OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

Objective To retrospective analyze the use of inpatients taking sacubitril/valsartan in Nanjing Drum Tower Hospital,and to provide references for rational clinical application.Methods The relevant data of inpatients taking sacubitril/valsartan in our hospital were systematically collected from July 2019 to September 2021,and the rationality of drug use was eval-uated.Results A total of 2 682 cases were collected,and 868 cases(32.36%)of them involved 918 times of irrational drug use.The specific situations of irrational drug use included off-label use(182 times),irrational usage and dosage(389 times),irrational conversation of drugs(251 times),and irrational drug use for special populations(96 times).Conclusion The use of sacubitril/valsartan exists in unreasonable situations in our hospital.Clinical pharmacists should participate in medication man-agement to a certain extent,strengthen the pharmaceutical care of patients,and improve the rational rate of drug use.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

OBJECTIVE To develop a standard of hierarchical management for patients with chronic obstructive pulmonary disease （COPD） from the perspective of pharmacists. METHODS The triangle hierarchical management model was used as the framework. Through literature research， the indicators of the hierarchical management standard for COPD patients were preliminarily compiled. A questionnaire was designed and administered to 18 experts， and Delphi method was conducted in two rounds to determine the contents of the standard. RESULTS The response rates for both rounds of expert consultation were 100%， with both authority coefficients of experts of 0.903 and Kendall coordination coefficiens of 0.279 and 0.189 for each indicator. The final established standard of hierarchical management for COPD patients included 25 stratified indicators and 17 pharmaceutical hierarchical management indicators. There were 9， 8 and 8 indicators in the high-risk， medium-risk， and stable layers， respectively， considering three aspects： disease， medication， and self-management level. The corresponding first-level， second- level， and third-level pharmaceutical management included 6， 6 and 5 indicators， respectively， including inhalation technical guidance， medication adherence guidance， treatment monitoring， and follow-up， etc. CONCLUSIONS The standard of hierarchical management for COPD patients established by Delphi method is scientific and reliable， which can provide a reference for pharmacists to carry out hierarchical management of COPD patients in China.

Objective:To explore the surgical treatment of lateral condylar fracture of the humerus combined with lateral dislocation of the elbow in adults.Methods:A retrospective study was conducted to analyze the 8 patients who had been treated at Department of Orthopaedic Trauma, Zhengzhou Orthopaedic Hospital for lateral condylar fracture of the humerus combined with lateral dislocation of the elbow from June 2020 to June 2023. There were 3 males and 5 females, with an age of (50.1±12.3) years. All the lateral condylar fractures of the humerus combined with lateral dislocations were treated by open reduction and internal fixation after swelling subsided. Flexion and extension of the elbow and rotation of the forearm were recorded at the last follow-up. Mayo elbow function score (MEPS) was used to evaluate the functional recovery of the elbow.Results:Elbow dislocation was corrected in 2 patients after rectification, but the elbow subluxation still existed because the displacement of the humeral lateral condyle was not reduced. The elbow dislocation still existed in 6 patients because it was difficult to maintain the correction of the dislocation after manual reduction. Follow-ups were conducted for 12.0 (12.0, 18.8) months. At the last follow-up, the flexion-extension was 85.6°±20.3°, rotation 133.1°±24.0°, and MEPS (91.9±8.0) points. The joint stability was significantly improved in the 8 patients compared with that before operation. Obvious pain was reported in none of the patients, and their joint limitation was acceptable.Conclusions:In adults, lateral condylar fracture of the humerus combined with lateral dislocation of the elbow is rare in clinic. Surgical treatment of the condition can achieve satisfactory clinical outcomes, but elbow dysfunction and limited rotation of the forearm may occur in the affected limb.

OBJECTIVE To analyze the research status and development trends of the use of sacubitril/valsartan. METHODS Related literature about the use of sacubitril/valsartan were retrieved from CNKI and the core database of Web of Science. CiteSpace 5.8.R3 software was used to analyze authors， countries/areas， institutions and keywords. RESULTS & CONCLUSIONS Totally 1 193 Chinese literature and 1 060 English literature were included. The number of literature increased， with numerous literature covering the United States （429）， the United Kingdom （185） and China （184）. ZHANG Jing （5） and Solomon S D （118） published the highest number of Chinese and English articles. The authors of Chinese literature had less cooperation while the authors of English literature were in close contact. Dept. of Cardiology in the First Affiliated Hospital of Zhengzhou University （9）， Dept. of Cardiology in the Affiliated Hospital of Xuzhou Medical University （9） and Novartis AG （134） had the highest quantity of publications of Chinese and English literature. The institutions of Chinese literature had a small number of overall publications and less cooperation while the institutions of English literature were closely connected. The clinical efficacy of sacubitril/valsartan for heart failure， hypertension and their complications were research hotspots in Chinese and English literature. Chinese scholars and research teams need to strengthen cooperation and communication in the future， as well as conduct research from the perspectives of sacubitril/valsartan in the treatment of heart failure， hypertension and related complication， the improvement of oxidative stress， and the evaluation of the efficacy of combination therapy with dapagliflozin.

Objective:To investigate the therapeutic effect and possible mechanism of low intensity pulsed ultrasound（LIPUS）on painful gait in mice with Achilles tendon injury.Methods:Male C57BL/6 mice were selected to establish the Achilles tendon injury model by surgically full-thinkness tear of the right Achilles tendon. The mice were divided into Achilles tendon injury group and Achilles tendon injury+LIPUS group according to the random number table method，with 7 mice per group. The Catwalk gait analysis system was used to evaluate the gait function of the mice by measuring the following five parameters 14 days after operation，including print area，standing time，step cycle，max intensity and stride length. Morphological changes of the Achilles tendon were observed by HE staining. Immunofluorescence staining was used to detect the expression level of nitric oxide synthase（iNOS）in the Achilles tendon tissues. At the same time，Achilles tendon cells were isolated and cultured in vitro. The cells were induced by 100 ng/ml lipopolysaccharide（LPS）for 12 hours to establish in vitro model（LPS group），and treated with LIPUS（LPS+LIPUS group）. The control group was set as well（without any treatment）. The nuclear translocation of nuclear transcription factor-κB（NF-κB）P65 was detected by immunofluorescence staining，and the expression of iNOS and phosphorylation（p）-NF-κB p65 protein was detected by Western blotting. Results:Compared with Achilles tendon injury group［（0.14±0.10）cm 2］，the print area of the affected limb in Achilles tendon injury+LIPUS group［（0.28±0.13）cm 2］was increased（ P<0.05）. Compared with Achilles tendon injury group［（0.11±0.04）seconds］，the standing time of the affected limb in Achilles tendon injury+LIPUS group［（0.21±0.03）seconds］was increased（ P<0.05）. Compared with Achilles tendon injury group［（0.25±0.05）seconds］，the step cycle of the affected limb in Achilles tendon injury+LIPUS group［（0.40±0.05）seconds］was increased（ P<0.05）. There was no significant difference in the max intensity and stride length between Achilles tendon injury group and Achilles tendon injury+LIPUS group（ P>0.05）. HE staining showed obvious hyperplasia of Achilles tendon tissues in Achilles tendon injury group，with loosely and randomly arranged fibers，accompanied by neovascularization and inflammatory cell infiltration. Achilles tendon injury+LIPUS group showed more orderly arranged fibers in Achilles tendon tissues，and the degree of neovascularization and inflammatory cell infiltration were reduced. Compared with Achilles tendon injury group［（5.70±0.81）%］，the expression level of iNOS in Achilles tendon injury+LIPUS group［（2.84±0.94）%］was decreased 14 days after operation（ P<0.05）. Immunofluorescence results of Achilles tendon cells showed that NF-κB p65 protein entered the nucleus in LPS group compared with control group，and that LIPUS treatment inhibited nuclear translocation. In control group，Western blotting showed that iNOS was not expressed，and that the expression of phosphorylated NF-κB p65 was 0.63±0.16. Compared with control group，the expression levels of iNOS（0.99±0.22）and p-NF-κB P65（1.02±0.19）in LPS group were significantly increased（ P<0.05）. Compared with LPS group，the expression levels of iNOS（0.62±0.10）and p-NF-κB P65（0.65±0.21）in LPS+LIPUS group were decreased（ P<0.05）. Conclusion:LIPUS treatment can alleviate pain gait in mice with Achilles tendon injury and inhibit iNOS expression in vivo and in vitro，which may be related to inhibition of NF-κB signaling pathway.

Objective Background and objective The Cox maze Ⅲ procedure has been considered the gold standard for the surgical treatment of atrial fibrillation (AF) and the modified Cox maze use bipolar radiofrequency ablation instead of the cut-and-sew technique,while also reducing the connecting lines in left atrium.This study was to understand whether completely isolation the posterior left atrium by increasing left atrium ablation lines can enhance the survival after modified Cox maze procedure.Methods From Jan 2009 to Dec 2009,all the patients underwent the Cox maze procedure,following the same examination,were divided into two groups (case-control): box lesion group (n =60),which is means the right and lefi pulmonary vein lesions were connected inferiorly by adding ablation lines,thereby completely isolating the posterior left atrium and the non-box lesion group (n =60).Similar interventions were given during the perioperative periods.Comparing the risk factors before surgeries,then follow-up was 100％ complete,and the mean follow-up was 9 ± 8.4 months.Results Except the box lesion had long time of extracorporeal circulation,the characteristics of the 2 groups were similar because there were no differences in age,AF duration,left atrial diameter,left ventricular ejection fraction or homochronous operation between the groups and there was no operative death.No patient was lost to follow-up.In the mean follow-up duration,a patient was died of intracerebral hemorrhage at 2 months postoperationly in the box lesion group and a patient suffered from stroke at 12 months postoperationly in the non-box lesion.The overall freedom from AF recurrence was higher in the box lesion group at 1 (70％ vs 51.2％,P =0.039) and 3 (78.3％ vs 60％,P =0.030) months.While it was 80％ vs 71.7％ (P =0.286) at 6 months.Eight patients wrere readmitted because of the recurrence of AF,4 and 2 patients underwent catheter ablation in box and non-box group respectively,one patient in each group underwent electrical conversion.After treatment,all of the patients were recovered to sinus rhythm and continued to take cordarone.Conclusion Compared to the single connecting between right and left pulmonary vein,isolating the entire posterior left atrium by creating a box lesion showed higher freedom from AF in the earlier months (1-3months).However,half a year after the surgery,there were no significant differences between the two groups.

[Objective] To study the apoptosis after long time of heart preservation,and the barrier of caspase (Ac-DEVD-CHO) in prolonged heart transplantation.To improve the techniques on the preservation of donor heart.[Methods] Donor rat hearts were subjected to group A (non-Ac-DEVD-CHO-treated),group B (Ac-DEVD-CHO-treated) of hypothermic storage,after 9 hours of heart preservation,then performed heterotopic heart transplantation,followed by 60 min of normothermic reperfusion (n ＝ 6 in each group).[Results] After 60 min reperfusion,compared with group A,① a significant improvement in the percent recovery of HR was observed in group B (P ＜ 0.05);② Caspase-3 activity was decreased in group B (P ＜ 0.01);③ an apparent decline in the expression of infarct area was observed in group B (P ＜ 0.01);④ an apparent decline in the expression of TUNEL-positive cardiomyocyte was observed in group B (P ＜ 0.01);⑤ Group B shows the least disease.[Conclusion] ① After preservation and reperfusion,cardiomyocyte apoptosis was observe evidently,which led to irreversible heart dysfunction.② The administration of caspase-3 inhibition after reperfusion attenuates ischemia-reperfusion injury by suppressing apoptosis in heart transplantation.Furthermore,the use of caspase inhibition was investigated as a strategy for the preservation donor heart in transplantation.③ The relationship of dose-response and time-effect is still unknown.