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 （20 133-49 283 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 25 193.49 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 26 010 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 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.

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 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 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.

OBJECTIVE：To prepare Azelnidipine enteric solid dispersion and evaluate its quality. METHODS ：Azelnidipine enteric solid dispersion was prepared by solvent method. Taking cumulative dissolution rate as the index ，single factor test was used to optimize carrier material type and its ratio. The quality of the product was evaluated by DSC ，XRD and FTIR ，and its stability was investigated. RESULTS ：After azelnidipine and carrier material of Eudragit L 100-55 acrylic resin were prepared to enteric solid dispersion at a ratio of 1∶5（m/m），its dissolution rate was significantly improved. DSC ，XRD and FTIR method had all verified the crystal form of azelnidipine changed and it existed in amorphous form. The results of stability test showed that Azelnidipine enteric solid dispersion was stable under high temperature （60 ℃），high humidity （75％）and strong light [ （4 500±500）lx] for 10 days. CONCLUSIONS ：Azelnidipine enteric solid dispersion by solvent method with Eudragit L 100-55 acrylic resin as carrier can eliminate the influence of crystal form ，improve dissolution and has good stability.

Objective    To explore the current situation of the readiness for hospital discharge and the quality of discharge teaching in lung cancer patients based on enhanced recovery after surgery, and to analyze their correlation. Methods    We conducted a cross-sectional study and 141 postoperative patients with lung cancer in our hospital from July to August 2018 were investigated by general information questionnaire, readiness for hospital discharge scale and quality of discharge teaching scale. There were 65 males and 76 females at age of 18-85 (55.35±12.15) years. Results    Totally 88.65% of postoperative patients with lung cancer reported that they were ready for discharge, and the total score of readiness for hospital discharge was 78.36±16.48, and the total score of quality of discharge teaching was 90.94±18.62. There was a positive correlation between the readiness for hospital discharge and the quality of discharge teaching in postoperative patients with lung cancer (r=0.57, P<0.01). Conclusion    The readiness for hospital discharge of postoperative patients with lung cancer keeps in medium level, while the quality of discharge teaching is good, and the readiness for hospital discharge is positively correlated with the quality of discharge teaching. Medical staff should pay more attention to the cognitive level of lung cancer patients' disease-related information and their physical function recovery, and enrich the discharge guidance content, in order to improve the readiness of postoperative patients with lung cancer.

Objective To understand the pathogenicity and multilocus sequence typing (MLST) characteristics of the pathogenic strain of Burkholderia pseudomallei (Bp) in Hainan,and provide a reference for studying the structural characteristics and phylogenetic characteristics of pathogenic Bp in Hainan.Methods The data of patients with melioidosis in Hainan,who were treated in Hainan General Hospital from 2011 to 2018,and Bp pathogenic strains isolated from patient infected specimens were collected.The Bp pathogenic strains were genotyped by MLST method,and the distribution characteristics of the sequence type (ST) were analyzed.The ST of all Bp pathogenic strains was analyzed by eBURST v3 software to establish the evolutionary relationship map.Results A total of 91 cases of melioidosis patients were studied,including 76 males and 15 females;the ages were mainly concentrated in 40-70 years old;clinical manifestations included sepsis,pulmonary infection and local abscess;and the most common diseases were diabetes.A total of 91 Bp pathogenic strains were observed,of which 85 Bp pathogenic strains were distributed in coastal areas of Hainan,accounting for 93.41％;identified by MLST method,39 ST were discovered,the most common were ST46 (13 strains),ST55 (12 strains),STS0 (8 strains) and ST58 (7 strains),accounting for 14.29％,13.19％,8.79％ and 7.69％,respectively;except ST46 was widely distributed in the coastal areas of Hainan,the ST55,ST50 and ST58 were concentrated in the southwest,northeast and southeast regions of Hainan.Compared with the MLST database,ST30 (3 strains) was currently found only in Hainan,ST562 (4 strains) had been reported in northern Australia,and the remaining ST models had been reported in southeast Asia.The eBURST v3 software divided the 39 ST into 3 subtypes and 18 individual types.Among them,the subtypes with ST300 as the original type had the most number of ST,including 17 ST,57 Bp pathogenic strains;compared with the MLST database,the ST300 was mainly distributed in southeast Asian regions such as Thailand.Conclusions The ST of Bp pathogenic strains in Hainan has high regional diversity and genetic diversity,and is closely related to Bp in southeast Asian regions such as Thailand.

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5-3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.
Child ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Recombinant Proteins ; therapeutic use ; Thyrotropin ; blood ; Thyroxine ; blood