OBJECTIVE:To investigate the significance of tacrolimus blood concentration monitoring to the therapy of mem-branous nephropathy. METHODS:41 patients with membranous nephropathy received tacrolimus,and the blood concentration of ta-crolimus reached to steady state. The trough concentration of tacrolimus was determined by EMIT. The patients were followed up, and clinical therapeutic efficacies were recorded. The relationship of blood concentration of tacrolimus with clinical efficacy was evaluated by SPSS 16.0 software. RESULTS:The blood concentration of tacrolimus was(7.47±2.74)ng/ml in complete remission (CR)group,(5.72±1.19)ng/ml in partial response(PR)group,and(3.30±1.08)ng/ml in no response(NR)group,with total remission rate of 75.61%. The blood concentration of CR group was the highest,followed by PR group and NR group,there was statistical significance among 3 groups(P<0.05). CONCLUSIONS:The clinical efficacy of tacrolimus in the treatment of nephrot-ic syndrome is correlate to the blood concentration intimately. Trough concentration monitoring of tacrolimus has important signifi-cance to the treatment of membranous nephropathy.

Objective To investigate the combined biological effects of low dose radiation,carbon monoxide,benzene and noise on rats.Methods Sixteen male SD rats were randomly divided into experiment group and control group.The experiment group was exposed to carbon monoxide,benzene,low dose radiation and noise daily,the control group was in common environment.Peripheral blood,organ index,and marrow DNA content were detected.Two-dimensional electrophoresis (2-DE) was performed on serum protein analysis.Differential expressed proteins were identified by a matrix assisted laser desorption/ionization time of flight mass spectrometry (MAIDI-TOF-MS).Results Compared to control group,the liver index,spleen index,thymus index,leukocytes,platelets count,and marrow DNA content of the experiment group were decreased significantly (t =2.732,4.141,3.053,2.211,2.668,11.592,P ＜0.05).12 altered proteins were detected and through identification,3 proteins were definite in terms of serum amyloid A-4 protein (SAA4),trichoplein keratin filament-binding protein (TCHP) and tubulin alpha-4A chain (TUBA4A).Conclusions The hematopoietic system and immune system of rats are damaged significantly with the changes of several serum protein expressions by the combined exposure of low dose radiation,carbon monoxide,benzene and noise.This study may provide new information for the mechanism of the combination effects.

Objects To study the protective effects of cimetidine against oxidative stress in rats induced by cumulative low-dose irradiation.Methods Sixty SD rats were randomly divided into 6 groups (10 each):normal control group,model control group,lentinan group [89mg/(kg.d)] and 3 dose groups of cimetidine.After oral administration,all the rats were exposed to γ-ray irradiation 8 hours/day for 12 days,and sacrificed on the 13th day.The activities of superoxide dismutase (SOD),glutathione peroxidase (GPx),catalase (CAT) and the content of malondialdehyde (MDA) in serum,liver,thymus and spleen were determined.By using the superoxide anion radical system,hydroxyl radical system,H2O2 radical system,oxidation system of linoleic acid induced by alkane radical system and diphenyl picryl hydrazinyl radical (DPPH) radical system,the antioxidation activities of cimetidine were detected.Results The activities of SOD in liver and thymus decreased significantly,the GPx activity in serum,liver and spleen decreased significantly and MDA level in serum,liver and spleen increased significantly after 0.3Gy cumulative ionizing radiation.Cimetidine enhanced the activities of antioxidant enzymes in serum and organs,and reduced the MDA level.In a certain concentration range,cimetidine had different scavenging effects onto these radical systems,and showed good performance in hydroxyl radical.Conclusion Cimetidine can effectively ameliorate the oxidative stress from low-dose cumulative irradiation by scavenging free radicals,increase the activity of antioxidant enzymes and reduce the content of lipid peroxidation products,thus presents a potential radio protective effect.

Objective:To prepare old tea buccal tablets using wet granulation method and optimize the preparation technology. Methods:The amount of each adjuvant was studied by single factor experiments, and the formula of the buccal tablets was optimized by the orthogonal experiments using taste and disintegration time as indices. Results:The optimal formula was composed of old tea ex-tract 30 g,mannitol 60g,PEG6000 20 g,aspartame 10 g,citric acid 10 g and menthol crystal 1 g. All the tested indices including ap-pearance, hardness and disintegration time met the requirements described in Chinese pharmacopeia. Conclusion: The preparation technology is reasonable and feasible for the industrial production.

OBJECTIVETo develop a method for elucidating " chromatography-efficacy" relation of the extract of Zanthoxylum nitidum on the gastric cancer cells.

METHODAfter obtaining the tumor inhibition rate and fingerprint peak data through MTT and HPLC, "chromatography-efficacy" relation was established by an appropriate statistical method.

RESULTThe gastric cancer "chromatography-efficacy" relation of Z. nitidum was established by step-back technique.

CONCLUSIONThe "chromatography-efficacy" relation has statistically significant and practical significance, so it has reference value in some way.

Antineoplastic Agents, Phytogenic ; analysis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Humans ; Stomach Neoplasms ; drug therapy ; physiopathology ; Zanthoxylum ; chemistry

Objective To evaluate the effect of hydrogen sulfide on myocardial exogenous apoptotic pathway in a rat model of hemorrhagic shock and resuscitation.Methods Sixty clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were divided into 4 groups (n =15 each) using a random number table method:sham operation group (group S),sham operation plus sodium sulphid (NaHS) group (group S+NaHS),hemorrhagic shock group (HS group),and hemorrhagic shock plus sodium sulphid group (group HS+NaHS).Rats only underwent arterial and intravenous puncture in group S.Hemorrhagic shock was induced by withdrawing blood from the femoral artery until mean arterial pressure (MAP) was reduced to 35-40 mmHg within 10 min and maintained for 1.5 h.NaHS 28 μmol/kg was intraperitoneally injected at 10 min before resuscitation in group HS+NaHS.The equal volume of NaHS was administered at the same time in group S+NaHS.Immediately before blood letting and at 0,1.5,2,3,4 and 6 h after blood letting (T1-5),MAP was recorded and blood samples were collected from the femoral vein for determination of serum creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations by chemical colorimetry.Rats were then sacrificed and hearts were removed for examination of the pathological changes of myocardial tissues (with a light microscope) and for determination of cell apoptosis (by TUNEL),expression of caspase-3 and caspase-8 (by Western blot) and expression of Fas and FasL (by immunohistochemistry).Apoptosis index was calculated.Results Compared with group S,MAP was significantly decreased at T1-5,the serum CK and LDH concentrations at T1-5 and apoptosis index at T5 were increased,and the expression of Fas,FasL,caspase-3 and caspase-8 was up-regulated in group HS (P＜ 0.05).Compared with group HS,MAP was significantly increased at T1-3,the serum CK and LDH concentrations at T3-5 and apoptosis index at T5 were decreased,and the expression of Fas,FasL,caspase-3 and caspase-8 was down-regulated in group HS+NaHS (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group HS+NaHS when compared with group HS.Concclusion The mechanism by which hydrogen sulfide attenuates myocardial injury induced by hemorrhagic shock and resuscitation is associated with inhibiting the exogenous apoptotic pathway in rats.

Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice.Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523) group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg). Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE) were determined 30d after 6.0Gy irradiation.Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC) and bone marrow DNA content were decreased significantly (P<0.01,P<0.05) in model group, and fMNPCE was increased significantly (P<0.05). Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01). In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 orP<0.05), and the fMNPCE was decreased significantly (P<0.01 orP<0.05) and tended towards normal.Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system.

Objective:To evaluate the effects of different concentrations of ropivacaine on the growth and migration of lung cancer cells.Methods:Human lung adenocarcinoma cell strain A549 cells and human lung squamous cell strain H520 cells were divided into 4 groups ( n=24 each) using a random number table method: control group (group C) and different concentrations of ropivacaine groups (Ⅰ-Ⅲ groups). Cells were commonly cultured in group C. Ropivacaine 3, 5 and 7 mmol/L were added and then the cells were cultured in Ⅰ-Ⅲ groups, respectively. The cell survival rate was determined using the CCK-8 method at 24, 48 and 72 h of treatment (T 1-3). The cell cycle and apoptosis were detected at T 1 using flow cytometry. The expression of Cyclin D1, cyclin-dependent kinase 4 (CDK4), cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and cleaved caspase-3 was detected using Western blot. Wound healing assay was used to measure cell migration distance. The activities of RhoA and Rac1 were detected by microplate spectrophotometry. Results:The cell viability of A549 and H520 cells sequentially decreased at T 1-3, the proportion of G0/G1 phase and apoptosis sequentially increased, the expression of Cyclin D1 and CDK4 was down-regulated sequentially at T 1, the expression of cleaved PARP-1 and cleaved caspase-3 was up-regulated sequentially, and the cell migration distance, RhoA, and Rac1 activity decreased sequentially in C, Ⅰ, Ⅱ and Ⅲ groups ( P<0.05). Conclusions:Ropivacaine can inhibit the growth and migration ability of lung cancer cells in a concentration-dependent manner, which is related to induction of cell cycle arrest and apoptosis.

Objective:To evaluate the anesthetic effect of remazolam when combined with sufentanil in elderly patients with liver cirrhosis and esophageal and gastric varices undergoing endoscopic sclerotherapy.Methods:A total of 150 cirrhotic patients with liver cirrhosis and esophageal and gastric varices, regardless of gender, aged 65-80 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, who underwent endoscopic sclerotherapy under non-intubated general anesthesia from March 2022 to September 2023 in our hospital, were selected and divided into 2 groups ( n=75 each) by a random number table method: sufentanil plus propofol group (PS group) and sufentanil plus remazolam group (RS group). Anesthesia was induced with intravenous propofol 1-2 mg/kg and sufentanil 0.1 μg/kg and maintained by intravenous infusion of propofol 4-10 mg·kg -1·h -1 in PS group. Anesthesia was induced with intravenous remimazolam 0.1-0.2 mg/kg and sufentanil 0.1 μg/kg and was maintained with intravenous infusion of remimazolam 0.5-2.0 mg·kg -1·h -1 in RS group. BIS values were maintained between 40 and 60 during operation in both groups. Endoscopy was placed when the patients lost consciousness (modified observer′s assessment of alertness/sedation score ≤1). Sclerosing agent laurosinol injection was injected into esophageal submucosal varices in both groups. The time to loss of consciousness and recovery of consciousness, intraoperative body movement and cardiovascular events, and postoperative hypoxemia and nausea and vomiting were recorded. The operator-patient satisfaction was assessed by the visual analogue scale. Results:Compared with PS group, no significant changes were found in the incidence of intraoperative bradycardia, time to loss of consciousness and time to recovery of consciousness( P>0.05), the incidence of intraoperative hypotension was significantly decreased, the incidence of postoperative hypoxemia and nausea and vomiting was decreased, and the satisfaction scores for operators and patients were increased in RS group ( P<0.05). No obvious body movement was found in the two groups. Conclusions:Sufentanil combined with remifentanil provides better anesthetic effect than sufentanil combined with propofol in elderly patients with esophageal and gastric varices undergoing endoscopic sclerotherapy.

Objective:To evaluate the role of Nod-like receptor family pyrin domain-containing 2 (NLRP2) in the dorsal root ganglion (DRG) in neuropathic pain (NP) in rats.Methods:Thirty-two male Sprague-Dawley rats in which intrathecal catheters were successfully implanted, aged 2-3 months, weighing 200-250 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (S group), NP group, NP plus NLRP2-siRNA group (NP+ siRNA group) and NP plus NLRP2-scrRNA group (NP+ scrRNA group). The right sciatic nerve was only exposed but not ligated in group S. NP was induced by chronic constriction injury (CCI) to the sciatic nerve in anesthetized rats in group NP, group NP+ siRNA and group NP+ scrRNA.NLRP2-siRNA and NLRP2-scrRNA were intrathecally injected at 3 days before CCI in group NP+ siRNA and group NP+ scrRNA, respectively.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before CCI (T 0) and 1, 3, 7 and 10 days after CCI (T 1-4). The rats were sacrificed after the last measurement of pain threshold, and the L 4, 5 segments of the DRG on the operated side were removed for determination of the expression of NLRP2 and caspase-1 (by Western blot), the expression of NLRP2 mRNA (by real-time polymerase chain reaction) and interleukin-1beta (IL-1β) content (by enzyme-linked immunosorbent assay). Results:The MWT was significantly lower at T 2-4 than at T 0 in group NP, group NP+ siRNA and group NP+ scrRNA ( P<0.05). Compared with group S, the MWT was significantly decreased at T 2-4, the expression of NLRP2 protein and mRNA and caspase-1 was up-regulated, and the content of IL-1β was increased in group NP ( P<0.05). Compared with group NP, the MWT was significantly increased at T 2-4, the expression of NLRP2 protein and mRNA and caspase-1 was down-regulated, and the content IL-1β was decreased in group NP+ siRNA ( P<0.05), and no significant change was found in the parameters mentioned above in group NP+ scrRNA ( P>0.05). Conclusion:NLRP2 in DRG is involved in the development of NP, and the mechanism is related to NLPR2 inflammasomes-induced peripheral neuroinflammation in rats.