ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Objective:To systematically review the prediction models of postoperative mortality risk in elderly patients with hip fracture.Methods:China National Knowledge Infrastructure, Wanfang, VIP, China Biology Medicine disc, PubMed, Embase, Cochrane Library and Web of Science were systematically searched for studies on mortality risk prediction models after hip fracture surgery in the elderly. The search period was from establishment of the databases to February 28, 2023. Two researchers independently screened the literature, extracted the data, and used the predictive model risk bias tool to evaluate the quality of studies. R4.1.1 software was used to perform meta-analysis of the data.Results:A total of 15 studies were included, of which five were for model development and ten were for model development and internal validation. The performance of the prediction models in the 15 studies was generally good ( AUC: 0.640-0.967), but all of them had bias risks, mainly due to the small sample size, unreported processing methods for missing data values, data complexity, the inappropriate screening method of predictor variables and the lack of consideration of model fitting. Meta-analysis showed that age increase [ OR=1.06, 95% CI (1.04, 1.08), P<0.01], male [ OR=1.92, 95% CI (1.48, 2.48), P<0.01] and reduced hemoglobin [ OR=1.53, 95% CI (1.35, 1.74), P<0.01] were independent risk factors for postoperative death in elderly patients with hip fracture. Conclusions:The prediction model of mortality risk after hip fracture surgery in elderly patients still has shortcomings. In the future, it is necessary to optimize the existing model and verify the model internally and externally. Medical staff should focus on elderly, male, postoperative patients with low hemoglobin and formulate targeted intervention strategies in advance.

OBJECTIVE：To provid e reference for hospital decision-maker to select and use repaglinide and naglinide reasonably. METHODS ：Through reviewing literautre ，guideline and instruction ，full score system was estalished for comunni- cation between pharmacists and physicians ；from the aspects of clinical necessity ，effectiveness，safety，economy，medical insu- rance attribute ，essential medicine attribute ，original research attribute ，drug packaging attribute ，drug market and enterprise attributes，the Mini health technology assessment （Mini HTA ）was carried out for repaglinide and nateglinide ，and scored on the basis of weight value. RESULTS ：Repaglinide and naglinide ’s final score were 77 and 74，respectively. For type 2 diabetes，both of them could reduce postprandial blood glucose ，and had less side effect and good safety. They were both included in the medical insurance list. Both of them were original varieties ，easy to store and had a long period of validity. Although they were expensive in the treatment of type 2 diabetes，their manufacturers had a good reputation and were widely used in the world ，which was a good choice for patients with type 2 diabetes. But they were different to certain extent ；repaglinide could be used in patients with poor renal function [eGFR ＜30 mL/min] without dose adjustment ；nateglinide should be adjusted according to eGFR for renal excretion. Repaglinide was essential medicine but nateglinide wasn ’t；repaglinide didn ’t need shading storage but nateglinide did. In addition ， a variety of liver drug enzyme inducers or inhibitors may interact with the two drugs ，and special groups should be used with. CONCLUSIONS ：Mini HTA provide reference for the selection and rational use of repaglinide and nateglinide ；patients with type 2 diabetes can select suitable drug according to their own conditions and needs. When combined with other drugs ，blood glucose should be closely monitored to prevent the occurrence of hypoglycemia.

Objective To investigate the clinical features of patients with multi-cranial nerves impairments as the onset of Guillain-Barré syndrome (GBS). Methods 10 patients of GBS with complaint of multiple cranial neuropathy were analyzed retrospectively. Results The cranial nerves Ⅶ, Ⅸ and Ⅹ were involved at the onset of GBS, tending to affect men rather than women (4∶1), aged of 18～55 years old (8/10), and with less the antecedent of infection. The knee and ankle jerk reflexes were minimal or absent in all the patients, and the meningeal irritation signs were observed in 4 patients. Assisted ventilation was required in 4 patients during the course of their illness. The cerebrospinal fluid (CSF) characterized with increased protein concentration but a normal cell count in 2 patients in the first week, and all the patients in the following 3 weeks. The incidence of motor conduction velocity (MCV) and F waves abnormalities of electrophysiological evaluation were 81.25% and 94.44% respectively. The Hughes scales were (4.00±0.82) before treatment, and were (2.25±0.96, P=0.012) and (0.50±1.00, P=0.000) 14 d and 28 d after intravenous immunoglobulin (IVIG). Conclusion The probability of GBS should be considered in patients with multiple cranial neuropathy, especially the cranial nerves VII, IX and X impairments without precise causes. The early electrophysiological studies and CSF examinations may be useful for diagnosis. IVIG can be preferred as an effective treatment.