Objective To observe the role of baicalin on the expression of phosphorylated protein of signal transduc-ers and activators of transcription signaling proteins (STATs) during the process that neural stem cells (NSCs) differentiating into neurons. Methods NSCs were isolated from the embryonic cerebral cortex of the 14-15-day pregnant SD rats, which were cultured and passaged in vitro. The 3rd generation of NSCs was used in the experiment. NSCs were randomized into nat-ural differentiation control group, three different doses of baicalin groups (7.5μmol/L, 15μmol/L and 30μmol/L), leukemia inhibitory factor (LIF)+basic fibroblast growth factor (bFGF) group and baicalin+LIF+bFGF group. After 6 d culture in vi-tro, the immunohistochemical method was used to observe the expressions of microtubule-associated protein 2(MAP-2) and glial fibrillary acidic protein (GFAP) in different groups. The expression levels of phosphorylation protein of STAT 3 in NSCs were detected by Western blotting method after 2 h and 6 d of culture. Results The expression of MAP-2 in NSCs was in-creased by baicalin, but the expression of GFAP in NSCs decreased. The expression of GFAP in NSCs was enhanced in LIF+bFGF group, which was inhibited by baicalin+LIF+bFGF. The phosphorylation level of STAT3 in NSCs was downregulat-ed by baicalin, but the phosphorylation level of STAT3 was upregulated in LIF+bFGF group. The upregulated phosphoryla-tion level of STAT3 was inhibited in baicalin+LIF+bFGF group(P＜0.05). Conclusion Baicalin can induce NSCs to dif-ferentiate into neurons, which may be caused by the downregulation of the phosphorylation level of STAT3 in NSCs.

OBJECTIVE:To provide reference for the sustainable development of pharmaceutical enterprises in Guizhou prov-ince. METHODS:A questionnaire was conducted for 55 pharmaceutical enterprises in Guizhou province,the basic situation of en-terprises,familiarity of related directors to Good Manufacture Practice of Drugs(GMP)and relevant policy,the current situation of implementing the new version GMP were investigated and statistically analyzed,problems were found,and corresponding coun-termeasures were put forward. RESULTS & CONCLUSIONS:Totally 55 questionnaires were sent out,49 valid ones were received with effectively recovery of 85.1%. The results showed 43 enterprises(87.8%)had passed the GMP authentication;only 13 enter-prises(26.5%)directors were very familiar with the new version GMP. In terms of personnel management,the head of production management and quality management and the authorized person of quality and personnel had not yet met related requirements of the new version GMP fully;in terms of equipment and production management,production area transformation(clean areas,lounges, warehouses,water use) and air purification system design in most enterprises met related requirements of the new version GMP, 23 enterprises (46.9%) still can not conduct fully inspection to products and materials;in terms of document management,there were still some enterprises not meeting the new version GMP standards fully,enterprises'documents(health area layout,air purifi-cation layout,management procedures,operating procedures,etc.) of production site were imperfect. According to the investiga-tion,the main existing problems included lack of funds in implementing the new version GMP reform,not enough understanding or familiarity with the new version GMP,relevant personnel management not reaching the designated position,equipment and pro-duction management needing to be strengthened,document management systemic being poor,risk management being not sound, etc. It is suggested that government should give all forms of capital policy and strengthen the training of the new version GMP;en-terprises should attach great importance to the relevant personnel management,strengthen the equipment and production manage-ment,set up perfect document management system and a sound system of risk management.

Objective To determine the relationship between neuronuscular block induced by cisatracurium for tracheal intubation during anesthesia induction and types of myasthenia gravis (MG).Methods Sixty-five patients of both sexes with MG,aged 20-75 yr,weighing 53-92 kg,with body height of 155-185 cm,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elective videoassisted thoracoscopic thymectomy,were enrolled in the study.Among the 65 patients,there were 8 patients with ocular MG (type Ⅰ),19 patients with mild generalized MG (type]Ⅱ a),33 patients with subacute generalized MG (type Ⅱ b),2 patients with acute MG (type Ⅲ) and 3 patients with late severe MG (type Ⅳ).Neuromuscular monitoring was initiated when the patients lost consciousness after induction of anesthesia.Cisatracurium was administrated with the initial dose of 0.05 mg/kg,and if T1 depression was less than 95％ within 6 min,cisatracurium 0.015 mg/kg was intravenously injected until T1 depression was more than 95％.The patients were then tracheally intubated.The amount of cisatracurium consumed for intubation,onset time (from the beginning of cisatracurium injection to T1 depression ＞95％) and recovery time (recovery of T4/T1 to 25％ of control height) of neuromuscular block were recorded.T1 depression ＞ 95％ within 6 min after administration of 1-fold ED95 cistracuriun was defined as sensitivity to muscle relaxants.The requirement for cistracurium ＞ 1-fold ED95 when T1 depression ＞ 95％ was defined as insensitivity to muscle relaxants.The proportion of sensitivity/insensitivity was calculated.Results There was no significant difference in the amount of cisatracurium consumed for intubation and onset time and recovery time of neuromuscular block between patients with type Ⅰ and those with type Ⅱ a (P＞0.05).Compared with patients with type Ⅰ and type]Ⅱ a,the amount of cisatracurium consumed for intubation was significantly decreased,the proportion of sensitivity/insensitivity was increased,the onset time was shortened,and the recovery time was prolonged in patients with type Ⅱ b (P＜0.05).Conclusion With the severity of MG,the consumption of cisatracurium is gradually decreased when used for tracheal intubation during anesthesia induction,and the sensitivity is gradually increased in the patients with MG.

Objective Extracorporeal membrane oxygenation (ECMO) provides a treatment for patients with acute heart-lung failure. However, as an invasive procedure, it associated with high incidence of complications. It is important to a-vert and reduce the complications for improving the success rate in critically ill patients. We investigate the complications associated with ECMO after cardiac surgery and their management. Methods Clinical data from 117 postoperative patients[32 male, mean age (48.7 ± 16.5) years]supported with ECMO in the cardiovascular intensive care unit( ICU) from March 2005 to June 2008 were analyzed retrospectively. The cardiac operations they had undergone included coronary artery bypass grafting (n = 20), coronary artery bypass grafting and remodeling of left ventricle(n =9), coronary artery bypass grafting and valvular operation(n =5), repair of ventricular septal perforation following acute myocardial infarction(n =2), valvular operation( n = 46), heart/lung transplantation (n = 20/1), correction of congenital heart defects ( n = 10), and aortic operations ( n = 4). Venoarterial bypass was established in 110 patients by cannulation of the right atrium and femoral artery, and that of the right atrium and ascending aorta in 5 cases. Left atrial drainage to ECMO was added in 2 cases. Venovenous bypass was established in 2 patients with hypoxemia following cardiac surgery. Heparin was infused for maintaining the activated coagulation time (ACT) at 160 to 200 seconds for centrifugal pump(114 cases),and 200 to 250 seconds for roller pump(3 cases) to avoid thrombotic events until decannulation was achieved. Results The mean ECMO duration was 61 hours (range 3 to 225 hours). 48(41.0% ) patients died, 18 of them died of complications after weaning from circulatory assistant successfully. Complications occurred in 74 (63.2% ) patients included reoperation for hemostasis (n = 24), renal failure requiring renal replacement therapy (n =29), nosocomial infections ( n = 32) , ischemia in the extremities(n = 5), plasma leakage of oxygenators ( n = 29), gastroenteral hemorrhage ( n = 14), hemolysis ( n = 7 ), neurological complications ( n = 4) and centrifugal pump failure (n =1). Conclusion Bleeding is an early complication associated with ECMO support. The risk of nosocomial infection, renal failure and plasma leakage of oxygenators increases with the duration of ECMO support.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of butoconazole in human plasma. Human plasma samples of 0.2 μL were pretreated by a single step protein precipitation procedure and analyzed using a high performance liquid chromatography (HPLC) electrospray tandem mass spectrometer system. The compounds were eluted isocratically on an Inertsil ODS-SP column (100 mm×2.1 mm, 3 μm), ionized using a positive ion atmospheric pressure electrospray ionization source and analyzed using multiple reaction monitoring (MRM) mode. The ion transitions monitored were m/z 412.8→165.1 for butoconazole and m/z 453.4→230.3 for the internal standard. The chromatographic run time was 3.5 min per injection, with retention time of 2.47 min and 2.15 min for butoconazole and repaglinide, respectively. The method was validated to be linear over the range of 20 to 8000 pg/mL (r>0.999) by using a weighted (1/x(2)) quadratic regression. The mean recovery rate was more than 86.7%, and the intra- and inter-day precision of the quality control samples (QCs) was less than 8.3% and the accuracy ranged from 96.0% to 110.2%, which indicated that the quantitative method was reliable and accurate. The method is simple, rapid, and has been applied successfully to a pharmacokinetics study of butoconazole nitrate suppositories in healthy Chinese females.

OBJECTIVETo evaluate the erectile and ejaculatory function of sacral tumor patients after sacral nerve root resection and investigate the relationship of erectile and ejaculatory dysfunction (EED) with the level of sacral nerve injury.

METHODSThis retrospective study included 47 male patients aged 16 to 63 (32.6 +/- 6.8) years treated by sacral tumor resection between January 2008 and August 2013. According to the levels of the sacral nerve roots spared in surgery, the patients were divided into four groups: bilateral S1-S3 (n=16), unilateral S1-S3 (n=21), unilateral S1-S2 (n=6), and unilateral S1 (n=4). The patients were followed up for 12 to 41 (27.2 +/- 10.9) months by questionnaire investigation, clinic review, and telephone calls about their erectile and ejaculatory function at 3, 6 and 12 months after surgery and in August 2013.

RESULTSIn the bilateral S1-S3 group, the incidence rates of EED were 31.25% (5/16), 25% (4/16), and 12.5% (2/16) at 3, 6, and 12 months respectively after surgery, with recovery of erectile and ejaculatory function in August 2013. The incidence rates of EED in the unilateral S1-S3 group were 85.71% (18/21), 71.43% (15/21), 52.38% (11/21), and 42.86% (9/21) at 3, 6 and 12 months and in August 2013, respectively; those in the unilateral S1-S2 group were 100% (6/6), 83.33% (5/6), 83.33% (5/6), and 66.67% (4/6) at the four time points; and those in the unilateral S1 group were all 100% (4/4). No statistically significant differences were found in the incidence rate of EED among the patients of different ages or tumor types (P > 0.05).

CONCLUSIONThe incidence of postoperative EED in male patients treated by sacral tumor resection is closely related to the mode of operation. Sparing the S3 nerve root at least unilaterally in sacral tumor resection is essential for protecting the erectile and ejaculatory function of the patient.

Adolescent ; Adult ; Ejaculation ; physiology ; Erectile Dysfunction ; epidemiology ; etiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Organ Sparing Treatments ; Peripheral Nervous System Neoplasms ; surgery ; Postoperative Complications ; epidemiology ; Postoperative Period ; Retrospective Studies ; Sacrum ; Spinal Nerve Roots ; injuries ; surgery ; Surveys and Questionnaires ; Young Adult

Objective To further research the urinary monitoring of the maternal thyroid functional status ,the levels of urine thyroid hormones were analyzed during pregnancy .Methods This study recruited 30 cases of healthy pregnant women at 9-12 ges-tational weeks .Their random urine specimens were collected every four weeks until delivery .The concentrations of urine thyrotro-pin(uTSH) ,urine free triiodothyronine(uFT3) and urine free tetraiodothyronine(uFT4) were detected by electrochemical lumines-cence immunoassay(ECLIA) .The urine retinol binding protein(uRBP) was detected by enzyme immunoassay (EIA) .After correc-ted by uRBP ,the statistical analysis was done to analyze the variation of the ratio of uTSH and uRBP (uTSH/uRBP) ,the ratio of uFT3 and uRBP(uFT3/uRBP)and the ratio of uFT4 and uRBP(uFT4/uRBP)during pregnancy .Results The median levels of u-rine thyroid hormone parameters were obtained from the healthy pregnant women every four weeks and were compared among dif-ferent stages .The difference of uFT3/uRBP and uFT4/uRBP was statistically significant (F= 6 .222 ,P< 0 .05 ;F= 5 .078 ,P<0 .05) ,and the levels of them varied linearity during pregnancy (F=27 .480 ,P<0 .05 ;F=23 .959 ,P<0 .05) .The difference of uT-SH/uRBP had no statistical significance(F=2 .731 ,P=0 .054) .Conclusion After corrected by uRBP ,the levels of uFT3 and uFT4 of healthy pregnant women decreased linearity among different gestational stages ,and the levels of uTSH had no noticeable change .

Objective To optimize the preparative procedure for stachydrine in Fructus Leonuri. Methods The preparation was screened by orthogonal experiment, and a mathematical model of relationship of extraction time, methanol concentration, and solid-liquid ratio with the content of stachydrine hydrochloride was established by using back-propagation (BP) neural network. And the process parameters were optimized with genetic algorithm (GA) . Results The optimum process parameters were as follows: extraction with 69% of methanol concentration and with solid-liquid ratio being 11 times for 62 min. The content of stachydrine obtained by BP neural network modeling and GA was higher than that achieved by orthogonal experiment. Conclusion The optimum preparative procedure could be achieved by combining BP modeling with GA. The model developed in this study was proved to be predictable and feasible for the optimization of process parameters of multi-dimension nonlinear system.

This paper points out the experimental animal ethics education in pharmacology teaching and the im-portance of the experiment,it is good to raises the student good humanity accomplishment and scientific research quality, and promote medical research and life ethics of benign interaction.It also expounds the basic content of ex-perimental animal ethics education,including:animal welfare, the 3R principle, AAALAC accreditation and analy-sis of the experimental animal welfare legislation status, raises questions about animal ethics education problems and thinking in the pharmacology experiment teaching in ourschool.The experimental animal ethics education should become an important part of pharmacology experimental teaching, which enhanced the students′s ethical awareness to better understand and respect for life, and contribute to the sustainable development of medical and pharmaceutical research.

Objective:Clinicopathological features, treatment and prognosis of urinary and male reproductive system soft tissue sarcoma (STS) and sarcomatoid carcinoma in adults were compared.Methods:A retrospective analysis was performed on the clinical data of 73 patients with STS and 15 patients with sarcomatoid carcinoma in adult urinary and male reproductive system in the First Affiliated Hospital of Zhengzhou University. There were 59 males and 14 females in STS group, with a median age of 41 (18-78)years old. The maximum tumor diameter ranged from 0.5 to 19.0 cm. The primary tumors were located in testis and peritesticular (23 cases), kidney (23 cases), prostate (15 cases), bladder (8 cases), ureter(3 cases), other parts(1 case). There were 18 cases of lymph node metastasis and 8 cases of distant metastasis. Among 73 patients with STS, 66 patients underwent surgical resection, of which 31 patients underwent radical resection. Among the 66 patients who underwent surgery, 3 patients received neoadjuvant chemotherapy; 22 patients received adjuvant chemotherapy; 5 patients were treated with adjuvant radiotherapy. Among 7 patients with STS did not receive surgical treatment, 2 patients received radiotherapy combined with chemotherapy, 2 patients received chemotherapy alone, and 3 patients received symptomatic support treatment.There were 11 males and 4 females in sarcomatoid carcinoma group, with a median age of 65 (23 - 84)years old. The measurable tumor diameter ranged from 0.4 to 16.9 cm. The primary tumors were located in kidney (6 cases), bladder (5 cases), ureter(2 cases) and prostate(2 cases). There were 2 patients of lymph node metastasis and 4 patients of distant metastasis. Of the 15 patients with sarcomatoid carcinoma, 12 patients underwent surgical resection, of which 5 patients underwent radical resection. 2 patients were treated with adjuvant therapy after operation. Among the 12 patients who received surgical treatment, 2 patients had distant metastasis before operation, all of which originated from the kidney. Among the 3 patients without surgical treatment, 1 patients received systemic chemotherapy and 2 patients received symptomatic supportive treatment. There was no significant difference in gender, tumor maximum diameter, distant metastasis and operation, chemotherapy, radiotherapy and operation combined with chemotherapy ( P>0.05) and there were significant differences in age, tumor primary location and lymph node metastasis ( P<0.05) between STS and sarcomatoid carcinoma patients.The categorical variables of the two groups were compared by χ2.With Kaplan-Meier method for univariate survival analysis, the Cox was used for multivariate analysis. Results:The median follow-up time was 18.3(0.3-90.4) months.In STS group, there were 14 patients of synovial sarcoma, 11 patients of liposarcoma, 15 patients of rhabdomyosarcoma, 16 patients of leiomyosarcoma, 10 patients of other types, and 7 patients of spindle cell sarcoma without specific classification. Among 66 patients with STS, 8 patients recurred, 14 patients metastasized after operation, 4 patients recurred and metastasized after operation. The 7 patients without surgical treatment all progressed. Among the 10 patients of sarcomatoid carcinoma without distant metastasis before operation, 3 patients recurred and 3 patients metastasized after operation. Two patients of renal sarcomatoid carcinoma with distant metastasis were treated with nephrectomy and chemotherapy. One of them had overall survival (OS) up to 2 years, and one recurred 2 months after operation. The 3 patients without surgical treatment all progressed without remission. The median OS of STS patients were 59.3 (95% CI 24.1-94.5) months and that of sarcomatoid carcinoma patients were 8.7 (95% CI 6.1-11.2) months. The OS of STS patients were better than those of sarcomatoid carcinoma patients ( HR=2.874, 95% CI 1.118-7.386, P=0.022). Conclusions:The onset age of STS in adult urinary and male reproductive system was lower than that in sarcomatoid carcinoma. The primary lesions of STS were mainly in testis, peritesticular and kidney. The primary lesions of sarcomatoid carcinoma were mainly in kidney. Among STS, leiomyosarcoma was the most common type.STS and sarcomatoid carcinoma should be diagnosed and treated with surgery quickly, and systemic therapy should be performed for patients who cannot be treated with surgery.