Objective To explore the correlation between residual cholesterol(RC)and lipoprotein-associated phospholipase A2(Lp-PLA2)in type 2 diabetes mellitus(T2DM).Methods A total of 362 T2DM patients visited our hospital from January 2022 to June 2023 were divided into RC≥0.78 mmol/L(HRC,n=196)group and RC<0.78 mmol/L(NRC,n=166)group based on the levels of RC.The clinical characteristics and related factors were compared between the two groups and the risk factors for RC were analyzed.Results Compared with NRC group,DM duration,SBP,DBP,TC,TG,rate of ACEI or ARBs use,non-HDL-C,Lp-PLA2 and IMT in HRC group increased(P<0.05)and LDL-C decreased(P<0.05).Pearson and Spearman correlation analysis showed that RC was positively correlated with age,DM duration,SBP,DBP,TC,TG,non-HDL-C,Lp-PLA2,IMT(P<0.05)and negatively correlated with LDL-C(P<0.05).Logistic multivariate regression analysis showed that TC,TG,LDL-C,non-HDL-C,Lp-PLA2 and IMT were the influencing factors of RC in T2DM patients.Receiver operating characteristic curve analysis showed that the cutoff value of RC was 0.85 mmol/L,and the cutoff value of Lp-PLA2 was 242 U/L.The predicted AUC of T2DM macroangiopathy respectively was 0.864 and 0.721,and the predicted AUC of RC combined with Lp-PLA2 was 0.896.Conclusions Serum RC is positively correlated with Lp-PLA2 in T2DM patients.The combined detection of these two indicators has a certain predictive value for T2DM macrovascular disease.

Objective To explore the correlation between residual cholesterol(RC)and lipoprotein-associated phospholipase A2(Lp-PLA2)in type 2 diabetes mellitus(T2DM).Methods A total of 362 T2DM patients visited our hospital from January 2022 to June 2023 were divided into RC≥0.78 mmol/L(HRC,n=196)group and RC<0.78 mmol/L(NRC,n=166)group based on the levels of RC.The clinical characteristics and related factors were compared between the two groups and the risk factors for RC were analyzed.Results Compared with NRC group,DM duration,SBP,DBP,TC,TG,rate of ACEI or ARBs use,non-HDL-C,Lp-PLA2 and IMT in HRC group increased(P<0.05)and LDL-C decreased(P<0.05).Pearson and Spearman correlation analysis showed that RC was positively correlated with age,DM duration,SBP,DBP,TC,TG,non-HDL-C,Lp-PLA2,IMT(P<0.05)and negatively correlated with LDL-C(P<0.05).Logistic multivariate regression analysis showed that TC,TG,LDL-C,non-HDL-C,Lp-PLA2 and IMT were the influencing factors of RC in T2DM patients.Receiver operating characteristic curve analysis showed that the cutoff value of RC was 0.85 mmol/L,and the cutoff value of Lp-PLA2 was 242 U/L.The predicted AUC of T2DM macroangiopathy respectively was 0.864 and 0.721,and the predicted AUC of RC combined with Lp-PLA2 was 0.896.Conclusions Serum RC is positively correlated with Lp-PLA2 in T2DM patients.The combined detection of these two indicators has a certain predictive value for T2DM macrovascular disease.

Objective:To investigate the relationship between ATPase Family AAA Domain Containing 3A (ATAD3A) expression level in gastric cancer tissue and chemotherapy sensitivity and prognosis.Methods:Eighty-six patients with advanced gastric cancer admitted to Shandong Second Rehabilitation Hospital from June 2020 to July 2021 were included in this study. Gastric cancer tissue and paracancer tissue samples were collected. ATAD3A expression level in gastric cancer tissue was detected using immunohistochemical staining with the SP method. ATAD3A expression was compared between gastric cancer tissue and paracancer tissue. The relationship between ATAD3A expression and clinical pathological parameters was analyzed. The relationship between ATAD3A expression level in gastric cancer tissue and chemotherapy sensitivity and prognosis was analyzed.Results:The ATAD3A-positive expression rate in the gastric cancer tissue was 75.58% (65/86), which was significantly higher than 43.02% (37/86) in the paracancer tissue ( χ2 = 18.89, P < 0.001). The expression level of ATAD3A in gastric cancer tissues was not correlated with gender, age, tumor diameter, clinical stage or lymph node metastasis (all P > 0.05). The proportion of low differentiation and distant metastasis in patients with ATAD3A-positive expression was significantly higher than that in patients with ATAD3A-negative expression ( χ2 = 5.71, 6.17, both P < 0.05). The total response rate of chemotherapy in patients with ATAD3A-positive expression was 60.00% (39/65), which was significantly lower than 85.71% (18/21) in patients with ATAD3A-negative expression ( χ2 = 4.55, P = 0.033). Of 86 patients, 59 were sensitive to paclitaxel and 56 to capecitabine. The sensitivity of paclitaxel and capecitabine in the ATAD3A-positive group was lower than that in the blank control group ( χ2 = 6.17, 5.19, both P < 0.05). After 1 year of follow-up, the cumulative survival rate in patients with ATAD3A-positive expression was 43.08% (28/65), which was significantly lower than 71.43% (15/21) in patients with ATAD3A-negative expression ( χ2 = 5.24, P < 0.05). The survival time of patients with ATAD3A-positive expression was (8.47 ± 2.13) months, which was significantly shorter than (13.62 ± 1.49) months for patients with ATAD3A-negative expression ( t = 6.29, P < 0.05). Cox multivariate regression analysis showed low differentiation ( HR = 6.22, 95% CI: 1.537-25.240), distant metastasis ( HR = 2.57, 95% CI: 1.396-4.742), and positive expression of ATAD3A ( HR = 10.60, 95% CI: 2.631-42.715) were independent factors that affect the survival time of patients with gastric cancer after chemotherapy ( P < 0.05). Conclusion:ATAD3A is expressed in gastric cancer tissue. Its expression level is closely related to chemotherapy sensitivity and prognosis. It provides an important reference value for the evaluation of chemotherapy efficacy and prognosis.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective To evaluate the efficacy and safety of X-ray guided endoscopic gastrojejunostomy using stent in treatment of malignant gastric outlet obstruction ( GOO ) . Methods Six hospitalized patients with malignant GOO underwent X-ray guided endoscopic gastrojejunostomy using stent in the department of gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University between March 2017 and June 2017. The technical success rate, clinical success rate, procedure time, adverse events and follow-up were recorded and analyzed in this retrospective study. Results The stent was successfully placed in the 6 patients with 100％ ( 6/6) technical success rate. The mean procedure time was 91. 7±51. 8 min. After the procedure, all patients were fed liquid or semi-liquid diet, and the GOO score system was increased from 0-1 before operation to 2-3 after operation. The clinical success rate was 100％(6/6). Peritonitis was observed in 2 patients during operation, and resolved by abdominal drainage. Gastrointestinal bleeding occurred in 1 patient after operation, which was resolved with conservative treatment. During a mean follow-up period of 78. 6 days (range 32-100 days), there was no recurrence of obstruction symptoms except that 1 patient died because of tumor progress 60 days after procedure. Conclusion The X-ray guided endoscopic gastrojejunostomy using stent is feasible and safe to treat malignant GOO with a reliable short-term efficacy.

Objective To analyze the risk factors of early acute kidney injury (AKI) after liver transplantation from donation after cardiac death(DCD) donor liver. Methods Clinical data of 184 donors and recipients undergoing liver transplantation from DCD donor liver were retrospectively analyzed. According to the incidence of early AKI, all participants were divided into the AKI and non-AKI groups. The patients in the AKI group were subject to AKI staging. Baseline data, preoperative, intraoperative and postoperative related parameters were statistically compared between two groups. The cumulative survival rate and clinical prognosis of patients in non-AKI group and AKI group with different staging were statistically analyzed by Kaplan-Meier curve analysis. Results Among 184 patients, 68 cases (37.0%) presented with early AKI after liver transplantation including 31 stage 1 AKI, 26 stage 2 AKI and 11 stage 3 AKI, mainly occurring within postoperative 3 d. Univariate analysis revealed that preoperative levels of albumin <35 g/L, preoperative levels of serum sodium ≤137 mmol/L, operation time>7.5 h, intraoperative hemorrhage volume>3 000 mL, intraoperative red cell infusion volume>15 U and intraoperative urine amount ≤100 mL/h were the risk factors of early AKI after liver transplantation (all P<0.05). Multi-variate Logistic regression analysis demonstrated that intraoperative red cell infusion >15 U was an independent risk factor of early AKI after liver transplantation [odds ratio(OR) 1.061, 95% confidence interval(CI)1.008-1.118,P=0.024].Result of Kaplan-Meier survival curve suggested that the cumulative survival rate was gradually reduced along with the aggravation of AKI with statistical significance (all P<0.05). Conclusions The incidence of early AKI following liver transplantation is relatively high. The severity of early AKI is intimately correlated with the short- and long-term prognosis of the recipients. A large quantity of intraoperative red blood cell infusion is an independent risk factor of AKI.

Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

Objective To introduce a new modified percutaneous dilational tracheostomy and compare the application effect of percutaneous dilational tracheostomy with modified percutaneous dilational tracheostomy in the treatment of critically ill patients. Methods A total of 60 critically ill patients undergoing tracheotomy were selected , and they were randomly divided into two groups according to the methods of tracheotomy. Sex, age, weight, body mass index, acute physiology and chronic health evaluation, operation time, incision size, intraoperative blood loss, incision healing time, incidences of complications after operation were compared between the two groups. Results There were not statistically significant differences of in sex, age, weight, body mass index, and acute physiology and chronic health evaluation between percutaneous dilational tracheostomy group and modified percutaneous dilational tracheostomy group (P>0.05). Operation time, incision size and intraoperative blood loss of modified percutaneous dilational tracheostomy group was statistically significantly shorter than that of percutaneous dilational tracheostomy group [(5.80 ± 1.19) min vs. (7.65 ± 1.05) min, (8.33 ± 3.30) ml vs. (11.33 ± 4.34) ml, (1.08 ± 2.96) cm vs. (1.27 ± 2.54) cm] (P<0.05). The incision healing time and incidence of complications after operation of percutaneous dilational tracheostomy group had no statistical significance compared with modified percutaneous dilational tracheostomy group (P>0.05). Conclusions The modified percutaneous dilational tracheostomy can save operation time, and reduce intraoperative blood loss, so it can be widely used.

Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24％ vs.23.08％).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07％ vs.21.37％).There was no significant difference in the incidence of DGF between SD group and MD group (12.07％ vs.6.84％,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55％ vs.98.29％,P =0.6714;94.83％ vs 98.29％,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.

BACKGROUND: Nowadays complex bone defects have become a great challenge to orthopedists. A synergistic contribution of various growth factors and a crosstalk between their signaling pathways have been suggested as determinatives for the overall osteogenic outcome.OBJECTIVE: To develop calcium phosphate cement (CPC) incorporated with γ-polyglutamic acid/carboxymethyl chitosan (PGA/CMCS), and to evaluate its physical and chemical properties and sustained-release function. METHODS: The γ-PGA/CMCS polymer composites were prepared by graft copolymerization and spray freeze drying methods, and then loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) growth factor. CPC served as control group, and γ-PGA/CMCS-CPC containing different contents of rhBMP-2 as experimental groups. A γ-PGA/CMCS-CPC scaffold with regular blade-like crystalline structure was fabricated by injection compression molding. Before mixed with the liquid phase, the solid additives were properly mixed by wet method of CPC solid and the γ-PGA/CMCS carrier, then the pre-blended mix was freeze-dried. The setting time and compressive strength of bone cement in each group were detected, and the microstructure of the material surface was observed under scanning electron microscopy. In vitro release of rhBMP-2 was investigated. The effect of bone cement extracts on cell proliferation was determined through MTS assay.RESULTS AND CONCLUSION: γ-PGA/CMCS-CPC had the same physicochemical properties to the CPC. Initial and final setting time, compressive strength of bone cement had no significant differences among groups. The scanning electron microscope results showed that the γ-PGA/CMCS-CPC scaffold was covered by regular blade-like crystalline structure and the γ-PGA/CMCS particles were uniformly dispersed in the CPC crystals. A sustained release of rhBMP-2 was observed from the γ-PGA/CMCS-CPC. The cell experiments exhibited that the samples with regular blade-like crystalline structure had better cell response compared to CPC control groups with irregular crystalline structure. These findings indicate that γ-PGA/CMCS-CPC can maintain good physicochemical properties, and release growth factor or drug to promote bone formation.