The access evaluation of new medical technology is an important part of the preclinical application of medical technology and plays a vital role in ensuring the quality and safety of medical services.However,in the con-crete practice of access evaluation,there are still some problems such as imperfect access theoretical framework,imperfect evaluation index system.With the strategic support of health policies,laws,and regulations,the theory and method of HB-HTA are used for reference,core elements such as assessment subject,assessment object,and assessment content are comprehensively considered,the index system is designed from the dimensions of tech-nical characteristics,safety,effectiveness,economy and applicability,and the access evaluation framework of im-ported medical new technologies is constructed.To offer a theoretical framework and evidence-based basis for medi-cal facility medical technology access management.

The establishment of an economic operating mechanisms for hospitals is a key factor in advancing the growth of public hospitals in the modern age.At present,the due value of key factors such as medical resources and labor value of medical personnel in public hospitals in China has not been fully reflected,which not only restricts the overall operation efficiency of hospitals,but also makes it difficult to realize the marginal value of hospital operation and management.The economic operating mechanisms of public hospitals is in urgent need of reform.Large public hospitals in Henan Province has established an economic operating mechanisms of public hospitals based on intelli-gent finance,comprehensive budget management as the core,and cost control and performance management as the major tools to realize the interconnection of various systems and promote the high-quality development of hospi-tals with the three major supports of industry and finance integration,financial integration and financial integration.

Bacteria have posed a threat to human health,and the emergence of super bacteria has made it more difficult to cure bacterial infections in clinical practice.Currently,vaccines are one of the effective means of preventing bacterial infections.With the rapid development of cutting-edge technologies in recent years in such disciplines as biology,medicine,and materials science,various innovative strategies have been provided for vaccine research and preparation.This article summarizes the status quo and prospects of innovative vaccines for treating bacterial infections in recent years,including subunit vaccines,mRNA vaccines and attenuated live vaccine in the hopes of providing data for subsequent development and research of bacterial vaccines.

Objective:To develop a U-Net-based quadruple numerical neural network (QU-Net) model for retinal vessel segmentation and to verify its precision and efficiency in extracting and segmenting retinal vessels from fundus images.Methods:This study used the concept of hypercomplex numbers, the three channels of color images, and a quaternion matrix representing all the information data of the images, which was then used as input for quaternion convolution and quaternion fully connected layers based on the U-Net architecture to form a QU-Net model.The QU-Net model was first tested on the DRIVE, STARE, and CHASE_DB1 datasets and compared with the traditional real-valued U-Net, M-Net, and SU-Net models in terms of accuracy, sensitivity, specificity, precision, F1 score, and Matthews correlation coefficient.Finally, the model was further optimized and the optimized QU-Net model was compared side-by-side with the well-known advanced models to comprehensively evaluate and analyze the efficiency and accuracy of the model in extracting and segmenting retinal blood vessels from fundus images.Results:The results showed that the QU-Net model achieved the following vessel segmentation results: accuracy 0.956 6, sensitivity 0.700 8, specificity 0.987 9, precision 0.595 4 on the DRIVE dataset, accuracy 0.975 5, sensitivity 0.890 7, specificity 0.984 2, precision 0.662 5 on the STARE dataset, and accuracy 0.979 4, sensitivity 0.747 0, specificity 0.990 6, precision 0.596 9 on the CHASE_DB1 dataset.Its specificity was better than U-Net, M-Net and SU-Net models, and its accuracy, sensitivity and precision were not inferior to the three models.After optimization, the sensitivity, precision and F1 value of the QU-Net model were effectively improved on the three datasets while maintaining its original accuracy and specificity.When compared with the performance indicators of other models on the three datasets, it was found that the optimized QU-Net model had good performance in accuracy, specificity, sensitivity, precision, and F1 score, indicating that its vessel segmentation ability was not inferior to the advanced models.Among all the models compared, the optimized QU-Net model had the best F1 score and Matthews correlation coefficient.Conclusions:The QU-Net model proposed in this study expands the data dimension space from the traditional real number space to the complex number space and greatly reduces the loss of data information.The optimized QU-Net model has good efficiency and accuracy in extracting retinal vessel segmentation from fundus images, and has certain advantages in detecting fine vessels.

Objective:To investigate the effect of decarbromodiphenyl ether(BDE-209)exposure on the migration ability of triple-negative breast cancer(TNBC)cells and to explore the underlying mechanism.Methods:Human TNBC MDA-MB-231 cells were divided into blank control group and BDE-209 exposure groups(treated with 0.02,0.20,2.00,20.00 and 200.00 ng/mL BDE-209 in high glucose DMEM).Extracellular vehicles(EVs)secreted by MDA-MB-231 cells were isolated by differential ultracentrifugation.Transmission electron microscopy(SEM),nanoparticle tracking analysis(NTA)and Western blotting were performed to characterize the EVs.The effect of the EVs induced by BDE-209 exposure(EVs-BDE-209)on the migration and invasion of MDA-MB-231 cells was detected by wound-healing assay and Transwell test.qRT-PCR was used to measure the miR-221 level in EVs-BDE-209.The expression of MMP9 in MDA-MB-231 cells was determined by Western blotting.Results:Compared with the blank control,BDE-209 exposure increased the tumor cell-derived EVs in dose-dependent manner.The MDA-MB-231 cells co-cultured with EVs released by 200.00 ng/mL BDE-209 exposure showed an 86%increase in cell migration rate,a 1.32-fold higher number of membrane-penetrating cells,a 2.71-fold higher expression level of miR-221,and a 1.62-fold higher expression level of MMP9 compared with the blank control group(all P<0.05).While transfection with anti-miR-221 antibody to decrease miR-221 level in EVs significantly reversed the increased invasion ability of the MDA-MB-231 cells treated with EVs-BDE-209.Conclusion:BDE-209 exposure may promote metastasis potential of MDA-MB-231 cells via EVs-BDE-209 transmitted miR-221.

OBJECTIVE To compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） acquired resistant advanced lung adenocarcinoma. METHODS The information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group （32 cases）， anlotinib combined chemotherapy group （24 cases） and bevacizumab combined chemotherapy group （28 cases）. Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection， and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy， patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally， once a day， for 14 consecutive days and 7 days of discontinuation， based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy， based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles， with one cycle every three weeks. The overall response rate （ORR）， disease control rate （DCR）， median progression-free survival （mPFS）， and the changes of serum tumor markers were compared among three groups before and after treatment； meanwhile， the occurrence of adverse drug reactions was recorded， and the 1-year survival rate was followed up. RESULTS After 4 treatment cycles， ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group （P＜0.05）； mPFS of the two groups were significantly longer than chemotherapy group， and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group （P＜0.05）. After 4 treatment cycles， the serum levels of tumor markers in three groups were significantly lower than before treatment， and both combined chemotherapy groups were significantly lower than chemotherapy group （P＜0.05）. There was no statistically significant difference in the incidence of adverse reactions such as nausea， vomiting， bone marrow suppression， and 1-year survival rate among the three groups of patients （P＞0.05）. CONCLUSIONS Bevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.

Ubiquitin (Ub) and ubiquitin-like (Ubl) pathways are critical post-translational modifications that determine whether functional proteins are degraded or activated/inactivated. To date, >600 associated enzymes have been reported that comprise a hierarchical task network (e.g., E1-E2-E3 cascade enzymatic reaction and deubiquitination) to modulate substrates, including enormous oncoproteins and tumor-suppressive proteins. Several strategies, such as classical biochemical approaches, multiomics, and clinical sample analysis, were combined to elucidate the functional relations between these enzymes and tumors. In this regard, the fundamental advances and follow-on drug discoveries have been crucial in providing vital information concerning contemporary translational efforts to tailor individualized treatment by targeting Ub and Ubl pathways. Correspondingly, emphasizing the current progress of Ub-related pathways as therapeutic targets in cancer is deemed essential. In the present review, we summarize and discuss the functions, clinical significance, and regulatory mechanisms of Ub and Ubl pathways in tumorigenesis as well as the current progress of small-molecular drug discovery. In particular, multiomics analyses were integrated to delineate the complexity of Ub and Ubl modifications for cancer therapy. The present review will provide a focused and up-to-date overview for the researchers to pursue further studies regarding the Ub and Ubl pathways targeted anticancer strategies.

Objective:To investigate the value of pulse oxygen saturation (SpO 2) monitoring in predicting children with moderate-to-severe obstructive sleep apnea (OSA). Methods:It was a retrospective study involving 341 children with snoring during nighttime sleep who had visited the Children′s Hospital of Soochow University from June 2017 to November 2020 and monitored for polysomnography (PSG) and SpO 2.The SpO 2 parameters mainly included oxygen desaturation index (ODI), oxygen desaturation index ≥3% (ODI3), oxygen desaturation index ≥4% (ODI4), mean pulse blood oxygen saturation (MSpO 2), lowest pulse blood oxygen saturation (LSpO 2), cumulative time spent with blood oxygen saturation below 95%, 92% and 90%(T95, T92 and T90). According to obstructive sleep apnea hypopnea index (OAHI), patients were divided into the snoring and mild OSA group (OAHI≤5 times/h) and moderate-to-severe OSA group (OAHI>5 times/h). Differences in SpO 2 parameters were compared between groups using the Chi- square test and Mann- Whitney U test. Spearman correlation analysis was used to analyze the correlation between SpO 2 parameters and OAHI in all children.The SpO 2 parameters were included in the Logistic regression model.Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of SpO 2 parameters on moderate-to-severe OSA. Results:A total of 341 patients were recruited, including 206 male and 135 female patients with the mean age, body mass index (BMI) and OAHI of 6.0 (4.0, 7.5) years, 16.2 (15.1, 18.0) kg/m 2 and 0.6 (0.1, 3.0) times /h, respectively.There were 283(83.0%) and 58 (17.0%) patients in the snoring and mild OSA group and moderate-to-severe OSA group.The ODI3[0.7 (0.3, 1.4) times/h vs.7.7 (4.4, 12.8) times/h], ODI4[0.4 (0.1, 0.8) times/h vs.5.3 (2.7, 9.1) times/h], T95[1.4 (0.3, 5.3) min vs.13.7 (7.0, 33.5) min], T92[0.1 (0, 0.5) min vs.1.8 (0.9, 6.0) min] and T90[0 (0, 0.1) min vs.0.6 (0.2, 2.2) min] were significantly lower in the snoring and mild OSA group than those of moderate-to-severe group, while LSpO 2[91.0 (89.0, 93.0)% vs.86.5 (82.0, 88.0)%] and MSpO 2[ 97.0 (97.0, 98.0)% vs.96.0 (96.0, 97.0)%] were significantly higher(all P<0.001). All SpO 2 parameters were significantly correlated with OAHI (all P<0.001), and the correlation coefficient between ODI3 and OAHI was 0.660.ODI3 was an independent predictor of moderate-to-severe OSA ( OR=3.117, 95% CI: 1.635-5.945, P=0.001). The area under the ROC curve of ODI3 in predicting the moderate-to-severe OSA was 0.957, and the cut-off value of 3.45 times/h and specificity of 95.4%.MSpO 2 was an independent predictor of moderate-to-severe OSA ( OR=2.917, 95% CI: 1.589-5.354, P=0.001). Conclusions:ODI3 can be used to predict the moderate-to-severe OSA in children.

Objective:To compare the efficacies of posterior long segment instrumentation combined with transpedicular impaction bone grafting or with bone cement augmentation in treating stage III Kümmell disease.Methods:A retrospective cohort study was conducted to analyze the clinical data of 38 patients with stage III Kümmell disease who were admitted to Zhengzhou Orthopedic Hospital between January 2016 and December 2020. The study included 8 male and 30 female patients, with ages ranging from 59 to 81 years [(68.9±4.9)years]. The vertebral fractures occurred at T 8 in 1 patient, T 11 in 9 patients, T 12 in 10 patients, and L 2 in 10 patients. Seventeen patients underwent posterior long segment instrumentation combined with transpedicular impaction bone grafting (impaction bone grafting group), and 21 patients underwent posterior long segment instrumentation combined with bone cement augmentation (bone cement group). The surgical duration, intraoperative blood loss, and incidences of postoperative complications were compared between the two groups. Additionally, the visual analogue score (VAS), Japanese orthopedic association (JOA) score, and Cobb angle were compared before the operation, at 1 week and 3 months post-operation, and at the final follow-up for both groups. The study also compared bone healing at the last follow-up and postoperative complication rates between the two groups. Results:All the patients were followed up for 24-35 months [(28.7±2.9)months]. The impaction bone grafting group had a surgical duration of (150.7±25.4)minutes and intraoperative blood loss of (285.3±48.6)ml, significantly different from those in the bone cement group [(132.0±21.1)minutes, (251.4±44.8)ml] (all P<0.05). Before the operation, there were no significant differences in the VAS, JOA score, or Cobb angle between the two groups (all P>0.05).The VAS was (3.2±0.8)points, (2.7±0.5)points and (2.2±0.7)points in the impaction bone grafting group and was (2.7±0.6)points, (2.6±0.7)points and (2.4±0.8)points in the bone cement group at 1 week and 3 months post-operation and at the final follow-up, respectively. The VAS in the impaction bone grafting group was significantly higher than that in the bone cement group at 1 week post-operation ( P<0.05); however, no significant differences were found at 3 months post-operation or at the last follow-up (all P>0.05). There was no significant difference in the JOA score between the two groups at 1 week or 3 months post-operation, or at the final follow-up (all P>0.05). The Cobb angle in the impaction bone grafting group was (5.1±1.3)°, (5.9±1.8)° and (6.5±2.5)° at 1 week and 3 months post-operation, and at the final follow-up, significantly lower than that in the bone cement group [(8.4±1.6)°, (12.6±2.1)°, and (14.5±3.3)°] (all P<0.01). All the patients in the impaction bone grafting group achieved bone healing at the last follow-up. One patient in the impaction bone grafting group experienced delayed incision healing, whereas two patients in the bone cement group had poor bone healing. The complication rate was 5.9% (1/17) in the impaction bone grafting group and 9.5% (2/21) in the bone cement group ( P>0.05). Conclusions:Posterior long segment instrumentation combined with transpedicular impaction bone grafting or with bone cement augmentation are both effective in alleviating pain and improving the spinal function for stage III Kümmell disease. The former procedure is associated with longer surgical duration and increased intraoperative blood loss, but it can provide superior correction and maintenance of kyphosis deformity, promoting the healing of the injured vertebrae.

Objective:To investigate the influence and mechanism of micro RNA (miR)-373-3p in autophagy and sunitinib sensitivity of glioblastoma cells.Methods:U251 cells were routinely cultured in vitro; and some U251 cells were subjected to 50 μmol/L sunitinib treatment for 72 h to construct sunitinib-resistant U251 cell line. (1) Real-time reverse transcription quantitative PCR (RT-qPCR) was used to detect the miR-373-3p expression in U251 and sunitinib-resistant U251 cells. Sunitinib-resistant U251 cells were divided into blank control group, nonsense sequence group and miR-373-3p mimic group; cells in the latter 2 groups were transfected with nonsense sequence and miRNA-337-3p mimic, respectively; miR-373-3p expression was detected by RT-qPCR. Cells were divided into U251 group, sunitinib-resistant U251 group, sunitinib-resistant U251+nonsense sequence group, and sunitinib-resistant U251+miR-373-3p mimic group; after each transfection, CCK-8 assay was used to evaluate the cell viability; TUNEL was used to detect the apoptotic rate; immunofluorescent assay was used to detect the expression of microtubule-associated protein light chain 3 (LC3); Western blotting was used to detect the expressions of apoptosis- and autophagy-associated proteins. (2) The pGL3-autophagy-related gene 7 (ATG7) wild-type (WT) and pGL3-ATG7 mutant type (MUT) plasmids were established; dual-luciferase reporter system was used to detect the cell luciferase activity in the miR-373-3p mimic group and nonsense sequence group. Cells were divided into U251 group, sunitinib-resistant U251 group, sunitinib-resistant U251+nonsense sequence group, and sunitinib-resistant U251+miR-373-3p mimic group; after each transfection, RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of ATG7 in the cells. (3) The sunitinib-resistant U251 cells were divided into blank control group, ATG7 negative control group, and ATG7 overexpression group; after each transfection, RT-qPCR and Western blotting were used to detect the ATG7 mRNA and protein expressions. U251 and sunitinib-resistant U251 cells were divided into U251 group, sunitinib-resistant U251 group, sunitinib-resistant U251+nonsense sequence group, sunitinib-resistant U251+miR-373-3p mimic group, sunitinib-resistant U251+miR-373-3p mimic+ATG7 negative control group, and sunitinib-resistant U251+miR-373-3p mimic+ATG7 overexpression group; after each transfection, CCK-8 assay was used to evaluate the cell apoptosis, TUNEL was used to examine the apoptotic rate, and Western blotting was employed to detect the expressions of apoptosis- and autophagy-associated proteins. Results:(1) As compared with that in the U251 cells, miR-373-3p was lowly expressed in sunitinib-resistant U251 cells, with statistic difference ( P<0.05). As compared with that in the blank control group and nonsense sequence group, miR-373-3p expression was significantly elevated in the miR-373-3p mimic group ( P<0.05). As compared with the U251 group, the sunitinib-resistant U251 group had significantly increased cell viability, significantly decreased cell apoptotic rate, statistically increased B lymphocytoma-2 (Bcl-2) and Beclin 1 protein expressions, and significantly increased LC3II/LC3I values, significantly decreased Bcl-2 associated X protein (Bax) and p62 protein expressions and cleaved Caspase3/Caspase 3 values ( P<0.05). As compared with the sunitinib-resistant U251+nonsense sequence group, the sunitinib-resistant U251+miR-373-3p mimic group had significantly decreased cell viability, significantly increased cell apoptotic rate, statistically decreased Bcl-2 and Beclin 1 protein expressions, and significantly decreased LC3II/LC3I values, significantly increased Bax and p62 protein expressions and cleaved Caspase3/Caspase 3 values ( P<0.05). As compared with the U251 group, the sunitinib-resistant U251 group had increased number of fluorescent particles labeled with LC3 and enhanced fluorescent intensity; as compared with the sunitinib-resistant U251+nonsense sequence group, the sunitinib-resistant U251+miR-373-3p mimic group had decreased number of fluorescent particles labeled with LC3 and reduced fluorescent intensity. (2) The luciferase activity of pGL3-ATG7 WT plasmids in the miR-373-3p mimic group was signficantly lower than that in nonsense sequence group ( P<0.05). As compared with those in the U251 group, ATG7 mRNA and protein expressions were both significantly increased in the sunitinib-resistant U251 group ( P<0.05); as compared with those in the sunitinib-resistant U251+nonsense sequence group, ATG7 mRNA and protein expressions were both significantly decreased in the sunitinib-resistant U251+miR-373-3p mimic group ( P<0.05). (3) As compared with the blank control group and ATG7 negative control group, the ATG7 overexpression group had significantly increased ATG7 mRNA and protein expressions ( P<0.05). As compared with the sunitinib-resistant U251+nonsense sequence group, the sunitinib-resistant U251+miR-373-3p mimic group had significantly decreased cell viability, significantly increased cell apoptotic rate, statistically decreased Bcl-2 and Beclin 1 protein expressions, significantly decreased LC3II/LC3I values, significantly increased Bax and p62 protein expressions, and significantly increased cleaved Caspase3/Caspase 3 values ( P<0.05). As compared with the sunitinib-resistant U251+miR-373-3p mimic+ATG7 negative control group, the sunitinib-resistant U251+miR-373-3p mimic+ATG7 overexpression group had significantly increased cell viability, significantly decreased apoptotic rate, statistically increased Bcl-2 and Beclin 1 protein expressions, significantly increased LC3II/LC3I values, significantly decreased Bax and p62 protein expressions, and significantly decreased cleaved Caspase3/Caspase 3 values ( P<0.05) Conclusion:MiR-373-3p can enhance sunitinib sensitivity by regulating autophagy in glioblastoma cells, whose mechanism might be related to targeting ATG7.