OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

MELAS syndrome is a genetic disease caused by mutations in mitochondrial DNA(mtDNA)or nuclear DNA.Eighty percent of the cases are caused by m.3243A>G mutation.Heteroplasmy,defined as the presence of both normal and mutant mtDNA in cells,is related with the severity of MELAS syndrome.This article reviews the research in mtDNA heterogeneity related to MELAS syndrome,aiming to provide an insight into new therapies for the syndrome.

Background and purpose:Currently,for patients with mid-to-low locally advanced rectal cancer and potentially resectable T4bM0 colon cancer,guidelines recommend neoadjuvant therapy strategies to enhance the response rate and increase the likelihood of conversion surgery.Among these patients,ypⅢ stage colorectal cancer(CRC)is assessed using the Union for International Cancer Control(UICC)/American Joint Committee on Cancer(AJCC)TNM staging system for postoperative pathological features.However,neoadjuvant therapy can lead to lymph node regression in the surgical area,resulting in an insufficient number of detected lymph nodes(less than 12),preventing classification according to conventional TNM staging.Thus,TNM staging often fails to predict the prognosis of ypⅢ patients who have undergone neoadjuvant therapy.This study aimed to evaluate the prognostic value of the positive lymph node ratio(LNR)in ypⅢ stage CRC patients treated with neoadjuvant therapy.Methods:Retrospective data was collected from ypⅢ stage CRC patients who received neoadjuvant therapy and underwent radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2018.Collect clinical pathological characteristics such as age,gender,primary tumor location,tumor differentiation grade,pathological staging,and whether the patient has relapsed or died during follow-up at the time of surgery.Inclusion criteria:CRC patients who have received neoadjuvant therapy and surgery and have been confirmed to be stage Ⅲ by postoperative pathological examination.Exclusion criteria:① Preoperative imaging examination or intraoperative exploration reveals distant organ metastasis;② History of malignant tumors in the past;③ Multiple primary CRC.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:050432-4-2108*).The R software survminer package(surv_cutpoint algorithm)was used to calculate the optimal cutoff value for LNR relative to disease-free survival(DFS),and patients were divided into low and high LNR groups accordingly.Clinical pathological characteristics and DFS were compared between the two groups.COX proportional hazards regression models were employed to identify adverse pathological features,and survival plots along with prediction models for DFS were generated using the survival and rms packages.Results:A total of 489 patients were included,comprising 289 males and 200 females,with a median age of 56 years(23-80 years)and a median follow-up time of 1 062 d.During the follow-up period,164 patients(33.5%)died.In the entire cohort,204(41.7%)patients had fewer than 12 lymph nodes detected.The optimal cutoff value for LNR was 0.29,classifying 317 patients into the low LNR group(LNR≤0.29)and 172 patients into the high LNR group(LNR＞0.29).The high LNR group exhibited shorter DFS compared to the low LNR group[hazard ratio(HR)=2.103,95%CI:1.582-2.796,P＜0.000 1].Multivariate COX regression indicated that LNR was an independent prognostic factor for DFS(HR=1.825,95%CI:1.391-2.394,P＜0.001).The inclusion of LNR in a multicategory DFS nomogram prediction model effectively assessed DFS in stage Ⅲ CRC patients who had undergone neoadjuvant therapy.Conclusion:LNR is an independent prognostic factor for ypⅢ stage CRC patients,showing good predictive power for DFS when combined with other adverse pathological features.Therefore,incorporating LNR as a supplement to TNM staging can improve the accuracy of CRC prognosis assessment.

Objective To explore the potential mechanism of Shuangshen Ningxin Capsules in the treatment of coronary microvascular disease(CMVD)using transcriptomics;To verify it.Methods Totally 30 male SD rats were randomly divided into sham-operation group,model group and Shuangshen Ningxin Capsules group,with 10 rats in each group.Shuangshen Ningxin Capsules group was given Shuangshen Ningxin Capsules solution(90 mg/kg)in advance for 7 days by gavage,while the sham-operation group and model group were given normal saline.CMVD rat model was established through left ventricular injection of embolic microspheres 2 hours after the last administration.The sham-operation group underwent open chest surgery and injected normal saline.24 hours after modeling,ultrasound was used to detect cardiac function[left ventricular systolic anterior wall thickness(LVAWs),left ventricular diastolic anterior wall thickness,left ventricular systolic posterior wall thickness,left ventricular diastolic posterior wall thickness,left ventricular end systolic diameter(LVIDs),left ventricular end diastolic diameter,left ventricular end diastolic volume,left ventricular end systolic volume(LVVs),stroke volume(SV),cardiac output(CO),ejection fraction(EF),fractional shortening(FS)];the reagent kit was used to detect the contents of serum CK,CK-MB and LDH;TTC staining was used to detect myocardial infarction area;HE staining was used to observe myocardial tissue morphology;transcriptome sequencing was used to detect common differentially expressed genes among the sham-operation group,model group and Shuangshen Ningxin Capsules group,GO and KEGG pathway enrichment analysis was performed on differentially expressed genes,and mRNA expression of differentially expressed genes were validated through RT-PCR.Results Compared with the sham-operation group,LVAWs,SV,CO,EF and FS of the model group significantly decreased,LVIDs and LVVs significantly increased(P<0.05,P<0.01),serum CK,CK-MB and LDH contents significantly increased(P<0.05,P<0.01),the area of myocardial infarction increased,the arrangement of myocardial cells was disorderly,and there was obvious infiltration of inflammatory cells.Compared with the model group,the rats in Shuangshen Ningxin Capsules group showed a significant decrease in LVIDs and LVVs,a significant increase in LVAWd,LVPWs,EF and FS(P<0.01),a significant decrease in serum CK,CK-MB and LDH contents(P<0.05,P<0.01),and a significant reduction in myocardial infarction area(P<0.01),the arrangement of myocardial cells was relatively neat,and the infiltration of inflammatory cells was reduced.The transcriptome sequencing results showed that there were 287 common differentially expressed genes among the sham-operation group,model group and Shuangshen Ningxin Capsules group,mainly enriched in chemokine signaling pathway,JAK-STAT signaling pathway,regulation of actin cytoskeleton,adrenergic signaling in cardiomyocytes,PPAR signaling pathway,NOD-like receptor signaling pathway,etc.RT-PCR validation results showed that Shuangshen Ningxin Capsules could significantly down-regulate the mRNA expressions of JAK2,STAT1,CXCL10,CXCL13 and CCR1 in myocardial tissue of model rats(P<0.05,P<0.01).Conclusion Shuangshen Ningxin Capsules can significantly improve cardiac function and reduce myocardial infarction area in CMVD rats,possibly by inhibiting the expressions of JAK-STAT signaling pathway JAK2 and STAT1,reducing the expressions of chemokines and their receptors(CXCL10,CXCL13,CCR1),reducing the recruitment of inflammatory cells,and exerting anti-inflammatory effects.

OBJECTIVE To observe the efficacy of cetrorelix combined with aspirin in preventing early-onset ovarian hyperstimulation syndrome （OHSS）. METHODS A retrospective analysis was conducted on clinical data from 38 early-onset OHSS patients， who received treatment in our hospital from January 1st to July 1st， 2022. These patients were divided into intervention group （19 cases） and control group （19 cases） according to the therapy regimen. On the first day after oocyte retrieval surgery， the control group was given aspirin enteric-coated tablets 100 mg orally until menstruation began. The intervention group was given cetrorelix for injection 0.25 mg subcutaneously， for consecutive 3 days+aspirin enteric-coated tablets （same usage and dosage as the control group）. The first luteal phase， the degree of OHSS， and the ovarian volume， ascites volume， serum estradiol （E2）， white blood cell count （WBC）， hematocrit （HCT）， neutrophil ratio （NEUT%）， D-dimer （DD）， prothrombin time （PT）， fibrinogen （Fib） after oocyte retrieval surgery were observed and measured in 2 groups. RESULTS The first luteal phase was significantly shorter， and the proportions of median and severe OHSS cases were significantly lower in the intervention group compared to the control group （P＜0.05 or P＜0.01）. After oocyte retrieval surgery， the intervention group showed significantly lower ovarian volume， ascites volume， serum E2， WBC， NEUT%， HCT， DD and Fib compared to the control group， but PT of intervention group was signiticantly higher than that of control group （P＜0.05）. CONCLUSIONS Cetrorelix combined with aspirin is more effective in preventing early-onset OHSS than aspirin alone.

OBJECTIVE To explore the safety， effectiveness， and cost-effectiveness of elderly patients with sarcopenia receiving Shenling baizhu powder combined with nutrition and exercise intervention， providing a reference for rational clinical drug use. METHODS A total of 237 elderly sarcopenia patients were randomly assigned to an observation group （118 cases） and a control group （119 cases）. Both groups of patients received nutrition and exercise intervention； the observation group added Shenling baizhu powder （6 g each time， three times daily） on this basis. The safety， effectiveness， and cost-effectiveness of the two plans were compared after 3 months. RESULTS Both groups of patients completed the follow-up. Before intervention， no significant difference was observed in skeletal muscle index （SMI）， grip strength， and 6-minute walk test （6MWT） speed between the two groups （P＞0.05）. After intervention， the grip strength of the patients in the observation group was significantly greater than that of the control group （25.05 kg vs. 23.18 kg， P＜0.01）； the treatment response rate of sarcopenia， SMI， and 6MWT speed were higher than those of the control group， butthe differences were not statistically significant （P＞0.05）. The adverse reaction/event rate of the patients in the observation group was lower than that of the control group （14.41% vs. 16.81%， P＝0.611）， but the difference was not statistically significant. Compared with the control group’s plan， the cost of the observation group’s plan was higher （981.25 yuan vs. 913.94 yuan）， and the effect was better （effectiveness rate： 0.618 6 vs. 0.563 0）， with an incremental cost-effectiveness ratio of 1 210.61 yuan. The results of the sensitivity analysis were consistent with the cost-effectiveness analysis results. CONCLUSION Elderly patients with sarcopenia who receive Shenling baizhu powder combined with nutrition and exercise intervention can significantly strengthen grip strength without increasing the incidence of adverse reactions/events. Compared with the control group plan， the observation group needs to spend an additional 1 210.61 yuan for each additional effective patient with sarcopenia.

Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.