Objective To explore the application value of stage rehabilitation intervention under the Health action process approach(HAPA)model(SRI-HAPAM)combined with tranexamic acid(TXA)in elderly patients with femoral neck fracture(FNF)undergoing total hip arthroplasty(THA).Methods Elderly FNF patients with unilateral THA in the First Affiliated Hospital of Wenzhou Medical University from December 2022 to June 2023 were enrolled.According to the random number table method,the patients were divided into routine nursing(RN)group and TXA+SRI-HAPAM group.The RN group received conventional treatment after surgery,and the TXA+SRI-HAPAM group received TXA combined with SRI-HAPAM after surgery.The bleeding indexes[hidden blood loss(HBL),explicit blood loss(EBL)and blood transfusion volume(BTV)],and the levels of hemoglobin(Hb),C-reactive protein(CRP)and D-dimer(DD)were compared between the two groups at 24 h after surgery.The hip function[joint deformity(JD),joint function(JF),joint pain(JP),joint motion(JM)and total hip function(THF)],anxiety and depression[self-rating anxiety scale and self-rating depression scale],satisfaction with care,and complications were compared between the two groups at 3 months after surgery.Results A total of 100 elderly patients with unilateral THA due to FNF were included in the study,including 54 in the TXA+SRI-HAPAM group and 46 in the RN group.Before operation,there was no significant difference in Hb,CRP,DD,JD,JF,JP,JM,THF and SAS between the two groups(P>0.05).At 24 hours after operation,Hb decreased in the two groups,while CRP and DD increased(P<0.05),and the decrease in Hb and the increase in CRP and DD,as well as HBL,EBL and BTV in the TXA+SRI-HAPAM group,were lower than those in the RN group(P<0.05).At 3 months after operation,JD,JF,JP,JM and THF in both groups increased compared with those before operation,while SAS and SDS decreased compared with those before operation(P<0.05),and the functional scores of JD,JF,JP,JM and THF in the TXA+SRI-HAPAM group were significantly higher than those in the RN group,and the scores of SAS and SDS were lower than those in the RN group(P<0.05).3 months after surgery,the nursing satisfaction of the TXA+SRI-HAPAM group was significantly higher than that of the RN group,and the total complication rate was lower than that of the RN group(P<0.05).Conclusion Compared the Routine nursing,TXA combined with SRI-HAPAM more effectively promotes postoperative recovery in patients with THA.

OBJECTIVE To predict the possible impact of pembrolizumab（PEM） as a first-line drug after being included in the national medical insurance system in the treatment of advanced or metastatic non-small cell lung cancer based on real-world data from the perspective of the national medical insurance payer， to provide a basis for the decision-making of the medical insurance department. METHODS A budget impact analysis model was constructed to compare the impact of pembrolizumab not included in medical insurance and included in medical insurance on medical insurance fund expenditure in the next five years（ 2024- 2028） with 2023 as the baseline year. The target population was the patients with EGFR gene mutation-negative and anaplastic lymphoma kinase （ALK）-negative locally advanced or metastatic non-small cell lung cancer； estimated cost mainly included the cost of drugs， the cost of adverse reaction treatment， the cost of examination， the cost of admission and monitoring， etc； equipment ratio of PEM in 183 hospitals of Guangdong province from 2020 to 2022 was used as the market share. Univariate sensitivity analysis was used to test the robustness of the basic analysis results. RESULTS When PEM was not included in the medical insurance， the medical insurance reimbursement amount of the target population from 2024 to 2028 was 4 933 623.5 thousand yuan-5 151 198.3 thousand yuan， respectively. If PEM was included in the medical insurance， the above data were 11 871 972.2 thousand yuan-14 540 571.0 thousand yuan， respectively； the increase in medical insurance reimbursement under the two scenarios was 6 720 773.9 thousand yuan-9 606 947.5 thousand yuan， respectively. The proportion of medical insurance reimbursement to the medical insurance expenditure of the year after PEM was included in medical insurance was 0.298 0%， 0.262 1%， 0.228 8%， 0.208 2%， and 0.185 7%， respectively. The increase in medical insurance reimbursement accounted for 1.084 0%， 0.995 7%， 0.888 6%， 0.886 3%， and 0.861 6% of the increase in the expenditure of the medical insurance fund in the current year， all of which showed a decreasing trend year by year. CONCLUSIONS If PEM is included in medical insurance， due to its high unit price， the medical expenditure will increase accordingly， which will have a great impact on the medical insurance fund expenditure. However， when the drug is used in patients with EGFR mutation-negative and ALK-negative locally advanced or metastatic non-small cell lung cancer， the proportion of the medical insurance reimbursement amount in the current year’s medical insurance fund expenditure and the proportion of the increase in medical insurance reimbursement in the current year’s increase in medical insurance fund expenditure are decreasing year by year.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective:To discuss the safety and feasibility for the use of 3D uniportal VATS sleeve resection.Methods:Totally 32 patients with central lung cancer received 3D uniportal VATS sleeve resection(group A) from June 2017 to May 2020 at Shanghai Chest Hospital. Meanwhile, 63 patients received conventional VATS sleeve resection(group B). The clinicopathological and perioperative outcome data were retrospectively collected and analyzed.Results:The baseline clinicopathological characteristics between these two groups were statistically similar. Compared with group B, the mean operative time[(174.19±73.69)min vs.(212.46±50.02)min, P=0.004] and blood loss[(73.13±42.70)ml vs.(130.48±133.72)ml, P=0.020] of group A were decreased, harvested lymph node stations was increased(7.63±1.59 vs. 6.76±1.70, P=0.018). Lymph nodes dissected showed no statistical difference(1.31±1.58 vs 1.21±1.96, P=0.803). There was no intraoperative death in both groups. Inspiringly, group A possessed lower rate of conversion to thoracotomy(0 vs. 36.5%, P=0.000), shorter chest drainage durations[(4.88±1.15)days vs.(6.81±3.8)days, P=0.007]. Although there were no deaths during hospitalization in both groups, the incidence of postoperative complications in group A was significantly lower than that in group B(25.0% vs. 47.6%, P=0.046). It also presented more complicated operations including pulmonary artery plasty(25.0% vs. 6.3%, P=0.024) and carina plasty(12.5% vs. 1.6%, P=0.005) against group B. Conclusion:3D uniportal VATS was a safe and feasible technique for the surgical treatment of central lung cancer when conducting a thoracoscopic sleeve resection.

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.

OBJECTIVETo explore the value of baseline serum alkaline phosphatase (ALP) for predicting 2-year fracture in patients with chronic kidney disease (CKD) on maintenance dialysis.

METHODSA total of 139 patients with CKD undergoing maintenance dialysis in our hospital were enrolled in this study. According to the median serum ALP level, the patients were divided into high ALP and low ALP groups. The demographic and clinical data of the patients including dialysis duration, serum calcium level, serum phosphorus level, and serum intact parathyroid hormone level were recorded, and their bone mineral density of the femur and the lumbar spine was measured using dual energy X-ray absorptiometry. The patients were followed up for 2 years and fracture events were recorded. The risk factors of fracture were analyzed using logistic regression analysis, and their predictive value for fracture was analyzed using receiver-operating characteristic (ROC) curve.

RESULTSThe mean baseline serum ALP level was 132.55±167.68 U/L in these patients, significantly higher than that in the normal population (=2.816, =0.006). Baseline serum ALP level was negatively correlated with the bone mineral density of the lumbar spine (=-0.203, =0.006) and the femur (=-0.196, =0.021). Fractures occurred in 21 (15.1%) of the patients during the 2-year follow-up, and the fracture rate was significantly higher in patients with high ALP levels. Logistic regression analysis identified serum ALP level as an independent risk factor of fracture (OR: 1.010, =0.001, 95%CI: 1.004-1.016). The areas under the ROC curve were 0.900 and 0.768 for serum ALP level and intact parathyroid hormone level in predicting 2-year fractures, respectively.

CONCLUSIONSSerum ALP may serve as a good indicator for predicting 2-year fractures in patients with CKD on maintenance dialysis.

Objective To explore the role and mechanism of microRNA-15b in the regulation of epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs).Methods PCR assay was used to determine the expression of microRNA-15b in the HMrSV5 induced by 138mmol/L high glucose for 24 h.MicmRNA-15b mimic or inhibitor was transfected into human peritoneal mesothelial cells (HMrSV5) to over-express or down-regulate microRNA-15b.The cells were then incubated with 138 mmol/L high glucose for 24 h,and the expressions of E-cadherin(E-Cad),Vimentin (VIM),Fibronectin(FN) and Smad7 were detected by real-time PCR and Western blotting respectively.Results microRNA-15b in the HMrSV5 ceils was over-expressed and down-regulated.Increased level of microRNA-15b was obtained in HMrSV5 cells treated with high glucose.In vitro,high glucose led to the up-regulation of vimentin as well as fibronectin and the down-regulation of E-cadherin in HMrSV5 cells (all P ＜ 0.05),which indicated EMT and fibrosis.Suppression of microRNA-15b by transfection with microRNA-15b inhibitor partially reversed the EMT and fibrosis changes (P ＜ 0.05),while over-expression of microRNA-15b by transfection with microRNA-15b mimic obviously enhanced the EMT and fibrosis changes (P ＜ 0.05).Conclusions MicroRNA-15b mediates high glucose induced EMT in human peritoneal mesothelial cells by the inhibition of Smad7 possibly.MicroRNA-15b maybe a new target for the prevention and treatment of peritoneal fibrosis during peritoneal dialysis (PD).

Objective To observe the effect ofTanreqinginjection combined with routine medicines on the treatment of senile patients with bronchial pneumonia.Methods A total of 146 patients were randomly divided into 2 groups according to the random number table, each group 73 patients. Control group was treated with routine medicines and treatment group was added 20 mlTanreqing once a day. All treatments lasta total of 7 days. The Th17 and Treg cells were detected by cytometry analysis. The expression of IL-17, IL-10, IL-6, and TNF-α were detected by ELISA analysis. The clinical effect and adverse effect of the two groups were compared. Results After treatment, the clinical effective rate of control group was 79.5% (58/73), which was significantly lower than that of 91.8% (67/73) in treatment group (χ2=2.406,P=0.045). After treatment, Th17 cells was significantly lower in the treatment group than that in the control group (5.16% ± 1.24%vs. 8.22% ± 1.84%;t=2.564,P=0.017); but Treg cells was significantly higher in the treatment group than that in the control group (6.32% ± 1.79%vs. 4.32% ± 1.23%;t=2.552,P=0.021). The expression of IL-17 (11.43 ± 2.52 ng/mlvs. 14.15 ± 2.61 ng/ml,t=2.684), IL-6 (12.47 ± 2.16 ng/mlvs. 15.58 ± 3.12 ng/ml,t=2.564), and TNF-α (25.43 ± 4.27 ng/ml vs. 32.55 ± 6.14 ng/ml,t=2.594) was significantly lower in the treatment group than those in the control group. However, the expression of IL-10 (10.07 ± 2.13 ng/mlvs. 7.94 ± 1.83 ng/ml;t=2.673,P=0.023) was significantly higher in the treatment group than that in the control group. The temperature decreased time (4.57 ± 1.24 dvs.
3.25 ± 0.92 d,t=2.628), cough disappeared time (7.53 ± 2.13 dvs.6.14 ± 1.59 d,t=2.416), pulmonary rales disappeared time (6.81 ± 1.82 dvs.5.17 ± 1.06 d,t=2.537) was significantly lower in the treatment group than those in the control group.Conclusions TheTanreqing injection combined with routine western medicine could regulate Th17/Treg cells balance in the senile patients with bronchial pneumonia, and showed the significantly clinical effect.

OBJECTIVE:To establish a method for the dissolution determination of Dronedarone hydrochloride tablet,and eval-uate the quality consistency of its generic and original preparations. METHODS:UV spectrometry was performed on the column of 288 nm,dissolution media of Phosphate buffer solution (pH4.5),0.1 mol/L Hydrochloric acid solution [adding into 0.5% sodium dodecyl sulfate(SDS)],Phosphate buffer solution [pH6.8,adding into 0.5%SDS] and water,volume of dissolution medium was 1 000 ml,rotation speed was 75 r/min,the dissolution of generic and original preparations of Dronedarone hydrochloride tablet was detected,and the similarity of dissolution curve was evaluated by calculating the similarity factor (f2). RESULTS:The linear range of dronedarone hydrochloride was 2.147-25.764 μg/ml;RSDs of precision,stability and reproducibility tests were lower than 2.0%;recoveries 4 dissolution media were 99.53%-101.05%(RSD=0.48%,n=9),98.95%-100.05%(RSD=0.39%,n=9), 99.54%-100.20%(RSD=0.24%,n=9)and 98.54%-100.06%(RSD=0.44%,n=9). In the 4 dissolution media,f2 of the dissolu-tion curve of 3 batches of generic and original preparations of Dronedarone hydrochloride tablet was 56,60,63,68,68,52,59, 67,65,68,76,62,respectively. CONCLUSIONS:The method is suitable for the dissolution determination of Dronedarone hydro-chloride tablet;meanwhile,the in vitro dissolution curves of generic and original preparations of Dronedarone hydrochloride tablet show similarity,so the quality consistency is good.