To screen potential hamster chymase 2 inhibitors, a high-throughput screening (HTS) model was established. Recombinant hamster chymase 2 with active form was cloned and expressed in E. coli. The HTS model with total volume of 50 microL in 384-well microplate was based on fluorescence analysis and was proved sensitive as well as specific (Z' = 0.84). A total of 40 080 samples (including 28 060 compounds and 12 020 natural products) were screened, and 613 samples with inhibition greater than 90% were selected for further rescreening. Finally, compounds J16647 and J16648 were identified with high inhibitory activity on chymase 2, and whose IC50 values were 0.823 and 0.690 micromol x L(-1), respectively.

To screen potential human soluble protein tyrosine phosphatase 1B (PTP1B) inhibitors, a high-throughput screening (HTS) model in 384-well microplate with total volume of 50 microL was established. Recombinant PTP1B was cloned and expressed in E. coli. with its specific substrate 4-nitrophenyl phosphate disodium salt hexahydrate (PNPP). The HTS model was based on enzyme reaction rate with enhanced sensitivity and specificity (Z' = 0.78). A total of 24,240 samples were screened, among them 80 samples with inhibition greater than 70% were selected for further rescreening. Finally, six compounds with high inhibitory activity were identified, whose IC50 values were 21.58, 18.39, 15.37, 11.92, 37.27, and 36.61 microg x mL(-1), separately. The results indicated that the method was stable, sensitive, reproducible and also suitable for high-throughput screening.

目的探讨应用非手术方法治疗老年患者腰椎管狭窄症的疗效。方法对74例老年(>60岁)腰椎管狭窄的患者采用手法矫正椎体的假性滑移、药物治疗、适当的腰背肌功能锻炼综合治疗。随访至少2年。采用自定标准评定疗效。结果优(无疼痛及间歇性跛行,无功能限制,不用止痛剂)34例,良(偶然疼痛及间歇性跛行,轻度功能受限,偶尔使用止痛剂)27例,一般(中度的疼痛及间歇性跛行,中度功能限制,无运动,经常使用止痛剂)11例,差(中度每天疼痛及间歇性跛行,或偶尔严重疼痛,每天日常生活活动受限,应用强止痛剂)2例。结论对老年腰椎管狭窄症采取综合的非手术方法能取得一定疗效。

Objective To investigate the effect of norepinephrine infusion at 0.03-0.3 μg·kg-1 ·min-1 on renal function in patients undergoing kidney transplantation. Methods Thirty-two ASA Ⅲ or Ⅳ patients aged 22-64 yr weighing 44-88 kg undergoing kidney transplantation were studied. Dialysis was performed within 36 h before operation. Blood pressure was fairly stable. Combined spinal-epidural anesthesia (CSEA) was performed. Spinal anesthesia was performed at L2,3 interspace and hyperbaric 0.5% bupivacaine 10-15 mg was injected into the subarachnoid space. The upper level of sensory block measured by pin-prick reached T6. Epidural catheter was placed at T11,12 interspace and 1% ropivacaine was given intermittently. The patients were randomly allocated into preoperative baseline level (increase or decrease amplitude ＜ 10% of baseline level) by dopamine or norepinephrine infusion during operation. Venous blood samples and urine samples were obtained at the end of operation and 12 h after operation for determination of serum concentrations of cystatin C and β2-microglobulin and urine α1- and β2-microglobulin concentrations. Urine was collected and the volume was recorded. Meanwhile the consumption of furosemide administration during the 12 h after operation was recorded. Results The two groups were comparable with respect to age, M/F sex ratio, body weight, the volume of urine and fluid infused, and the consumption of furosemide. There was no significant difference in serum cystatin C and β2-microgiobulin and urine α1- and β2-microglobulin concentratious, urine volume and consumption of furosemide administration between the transplantation without adverse effect on kidney allograft function.

The low-risk mild hypertension constitutes a considerable proportion in hypertension. Through searching CNKI, Wanfang database, VIP database and PubMed database, literature during the last 10 years was collected and reviewed. It was indicated that excessive diagnosis, insufficient evidence of drug treatment, and poor drug adherence existed in low-risk mild hypertension, however, acupuncture at Renying (ST 9) and other therapies had remarkable effects. This paper mainly expounded the diagnosis and treatment status of low-risk mild hypertension as well as the research summary of acupuncture for low-risk mild hypertension.
Acupuncture Points ; Acupuncture Therapy ; trends ; Humans ; Hypertension ; therapy ; PubMed ; statistics & numerical data

[ ABSTRACT] AIM:To illustrate the effect of methylene blue ( MB) on T-lymphocyte subsets and oxidative stress of the thymus in rats with paraquat ( PQ) poisoning.METHODS: Male SD rats ( n=40) were randomly assigned to 4 groups:normal group, control group, low-dose (2 mg? kg-1? d-1 ) MB group and high-dose (4 mg? kg-1? d-1 ) MB group.After 72 h, the pathological morphological changes of the thymus were observed under microscope with HE staining. The SOD activity and MDA content were measured by colorimetry method.The expression of Bcl-2, Bax, CD4 and CD8 was determined by immunohistochemical method.RESULTS:In MB group, the thymus tissue showed good corticomedul-lary demarcation.MDA content decreased and SOD activity increased, indicating that the ability of antioxidation enhanced. Bcl-2 and Bax expression was down-regulated, Bcl-2/Bax ratio increased, and CD4 positive cells increased.CONCLU-SION:MB protects against oxidative damage induced by PQ, and regulates the distribution of T-lymphocyte subsets in the cortex and medulla, thus relieving the persistent body damage.

Objective To evaluate the results of surgically treated Chiari Ⅰ malformation (CMI) with posterior fossa decompression and reconstruction techniques.Methods Sixty-nine patients with CMI malformation underwent posterior fossa reconstruction.The operation involes dissection soft tissue from the suboccipital region,decompression by removing the posterior rim of the foramen magnum.Then the dura was opened widely with Y shape,as it often acts as a constricting band,particularly at the level of the foramen magnum.After dissecting the subarachnoid adhesions in cisterna magna with microsurgery techniques,dissecting part of the tonsillar hernia,opening the foramen of Magendie into the 4th ventricle and closing the dura using artificial dura mater,cranial bone flaps was repositioned centrally along the inferior edge of the craniectomy defect,so as to support the dura over the cerebellar hemispheres.Results Until the final follow-up,the clinical symptoms were improved in 56 patients,3 had recurrence after 1 year postoperatived,4 had recurrenced after 2 years postoperatived,and 87.5％ patients were stable.The patients took followed-up MRI at least once form 3 months to 6 months,and 13 cases were lost.One case with tension pneumocephalus,and 5 cases with subcutaneous effusion and cerebro-spinal fluid (CSF) incision leakage.There were no death and disability.Thirty-one cases favors the development of syringomyelia,6 showed the stable of syringomyelia,and 2 had an increased size of the cavity.Conclusion Dissecting the subarachnoid adhesions in cisterna magna with microsurgery techniques,dissecting part of the tonsillar hernia,opening the foramen of Magendie into the 4th ventrica,and circulation of CSF pathway are important to improve thetherapeutic effect of CMI.It is also very important to decompression with small cranial bone flaps,closing the dura using artificial dura mater under no tension,and bone structure reconstruction in the clinical practice.

[ ABSTRACT] AIM:To explore the regulatory effect of intermedin ( IMD) on pulmonary collagen synthesis and ac-cumulation in rats with pulmonary hypertension induced by high pulmonary blood flow.METHODS: Healthy male SD rats (n=20) were randomly divided into control group (n=7), shunt group (n=7) and shunt with IMD group (n=6).The shunting of abdominal aorta and inferior vena cava was produced in rats of shunt group and shunt with IMD group.After 8 weeks, IMD was administered into the rats of shunt with IMD group subcutaneously by mini-osmotic pump for 2 weeks.Mean pulmonary artery pressure (mPAP), relative medial thickness (RMT) of pulmonary arteries, contents of hydroxyproline, collagen type I and III, bone morphogenetic protein-2 (BMP-2), and the mRNA expression of procollagen I and III in lung tissues were measured and compared.RESULTS:Compared with control group, mPAP and RMT of medium and small pul-monary arteries in the rats of shunt group were significantly increased.Meanwhile, the lung hydroxyproline, collagens I and III and BMP-2 contents, and the mRNA expression of lung procollagen I and III were all significantly increased compared with control group.However, IMD significantly decreased mPAP, alleviated the changes of pulmonary vascular micro-struc-ture, decreased the collagen accumulation and pulmonary tissue homogenate BMP-2 contents, and inhibited the mRNA ex-pression of procollagen I and III in the lung tissue of shunting rats.CONCLUSION:IMD plays a protective role in the de-velopment of pulmonary hypertension and pulmonary vascular structural remodeling induced by high blood flow by inhibiting pulmonary collagen synthesis and accumulation, possibly in association with the BMP-2 pathway.

Objective To investigate the clinical application of 3.0 T mobile iMRI and neuronavigation in the microsurgical operation for the high grade gliomas in brain functional area.Methods The clinical data of 47 cases which were operated from April,2012 to August,2014 assisted by intraoperative magnetic resonance and neruonavigation system were analyzed retrospectively,including 19 cases of near the frontal motor areas,21 cases of closed to the dominant hemisphere language areas,and 7 cases of involved multiple lobes of the brain.The operative plans were made before the operative day using 3.0 T iMRI for T1-MPRAGE plain and enhancement magnetic resonance imaging sequence,diffusion tensor imaging (DTI) sequence and blood oxygenation level dependent functional MRI (BOLD-fMRI) sequence scanning.Before the start of operation,the margin of the tumor was marked on the scalp,and removed the tumor under the microscopy,according to the need 1-4 iMRI plain scan and enhanced scan were applied to reconstruct the real-time imaging of the residual tumors and corticospinal tract,and gained once more chances to remove the tumor repeatedly,until the tumor was removed totally,accurately and safely.Results The total resection rate increased from 63.8％ (30/47) to 95.7％ (45/47) by repeated resection,and 2 cases (4.3％ lesions) with subtotal resection.The dysfunction of motion and the language barrier got worse in 4 patients (8.5％).No cases with sever complication such as death and severe disability after operation.There were no intracranial hemorrhage,infection and other adverse events.Patients were followed up with nervous system symptoms and head MRI,the follow-up period was 3 months-2 years.Twenty-eight cases (59.6％) ob-tained good clinical efficacy;the dysfunction of motion and the language barrier got worse in 4 cases (8.5％);the symptoms and tumors recurrenced in 15 cases (31.9％).Conclusion The 3.0 T mobile iMRI system combined with functional neuronavigation can accurately display the relationships among the motor and language cortex,tumors and white matter fiber bundles real-timely.The extent of the tumor resection can be assessed accurately by real-time images provided by iMRI,and the residual tumor have chames to be resected repeatedly,until the tumors were resected totally before operation finished.The iMRI system can correct intraoperative brain shift timely.The total resection rate can be improved safely and accurately by one or more times resection.

AIM: Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert cytoprotection during metal exposure and oxidative stress. The present study was designed to investigate whether MT can directly protect NTPase on nuclear envelope from damage induced by hydroxyl radical.METHODS: Isolated hepatic nuclei from rat liver were exposed to Fe 2+ /H 2O 2 with or without MT, and the NTPase activity on nuclei was assayed using ATP and GTP as substrate, respectively. RESULTS: Incubation of rat hepatic nuclei with the Fe 2+ /H 2O 2 (in ?mol?L -1 / ?mol?L -1 : 0 1/0 5, 0 5/2 5, 1/5, 5/25) resulted in a concentration-dependent decrease in nuclear NTPase activities ( P0 05 ). In addition, incubation of hepatic nuclei with only MT had no effect on nuclear NTPase activity. CONCLUSION: These data demonstrate that hydroxyl radical generated from Fe 2+ /H 2O 2 might attack nuclear NTPase. MT antagonistically reduces toxicity of Fe 2+ /H 2O 2 system to the NTPase.