期前,右边的大阴唇上面好像长了个疙瘩,奇痒无比,我也没太在意,用手抓了抓。这几天不怎么痒了,但是我发现右边的大阴唇明显比左边小了很多。