[Initial experience of transcatheter edge-to-edge repair guided by only transesophageal echocardiography in the treatment of tricuspid insufficiency].

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

[Analysis of biofilm-forming ability and drug resistance for Hypervirulent Klebsiella pneumoniae].

Investigate the biofilm-forming ability and drug resistance of Hypervirulent Klebsiella pneumoniae (HvKP) to provide scientific basis for the treatment of HvKP-infection. A total of 96 Klebsiella pneumoniae strains isolated from clinical infection specimens in Changsha Central Hospital from January to December in 2021 were retrospectively collected, and the clinical data of patients were collected. The string test preliminarily distinguished between HvKP and classic Klebsiella pneumoniae (CKP). The biofilm-forming ability of clinical strains of Klebsiella pneumoniae (KP) was determined by microplate method. The Vitek 2 Compact automatic microbial identification/drug sensitivity analysis system was used for bacterial identification and drug sensitivity test. The clinical data of patients, biofilm forming ability and drug resistance in the HvKP group and those in the CKP group were compared and analyzed. The results showed that a total of 20 strains of HvKP were isolated from 96 non-repetitive KP, and the detection rate was 20.8%. HvKP mainly come from respiratory specimens, up to 75.0%.The prevalence of hepatobiliary diseases and the infection rate of multiple sites in patients with HvKP infection were higher than those in patients with CKP infection, and the difference was statistically significant(χ2=5.184,7.488;P=0.023,0.006).There was no significant difference between the two groups in terms of gender, age, ICU admission, hypertension, diabetes, coronary heart disease, lung disease, urinary system disease, central nervous system disease and laboratory test indexes (all P>0.05).17 (85.0%) strains of HvKP can form biofilm, including 2 strains with weak biofilm-forming ability (10.0%), 10 strains with moderate biofilm-forming ability (50.0%) and 5 strains with strong biofilm-forming ability (25.0%). Among the 76 CKP, 71 (93.4%) could form biofilm, including 13 (17.1%) with weak biofilm-forming ability, 30(39.5%) with moderate biofilm-forming ability and 28 (36.8%) with strong biofilm-forming ability. There was no significant difference in biofilm-forming ability between HvKP and CKP (χ2=1.470,P=0.225).The overall resistance rate of HvKP was not high, but a multi-resistant HvKP resistant to carbapenems was found. The detection rate of multi-resistant HvKP (5.0%) was lower than that of multi-resistant CKP (28.9%), and the difference was statistically significant (χ2=4.984, P=0.026).The resistance rate of HvKP to piperacillin/tazobactam, aztreonam, ciprofloxacin, levofloxacin, ceftazidime, cefepime, tobramycin, minocycline, doxycycline, and compound sulfamethoxazole was lower than that of CKP, and the difference was statistically significant (all P<0.05). In conclusion, most of hypervirulent Klebsiella pneumoniae can form biofilm in this study, but the difference of biofilm-forming ability is not obvious compared with classic Klebsiella pneumoniae. HvKP maintains high sensitivity to commonly used antibacterial drugs, but the drug resistance monitoring of the bacteria cannot be ignored.

[Comparison on the efficacy of Chinese-made novel-designed mechanical-locked and elastic self-locked transcatheter edge-to-edge repair system in the treatment of patients with functional mitral regurgitation].

Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.

[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[Spatiotemporal distribution of measles in China, 2001-2016].

Objective: To understand the spatial-temporal distribution and spatial clusters of measles cases in China. Methods: Measles incidence data was collected from the National Notifiable Disease Reporting System of Chinese Center for Disease Control and Prevention. The global and local spatial autocorrelation analyses were conducted by using software ArcGIS 10.2 and spatial-temporal scan was conducted by using software SaTScan 9.6. Results: A total of 1 012 537 cases of measles were reported in China from 2001 to 2016 and the annual incidence showed a sharp downward trend. There was global spatial clustering of measles cases during 2001-2004, 2005-2008, and 2009-2012, and their Moran's I coefficients were 0.29, 0.26, and 0.31, respectively. The results of local spatial autocorrelation analysis showed that there were high- high clustering areas of measles at all time periods, especially in western China. Guangdong province was detected as a separate high-low scattered area from 2005 to 2008 and no low-low clustering area was detected. The spatial-temporal scan statistics showed that there was a wide clustering area covering western, central and northern China, and Shanxi province and Guangxi Zhuang Autonomous Region from 2001-2008. Conclusion: The incidence of measles in China has a certain clustering in both space and time during 2001-2016, the results provide evidence for the development of future strategy of measles prevention and control in China.

[Trend analysis and prediction of viral hepatitis incidence in China, 2009-2018].

Objective: To explore the time series characteristics of 5 types of viral hepatitis in China and predict their incidence through effective models. Methods: The monthly incidence data of 5 types of viral hepatitis (A, B, C, D and unspecified) in China from 2009 to 2018 were collected for descriptive and time series analyses, decomposition methods were used to explore the seasonality in the form of seasonal indices and the long-term trend in the form of a linear regression model. Autoregressive integrated moving average (ARIMA) models were established for each type of viral hepatitis. Results: From 2009 to 2018, a total of 14 856 990 cases of viral hepatitis were reported, the seasonal index range of 5 types of viral hepatitis were all lower than 1, the seasonality of hepatitis E was significant, and its incidence was unimodal, but no obvious seasonality characteristics were observed for other four types of viral hepatitis. The incidences of hepatitis A, hepatitis E and unspecified hepatitis remained at lower levels, showing slow declines. Although the cases of hepatitis B accounted for the highest proportion (79.59%, 11 824 262/14 856 990) among 5 types of viral hepatitis, the decline was fastest (-0.01/100 000). The incidence of hepatitis C was on rise, and the rate of increase remained stable (0.005/100 000). The predicted incidences of 5 types of viral hepatitis in China from January 2009 to December 2018 fitted by ARIMA model were consistent with the actual incidences, and the mean absolute error percentage (MAPE) ranged from 3.756 8 to 8.068 3. Conclusions: Time series analysis on surveillance data is useful for better understanding the incidence of the viral hepatitis. The ARIMA model has good application value in the short-term prediction of viral hepatitis incidence in China.

[Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province, 2002-2018].

Objective: To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018. Methods: All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis. Results: 871 (40.1%) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1%) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7%) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions: HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

[Evaluation of tumor vascular normalization in colorectal cancer mouse mode induced by recombinant human endostatin by intravoxel incoherent motion diffusion-weighted magnetic resonance imaging].

Objective: To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods: The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg(-1)·d(-1) once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D(*)) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results: The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm(3) and (174.24±28.27)mm(3,) respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P<0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P>0.05). The D(*) values of the rhES group were (10.940±2.834)×10(-3)mm(2)/s and (12.940±2.801)×10(-3)mm(2)/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10(-3)mm(2)/s and (7.898±1.603)×10(-3)mm(2)/s of control group (P<0.05). Moreover, compared with control group, the D(*) value of rhES group was significantly lower in day 12 (6.848±1.460)×10(-3)mm(2)/s vs (9.950±2.596)×10(-3)mm(2)/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D(*) value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05). Conclusions: IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D(*) and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.

The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target.

BACKGROUND: Opioid receptors are implicated in cancer progression and long-term patient outcomes. However, the prognostic significance, underlying mechanisms, and therapeutic value of mu-opioid receptor (MOP) in hepatocellular carcinoma (HCC) remain unclear. METHODS: MOP expression in human biopsy HCC samples was evaluated using RNA microarrays, quantitative real-time polymerase chain reaction (qRT-PCR), and immunochemical analyses. Molecular and cellular techniques, including siRNA-mediated depletion and lentiviral vector-mediated overexpression, were used to elucidate the functions and mechanisms of MOP. The effect of the MOP agonist morphine in HCC was evaluated both in vitro and in vivo. The therapeutic value of MOP inhibitors in HCC progression and metastasis was investigated with in vitro experiments and subcutaneous and orthotopic HCC mouse models in vivo. RESULTS: Through microarray analysis and qRT-PCR, we identified that MOP is highly expressed in human HCC tumours. High MOP expression in HCC tumours was confirmed by immunocytochemistry and correlated with aggressive clinicopathological features and a worse prognosis. Depletion of MOP suppressed cell proliferation, migration, and invasion, whereas overexpression of MOP promoted cell growth and metastasis in human HCC cell lines. Both clinical and biological evidence revealed that MOP-mediated epithelial-mesenchymal transition promotes HCC metastasis and poor prognosis. Morphine promotes cell proliferation, migration, and invasion in vitro and in vivo in mouse models. More importantly, MOP inhibitors suppressed cell growth, invasion, and metastasis in vitro and in the subcutaneous and orthotopic xenograft models. CONCLUSIONS: MOP plays a key oncogenic function in hepatocarcinogenesis. Its overexpression is associated with poor prognosis in patients with HCC. Furthermore, MOP inhibitors may be a promising strategy for HCC therapy.

[Analysis on spatial distribution of tuberculosis in China, 2012-2014].

Objective: To analyze the spatial distribution of the incidence of tuberculosis (TB) in China from 2012 to 2014 and provide evidence for the prevention and control of TB. Methods: The database of TB in China from 2012 to 2014 was established by using geographical information system, the spatial distribution map was drawn, trend analysis and spatial autocorrelation analysis were conducted to explore the spatial distribution pattern of TB and identify hot areas. Results: The trend surface analysis showed that the incidence of TB decreased gradually from the west to the east in China, and the U type curve could reflect the TB distribution from the south to the north; Global spatial autocorrelation analysis showed the 2012-2014 global Moran's I were 0.366, 0.364 and 0.358 (P<0.01), suggesting that the incidence of TB had a spatial clustering in China; Local Getis-OrdG(i) spatial autocorrelation analysis by ArcGIS software showed that there was 11 cluster areas, 3 high incidence areas (Xinjiang, Tibet, Qinghai) and 8 low incidence areas (Beijing, Tianjin, Shanghai, Hebei, Inner Mongolia, Shanxi, Shandong, Jiangsu). Conclusion: The incidence of TB had obviously spatial clustering characteristic, the areas at high risk were mainly in the northwestern and plateau area in China.

[Value of perineural invasion in prostatectomy specimen in the assessment on tumor progression and prognosis].

OBJECTIVE: To assess perineural invasion in prostatectomy specimen(PNIp)on tumor progression and prognosis after radical prostatectomy. METHODS: Retrospective analysis including 502 prostate cancer patients admitted in Renji Hospital, School of Medicine, Shanghai Jiaotong University from December 2002 to May 2014 was studied.Differences of serum prostate specific antigen(PSA), Gleason score of prostate biopsy, Gleason score of prostatectomy specimen, tumor stage, capsular invasion, positive surgical margin, seminal invasion, pelvic lymph node metastasis, nadir PSA were analyzed in patients with PNIp and without PNIp. Logistic regression analysis, Log-rank test and Cox regression analysis was used to analyzed the data, respectively. RESULTS: There were 91 patients with PNIp(18.1%) and 411 patients without PNIp(81.9%). Differences of serum PSA, Gleason score of prostate biopsy, Gleason score of prostatectomy specimen, tumor stage, capsular invasion, seminal invasion, nadir PSA between the two groups were found(all P<0.05). In the multivariable logistic regression analysis, PNIp was independent predictor of Gleason score of prostate biopsy, Gleason score of prostatectomy specimen, tumor stage, capsular invasion(OR=1.515, 1.955, 2.069, 1.859, all P<0.05). One hundred and twenty-one patients with biochemical serum recurrence(26.7%). Serum PSA, Gleason score of prostate biopsy, Gleason score of prostatectomy specimen, tumor stage, PNIp, seminal invasion were related to biochemical serum recurrence(P<0.05). In the multivariable cox regression analysis, serum PSA, Gleason score of prostate biopsy, PNIp, seminal invasion were independent predictors of biochemical serum recurrence(HR=1.021, 1.441, 1.663, 3.257, all P<0.05). CONCLUSION: PNIp is the important predictor of the tumor progression and prognosis of prostate cancer.

Shock wave treatment enhances endothelial proliferation via autocrine vascular endothelial growth factor.

Extracorporeal cardiac shock wave (SW) therapy is an effective, safe, and non-invasive therapeutic strategy for severe coronary artery disease. Shock wave therapy might affect cardiac tissues because of its ability to promote angiogenesis. In this report, we investigated if the up-regulation of vascular endothelial growth factor (VEGF) by SW therapy is involved in cell proliferation in cultured endothelial cells. After human umbilical vein endothelial cells were treated with SW, the expression and secretion of VEGF as well as cell proliferation were analyzed. We also determined the mechanism underlying SW-induced the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) using western blotting. Our results demonstrated that SW treatment induced VEGF expression in endothelial cells in a hypoxia-inducible factor 1-independent manner. Up-regulation of VEGF expression led to an increase in its concentration in the cultured medium. The autocrine VEGF in the medium activated the ERK MAPK signaling, which in turn enhanced cell proliferation. Therefore, we concluded that VEGF mediates SW application-induced endothelial cell proliferation in a cell-autonomous manner.

Ethanolic extracts of Antrodia cinnamomea mycelia fermented at varied times and scales have differential effects on hepatoma cells and normal primary hepatocytes.

Mycelia of Antrodia cinnamomea (AC), an edible fungus native to Taiwan, were produced by submerged fermentation with various fermentation times in 250 mL, 5 and 500 L fermentors and were evaluated for the effect of fermentation products on the viabilities of Hep3B and HepG2 hepatoma cells and normal primary rat hepatocytes. The results showed that the ethanolic extracts of AC mycelia (from 250 mL fermentation for 8 wk and 5 and 500 L fermentations for 4 wk) possessed high antihepatoma activity. The IC(50) of ethanolic extract of AC mycelia fermented for 8 wk in a 250 mL fermentor against Hep3B and HepG2 cells were 82.9 and 54.2 microg/mL, respectively. Furthermore, the IC(50) for Hep3B and HepG2, treated with ethanolic extract of AC mycelia fermented for 4 wk in the 5 L fermentor were 48.7 and 3.8 microg/mL, respectively. Those treated with ethanolic extract of AC mycelia fermented for 4 wk in the 500 L fermentor were 36.9 and 3.1 microg/mL, respectively. No adverse effects of all samples on normal primary rat hepatocytes were observed.

EGF-IL-18 fusion protein as a potential anti-tumor reagent by induction of immune response and apoptosis in cancer cells.

We report here the generation and characterization of EGF-IL-18 fusion protein as an anti-tumor reagent. The epidermal growth factor (EGF) and interleukin-18 (IL-18) fusion protein was shown to induce interferon-gamma (IFNgamma) expression and secretion in KG-1 cells, and to promote PBMNC proliferation. It also stimulated activation of CD4+ T cells, and increased other immune responses. Moreover, EGF-IL-18 could induce significant tumor regression in SMMC-7721-xenografted Balb/c nude mice when administered together with peritumoral injection of X-ray-irradiated NK-92 cells, and this regression is associated with arresting of the tumor cells in G1 phase and induction of apoptosis.

Estimation of single-root surface area from true thickness data and from thickness derived from digital dental radiography.

OBJECTIVES: The prognosis of a tooth affected by periodontitis may depend on the amount of bone remaining around the root surface. The aim of this study was to find how the surface area of a single root is related to the true thickness data and the calculated thickness data from digital dental radiographs. METHODS: Eight extracted single-root teeth were digitized three-dimensionally for direct surface area measurement. Meanwhile, they were also exposed to a digital dental X-ray system. The true thickness of the tooth root was measured. The estimated circumference data were calculated from both the measured thickness and the thickness estimated from the digital image and then measured and estimated circumferences were compared. RESULTS: (1) The largest circumference difference mean for measured thickness and for estimated thickness was -4.94% (+/-0.07%) and 23.02% (+/-1.12%) respectively. (2) The largest 95% confidence interval for difference means for measured thickness and for estimated thickness was (-2.82%, -1.87%) and (-5.42%, 2.22%), respectively. CONCLUSIONS: When the thickness data are available, the surface area of a single-root tooth can be estimated to an error of less than 5%. Theoretically, the root thickness can be derived from the projected radiological image of the tooth. However, the error of estimated circumference from digital dental radiography may be over 20%. This error can be minimized if the estimated thickness from digital dental radiography can be made more accurate.

Deficiency of the cysteine protease cathepsin S impairs microvessel growth.

During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S-deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S-deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.

[Study of protective effect of leech, radix Salviae miltiorrhizae and its composite recipe on vascular endothelial cells in rats with blood stasis syndrome].

OBJECTIVE: To study the protective effect for Chinese medicine of promoting blood circulation and removing blood stasis (PBCRBS) on vascular endothelial cells (VEC) in rats, aiming at further research on the mechanism of blood stasis syndrome and PBCRBS. METHOD: Establishing a model of blood stasis with endothelial damage by means of giving rats an injection of adrenalin and making it swim in ice-cold water, then measuring the number of circulating endothelial cells (CEC) in whole blood and rheology. Moreover observing the change of the above indexes after the rats have taken Leech, Radix salviae miltrorrhizae (RSM) and its composite recipe for 5 days or 10 days. RESULT: It could increase the number of CEC accompanied by whole blood viscosity, fibrinogen and hematocrit in rats with blood stasis. But for groups taking Chinese medicine, the number of CEC was decreased distinctively and blood rheology was improved. CONCLUSION: The rat with blood stasis syndrome suffered from obvious injury of VEC. The Leech, RSM and its composite recipe could protect VEC.

Study on the supramolecular system of meso-tetrakis (4-sulfonatophenyl) porphyrin and cyclodextrins by spectroscopy.

The ability of beta-cyclodextrin (beta-CD), sulfurbutylether-beta-CD (SBE-beta-CD) and hydroxypropyl-beta-CD (HP-beta-CD) to break the aggregate of the meso-Tetrakis (4-sulfonatophenyl) porphyrin (TPPS4) and to form 2:1 inclusion complexes has been studied by adsorption and fluorescence spectroscopy. The formation constants are calculated, respectively by fluoremetry, from which the inclusion capacity of different CDs is compared and the inclusion mechanism of charged-beta-CD (SBE-beta-CD) is quite different from that of parent beta-CD. At lower pH, the complexation between HP-beta-CD and H2TPPS(2+)4 (the form of the diprotonated TPPS4) hampers the continuous protonation of the pyrrole nitrogen of TPPS4 and the hydrophobic cavity may prefer to bind an apolar neutral porphyrin molecule. 1HNMR data support the inclusion conformation of the porphyrin-cyclodextrin supramolecular system, indicating the interaction of meso-phenyl groups of TPPS4 with the cavity of CDs. For this host-guest inclusion model, cyclodextrin, being regarded as the protein component, which acts as a carrier enveloping the active site of heme prosthetic group within its hydrophobic environment, provides a protective sheath for porphyrin, creating artificial analogues of heme-containing proteins. However, the TPPS4, encapsulated within this saccharide-coated barrier, its physico-chemical, photophysical and photochemical properties changed strongly.