Peripheral chemoreceptors in the carotid body play a significant role in the transduction of chemical stimuli in the arterial blood notably hypoxia,hypercapnia and acidosis to the central for eliciting the chemoreflex,which is central to the hypoxic ventilatory response and is also important for the circulatory responses to hypoxia.It is known that interactions between the peripheral and central chemoreceptors are crucial to the magnitude of the reflex response for the ventilatory control.In addition,the carotid chemoreceptor activity contributes to the ventilatory and humoral responses to exercise and also significantly to the ventilatory acclimatization to chronic hypoxia at high altitude.Under diseased conditions,there are augmented chemoreceptor activity and chemoreflex sensitivity in patients with hypertension or sleep-disordered breathing including obstructive sleep apnea (OSA) and congestive heart failure and also in experimental animal models mimicking these diseases.Thus,the carotid body functions to maintain the oxygen homeostasis； whereas anomalous carotid chemoreceptor activities associated with diseases could be both adaptive and pathogenic in nature,for which cellular and molecular mechanisms have been proposed for the pathophysiogical consequences.

OBJECTIVES:To study the pharmacokinetics of racemic benzeneacetic acid of chirality(RBAC)sustained re-lease tablet in human body of healthy volunteers,and to evaluate the bioequiavailability of RBAC and benzeneacetic acid of chirality(BAC)sustained release tablet.METHODS:18healthy volunteers studies were administered with multidoses of RBAC or BAC by randomized crossover and own control,the plasma concentrations of RBAC and BAC were determined by RP-HPLC,the pharmacokinetic parameters were calculated and ANOVA and two&one side t tests were carried out as well.RESULTS:The pharmacokinetic parameters of RBAC and BAC were respectively as follows:t 1/2 were(8.14?1.95)h and(8.81?2.27)h;t max were(3.44?0.62)h and(3.44?0.70)h;C ss max were(3.69?0.50)mg/L and(3.68?0.76)mg/L,AUC 0～t were(23.49?2.53)(mg?h)/L and(22.48?2.59)(mg?h)/L;DF were(138.21%?23.10)%and(134.53%?28.14)%;C ss were(1.96?0.21)mg/L and(1.85?0.22)mg/L;The relative bioavailability of RBAC to BAC was(102.45?8.07)%.CON-CLUSION:RBAC and BAC were bioequivalent.

BACKGROUND:Traditional bladder repair methods have many problems such as damage to normal organ function and many postoperative complications. Tissue engineering technology provides a new way for bladder repair.
OBJECTIVE:To explore the feasibility of constructing tissue-engineered bladder with vascular endothelial growth factor (VEGF) nanoparticle-bacterial celulose (BC) composite scaffold with rabbit lingual epithelial cels andtonguemuscle cels.
METHODS:Rabbit lingual epithelial cels andmuscle cels were successively implanted onto the BC scaffold (control group) and VEGF-BC scaffold (experimental group). Six rabbits were taken to make bladder defect models and randomized into two groups: experimental group implanted with VEGF-BC scaffold carrying autologous lingual epithelial cels andtonguemuscle cels,and control group implanted with BC scaffold carrying autologous lingual epithelial cels andtonguemuscle cels. Specimens were taken from the two groups for urographic evaluation and histological examination at 3 months after implantation. Meanwhile, the urodynamic tests were performed.
RESULTS AND CONCLUSION:The experimental group showed the relatively complete bladder, and the control group showed a smal-area filing defect of the bladder. The maximum bladder capacity and bladder compliance in both two groups were decreased after implantation, especialy significantly in the control group (P< 0.05). In the control group, it failed to build a complete epithelial cel layer, and the muscle layer and microvessels were formed a little. In the experimental group, the complete epithelial cel layer was formed, and a larger amount of muscle layers and capilaries appeared. These findings indicate that the VEGF-BC scaffold carrying lingual epithelial cels andtonguemuscle cels can be used to construct thetissue-engineered bladder.

Objective:To investigate the mechanism of endoplasmic reticulum (ER) stress-induced chemoresistance to cisplatin in gastric cancer cells. Methods:ER stress models were established in both BGC823 and SGC7901 gastric cancer cells. The expression of GRP78, an ER stress marker, was examined by Western blot analysis. Moreover, whether ER stress can decrease the sensitivity of gastric cancer cells to cisplatin and activate P38 was explored by flow cytometry and Western blot analysis, respectively. Whether ER stress-induced chemoresistance to cisplatin can be abrogated by blocking P38 activity in gastric cancer was also elucidated using flow cytometry. Results:GRP78 protein expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with tunica-mycin (TM) or thapsigargin (TG) for 8, 16, and 24 h (P<0.05), compared with that in the group treated for 0 h. The apoptotic rates of TM-(or TG)-, cisplatin-, and TM (or TG) plus cisplatin-treated groups significantly increased (P<0.05) in both BGC823 and SGC7901 gastric cancer cells compared with the rate in the control group. The apoptotic rate of TM (or TG) plus cisplatin-treated group signifi-cantly decreased (P<0.05) in both BGC823 and SGC7901 gastric cancer cells compared with that of the cisplatin-treated group. Com-pared with the group treated for 0 h, phospho-P38 expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with TM (or TG) for 8, 16, and 24 h (P<0.05). No difference in P38 protein expression was observed between each group in both BGC823 and SGC7901 gastric cancer cells (P>0.05). Both P38 inhibitors, either SB203580 or PD169316, can inhibit the activation of P38. The inhibition of P38 activity can overcome ER stress-induced chemoresistance to cisplatin in gastric cancer cells (P<0.05). Con-clusion:ER stress can trigger the chemoresistance to cisplatin by activating P38 in gastric cancer cells.

To establish a method of directional differentiation and efficient production of neurons from embryonic stem cells (ES cells) in vitro, based on the 4-/4+ protocol described by Bain, a new method was established to induce ES cells differentiating into neurons by means of three-step differentiation using all-trans retinoic acid (ATRA) combined with astrocyte-conditioned medium (ACM) in Vitro. The totipotency of ES cells was identified by observation of cells' morphology and formations of teratoma in immunocompromised mice. The cells' differentiation was evaluated continuously by the detection of the specific cellular markers of neural stem cells, neurons and astrocytes, including nestin, NSE and GFAP using immunohistochemistry assay. The NSE positive cells' ratio of the differentiated cells was determined by flow cytometry. It was found that the transparent circular clusters surrounding embryoid bodies induced with combining induction protocol formed just after 24 h and gradually enlarged later. This phenomenon could not be observed in EBs induced only by ATRA. The NSE positive cells' ratio in the cells induced with ATRA and ACM was higher than that of the cells induced by ATRA at different time points of differentiation, and finally reached up to 73.5% among the total differentiated population. It was concluded that ES cells could be induced into neurons with high purity and yield by means of inducing method combining with ATRA and ACM.
Astrocytes/*cytology ; Cell Differentiation ; Cells, Cultured ; Embryo, Mammalian ; Neurons/*cytology ; Stem Cells/*cytology ; Tretinoin/pharmacology

Objective To summarize the experience in the diagnosis and management of insulinoma. Methods From January 1966 to December 2007, the clinical data of 131 patients with insulinoma were retrospectively analyzed. Results All the 131 cases had Whipple triad syndrome and 64 eases suffered from psychoneurosis symptoms. The fasting blood glucose or insultus blood glucose concentration of all the cases was lower than 2.8 mmol/L. The ratios of serum insulin to glucose were all higher than 0.3. Before operation, tumor was detected in 8 of 75 patients by B-us scan, and in 17 of 68 by CT, and in 5 of 10 by MRI. The intraoperative ultrasonography(IOUS) was applied in 44 eases, and tumor was found in 43 cases. Surgery included enucleation of insulinoma (88 cases), resection of the corpus and eauda of the pancreas (40 cases), duodenopancreatectomy (2 cases), and biopsy (1 case). The low blood glucose symptoms disappeared postoperatively in 130 cases. Pancreatic fistulae occurred in 20 cases, acute pancreatitis occurred in 32 cases. Conclusions Insulinoma can be diagnosed based on symptoms of Whipple triad and the ratio of serum insulin to glucose. Exploration and IOUS are the simple and effective methods to localize insulinoma.

AIM　To explore the biotransformation of compound 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine in the rabbit. METHODS　Analyze the rabbit bile sample with HPLC, LC/MS and LC/NMR. RESULTS　A metabolite and unchanged 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine were found in the rabit bile, the metabolite was characterized and its structure was elucidated. CONCLUSION　Compound 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine is metabolized by demethylation at 10-OCH3 position.

Objective To explore the relation between vitamin D deficiency and susceptibility to spinal tuberculosis. Methods A total of 163 hospitalized patients with untreated spinal tuberculosis in Tianjin Haihe hospital were enrolled in this study from June 2013 to May 2016. A total of 170 individuals participated in health examination program at the same period were enrolled as the control group. The serum level of 25-hydroxyvitamin D [25(OH)D] was measured by enzyme linked immunosorbent assay. The 25(OH)D grading included serious deficiency group (<25 nmol/L), deficiency group (≥25 nmol/L and <50 nmol/L), insufficiency group (≥50 nmol/L and <75 nmol/L) and sufficiency group (≥75 nmol/L). Histopathological classification was confirmed by intraoperative findings. Results The serum level of 25(OH)D was significantly lower in patient group [23.99(20.55,29.54)nmol/L] than that of control group [42.94(35.68,51.04) nmol/L] (P<0.01), and which was also significantly lower in four seasons than that of controls (P<0.05). The serum levels of 25(OH)D were significantly higher in summer group than those of winter group in both patient and control groups (P<0.008 3). The proportion of patients with serious deficiency of 25(OH)D was significantly higher in spring and winter groups in patient group, which was significantly lower in summer group (P<0.01). There was no significant difference in patients with serious deficiency of 25(OH)D between four seasons (P<0.01). For control group, there was a higher proportion of cases with deficiency of 25(OH)D in four seasons, and there was no significant difference in the distribution of seasons (P>0.05). In patient group, there were 107 cases of caseous necrosis type, 56 cases of hyperplasia type, and the proportion of caseous necrosis type was significantly higher in the severe deficiency group (79.17%, 76/96) than that of deficiency group (46.27%, 31/67, P<0.01). Conclusion Excluding the effect of season, vitamin D deficiency is associated with susceptibility to spinal tuberculosis and histopathologic classification.

Objective To investigate the micro-vessel density and vascular endothelial growth factor receptor 2 (VEGFR2) expression in mucosa and submucosa tissue of the patients with hemorrhoids. Methods Sixty hemorrhoids patients were randomly recruited and involved into experiment group and 20 cases of normal patients involved in control group. RASP, MASP, RSTV, RMTV, Expression of VEGFR2 and microvessel density in two groups were detected by immunohistochemistry. The expression abundance of VEGFR2 mRNA was detected by RT-PCR. Results Excessive angiogenesis was found in hemorrhoids tissue (5.59 ± 0.98) in experiment group as compared with that in control group (3.92 ± 0.81), the difference was statistically significant (P < 0.05). Staining score of hemorrhoid tissue and the control tissue were 5.95 ± 1.01, 2.32 ± 0.72, respectively (P < 0.05). Abundance of VEGFR2 mRNA expression in hemorrhoid tissue was significantly higher than that in control tissue (P < 0.05). Conclusion VEGFR2 plays an important role in angiogenesis during the development of hemorrhoids, which may be closely related to the occurrence of hemorrhoid disease and clinical symptoms.

AIM:To observe the expression of nuclear factor-kappa B ( NF-κB) , N-methyl-D-aspartic acid re-ceptor 2B (NR2B) and inducible nitric oxide synthase (iNOS) in the spinal cord in a rat model of chronic constriction in-jury (CCI) of the sciatic nerve.METHODS:Fifty-six adult male Sprague-Dawley rats weighing 180~220 g were random-ly divided into sham group (n=8) and CCI group (n=48).The mechanical withdrawal threshold (MWT) and paw with-drawal latency (PWL) of the hind paws were measured 1 d before CCI and 1 d, 4 d, 7 d, 14 d and 21 d after surgery.The L4~L6 segment of the spinal cord was taken for determining the expression of NF-κB, NR2B and iNOS by RT-PCR and Western blotting.RESULTS:At 1 d, 4 d, 7 d, 14 d and 21 d after surgery, the MWT and PWL in CCI group were obviously lower than those in sham group .The expression of NF-κB, NR2B and iNOS at mRNA and protein levels in-creased significantly.Positive correlations were found between the mRNA expression of NF-κB and iNOS (r=0.842, P<0.05), and between the mRNA expression of NR2B and iNOS (r=0.833, P<0.05).CONCLUSION:The generation and maintenance of hyperalgesia in sciatic nerve injury rats may attribute to the activation of NF -κB and NR2B and concom-itant increase in iNOS .