Objective To investigate the expression level of soluble Programmed cell death ligand2 (sPD-L2) in the peripheral blood of patients with Brucella infection and their correlation with helper T cells (Th) subsets. Methods Data from eighty-three patients with confirmed Brucella infection, including 37 patients with acute phase Brucella infection and 46 patients with chronic phase Brucella infection, collected from the People's Hospital of Xinjiang Uygur Autonomous Region between January 2019 and December 2021, were analyzed. Fifty healthy individuals undergoing regular medical check-ups during the same period were included as the Healthy Control (HC) group. Flow cytometry was used to detect the percentage of Th1 and Th2 cells as CD4+ T cells in the peripheral blood of the three groups of samples. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to measure the mRNA expression levels of Th1 and Th2 cell-associated transcription factors T-bet and GATA-3 in the peripheral blood of the three samples. The expression levels of cytokines sPD-L2, IFN-γ, and IL-4 in the serum of the three groups of samples were measured by the cytometric bead array (CBA) technique. Results Th1 cells in the acute phase brucellosis infection group (45.33±4.96)%, mRNA expression levels of T-bet (1.91±0.41), and IFN-γ expression levels (74.42±13.95) pg/mL were significantly higher in the acute phase Brucella disease group compared to the chronic phase group (21.78±4.42)%, (0.65±0.24), and (10.64±3.04) pg/mL, as well as the HC group (28.87±6.67)%, (1.12±0.25), and (7.48±2.92) pg/mL, respectively (P<0.05). Th2 cells (59.80±10.09)%, GATA-3 mRNA expression level (1.50±0.44), and IL-4 level (8.76±2.06) pg/mL were significantly higher in the chronic phase brucellosis infection group compared to the acute phase brucellosis patient group (40.61±9.32)%, (1.02±0.23), and (2.08±0.50) pg/mL, as well as the HC group (46.06±8.84)%, (1.18±0.28), and (2.70±0.75) pg/mL, respectively (P<0.05). Compared to the HC group (91.61±11.44) pg/mL, the sPD-L2 levels were significantly higher in the acute phase brucellosis patient group (156.77±24.69) pg/mL and slightly higher in the chronic phase brucellosis patient group (110.99±29.44) pg/mL, with a statistically significant difference between the acute and chronic phase brucellosis patient groups (P<0.05). Correlation analysis of the brucellosis patient group showed that sPD-L2 levels were positively correlated with the percentage of Th1 cells (r=0.540, P<0.01) and the levels of IFN-γ (r=0.692, P<0.01), and negatively correlated with the percentage of Th2 cells (r=-0.565, P<0.01) and the levels of IL-4 (r=-0.528, P<0.01). Conclusions In patients with acute brucellosis, sPD-L2 levels are significantly increased, which may resist brucellosis by promoting Th1 cells to secrete more pro-inflammatory factors to defend against Brucella infection. In chronic Brucella disease patients, the tilting of immune response types from Th1 to Th2 may be due to a decrease in sPD-L2 expression, which reduces the inhibitory effect of Th2, leading to incomplete clearance of Brucella and thus immune escape. Brucella may affect the conversion of Th1 to Th2 through the sPD-L2 pathway, exerting negative regulatory effects and resulting in difficulty in complete Brucella clearance, thus turning into a chronic phase.

Objective:To explore the correlation between the index of hemodynamics in perinatal period and retinopathy of prematurity(ROP), so as to provide basis for the better prevention and treatment of ROP.Methods:From May 2017 to April 2019, the preterm infants were admitted to the Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University at birth and were hospitalized for more than 2 weeks, gestational age ≤ 35 weeks and birth weight ≤ 2 500 g. They were selected as the study objects.The perinatal data including heart rate, blood pressure, patent ductus arteriosus, ventricular septal defect, and NT-proBNP level on the 1 st, 7 th and 14 th day, respectively after birth were collected.They were divided into ROP group and non ROP group according to the results of the retinopathy screening report.The influencing factors of ROP were screened out by univariate analysis and multivariate regression analysis. Results:A total of 1 119 subjects were included, 105 infants with ROP were detected, and the prevalence of ROP was 9.4%.Among them, 12 cases of pre-threshold lesion type 1 and threshold lesions required treatment, accoun-ting for 1.07% of screened preterm infants .Univariate analysis and multivariate regression analysis revealed that gestational age, birth weight, total oxygen therapy time, and intrauterine growth restriction were all factors affecting ROP, and 2 hemodynamic related indicators, such as the level of NT-proBNP in plasma on the 14 th day after birth, and placenta previa or abruption were also related to ROP( OR=0.604, 0.647, 1.276, 2.361, 1.688 and 2.506, respectively, all P<0.05). Conclusion:The hemodynamic changes in perinatal period may be involved in the formation of ROP, and it is necessary to further clarify its mechanism.

BACKGROUNDHepatocyte growth factor (HGF) inhibits the development of pulmonary artery hypertension (PAH) by reducing pulmonary artery pressure and right ventricle (RV) hypertrophy. However, whether HGF can prevent RV remodeling via inhibiting apoptosis in RV cardiomyocytes and decreasing neurohormonal activation remains unknown.

METHODSThe PAH and subsequent RV remodeling in rats were induced by subcutaneous injection of monocrotaline (MCT). The PAH rats were transfected with adenovirus carrying HGF (Ad-HGF) via intratracheal instillation. Three weeks after transfection, the hemodynamics indexes were measured, serum levels for angiotonin II (ANG II) and brain natriuretic peptide (BNP) were determined by ELISA. Histological analysis was used to assess the RV hypertrophy and fibrosis. The cardiomyocyte apoptosis in RV was assayed by TUNEL staining. The mRNA expression of BNP, angiotensin-converting enzyme (ACE), Bax and Bcl-2 in RV was determined by reverse transcriptase polymerase chain reaction (RT-PCR), the protein expression of transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α in RV was determined by Western blotting.

RESULTSHGF treatment significantly decreased the mean PAH, RV systolic pressure, serum ANG II and BNP levels. HGF treatment also significantly decreased the RV hypertrophy, collagen deposition, and the number of apoptotic cardiomyocytes. Moreover, HGF treatmemt significantly decreased the expression of BNP, ACE, Bax, TGF-β1, and TNF-α, while it significantly increased the expression of Bcl-2.

CONCLUSIONSGene transfer of HGF decreases MCT-induced PAH and improves RV remodeling. This effect is mediated not only by improving the hemodynamics but also by decreasing neurohormonal activation and inhibiting cardiomyocytes apoptosis. HGF gene treatment may be an effective strategy for improving RV remodeling in MCT-induced PAH.

Animals ; Apoptosis ; genetics ; physiology ; Hepatocyte Growth Factor ; genetics ; physiology ; therapeutic use ; Humans ; Hypertension, Pulmonary ; metabolism ; therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling ; genetics ; physiology

Objective To investigate the effects of swimming exercise training on left ventricular (LV)remodeling and its possible mechanism in spontaneous hypertensive rats (SHR).Methods Twenty eightweek-old male SHRs were divided into SHR control (SC) group and SHR exercise training (ST) group,with 10 rats in each group.Ten eight-week-old male Wistar rats were used as normal control (WC) group.The ST group was subject to 60-min moderate swimming exercise without loading once daily,6 times a week,for a total of 12 weeks; while the SC and WC group had no special intervention.The blood pressure was examined once weekly.After 12 weeks,the norepinephrine (NE)and serum angiotonin Ⅱ (ANG Ⅱ) levels were determined by ELISA.The LV hypertrophy was assessed by analysing the ratio of LV weights to body weights (LVW/BW) and cardiomyocyte diameter.The collagen deposited in LV was detected by sirius red staining.The expressions of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) in LV were determined by semi-quantitative real time-polymerase chain reaction (RT-PCR) and Western blotting.Results After 12 weeks,the blood pressure,serum NE and ANG Ⅱ levels,LVW/BW ratio,cardiomyocyte diameter and collagen volume fraction (CVF) increased significantly in SC group compared with WC group; while those in ST group decreased significantly.In addition,in ST group the mRNA and protein expressions of TNF-α,IL-6,IL-1 βand TGF-β1 also decreased significantly.Conclusions The swimming exercise could reduce the blood pressure of SHR and improve LV remodeling.This effect was mediated not only by improving the hemodynamics,but also by decreasing sympathetic nerve and renin-angiotensin system (RAS) activities,decreasing the gene expressions of cytokines.The swimming exercise may be an effective strategy for improving LV remodeling in hypertension.

OBJECTIVETo evaluate the changes in the renal function of patients with chronic hepatitis B (CHB) receiving adefovir dipivoxil (ADV) or telbivudine (L-DT) monotherapy.

METHODSThis retrospective analysis involved 101 patients with CHB and liver cirrhosis receiving either ADV or L-DT monotherapy for 52 weeks. Serum creatinine, estimates of glomerular filtration rate (eGFR), and the percentage of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) at week 52 were compared with the baseline data between the two groups.

RESULTSThe mean changes of CR at week 52 from baseline were +0.05 mg/dl in ADV group and -0.12 mg/dl in L-DT group, showing a significant difference between the two groups (P=0.000). No patient was found to have an elevation of creatinine over 0.50 mg/dl. The median change of eGFR at week 52 from baseline differed significantly between ADV and L-DT groups (-4.09 vs+18.32 ml·min(-1)·1.73 m(-2), P=0.000). Ninety-two percent (12/13) of the patients with baseline eGFR<90 ml·min(-1)·1.73 m(-2) shifted to eGFR ≥90 ml·min(-1)·1.73 m(-2) after 52 weeks of L-DT treatment, as compared to 38% (3/8) in ADV group. The proportion of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) in L-DT group increased from 76.36% (42/55) at baseline to 94.55% (52/55) at week 52, while that in ADV group decreased from 82.61% (38/46) at baseline to 78.26% (36/46). The constituent ratios of eGFR at different levels were similar at baseline (P=0.443) but significantly different at week 52 between the two groups (P=0.015).

CONCLUSIONL-DT treatment is associated with a renoprotective effect in patients with CHB, but the mechanism remains unclear.

Adenine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; Hepatitis B, Chronic ; drug therapy ; physiopathology ; Humans ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Retrospective Studies ; Thymidine ; analogs & derivatives ; therapeutic use ; Young Adult

ObjectiveTo explore the effects of recombinant human growth hormone(rhGH)on myocardial inflammatory cytokine expression and heart function in rats with acute myocardial infarction (AMI). MethodsRats with AMI induced by left anterior descending coronary branch ligation were randomized to rhGH and control groups compared with sham-operated group. The effects of 4 weeks of therapy with GH starting 24 hours after myocardial infarction on myocardial cytokines expression and heart function were studied. Myocardial inflammation was examined by analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. ResultsThe levels of TNF-α, IL-1β, IL-6 and IL-10 in the infarcted and non-infarcted region of control group were markedly elevated compared to sham-operated group (all P＜0.05). After 4 weeks therapy, rhGH reduced the expression of TNF -α, IL-1β, IL-6 and increased IL-10 expression in the infarcted and non-infarcted region of rhGH group compared to control group (all P＜0. 05 ). Echocardiography showed that rhGH markedly improved left heart function (P＜0. 05 ). ConclusionsEarly rhGH treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One of immunopharmacologic mechanisms underlying the beneficial effects of rhGH on heart function improvement may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.

This study examined the change of p16(INK4a) and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18 post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16(INK4a) and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16(INK4a) and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P<0.01). Moreover, the percentage of p16(INK4a)-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group (P<0.01). The percentage of p16(INK4a)-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week (P>0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P<0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P<0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16(INK4a) and PCNA protein (r=-0.323, P<0.05; r=0.647, P<0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16(INK4a) protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.

This study examined the change of p 16INK4a and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16INK4a and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16INK4a and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P＜0.01). Moreover, the percentage of p16INK4a-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group (P＜0.01). The percentage of p16INK4a-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week (P＞0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P＜0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P＜0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16INK4a and PCNA protein (r=-0.323, P＜0.05; r=0.647, P＜0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16INK4a protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.

Baculoviridae ; genetics ; Cloning, Molecular ; DNA, Recombinant ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Genetic Vectors ; Hepatitis A virus ; genetics ; immunology ; Humans ; Immunoglobulin Fab Fragments ; genetics ; Plasmids ; genetics ; Polymerase Chain Reaction ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection

Aim To study the effect of gamma-hydroxybutyric acid receptor(GHBR ) on neuronal apoptosis suffering from focal cerebral ischemia-reperfusion injury in rats. Methods The male Sprague-Dawley rats weighing 240～280 g were randomly divided into seven groups: sham operation group(sham), ischemia-reperfusion group(Isc/R) ,NCS-356 160、320、640 ?g?kg-1 group(N1、N2、N3),NCS-382 640+NCS-356 640 ?g?kg-1 group(NCS-382+N3),and nimodipine 600 ?g?kg-1 group(Nim).The middle cerebral artery occlusion(MCAO) model invented by Zea Longa with modifications was adopted. The experiment was divided into two parts after ischemia reperfusion for 24h:In the first part,we measured the cerebral expression of Bax, Bcl-2, Caspase-3 by immuneohistochemical method. In the second part,we measured neuronal apoptotic rate by flow cytometry in the ischemic cortex region. Results The expression rate of Bcl-2 and Bcl-2/Bax ratio of N1,N2,N3 and Nim groups were all higher than that of Isc/R group(P