This paper is to report the development of a high-throughput in vitro system to screen hPXR/CAR mediated CYP2B6 drug inducers, and the application of it into the quick determination of induction activity toward CYP2B6 by various commonly used traditional Chinese medicines (TCMs) extract. Dual reporter gene assays were performed. The hPXR/CAR expression vectors and the reporter vector pGL3-CYP2B6-Luc involved in the distal and proximal promoters of CYP2B6 were co-transfected into HepG2 cells. Relative luciferase activities in cell lysate were analyzed after 48 h treatment of blank vehicle or drugs to determine the induction activity toward CYP2B6 by various commonly used TCMs extract. The positive hPXR/hCAR activators rifampicin and CITCO were applied to make sure that the reporter gene model was successfully established. Then 5 kinds of commonly used TCM extracts and 1 herbal compound were successfully investigated, some were found to activate hPXR or hCAR and therefore have the potential to induce CYP2B6 enzyme. This is the first domestic article to report the hCAR3-mediated CYP2B6 induction model and the establishment of a reporter gene system for hPXR/CAR-mediated CYP2B6 induction can be an effective and systemic in vitro method to investigate the drug inducers of CYP2B6 and to explain the mechanism involved.
Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP2B6 ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Genes, Reporter ; Genetic Vectors ; Hep G2 Cells ; High-Throughput Screening Assays ; Humans ; Luciferases ; genetics ; metabolism ; Oximes ; pharmacology ; Plants, Medicinal ; chemistry ; Plasmids ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; Receptors, Steroid ; genetics ; metabolism ; Rifampin ; pharmacology ; Thiazoles ; pharmacology ; Transfection

OBJECTIVETo determine the incidence of post-operative delirium after oral and maxillofacial surgery under general anesthesia in elderly patients, and to examine its association with plasma concentrations of beta amyloid protein 1-40 (Abeta1-40).

METHODSFifty patients underwent elective oral and maxillofacial surgery were divided into two groups: Group C (n=20) aged from 20 to 60 years old, and Group T (n=30) aged from 62 to 78 years old. The two group received the same general anesthesia. Delirium rating scale-revised-98 (DRS-R-98) was used as an instrument to diagnose and access the postoperative delirium of the two groups. The scores of DRS-R-98 were recorded before operation (T0) and at 24 h (T1), 48 h (T2), 72 h(T3) and 96 h(T4) after the operation. Serial measurements of serum concentrations of Abeta1-40 were also performed at the same time.

RESULTSThe incidence of post-operative delirium after oral and maxillofacial surgery in Group T was 20.0%. The concentrations of plasma Abeta1-40 in group T were much higher than group C at TO, T1, T2 and T3 significantly (P < 0.01). The concentrations of plasma Abeta1-40 at T1 and T2 were higher than those at TO in the same group (P < 0.05). The scores of DRS-R-98 in Group T at T3 and T4 were much higher than those at T1 and Group C significantly (P < 0.01).

CONCLUSIONThe constant increase of plasma Abeta1-40 may be one of the important factors related to post-operative delirium in elderly patients underwent oral and maxillofacial surgery.

Aged ; Amyloid beta-Peptides ; Delirium ; Female ; Humans ; Male ; Peptide Fragments ; Surgery, Oral

OBJECTIVETo study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the recipient.

METHODSLiver transplantation was performed using male Lewis rats as donors and male DA rats as recipients. These rats were randomly allocated into the following groups:Control group, Homogeneity Liver Transplantation group, Idio-immunotolerance group and Acute Rejection group. After transplantation, survival time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of GITR on T cell subgroup, histopathology of the hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured.

RESULTSIn the Idio-immunotolerance group, the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long. In the Acute Rejection group, the donors were preconditioned with total body irradiation before liver transplantation. All recipients died between day 17 to 21. Serum ALT and TB increased significantly and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation.

CONCLUSIONSPreconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft, decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells, thus affected the course of tolerance and induced acute rejection after liver transplantation.

Animals ; Liver Transplantation ; immunology ; Male ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Regulatory ; immunology ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; immunology ; Whole-Body Irradiation

OBJECTIVETo compare the influence of propofol and isoflurane on pro-inflammatory and anti-inflammatory cytokine response to perioperative period of tongue cancer surgery.

METHODSTwenty-four adult patients undergone the operation of tongue cancer were assigned to two groups randomly, propofol group (Group P) and isoflurane group (Group I). In group P, anesthesia was induced with fentanyl 2-3 microg/kg, propofol 2 mg/kg, atracurium 0.6 mg/kg and maintained with propofol 5-8 mg x kg(-1) x h(-1) and inhalation of 50% nirous oxide (N2O:O2=50%:50%). In group I, anesthesia was induced with 3%-4% isoflurane, fentanyl 2-3 microg/kg, diazepam 0.06-0.1 mg/kg, atracurium 0.6 mg/kg and maintained with inhalation of 50% N2O and isoflurane (ended-tidal isoflurane was maintained at 0.6%), in two groups atracurium was given intermittently. Blood samples were taken from peripheral vein before anesthesia (TO), at the end of operation (T1), 24 h (T2) and 48 h (T3) after operation for determination of serum IL-6 and IL-10 concentrations. The mean arterial pressure (MAP) and body temperature in two groups were recorded.

RESULTSIL-6 and IL-10 levels increased significantly in two groups at T1, T2 and T3 compared with T0 (P < 0.01). The increasing trend of IL-6 and IL-10 levels were similar in both groups, whereas the level of IL-6 at T1 in propofol group was lower than that of isoflurane group significantly (P < 0.01), however the level of IL-10 was much higher in propofol group than that of isoflurane group at T1 and T2 (P < 0.05).

CONCLUSIONThe influence of total intravenous anesthesia of propofol on post-operation inflammatory response is much gentler than isoflurane.

Adult ; Anesthesia, Intravenous ; Cytokines ; Female ; Humans ; Interleukin-10 ; Interleukin-6 ; Isoflurane ; Male ; Middle Aged ; Neoplasms ; Perioperative Period ; Postoperative Period ; Propofol

Abdomen ; Hernia ; Humans ; Prostheses and Implants ; Prosthesis Implantation ; Treatment Outcome

OBJECTIVETo observe the changes of sex hormones and sexual function in male patients with Graves' disease (GD) after Radioiodine-131 (I-131) therapy.

METHODSThirty-four male GD patients, aged 21 -40 (32.3 +/- 6.7) years, were treated with I-131 at the dose of 111 - 407 (237.8 +/- 51.8) MBq. The levels of serum sex hormones were measured, and the patients'scores on erectile function (IIEF-5) were obtained before and 3 and 6 months after the treatment. Another 20 healthy men aged 25 - 37 (31 +/- 3.1) years were enlisted as controls.

RESULTSThe baseline levels of estrogen (E2), testosterone (T) and luteinizing hormone (LH) were (132.5 +/- 40.4) pmol/L, (21.6 +/- 4.6) nmol/L and (10.1 +/- 4.4) IU/L in the GD patients, significantly higher than (80.4 +/- 31.2) pmol/L, (14.5 +/- 4.2) nmol/L and (6.2 +/- 1.9) IU/L in the healthy controls (P < 0.05). The E2, T and LH levels showed a significant decrease in the GD patients after 3 months of treatment ([110.2 +/- 20.6] pmol/L, [17.7 +/- 5.5] nmol/L and (9.4 +/- 3.9) IU/L, P < 0.05), but exhibited no statistically significant differences from the healthy controls at 6 months ([82.6 +/- 30.1] pmol/L, [13.8 +/- 3.4 ] nmol/L and [6.6 +/- 1.5] IU/L, P > 0.05). The IIEF-5 score of the GD patients was 5 - 25 (15.5 +/- 3.5) before I-131 treatment, significantly lower than that of the controls (19 - 25, 24 +/- 0.5) (P < 0.05), and it was 8 - 25 (19.5 +/- 1.0) at 3 months and 10 - 25 (23.5 +/- 1.5) at 6 months, significantly higher in the latter than in the former (P < 0.05), and with no significant difference between the 6-month treated patients and the healthy controls (P > 0.05).

CONCLUSIONThe E2, T and LH levels are increased while the IIEF-5 score decreased markedly in male GD patients. Six-month treatment with I-131 can not only restore the E2, T and LH levels to normal but also significantly improve the patient's sexual function.

Adult ; Case-Control Studies ; Estrogens ; blood ; Follicle Stimulating Hormone ; blood ; Graves Disease ; blood ; therapy ; Humans ; Iodine Radioisotopes ; therapeutic use ; Luteinizing Hormone ; blood ; Male ; Testosterone ; blood ; Young Adult

Objective:Our study was aimed to analyze the therapeutic effect of early sequential enteral nutrition on postoperative rehabilitation in patients with gastric cancer.Methods:Patients with gastric cancer receiving surgery at our hospital from 2016 to 2017 included and the clinical information was prospective collected and analyzed.Patients were randomly divided into two groups using random number table.Patients in group A were sequentially given amino acid type,short peptide type and then whole protein type,while those in group B received whole protein formulation only.The recovery of gastrointestinal function,postoperative systemic inflammatory response,six-minutes walking test,and enteral nutrition-related complications were compared between the two groups.Results:A total of 71 patients were included in this study (Group A 36 cases,Group B 35 cases).There was no significant difference in terms of the restart anal exhaust between the two groups (P ＞ 0.05).Patients in group A had a significantly shorter postoperative hospitalization (t =4.070;P ＜ 0.01) and the earlier restoration of oral intake than that of Group B (t =3.400;P =0.001).One week after surgery,the levels of CRP (t =2.547;P =0.013) and IL-6 (t =3.172;P =0.002) were significant lower in group A when compared with group B.In addition,patients in group A had a significant higher six minutes walk steps than those in Group B [(416.1 + 36.7) m vs (358.9 ± 32.7) m;t =6.927,P ＜ 0.01].However,no significant difference in enteral nutrition-related complications was found between the two groups (P ＞ 0.05).Conclusion:In patients with gastric cancer,early sequential enteral nutrition can effectively accelerate the postoperative rehabilitation.

OBJECTIVETo observe the difference in the efficacy on traumatic nerve injury among electroacupuncture, warm needling therapy and electroacupuncture plus warm needling therapy and explore the better therapeutic method.

METHODSThe electromyography (EMG) and electroneurography (ENG) of 93 cases showed traumatic nerve injury of moderate damage. According to the single blind randomization principle, they were divided into an electroacupuncture (EA) group, a warm needling therapy (WN) group and an EA plus WN group, 31 cases in each one. The main acupoints were selected from Yangming Meridian and Shaoyang Meridian corresponding to the distribution of damaged nerves. EA, WN and EA plus WN were applied separately. The treatment was given once every day, 15 treatments made one session. After 3 sessions of treatment (45 treatments in total), EMG and ENG were re-checked and the results were analyzed statistically.

RESULTSRegarding the total effective rate and effective rate, it was 96. 8% (30/31) in the EA plus WN group, which was better than 74.2% (23/31) in the EA group and 77. 4% (24/31) in the WN group (P<0. 05). Concerning to the improvements of EMG, the result in the EA plus WN group was 96.8% (30/31), which was better than the other two groups [74. 2%(23/31),74. 2%(23/31)] (P<0. 05). In terms of the recovery of nerve conduction and amplitude, the results in EA plus WN group [(50.9+/-4. 6)m/s,(8. 8+/-2. 9),microVx1 000] were better than the other two groups [(43.7+/-3.1)m/s,(4. 2+/-1. 9)microV X 1 000,(43. 8+/-3. 3)m/s,(4. 5+/-2. 2)microV X 1 000] (P<0. 05).

CONCLUSIONEA combined with WN is a better therapy of acupuncture and moxibustion in the treatment of traumatic nerve injury.

Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Peripheral Nerve Injuries ; therapy ; Treatment Outcome ; Young Adult

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of amlodipine in human plasma. The influence of alkalizer, extraction solvent and the chromatographic conditions on the matrix effects was investigated. The stable isotope-labeled amlodipine (amlodipine-d₄) was used as an internal standard. Sample preparation involved simple liquid-liquid extraction procedure using methyl tertiary butyl ether. Chromatographic separation was achieved on a Welch Ultimate XB-C18(100 mm×2.1 mm, 3 μm) column with acetonitrile/2 mmol·L^-1 ammonium formate (pH 3.0) under gradient condition at a flow rate of 0.6 mL·min^-1. Detection was performed using electrospray ionization (ESI) in positive ion multiple reaction monitoring (MRM) mode. The linear range of the analyte was 0.1-20.0 μg·L^-1, with the lower limit of quantitation (LLOQ) of 0.1 μg·L^-1. The matrix factor for low, medium, high concentration quality control samples and internal standard was (93.9±1.8)%, (95.8±4.9)%, (93.9±1.5)% and (97.9±5.3)%, respectively. The method showed excellent specificity, linearity, intra-day and inter-day accuracy and precision, extraction recovery and stability, according to the CFDA guidance for bioanalytical method validation. The matrix effect was significantly improved through optimizing the chromatographic conditions. This economical, simple, robust, sensitive and specific method is entirely able to meet the requirement of the determination of amlodipine in human plasma samples obtained from bioequivalence studies.

AIM:To evaluate the macular microstructural changes in patients with rhegmatogenous retinal detachment(RRD)after silicone oil tamponade by spectral-domain optical coherence tomography(SD-OCT).METHODS:From November 2019 to July 2021, 27 patients with 27 eyes in RRD who underwent vitrectomy combined with silicone oil tamponade in Cangzhou Aier Eye Hospital were enrolled in this study as the observation group, other 30 healthy volunteers with 30 eyes were included in the control group. The best corrected visual acuity(BCVA)of patients before and after operation were observed, and quantified evaluation of the postoperative macular microstructural changes were performed by SD-OCT.RESULTS: The BCVA(LogMAR)of the observation group at 1wk and 3mo after operation(0.61±0.23, 0.69±0.34)were improved compared with those before operation(1.43±0.77)(all P<0.01). The cube volume and average cube thickness in the macular area at 3mo after operation in the observation group were lower than those at 1wk and 1mo after operation in the control group(all P<0.05). There were no differences in the average ganglion cell-inner plexiform layer(GCIPL)thickness, minimum GCIPL thickness, average macular retinal nerve fiber layer(mRNFL)thickness and minimum mRNFL thickness at 1wk, 1 and 3mo after operation in the observation group, but all decreased compared with the control group(all P<0.01). There were 9 eyes with subretinal fluid(SRF)in the observation group during postoperative follow-up, SRF had a tendency to be gradually absorbed, but 1 eye had a secondary macular hole; 3 eyes had ellipsoid zone disruption, which had a tendency to be gradually repaired; 2 eyes had submacular perfluorocarbon liquid; 2 eyes had macular edema.CONCLUSION: SD-OCT can show the microstructure and morphological changes very well in macular area in patients with RRD after silicone oil tamponade, and has important clinical value for the preoperative and postoperative follow-up evaluation of RRD.