Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

OBJECTIVE To evaluate the cost-effectiveness of regorafenib in the treatment of hepatocellular carcinoma after failure of sorafenib from the perspective of Chinese health system. METHODS Based on a phase Ⅲ trial（RESORCE）， the partition survival model （PSM） and Markov model were constructed. The cycle was set as four weeks， the duration of the study lasted for lifetime， the annual discount rate was 5%. Drug cost data was obtained from yaozhi.com， other cost data were obtained from Anhui Provincial Medical Insurance Bureau and related literature， and utility values were obtained from literature. The incremental cost-effectiveness ratio （ICER） was used as the evaluation index， and the value of willingness to pay （WTP） was three times of China’s gross domestic product （GDP） per capita in 2022； one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The incremental cost of regorafenib group versus placebo group in PSM and Markov model was 112 116.95 yuan and 96 617.19 yuan， respectively. The incremental effectiveness was 0.31 QALYs and 0.32 QALYs， respectively. The ICERs were 360 751.01 yuan/QALY and 301 114.45 yuan/QALY， which were both greater than the value of WTP； regorafenib was not cost-effective. Results of one-way sensitivity analysis showed that the utility of progression-free survival and progressive disease， the unit cost of regorafenib had the greatest influence on the results， but ICER was always greater than the WTP within the floating range of each parameter. Under the WTP of 3 times China’s per capita GDP in 2022， the probabilities of regorafenib with cost-effectiveness were 0.8% （PSM） and 11.4% （Markov）. CONCLUSIONS Under the WTP of 3 times the per capita GDP of China， regorafenib is not cost-effective in the treatment of hepatocellular carcinoma after failure of sorafenib treatment， compared with placebo.

Objective:To compare postoperative analgesic effect of flurbiprofen axetil and parecoxib sodium in patients with humeral shaft fracture in painless ward.Methods:All of 200 hospitalized humeral fractures patients were retrospectively studied in the painless ward of the Forth Medical Center of PLA General Hospital from January 2017 to September 2019 , the clinical effects of flurbiprofen axetil and parecoxib were compared.Results:Postoperative visual analogue scale (VAS) scores after 3 d of two groups of patients were significantly lower, compared with preoperative results: (4.26±0.96) scores vs. (6.09±1.38) scores, (4.04±1.19) scores vs. (6.04±1.11) scores, and the differences were statistical significantly ( P<0.01). Postoperative VAS score after 3 d of two groups had no statistical significance ( P>0.05). Two groups had different degree of adverse reactions after operation, and flurbiprofen axetil group had singnificant gastrointestinal adverse reaction: 22 patients vs. 3 patients( P<0.05). The number of patients in the parecoxib group were more than that in the flubiprofen axetil group without troubled sleep: 20 patients vs. 8 patients. Two groups of patients were satisfied with the pain care during hospitalization. Conclusions:Two analgestic drugs can obtain obvious analgesic effect in the treatment of bones surgery. The side effects and sleep disturbance in the flurbiprofen axetil group are higher than those in the parecoxib group. Good pain control can improve patients satisfaction with pain care.

Objective To set up a computer-assisted polyp detection system under colonoscopy,and to preliminarily verify its effectiveness.Methods Based on Faster R-CNN algorithm and the open source implementation of the open source framework tensorflow and Faster R-CNN,a computer-assisted polyp detection system under colonoscopy was constructed.According to the size and difficulty of the training set,five test groups were set up:test group one,two,three and four contained 1 000,2 000,4 000 and 6 000 training samples,respectively.Test group five increased the probability of selecting the difficult samples based on 6 000 training samples.In different training sets,the sensitivity,specificity,other classification evaluation parameters,and the evaluation parameters of target detection such as recall and precision of this polyps detection system were calculated.Results Classification evaluation parameters showed that the sensitivities of test group one,two,three,four and five were 90.1％,93.3％,93.3％,93.3 ％ and 93.5 ％,respectively,and the difference was statistically significant (x2 =25.324,P＜0.01).The sensitivities of test group two,three,four and five were all higher than that of test group one,and the differences were statistically significant (x2 =13.964,13.508,13.508 and 13.386,all P＜ 0.006 25).There were no significant differences in specificity and positive predictive value among test groups (both P＞0.05).The negative predictive values of test group one,two,three,four and five were 90.4％,93.3％,93.3％,93.3％ and 93.5％,respectively,and the differences were statistically significant (x2 =21.862,P＜0.01).The negative predictive values of test group two,three,four and five were higher than that of test group one,and the differences were statistically significant (x2=11.447,11.564,11.755,13.760;all P＜0.006 25).As the training sample size increased from 1 000 to 2 000,the area under curve (AUC) increased by 2％,and further increased the sample size to 6 000,AUC increased by less than 1 ％.At this point maintaining the same sample size while increasing the proportion of difficult samples,AUC increased by 0.4％.The results of evaluation parameters of target detection showed that the recall rate of each test group was 73.6％,79.8％,79.5％,79.8％ and 83.3％,respectively,and the differences were statistically significant (x2 =71.936,P＜0.01).Among them,the recall rates of test group two,three and four were higher than that of test group one,and the differences were statistically significant (x2 =25.960,23.492 and 25.960,all P＜0.006 25),and the recall rate of test group five was higher than those of test group one,two,three and four,and the differences were statistically significant (x2=67.361,9.899,11.527 and 9.899;all P＜0.006 25).In addition,the precision rates of test group one,two,three,four and five were 87.9％,85.3％,90.2％,91.4％ and 89.2％,respectively,and the difference was statistically significant (x2=48.194,P＜0.01).The precision rates of test group three and five were higher than that of test group two,and the differences were statistically significant (x2 =24.508 and 15.223,both P＜0.006 25),and the precision rate of test group four was higher than those of test group one and two,and the differences were statistically significant (x2=13.524 and 39.120,both P＜0.006 25).As samples size and training difficulty increased,the values of F1-score and mean average precision increased steadily.Conclusions This study initially constructed a computer-assisted polyp detection system under colonoscopy.Currently the maximum sensitivity reached 93.5％,and the maximum recall rate reached 83.3％.Increasing the training set size may improve the polyp detection result to a certain degree,however it will reach a bottleneck.At this time,increasing the training difficulty can further improve the detection scores,especially the recall rate.

Objective:To explore the effect of endothelin-1 on atrial ifbrosis in patients with atrial ifbrillation (AF).
Methods: A total of 72 patients with thoracotomy were studied, the patients were divided into 2 groups:AF group, n=39 and Sinus rhythm (SR) group, n=33. The mRNA and protein expressions of endothelin-1 (ET-1), platelet derived growth factor-B (PDGF-B) and collagen I (COL1) in right atrial appendage (RAA) tissue were measured by RT-PCR and Western blot analysis;meanwhile, the impact of ET-1 stimulation and non-selective ET-1 receptor antagonist (sulfafurazole SIZ) on PDGF-B mRNA and protein expressions in H9c2 cells were measured.
Results: ①The RAA tissue mRNA and protein expressions in AF group were higher than those in SR group, as for ET-1 (2.830 ± 2.276) vs (1.220 ± 0.887) and (0.835 ± 0.241) vs (0.286 ± 0.083), both P<0.01;for PDGF-B (2.568 ± 2.348) vs (1.567 ± 0.831) and (0.807±0.241) vs (0.381 ± 0.105), both P<0.05;for COL1α1 (3.376 ± 1.598) vs (1.629 ± 0.833) and (0.652 ± 0.210) vs (0.312 ± 0.12), both P<0.05.②The protein expressions of ET-1 and COL1 had positive correlation (r=0.580, P<0.01).③ET-1 promoted PDGF-B secretion in H9c2 cells in a concentration and time-dependent manner;SIZ could reduce such promotion.
Conclusion: ET-1 plays an important role in AF occurrence which might be related to PDGF-B regulation.

OBJECTIVETo detect the methylation status of gastric cancer tissue genome by DNA methylation chip.

METHODSMethylation status of 6 samples of gastric cancer tissues and their matched adjacent tissues was analyzed using methylated DNA immunoprecipitation(MeDIP) combined with NibleGen chip. Significantly different methylated genes in promoter region and CpG island between two tissues were searched. Functions of these significantly different methylated genes were analyzed by Gene Ontology and Pathway assays.

RESULTSIn gene promoter regions, 113 significantly different methylated genes were identified in gastric cancer tissues, such as SHP1, FGF8 and CSF2RA, while 161 significantly different methylated genes were identified in their matched adjacent tissues, such as TNF, IGF2 and BMP7. In the CpG islands, 123 significantly different methylated genes were identified in gastric cancer tissues, such as WNT2B, JAK2 and TPT1, while 139 significantly different methylated genes were identified in their matched adjacent tissues, such as TNFRSF4, HOXC8 and NFYA. These genes located on different chromosomes. In gastric cancer tissues, the 1st and the 4th chromosomes had the most (both 11), the 18th and the 20th chromosomes had the least(both 1). In matched adjacent normal tissues, the 11th chromosome had the most (17), and no significantly different methylated gene was found on Y chromosome. These genes involved in many functions, such as protein phosphorylation, regulating cellular catabolism, ion transport, enzyme activity, transcriptional regulation, cell division, cell cycle regulation, and signal transduction.

CONCLUSIONSThere are significant differences between gastric cancer tissues and their matched adjacent tissues in DNA methylation. DNA methylation genes locate on different chromosomes, and their number and distribution vary widely. These genes may be associated with many pathways in carcinogenesis.

[Summary] 2015 AACE/ACE Clinical Practice Guidelines for Integrated Management of Diabetes are updated and revised on the basis of 2011 edition. The guidelines highlight the comprehensive consideration of micro- and macro-vascular risks rather than merely focusing on the strategies and approaches of glycemic control. The guidelines also emphasize individualized targets for weight loss and the management of hyperglycemia ,dyslipidemia and hypertension and that more attention should be paid to safety of individualized treatment other than efficacy.

Objective To investigate the effect of microRNA-101 (miRNA-101) on atrial fibrosis in human chronic atrial fibrillation (AF). Methods Right atrial appendages were obtained from 59 patients (30 with AF) undergoing cardiac surgery, including 47 patients with valve heart disease and 12 patients with congenital heart disease. The expression of miRNA-101 was determined by quantitative real-time PCR in the right atrial appendages of patients with and without AF. The cell-specific localization of miRNA-101 was detected by in situ hybridization assay. The mRNA and protein expression levels of transforming growth factor β typeⅠreceptor (TGFβRⅠ) and collagen type I (COL1) were determined by quantitative real-time PCR and Western-blot assay, respectively. Collagen in the right atrial appendages was observed by Masson staining assay. Results The expression of miRNA-101 was found to be significantly down-regulated in AF patients compared with patients with sinus rhythm (SR) (P < 0.05). The result of miRNA-ISH showed that miRNA-101, which was highly distributed within the connective tissues of heart, was down-regulated at about 24.9% in patients with AF compared with patients with SR. No significant differences at the mRNA expression level of TGFβRI was found between patients with AF and patients with SR (P > 0.05). But the protein expression of TGFβRI in patients with AF was significantly higher than that of patients with SR (P < 0.05). The mRNA and protein expressionsl of COL1 were significantly higher in patients with AF than thoset of patients with SR (P < 0.05). The collagen was significantly increased in patients with AF than that of patients with SR (P < 0.05). Conclusions Downregulation of miRNA-101 may contribute to atrial fibrosis in human atrial fibrillation by targeting TGFβRⅠ.

Objective To evaluate the diagnostic and prognostic value of BRAF V600E mutation screening of ultrasound-guided fine-needle aspiration (FNA)specimens in patients with thyroid nodule. Methods The BRAF V600E mutation status were assessed in FNA specimens of 104 patients with thyroid nodules before operations.The BRAF mutation status,clinical,and pathology records of the patients were reviewed and the associations between these characteristics and papillary thyroid cancer (PTC ) were analyzed.Results Seventy-one PTC and 14 benign thyroid nodules were included in this study.BRAF V600E mutations were found in 57/71 (80%)PTC.All benign thyroid nodules had no BRAF V600E mutation.The sensitivity,specificity,positive predictive value and negative predictive value of BRAF V600E mutations in differentiation between PTC and benign thyroid nodules were 80%,100%,100% and 50%(P < 0.001 ).In 44 patients with PTC who underwent surgery,the central compartment lymph node metastases and extrathyroidal invasion were not significantly different between BRAF-positive and BRAF-negative PTC (P = 0.283 and 0.307 ).Conclusions BRAF V600E mutation may be a potential tool to facilitate ultrasound in diagnosis of PTC.In patients with PTC,the presence of the BRAFV600E mutation was not significantly associated with prognostic factors.

Objective To detect the methylation status of gastric cancer tissue genome by DNA methylation chip. Methods Methylation status of 6 samples of gastric cancer tissues and their matched adjacent tissues was analyzed using methylated DNA immunoprecipitation ﹙MeDIP) combined with NibleGen chip. Significantly different methylated genes in promoter region and CpG island between two tissues were searched. Functions of these significantly different methylated genes were analyzed by Gene Ontology and Pathway assays. Results In gene promoter regions, 113 significantly different methylated genes were identified in gastric cancer tissues, such as SHP1, FGF8 and CSF2RA, while 161 significantly different methylated genes were identified in their matched adjacent tissues, such as TNF, IGF2 and BMP7. In the CpG islands, 123 significantly different methylated genes were identified in gastric cancer tissues, such as WNT2B, JAK2 and TPT1, while 139 significantly different methylated genes were identified in their matched adjacent tissues, such as TNFRSF4, HOXC8 and NFYA. These genes located on different chromosomes. In gastric cancer tissues, the 1st and the 4th chromosomes had the most ﹙both 11), the 18th and the 20th chromosomes had the least ﹙both 1). In matched adjacent normal tissues, the 9th, 19th and 20th chromosomes had the most ﹙11), and no significantly different methylated gene was found on Y chromosome. These genes involved in many functions, such as protein phosphorylation, regulating cellular catabolism, ion transport, enzyme activity, transcriptional regulation, cell division, cell cycle regulation, and signal transduction. Conclusions There are significant differences between gastric cancer tissues and their matched adjacent tissues in DNA methylation. DNA methylation genes locate on different chromosomes, and their number and distribution vary widely. These genes may be associated with many pathways in carcinogenesis.