Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

Objective:Construct a combined detection model of miR-202-5p and interleukin-6 (IL-6) and explore its diagnostic value for acute myocardial infarction (AMI).Methods:Clinical data of 202 patients with coronary atherosclerotic heart disease (CHD) who were admitted to the Department of Cardiology and Emergency Department of Hebei People's Hospital from August 2020 to August 2022 were retrospectively analyzed, including 106 AMI patients and 96 non AMI patients. The clinical characteristics and blood levels of miR-202-5p and IL-6 were compared between the two groups, T-test was used for inter group comparison of measurement data that conforms to normal distribution, non parametric rank sum test was used for inter group comparison of measurement data that does not conform to normal distribution, and χ2 test was used for inter group comparison of count data. Binary Logistic regression model was used to determine the independent influencing factors of AMI, and a combined diagnostic model was constructed according to the analysis results, the diagnostic efficacy of miR-202-5p, IL-6 and combined detection for AMI was evaluated by ROC curve, and the clinical diagnostic effect was observed. Results:The expression levels of serum total cholesterol (4.40 (3.71, 5.00) mmol/L), low density lipoprotein cholesterol (2.99 (2.39,3.47) mmol/L), lipoprotein a (276.80 (182.58,390.13) mg/L), interleukin-4(IL-4)(2.69(2.29,3.16) μg/L), IL-6(89.82(68.26,107.16) μg/L) in AMI group were significantly higher than those of non-AMI group (4.04 (3.12, 4.73) mmol/L, 2.75 (2.15, 3.21) mmol/L, 213.45 (146.73, 348.80) mg/L, 2.46 (1.92, 3.01)] μg/L, 45.89 (32.38, 62.83) μg/L, while miR-202-5p(0.33 (0.27,0.38)) was lower than that in the non-AMI group (0.51 (0.36,0.68)), ( H values were 4 167.50, 4 234.00, 4 262.50, 4 228.00, 1 513.00, and 2 098.50, respectively; P values were 0.027, 0.040, 0.047, 0.038, <0.001, <0.001, respectively). Multivariate binary logistic regression analysis showed that high levels of IL-6 and low levels of miR-202-5p were independent risk factors for AMI. The joint diagnostic model of IL-6 and miR-202-5p was Logit (P)=-1.046-5.236 × miR-202-5p+0.051 × IL-6, with probability value P as the diagnostic indicator and P=0.45 as the diagnostic threshold. ROC curve results showed that the area under curve (AUC) of IL-6 and miR-202-5p were 0.851 and 0.794, respectively, while the AUC of the combined diagnosis model was 0.894, indicating that the diagnosis accuracy was higher than that of a single index. Compared with isolated detection, the sensitivity, specificity and Kappa value of the IL-6+miR-202-5p collaborative test for AMI prediction were increased, especially the diagnosis results were close to a high degree of agreement with the actual results ( Kappa=0.732). Conclusion:High levels of IL-6 and low levels of miR-202-5p are independent influencing factors for AMI, and the combined diagnosis model of the two has clinical application value.

Objective To evaluate the potential of miR-30a-5p as a novel indicator of acute myocardial infarction(AMI)and the underlying molecular mechanisms.Methods AMI-associated microRNAs(miRNAs)and mRNA microarray datasets were downloaded from the GEO database.Real-time fluorescence quantitative PCR(qRT-PCR)technique was used to detect the level of miRNAs in serum samples;automatic biochemistry was used to detect other biochemical indicators.Receiver operating characteristic(ROC)curve analysis and Spearson correlation analysis were performed to assess the value of miR-30a-5p as a diagnostic AMI marker.The target genes of miR-30a-5p were predicted with the R language multiMiR package,and the protein interaction network was constructed by the STRING database.The results were imported into Cytoscape 3.7.1 software to screen the pivotal genes of the network.The R language clusterProfiler package performed KEGG and GO analyses on the hub genes to explore the clinical significance of miR-30a-5p in AMI and its potential molecular mechanisms.Results Compared with the control group,miR-30a-5p was upregulated significantly in the serum of patients in the AMI group(P＜0.05);miR-30a-5p was positively correlated with the levels of CK-MB,CK,TnT,proBNP and CRP(rs=0.489,P＜0.001;rs=0.347,P＜0.001;rs=0.545,P＜0.001;rs=0.533,P＜0.001;rs=0.206,P＜0.05).The area under the ROC curve was 0.862,with sensitivity of 84.4％and specificity of 74.2％.A total of 780 differentially expressed genes(DEGs)were obtained from the two datasets.A total of 1 061 target genes of miR-30a-5p and 61 common genes were identified by taking the intersection set.Among the central genes of PPI,BCL6,FOSL2,JDP2,LYN,PDE4D,SOCS3 and SOX4 scored high and were closely associated with the occurrence of AMI.KEGG and GO enrichment analyses showed that miR-30a-5p might regulate JAK-STAT,NF-kappaB and Wnt signaling pathways,which were involved in inflammatory response,apoptosis,autophagy and post-infarction remodeling,and thus participated in the process of AMI.Conclusion Serum miR-30a-5p is up-regulated in the early stage of AMI,and the study on miR-30a-5p and its regulatory pathways can help with the diagnosis and treatment of myocardial infarction.

Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

ObjectiveTo observe the effects of modified Shenqiwan on renal function and fibrosis in diabetic nephropathy mice and explore the underlying mechanism based on the glycogen synthase kinase-3β （GSK-3β）/cyclic adenosine monophosphate （cAMP） response element-binding protein （CREB） signaling pathway. MethodFifty male db/db mice and 10 db/m mice were used in this study. The fifty db/db mice were randomly divided into model group， irbesartan group， and low-， medium-， and high-dose modified Shenqiwan groups. The 10 db/m mice were assigned to the normal group. The mice in the low-， medium-， and high-dose modified Shenqiwan groups were administered with modified Shenqiwan in the dosage form of suspension of Chinese medicinal granules by gavage， those in the irbesartan group were given irbesartan suspension by gavage， and those in the normal and model groups were given distilled water of equal volume by gavage. The intervention lasted for 12 weeks. The blood glucose levels， urine albumin-to-creatinine ratio （UACR）， and the protein expression levels of GSK-3β， CREB， transforming growth factor-β₁ （TGF-β₁）， E-cadherin， Vimentin， fibronectin （FN）， plasminogen activator inhibitor-1 （PAI-1）， and Collagen type Ⅳ （Coll Ⅳ） in the mouse kidneys were recorded before and after treatment. The extent of renal pathological damage was also observed. ResultCompared with the normal group， the model group showed significant increases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β₁， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， decreased protein expression level of CREB （P<0.05）， and severe renal pathological damage. Compared with the model group， the low-， medium-， and high-dose modified Shenqiwan groups and the irbesartan group showed varying degrees of decreases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β₁， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， increased expression level of CREB protein （P<0.05）， and improved renal pathological damage. ConclusionModified Shenqiwan can effectively reduce blood glucose levels， improve renal function， and alleviate fibrosis， and the mechanism of action is related to the inhibition of the GSK-3β/CREB signaling pathway.

ObjectiveTo explore the effect of trunk control training during unstable sitting on knee pain and function in patients with patellofemoral pain syndrome. MethodsFrom January, 2019 to December, 2021, 41 patients with patellofemoral pain syndrome in Beijing Rehabilitation Hospital were randomly divided into control group (n = 20) and experiment group (n = 21). Both groups accepted routine rehabilitation, and the experiment group accepted trunk control training during unstable sitting in addition, for four weeks. They were assessed with Visual Analogue Scale for pain (VAS) and Anterior Knee Pain Scale (AKPS), and measured stability indexes with Balancer before and after treatment. ResultsAll the VAS score, AKPS score, and the overall, anterior-posterior and left-right stability indexes improved in both groups after treatment (|t| > 12.089, P < 0.001); and improved more in the experiment group than in the control group (|t| > 5.864, P < 0.001). ConclusionTrunk control training during unstable sitting may improve knee pain and function, and motor control.

Objective: To investigate the mechanisms of miR-375 affecting the proliferation and invasion of hepatoma cells via targeting YAP (Yes-associated protein). Methods: The cancerous tissues and corresponding para-cancerous tissues of 70 patients with hepatocellular carcinoma (HCC) who underwent surgical resection at the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2016, as well as the hepatoma cell lines SMMC-7721, Hb611, HepG2 and BEL-7405 were collected for this study. qPCR method was used to detect the expression level of miR-375 in collected HCC tissues and different hepatoma cell lines; Dual luciferase reporter gene assay was used to verify the interaction between miR-375 and YAP; The relationship between miR-375 and clinicopathological features of HCC patients was also analyzed; MTT assay was used to detect the effect of miR375 on the proliferation of hepatoma cells; Transwell invasion assay was used to detect the invasive ability of hepatoma cells after inhibiting the expression of miR-375; Western blotting was used to detect the expression of YAP in HepG2 cells. The nude mouse model of subcutaneously transplanted xenograft was established, and the tumor volume and mass of transplanted hepatoma cells were detected after inhibiting the expression of miR-375. The expression of YAP in xenograft of nude mice was detected by immunohistochemistry and Western blotting. Results: The expression of miR-375 and YAP in HCC tissues was significantly higher than that in para-cancerous tissues (all P<0.05). The expression of miR-375 in HepG2 cells was the highest (P<0.05). miR-375 could specifically bind to the 3' UTR of YAP and regulate the expression activity of YAP. After inhibiting the expression of miR-375, the proliferation and invasion abilities of HepG2 cells were reduced (all P<0.05); The tumor volume and mass of transplanted xenografts were significantly reduced (both P<0.05); The expression of YAP protein in the transplanted xenografts was down-regulated (P<0.05). Conclusion: miR-375 plays an important role in the occurrence and development of liver cancer, and can influence the malignant biological behaviors of hepatoma cells by targeting and regulating the expression ofYAP.

Current trends in chiral analysis of pharmaceutical drugs are focused on faster separations and higher separation efficiencies. Core-shell or superficially porous particles (SPP) based chiral stationary phases (CSPs) provide reduced analysis times while maintaining high column efficiencies and sensitivity. In this study, mobile phase conditions suitable for chiral analyses with electrospray ionization LC-MS were systematically investigated using vancomycin as a representative CSP. The performance of a 2.7 μm SPP based vancomycin CSP (SPP-V) 10 cm × 0.21 cm column was compared to that of a corresponding 5 μm fully porous particles based analogue column. The results demonstrated that the SPP-V column provides higher efficiencies, 2–5 time greater sensitivity and shorter analysis time for a set of 22 basic pharma-ceutical drugs. The SPP-V was successfully applied for the analysis of the degradation products of racemic citalopram whose enantiomers could be selectively identified by MS.

Objective To comparatively analyze the image characteristic of contrast-enhanced ultrasound(CEUS)and contrast-enhanced computed tomography(CECT),and explore the diagnostic value of the two methods in benign and malignant lesions of gallbladder.Methods comparative analysis the image characteristic of CEUS and CECT,the preoperative diagnostic results of 86 cases of gallbladder diseases were confirmed by pathology.Results The enhancement patterns of CEUS and CECT in benign and malignant lesions of gallbladder are similar.The sensitivity,specificity and accuracy of CEUS were 77.9%(53/68),77.8%(14/18),77.9%(67/86),respectively.The sensitivity,specificity and accuracy of CECT were 75%(51/68),55.6%(10/18),70.9%(61/86),respectively.The sensitivity,specificity and accuracy of the combination of CEUS and CECT were 83.8%(57/68),55.6%(10/18),77.9%(67/86),respectively.The accuracy of the combination of CEUS and CECT was higher than that of CECT in the diagnosis of malignant gallbladder lesions [(53.9±10.00)s vs(35.50±6.72)s],the differences were statistically significant(t=6.729,P＜0.001).Conclusions The enhancement patterns of CEUS and CECT in benign and malignant gallbladder lesions are similar.The combination of CEUS and CECT is helpful for improving the diagnostic accuracy of malignant gallbladder lesions.CEUS and CECT could corroborate and complement each other,and provide more valuable information for the differential diagnosis of benign and malignant gallbladder lesions.