ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

There are three types of bioanalytical methods for nucleic acid drugs， including ligand binding assay， quantitative polymerase chain reaction and liquid chromatography-based bioanalytical technologies. Although the first two assays have high sensitivity， they have poor selectivity and can not differentiate between intact and truncated metabolites. Liquid chromatography- based bioanalytical technologies which are less sensitive， offer high selectivity for the identification of intact and truncated metabolites. They have broad application prospects in both preclinical and clinical investigations of therapeutic nucleic acid drugs. This paper provides a critical review on the characteristics of these technologies and their application to analyze nucleic acid drugs， including high performance liquid chromatography-ultraviolet detection （HPLC-UV）， high performance liquid chromatography- fluorescence （HPLC-FL）， liquid chromatography-tandem mass spectrometry （LC-MS/MS）， liquid chromatography-high resolution- mass spectrometry， microflow liquid chromatography-tandem mass spectrometry （microflow LC-MS/MS） and hybridization liquid chromatography-tandem mass spectrometry. Although these technologies have high sensitivity except for HPLC-UV， they still have some shortcomings， such as suitable probes need to be designed for HPLC-FL， standard substance for LC-MS/MS， and high cost for microflow LC-MS/MS. In addition， the development of some related strategies or technologies （e.g. non-specific adsorption strategy， sample pretreatment） which can improve the sensitivity， has hastened the development of liquid chromatography-based bioanalytical technologies for nucleic acid drugs.

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 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 explore the mechanism of Buyang Huanwu Decoction for"treating different diseases with same therapies"in type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)based on network pharmacology and molecular docking techniques.Methods Firstly,the active ingredients of seven herbs in Buyang Huanwu Decoction were searched and screened by TCMSP,SymMap and other databases,the target prediction of these active ingredients was carried out by PharmMapper.The disease targets of T2DM and AD were collected from OMIM,DrugBank,GeneCards and Disgenet databases.The potential targets of Buyang Huanwu Decoction for"treating different diseases with same therapies"in T2DM and AD were obtained by intersecting with targets of active ingredients and the disease targets.Then STRING database and Cytoscape software were used to construct the PPI network and"herbs-components-targets"network,respectively.The core targets and pharmacodynamic components were screened through network topology analysis.Furthermore,GO functional and KEGG enrichment analysis was performed for potential targets using Metascape database.Finally,AutoDock software was used to verify the molecular docking between the selected components and targets.Results Ninety-four active components of Buyang Huanwu Decoction can act on 342 protein targets,and 100 intersection targets were obtained by comparing with 3 140 AD targets and 1 708 T2DM targets.GO functional enrichment analysis showed that these targets were mainly involved in MAPK cascade-mediated regulation,hormone-mediated signaling pathways,cellular response to lipids,regulation of inflammation response and other biological processes.MAPK,PI3K/Akt,FoxO,AGE/RAGE,insulin resistance,lipid and atherosclerosis,and non-alcoholic fatty liver signaling pathway were significantly enriched in KEGG analysis.PPI and topology analysis of"herbs-components-targets"network were used to screen out 10 core targets such as MAPK8,MAPK14,GSK3B,PPARG,and 10 core pharmacodynamic components such as paeoniflorin,benzoyl paeoniflorin,(+)-catechin.The results of molecular docking showed that these components had strong binding ability to the targets.Conclusion The core components of Buyang Huanwu Decoction,such as paeoniflorin and catechin,may act on PPARG,GSK3B and other key targets,and participate in the regulation of signaling pathways including MAPK and PI3K/Akt,which play a role in"treating different diseases with the same therapies"of T2DM and AD.

Objective:To investigate the utilization of health management services and its influencing factors among new urban population.Methods:It is a cross-sectional study. From July 2020 to March 2021, a stratified random sampling method was used to extract 1978 new urban population in Jining city, and an anonymous self-administered questionnaire survey was conducted using a self-made questionnaire ′Residents Health Questionnaire′. The survey included general demographic characteristics, personal behavior lifestyle and medical care status. The χ2 test and binary logistic regression were used to analyze the factors influencing the utilization of health management services by new urban population. Results:The overall utilization of health management services in the new urban population was 47.22%. There were significant differences in utilization of health management services among new urban population with different gender, age, education level, occupation and monthly income. Binary logistic regression analysis showed that female ( OR=1.354, 95% CI: 1.094-1.676), people aged over 60 years ( OR=1.873, 95% CI: 1.413-2.483), people with a mean monthly income over 3 000 yuan ( OR=1.498, 95% CI: 1.123-1.997), people engaged in light manual labor ( OR=1.596, 95% CI: 1.003-2.539), people who exercise regularly( OR=2.400, 95% CI: 2.028-2.841) and people having social basic medical insurance ( OR=2.633, 95% CI: 2.042-3.394) had better utilization of health management projects. People who sat more than 3 hours a day ( OR=0.630, 95% CI: 0.532-0.745) had lower utilization of health management care. Conclusion:The utilization of health management projects in the new urban population is low. Gender, age, monthly income, physical exercise, sedentary time, daily labor intensity and social basic medical insurance status are the main influencing factors.

【Objective】 To investigate the effects of 80 kVp combined with multi-model adaptive statistical iterative reconstruction algorithm （ASiR-V） on the image quality of CT angiography （CTA） of iliac artery in kidney transplantation candidates before operation. 【Methods】 Totally 50 kidney transplantation candidates underwent “one-stop” scanning combined CTA for coronary and iliac arteries were recruited consecutively. After the scanning， images were reconstructed with different ASiR-V levels on the iliac artery from 50% to 100% at a 10% interval， and 6 groups of images were obtained. We evaluated and compared all image qualities， DLP and CTDI in the patients’ examination were recorded， and the effective dose （ED） was calculated. 【Results】 All of the image quality objective scores of different ASiR-V levels on the iliac artery were above 3 points （3.32±0.24）， and the average CT value was （344.30±74.53）HU. The ED received by the patient throughout the examination was （2.71±0.42)mSv. The image noise decreased while SNR and CNR increased monotonically as the ASiR-V levels increased， among which 80% ASiR-V image quality score was the highest with 3.41±0.26. 【Conclusion】 For patients who need to have both coronary and iliac arteries evaluated before kidney transplantation operation， low tube voltage （80 kVp） combined with 80% ASiR-V can obtain high-quality iliac artery images under the premise of reducing the ED dose， which can provide practical basis for further reducing the dose in personalized scanning scheme for such patients. It has good feasibility and clinical application value.

Objective To detect the value of autoantibedy profile in primary biliary cirrhosis (PBC). Methods 96 serum samples of patients with primiary biliary cirrhosis, 100 serum samples of other antoimmune disease and 49 serum samples of healthy were tested for anti- M2, anti-3E(BPO), anti-Sp100,anti-PML,anti-gp210,anti-LKM-1 ,anti-LC-1 ,anti-SLA/LP by EUROLine. Results The positive of the anti-M2,anti-BPO, anti-Sp100, anti-PML and anti-gp210 for PBC was 76. 0%, 84.4%, 32. 3%, 28. 1% and 35.4% ,respectively. The positive of the anti-M2, anti-BPO, anti-Sp100, anti-PML and anti-gp210 for other autoimmune disease was 13.0% ,9. 0% ,3.0% ,2.0% and 1. 0%, respectively. The sensitivity of the anti-M2 for PBC was 76. 0% ,with specificity of 87. 0%. The sensitivity of the anti-BPO for PBC was 84. 4%, with specificity of 91.0% ;the sensitivity of the anti-Sp100 for PBC was 32. 3%, with specificity of 97.0%. The sensitivity of the anti-PML for PBC was 28. 1% ,with specificity of 98.0%. The sensitivity of the anti-gp210 for PBC was 35.4%, with specificity of 99. 0% . Anti-LKM-1, anti-LC-1, anti-SLA/LP positive patients with PBC were not detected;the incidence rate of liver function failure in anti-gp210 positive serum higher than anti-gp210 negative serum (χ2 = 11.17, P < 0. 01). Conclusions Multiple autoantibedies can be detected in the sera of PBC patients. The detection of autoantibody profile is useful for the diagnosis and differential diagnosis of PBC, and may he helpful for therapy and prognosis of PBC.

Objective To detect the expression of TGF-β1 mRNA and ERβwt mRNA in peripheral blood monoanclear cells (PBMCs) in patients with chronic fatigue syndrome (CFS), and their relationship with pathogenesis of CFS. Methods Fluorescence quantitative RT-PCR (FQ-RT-PCR) was used to examine TGF-β1 mRNA and ERβwt mRNA expression of peripheral blood monocytes in 63 cases with CFS,50 cases with other diseases, and 50 healthy controls. The gene expression levels were calculated with the formula △Ct=Ct(target gene) - Ct(internal control). Results The mean TGF-β1 mRNA expression of CFS patients (△Ct = 3.27 ± 0. 58) was higher than that of disease controls (△Ct = 4. 54 ± 1.05, t = 8. 11, P <0.01) and that of healthy controls (△Ct = 4. 37 ± 1.00, t = 7. 02, P < 0. 01). The mean ERβwt mRNA expression of CFS patients (△Ct =9. 34 ±0. 92) was lower than that of disease controls(△Ct =7.12±0. 47, t = 15.44 ,P < 0. 01) and that of healthy controls(△Ct = 7. 10 ±0. 48, t = 15.47, P < 0. 01). Conclusions The TGF-β1 mRNA and ER βwt mRNA expression levels of PBMCs are siguificantly elevated in patients with CFS. It may be implicated in the pathogenesis of CSF.

Objective To investigate the relationship between the PTPN22 gene polymorphism and rheumatoid arthritis(RA).Methods Real time fluorescent quantitation PCR was used to detect the 1123G＞C polymorphism of the PTPN22 gene from 200 RA patients,100 others rheumatic diseases and 200 the normal controls.The results were analyzed by SPSS 11.0 software.Results The CC genotype frequencies of RA patients.others rheumatic diseases and the normal controls were 0.120,0.020 and 0.015 respectively.There was a significant difiefence between BA patients and others rheumatic diseases (X=18.708.P＜0.01).1'here Wag a significant difference between RA patients and the normal controls(X2=24.337,P＜0.01).There was not statistically significant between others rheumatic diseases and the normal controls(X2=1.066,P＞0.05).The C allele frequency of RA patients,others rheumatic diseases and the normal controls were 0.360.0.190 and 0.215 respectively.The results were significant difference.Conclusion The PTPN22 gene could be one of predisposing genes and the therapeutic target genes with RA patients.