OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.

【Objective】 To investigate the effects of one-stage additional posterior pedicle screws （PPS） internal fixation on early Cage subsidence after oblique lateral interbody fusion （OLIF）. 【Methods】 We made a retrospective analysis of 118 patients with lumbar degenerative diseases treated with OLIF at the Department of Orthopedics， Sir Run Run Shaw Hospital， School of Medicine， Zhejiang University， from January 2016 to December 2019. We divided the patients into OLIF stand-alone group （58 ones） and OLIF with PPS fixation group （60 ones） according to the surgical procedure. All the patients had preoperative frontal and lateral radiographs of the lumbar spine， and CT and MR scans were performed. The clinical outcomes and reoperation rates of the two groups were compared at immediate postoperative follow-up and at 1， 3， 6 and 12 months. X-ray and CT examinations were performed to assess Cage subsidence in both groups at each postoperative follow-up. 【Results】 There was no statistical difference between the two groups in baseline data and surgical segmentation. Of the 118 patients with 141 discs who underwent OLIF surgery， 58 patients with 68 discs received OLIF stand-alone surgery and 60 ones with 73 discs received OLIF with PPS fixation. There were no significant differences in intraoperative bleeding， complications， or postoperative clinical outcomes between the two groups （P>0.05）， and the Cage subsidence rate was 22.4% in OLIF stand-alone group and 5% in OLIF with PPS fixation group， with significant difference between the two groups （P<0.01）. 【Conclusion】 Both OLIF stand-alone and OLIF additional PPS fixation can achieve good early clinical outcomes， and first-stage additional PPS fixation can significantly reduce the occurrence of Cage subsidence in the early postoperative period after OLIF.

A 57-year-old male patient with type 2 diabetes mellitus and hypertension was changed to metformin 0.5 g orally thrice daily, acarbose 0.1 g orally thrice daily, and subcutaneous injection of lixisenatide 20 μg once daily due to poor control of blood glucose with sitagliptin, glimepiride, and metformin. The drugs used at the same time included mecobalamin injection, alprostadil injection, irbesartan, and bisoprolol. The blood pressure before treatment was 116/71 mmHg. Two hours after the first injection of lixisenatide, the patient′s blood pressure rose to 179/98 mmHg, accompanied by facial flushing and mild nausea. The blood pressure decreased to 125/74 mmHg after oral administration of 10 mg nitrendipine. Next day, the patient received subcutaneous injection of lixisenatide 10 μg, facial flushing recurred and blood pressure rose to 160/90 mmHg, which returned to normal after treatment with oral 10 mg nitrendipine. Thereafter, lixisenatide was discontinued and blood pressure elevation did not recur.

A 57-year-old male patient with type 2 diabetes mellitus and hypertension was changed to metformin 0.5 g orally thrice daily, acarbose 0.1 g orally thrice daily, and subcutaneous injection of lixisenatide 20 μg once daily due to poor control of blood glucose with sitagliptin, glimepiride, and metformin. The drugs used at the same time included mecobalamin injection, alprostadil injection, irbesartan, and bisoprolol. The blood pressure before treatment was 116/71 mmHg. Two hours after the first injection of lixisenatide, the patient′s blood pressure rose to 179/98 mmHg, accompanied by facial flushing and mild nausea. The blood pressure decreased to 125/74 mmHg after oral administration of 10 mg nitrendipine. Next day, the patient received subcutaneous injection of lixisenatide 10 μg, facial flushing recurred and blood pressure rose to 160/90 mmHg, which returned to normal after treatment with oral 10 mg nitrendipine. Thereafter, lixisenatide was discontinued and blood pressure elevation did not recur.

Objective To investigate the value of optical trocar insertion technique in establishing pneumoperitoneum in patients undergoing laparoscopic surgery after previous abdominal surgery. Methods A total of 29 patients, with a history of abdominal surgery, who planned to undergo laparoscopic liver surgery were enrolled and randomly divided into optical trocar insertion group and open approach group. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U test was used for comparison of ranked data between groups. Results There were no procedure-related complications in either group. Compared with the open approach group, the optical trocar insertion group had a significantly shorter time required to establish pneumoperitoneum [35.00 (21.00-46.00) seconds vs 180.00 (152.50-252.50) seconds, U =0, P < 0.001] and a significantly smaller incision length [1.10(1.00-1.20) cm vs 2.80(2.45-3.00) cm, U =0, P < 0.001]. Conclusion Both optical trocar insertion and open approach for establishing pneumoperitoneum is relatively safe in patients undergoing laparoscopic liver surgery after previous abdominal surgery, while optical trocar insertion has the advantages of high efficiency and minimal invasiveness in establishing pneumoperitoneum.

Objective To establish WeChat official account-based platform for evidence dissemination,and to evaluate the effects of the platform.Methods The WeChat official account-based platform for evidence dissemination was established,and big data analysis and sampling survey were adopted to analyze information and its communication effects published from December,2014 to September,2016.Results Totally 22 369 followers used the platform and conducted 404 232 hits on its pages in total.The most frequent searches were Evidence and Knowledge of evidence-based nursing.The WeChat Communication Index was 433.07.The overall evaluation score was 4.34± 0.67.Conclusion WeChat official account-based platform for evidence dissemination can promote the accessibility of evidence and receives high evaluation score from followers.

Objective Study cisplatin intraperitoneal hot perfusion chemotherapy for colorectal cancer effect a radical cure the prognosis of the patients and the influence of immune function.Methods120 patients who underwent radical resection of colorectal cancer patients, divided into observation group and control group, 60 cases in each group.The observation group were treated with cisplatin in postoperative continuous hyperthermic perfusion chemotherapy (chemotherapy for 200mg/m2 solution to cisplatin and injected with 1L), once a week, continuous treatment three weeks.The control group was treated with mFOLFOX6 intravenous chemotherapy (oxaliplatin 100mg/m2 fluorouracil leucovorin 400mg/m2, 400mg/m2), once every two weeks, 12 times of treatment.After the treatment, observation and analysis of two groups of patients before and after treatment of tumor markers (CEA, cancer antigen 19-9, cancer antigen 242), immune function (CD3+ cells, CD4+ cells, CD8+ cells, CD4+ cell ratio/CD8+ cell natural killer cells), quality of life, and the incidence of recurrence and metastasis.ResultsAfter treatment, the quality of life of patients in the observation group the total effective rate was 91.67%, significantly higher than the control group 70.00% (P<0.05), the recurrence rate is 8.33%, the metastasis rate of 10.00% was significantly higher than the control group 28.33% and 25.00% (P<0.05).The observation group of patients with carcinoembryonic antigen, cancer antigen 19-9, cancer antigen 242 level respectively (3.4±1.1)% and (17.5±7.1)% and (4.7±1.9)% was significantly lower than the control group (10.2±2.8)% and (30.1±10.3)% and (20.3±4.5)% (P<0.05), the observation of immune function effect is improved significantly better than the control group, significant differences (P<0.05).ConclusionChemotherapy after radical resection of colorectal cancer patients using cisplatin intraperitoneal hyperthermic perfusion, can significantly reduce the recurrence rate and metastasis rate, improve immune function, reduce the level of tumor markers, so as to improve the quality of life of patients.

Objective To summarize the experience in the diagnosis and treatment of hepatic trauma. Methods The clinical data of 260 patients with hepatic trauma admitted from January 1988 to December 2007 were retrospectively reviewed with regard to degree of trauma, treatment methods, therapeutical effects, complications and SO on. Results One hundred and fifty-three eases were treated by operative management,1 07 cases by nonoperative management.236 cases were cured,24 cases died,and the case fatality rate was 10.2%.There were no death among 139 patients with hepatic trauma grades Ⅰ～Ⅱ,22 death among 119 grades Ⅲ～Ⅴ patients, all death of 2 in grade VI, which demonstrated the correlation between death and hepatic trauma grade was statistically significant. Complications appeared in 82 eases, mainly including Secondary hemorrhage, abdominal infection and so on. Conclusions Nonoperative management is suitable for hepatic trauma with stable hemodynamics. Operative management is rapidly selected when the hemodynamics aren't stable. The cooperation of many specialities can enlarge the application of nonoperative management and decrease complications.

OBJECTIVETo investigate the inhibitory effect of ampelopsin (AMP) combined with adriamycin (ADR) on growth of human leukemia multidrug resistant cell line K562/ADR.

METHODMTT assay was used to detect the effect of AMP on the cytotoxicity of ADR. Jin's formula was used to analyze the effect of combined drug therapy. The expression of P-glycoprotein (P-gp) on cell membrane of K562/ADR was detected using PE-labeled antibody. Flow cytometry was used to determine the influence of AMP on the intracellular accumulation of ADR.

RESULTAMP at the concentration of 1.25 to 5 mg x L(-1) could significantly reverse the multidrug resistance (MDR) to ADR in K562/ADR cells. Co-administration of 1.25 mg x L(-1) AMP and low concentrations of ADR showed an antagonistic effect, while there was an additional to synergistic effect when the concentration of AMP was above 2.5 mg x L(-1). AMP could decrease the expression of P-gp in a concentration-dependent manner and increase the intracellular accumulation of ADR in K562/ADR cells.

CONCLUSIONAMP could increased the cytotoxicity and the intracellular accumulation of chemotherapeutic drugs in MDR associated tumor cells through inhibiting the efflux of drugs by P-gp. AMP may be a promising MDR modulator.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Antineoplastic Agents ; metabolism ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Doxorubicin ; metabolism ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Flavonoids ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Intracellular Space ; drug effects ; metabolism