Effect of Valeriana jatamansi extract on fecal UPLC-MS/MS metabolomics in rats with diarrheal irritable bowel syndrome / 中国中药杂志

The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.

Novel Patched 1 Mutations in Patients with Gorlin-Goltz Syndrome Strategic Treated by Smoothened Inhibitor

We studied a family with Gorlin-Goltz syndrome. The novel mutations of our cases were located on the 21st exon of the PTCH1 gene (c.3450C>G). The father, who received a strategic 56-day vismodegib treatment for disease control, was the first patient with Gorlin syndrome treated with the hedgehog inhibitor in Taiwan. The lesions regressed gradually, with scar formation, and were subsequently removed via a wide excision. Further details are provided below.

Role of Methylprednisolone in Treatment of Spinal Cord Injured with Bone Marrow Mesenchymal Stem Cells Transplantation in Rats and Its Effect on the Expressions of Tumor Necrosis Factor-α and Interleukin-1β / 中国医学科学院学报

Objective To investigate the role of methylprednisolone (MP) in treatment of spinal cord injured (SCI) with bone marrow mesenchymal stem cells (BMSCs) transplantation in rats and its effect on the expressions of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) at the local tissues.Methods Forty male Sprague-Dawley(SD) rats were used to establish the models of SCI according to the modified Allen's contusion method and then divided into four groups (n=10 in each group) by using random numbers table:MP group,BMSCs group,BMSCs+MP group,and control group.MP was intravenously administrated immediately after SCI.BMSCs labeled by 5-bromo-2-deoxyuridine(BrdU)were transplanted into the injured sites of spinal cord after two hours of SCI.On the 1 st,7 th,and 14th days after SCI,when functional outcome measurements were evaluated by the Basso-Beattie-Bresnahan (BBB) score.On the 14th day after treatment,the spine cord tissues were harvested for the TNF-α/IL-1β immunohistochemistry,and Tunel staining method was used to detect cell apoptosis rate.BrdU-positive BMSCs were examined in BMSCs group and BMSCs+MP group.Results Functional recovery of hind limb in MP+BMSCs group was the best among the four group.On the 1 st day after injury,the BBB scores showed no significant difference among four group(χ=1.0756,P=0.7829).On the 7th and 14th day,the BBB score of MP+BMSCs group was significantly higher than MP group (χ=17.7186,P=0.0002;χ= 24.7259,P<0.0001) and BMSCs group (χ=15.8110,P=0.0024;χ=25.6014,P<0.0001),respectively.The BBB score of the control group was significantly lower than MP group (χ=8.3265,P=0.0325;χ=13.5060,P=0.0062) and BMSCs group (χ=14.1166,P=0.0036;χ=8.9613,P=0.0299),respectively.On the 14th day,immunohistochemical staining presented that the TNF-α and IL-1β-positive cells in MP+BMSCs group were significantly lower than MP group (q=5.573,P=0.0004;q=4.596,P=0.0025) and BMSCs group (q=13.780,P<0.0001;q=8.456,P<0.0001),and control group was significantly higher than MP group (q=14.710,P<0.0001;q=6.710,P<0.0001) and BMSCs group (q=6.502,P=0.0001;q=2.849,P=0.0514).Tunel staining showed the apoptotic rate of spinal cord cells in four group were (48.47±5.70)%,(31.95±3.58)%,(41.39±2.33)%,and (23.48±2.69)%.The number of apoptotic cells in MP+BMSCs group was least in four groups;compared with the control group,the apoptotic rate significantly decreased in MP group (q=14.840,P<0.0001) and BMSCs group (q=6.716,P=0.0002);compared with the MP+BMSCs group,the apoptotic rate was significantly increased in the MP group (q=7.332,P=0.0001) and BMSCs group (q=15.460,P<0.0001). BrdU staining revealed BrdU-positive rate in MP+BMSCs group [(9.3000±0.5175)%] was significantly higher than that in BMSCs group [(6.6000±0.3399)%](t=4.361,P=0.0004).Conclusion MP can improve the function of the hind limbs of SCI rats treated with BMSCs transplantation and lower the expressions of TNF-α and IL-1β in injured tissue.

Titanium Elastic Bone Nail in Treatment of 45 Cases of Children Unstable Double Radius and Ulna Fracture / 昆明医科大学学报

Objective To evaluate the clinical outcome and discuss the method of treatment both-bone forearm fracture in children (4 to 15 years old) with elastic intramedullary nail (EIN).Methods We retrospectively analyzed the clinical result of forty-five cases to treat both-bone forearm fracture in children (4 to 15 years old) with elastic intramedullary nail from April,2008 to June,2014.Then we Discussed and analyzed the complication,surgery technique,limb function.Patients were followed up for more than 24 to 30 months after the surgery to continuously evaluate the limb function and fracture healing by physical examination and x-ray image.Results There were 38 children with excellent recovery,7 good and no fair by followed up for 24 to 30 months,9 cases with observed complication due by prominent nail ends,3 patients slightly declined after the surgery,1 patient was observed with ulna fracture delayed recovery during 3 to 8 months of fracture healing.Apposition rate in all cases was ＞50％ in anterior-posterior view and the apposition rate ＞90％ in lateral view.No fracture of ESIN,Nerve injuries,severe displacement were observed during this study.Conclusion The elastic intramedullary nail is a good method to treat children both-bone forearm fracture with lower surgery technique,minimall invasion,if less complications,does not interfere with growth,has good forearm function recovery.

Long-term outcomes of carotid artery stenting versus endarterectomy for carotid stenosis: A meta-analysis of randomized controlled trials / 国际脑血管病杂志

ObjectiveTo evaluate the long-term outcomes of carotid endarterectomy versus carotid artery stenting for carotid stenosis.MethodsPubMed, EMBASE, and the Cochrane databases were retrieved.The randomized controlled trials of comparing CEA with CAS in patients with carotid artery stenosis were enrolled.The data such as the research basic characteristics and the long-term outcomes including stroke or death combined endpoints, any stroke or any death were extracted.The Stata software was used to conduct statistical analysis.ResultsA total of 7 randomized controlled trials and 8 210 patients were included.The median follow-up time was 2-7.4 years.The overall quality of the included studies was high and the risk of bias was low.The meta-analysis showed that the risks of the combined endpoint of stroke or death (hazard risk [HR] 1.21, 95% confidence interval [CI] 1.04-1.39), any stroke (HR 1.32, 95% CI 1.15-1.51) and ipsilateral stroke (HR 1.26, 95% CI 1.02-1.55) in the CAS group were significantly higher than those in the CEA group;the risks of death (HR 1.06, 95% CI 0.95-1.18), disabling stroke (HR 1.23, 95% CI 0.95-1.60), non-ipsilateral stroke (HR 1.12,95% CI 0.81-1.55) and restenosis (HR 1.18,95% CI 0.91-1.52) were not significantly different between between the CAS group and the CEA group.Conclusions CAS and CEA are associated with similar risks of long-term death, disabling stroke, non-ipsilateral stroke and restenosis.The risks of long-term combined endpoint of stroke or death, any stroke and ipsilateral stroke significantly higher with CAS.These results suggest that CEA remains the treatment of choice for carotid stenosis.

Endovascular mechanical thrombectomy for anterior circulation stroke：a meta-analysis of randomized controlled trials / 国际脑血管病杂志

Objective To evaluate the efficacy and safety of endovascular mechanical thrombectomy in patients with anterior circulation stroke. Methods PubMed, EMBASE, Cochrane database, Clinical Trials and the related supplement resources were retrieved. The randomized controled trials for comparing intravenous thrombolysis and endovascular mechanical thrombectomy in patients with anterior circulation stroke were selected. The bias risk assessment was performed. The basic characteristics of studies and the clinical outcome data at day 90, including good outcome (defined as the modified Rankin scale score 0-2), death and symptomatic intracranial hemorrhage (sICH) were extracted. Review Manager 5.3 software was used to conduct the statistical analysis. Results A total of 10 articles were enroled, including 1 557 patients in the endovascular mechanical thrombectomy group and 1 359 in the intravenous thrombolysis group. The overal quality of the included trials was higher. The risk of bias was lower. The good outcome rate in the endovascular mechanical thrombectomy group was significantly higher than that in the intravenous thrombolysis group (odds ratio [ OR] 2. 15, 95% confidence interval [ CI] 1. 34-3. 46; P < 0. 01). The death risk at day 90 was significantly lower than that in the intravenous thrombolysis group (OR 0. 86, 95% CI 0. 69-1. 06; P = 0. 16), and there was borderline statistical significance for the risk of sICH (OR 1. 35, 95% CI 1. 00- 1. 84; P = 0. 05 ). Conclusions The effectiveness of the endovascular mechanical thrombectomy is superior to the intravenous thrombolysis in patients with anterior circulation stroke;however, in terms of safety, further evaluation is needed.

A new anti-hypoxia sesquiterpene from the rhizome of Petasites japonicus / 药学学报

A new sesquiterpene, bakkenolide-Ⅵa (1), was isolated from the rhizome of Petasites japonicas (Sieb. et Zucc.) Maxim. The structure was characterized on the basis of various NMR (1H, 13C, 1H-1H COSY, HMQC, HMBC and NOESY) and mass spectrometry data. Bakkenolide-Ⅵa showed potent cerebral hypoxia-ischemia protective activity in mice subjected to decapitation through prolonging the survival time and gasping time. It also exhibited a protective activity against hypoxia injury in PC12 cells in anaerobic culture by inhibition of lactate dehydrogenase (LDH) release.

Comparison of wavefront aberrations under cycloplegic, scotopic and photopic conditions using WaveScan / Comparação de aberrações de frente de onda sob cicloplegia, condições escotópica e fotópica usando WaveScan

PURPOSE: To evaluate the differences of wavefront aberrations under cycloplegic, scotopic and photopic conditions. METHODS: A total of 174 eyes of 105 patients were measured using the wavefront sensor (WaveScan® 3.62) under different pupil conditions: cycloplegic 8.58 ± 0.54 mm (6.4 mm - 9.5 mm), scotopic 7.53 ± 0.69 mm (5.7 mm - 9.1 mm) and photopic 6.08 ± 1.14 mm (4.1 mm - 8.8 mm). The pupil diameter, standard Zernike coefficients, root mean square of higher-order aberrations and dominant aberrations were compared between cycloplegic and scotopic conditions, and between scotopic and photopic conditions. RESULTS: The pupil diameter was 7.53 ± 0.69 mm under the scotopic condition, which reached the requirement of about 6.5 mm optical zone design in the wavefront-guided surgery and prevented measurement error due to the pupil centroid shift caused by mydriatics. Pharmacological pupil dilation induced increase of standard Zernike coefficients Z3-3, Z4(0) and Z5-5. The higher-order aberrations, third-order aberration, fourth-order aberration, fifth-order aberration, sixth-order aberration, and spherical aberration increased statistically significantly, compared to the scotopic condition (P<0.010). When the scotopic condition shifted to the photopic condition, the standard Zernike coefficients Z4(0), Z4², Z6-4, Z6-2, Z6² decreased and all the higher-order aberrations decreased statistically significantly (P<0.010), demonstrating that accommodative miosis can significantly improve vision under the photopic condition. Under the three conditions, the vertical coma aberration appears the most frequently within the dominant aberrations without significant effect by pupil size variance, and the proportion of spherical aberrations decreased with the decrease of the pupil size. CONCLUSIONS: The wavefront aberrations are significantly different under cycloplegic, scotopic and photopic conditions. Using the wavefront sensor (VISX WaveScan) to measure scotopic wavefront aberrations is feasible for the wavefront-guided refractive surgery.

OBJETIVO: Avaliar as diferenças de aberrações de frente de onda, em diferentes condições pupilares: sob cicloplegia, escotópica e fotópica. MÉTODOS: Um total de 174 olhos de 105 pacientes foram avaliados utilizando o sensor de frente de onda (WaveScan® 3.62) em diferentes condições pupilares: sob cicloplegia 8,58 ± 0,54 mm (6.4 mm-9.5 mm), escotópica 7,53 ± 0,69 mm (5,7 mm - 9,1 mm) e fotópica 6,08 ± 1,14 mm (4,1 mm - 8,8 mm). Diâmetro da pupila, coeficientes de Zernike, RMS ("Root Mean Square") das aberrações de alta ordem e as aberrações dominantes foram comparados entre as condições sob cicloplegia e escotópica, e entre as condições escotópica e fotópica. RESULTADOS: O diâmetro da pupila foi 7,53 ± 0.69 mm sob a condição escotópica e atingiu a exigência de cerca de 6,5 mm de zona óptica na cirurgia baseada em análise de frentes de ondas, evitando erros de medição consequentes à mudança de centroide pupilar provocada por midriáticos. A dilatação farmacológica da pupila induziu aumento dos coeficientes de Zernike Z3-3, Z4(0) e Z5-5. As aberrações de mais alta ordem (terceira, quarta, quinta e sexta ordem) e a aberração esférica aumentaram de forma estatisticamente significativa, em comparação com a condição escotópica (P<0,010). Quando a condição escotópica se mudou para a condição fotópica, os coeficientes de Zernike Z4(0), Z4², Z6-4, Z6-2, Z6² e todas as aberrações de alta ordem diminuíram de forma estatisticamente significativa (P<0,010), demonstrando que a miose acomodativa pode significativamente melhorar a visão sob a condição fotópica. Sob as três condições, a aberração coma vertical apareceu mais frequentemente dentro das aberrações dominantes, sem influência significativa da variação do tamanho da pupila, e a proporção de aberração esférica diminuiu com a diminuição do tamanho da pupila. CONCLUSÕES: As aberrações de frente de onda são significativamente diferentes sob cicloplegia, condições escotópica e fotópica. O uso do sensor de frentes de onda (VISX WaveScan) para medir as aberrações de frente de onda escotópicas é uma opção viável para a cirurgia refrativa baseada em análise de frentes de onda.

Imaging and biodistribution of 99Tcm labeled cyclic RGD peptide in nude mice with xenografted lung adenocarcinoma / 中华核医学杂志

ObjectiveTo synthesize 99Tcm labeled hydrazine-nicotinamide ( HYNIC)-c (RGDfK)and evaluate its biodistribution and imaging in the severe combined immunodeficiency (SCID) nude mice bearing human lung adenocarcinoma.Methods( 1 )Tcm-HYNIC-c(RGDfK) was prepared by a two-step method using tricine and ethylenediamine diacetate (EDDA) as coligands and HYNIC as the dual functional chelator.The bioactivity of 99Tc m-HYNIC-c (RGDfK) was measured by cell binding experiments.(2) The nude mice bearing human A549 lung adenocarcinoma were randomly divided into 7 groups with 5 in each group.The 7 th group was the competitive inhibition control group and was administrated 100 μg HYNIC -c (RDGfK) 30 min earlier before the injection of 99Tcm-H Y N IC-c ( RGDfK ).The nude mice were scanned at 0.5,1,2,4,8 and 12 h respectively after intravenous injection of 7.4 MBq 99Tcm-HYNIC-c(RGDfK).The biodistribution of the agent was measured as ％ ID/g.The uptake ratio of tumor to muscle (T/NT) was also measured by placing ROI on 99Tcm-HYNIC-c(RGDfK) SPECT imaging.(3)Gamma imaging was performed in 6 mice including 3 in the competitive inhibition control group at 0.5,1,2,4,8 and 12 h post injection.ResultsThe labeling yield of 99Tcm-HYNIC-c(RGDfK) was more than 90％,and the radiochemical purity was more than 95％.99Tcm-HYNIC-c(RGDfK) can specifically bind with A549 adenocarcinoma cells with a binding rate up to 36.14％.Biodistribution study showed that the uptake in the kidney was above 20 ％ ID/g during 0.5 - 8 h post injection.The ％ ID/g in tumor was 10.52 ± 1.48 at 0.5 h,17.26 ±2.81 at 8 h,and 8.93 ±0.90 at 12 h.However,the ％ ID/g in tumor was only 2.29 ±0.85 in the competitive inhibition control group at 0.5 h.The highest T/NT was 6.87 at 8 h by the ROI analysis.Xenograffted tumors could be visualized at 1 h and delineated more clearly from 4 to 8 h post injection of 99Tcm-HYNIC-c(RGDfK).Conclusions99 Tcm-HYNIC-c (RGDfK) can be readily synthesized.Its binding with A549 lung adenocarcinoma cells is specific and the binding rate is high.

Recent progress in establishment and application of animal models of cerebral arteriovenous malformation / 国际脑血管病杂志

A cerebral arteriovenous malformation is a congenital disorder characterised by an abnormal connection between the arteries and the veins in the brain. It causes intracranial bleeding, seizures, severe headache, and progressive neurological deficits. The therapeutic strategies were usually established on the basis of clinical experiences due to lack of ideal models of arteriovenous malformation in the past .In order to further increase the success rate of surgery and decrease complications, this article reviews the advances in establishment and application of animal models of cerebral arteriovenous malformation in recent years.

Optimization of antibiotics in combination / 中华烧伤杂志

<p><b>OBJECTIVE</b>To evaluate the antibacterial activity of Ciprofloxacin, Amikacin in combination with beta-lactams against Pseudomonas aeruginosa strains in vitro, to optimize treatment regime for antibiotics on the basis of pharmacokinetics (PK)/pharmacodynamics (PD) and drug sensitivity tests. Methods With checkerboard titration method, the minimal inhibitory concentrations (MIC) of a combination of antibiotics in different concentrations for 33 clinically isolated Pseudomonas aeruginosa strains were determined by broth dilution. Fractional inhibitory concentrations (FIC) were calculated for judging synergic effect of antibiotics.</p><p><b>RESULTS</b>The combination of Amikacin and Ceftazidime showed synergic effects (accounting for 57.6%). The combinations of Ciprofloxacin with Ceftazidime, Cefepime, Imipenem/Cilastatin, Meropenem showed synergic or additive effect. In the study with PK/PD, C(max)/MIC was the principal parameters for evaluation of aminoglycoside and fluoroquinolone antibiotics, while T > MIC was the principal parameter to be used to evaluate beta-lactams antibiotics.</p><p><b>CONCLUSION</b>When antibiotics are used in combination, MICs can be reduced significantly and antibacterial activities are enhanced remarkably. The combination of antibiotics results mainly in synergic or additive effect, and no inhibitory effect is observed. PK/PD analysis plays an important role in planning optimal combination regime to raise clinical efficacy.</p>

Intra-Arterial Thrombolysis and Stenting for Acute Basilar Artery Occlusion / 国际脑血管病杂志

Objectire:To explore and evaluate the predictors for the prognosis of acute besilar artery occlusion(BAO)and the clinical efficacy of intra-arterial thrombolysis and stenting for BAO.Methods:Intra-arterial thrombolysis was administered with recombinant tissue plasminogen activator or urokinase in 52 patients with BAO within 3 to 48 hours.Stenting was performed in patients whose partial recanalization of residual stenosis＞50%after the thrombolysis.National Institutes of Health Stroke Scale(NIHSS)score was measured before the procedure,and the modifled Rankin scale(mRS)score was obtained at 3 months after the procedure.The clinical data were evaluated with the multivariable stepwise logistic regression analysis and Fisher's exact test.Results:Complete recanalization achieved in 24 patients(46.2%),partial recanalization in 16 patients(30.7%),and non-recanalization in 12 patients(23.1%).mRS scores:22 patients(42.3%)had a favorable outcome,32 survived(61.5%),and 20 died (38.5%).The prognosis of BAO was significantly correlated with the NIHSS score(P＜0.01),therapeutic time window (P ＜0.05) and recanalization level (after the thrombolysis and stenting)(P＜0.01 );the good recanalization after the intra-arterial thrombolysis was significantly correlated with the NIHSS score (P ＜0.01) and therapeutic time window (P ＜0.05).Multivariate analysis showed that the NIHSS score ＜ 14 (P ＜ 0.01 ) and good recanalization could independently predict the favorable prognosis of BAO.Conclusions:The NIHSS score ＜ 14 and good recanalization were the independent predictors for good prognosis of BAO.The rapid and timely treatment of BAO with intra-arterial thrombolysis and stenting is a safe and effective measure.

Response of early stage bulky cervical squamous carcinoma to preoperative adjuvant chemotherapy / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the potential role of preoperative adjuvant chemotherapy on early stage cervical squamous carcinoma with bulky tumor.</p><p><b>METHODS</b>One hundred and forty-five patients with cervical squamous cancer stages Ib-IIa were investigated, among which 17 patients with bulky tumors (> or = 4 cm) were managed by cisplatin-based chemotherapy for 1-2 courses followed by radical hysterectomy and pelvic lymphadenectomy (BC group). The change of tumor size, pelvic lymph nodes metastasis, cervical wall invasion, the involvement of surgical specimen margin, and the blood loss during operation were assessed after operation and compared with those in 51 patients with bulky tumors (BN group) and 77 patients with small local tumors (S group) who underwent surgery directly.</p><p><b>RESULTS</b>(1) The tumor size of 17 patients in BC group were decreased in various degrees after chemotherapy, with 13 patients of clinical effectiveness (76.47%). And the responsiveness pertained to neither histological differentiation nor size of local tumors. (2) Post-operative histology has showed that patients in BC and BN group have higher incidence of lymph node metastasis and deep cervical infiltration (5/68 and 3/68, respectively) than in S group (1/77 and 1/77, respectively) while with no statistical significance. (3) Blood loss during operation in BC group was less than BN and S group. (4) Seventeen patients, including those underwent surgeries of vaginal prolongation and/or ovarian transposition, appeared disease-free survival within the follow-up time.</p><p><b>CONCLUSIONS</b>Most of patients with bulky early stage cervical squamous carcinoma are sensitive to cisplatin-based chemotherapy, which could greatly reduce local tumor size and in turn facilitate the following operation by well controlling blood loss.</p>

Study on preparation of papaverine-gelatin microspheres and its release in vitro / 医学研究生学报

Objective To sustain drug concentration of papaverine in subarachnoid for treatment of vasospasm following subarachnoid hemorrhage and confirm whether controlled releasing system is appropriate for the prevention of vasospasm following subarachnoid hemorrhage.To prepare appropriate gelatin microspheres by optimizing experiment conditions,load them with papaverine and observe its release characteristics in vitro.Methods Degradable gelatin was used as a carrier with liquid paraffin as oil phase and Span-80 as emulsifier.Orthogonal experimental design was introduced to optimize the preparation conditions of the blank gelatin microspheres.Furthermore,papaverine gelatin microspheres were prepared using improved emulsified cold-condensation method.Results After optimizing,microspheres with good shape,smooth surface and narrow size distribution were prepared.The amount of drug carried by microspheres was 28%.Studies on the release in vitro showed that newly no initial burst release could be seen,the drug could be released slowly in two weeks.Conclusion The preparation procedure established was stable and practical,and the microspheres obtained showed good sustained-release characteristics.