OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Congenital lower urinary tract obstruction (CLUTO) is a spectrum of fetal malformations caused by anatomical abnormalities of the urethra, characterized by high rates of perinatal complications and mortality. The 2024 joint guideline from the European Association of Urology (EAU) and the European Society for Paediatric Urology (ESPU) introduced systematic revisions to the comprehensive management of CLUTO. Key updates encompass advancements in prenatal and postnatal screening and precise diagnosis, refined fetal prognosis assessment, clearer indications and modality selection for prenatal intervention, optimization of postnatal treatment strategies, and the establishment of a lifelong follow-up framework within an integrated care pathway. This article elucidates these key updates by comparing the 2024 EAU/ESPU guideline with the 2022 European Rare Kidney Disease Reference Network (ERKNet) consensus. It also discusses ongoing controversies and future research directions. The aim is to provide clinicians with the latest evidence-based insights to inform practice, ultimately improving outcomes and quality of life for children with CLUTO.
Humans ; Urology ; Female ; Urethral Obstruction/therapy* ; Pregnancy ; Child ; Europe ; Prenatal Diagnosis ; Infant, Newborn ; Urethra/abnormalities*

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

Objective To explore the mechanism of Huoxin pill(HXP)in the prevention and treatment of heart failure(HF)based on transcriptomics and network pharmacology.Methods The mice were randomly divided into the normal control group,model control group,positive control group treated with sacubitril/valsartan(60 mg·kg-1),low-dose group treated with HXP(31.2 mg·kg-1),and high-dose group treated with HXP(62.4 mg·kg-1).The model control group and each drug treat-ment group were subcutaneously injected with an equal volume of ISO(5 mg·kg-1)for modeling,while the normal control group was given an equal volume of sterile saline.Six hours later,each drug administration group was gavaged with the corresponding drug for intervention,and the normal control and model control groups were gavaged with an equal volume of sterile water.The modeling and drug administration were continued for 21 days.The cardiac function parameters of the mice were measured using color Doppler ultrasound imaging;ELISA was used to detect the levels of mouse serum cAMP,NT-proBNP,and BNP;HE staining and Masson's trichrome staining were used to evaluate the pathological morphology of cardiac tissue,and the CVF was calculated.Network pharmacology combined with transcriptomics was used to predict potential targets and signaling pathways of HXP in the prevention and treatment of HF,and molecular biology methods were used for validation.Results Compared with the normal control group,the model control group showed an increase in LVESd and LVEDd(P＜0.01),and a decrease in LVEF and LVFS(P＜0.01);BNP,NT-proBNP,and cAMP levels were increased(P＜0.01);myocardial collagen fibers increased and CVF in-creased(P＜0.01).Compared with the model control group,the HXP low-dose group,HXP high-dose group,and positive control groups showed a decrease in LVESd and LVEDd(P＜0.01),and an increase in LVEF and LVFS(P＜0.01);serum levels of BNP,NT-proBNP,and cAMP decreased(P＜0.05);the degree of myocardial fibrosis decreased and CVF decreased(P＜0.01).Network pharmacology combined with transcriptomics predicted 10 key targets for HXP in the prevention and treatment of HF:CACNA1H,SCN10A,FGF12,PVALB,ACAN,LGALS3,SERPINE1,MMP3,GSTM1,VDR.Western blot results showed that the protein activation levels of PKA and CREB in myocardial tissue were increased in the model control group compared with the nor-mal control group(P＜0.01).Compared with the model control group,HXP low-dose group、HXP high-dose group,and positive control groups showed a decrease in the protein activation levels of PKA and CREB in myocardial tissue(P＜0.05).Conclusion HXP has an improvement effect on ISO-induced HF in mice,which may involve numerous targets and the cAMP/PKA signaling pathway.

OBJECTIVE To compare the long-term cost-effectiveness of gonadotrophin-releasing hormone analogue (GnRHa) combined with recombinant human growth hormone (rhGH) (combination therapy regimen) versus GnRHa monotherapy (monotherapy regimen) in the treatment of central precocious puberty (CPP).METHODS From the societal perspective and based on a real-world study conducted at West China Second Hospital of Sichuan University,the cost-effectiveness analysis was performed to compare the long-term cost-effectiveness of two pharmacotherapy regimens for CPP girls,with final height as outcome indexes,using per capita disposable income of rural residents and urban residents (20133-49283 yuan) in 2022 as the social willing-to-pay (WTP) threshold.The robustness of the basic analysis result was verified by using one-way sensitivity analysis and probability sensitivity analysis,and the cost-effectiveness of different combinations of long-acting preparations was compared using scenario analysis.RESULTS The basic analysis result showed that the combination therapy regimen required an additional cost of 25193.49 yuan for every one-centimeter improvement in the final height of girls with CPP compared with the monotherapy regimen,which was not cost-effective for residents in rural areas,but it was cost-effective for residents in urban areas.One-way sensitivity analysis showed that the uncertain factors with potential impacts on the results were,in order,the price of rhGH,the final height of pediatric patients in the combination therapy regimen group,the course of rhGH in the combination therapy regimen group,and the final height of pediatric patients in the monotherapy regimen group.Probabilistic sensitivity analysis indicated that the probability of the combination therapy regimen being cost-effective was higher than that of the monotherapy regimen when WTP was more than 26010 yuan/cm.When GnRHa long-acting preparation was used for intramuscular injection every 3 months,the combination therapy regimen was not cost-effective for rural residents,but was cost-effective for urban residents;when rhGH long-acting preparation was injected subcutaneously once a week,the combination therapy regimen was not cost-effective for residents in both rural areas and urban areas.CONCLUSIONS The combination of GnRHa and rhGH is only recommended for CPP children with better affordability to improve final height.The benefits,risks,and affordability of treatment should be comprehensively considered before the decisions on pharmacotherapy,to avoid abuse of rhGH due to the blind pursuit of height growth.

Objective To evaluate the cost-effectiveness of enzalutamide in the treatment of metastatic prostate cancer from the perspective of healthcare in China.Methods Based on the published phase Ⅲ randomized controlled trial(ENZAMET),the disease process of metastatic prostate cancer was classified into three states:progression-free survival,progression survival and death,and the model period was defined as 28 days,and the study period was lifelong,and a Markov model was established to evaluate the cost-effectiveness of the treatment of enzalutamide versus standard antiandrogen drugs in metastatic prostate cancer.Setting the willingness-to-pay(WTP)threshold at 3 times our 2022 gross domestic product(GDP)per capita and the robustness of the model analysis was verified by sensitivity analysis.Results Compared to the control group standard antiandrogen therapy,the incremental effect of enzalutamide was 0.92 quality-adjusted life years(QALYs),the incremental cost was 311 863.30 yuan,and the incremental cost-effectiveness ratio(ICER)was 338 981.85 yuan/QALY,which was higher than WTP threshold(257 094 yuan/QALY).The results of univariate sensitivity analyses showed that the total cost of the enzalutamide group,the PFS utility value,the cost of the PD status of enzalutamide group,and the unit price of enzalutamide had a greater impact on the model results.The results of the probabilistic sensitivity analysis suggested that the enzalutamide treatment regimen was not economical within the willingness-to-pay threshold of 3 times our 2022 GDP per capita.Conclusion Compared with the standard anti-androgen drugs,enzalutamide does not offer a cost-effectiveness advantage in the treatment of metastatic prostate cancer.

Objective To investigate the investigation of co-morbidity etiology and prognosis analysis of chronic diseases in the elderly population. Methods The data of 1 475 elderly patients who were seen and treated in Chengdu Fifth People's Hospital from January 2019 to December 2021 were screened to analyze their disease status, co-morbidity combinations and patterns, co-morbidity influencing factors, and prognosis. Results The top four prevalence rates among 1 475 elderly patients with chronic diseases were hypertension 555 (37.63%), gastric or gastrointestinal diseases 445 (30.17%), arthritis or rheumatism 427 (28.95%), and diabetes 329 (26.58%). 1034 co-morbidities were found in 1475 elderly patients with chronic diseases, with a co-morbidity rate of 70.10%. The binary disease combination accounted for 58.41% and the ternary disease combination accounted for 41.59%. Female, age >70 years, family history of chronic diseases, overweight/obesity, daily physical inactivity, history of alcohol/smoking, poor sleep quality, and poor dietary habits were the independent influencing factors for co-morbidity in elderly patients with chronic diseases (OR_female=2.413, ORage ≥ 70=1.670, OR_{history of alcohol consumption}family history of chronic diseases=2.846, OR_{history of alcohol consumption}overweight/obesity=2.570, ORdaily inactivity=1.802, OR_{history of alcohol consumption}=3.543, ORhistory of smoking=1.784, OR_{poor sleep quality}=2.128, OR_{unhealthy dietary habits}=2.085, all P<0.05). Compared with elderly patients with chronic diseases without co-morbidity, patients with co-morbidity had higher odds of exacerbation of the original disease/acute readmission and lower odds of new chronic disease (χ²_{primary exacerbation/emergency readmission}=10.726, χ²_{new chronic disease}=5.873 , all P<0.05). Conclusion Gender, age, chronic disease history, BMI, and lifestyle habits are important factors influencing co-morbidity in elderly patients with chronic diseases, and patients with co-morbidity have a relatively poor prognosis.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.