Background and purpose:Hypoxia induced the decreased radiosensitivity of tumor cells, which was the cause of tumor radioresistance and relapse and metastasis. During the course, HIF-1a played the most important role in the regulation of hypoxia. However, it’s still unknown about the effect of HIF-1a on the radiosensitivity of hypoxia tumor cells and the relationship with autophagy. This study was to inhibit HIF-1αexpression in hypoxic lung adenocarcinoma cell line A549 with RNA interference (RNAi), and explore its effect on hypoxic cell radiosensitivity and autophagy. Methods: Plasmids pHIF-1α-shRNA and Neg-shRNA (negative control) were constructed and transfected into hypoxic A549 cells, this positive clone was named A549/HIF-1α-shRNA. Clone formation array was applied to calculate the value of D0, SF2, SER. The expression of HIF-1α, LC3, c-parp was detected by Western blot. Results:The SF2 of hypoxic A549 cell was 0.62, which was higher than that of normoxic A549 cell, SER was 1.45. The level of LC3Ⅱincreased significantly and the level of c-parp decreased after the radiation of hypoxic A549 cell. The level of HIF-1a increased in hypoxic A549 cells. The expression of HIF-1αin hypoxic A549 cells was suppressed markedly after transfection of HIF-1α-shRNA;this clone was named A549/HIF-1α-shRNA. The SF2 and SER were significantly lower in A549/HIF-1α-shRNA cells, 0.45 and 0.72 respectively. Under the hypoxic condition and after the inhibition of HIF-1α, the expression of LC3Ⅱ decreased significantly and the expression of c-parp increased. Conclusion:We successfully established a cell model that HIF-1αexpression was suppressed almost completely by RNAi. The inhibition of HIF-1αby shRNA may raise the radiosensitivity and decrease the autophagy of hypoxic A549 cells in vitro.

Objective To investigate the effects of Qinma Formula on endogenous anti-inflammatory system in rats with chronic obstructive pulmonary disease (COPD); To discuss its mechanism of action. Methods Rat models of COPD were made by modified smoked lipopolysaccharide method. 70 healthy SPF male Wistar rats were randomly divided into normal group, model group, Western medicine control group (aminophylline group), TCM medicine control group (Liujunzi Decoction group) and Qinma Formula high-, medium-, and low-dose groups, with 10 rats in each group. Each medication group was given relevant medicine for gavage. The pathological changes of lung tissue were observed under light microscope; the alveolar lavage fluid (BALF) and venous blood were collected and the related indexes were tested; the levels of serum IL-1β, IL-6 and IL-10 were detected by ELISA. Results Compared with normal group, BALF white blood cells, neutrophils, macrophages, lymphocyte, hemoglobin and platelet count in rats of model group increased significantly (P<0.05). Compared with the model group, BALF white blood cells, neutrophils, and macrophages in rats of Qinma medium- and high-dose groups and Liujunzi Decoction group decreased significantly (P<0.05); white blood cells, hemoglobin, and platelet count in rats of Qinma medium-, high-dose groups and aminophylline group decreased significantly (P<0.05); levels of IL-1β and IL-6 in serum decreased significantly (P<0.05); level of IL-10 in serum increased significantly (P<0.05). Conclusion Qinma Formula can effectively inhibit the inflammatory response through the regulation of inflammatory response-related cytokines.

Objective To look into the experience and feels of the family caregivers of brain tumor patients undergoing surgery. Methods The phenomenological methodology was used in the study. Eighteen family caregivers nursing brain tumor patients were selected as our target. Semi-structured interviews were performed to investigate their feelings and experience during the preoperative period. Result Three topics from our study were concluded: inappropriate emotional reaction, inexperience in the disease management and insufficiency in social support. Conclusion Medical staff and institutions should provide emotional, nursing technical support and professional knowledge for the caregivers so that they can improve their adaption ability and relieve the stress.

Objective To investigate the therapeutic effect and side effects of concurrent chemotherapy and intensity-modulated radiotherapy (IMRT) following induction chemotherapy (IC) in patients with locally advanced nasopharyngeal carcinoma (NPC).Methods From January 2005 to January 2009,62 cases of locally advanced NPC confirmed by pathological and cytological examination received IC with vinorelbine (25 mg/m2) plus cisplatin (25 mg/m2) for 2-4 cycles and then concurrent chemotherapy and IMRT.Conventional fractionated radiotherapy was adopted in IMRT.The radiotherapy for the nasopharyngeal region was performed a dose of 72-76 Gy/36-38 fractions,and additional 5-Gy gammaknife treatment was carried out in case of local tumor residue.Prophylactic irradiation to the cervical lymph nodes was performed at a dose of 50 Gy,and the dose was increased to 60-70 Gy in case of lymph node enlargement.Results The follow-up rate was 100％.The patients showed a response rate (RR) of 89％ in the nasopharyngeal region and an RR of 90％ in the cervical lymph nodes.The 1-,2-,and 3-year overall survival rates,disease-free survival rates,local relapse-free survival rates,and distant metastasis-free survival rates were 97％,92％,and 82％,94％,73％,and 65％,97％,89％,and 87％,and 97％,84％,and 77％,respectively.The incidence rates of grade 3-4 acute reactions were 37％ for leucopenia,18％ for thrombocytopenia,and 6％ for mucositis.No grade 3-4 long-term temporomandibular joint injury and xerostomia were observed.Conclusions Concurrent chemotherapy and IMRT following IC with vinorelbine (25 mg/m2) plus cisplatin (25 mg/m2) have tolerable adverse effects and can achieve high survival rate in the patients with locally advanced NPC.

ated acute peritonitis induced by LPS in rats.

Objective To explore the effects of peroxisome proliferator-activated receptorγ (PPARγ) agonist rosiglitazone and 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2) on the expression of PPARγ, toll-like receptor 4 (TLR4) and the activation of STAT1 as well as the local inflammation reaction of abdominal cavity in sprague dawley (SD) rats with peritoneal dialysis- related acute peritonitis induced by lipopolysaccharide (LPS). Methods Twenty-four male SD rats were equally randomized to four groups(n=6 each): control group, injected with 4.25% dextrose peritoneal dialysate (PDF) via abdominal cavity(90 ml/kg); LPS group, injected with LPS(1 mg/kg) via abdominal cavity 4 hours later follewed by PDF injection; rosiglitazone plus LPS group (Rosi group), preconditioned with rosiglitazone (20 mg·kg-1·d-1) by intragastric way for 3 days, then injected with LPS and PDF via abdominal cavity; 15d-PGJ2 plus LPS group (15d-PGJ2 group), preconditioned with 15d-PGJ2 (0.3 mg·kg-1·d-1)via abdominal cavity injection for 3 days, then injected with LPS and PDF via abdominal cavity. The rats were killed 4 hours after PDF injection, IL-6 level in abdominal dropsy was determined by ELISA. Peritoneum tissue was stained by Masson. Leucocyte count in abdominal dropsy was performed. The mRNA expression of PPARγ and TLR4 in peritoneum tissue was determined by RT-PCR; the protein expression of PPARγ, TLR4, p-STAT1 and STAT1 in peritoneum tissue was analyzed by Western blot. Results IL-6 level of abdominal dropsy in LPS group [median 268.53 (range 201.87-335.19) ng/L] was significantly higher than that of control group [median 147.62 (range 130.60-164.64) ng/L] (P<0.01). The IL-6 level of abdominal dropsy in Rosi group [median 110.20 (range 77.60-142.80) ng/L] was significantly lower than that of LPS group (P<0.05). Compared to that of control group, the edematous degree of peritoneum in LPS group was significantly severer, meanwhile, mRNA and proteins expression of PPARγ and TLR4 in rat peritoneum were also significantly higher (P<0.05, P<0.01). Compared to that of LPS group, the edematous degree of peritoneum in Rosi group was lighter, the expression of PPARγ and TLR4 mRNA was significantly up-regulated (P<0.05), meanwhile their proteins expression was down-regulated (P<0.05); and in 15d-PGJ2 group, the edematous degree of peritoneum, the expression of PPARγ mRNA and protein was also decreased (P<0.05), but TLR4 mRNA expression was up-regulated (P<0.01), however, its protein expression was down-regulated (P<0.05). There were no significant differences in leucocyte count of abdominal dropsy among the four groups. The p-STAT1 expression in the rats peritoneum induced by LPS was markedly increased by both rosiglitazone and 15d-PGJ2 (P<0.01). Conclusions Both rosiglitazone and 15d-PGJ2 can down-regnlate the inflammatory reaction in rat peritonitis induced by LIPS, which may be involved in modulating the expression of associated functional protein during LPS signal pathway.

Objective To investigate the expression of CD40 and intercellular adhesion molecule-1 (ICAM-1) treated with lipopolysaccharide (LPS) in rat peritoneal mesothelial cells(RPMC) and the role of NF-κB signal transduction pathway. Methods RPMCs were harvested from Sprague-Dawley rat peritoneal cavity and maintained under defined in vitro conditions. The cells were exposed respectively to different concentrations of LPS for 12 h or treated with LPS (5 μg/ml) for different time points. To observe the effect of LPS on the expression of CD40 and ICAM-1, the RPMCs were treated with LPS (5 μg/ml) for different time points. To observe the effect of LPS on the expression of NF-κB and p-NF-κB protein, the RPMCs were treated by LPS or pretreated with BAY11-7085 (5 μmol/L or 1 μmol/L ) for 3 h, then treated with LPS for another 3 h, respectively. Expression of CD40 and ICAM-1 mRNA was examined by RT-PCR. Expression of NF-κB and p-NF-κB protein was detected by Western blot. Results Compared with medium control group, stimulation of RPMCs with 1 μg/ml and 5 μg/ml of LPS resulted in a significant increase in the expression of CD40 and ICAM-1 mRNA(P<0.05). 10 μg/ml of LPS had strongest effect on CD40 and ICAM-1 expression compared with that of 1 μg/ml and 5 μg/ml of LPS. Treatment with 5 μg/ml of LPS resulted in time-dependent increase in the gene level of CD40 and ICAM-1, with the peak at 3 h. However, after that time point, the gene level of them was gradually attenuated. Following treatment with LPS (5 μg/ml), the level of p-NF-κB began to increase at 15 min, gradually reached the peak at 1 h, and then decreased. But the level of p-NF-κB at 2 h was still significantly higher than that of medium control. 5 μmol/L of BAY11-7085 decreased significantly the up-regulation of CD40 and ICAM-1 induced by LPS. Conclusion LPS enhanced the expression of CD40 and ICAM-1 on RPMCs in a concentration-dependent and a time-dependent manner. LPS induced expression of CD40 and ICAM-1 depend on the NF-κB signal transduction pathway.

Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms.
Animals ; Humans ; Lipid Metabolism ; drug effects ; Metabolic Diseases ; drug therapy ; metabolism ; Polyphenols ; pharmacology

The concentrations of berberine (BBR) and 8-cetylberberine (8-BBR-C16) in rat plasma and tissue were determined by RP-HPLC. Both the plasma pharmacokinetics characteristic and tissue distribution differences of BBR and 8-BBR-C16 were compared to provide experimental data for the mechanism research and further drug development. After the oral administrations of BBR and 8-BBR-C16 at the dose of 80 mg x kg(-1) for rats, the pharmacokinetics result showed that compared with BBR, the C(max) and AUC(0-t), of 8-BBR-C16 increased by 2.8 times and 12.9 times respectively, t1/2 extended from 3.61 h to 11.90 h. The tissue distribution result showed that compared with BBR, the concentration of 8-BBR-C16 in various organizations increased and the retention time extended remarkably. The maximum concentration was achieved in lung and the highest concentration in it was 3 731.82 ng x g(-1). After being derived, the C(max) in plasma and bioavailability of 8-BBR-C16 increased remarkably and the circulation time in vivo extended. The drug concentration in tissue increased remarkably, and the distribution ratio changed too, with strong targeting selection in lung.
Administration, Oral ; Animals ; Berberine ; analogs & derivatives ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Rats ; Tissue Distribution

Objective To explore the cinical ,endoscopic and endoscopic ultrasonography (EUS) manifestations of upper gastro-intestinal heterotopic pancreas(HP) and the treatment value .Methods The clinical data in 35 cases of upper gastrointestinal HP confirmed by pathology in our hospital were retrospectively analyzed for summarizing its clinical symptoms ,endoscopic and EUS manifestations and the treatment effect under endoscopy .Results Among all the 35 cases ,the cinlincal symptoms were in 30 cases , upper abdominal pain in 18 cases ,abdominal distension in 5 cases ,belching in 4 cases ,melena in 3 cases ,the lesion was located in gastric antrum in 23 cases ,in gastric body in 3 cases ,in gastric fundus in 3 cases ,in gastric angle in 2 cases ,in the junction of gastric antrum and corpus ventriculi in 2 cases ,in durodenal bulb in 2 cases ,most HP were represented by protuberant lesions under endos-copy ,the diameter of the lesions ranged 0 .5-2 .0 cm .20 cases were centrally umbilicated hollow with ducts opening on the top of the protuberant lesion .Under EUS ,the lesions involved submucosa in 28 cases ,mucosa in 2 cases ,muscularis mucosae in 4 cases , and muscularis propria in 1 case .4 cases appeared as the midium echo ,24 cases as hypoecho and 7 cases as mixed echo ,among them ,the tubular structure echo within the lesions were found in 10 cases .20 cases were treated by endoscopic mucosal resection (EMR) ,15 cases were performed the ligation combined with the high frequency electroresection .Intraoperative bleeding occurred in 3 cases and no other complicntions such as perforation occurred .Conclusion The clinical manifestations of upper gastrointestinal HP have no specificity .Gastroendoscopy combimed with EUS has the important value in the diagnosis and endoscopis therapy .En-doscopic EMR and ligation combined with the high frequency electroresection are the safe and effective means for treating upper gastrointestinal HP .