Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

The application of function-preserving pancreatic surgery as a restrictive resection technique is primarily targeted towards benign or those with borderline or low-grade lesions. This approach has been shown to significantly improve both short-term and long-term quality of life outcomes for patients following surgical intervention. In comparison to conventional laparoscopic procedures, robotic surgical systems have demonstrated superior efficacy and precision when employed in pancreas surgeries, and the safety and reliability are widely recognized within the medical community. Nevertheless, there remains a dearth of research investigating the specific appli-cations of robotic-assisted function-preserving pancreatic surgery. Consequently, the authors compre-hensive review the latest progress on robot-assisted function-preserving pancreatic surgery, while highlighting of surgical scope, techniques utilized during these procedures as well as associated prognostic considerations.

Compared with conventional treatments, oncolytic virotherapy has the advantages of enhanced cytotoxicity, improved targeting, and minimal side effects. However, its efficacy is not as good as expected for the single drug treatment. The purpose of synergistic effect is one of the development directions of existing oncolytic virus therapy. In this paper, through a systematic review of the current preclinical and clinical trials progress of oncolytic virus combination therapy, the combined treatment strategies of oncolytic virus and immune checkpoint inhibitors, chemotherapy, targeted therapy,and cell therapy are reviewed to provide reference for further clinical application.

Compared with conventional treatments, oncolytic virotherapy has the advantages of enhanced cytotoxicity, improved targeting, and minimal side effects. However, its efficacy is not as good as expected for the single drug treatment. The purpose of synergistic effect is one of the development directions of existing oncolytic virus therapy. In this paper, through a systematic review of the current preclinical and clinical trials progress of oncolytic virus combination therapy, the combined treatment strategies of oncolytic virus and immune checkpoint inhibitors, chemotherapy, targeted therapy,and cell therapy are reviewed to provide reference for further clinical application.