OBJECTIVE To introduce the clinical value assessment model for innovative drugs in Canada’s health insurance access， providing a reference for improving the clinical value assessment system for innovative drugs in China. METHODS The clinical value assessment system for innovative drugs in Canada’s health insurance access was organized from four aspects： the assessment body， the assessment process， the assessment dimensions， and the application of assessment results. A deep analysis was also conducted with the clinical value assessment of health insurance access for blinatumomab as an example. Then the suggestions were proposed for the improvement of relevant work in China. RESULTS & CONCLUSIONS Canada has established an independent clinical value assessment agency， the Canadian Agency for Drug and Technologies in Health （CADTH）， which is responsible for the health technology assessment of innovative drugs. The health insurance access to clinical value assessment system for innovative drugs is built with patient needs as the guide， and the review process includes stages such as opinion review and expert assessment. Different evaluation dimensions are set for oncology and non-oncology drugs， and the assessment is based on sufficient evidence and a transparent process. The assessment results include four types： reimbursement， conditional reimbursement， time-limited reimbursement， and non-reimbursement， balancing efficacy and accessibility. It is suggested that China should strengthen the clinical value assessment system for innovative drugs in health insurance access from four aspects： establishing a specialized institution for the clinical value assessment of innovative drugs， increasing the clarity of policy expectations， including patient benefit assessment indicators， and adding special reimbursement pathways for drugs.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

Pan-immune inflammation value (PIV) is a comprehensive immune inflammatory biomarker based on complete blood cell counts, which has been proven to predict treatment response and survival outcomes for different types of tumors. However, the predictive value of the PIV varies in different strategies for tumor treatment. This paper aims to systematically review the latest progress of PIV in predicting survival outcomes and tumor prognosis for immunotherapy, radiotherapy, targeted therapy, endocrine therapy, surgical treatment and neoadjuvant therapy, and analyze its existing challenges and issues, as well as look forward to its future development direction and application prospects.

Objective To investigate the correlation between pre-treatment pan-immune inflammation value (PIV) and clinicopathological features in esophageal squamous cell carcinoma (ESCC) patients with postoperative adjuvant radiotherapy and evaluate its value in prognosis assessment combined with T stage. Methods A retrospective analysis was conducted on data of 85 ESCC patients with postoperative adjuvant radiotherapy in the Department of Radiation Oncology of the Affiliated Hospital of Yangzhou University from January 2019 to January 2023. The receiver operating characteristic (ROC) curve was drew to obtain the optimal cut-off value of PIV and other immune-inflammatory biomarkers. The area under the curve (AUC) and clinical applicability of PIV and other immune-inflammatory biomarkers were compared based on the ROC curve and decision curve analysis (DCA). According to the optimal cut-off value, patients were divided into high PIV group and low PIV group, and the correlation between PIV level and clinicopathological features of ESCC was evaluated. Kaplan-Meier method was used for survival analysis, the Cox proportional hazards model was used for multivariate analysis, and a risk stratification model combining PIV and T stage was established by recursive partitioning analysis (RPA). Results The optimal cut-off value of pre-treatment PIV was determined as 187.22 based on the ROC curve. The AUC of PIV was 0.679, which was greater than 0.640, 0.583, 0.656 and 0.644 of the other four immune-inflammatory biomarkers such as the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR). The 85 patients were divided into low PIV group (< 187.22, n=48) and high PIV group (≥187.22, n=37). The level of PIV was significantly correlated with tumor diameter (P < 0.05). The 3-year overall survival (OS) (75.6% versus 30.6%, P < 0.001) and 3-year disease-free survival (DFS) (56.1% versus 21.0%, P < 0.001) were significantly higher in the low PIV group than the high PIV group. Tumor diameter, T stage and PIV were independent factors affecting OS in ESCC patients (P < 0.05), and T stage and PIV were independent factors affecting DFS in ESCC patients (P < 0.05). A new staging system with three risk groups was established by the RPA stratification model based on T stage and PIV, which further improved the predictive value of prognosis compared with T stage or PIV alone. Conclusion Pre-treatment PIV is helpful in predicting the prognosis of ESCC patients with postoperative adjuvant radiotherapy, and the combination of PIV and T stage can improve the predictive value.

Objective:To investigate the expression and clinical significance of decoy receptor 3 (DcR3) and its signal pathway-related molecules in PBMCs of patients with ankylosing spondylitis (AS).Methods:Peripheral blood samples, clinical data and laboratory test results were collected from 100 patients with ankylosing spondylitis [50 patients with AS activity (ASA), 50 patients with AS stability (ASS)], 30 patients with osteoarthritis and 30 patients with gouty arthritis (as disease control group), and 60 healthy controls (HC). The mRNA expression levels of DcR3 and its signal pathway related genes (DR3, TL1A, Fas, FasL, LIGHT, LIGHTR, LTβR) were measured by real-time fluorescence quantitative polymerase chain reaction. Measurement data among the three groups in normal distribution were analyzed by t test or one-way analysis of variance, pairwise comparisons using LSD- t test, non-normal distribution data were analyzed by Mann-Whitney test or Kruskal-Wallis H test, χ2 test was used for correlation analysis of categorical variables. Correlation analysis between variables were analyzed using Spearman correlation analysis. Results:① By comparing the AS group, disease control group and HC group, the expression levels of DcR3 mRNA and DR3 mRNA in the AS group were lower than those in disease control group and HC group, and DcR3 mRNA and DR3 mRNA in disease control group were lower than those in the HC group {DcR3mRNA: [6.21 (3.89, 10.70)]×10 -4vs [9.51 (5.89, 16.65)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=55.28, P<0.001; DR3 mRNA: [41.05 (24.09, 66.95)]×10 -4vs [58.28 (28.41, 94.38)]×10 -4vs [94.79 (54.07, 144.51)]×10 -4, H=37.10, P<0.001}. The expression level of TL1A mRNA in the AS group was higher than that in disease control group {[14.71(4.91, 42.22)]×10 -4vs [4.00(1.07, 16.60)]×10 -4vs [7.70 (3.52, 27.83)]×10 -4, H=17.71, P<0.001}; The expression level of Fas mRNA in AS group and disease control group was lower than that in HC group {[20.99(4.63, 62.89)]×10 -4vs [23.97(15.82, 38.99)]×10 -4vs [78.45 (27.32, 146.46)]×10 -4, H=31.17, P<0.001}. The expression level of FasL mRNA in AS group was higher than that in disease control group and HC group {[42.87(6.57, 91.21)]×10 -4vs [5.45(2.83, 10.32)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=46.42, P<0.001}. The expression level of LIGHTR mRNA in AS group was lower than that in disease control group {[52.66 (7.20, 143.21)]×10 -4vs [98.80 (53.11, 166.24)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.96, P<0.001}. There were no significant differences in LIGHT mRNA and LTβR mRNA among all groups ( H=0.86, P>0.05; H=3.18, P>0.05). ②The expression levels of DcR3 mRNA, DR3 mRNA and Fas mRNA in ASA group and ASS group were lower than those in HC group. DcR3 mRNA in ASA group was higher than that in ASS group, and DR3 mRNA in ASA group was lower than that in ASS group {DcR3 mRNA: [7.28 (4.92, 16.56)]×10 -4vs [4.59 (2.49, 7.03)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=62.63, P<0.001; DR3 mRNA: [30.93(16.18, 66.66)]×10 -4vs [47.17(29.91, 67.40)]×10 -4vs [94.79(54.07, 144.51)]×10 -4, H=41.48, P<0.001; Fas mRNA: [20.04(3.29, 62.30)]×10 -4vs [22.49(5.63, 64.79)]×10 -4vs [78.45(27.32, 146.46)]×10 -4, H=23.54, P<0.001}. The expression levels of TL1A mRNA and LTβR mRNA in the ASA group were higher than those in the ASS group and the HC group {TL1A mRNA: [32.36(10.09, 97.84)]×10 -4vs [9.98(1.29, 21.63)]×10 -4vs [7.70(3.52,27.83)]×10 -4, H=21.14, P<0.001; LTβR mRNA: [6.13(2.16,20.06)×10 -4vs [2.13(0.53,8.04)]×10 -4vs [2.72 (1.24,5.73)]×10 -4, H=12.86, P<0.001}. The expression level of FasL mRNA in the ASA group and the ASS group was higher than that in the HC group {[60.70 (8.16, 106.16)]×10 -4vs [30.14 (5.37, 78.40)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=18.99, P<0.001}. The expression level of LIGHTR mRNA in ASS group was lower than that in HC group {[49.79(10.75, 168.48)]×10 -4vs [15.92(3.27, 105.91)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.80, P<0.001]. There was no significant difference in LIGHT mRNA among all groups ( H=4.15, P>0.05). ③Spearman correlation analysis showed that DcR3 level was positively correlated with BASDAI score and hsCRP in AS patients ( r=0.52, P<0.001; r=0.35, P<0.01), and DR3 level was negatively correlated with BASDAI score, ESR and hsCRP level ( r=-0.28, P<0.001; r=-0.25, P<0.001; r=-0.31, P<0.001). TL1A was positively correlated with BASDAI score, ESR and hsCRP level ( r=0.23, P=0.046; r=0.26, P=0.015; r=0.25, P=0.017). Conclusion:DcR3 and its signal pathway-related molecules are differentially expressed in PBMCs of patients with AS, suggesting that they may participate in the occurrence and development of AS.

Circular RNAs (circRNAs), covalently closed continuous RNA loops, are generated from cognate linear RNAs through back splicing events, and alternative splicing events may gener-ate different circRNA isoforms at the same locus. However, the challenges of reconstruction and quantification of alternatively spliced full-length circRNAs remain unresolved. On the basis of the internal structural characteristics of circRNAs, we developed CircAST, a tool to assemble alter-natively spliced circRNA transcripts and estimate their expression by using multiple splice graphs.Simulation studies showed that CircAST correctly assembled the full sequences of circRNAs with a sensitivity of 85.63％-94.32％and a precision of 81.96％-87.55％. By assigning reads to specific iso-forms, CircAST quantified the expression of circRNA isoforms with correlation coefficients of 0.85-0.99 between theoretical and estimated values. We evaluated CircAST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circRNAs and identified 380 cir-cRNAs with full-length sequences different from those of their corresponding cognate linear RNAs. RT-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms, thus further indicating the good performance of CircAST, especially for isoforms with low abundance. We also applied CircAST to published experimental data and observed substantial diversity in circular transcripts across samples, thus suggesting that circRNA expression is highly regulated. CircAST can be accessed freely at https://github.com/xiaofengsong/CircAST.

Objective To investigate the effects of azithromycin and clarithromycin on biofilm formation of Pseudomonas aeruginosa.Methods The minimal inhibitory concentrations (MIC) of azithromycin,clarithromycin,ceftazidime,ciprofloxacin and gentamicin against 4 strains of Pseudomonas aeruginosa (ATCC 27853,PA1,PA2 and PA3) were determined by broth microdilution method.The biofilm formation of Pseudomonas aeruginosa was identified by silver dyeing method on the biofilm model with medical microporous membranes in vitro.The effects of azithromycin and clarithromycin on the adhesion of biofilm were detected by crystal violet staining.The synergistic bactericidal effects of azithromycin and clarithromycin with ceftazidime,ciprofloxacin or gentamicin were detected by thiazolyl blue method respectively.Results The MIC values of Pseudomonas aeruginosa ATCC 27853,PA1,PA2 and PA3 for azithromycin,clarithromycin,cefiazidime,ciprofloxacin and gentamycin were 32,64,1,≤0.125 and 0.25 μg/mL;32,256,8,0.25 and 1 μg/mL;64,128,＞ 256,32 and 2 μg/mL and 64,128,8,2 and 0.25 μg/mL.The results of silver staining showed that the microfiltration membranes of all the four P.aeruginosa cultures appeared to be grayish black,thick and dense,and cotton-like.Compared with the control group in which no antibacterial drugs were added,both azithromycin and clarithromycin (1/16 or 1/4 MIC) reduced significantly the adhesion of the 4 strains of Pseudomonas aeruginosa (ATCC 27853,PA1,PA2 and PA3) on the microporous membrane (Pall ＜ 0.05).Compared with the use of 1 MIC of ceftazidime,ciprofloxacin or gentamycin alone,the combination of anyone of the four antimicrobial drug with azithromycin or clarithromycin (1/16 MIC) reduced the counts of viable bacteria on each biofilms with significant differences (P all ＜ 0.01).Conclusion Azithromycin and clarithromycin could effectively inhibit the biofilm formation of Pseudomonas aeruginosa and may present synergistic effects combined with cefiazidime,ciprofloxacin or gentamicin.

Objective To evaluate the agreement between regional cerebral oxygen saturation (rSO2) and jugular bulb venous oxygen saturation (SjvO2) during one-lung ventilation (OLV) in elderly patients.Methods Twenty-two patients of both sexes,aged 65-76 yr,with body mass index of 21-32 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing open pulmonary lobectomy or radical resection of esophageal cancer with combined intravenous-inhalational anesthesia,were selected.Immediately after beginning of two-lung ventilation (T0),at stable two-lung ventilation in the lateral position (T1),at 5,25 and 45 min of OLV in the lateral position (T2-4) and at the end of OLV in the lateral position (T5),blood samples were collected from the jugular bulb for blood gas analysis,and SjvO2 was recorded,rSO2 was also recorded at the time points mentioned above.Bland-Altman analysis was used to evaluate the agreement.Results SjvO2 was significantly lower at T0-5 than rSO2 (P＜0.05).rSO2 and SjvO2 were gradually decreased at T1-5 (P＜0.05).The results of Bland-Altman analysis showed that the difference between rSO2 more than 95％ and SjvO2 was within the range of 95％ limits of agreement,and the absolute value of the maximum difference was 20.8％.Conclusion There is a good agreement between rSO2 and SjvO2 during OLV in elderly patients,and SjvO2 can be recommended as an alternative to rSO2 clinically.

Objective To evaluate the effects of biological rhythm disturbance on sedation induced by propofol in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups (n =8 each) using a random number table:circadian rhythm + administration during night-time group (group CN),circadian rhythm + administration during day-time group (group CD),biological rhythm+administration during night-time group (group BN),and biological rhythm+administration during day-time group (group BD).In CN and CD groups,the rats were fed for 2 weeks in the experimental boxes in a 12 (7:00-19:00):12 h (19:00-7:00) light:dark cycle.While the rats were fed for 2 weeks in the experimental boxes in a 24 h light cycle.Propofol 75 mg/kg was intraperitoneally injected at 14:00 in CN and BN groups,or at 22:00 in CD and BD groups.The duration of loss of righting reflex was recorded.At 20 min after recovery of righting reflex,the cognitive function was assessed.The latency of passive avoidance was measured at 6,12,24 and 48 h after training.Results Compared with group CN,the duration of loss of righting reflex was significantly shortened,and the latency of passive avoidance was prolonged at 12 and 24 h after training in group CD,and the duration of loss of righting reflex and latency of passive avoidance at 12 and 24 h after training were shortened in group BN.Compared with group CD,no significant change was found in the duration of loss of righting reflex,and the latency of passive avoidance was significantly shortened at 24 h after training in group BD.There was no significant change between BN group and BD group in the duration of loss of righting reflex and latency of passive avoidance.Conclusion Biological rhythm disturbance can counteract circadian rhythmproduced effects on sedation induced by propofol in rats.

Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.