[Objective] To explore the incidence and risk factors of blood transfusion undergoing total knee revision (TKR) using a nationwide database. [Methods] A retrospective data analysis was conducted based on the Nationwide Inpatient Sample (NIS), enrolling patients who underwent TKR from 2015 to 2019 with complete information. Patients under 18 years old and those using anticoagulants, antiplatelets, antithrombotic and non-steroidal were excluded. The patients were divided into two groups based on whether they received blood transfusion or not. The demographic characteristics, length of stay (LOS), total charge of hospitalization, hospital characteristics, hospital mortality, comorbidities and perioperative complications by Wilcoxon rank test for continuous data and chi-square test for categorical data. Logistic regression was performed to identify risk factors of blood transfusion undergoing TKR. [Results] The NIS database included 63 359 patients who underwent TKR. Among them, 5 271 patients received blood transfusion, with an incidence of blood transfusion of 7.8%. There was a decrease in the incidence over the years from 2015 to 2019, dropping from 10.2% to 6.5%. TKR patients requiring transfusions had experienced longer LOS, incurred higher total medical expenses, utilized Medicare more frequently, and had increased in-hospital mortality rates (all P<0.001). Independent risk factors for blood transfusion included female gender, iron-deficiency anemia, rheumatoid disease, collagen vascular disease, chronic blood loss anemia, congestive heart failure, coagulopathy, diabetes with chronic complications, lymphoma, fluid and electrolyte disorders, peripheral vascular disorders, renal failure, valvular disease and weight loss (malnutrition). In addition, risk factors for transfusion in TKR surgery included sepsis, acute myocardial infarction, deep vein thrombosis, gastrointestinal bleeding, heart failure, pneumonia, urinary tract infection, acute renal failure, postoperative delirium, wound infection, lower limb nerve injury, hemorrhage, seroma, hematoma, wound rupture and non healing. [Conclusion] Our findings highlight the importance of recognizing the risk factors of blood transfusion in TKR and establishing corresponding clinical pathways and intervention measures to reduce the occurrence of adverse events.

OBJECTIVE To investigate the effects of ertugliflozin on pharmacokinetic of sorafenib and donafenib in rats and explore the mechanism. METHODS Twenty-four male SD rats were randomly divided into four groups， with 6 rats in each group. Groups A and B were respectively gavaged with 0.5% sodium carboxymethyl cellulose solution and ertugliflozin （1.5 mg/kg） for 7 consecutive days， and both were given sorafenib （100 mg/kg） on the 7th day. Groups C and D were administered intragastrically in the same way as those in Groups A and B， respectively， for the first 7 days； after the drug administration on the 7th day， all rats in Groups C and D were further gavaged with donafenib （40 mg/kg）. Blood samples were collected at different time points before and after administration of sorafenib or donafenib， the concentrations of sorafenib in plasma of rats in groups A and B and donafenib in groups C and D were determined by UPLC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 2.1.1 software. Six additional rats were randomly divided into blank control group and ertugliflozin group， with three rats in each group. Blank control group was given 0.5% sodium carboxymethyl cellulose intragastrically， while rats in ertugliflozin group were given ertugliflozin （1.5 mg/kg） once a day for 7 consecutive days. After the last administration， the mRNA expression levels of uridine diphosphate glucuronosyl transferase 1A7 （UGT1A7）， breast cancer resistance protein （BCRP）， and P-glycoprotein （P-gp） in the liver and small intestine tissues of the rats were detected. RESULTS Compared with group A， the AUC0-t， AUC0-∞， cmax， tmax， MRT0-t and MRT0-∞ of sorafenib in group B were decreased significantly， while CL and V were increased significantly. Compared with group C， the AUC0-t， AUC0-∞ ， tmax， cmax and MRT0-t of Δ donafenib in group D were decreased significantly， while V and CL were increased significantly （P＜0.05）. mRNA expression of UGT1A7， P-gp and BCRP in the liver tissue and small intestine of rats were not significantly affected after intragastric administration of ertugliflozin for 7 consecutive days. CONCLUSIONS Ertugliflozin can affect the pharmacokinetics of sorafenib and donafenib in rats and decrease the plasma exposure of them significantly. However， its mechanism of action may not be through the regulation of related metabolic enzymes and transporters. When using drugs in combination clinically， one should be vigilant about the potential for disease progression due to poor therapeutic effects.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

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.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

In non-small cell lung cancer(NSCLC),as an improtant oncogenic driver gene,epidermal growth factor receptor exon 20 insertion(EGFR ex20ins)has a unique protein structure and is primarily drug-resistant to tradi-tional EGFR-tyrosine kinase inhibitors(EGFR-TKIs).In recent years,exploration of targeted therapy for EGFR ex20ins has never stopped.Firstly Mobocertinib and Amivantamab obtained approval from U.S.Food and Drug Administration(FDA)for EGFR ex20ins mutant NSCLC patients,then other drugs,such as Sunvozertinib,made breakthroughs and combination therapies also obtained gains.Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance.As men-tioned above,it's definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess ef-fect and difference between novel drugs.This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.