OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

Objective To analyze the effectiveness of a tele-diet combined exercise intervention program in elderly patients with type 2 diabetes mellitus combined with sarcopenia.Methods The selection of 80 cases of elderly patients with type 2 diabetes mellitus combined with sarcopenia was conducted from December 2022 to February 2023 in 2 communities in Urumqi City,and the 2 communities were randomly divided into an experimental group and a control group,with 40 cases in each group.The experimental group carried out the intervention of dietary combined with exercise through tele-technology on the basis of the routine health education,and the control group implemented the routine health education.The scores of somatic functions,muscle strength and quality of life of patients with sarcopenia were compared between the 2 groups before and after the intervention.Results After the intervention,6-meter step speed,5 sit-to-stand tests,grip strength index,and quality of life in the experimental group were better than those in the control group,and the difference was statistically significant(P＜0.05).Conclusion Tele-diet combined with exercise intervention positively affects somatic function,muscle strength,and quality of life in elderly patients with T2DM combined with sarcopenia.

Objective To investigate the levels and prognostic value of serum fragment crystallizable gam-ma binding protein(FCGBP)and integrin β4(ITGB4)in elderly patients with severe Mycoplasma pneumoni-ae pneumonia(SMPP).Methods A total of 87 elderly patients with SMPP admitted to Department of Inten-sive Care Medicine in the hospital from January 2020 to December 2023 were selected as the SMPP group,87 elderly patients with general Mycoplasma pneumoniae pneumonia(GMPP)were selected as the GMPP group,and another 87 healthy elderly individuals who underwent physical examinations during the same period were selected as the control group.According to the prognosis after 28 days of treatment,elderly patients with SMPP were divided into a poor prognosis group(31 cases)and a good prognosis group(56 cases).Enzyme linked immunosorbent assay was used to detect serum FCGBP and ITGB4 levels.A multivariate unconditional Logistic regression model was established to determine the factors affecting the poor prognosis of elderly pa-tients with SMPP,and receiver operating characteristic curve was drawn to evaluate the predictive value of se-rum FCGBP and ITGB4 levels for the poor prognosis.Results The serum FCGBP levels in the control group,GMPP group,and SMPP group increased sequentially,while the ITGB4 levels decreased sequentially(P＜0.05).The incidence of poor prognosis in 87 elderly patients with SMPP was 35.63％(31/87).Compared with the good prognosis group,the poor prognosis group showed an increase in serum FCGBP levels and a de-crease in ITGB4 levels(P＜0.05).Age increase(OR=1.200,95％CI:1.036-1.391),high CURB-65 score(OR=2.303,95％CI:1.204-4.403),and high FCGBP level(OR=1.057,95％CI:1.011-1.105)were the independent risk factors for poor prognosis of elderly patients with SMPP(P＜0.05).High oxygenation index(OR=0.980,95％CI:0.963-0.997)and high ITGB4 level(OR=0.961,95％CI:0.929-0.994)were inde-pendent protective factors(P＜0.05).The area under the curve of serum FCGBP combined with ITGB4 level for predicting the poor prognosis was 0.886(95％CI:0.800-0.944),which was larger than 0.789(95％CI:0.689-0.869)and 0.781(95％CI:0.680-0.863)predicted by serum FCGBP and ITGB4 alone(P＜0.05).Conclusion Elevated serum FCGBP levels and decreased ITGB4 levels in elderly patients with SMPP are in-dependently associated with poor prognosis.The combination of serum FCGBP and ITGB4 levels has a high predictive value for poor prognosis in elderly patients with SMPP.

Objective To systematically evaluate the medication experience of patients with chronic multimorbidities and to provide a reference for developing precise intervention programs to improve the medication experience of patients with chronic multimorbidities.Methods PubMed,Cochrane Library,Web of Science,Embase,CINAHL,PsycINFO,CNKI,Wanfang database,VIP database,and Chinese biomedical literature database were searched from the year of database establishment to October 2022,and qualitative studies on medication experiences of patients with chronic multimorbidities were retrieved.The Joanna Briggs Institute Critical Appraisal Tool for qualitative research(2016)in Australia was used to evaluate quality of the studies.A meta-synthesis method was used to integrate the results.Results A total of 11 articles were included,and 56 research results were extracted and integrated into 12 new categories,which were summarized into 4 integrated results:poor sensory experience of drugs,negative emotional and related experiences,reflective and behavioral experiences,and multi-dimensional debugging to improve medication experience.Conclusion The medication experience of patients with chronic multimorbidities should receive extensive attention from society and medical workers,and future research should be conducted to improve the level of patients'medication experience in 5 dimensions,including sensory experience,emotional experience,reflective experience,behavioral experience and associative experience,so as to provide a basis for further improving the medication experience of patients with chronic multimorbidities in China.

Objective:To collect and analyze laboratory indicators of patients of different sexes after blood transfusion, evaluate the effectiveness of blood transfusion, and provide a theoretical basis for formulating more scientific blood transfusion plans.Methods:The clinical data of 808 patients who underwent blood transfusion in The First Affiliated Hospital of Anhui University of Science and Technology from January 2020 to December 2021 were retrospectively analyzed. According to the blood transfusion strategy and the department to which the patients were admitted, these patients were divided into four groups: surgical restrictive blood transfusion group (group A: 72 males and 69 females), surgical non-restricted blood transfusion (group B: 77 males and 118 females), medical restrictive blood transfusion (group C: 184 males and 126 females), and medical non-restricted blood transfusion (group D: 110 males and 52 females). Univariate and multivariate Logistic regression analyses were performed.Results:In group A, after blood transfusion, hemoglobin level in female patients was significantly higher than that in male patients [79.0 (71.5, 87.0) g/L vs. 75.5 (69.0, 82.8) g/L, Z = -2.18, P = 0.029], and C-reactive protein in female patients was significantly lower than that in male patients [21.3 (0.0, 56.0) mg/L vs. 37.0 (3.3, 95.5) mg/L, Z = -1.97, P = 0.049]. In groups B, C, and D, there were no significant differences in hemoglobin, C-reactive protein, and hematocrit between male and female patients (all P > 0.05). Multivariate analysis showed that the difference in hemoglobin levels between before and after blood transfusion was statistically significant ( P = 0.009). After a blood transfusion, hemoglobin level in female patients was 1.44 times that in male patients. Conclusion:The tolerance of female patients to blood loss is higher than that of male patients in surgical restrictive blood transfusion, so the threshold value of hemoglobin given to female patients during blood transfusion can be lower than that of male patients. In the case of the same blood loss, priority of blood transfusion can be given to male patients. In the case of scarce blood resources, the total amount of blood transfused for female patients can be approximately reduced.

The standardized training of resident doctors has entered a new stage of quality construction.The multi-station assessment in clinical context takes clinical problems as the core and residents as the main body,and uses the way of integrating practice and clinical thinking training to help residents build the comprehensive ability to solve clinical practical problems.This paper reviews and summarizes the practice of multi-station assessment mode in a tertiary hospital in Tianjin in recent three years from the aspects of assessment scheme,examination station setting,examination content,requirements and characteristics of ex-amination questions.Problem-oriented,find out the problems existing in the operation process and put forward solutions,so as to provide a reference for further improving the assessment and training system,promoting the training management of residential training bases and improving the training quality.

Objective:To investigate the value of α-synuclein (α-syn) concentration in cerebrospinal fluid (CSF) in predicting postoperative delirium (POD).Methods:One thousand patients underwent elective surgery with combined epidural-spinal anesthesia in our hospital from January 2018 to September 2020 were selected.The epidural puncture was performed at L 3, 4 interspace, and 2 ml of CSF was collected after the needle reaching the subarachnoid space.The concentrations of α-syn, β-amyloid (Aβ)40, Aβ42, total tau protein (T-tau), and phosphorylated tau protein (P-tau) in CSF were determined by enzyme-linked immunosorbent assay.The concentrations of α-syn in CSF and occurrence of POD in patients of different ages were recorded.Patients were divided into POD group and non-POD group according to whether POD occurred, and frequency matching (1∶1) was performed based on five matching variables of age, ASA physical status, education level, duration of operation, and intraoperative blood loss. Results:Eight hundred and forty-one patients were finally included in the study, and the incidence of POD was 15.0%. There were 126 cases in POD group and 126 cases in non-POD group after matching. The concentrations of α-syn in CSF and incidence of POD were gradually increased with age ( P<0.05). Compared with non-POD group, the concentrations of α-syn, T-tau and P-tau in CSF were significantly increased, the concentrations of Aβ40 and Aβ42 were decreased, Aβ40/P-tau, Aβ42/P-tau, Aβ42/Aβ40 and P-tau/T-tau were decreased in POD group ( P<0.05). After confounding factors were corrected by logistic regression analysis, increased concentrations of α-syn, p-tau, and T-tau in CSF were risk factors for POD ( P<0.05). Increased concentrations of Aβ40 and Aβ42 in CSF and increased Aβ40/P-tau and Aβ42/P-tau were protective factors for POD ( P<0.05). Multiple linear regression analysis showed that the concentration of α-syn in CSF was negatively correlated with Aβ40 and Aβ42 concentrations and positively correlated with P-tau and T-tau concentrations ( P<0.05). The area under the receiver operating characteristic curve of concentrations of α-syn in CSF predicting POD was 0.895, Youden index was 0.664, sensitivity was 80.00%, and specificity was 86.36% ( P<0.001). Conclusion:The concentration of α-syn in CSF is related to the occurrence of POD, and it provides higher accuracy in predicting POD.

Objective:To evaluate the value of cerebrospinal fluid (CSF) nerve injury-related proteins levels in predicting postoperative delirium (POD) in patients.Methods:A total of 1 000 patients of both sexes, aged 40-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with Mini-Mental State Examination score>24 at 1 day before operation, undergoing elective knee/hip arthroplasty under spinal-epidural anesthesia , were enrolled in this study.Cubital venous blood samples were drawn before anesthesia for detection of the concentrations of plasma total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride.CSF 2ml was extracted after successful spinal-epidural anesthesia puncture for measurement of concentrations of α-synuclein (α-syn), β-amyloid protein 1-40 (Aβ 1-40), Aβ 1-42, total-Tau (t-Tau), phosphorylated Tau (p-Tau), progranulin (PGRN) and soluble myeloid cell triggering receptor 2 (sTREM2) (by enzyme-linked immunosorbent assay). The Confusion Assessment Method was used at 1, 3 and 7 days after surgery to evaluate the occurrence of POD.The patients were divided into POD group and non-POD group according to whether POD occurred after operation.Logistic regression analysis was used to analyze the variables of which P values were less than 0.05 to analyze the risk factors for POD.The receiver operating characteristic (ROC) curve was drawn and area (AUC) under the curve was calculated to evaluate the accuracy of the related risk factors in predicting POD. Results:A total of 964 patients were enrolled in the study, and 108 patients were diagnosed with POD, and the incidence was 11.2%.The results of logistic regression analysis found that age and and increased α-syn in CSF concentration were risk factors for POD, and decreased PGRN in CSF concentration and Aβ 1-42/p-Tau in CSF were the protective factors for POD ( P<0.05). ROC curve analysis showed that α-syn (AUC 0.69, 95% confidence interval (CI) 0.634-0.748, sensitivity 57.41%, specificity 82.10%, Youden Index 0.3951), PGRN in CSF concentration (AUC 0.695, 95%CI 0.637-0.750, sensitivity 59.26%, specificity 80.86%, Youden Index 0.4012) and Aβ 1-42/p-Tau in CSF (AUC 0.635, 95%CI 0.574-0.692, sensitivity 93.52%, specificity 30.25%, Youden Index 0.2377) could predict the occurrence of POD. Conclusion:PGRN, α-syn concentration and Aβ 1-42/p-Tau in CSF can predict the occurrence of POD in patients.

Objective:To evaluate the relationship between preoperative cerebrospinal fluid/serum albumin ratio (Q-alb) and postoperative delirium (POD) in patients undergoing neuraxial anesthesia.Methods:The patients, aged 40-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, underwent total knee/hip replacement under combined spinal-epidural block in our hospital from January 2018 to December 2020, were collected.After admission to the operating room, venous blood and cerebrospinal fluid samples were collected for determination of cerebrospinal fluid albumin, β-amyloid (Aβ) 1-42, Aβ 1-40, total tau protein (t-Tau), phosphorylated tau protein (p-Tau) and serum albumin levels (by enzyme-linked immunosorbent assay) and for calculation of Q-alb.When Q-alb was more than 10.2, the patient was considered to have blood-brain barrier disruption.Mini-Mental State Examination scale was used to evaluate the cognitive level on 1 day before surgery. The development of POD was evaluated using Confusion Assessment Method Chinese Reversion and Memorial Delirium Assessment Scale at 1-7 days after surgery.The patients were divided into POD group (P group) and non-POD (NP group) according to whether POD occurred.The receiver operating characteristic (ROC) curve was used to analyze the accuracy of Q-alb in predicting POD. Results:There were 49 cases in each group.Compared with group NP, concentrations of Aβ 1-42 and Aβ 1-40 were significantly decreased, concentrations of t-Tau and p-Tau albumin were increased, the ratio of Q-alb and blood-brain barrier disruption was increased in group P ( P<0.05). Before and after adjusting for confounding factors, Q-alb, cerebrospinal fluid Aβ 1-42, Aβ 1-40, t-Tau and p-Tau levels were risk factors for POD ( P<0.05). There was a positive linear regression relationship between Q-alb and levels of t-Tau and p-Tauin cerebrospinal fluid (t-Tau: β=0.587, P<0.001; p-Tau: β=0.427, P<0.001), and there was a negative linear regression relationship between Q-alb and levels of Aβ 1-42 and Aβ 1-40 in cerebrospinal fluid (Aβ 1-42: β=-0.762, P<0.001; Aβ 1-40: β=-0.531, P<0.001). There was no linear regression relationship between Q-alb and level of p-Tau in group P ( P=0.121). There was no linear regression relationship between Q-alb and level of Aβ 1-40 in group NP ( P=0.467). The results of ROC curve analysis showed that the area under the curve for Q-alb in predicting POD (95% confidence interval) was 0.827 (0.738-0.896). Conclusion:Preoperative higher Q-alb is the risk factor for POD in patients undergoing neuraxial anesthesia, and is more accurate in predicting POD.