AIM:This study aimed to investigate the effect of ischemic post-conditioning(I-post-C)on lung ischemia-reperfusion injury(LIRI)in rats and relationship between I-post-C and zinc homeostasis.METHODS:SPF SD rats(6～8 weeks old)were randomly divided into four groups,with eight rats in each group:control group,ischemia/reper-fusion(I/R)group,I-post-C group and I-post-C+zinc ion chelator TPEN group.Inductively coupled plasma mass spec-trometry(ICP-MS)was used to measure the concentration of zinc ions in lung tissues.HE staining,lung wet/dry weight ra-tio(W/D),total lung water content(TLW),and index of quantitative assessment(IQA)of lung injury were used to detect the degree of lung tissue injury in each group.Mitochondrial membrane potential was measured using extraction and JC-1 mitochondrial membrane potential detection kits.TUNEL assay was used to detect the level of apoptosis in lung tissues.Western blot was used to detect the protein expression levels of caspase-3,solute carrier family 39 member 8(SLC39A8/ZIP8),solute carrier family 30 member 9(SLC30A9/ZNT9),and PI3K/AKT/GSK-3β in lung tissues of each group.RT-qPCR was used to detect ZIP8 and ZNT9.RESULTS:Compared to the control group,the I/R group showed significantly aggravated lung tissue injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced cell apoptosis(P<0.05),re-duced mitochondrial membrane potential(P<0.01),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved caspase-3/pro-caspase-3 ratio(P<0.01),and reduced ZIP8 expression(P<0.05).Compared to the I/R group,the I-post-C group exhibited alleviated injury(P<0.05 or P<0.01),increased zinc ion levels(P<0.01),reduced apoptosis(P<0.01),restored mitochondrial membrane potential(P<0.01),elevated PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),decreased cleaved caspase-3/pro-caspase-3 ratio(P<0.05),and in-creased ZIP8 expression(P<0.05).Compared to the I-post-C group,the I-post-C+TPEN group demonstrated aggravated injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced apoptosis(P<0.01),reduced mitochondrial membrane potential(P<0.05),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved cas-pase-3/pro-caspase-3 ratio(P<0.05),and reduced ZIP8 expression(P<0.05).ZNT9 expression showed no significant differences among the groups(P>0.05).CONCLUSION:Ischemic postconditioning can improve LIRI by regulating zinc homeostasis,activating PI3K/AKT signaling pathway,inactivating glycogen synthase kinase 3β,inhibiting the de-cline of mitochondrial membrane potential,and antagonizing cell apoptosis in rats.

Objective:To explore the current therapeutic status of rhythm control versus rate control in elderly patients with atrial fibrillation(AF)and the related factors that may influence treatment decisions.Methods:A retrospective study was conducted on AF patients aged ≥75 years old who were hospitalized in the Healthcare Department of Beijing Hospital from January 2010 to May 2020.The patients were grouped and compared according to whether they underwent rhythm control or rate control.Multivariate logistic regression analysis was used to investigate the factors that may influence the treatment decision of rhythm control or rate control.Results:A total of 167 patients was included, with a median age of 90 years old.Among them, 21 patients(12.6%)received rhythm control, and 109 patients(65.3%)received rate control.Compared with the group not receiving rhythm control, the rhythm control group had a younger age, higher BMI, higher diastolic blood pressure, a higher proportion of multiple medication use, a lower proportion of chronic kidney disease stage 3 or above, and higher hemoglobin levels(all P<0.05). Compared with the group not receiving rate control, the rate control group had a lower proportion of paroxysmal AF, a faster resting ventricular rate, a higher proportion of smoking history, a higher proportion of multiple medication use, coronary heart disease, pacemaker treatment, chronic obstructive pulmonary disease and/or asthma, and a lower proportion of cognitive impairment(all P<0.05). Multivariate logistic regression analysis revealed that multiple drug use( OR=11.578, 95% CI: 1.341-99.993, P=0.026)was positively associated with rhythm control therapy, while chronic kidney disease stage 3 or above( OR=0.248, 95% CI: 0.063-0.968, P=0.045)was negatively associated with rhythm control therapy.For rate control therapy, multiple drug use( OR=5.056, 95% CI: 2.253-11.347, P<0.001), resting ventricular rate( OR =1.033, 95% CI: 1.005-1.062, P=0.021), and chronic obstructive pulmonary disease(COPD)and/or asthma( OR=2.739, 95% CI: 1.124-6.672, P=0.027)showed positive associations. Conclusions:The application rate of rhythm control therapy is low in elderly AF patients, and ventricular rate control is the main treatment.Complex clinical conditions are the main constraints, and it is urgent to optimize individualized strategies based on prospective studies and develop new treatment techniques to improve clinical practice.

AIM:This study aimed to investigate the effect of ischemic post-conditioning(I-post-C)on lung ischemia-reperfusion injury(LIRI)in rats and relationship between I-post-C and zinc homeostasis.METHODS:SPF SD rats(6～8 weeks old)were randomly divided into four groups,with eight rats in each group:control group,ischemia/reper-fusion(I/R)group,I-post-C group and I-post-C+zinc ion chelator TPEN group.Inductively coupled plasma mass spec-trometry(ICP-MS)was used to measure the concentration of zinc ions in lung tissues.HE staining,lung wet/dry weight ra-tio(W/D),total lung water content(TLW),and index of quantitative assessment(IQA)of lung injury were used to detect the degree of lung tissue injury in each group.Mitochondrial membrane potential was measured using extraction and JC-1 mitochondrial membrane potential detection kits.TUNEL assay was used to detect the level of apoptosis in lung tissues.Western blot was used to detect the protein expression levels of caspase-3,solute carrier family 39 member 8(SLC39A8/ZIP8),solute carrier family 30 member 9(SLC30A9/ZNT9),and PI3K/AKT/GSK-3β in lung tissues of each group.RT-qPCR was used to detect ZIP8 and ZNT9.RESULTS:Compared to the control group,the I/R group showed significantly aggravated lung tissue injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced cell apoptosis(P<0.05),re-duced mitochondrial membrane potential(P<0.01),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved caspase-3/pro-caspase-3 ratio(P<0.01),and reduced ZIP8 expression(P<0.05).Compared to the I/R group,the I-post-C group exhibited alleviated injury(P<0.05 or P<0.01),increased zinc ion levels(P<0.01),reduced apoptosis(P<0.01),restored mitochondrial membrane potential(P<0.01),elevated PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),decreased cleaved caspase-3/pro-caspase-3 ratio(P<0.05),and in-creased ZIP8 expression(P<0.05).Compared to the I-post-C group,the I-post-C+TPEN group demonstrated aggravated injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced apoptosis(P<0.01),reduced mitochondrial membrane potential(P<0.05),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved cas-pase-3/pro-caspase-3 ratio(P<0.05),and reduced ZIP8 expression(P<0.05).ZNT9 expression showed no significant differences among the groups(P>0.05).CONCLUSION:Ischemic postconditioning can improve LIRI by regulating zinc homeostasis,activating PI3K/AKT signaling pathway,inactivating glycogen synthase kinase 3β,inhibiting the de-cline of mitochondrial membrane potential,and antagonizing cell apoptosis in rats.

Objective:To explore the current therapeutic status of rhythm control versus rate control in elderly patients with atrial fibrillation(AF)and the related factors that may influence treatment decisions.Methods:A retrospective study was conducted on AF patients aged ≥75 years old who were hospitalized in the Healthcare Department of Beijing Hospital from January 2010 to May 2020.The patients were grouped and compared according to whether they underwent rhythm control or rate control.Multivariate logistic regression analysis was used to investigate the factors that may influence the treatment decision of rhythm control or rate control.Results:A total of 167 patients was included, with a median age of 90 years old.Among them, 21 patients(12.6%)received rhythm control, and 109 patients(65.3%)received rate control.Compared with the group not receiving rhythm control, the rhythm control group had a younger age, higher BMI, higher diastolic blood pressure, a higher proportion of multiple medication use, a lower proportion of chronic kidney disease stage 3 or above, and higher hemoglobin levels(all P<0.05). Compared with the group not receiving rate control, the rate control group had a lower proportion of paroxysmal AF, a faster resting ventricular rate, a higher proportion of smoking history, a higher proportion of multiple medication use, coronary heart disease, pacemaker treatment, chronic obstructive pulmonary disease and/or asthma, and a lower proportion of cognitive impairment(all P<0.05). Multivariate logistic regression analysis revealed that multiple drug use( OR=11.578, 95% CI: 1.341-99.993, P=0.026)was positively associated with rhythm control therapy, while chronic kidney disease stage 3 or above( OR=0.248, 95% CI: 0.063-0.968, P=0.045)was negatively associated with rhythm control therapy.For rate control therapy, multiple drug use( OR=5.056, 95% CI: 2.253-11.347, P<0.001), resting ventricular rate( OR =1.033, 95% CI: 1.005-1.062, P=0.021), and chronic obstructive pulmonary disease(COPD)and/or asthma( OR=2.739, 95% CI: 1.124-6.672, P=0.027)showed positive associations. Conclusions:The application rate of rhythm control therapy is low in elderly AF patients, and ventricular rate control is the main treatment.Complex clinical conditions are the main constraints, and it is urgent to optimize individualized strategies based on prospective studies and develop new treatment techniques to improve clinical practice.

Objective:To assess the association of cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC). Methods:From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+ 49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group ( n=166) and poor prognosis group ( n=86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis. Results:No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups ( P>0.05). The frequencies of GG genotype and G allele for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group ( P<0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups ( P>0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group ( P<0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P<0.001). Conclusion:The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome, and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors, including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high-precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening in the fetal gene reprogramming in HCM.
Cardiomyopathy, Hypertrophic/metabolism* ; Humans ; Animals ; DNA Methylation ; Mice ; Transcriptome ; Chromatin/genetics* ; Early Growth Response Protein 1/metabolism* ; Male ; Epigenome ; Nucleosomes/genetics* ; Female ; Middle Aged ; Disease Models, Animal ; Adult

Objective:To analyze the application value of negative pressure closed drainage in tuberculous surgery infected wounds and its effect on wound healing and Th1/Th2 expression.Methods:A prospective study was conducted on 120 patients with tuberculous surgery infected wounds admitted to Hebei Provincial Chest Hospital from January 2019 to June 2021. The patients were divided into observation group and control group according to the random envelope method, with 60 cases in each group. The control group received conventional suture drainage tube intervention, while the observation group received negative pressure closed drainage intervention. The survival rate of skin grafting at 2 weeks after operation, the wound healing rate at 8 weeks after operation, and the pain situation during the first 3 dressing changes were observed. The levels of interferon γ (IFN-γ), interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), IL-6, alkaline phosphatase (ALP), phosphorus (P), calcium (Ca), Th1 and Th2 in serum were detected before treatment and 14 days after treatment.Results:The survival rate of skin grafting at 2 weeks and the wound healing rate at 8 weeks in the observation group were significantly higher than those in the control group, with statistically significant differences (all P<0.05). The Visual Analog Scale (VAS) scores of the observation group were significantly lower than those of the control group during the second and third dressing changes (all P<0.05). At 14 days after treatment, the serum levels of Th1 and Th2 in the observation group were significantly higher than those in the control group, while the levels of IFN-γ, IL-2, TNF-α, IL-6, ALP, P, Ca, Th1/Th2 in serum were significantly lower than those in the control group (all P<0.05). Conclusions:Using negative pressure closed drainage technology can effectively promote wound healing in patients with tuberculous surgery infected wounds and improve the balance of Th1/Th2 in blood.

Objective:To investigate the expression of miR-527 in bladder cancer (BC) and its effect on the proliferation, migration and invasion of bladder cancer cells.Methods:From February 2018 to June 2019, the immortalized human bladder epithelial cell line SV-HUC-1 and human bladder cancer cell lines T24, UM-UC-3, 5637 and RT-112 were cultured in vitro. Real time quantitative PCR (qRT-PCR) was used to detect the expression of miR-527 in BC bladder cancer tissues and adjacent normal bladder tissues, human bladder cancer cell lines and human bladder epithelial immortalized cell lines. MiR-527 mimics, miR-527 inhibitor, ENO1 overexpression plasmid, ENO1 siRNA and corresponding negative control were transfected into bladder cancer cell line. CCK8 test, clone formation test and Transwell test were used to study the cell proliferation, migration and invasion. Luciferase reporter gene assay was used to verify the target gene of miR-527. Western blotting was used to analyze the regulation of miR-527 on target gene expression.Result:Compared with normal bladder tissue, the expression of miR-527 in bladder cancer was significantly lower (1.723±1.070 vs. 1.148±0.760, P<0.05). The relative expression of miR-527 in T24 (0.540±0.082), UM-UC-3 (0.230±0.053), 5637(0.463±0.085) and RT-112 (0.310±0.056) were significantly lower than those in SV-HUC-1 cells (0.987±0.111) with statistical significance ( P<0.05). Compared with the negative control (NC) group, CCK8 assay results showed that the cell viability was significantly decreased after transfection of miR-527 mimics into UM-UC-3 cells ( P<0.05). The clone formation test showed that the number of cell clones in UM-UC-3 cells transfected with miR-527 mimics was significantly lower than that in the control group (157.00±15.52 vs 57.33±15.50, P<0.05). Compared with the control group, the cell activity of T24 cells transfected with miR-527 inhibitor was significantly increased ( P<0.05). Compared with the control group, the number of cell clone formation was significantly increased (76.67±9.07 vs. 141.70±10.50, P<0.05). According to the prediction of targetscan database, ENO1 was the target gene of mir-527. Luciferase reporter gene experiment showed that the luciferase activity of mir-527 mimics group was significantly lower than that of control group (0.99±0.02 vs. 0.47±0.10, P<0.05), while the luciferase activity of miR-527 mimics group was significantly lower than that of control group (0.99 ± 0.02 vs. 0.47 ± 0.10, P<0.05), without statistical significance (1.03±0.04 vs. 0.96±0.05, P>0.05). Western blot analysis showed that the expression of ENO1 in miR-527 mimics group was significantly lower than that in NC mimics group (1.09±0.17 vs. 0.31±0.13, P<0.05), and the expression of ENO1 in miR-527 inhibitor group and NC inhibitor group were significantly increased (0.97±0.09 vs. 2.17±0.15, P<0.05). Compared with miR-527 mimics group, transfection of miR-527 mimics+ ENO1 overexpression plasmid could reduce the inhibitory effect of miR-527 mimics on proliferation, migration and invasion of bladder cancer cell line ( P<0.05). Compared with miR-527 inhibitor group, transfection of miR-527 inhibitor+ ENO1 siRNA could weaken the inhibit effect of miR-527 on the proliferation, migration and invasion of bladder cancer cell lines ( P<0.05). Conclusion:miR-527 is low expressed in BC and can be used as a tumor suppressor gene to inhibit the proliferation, migration and invasion of BC cells.

Objective To detect the changes of the NJ001 specific antigen expression before and after surgery, and evaluate whether the NJ001 specific antigen could be used as a serum biomarker for the diagnosis of pancreatic cancer.Methods With the method of sandwich ELISA, the serum samples from 85 pancreatic cancer patients, 22 pancreatic benign tumor and 40 healthy controls were detected respectively. The results of the NJ001 specific antigen in the serum samples from 85 pancreatic cancer patients were compared with CA19-9 detected by ECLIA.Results The positive rate of NJ001 for the pancreatic cancer group was obviously higher than that for the benign pancreatic tumor and health control groups[50.6%(43/85) vs 18.2%(4/22), χ2 =7.451, P<0.05; 50.6%(43/85) vs 10.0%(4/40), χ2 =19.098, P<0.05].The difference between benign pancreatic tumor group and health control group had no statistical significance[18.2%(4/22) vs 10.0%(4/40),χ2 =0.845, P>0.05].The positive rate in the group of pancreatic cancer before surgery was higher than that after surgery[50.6%(43/85) vs 23.5%(20/85),χ2=13.341, P<0.05].In addition, the results from 85 pancreatic cancer patients showed the specificity of NJ001 specific antigen was up to 87.1%.Although the positive rate of NJ001 specific antigen for pancreatic cancer was lower than that of CA19-9[50.6%(43/85) vs 75.3%(64/85), χ2 =11.121, P<0.05], it was higher when they combined [ 85.9%( 73/85 ) ] .Conclusions It shows high positive rate of NJ001 specific antigen in the patients of pancreatic cancer in this study, which suggests that NJ001 specific antigen might be a potential valuable biomarker for the diagnosis of pancreatic cancer.

BACKGROUNDInsulin resistance (IR) plays an important pathophysiological role in the development of diabetes, dyslipidemia, hypertension, and cardiovascular disease. Moreover, IR can occur even in non-obese people without diabetes. However, direct detection of IR is complicated. In order to find a simple surrogate marker of IR early in non-obese people, we investigate the association of commonly-used biochemical markers (liver enzymes and lipid profiles) with IR in urban middle-aged and older non-obese Chinese without diabetes.

METHODSThis cross-sectional study included 1 987 subjects (1 473 women). Fasting blood samples were collected for measurement of glucose, insulin, liver enzymes, lipid profiles and creatinine. Subjects whose homeostasis model of assessment-IR (HOMA-IR) index values exceeded the 75th percentile (2.67 for women and 2.48 for men) of the population were considered to have IR. The area under the receiver operating characteristic curve (ROC) was used to compare the power of potential markers in identifying IR.

RESULTSTriglycerides (TG) and ratio of TG to high-density lipoprotein cholesterol (TG/HDL-C) discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic (ROC) curves (AUC) values were 0.770 (95% confidence interval 0.733-0.807) and 0.772 (0.736-0.809), respectively, for women and 0.754 (0.664-0.844) and 0.756 (0.672-0.840), respectively, for men. To identify IR, the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L (sensitivity 74.3%, specificity 71.0%) and 0.873 (sensitivity 70.1%, specificity 73.4%), respectively, for women, and 1.275 mmol/L (sensitivity 66.7%, specificity 74.4%) and 0.812 (sensitivity 75.8%, specificity 69.2%), respectively, for men.

CONCLUSIONTG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.

Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Cholesterol, HDL ; blood ; Cross-Sectional Studies ; Diabetes Mellitus ; blood ; Female ; Humans ; Insulin Resistance ; physiology ; Liver ; enzymology ; Male ; Middle Aged ; Triglycerides ; blood