Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Background/Aims@#Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. @*Methods@#In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. @*Results@#Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). @*Conclusion@#Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Ginsenoside Rg1 regulating BV2 microglia polarization in lipopolysaccharide-induced inflammatory response via peroxisome proliferator activated receptor γ / 解剖学报

[Abstract] Objective To establish an inflammation model by stimulating BV2 microglia by lipopolysaccharide, and to explore the regulation effect of ginsenoside Rg1 on inflammation by activating peroxisome proliferator activated receptor γ(PPARγ) receptor protein. Methods BV2 microglia were randomly divided into control group, model group, ginsenoside Rg1 group, rosiglitazone group and GW9662 group. The control group did not do any treatment, the model group was treated with 1 mg/ L lipopolysaccharide, and the other groups were treated with lipopolysaccharide added with 0. 4 mmol/ L ginsenoside Rg1, 10 μmol/ L rosiglitazone or 10 μmol/ L respectively. GW9662. The proliferation of BV2 microglia in each group was detected by CCK-8 method; PPAR-γ, phospho-NF-κB p65 (p-NF-κB p65), induced expression of inducible nitric oxide synthase(iNOS) and human arginase 1(ARG-1) proteins. ELISA was used to detect the inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8) and the content of tumor necrosis factor-α (TNF-α). Results Compared with the control group, the cell proliferation rate in the model group was significantly increased, and the contents of IL-1β, IL-6, IL-8 and TNF-α increased significantly. The result of immunofluorescence and Western blotting showed that iNOS and p-NF-κB p65 increased significantly, and the positive expressions of PPARγ and ARG-1 decreased significantly(both P<0. 01). The expression level of TNF-α decreased, the positive expressions of iNOS and p-NF-κB p65 decreased significantly, and the positive expressions of PPARγ and ARG-1 increased significantly(all P<0. 01). Conclusion Ginsenoside Rg1 inhibits the inflammatory response of BV2 microglia after lipopolysaccharide stimulation, and its mechanism may be related to the regulation of PPARγ/ NF-κB pathway to promote the M2-type polarization of microglia.

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Background/Aims@#Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. @*Methods@#We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. @*Results@#A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. @*Conclusion@#Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Chicken antibodies against venom proteins of Trimeresurus stejnegeri in Taiwan

The venom of bamboo vipers (Trimeresurus stejnegeri - TS), commonly found in Taiwan, contains deadly hemotoxins that cause severe envenomation. Equine-derived antivenom is a specific treatment against snakebites, but its production costs are high and there are some inevitable side effects. The aim of the present work is to help in the development of an affordable and more endurable therapeutic strategy for snakebites. Methods: T. stejnegeri venom proteins were inactivated by glutaraldehyde in order to immunize hens for polyclonal immunoglobulin (IgY) antibodies production. After IgY binding assays, two antibody libraries were constructed expressing single-chain variable fragment (scFv) antibodies joined by the short or long linker for use in phage display antibody technology. Four rounds of biopanning were carried out. The selected scFv antibodies were then further tested for their binding activities and neutralization assays to TS proteins. Results: Purified IgY from egg yolk showed the specific binding ability to TS proteins. The dimensions of these two libraries contain 2.4 × 107 and 6.8 × 107 antibody clones, respectively. An increase in the titers of eluted phage indicated anti-TS clones remarkably enriched after 2nd panning. The analysis based on the nucleotide sequences of selected scFv clones indicated that seven groups of short linkers and four groups of long linkers were identified. The recombinant scFvs showed significant reactivity to TS venom proteins and a cross-reaction to Trimeresurus mucrosquamatus venom proteins. In in vivo studies, the data demonstrated that anti-TS IgY provided 100% protective effects while combined scFvs augmented partial survival time of mice injected with a lethal amount of TS proteins. Conclusion: Chickens were excellent hosts for the production of neutralization antibodies at low cost. Phage display technology is available for generation of monoclonal antibodies against snake venom proteins. These antibodies could be applied in the development of diagnostic kits or as an alternative for snakebite envenomation treatment in the near future.(AU)

Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke

This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.

Intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats / 中国应用生理学杂志

OBJECTIVE@#To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats.@*METHODS@#Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method.@*RESULTS@#The levels of fast blood glucose and MDA in DM group were increased significantly(P＜0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P＜0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P＜0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P＜0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P＜0.05), and the mRNA expression of CAT was increased in the J+ group (P＜0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P＜0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P＜0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats.@*CONCLUSION@#Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.

СОНСГОЛЫН ХҮНД ХЭЛБЭРИЙН БУУРАЛТТАЙ ХҮНД CONNEXIN 26 ГЕНИЙН МУТАЦИЙГ ТОДОРХОЙЛСОН ТӨСӨЛТ АЖЛЫН ЗАРИМ ҮР ДҮН / Шинэ санаа Шинэ нээлт

@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearingimpaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.

Efficacy and prognostic factors of abiraterone combined with prednisone treating metastatic castration-resistant prostate cancer patients / 上海交通大学学报（医学版）

Objective· To assess the efficacy of abiraterone acetate (AA) plus prednisone treating metastatic castration-resistant prostate cancer (mCRPC) patients and analyze the prognostic factors for this treatment. Methods · The medical history of 112 patients with mCRPC treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, including 70 patients in the chemotherapy-na?ve setting and 42 in the post-chemotherapy setting, were retrospectively reviewed. Coprimary end points were prostate specific antigen progression-free survival (PSA PFS), radiographic PFS (rPFS) and overall survival (OS). Univariable and multivariable Cox analyses were performed to determine prognostic factors that were associated with PSA PFS, rPFS and OS. Results · At a median follow-up of 20.2 months, 59 (52.7%) patients had died. The median PSA PFS, rPFS and OS were 8.9 (7.8~10.0) months, 9.7 (9.0~10.4) months, and 22.2 (20.3~24.1) months, respectively. In multivariate analysis, previous chemotherapy, neutrophil lymphocyte ratio(≥3 vs<3),serum lactate dehydrogenase level(≥196 U/L vs<196 U/L)and ECOG PS(≤?1 vs 2)were independent predictors for PSA PFS and rPFS,and previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS. Conclusion·These results further support the favourable profile of AA plus prednisone in patients with mCRPC in China.Previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS.

МОНГОЛ ХҮНИЙ ТӨРӨЛХИЙН БОЛОН ОЛДМОЛ ХЭЛБЭРИЙН ДҮЛИЙН ҮЕИЙН CONNEXIN 26 ГЕНИЙН МУТАЦИЙГ ТОДОРХОЙЛСОН СУДАЛГААНЫ АЖЛЫН ЗАРИМ ҮР ДҮН / Шинэ санаа Шинэ нээлт

@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearing-impaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.

A fourfold increase of oesophageal variceal bleeding in cirrhotic patients with a history of oesophageal variceal bleeding

<p><b>INTRODUCTION</b>Large, recent population-based data for evaluating the predictors of oesophageal variceal bleeding (OVB) among cirrhotic patients is still lacking. This study aimed to determine the cumulative incidence of OVB among cirrhotic patients and identify the predictors of OVB occurrence.</p><p><b>METHODS</b>Patient information on 38,172 cirrhotic patients without a history of OVB, who were discharged between 1 January 2007 and 31 December 2007, was obtained from the Taiwan National Health Insurance Database for this study. All patients were followed up for three years. Death was the competing risk when calculating the cumulative incidences and hazard ratios (HRs) of OVB.</p><p><b>RESULTS</b>OVB was present in 2,609 patients (OVB group) and absent in 35,563 patients (non-OVB group) at hospitalisation. During the three-year follow-up period, the cumulative incidence of OVB was 44.5% and 11.3% in the OVB and non-OVB group, respectively (p < 0.001). Modified Cox regression analysis showed that the HR of OVB history was 4.42 for OVB occurrence (95% confidence interval [CI] 4.13-4.74). Other predictors for OVB occurrence included hepatocellular carcinoma (HR 1.16, 95% CI 1.09-1.24), young age (HR 0.98, 95% CI 0.98-0.98), ascites (HR 1.46, 95% CI 1.37-1.56), alcohol-related disorders (HR 1.20, 95% CI 1.12-1.28), peptic ulcer bleeding (HR 1.26, 95% CI 1.13-1.41) and diabetes mellitus (HR 1.14, 95% CI 1.06-1.23).</p><p><b>CONCLUSION</b>Cirrhotic patients have a fourfold increased risk of future OVB following the first incidence of OVB.</p>

The Effect of the First Spontaneous Bacterial Peritonitis Event on the Mortality of Cirrhotic Patients with Ascites: A Nationwide Population-Based Study in Taiwan

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) contributes to poorer short-term mortality in cirrhotic patients with ascites. However, it is unknown how long the effect of the first SBP event persists in these patients. METHODS: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify and enroll 7,892 cirrhotic patients with ascites who were hospitalized between January 1 and December 31, 2007. All patients were free from episodes of SBP from 1996 to 2006. RESULTS: The study included 1,176 patients with SBP. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in this group were 21.8%, 38.9%, 57.5%, and 73.4%, respectively. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in the non-SBP group were 15.7%, 32.5%, 53.3%, and 72.5%, respectively. After adjusting for gender, age, and other medical comorbidities, the adjusted hazard ratios of SBP for 30-day, 30- to 90-day, 90-day to 1-year, and 1- to 3-year mortality were 1.49 (95% confidence interval [CI], 1.30 to 1.71), 1.19 (95% CI, 1.02 to 1.38), 1.04 (95% CI, 0.90 to 1.20), and 0.90 (95% CI, 0.77 to 1.05), respectively, compared with the non-SBP group. CONCLUSIONS: The effect of SBP on the mortality of cirrhotic patients with ascites disappeared in those surviving more than 90 days after the first SBP event.

Liver cirrhosis as a real risk factor for necrotising fasciitis: a three-year population-based follow-up study

<p><b>INTRODUCTION</b>Necrotising fasciitis (NF) is often found in patients with diabetes mellitus, chronic renal failure, alcoholism, malignancy or liver cirrhosis. However, it remains unknown whether liver cirrhosis is an independent risk factor for the occurrence of NF. This study aimed to determine whether liver cirrhosis is an independent risk factor for the occurrence of NF, and to identify the relationship between severity of liver cirrhosis and occurrence of NF.</p><p><b>METHODS</b>The National Health Insurance Research Database, maintained by Taiwan's National Health Insurance programme, was retrospectively analysed, and the hospitalisation data of 40,802 cirrhotic patients and 40,865 randomly selected, age‑ and gender‑matched non‑cirrhotic control patients was collected. The medical records of all patients were individually followed for a three‑year period from the patients' first hospitalisation in 2004.</p><p><b>RESULTS</b>During the three‑year follow‑up period, there were 299 (0.7%) cirrhotic patients with NF and 160 (0.4%) non‑cirrhotic patients with NF. Cox regression analysis showed that liver cirrhosis was a risk factor for the occurrence of NF during the study period (hazard ratio 1.982; p < 0.001). Among cirrhotic patients, those with complicated liver cirrhosis had a higher risk for the occurrence of NF than patients with non‑complicated liver cirrhosis (hazard ratio 1.320; p = 0.028).</p><p><b>CONCLUSION</b>Cirrhotic patients had a higher risk for the occurrence of NF than non‑cirrhotic patients, and the risk for NF was especially high among patients with complicated liver cirrhosis.</p>

The Risk of Cellulitis in Cirrhotic Patients: A Nationwide Population-Based Study in Taiwan

BACKGROUND/AIMS: Cellulitis is a common infectious disease. However, the risk of cellulitis in cirrhotic patients is not well established, and whether liver cirrhosis is a risk factor for cellulitis remains unknown. This study evaluated the relationship between cellulitis and liver cirrhosis. METHODS: The National Health Insurance Database, which was derived from the Taiwan National Health Insurance program, was used to identify patients. The study group consisted of 39,966 patients with liver cirrhosis, and the comparison group consisted of 39,701 randomly selected age- and sex-matched patients. RESULTS: During the 3-year follow-up period, 2,674 (6.7%) patients with liver cirrhosis developed cellulitis, and 1,587 (4.0%) patients without liver cirrhosis developed cellulitis (p<0.001). Following a Cox's regression analysis adjusted for age, sex, and underlying medical disorders, the cirrhotic patients demonstrated a greater risk for the occurrence of cellulitis than the non-cirrhotic patients during the 3-year period (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.55 to 1.77; p<0.001). Additionally, cirrhotic patients with complications also had a greater risk for the occurrence of cellulitis than those patients without complications (HR, 1.23; 95% CI, 1.14 to 1.33; p<0.001). CONCLUSIONS: We conclude that cirrhotic patients have a greater risk of cellulitis than non-cirrhotic patients.

Different Clinical Characteristics Among Aeromonas hydrophila, Aeromonas veronii biovar sobria and Aeromonas caviae Monomicrobial Bacteremia

This study aimed to compare the clinical presentations of Aeromonas hydrophila, A. veronii biovar sobria and A. caviae monomicrobial bacteremia by a retrospective method at three hospitals in Taiwan during an 8-yr period. There were 87 patients with A. hydrophila bacteremia, 45 with A. veronii biovar sobria bacteremia and 22 with A. caviae bacteremia. Compared with A. hydrophila and A. veronii biovar sobria bacteremia, A. caviae bacteremia was more healthcare-associated (45 vs 30 and 16%; P = 0.031). The patients with A. caviae bacteremias were less likely to have liver cirrhosis (27 vs 62 and 64%; P = 0.007) and severe complications such as shock (9 vs 40 and 47%; P = 0.009) and thrombocytopenia (45 vs 67 and 87%; P = 0.002). The APACHE II score was the most important risk factor of Aeromonas bacteremia-associated mortalities. The APACHE II scores of A. caviae bacteremias were lower than A. hydrophila bacteremia and A. veronii biovar sobria bacteremia (7 vs 14 and 16 points; P = 0.002). In conclusion, the clinical presentation of A. caviae bacteremia was much different from A. hydrophila and A. veronii biovar sobria bacteremia. The severity and mortality of A. caviae bacteremia were lower than A. hydrophila or A. veronii biovar sobria bacteremia.

Investigation of morphology and anatomic variations of circle of Willis and measurement of diameter of cerebral arteries by 3D-TOF angiography / 生物医学工程学杂志

To observe the morphology and anatomic variations of the circle of Willis and its clinical significance. To measure and establish the normal reference parameters of average diameters of its component vessels in the healthy Chinese by using 3D-TOF MR angiograms and to determine whether age-or sex-related differences exists in the circle' anatomy. MRA was performed in 153 healthy subjects. According to its integrity, Willis'circle was divided into four types: (1) Type I, showing an intact circle. (2) Type II, having a complete anterior circulation but an incomplete posterior circulation. (3) Type III, having an incomplete anterior circulation but a complete posterior circulation. (4) Type IV, having an incomplete anterior and posterior circulation. Based on the development of the components of the circle, each type was subdivided into four subtypes: typical, variable, hypoplastic and mixed. The statistically significant differences were not found in each type or subtypes between the different age and sex groups. Result of 153 cases, Type I, II, III and IV was found in 53 (34.64%), 73 (47.71%), 8 (5.23%), and 19 (12.42%) respectively. The display rate of the anterior and the posterior communicating arteries was 87.58%o (134/153) and 65.34% (100/153) respectively. Display rate of fetaltype posterior cerebral artery(PCA) was 20.92%. 3D-TOF MR angiography has important clinical significance for evaluating morphology and anatomic variations of circle of Willis. The normal values of diameter of cerebral arteries on MR angiograms may play a reference role in diagnosing cerebral vascular diseases.

Determination of Seratrodast Concentration in Human Plasma by RP-HPLC / 中国药房

OBJECTIVE:To establish a RP-HPLC method for the determination of seratrodast concentration in human plasma.METHODS:The sample was determined on Lichrospher C18 column with the mobile phase consisted of 0.02 mol?L-1 potassium dihydrogen phosphate(containing 0.1% triethylamine,pH=5.0)-acetonitrile(70∶30)at a flow rate of 1.0 mL?min-1.The column temperature was 30℃ and the detective wavelength was set at 268 nm.RESULTS:The linear range of seratrodast was 28～5 600 ng?mL-1(r=0.999 5)with the lowest detection concentration at 28 ng?mL-1.The recovery rates of seratrodast at low,middle and high concentrations were 102.9%,100.4% and 99.7%,respectively;and both intra-day RSD and inter-day RSD were all less than 6%.CONCLUSION:The method developed in this study is applicable for the determination of plasma concentration and pharmacokinetic study of seratrodast.

Evaluating the therapeutic efficacy of vascular endothelium growth factor plasmid in treating dog cerebral infarction with diffusion-weighted magnetic resonance imaging / 中国组织工程研究

BACKGROUND: Vascular endothelium growth factor (VEGF) is an endothelium mitogen and angiogenic factor with strong potential during recovery from cerebral infarction (CI). Can such therapeutic effect be detected with magnetic resonance diffusion imaging?OBJECTIVE: To study the therapeutic efficacy of VEGF plasmid in treating focal cerebral infarction in a dog experimental model with the aid of diffusion- and hemodynamic-weighted magnetic resonance imaging (MRI),with the morphological results compared with those of immunohistochemical examination.DESIGN: Completely randomized controlled, double blind evaluation,analysis of variance, Pearson correlation analysis, follow-up for 2 weeks.SETTING: Department of Medical Iconography, the Second Affiliated Hospital of Hebei Medical University.MATERIALS: This study was carried out at the Department of Medical Iconography, the Second Affiliated Hospital of Hebei Medical University,between April 2001 and March 2002. Totally 18 healthy adult dogs weighing 10-15 kg were randomly divided into control group and experiment group with half in each.METHODS: All dogs were subjected to femoral intubation and then made into CI model by the occlusion of middle cerebral artery with an embolus injected through the internal carotid artery. Dogs in control group were put to death at postoperative 24 hours, 1 week and 2 weeks with three at each time point, while four dogs in experiment group were put to death at postoperative 1 week and five at 2 weeks. Dogs in experiment group received microinjection of 0.5 mL fluid containing pcD2/hVEGF121 (500-600 μg)instantly after operation, which was replaced with physical saline of the same volume at the same time point in control group. Then they were subjected to MRI scanning once an hour for 4 times, with the sequence of T1WI, T2WI, 3D-TOFMRA, DWI and CET1WI, which was repeated at postoperative 24 hours, 3 days, 1 week and 2 weeks. Based on the MR images, pathological focuses were selected for morphological observation of cells with the aid of HE staining, and CD34 IHC staining was used for counting micrangium, as well as VEGF staining for VEGF positive cells.Then the apparent distribution coefficient (ADC) was calculated, and the differences between different time points and groups were analyzed by analysis of variance. The number of capillaries and VEGF positive cells of each high-power field was counted, with the results compared with those of MR scanning so as to explore the correlation between MR signal changes and IHC results.MAIN OUTCOME MEASURES: ① The number of capillaries and VEGF positive cells in each high-power field was counted at postoperative 24 hours, 1 week and 2 weeks; ② MR images of each group.RESULTS: Data of the 18 dogs entered the final analysis. ① Diffusionweighted imaging (DWI) showed higher signals at infarctional region at postoperative 1 hour, which became strengthened as time went by. ②ADC decreased to (5.61 ±1.39) mm2/s at postoperative 3-4 hours, about 43% lower than that of the opposite hemisphere [(9.85±2.04) mm2/s]. It resumed to (9.83±1.11) mm2/s, but was still lower than the normal level.③ The subsequent MR scanning proved that ADC ratio presented an increasing tendency in contrast with the decreasing tendency at super-acute stage. The increment was even more marked in control group and the difference was significant at postoperative 2 weeks (P=0.032, 0.006). ④ The number of capillary positive cells on the affected side in experiment group was significantly higher than that in control group at postoperative 2 weeks [(28.80±3.29)/field, (20.70±4.47)/field, (P ＜ 0.01)]. ⑤ The number of VEGF positive cells on the affected side in experiment group was significantly higher than that in control group at postoperative 1 and 2weeks [(64.20±9.40)/field, (51.90±5.74)/filed; (72.70±6.98)/filed,(58.40±6.35)/field, (P ＜ 0.01)].⑥ The results of MR scanning and IHC were subjected to correlation analysis and revealed that ADC ratio was closely correlated with the number of capillary positive cells, with Pearson correlation coefficient being 0.679 (P ＜ 0.01). Moreover, the number of capillaries and the number of VEGF positive cells were significantly correlated (r=0.668, P ＜ 0.01).CONCLUSION:Morphological observation and IHC revealed that both the local capillaries and VEGF protein content increased markedly in timedependant manner due to VEGF plasmid gene therapy.Meanwhile,the change of ADC ratio was found to be closely correlated with the number of VEGF positive cells and the number of capillaries.