Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

Objective To explore the possible mechanisms of myocardial injury induced by simulated weightlessness in space flight and the recovery of myocardium in rats by aerobic exercise intervention.Methods The body weight of rats was weighed using an electronic balance;the cardiac function indexes of rats in each group were detected using echocardiography and isolated cardiac perfusion;and the expression of proteins related to the AMPK/ULK1/Beclin1 pathway in the myocardial tissues of rats in each group was detected using Western Blot.Results(1)When compared with the C1 group,the T1 group not statistically significant in body weight(P?>?0.05),and the wet weight of the flounder muscle,the wet weight-to-weight ratio of the flounder muscle,and the heart weight were all significantly decreased(P??0.05).After 4 weeks of aerobic exercise,when compared to group C2,group R showed a significant rise in the expression of AMPK and ULK1(P??0.05),and a rise in the expression of Beclin1,but not statistically significant(P?>?0.05);and group A showed a slight increase in the expression of AMPK,ULK1 and Beclin1 expression decreased slightly but not statistically significant(P?>?0.05),p-AMPK expression decreased significantly(P??0.05),and a significant decrease in the expression of ULK1(P??0.05);the expression of p-ULK1 decreased significantly(P?

Objective To evaluate the efficacy,safety,and economy of 4 intravenous iron formulations in the treatment of iron deficiency anemia(IDA)by rapid health technology assessment,and to provide evidence for clinical decision-making.Methods PubMed,Embase,the Cochrane Library,CNKI,WanFang,SinoMed,and official websites of international health technology assessment agencies were electronically searched to collect health technology assessment reports,systematic reviews/Meta-analysis,and pharmacoeconomic studies concerning the treatment of IDA with iron sucrose(IS),iron dextran(ID),ferric carboxymaltose(FCM),and iron isomaltoside(IIM)from the inception to August 15,2024.Two researchers independently screened the studies,extracted data and assessed the quality of included studies.The results were then qualitatively described and analyzed.Results A total of 32 studies were included,including one health technology assessment report,16 systematic reviews/Meta-analysis,and 15 pharmacoeconomic evaluations.In terms of effectiveness,FCM had a higher response rate than that of IS(P＜0.05),FCM and IIM had no statistical difference(P＞0.05).Regarding hemoglobin level change,patients treated with FCM had higher hemoglobin levels than those treated with IS(P＜0.05);the improvement in hemoglobin levels between IIM and FCM was inconclusive.In terms of ferritin level change,FCM might be superior to the other three intravenous iron formulations.In terms of safety,the adverse event rates for FCM,IS,ID and IIM were 12.0％,15.3％,12.0％and 17.0％,respectively;IIM was significantly associated with a lower rate of cardiovascular adverse events compared to FCM and IS(P＜0.05);FCM had the highest rate of hypophosphatemia among the four formulations(P＜0.05),and there was no significant difference among IIM,IS and ID(P＞0.05);IIM had a lower risk of severe or serious hypersensitivity reactions compared to FCM and IS.In terms of economy,FCM and IIM had an economic advantage compared to IS.The economic efficiency ranking among IS,ID,and FCM was in the order of FCM,ID,and IS,the economic comparison between FCM and IIM remains inconclusive and needs to be further demonstrated.Conclusion FCM and IIM have good efficacy,safety and economy in the treatment of IDA,but most of the included economy studies based on foreign populations,and domestic economic studies need to be further demonstrated.

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.

OBJECTIVE： To investigate the current situation of medication safety in 24 public medical institutions（referred to as “hospital”） from Linyi city and the differences in medication safety between urban and rural areas. METHODS： ISMP self-assessment scale [including 10 key elements （Ⅰ-Ⅹ，such as “Ⅰ patient’s information” “Ⅱ drug information”）， 20 key characteristics and 270 evaluation projects] developed by Institute of Safe Medication Practices was used to investigate 24 hospitals in Linyi city. The implementation rates of 10 key elements in urban and rural hospitals were analyzed statistically， and the top 10 evaluation projects were listed for the key elements with the lowest implementation rate. The key elements and top 10 evaluation projects with the largest difference in the implementation rate were compared between urban and rural hospitals. Radar maps were used for comparison and analysis intuitively. RESULTS： A total of 24 hospitals were surveyed， including 12 in urban and 12 in rural areas； there were significant differences in the implementation rate of 10 key factors among 24 hospitals； the elements with the highest implementation rate were “Ⅶ environmental factors， workflow and staffing pattern”（56.55％）；the elements with the lowest implementation rate was “Ⅱ drug information” （26.77％）. Among 33 evaluation projects of “Ⅱ drug information”， the implementation rate of No. 36 project （12.50％， related to opioids） was the lowest. Among the implementation rates of 10 key elements in 12 urban hospitals and 12 rural hospitals， the key elements with the greatest difference was “Ⅳ drug label， packaging and naming” （differing by 44.44％，59.72％ vs. 15.28％）； Among“Ⅸ patient education”evaluation project with the greatest gap， there was the greatest difference in No. 199 project （related to patients’ active participation in medication， 58.33％ in urban， 4.17％ in rural）. CONCLUSIONS： The results of medication safety investigation in 24 hospitals from Linyi city show that all the item in each hospital needs to be improved expecially in the implementation of “Ⅱ drug information”. Rural hospitals should strengthen medication education for patients.

Objective To investigate the effect of anesthesia factor on lung injury in patients un?dergoing thoracoscopic radical lung cancer surgery and to evaluate efficacy of combination of thoracic para?vertebral block(TPVB)with dexmedetomidine mixed with ropivacaine and general anesthesia. Methods One hundred patients of both sexes, aged 18-64 yr, with body mass index of 18-25 kg∕m2, of American Society of Anesthesiologists physical statusⅡorⅢ, scheduled for elective thoracoscopic radical lung cancer surgery, were divided into 5 groups(n=20 each)using a random number table: general anesthesia group (group G), TPVB with ropivacaine combined with general anesthesia group(group R), intravenously in?fused dexmedetomidine combined with general anesthesia group(group Div), intravenously infused dexme?detomidine plus TPVB with ropivacaine combined with general anesthesia group(group Div+R), and TPVB with dexmedetomidine mixed with ropivacaine combined with general anesthesia group(group Dtp+R). In group R, TPVB was performed under ultrasound guidance, two?point method was selected accord?ing to the position of intercostal space at surgical incision, and 0.5% ropivacaine 10 ml was injected into each puncture site. Dexmedetomidine 0.5 μg∕kg was intravenously infused over 10 min in group Div. Dexmedetomidine was intravenously infused for TPVB in group Div+R. TPVB solution contained dexmedeto?midine 0.5 μg∕kg and ropivacaine in group Dtp+R. Anesthesia was then induced and maintained by IV in?fusion of propofol and remifentanil. The intraoperative consumption of propofol and remifentanil and develop?ment of adverse reactions such as hypoxemia, hypotension and bradycardia were recorded. Normal lung tis?sues around the tumor margin were obtained immediately after tumor resection for determination of the ex?pression of hypoxia?inducible factor 1 alpha(HIF?1α), BCL2∕adenovirus E1B 19kDa interacting protein 3 (BNIP3)and microtubule?associated protein 1 light chain 3Ⅱ(LC3Ⅱ)(by Western blot), contents of tumor necrosis factor?alpha(TNF?α)and interleukin?6(IL?6)in lung tissues(by enzyme?linked immu?nosorbent assay)and cell apoptosis(by TUNEL)and for examination of the pathological changes(with a light microscope)which were scored. Apoptosis index was calculated. Results The amount of propofol consumed was significantly lower in Div+R and Dtp+R groups than in the other three groups, and the a?mount of remifentanil consumed was significantly higher in G and Div groups than in the other three groups (P<0.05). The incidence of hypertension and tachycardia was significantly lower in R and Div groups than in group G(P<0.05). The incidence of hypotension was significantly lower in R, Div and Dtp+R groups than in group Div+R(P<0.05). The incidence of bradycardia was significantly higher in Div and Div+R groups than in group R(P<0.05). Compared with G and R groups, apoptosis index, contents of TNF?α and IL?6 and lung injury scores were significantly decreased, and the expression of HIF?1α, BNIP3 and LC3Ⅱ was up?regulated in Div, Div+R and Dtp+R groups(P<0.05). Compared with group Div, the TNF?α content and lung injury scores were significantly decreased, and the expression of HIF?1α and LC3Ⅱwas up?regulated in Div+R and Dtp+R groups, and the IL?6 content was significantly decreased in group Dtp+R(P<0.05). Conclusion Combination of TPVB with dexmedetomidine mixed with ropivacaine and general anesthesia produces better efficacy in reducing lung injury in patients undergoing thoracoscopic radi?cal lung cancer surgery.

Humans ; Models, Molecular ; Repressor Proteins ; chemistry ; metabolism ; Retinoblastoma-Binding Protein 4 ; chemistry ; metabolism

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.