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: This study aimed to elucidate the mechanisms underlying the impaired bone healing capacity in type 1 diabetes (T1DM) by investigating the role of the Hedgehog (Hh) signaling pathway in the impaired healing of cranial defects caused by T1DM. Methods: This study was approved by the experimental animal ethics committee of our hospital. A cranial defect model was established using Akita transgenic mice with spontaneous type I diabetes. The impact of T1DM on osteogenic differentiation and the Hh signaling pathway during cranial defect healing was explored by MicroCT scanning and immunohistochemical (IHC) analysis of osteocalcin (Ocn), Indian Hedgehog (Ihh), Patched1 (Ptch1), and zinc finger protein GLI1 (Gli1). Subsequently, the Hh signaling pathway was activated using smoothened agonist (SAG) (10 mg/kg, gavage), and its potential to improve cranial defect healing in T1DM was assessed by MicroCT and IHC staining. Finally, the ability of SAG (1 000 nmol/L) to counteract the inhibitory effects of a high-glucose environment (25 mol/L) on osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs) was investigated through in vitro experiments. Detection methods included Alkaline Phosphatase and Alizarin Red staining, as well as quantitative real-time PCR (qPCR) analysis of the osteogenesis-related genes Alp, Spp1, Bglap, and Sp7. Results: Akita mice exhibited early, stable, and significant spontaneous T1DM characteristics. On postoperative day 21, the newly formed bone in the cranial defect area of Akita mice showed significant decreases in the bone volume-to-tissue volume ratio, volumetric bone mineral density, and Ocn expression (P < 0.05), with significant downregulation of Ihh, Ptch1, and Gli1 (P < 0.05). Activation of the Hh signaling pathway by SAG significantly mitigated the negative impact of T1DM on cranial defect healing in Akita mice (P < 0.05). Moreover, after SAG treatment, the inhibitory effects of the high-glucose environment on the alkaline phosphatase activity and in vitro mineralization capacity of BMSCs were significantly alleviated (P < 0.05), and the expression levels of osteogenic differentiation-related genes were significantly upregulated (P < 0.05). Conclusion T1DM inhibits cranial defect healing in Akita mice by suppressing the expression of the Hh signaling pathway, whereas activation of the Hh signaling pathway promotes osteogenesis and ameliorates the inhibitory effects of T1DM on bone healing.

Objective:To investigate the effects of dexmedetomidine and urapidil on postoperative extubation stress response, postoperative shivering, and cerebral oxygen metabolism in patients with hypertensive intracerebral hemorrhage.Methods:A total of 120 patients with hypertensive intracerebral hemorrhage admitted to the Seventh People′s Hospital of Hebei Province from January 2021 to December 2022 were selected as the research subjects. They were randomly divided into an observation group (60 cases) and a control group (60 cases) according to the random number table method. All patients underwent intracranial hematoma removal surgery under general anesthesia combined with bone flap decompression surgery for treatment. The observation group patients received sedation and analgesia with dexmedetomidine and urapidil after surgery, while the control group patients received sedation and analgesia with dexmedetomidine after surgery. The differences in vital signs, stress indicators, cerebral oxygen and cerebral glucose metabolism, and adverse reactions between two groups of patients were compared.Results:There was no statistically significant difference in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and bispectral index (BIS) between the two groups after entering the room (T 0) and before anesthesia medication (T 1) (all P>0.05). The HR, SBP, DBP, and BIS of the observation group were significantly lower than those of the control group at extubation (T 2), immediately after extubation (T 3), 1 minute after extubation (T 4), and 3 minutes after extubation (T 5), and the differences were statistically significant (all P<0.05). There was no statistically significant difference in various stress indicators between the two groups of patients at T 0 (all P>0.05), while the stress indicators of the observation group were significantly lower than those of the control group at T 5 (all P<0.05). There was no statistically significant difference in the cerebral oxygen uptake rate (CERO 2) and cerebral arteriovenous blood glucose difference (AVDG) between the two groups of patients at T 0 (all P>0.05), while the CERO 2 and AVDG in the observation group at T 5 were significantly higher than those in the control group (all P<0.05). There was no statistically significant difference in the incidence of hypoxemia, hypotension, and bradycardia between the two groups of patients after surgery (all P>0.05). The incidence of postoperative shivering in the observation group was lower than that in the control group ( P<0.05). The Glasgow Coma Index of both groups of patients after surgery was higher than that before surgery (all P<0.05), and there was no statistically significant difference in Glasgow Coma Index between the two groups before and after surgery (all P>0.05). Conclusions:Dexmedetomidine and Urapidil have significant improvement effects on postoperative extubation stress response, postoperative shivering, and cerebral oxygen metabolism in patients with hypertensive intracerebral hemorrhage. It is recommended to promote them clinically.

Objective To investigate the relationship between structural changes and imaging changes of quadriceps fat pad(QFP)and prefemoral fat pad(PFP)in patients with knee osteoarthritis.Methods A retrospective analysis was conducted on the clinical data of 100 patients with knee osteoarthritis admitted to our hospital from June 2020 to June 2022,all of whom underwent magnetic resonance examination.100 patients had a total of 150 knees,and the 150 knees were divided into two groups:non-knee radiologic Osteoarthritis(ROA)group and ROA group.The basic data,QFP and PFP parameters of the two groups were compared,and the correlation between each parameter and KLG grade,Hoffa synovitis and exudative synovitis was analyzed.Results The head and tail diameter of QFP in ROA group was significantly longer than that in non-ROA group,the number of QFP high signal and PFP patellofemoral high signal cases was significantly higher than that in non-ROA group,the number of QFP mass effect cases was significantly lower than that in non-ROA group,and the maximum thickness of PFP was significantly lower than that in non-ROA group.QFP high signal and PFP patellar high signal were positively correlated with KLG grading(r=0.271,0.399).The maximum thickness of PFP was negatively correlated with KLG grade(r=-0.418).QFP high signal was positively correlated with Hoffa synovitis(r=0.330).QFP mass effect and PFP maximum thickness were negatively correlated with Hoffa synovitis(r=-0.291,-0.441).PFP maximum thickness was negatively correlated with exudative synovitis(r=-0.561).PFP patellar high signal was positively correlated with cartilage defects at different sites(r=0.320,0.418,0.358,0.410,0.291).QFP mass effect and PFP maximum thickness was negatively correlated with different sites of cartilage defects(r=-0.358,-0.287,-0.287,-0.287,-0.170,-0.399,-0.438,-0.498,-0.457,-0.350).The anteroposterior diameter of the QFP was negatively correlated with the medial tibial cartilage defect(r=-0.260).Conclusion Imaging changes of QFP and PFP are closely related to KLG grade,synovitis,articular cartilage defect,and subchondral myelopathy in patients with knee osteoarthritis,and play an important role in the occurrence and development of knee osteoarthritis.

Objective:To analyze the survival and prognostic factors of male patients with breast cancer after mastectomy.Methods:Male patients with invasive breast ductal cancer who underwent mastectomy from January 1, 2000 to December 31, 2018 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed by Kaplan-Meier method, and compared by log-rank test. Prognostic factors were identified by Cox proportional hazards regression analysis.Results:A total of 1231 cases were included, with an onset age of (67 ± 12) years. The proportion of stage I-II was 81.1%. The 10-year cancer-specific survival (CSS) rates for stage IA, IIA, IIB, IIIA, IIIB, and IIIC patients were 85.4%, 84.9%, 69.0%, 68.1%, 51.9%, and 48.3%, respectively (all P<0.001). For stage IA-IIB patients, the 10-year CSS rate was 79.2% in the postoperative radiotherapy group, compared to 83.0% in the non-radiotherapy group ( P=0.019). For stage IIIA-IIIC patients, the 10-year CSS rate was 61.7% in the postoperative radiotherapy group, compared to 52.9% in the non-radiotherapy group ( P=0.021). For stage IA-IIB patients, the 10-year CSS rate was 83.8% in the postoperative chemotherapy group, compared to 79.8% in the non-chemotherapy group ( P=0.342). For stage IIIA-IIIC patients, the 10-year CSS rate was 59.7% in the postoperative chemotherapy group, compared to 54.1% in the non-chemotherapy group ( P=0.052). Multivariate analysis showed that younger age, married and grade I-II differentiation were favorable prognostic factors. The earlier the tumor staging, the better the prognosis. Conclusions:Postoperative radiotherapy can improve the CSS of stage III male patients with breast cancer. Younger age, married, grade I-II differentiation are favorable prognostic factors. The earlier the tumor staging, the better the prognosis.

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:In order to cope with the rising risk pressure on the economic operation of public hospitals,it aims to re-search and construct a comprehensive economic operation evaluation index,and improve the comprehensiveness,scientific and dynamic nature of monitoring and analysis of the economic operation of public hospitals.Methods:Literature research,expert consultation and hierarchical analysis were adopted.Results:A comprehensive evaluation model of public hospitals'economic operation covering 5 dimensions and 25 indexes,including structural optimization,controllable risk,efficiency enhancement,smooth operation and sustain-able development,has been constructed;empirical analyses of the overall index,sub-indexes and monthly indexes have been carried out on the data of some of the tertiary hospitals in Shanghai,which have verified the validity of the above index model in enhancing the monitoring,analysis and evaluation of the hospitals'economic operation,and revealed the role of the above index model in the changes of the economic conditions of the hospitals and the factors.Conclusion:Constructing a comprehensive evaluation index can effectively complement management such as comprehensive assessment and evaluation of public hospitals and traditional financial descriptive analysis.

Objective:To evaluate the effect of general anesthesia on microelectrode recording (MER) during deep brain stimulation (DBS) of subthalamic nucleus (STN) in the patients with primary Parkinson′s disease (PD).Methods:Forty-four patients of both sexes with primary PD (duration of disease ≥ 5 yr and/or obvious symptom fluctuation), undergoing bilateral STN DBS from March 2008 to March 2018, aged<80 yr, were selected and divided into 2 groups by a random number table method: awake group ( n=26) and general anesthesia group ( n=18). In awake group, 0.5% ropivacaine was used for incision infiltration at skin incision.Patients in GA group received propofol and remifentanil by target-controlled infusion with Narcotrend to monitor the depth of anesthesia, and 0.5% ropivacaine was used for incision infiltration at skin incision.The total number of trajectories and length of STN were recorded during MER.Movement disorders were evaluated at 1 week before surgery and 6 months after surgery, and the improvement rate of dyskinesia was calculated.The postoperative anesthesia-, hardware- and stimulation-related complications were recorded. Results:There were no significant differences between the two groups in the total number of trajectories, length of STN and improvement rate of postoperative movement disorders ( P>0.05). Conclusion:General anesthesia does not affect the MER during STN DBS in the patients with primary PD.

OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.

Objective: To investigate the clinical features and prognosis of intracranial embryonal tumors in children. Methods: Clinical data of 27 patients with intracranial embryonal tumors who were admitted to Beijing Shijitan Hospital, Capital Medical University be-tween May 2011 and December 2018 were retrospectively analyzed. Results: The study included 27 patients, comprising 17 male and 10 female children, with a median age of 7 years. Twelve patients underwent gross total resection, and 15 patients underwent subto-tal resection. After surgery, all 27 patients underwent craniospinal irradiation. The dose of craniospinal irradiation was 27-30.6 Gy, and the dose of the tumor bed was 55.8-60 Gy. Twenty-two patients underwent chemotherapy regimen composed of irinotecan, vtncris-tine, etoposide, nedaplatin after radiotherapy. The median follow-up period was 22 (4-93) months. Nine patients are alive without lo-cal or distant recurrence. Eighteen patients died; the causes of death were intracranial recurrence and spinal cord metastasis. The 1-, 3-, and 5-year survival rates were 79.4%, 50.2%, and 36.5%, respectively. Conclusions: Intracranial embryonal tumors in children are rare and malignant and can metastasize along the neuroaxis. Surgery, adjuvant radiotherapy, and chemotherapy are important for pa-tients with intracranial embryonal tumors. Moreover, the prognosis is poor.