AIMTo investigate the effects of simulated microgravity on dilatory responsiveness and NOS expression of abdominal aorta in rats.

METHODSTwenty male healthy SD rats, which body weight ranged from 300 g to 330 g, were divided into control group and simulated microgravity group randomly. After 4 weeks, using isolated arterial rings from rats, arterial dilatory responsiveness of abdominal aorta were examined in vitro. And the expression of nitric oxide synthase (NOS), including endothelial NOS (eNOS) and inducible NOS (iNOS), were observed by Western blot.

RESULTSDilatory responses of arterial rings to L-Arginine (10(-8)-10(-3) mol/L), and Acetylcholine mol/L) were decreased in simulated microgravity rats compared with that of controls; but dilatory responses of isolated aortic rings to sodium nitroprusside (mol/L) and 8-bromo-cGMP(mol/L) were similar in both simulated microgravity rats and control rats. The expression of both eNOS and iNOS had not showed significant differences between two groups.

CONCLUSIONThe data indicate that endothelium dependent vasorelaxation in abdominal aortic rings are decreased by 4-week simulated microgravity, and this change may be result from altered NOS activity in endothelium.

Animals ; Aorta, Abdominal ; metabolism ; Arginine ; metabolism ; Cyclic GMP ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Sprague-Dawley ; Weightlessness Simulation

Objective To investigate the relationship between drinking-water type of endemic arsenicosis and adult carotid artery atherosclerosis. Methods In 2009, 285 participants aged over 40 from drinking-water type of endemic arsenism areas and 293 residents aged over 40 from control areas were investigated in Yingxian county,Shanxi province. Portable-type B mode color ultrasound was used to examine the carotid artery of all participants.The carotid atherosclerosis were diagnosed and graded through the ultrasonograms. Content of water arsenic and hair arsenic of 10 people randomly selected in every villages were detected. Results A total of 5 villages with drinkingwater type of endemic arsenicosis as observation group and 5 villages without drinking-water type of endemic arsenicosis as control group were investigated. The prevalence rates of adult carotid atherosclerosis within observation group were 35.09%(20/57), 55.74%(34/61), 38.46%(20/52), 36.51%(23/63) and 46.15%(24/52), respectively,and standardized prevalence rates were 32.5%, 33.8%, 34.9%, 46.2% and 47.3%, respectively and the prevalence rates of adult carotid atherosclerosis within control group were 18.18%(10/55), 30.77%(16/52), 20.00%(10/50),18.67% (14/75) and 21.31% ( 13/61 ), respectively; the standardize prevalence rates were 22.4%, 17.7%, 10.7%,24.6%, 18.9%, respectively. The standardize prevalence rates were higher in observation group [39.50%(113/285) ]than that in control group[39.50%(113/285), T = 26, P ＜ 0.01 ]. The severity of adult carotid atherosclerosis (composition of 4 - 7 scores ) was compared between observation group [ 17.70%(20/113 )] and control group [ 14.06% (9/64) ], and the difference was insignificant(x2 = 0.26, P ＞ 0.05). Conclusions The prevalence rate of carotid atherosclerosis in drinking-water type of endemic arsenicosis areas is higher than that of the control areas.The study provides evidence that arsenic poisoning can cause atherosclerosis.

OBJECTIVETo investigate the interferon alpha regulation mechanisms by screening binding proteins of interferon alpha promoter by phage display.

METHODSPCR product of interferon-alpha promoter was incubated with a phage display cDNA library that expressed a library of human liver proteins on the surface of bacteriophage T7. Unbound phages were washed off and the phages bound to the interferon alpha promoter were amplified. Positive plaques were amplified by PCR and cloned into a pGEM-Teasy vector in order to perform DNA sequence analysis and subsequent computer blasting analysis.

RESULTSPositive phage-displayed proteins binding with interferon alpha promoter were enriched after five rounds of biopanning. We found that the following proteins were relevant to interferon alpha: mitochondrial ribosomal protein, chromosome clone, fibrinogen A alpha polypeptide, enoyl coenzyme A hydratase short chain, eukaryotic translation elongation factor 1 alpha, PI-3-kinase-related kinase SMG-1-like, xeroderma pigmentosum C group, and Homo sapien activity-dependent neuroprotector (ADNP).

CONCLUSIONMany proteins with different functions could bind with interferon alpha promoter.

DNA, Complementary ; genetics ; DNA-Binding Proteins ; biosynthesis ; genetics ; Gene Library ; Hepatocytes ; cytology ; metabolism ; Humans ; Interferon-alpha ; biosynthesis ; genetics ; Promoter Regions, Genetic ; genetics ; Two-Hybrid System Techniques

BACKGROUNDSirolimus-eluting stents (SES) are reported to be associated with reduced late lumen loss (LLL), resulting in less frequent restenosis when compared to bare-metal stent. The current study aimed to assess the difference in LLL between SES with biodegradable and with permanent polymer.

METHODSFrom March 2010 to June 2011, 300 consecutive patients having only biodegradable polymers or permanent polymer SES for all diseased vessels were included. Serial quantitative coronary analysis was performed on both the "in-stent" and "segment" area, including the stented segment, as well as both five mm margins proximal and distal to the stent. The primary endpoint was the LLL defined as the minimal lumen diameter (MLD) post-stenting minus the MLD at nine-month after the indexed procedure.

RESULTSLLL was comparable between the two stents. Importantly, LLL for the distal segment (median 0.05 mm, interquartile 0 to 0.09 mm) was less severe compared with in-stent (median 0.13 mm, interquartile 0.08 to 0.18 mm) and proximal segment LLL (median 0.12 mm, interquartile 0.06 to 0.14 mm, all P < 0.001). In general, the LLL was associated with the post-procedure MLD (b = 0.28, P = 0.002), hyperlipidemia (b = 0.14, P = 0.021), and calcified lesions (b = 0.58, P = 0.001). The R(2) and Radj of the multiple regression model were 0.651 and 0.625, respectively.

CONCLUSIONSSES with either biodegradable or permanent polymer had lower value of LLL. The small amount of LLL at the distal segment possibly contributed to the less distal edge stenosis.

Aged ; Aspirin ; therapeutic use ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Polymers ; chemistry ; Regression Analysis ; Sirolimus ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

Objective To investigate the potential risk factors for immune checkpoint-related pneumonia(CIP)in non-small cell lung cancer(NSCLC)patients treated with immune checkpoint inhibitors(ICIs),to identify high-risk patients with CIP at an early stage.Methods A total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected,including 47 cases with CIP(CIP group),and 141 matched NSCLC patients without CIP(control group).Clinical data,laboratory tests,and CT images before the first immunotherapy were collected for all patients in two groups.The FACT medical imaging software was utilized for quantitative emphysema assessment in patients'CT scans.Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients.Results Among the 47 CIP patients,40(85.1%)were male,with 25(53.0%)aged between 41 and 65 years.Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events(CTCAE)was found in 28(59.6%)cases,characterized by a predominant reticular radiographic pattern.Multivariate logistic regression analysis showed that a low albumin level(OR=0.889,95%CI 0.808-0.979,P=0.017),targeted therapy(OR=9.204,95%CI 1.678-50.486,P=0.011),anti-angiogenic therapy(OR=0.056,95%CI 0.020-0.161,P<0.001),and a high percentage of low attenuation area(LAA%)(OR=1.227,95%CI 1.053-1.430,P=0.009)were significant factors influencing CIP occurrence.The combined predictive model using these four factors showed an area under the ROC curve of 0.888(95%CI 0.838-0.939),with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients.Conclusions Low serum albumin,first-line targeted therapy,and high LAA%are identified as risk factors for CIP occurrence,while anti-angiogenic therapy is a protective factor.The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.

OBJECTIVETo explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis, thus revealing its partial mechanisms for intervening chronic diabetic complications.

METHODSRecruited 40 Goto-Kakisaki (GK) Wistar rats were fed with high fat forage containing metabolic inhibition Propylthiouracil, and peritoneally injected with endothelial NOS inhibitor N-nitro-L-arginine methyl ester to establish a high fat diabetes model with atherosclerosis. The modeled GK rats were stratified by body weight, and then, by blood glucose level from high to low, randomly divided into the DGR group (at the daily dose of 8 mL/kg), the metformin group (MET, at the daily dose of 150 mg/kg), the simvastatin group (SIM, at the daily dose of 2 mg/kg), and the model group (MOD, fed with pure water, at the daily dose of 8 mL/kg) according to the random number table, 10 in each group. Another 10 Wistar rats of the same ages and comparable body weight level were recruited as the normal control group. All the interventions lasted for 24 weeks by gastrogavage. The fasting blood glucose (FBG) and body weight were monitored. The HbA1c, TC, LDL-C, HDL-C, TG, serum ROS were determined. The aortic NF-kappaB level was analyzed with immunohistochemical assay. The expression of NF-kappaB (P65) mRNA in the aorta was detected with Real-time PCR.

RESULTSThe body weight in the normal control group was eventually heavier than others (P < 0.01). There was no difference among the four groups of GK modeled rats (P > 0.05). The FBG in the four GK modeled groups were higher than that in the normal control group (P < 0.01, P < 0.05). There was no statistical difference in the blood glucose level at the first visit and at the baseline among the GK modeled groups (P > 0.05). The last FBG level was obviously lower in the MET and DGR groups than in the MOD group (P < 0.01) and the SIM group (P < 0.05). Twenty-four weeks after intervention, the level of FBG, HbA1c, TC, LDL-C, HDL-C, and NF-kappaB positive expression rate of the thoracic aorta of the four groups of GK modeled rats, and NF-kappaB mRNA expression in the thoracic aorta in the MOD group, the MET group, and the DGR group were significantly higher than those in the normal control group (P < 0.01, P < 0.05). The TG level, serum ROS in the MET, DGR, and SIM groups, and the NF-kappaB mRNA expression level in the thoracic aorta in the SIM group were significantly lower than those in the normal control group (P < 0.01, P < 0.05). The levels of FBG, TC, LDL-C, serum ROS, NF-kappaB mRNA expression level in the thoracic aorta in three drug intervention groups, and NF-kappaB positive expression rate in the DGR and MET groups, and the levels of HbA1c, TG in the DGR group were significantly lower than those in the MOD group (P < 0.01, P < 0.05). The level of FBG in the MET and DGR groups were lower than that in the SIM group (P < 0.05). The level of NF-kappaB mRNA expression in the thoracic aorta of the SIM and DGR groups, and the levels of TC and LDL-C in the DGR group were significantly lower than those in the MET group (P < 0.01).

CONCLUSIONDGR played a role in preventing and treating chronic diabetic complications by comprehensively regulating blood glucose and serum lipids, as well as down-regulating oxidative stress.

Animals ; Aorta, Thoracic ; metabolism ; Atherosclerosis ; complications ; drug therapy ; metabolism ; Blood Glucose ; analysis ; Diabetic Angiopathies ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Lipid Metabolism ; Male ; NF-kappa B ; metabolism ; Oxidative Stress ; Phytotherapy ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; blood

OBJECTIVESTo analyze HBV drug-resistant mutations against nucleos(t)ide analogues at 12 reported sites in 340 patients with chronic hepatitis B.

METHODSSerum HBV DNA was extracted and a nested PCR assay was employed for the reverse transcriptase (RT) gene amplification. Direct sequencing of PCR product was performed. The significance of detected mutations was analyzed in view of clinical data of the patients.

RESULTSDrug-resistant mutations were detected in 68 patients taking lamivudine (LAM), 10 taking adefovir (ADV), 8 taking entecavir, and 1 taking telbivudine (LdT). M204V and M204I were the most common LAM-resistant mutations. The former usually emerged with L180M while the latter often emerged alone. N236T +/- A181 substitution was the most frequently seen ADV-resistant mutation. ETV-resistant mutations occurred on the basis of LAM-resistant mutations and T184 change was the most common form. LdT-resistance was observed as M204I. Interestingly, these drug-resistant mutations were detected in a few patients who had not been treated with nucleos(t)ide analogues.

CONCLUSIONDetection of HBV drug-resistant mutations at multiple sites of the viral RT gene is valuable for discovering and verifying drug resistance and thus is very helpful in planning anti-HBV therapy.

Adult ; DNA Mutational Analysis ; DNA, Viral ; genetics ; Drug Resistance, Viral ; genetics ; Female ; Genotype ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; virology ; Humans ; Male ; Middle Aged ; Mutation ; Young Adult

OBJECTIVETo analyze the cytogenetic characteristics of different age subgroups in patients with acute myeloid leukemia (AML), and to explore the relationship between age and cytogenetics.

METHODSBetween January 2004 and December 2011, Bone marrow (BM) samples from 640 patients with de novo AML were analyzed retrospectively. The analyses were performed according to standard culturing and banding techniques, and clonal abnormalities were defined and described according to the International System for Human Cytogenetic Nomenclature (ISCN 2009). The cytogenetic subtypes were performed as normal, balanced, and unbalanced karyotypes. In the last group, the age distribution of complex and monosome karyotypes were further analyzed. The patients were divided into 8 age groups: 0 - 9, 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 year old groups.

RESULTSThe distribution of normal, balanced, and unbalanced karyotypes showed age specific characteristics. The incidence of normal karyotype increased from 6.67% (0 ∼ 9 year old) to 58.33% (≥ 70) (χ(2) = 20.68, P = 0.001) and balanced karyotype decreased from 73.33% (0 ∼ 9) to 11.11% (≥ 70) (χ(2) = 48.22, P < 0.01). The frequency of unbalanced karyotypes increased from 20.0% (0 ∼ 9) to 30.56% (≥ 70) (χ(2) = 18.963, P = 0.008). The frequency of complex karyotype was 6.67% in 0 - 9 year old group, followed by 0% in 10 - 19 and 20 - 29 year old group, and from 1.72% to 11.11% from 30 - 39 to ≥ 70 year old group (χ(2) = 8.341, P = 0.08). Monosome karyotype was only detected in patients in 30 year old or older groups. Although an increased tendency was observed with ages, there was no significant difference (χ(2) = 4.778, P = 0.311).

CONCLUSIONThe different age profiles of the cytogenetic subtypes may indicate the different mechanisms of the pathogenesis of AML, which may also offer beneficial information for etiological research of AML.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Karyotype ; Karyotyping ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Induction Chemotherapy ; Retrospective Studies ; Neoplasm, Residual ; Prognosis