Validamycin A Inhibited FB1 Biosynthesis by the Target FvNth in Fusarium verticillioides.

Validamycin A (VMA) is an antifungal antibiotic derived from Streptomyces hygroscopicus commonly used in plant disease management. Surprisingly, VMA was discovered to impede the production of fumonisin B1 (FB1) in agricultural settings. However, the specific target of VMA in Fusarium verticillioides remained unclear. To unravel the molecular mechanism of VMA, ultrastructural observations unveiled damage to mitochondrial membranes. Trehalase (FvNth) was pinpointed as the target of VMA by utilizing a 3D-printed surface plasmon resonance sensor. Molecular docking identified Trp285, Arg447, Asp452, and Phe665 as the binding sites between VMA and FvNth. A ΔFvnth mutant lacking amino acids 250-670 was engineered through homologous recombination. Transcriptome analysis indicated that samples treated with VMA and ΔFvnth displayed similar expression patterns, particularly in the suppression of the FUM gene cluster. VMA treatment resulted in reduced trehalase and ATPase activity as well as diminished production of glucose, pyruvic acid, and acetyl-CoA. Conversely, these effects were absent in samples treated with ΔFvnth. This research proposes that VMA hinders acetyl-CoA synthesis by trehalase, thereby suppressing the FB1 biosynthesis. These findings present a novel target for the development of mycotoxin control agents.

Blood Coagulation-Inspired Fibrin Hydrogel for Portable Detection of Thrombin Based on Personal Glucometer.

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0-0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs.

FvOshC Is a Key Global Regulatory Target in Fusarium verticillioides for Fumonisin Biosynthesis and Disease Control.

Fusarium verticillioides has a substantial impact on maize production, commonly leading to maize ear rot and the production of fumonisin, a mycotoxin that poses health risks to both humans and animals. Currently, there is a lack of molecular targets for preventing the disease and controlling the toxin. The biological functions of oxysterol-binding proteins (OSBP) in filamentous fungi remain unclear. In this research, 7 oxysterol-binding protein-related proteins were identified in F. verticillioides, and these proteins were obtained through prokaryotic expression and purification. FvOshC was identified as the specific protein that binds to ergosterol through fluorescence titration. Gene knockout complementation techniques confirmed that FvOSHC plays a positive role, establishing it as a novel global regulatory protein involved in the pathogenicity and FB1 biosynthesis in F. verticillioides. Additionally, the interaction between FvOshC and FvSec14 was identified using yeast two-hybrid techniques. Moreover, computer-aided drug design technology was utilized to identify the receptor molecule Xanthatin based on FvOshC. The inhibitory effect of Xanthatin on the growth of F. verticillioides and the synthesis of FB1 was significantly demonstrated. These findings provide valuable insights that can aid in the management of mycotoxin pollution.

Efficacy and safety of natural killer cells injection combined with XELOX chemotherapy in postoperative patients with stage III colorectal cancer in China: a prospective randomised controlled clinical trial study protocol.

BACKGROUND: Colorectal cancer (CRC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in China. However, resistance to multiple chemotherapeutics after surgery leads to failure of the main therapy to CRC. Natural killer (NK) cells are innate cytotoxic lymphocytes that exhibit strong cytotoxic activity against tumour cells. NK cell-based therapy, either alone or in combination with chemotherapy, has achieved favourable results and holds promise for addressing recurrence and metastasis in CRC patients after surgery. METHODS AND ANALYSIS: This is a prospective, randomised controlled clinical trial to evaluate efficacy and safety of interleukin 2 activated NK cells injection combined with XELOX (capecitabine plus oxaliplatin)-based chemotherapy for postoperative CRC patients. Participants will be randomly divided into treatment group and control group, and every group includes 40 patients. The treatment group will also receive NK cells (5×109) with+XELOX-based chemotherapy, while the control group will receive only XELOX-based chemotherapy. This treatment will be repeated for eight cycles (6 months). The follow-up period lasts about 3 years, during which CEA, CA19-9, CA125, enhancement CT and colonoscopy will be conducted. The primary endpoints of this study are progression-free survival and overall survival, while the secondary endpoint is safety (number and severity of adverse events). Additionally, we aim to identify cancer stem cells in peripheral blood and predictive biomarkers (cytokines secreted by NK cells and activated markers of NK cells) that indicate patients who achieve an effective response. ETHICS AND DISSEMINATION: The study has been approved by the Clinical Research Ethics Committee of our hospital (approval number 2023LLSC006) and the Chinese Clinical Trials. It will be conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The study findings will be submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2300075861).

Recent Developments in Paper-Based Sensors with Instrument-Free Signal Readout Technologies (2020-2023).

Signal readout technologies that do not require any instrument are essential for improving the convenience and availability of paper-based sensors. Thanks to the remarkable progress in material science and nanotechnology, paper-based sensors with instrument-free signal readout have been developed for multiple purposes, such as biomedical detection, environmental pollutant tracking, and food analysis. In this review, the developments in instrument-free signal readout technologies for paper-based sensors from 2020 to 2023 are summarized. The instrument-free signal readout technologies, such as distance-based signal readout technology, counting-based signal readout technology, text-based signal readout technology, as well as other transduction technologies, are briefly introduced, respectively. On the other hand, the applications of paper-based sensors with instrument-free signal readout technologies are summarized, including biomedical analysis, environmental analysis, food analysis, and other applications. Finally, the potential and difficulties associated with the advancement of paper-based sensors without instruments are discussed.

Serum levels of Vanin-2 increase with obesity in relation to inflammation of adipose tissue and may be a predictor of bariatric surgery outcomes.

Objective: Excessive obesity can lead to dysfunction in adipose tissue, which contributes to the development of comorbidities associated with obesity, such as type 2 diabetes (T2D), cardiovascular and cerebrovascular disease, among others. Previous research has mainly focused on the Vanin family in systemic inflammatory diseases or predicting its role in tumor prognosis, while neglecting its role as a secretory protein in adipose tissue inflammation and metabolism. The objective of this study was to compare the changes in Vanin-2 levels in the circulating blood of normal and obese individuals, and to assess its correlation with inflammatory factors in vivo. Furthermore, the study aimed to systematically evaluate its effectiveness in human weight loss surgery. Methods: Serum concentrations of Vanin-2 and inflammatory indicators were measured in 518 volunteers. Furthermore, the concentrations of Vanin-2 were measured both before and after weight loss through a dietetic program or laparoscopic sleeve gastrectomy (LSG). Additionally, we assessed the levels of insulin, adiponectin, and inflammation-related factors. The hormonal profile and changes in body weight were evaluated at baseline and 3 months after surgery. Results: Serum levels of Vanin-2 were found to be significantly increased in individuals with overweight/obesity (OW/OB) group (controls 438.98 ± 72.44, OW/OB 530.89 ± 79.39 ug/L; p < 0.001). These increased levels were associated with IL-18, BMI, FAT%, and HOMA-IR. However, levels of Vanin-2 remained unchanged after conventional dietary treatment. On the other hand, weight loss induced by LSG resulted in a significant decrease in Vanin-2 concentrations from 586.44 ± 48.84 to 477.67 ± 30.27 ug/L (p < 0.001), and this decrease was associated with the Vanin-2 concentrations observed before the operation. Conclusion: Serum Vanin-2 is a highly effective biomarker for assessing adipose tissue inflammation in obesity and has the potential to serve as a predictor of bariatric surgery outcomes.

A family associated outbreak of Mycoplasma pneumoniae infection in a hospital ward / 中华流行病学杂志

Objective To describe the epidemiological and serological features on a family associated outbreak caused by Mycoplasma pneumoniae (MP) infection occurred in Beijing in August 2007.Methods Mutual exposure of the family members was investigated and retrospective medical record was reviewed for the hospitalized patients.Serum antibodies to MP were measured and chest X-rays were taken for all the family members.Results This family consisted of 5 members,with fixed members as the boy (13 years old ),his father (43 years old) and mother (44 years old),grandmother (64 years old) and uncle (32 years old ) who was involved in taking care of the sick boy and his father.During 23 days of the event,four of all the five family members were ill.Three (boy,father and uncle) had radiographic pneumonia,whose paired sera all showed a ≥ fourfold increase in antibody titer,and two of them were confnrmed by chest X-ray on day 2 after onset of fever.The grandmother suffered from bronchitis,with positive(PA) serum antibody to MR Serum MP-IgG from the father and uncle was positive,3 days and 2 days after the onset of fever.The chances of contact between grandmother with the boy and uncle with the father were both only in the hospital wards.Only the mother remained asymptomatic,with her serum MP-IgM (-)and MP-IgG ( + )for which the blood sample was collected 37 days after close contact with the boy.The longest time of exposure to the patients was between mother and the boy but only the mother did not increase her total workload or feeling for fatigue.Conclusion Results of MP-IgG from post-infection did not completely defend against the repeated MP infection.Combined risk factors as index patients with severe cough,prolonged close contact,poorly ventilation of the environment,and family members with excessive fatigue might work as the causes of this family MP outbreak.

Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (I(Na)) of isolated ventricular myocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits.</p><p><b>METHODS</b>Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent I(Na). Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early after depolarization (EAD) and/or delay after depolarization (DAD) were measured in vivo in rabbits post aconitine (100 microg/kg, iv) in the absence or presence of BmKIM (50 microg/kg iv).</p><p><b>RESULTS</b>(1) BmKIM significantly inhibited I(Na) in a voltage-dependent manner and significantly shifted the I-V curves of I(Na) upward. BmKIM left shifted the inactivation curve of I(Na) and voltages at 50% inactivation of I(Na) were changed from (-70.8 +/- 2.6) mV to (-84.8 +/- 3.5) mV (P < 0.05). BmKIM prolonged the recovery of inactivation of I(Na). In the presence of BmKIM, the time constants of recovery (both tau(f) and tau(s)) of I(Na) were significantly prolonged from (28.9 +/- 6.1) ms and (107 +/- 21.6) ms in control group to (54.2 +/- 7.9) ms (P < 0.05) and (211.1 +/- 34.6) ms (P < 0.01), respectively. (2) BmKIM significantly shortened 50% and 90% of action potential duration (APD(50) and APD(90)), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential (V(max)) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventricular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P < 0.01).</p><p><b>CONCLUSIONS</b>BmKIM significantly blocked I(Na) through affecting the inactivated state of I(Na) in rabbit ventricular myocytes. BmKIM could attenuate the influx of I(Na), therefore shorten action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.</p>

An analysis of clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas in patients with hepatitis C virus infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the epidemiological and clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas (HCC) in patients with hepatitis C virus (HCV) infection.</p><p><b>METHODS</b>Eighty-nine compensated and decompensated HCV cirrhosis patients were analyzed and followed-up. The main clinical and laboratory variables were analyzed as incidence factors of HCC with univariate analysis and multivariate analysis regression models.</p><p><b>RESULTS</b>The patients were followed-up for 86 months. Thirty-five of the 89 patients had HCC during the 86 months follow-up. Their five and ten-year cumulative incidences were 16.9% and 40.4% respectively. Of the 35 HCC patients, 4 had a family history of hepatitis C, 12 had a familial history of HCC, and 7 had a history of alcohol ingestion. Five and ten-year cumulative incidences of HCC in patients with hepatic steatosis were 24.6% and 51.0% respectively. Five-year and ten-year cumulative incidences of HCC in patients with non-hepatic steatosis were 8.7% and 26.2% respectively, and the difference in the cumulative incidences between them was significant (P < 0.05). Hepatic steatosis severity was associated with the severity of the cirrhosis. ALT and TBil levels were higher in the HCC group than in the non-HCC group, ALB was lower in the HCC group than in the non-HCC group, and the differences between them were significant (P < 0.05). Child-Pugh score and the severity of the hepatic steatosis during follow-up were independently correlated with HCC.</p><p><b>CONCLUSION</b>HCC is the most important and frequent outcome of chronic hepatitis C cirrhosis. Child-Pugh score and the severity of the hepatic steatosis are related to the risk factors. History of alcohol ingestion and family history of hepatitis C are also related to liver cancer.</p>

An analysis of the pathohistology of liver tissues, clinical features and prognostic factors of chronic hepatitis B virus carriers / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the correlations between clinical features and liver pathohistological changes of chronic hepatitis B virus (HBV) carriers and to discuss the factors which may influence the prognosis.</p><p><b>METHODS</b>Ninety HBV carriers who had liver biopsies were enrolled in this study.</p><p><b>RESULTS</b>(1) The mean follow-up period of the patients was 118 weeks. (2) Fifty-four patients (60.0%) had G1 hepatitis and 21 (23.3%) had G2 hepatitis. The fibrosis stages were graded as S1(42) and S2(21). (3) There were significant age differences among S0, S1 and S2. (4) There were significant differences in aminotransferase levels between patients who had a normal liver histology and those who had mild hepatitis. (5) The grades of liver inflammation were not correlated with the titers of HBeAg and HBV DNA in sera. The stages of liver fibrosis were not correlated with the titers of HBVDNA in sera. Most of the HBeAg negative patients progressed to S2. (6) There were significant differences in spleen dimensions measured by ultrasonography between S0, S1 and S2 patients. (7) During the follow-up period serum aminotransferase (ALT) levels remained normal in 60 patients (group A); 22 patients had transient elevations (group B), and 8 patients had persistent increases (group C). There were significant differences of the ratios of S0 and S2 cases among patients in groups A, B and C. (8) Age and fibrosis stages were predictive factors of liver cirrhosis.</p><p><b>CONCLUSIONS</b>Most chronic HBV carriers had mild inflammatory histological changes in their livers and also had different degrees of liver fibrosis. This follow-up study shows that some of those carriers should have had antiviral therapy.</p>

COX-2 and mPGES-1 expression in carotid atherosclerotic plaques / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the changes in the expressions of inducible cyclooxygenase type 2 (COX-2) and membrane associated prostaglandin E-1(mPGES-1) in human carotid atherosclerotic plaques and to explore possible mechanisms of inflammatory process involved in plaque stability.</p><p><b>METHODS</b>The mRNA and protein levels of COX-2 and mPGES-1 were compared between minimally and grossly atherosclerotic arterial tissues. COX-2 and mPGES-1 gene expression were established by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) in 10 mesenchymal artery controls and 24 atherosclerotic specimens. Presence of COX-2 and mPGES-1 protein was assessed by Western blotting.</p><p><b>RESULTS</b>Immunohistochemical staining showed that the COX-2 and mPGES-1 immunoreactive substances were present in the cytoplasm of smooth muscle cell. Compared with the control group, immunostaining positive cells increased in carotid atherosclerotic plaque group. COX-2 and mPGES-1 gene expression was significantly elevated in atherosclerotic plaques (P< 0.05, respectively). The increased mRNA and protein levels of COX-2 and mPGES-1 were correlated in atherosclerotic tissue (P< 0.05). The mRNA and protein levels of COX-2 and mPGES-1 related to degree of pathological damage in atherosclerotic tissue (P< 0.05). COX-2 and mPGES-1 were not found in the control group (mesenteric vascular walls).</p><p><b>CONCLUSION</b>COX-2 and mPGES-1 expression in plaques is significantly higher than that in the control group. These findings suggests that COX-2 and mPGES-1 might play a role in pathogenesis of atheroscleros and modulation of inflammatory process involved in plaque stability, and COX-2 may have proinflammatory enzyme properties.</p>

Significance of serum carnitine in patients with liver diseases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine serum carnitine levels in patients with liver diseases and to investigate their significance.</p><p><b>METHODS</b>25 patients with acute viral hepatitis, 34 with chronic viral hepatitis, 22 with post hepatitis cirrhosis with normal renal function, 9 with post hepatitis cirrhosis but with renal disfunction, and 40 healthy subjects (serving as controls) were enrolled in this study. An enzymatic cycling method was used to determine the serum free carnitine levels.</p><p><b>RESULTS</b>The serum free carnitine level was (48.3+/-10.2)micromol/L in the healthy control group. It was (35.2+/-13.2)micromol/L in the acute viral hepatitis group, (36.5+/-9.9)micromol/L in the chronic viral hepatitis group, (45.0+/-11.0)micromol/L in the post hepatitis cirrhosis with normal renal function group, and (83.6+/-50.4)micromol/L in the post hepatitis cirrhosis with renal dysfunction group. Serum free carnitine levels in the acute viral hepatitis and chronic viral hepatitis groups were significantly lower than those in the healthy controls. There were no significant differences in serum free carnitine levels of the post hepatitis cirrhosis group and the normal control group.</p><p><b>CONCLUSIONS</b>Patients with liver diseases can have carnitine metabolism errors. One of the secondary carnitine lack causes is liver disease.</p>

Interleukin-6-597G/A and -572C/G polymorphisms and risk of coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between interleukin-6 (IL-6) gene polymorphisms and the risk of coronary heart disease (CHD).</p><p><b>METHODS</b>IL-6/-597G/A and -572C/G polymorphisms were genotyped in 245 CHD patients and 260 healthy adults by PCR-RFLP. Serum IL-6 level was examined by ELISA. Logistic regression was performed to observe the relationship between IL-6/-572C/G polymorphism and other risk factors of CHD.</p><p><b>RESULTS</b>IL-6/-597G/A genotype was similar between the two groups. The frequencies of IL-6/-572C/G genotype and G allele were more frequent in patients with CHD than that in controls (P < 0.01). Compared with CC genotype, the relative risk for CHD in people with CG and GG genotypes was 1.46 (95% CI: 1.01 - 2.10, P < 0.05) and 5.19 (95% CI: 1.69 - 15.89, P < 0.01), respectively. The serum levels of IL-6 were similar between carriers of the IL-6/-572G allele and patients with CC genotype (P > 0.05). IL-6/-572 C/G is related to total cholesterol (OR 1.76, 95% CI: 1.05 - 3.16, P < 0.05) and triglyceride (OR = 2.51, 95% CI: 1.04 - 6.45, P < 0.05), respectively.</p><p><b>CONCLUSION</b>IL-6/-597G/A polymorphism was not associated with susceptibility to CHD, but IL-6-572C/G polymorphism may be a possible genetic susceptibility factor for CHD in Chinese Hans population.</p>

Study on linkage between polymorphism of interleukin 6 gene -572C/G and susceptibility to myocardial infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To observe the polymorphism and gene frequency of interleukin 6 (IL6) gene -572C/G in Chinese Han nationality population, that associating with susceptibility to myocardial infarction(MI) and impacting on the extent of coronary artery lesions; to analyze the function of IL6 gene -572C/G polymorphism.</p><p><b>METHODS</b>With PCR-RFLP method, IL6 gene -572C/G polymorphism was genotyped to 232 MI patients and 260 healthy adults. The effect of IL6 gene -572C/G polymorphism was observed to the extent of coronary artery lesions and the ability of IL6 production from peripheral blood mononuclear cells (PBMC).</p><p><b>RESULTS</b>There was IL6 gene -572C/G polymorphism in Chinese Hans. -572CG+GG genotype and G allele were more frequent in patients than in controls (P< 0.01). The relative risk for G allele carrier to suffer from MI was 1.68 times of CC genotype individual (95%CI 1.17-2.41, P< 0.01). However, the distribution of IL6 gene -572C/G polymorphism was no significant difference among patients with single-vessel, two-vessel and three-vessel lesions (P> 0.05). After PBMC cultured for 24 hours, the IL6 concentration in supernatant was significantly higher in subjects with CG genotype than those with CC genotype (P< 0.05).</p><p><b>CONCLUSION</b>IL6 gene -572G allele may be a genetic susceptibility factor to MI attack of Chinese Hans population, and related to the high expression of IL6.</p>

Significance of blood HCV RNA screening in the prevention of post-transfusion hepatitis C / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate the significance of blood HCV RNA screening in the prevention of post-transfusion hepatitis C.</p><p><b>METHODS</b>Totally 56,400 anti-HCV negative blood samples collected from Jan. 2000 to Dec. 2003 were tested for HCV RNA by RT-PCR, and the patients who received the HCV RNA negative blood were followed up.</p><p><b>RESULTS</b>The HCV RNA positive rate was 2.5 per thousand (146/56,000) and none of the patients followed up suffered from HCV infection.</p><p><b>CONCLUSION</b>HCV RNA screening for the anti-HCV negative blood samples is very effective and feasible for prevention of post-transfusion hepatitis C.</p>

Serum HBV-DNA level can predict treatment effectiveness in patients with chronic hepatitis B using interferon-alpha-2a / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the correlation between the efficacy of interferon-alpha-2a and the kinetics of viral load in serum.</p><p><b>METHODS</b>The authors conducted a trial including 58 patients with chronic hepatitis B. Patients were treated with interferon-alpha-2a three times a week for 6 months. Viral kinetics were assessed by serial quantitive measurements of HBV-DNA.</p><p><b>RESULTS</b>A significant decline of serum HBV-DNA was seen after interferon-alpha-2a administration for 1 month, the decreases were (2.50 +/- 0.44) log10, (1.62 +/- 1.12) log10 and (1.05 +/- 1.35) log10 for complete responders, partial responders and no-responders, respectively. After 1 month of treatment, HBV-DNA level was (3.99 +/- 0.91) log10 for complete responders versus (5.63 +/- 1.31) log10 for partial responders, and (6.69 +/- 1.42) log10 for no-responders (P < 0.05). Multivariate analysis suggested that undetectable serum HBV-DNA after 1 month of interferon-alpha-2a treatment was associated with better efficacy; higher baseline ALT or/and no family history were also correlated with better treatment outcomes.</p><p><b>CONCLUSION</b>Kinetics of HBV-DNA level under interferon-alpha-2a treatment are highly predictive of therapeutic response.</p>

The role of isoprenaline-induced, calcium-activated transient outward chloride current in atrial electrical remodeling of rabbit / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the changes of the L-type calcium current (I(Ca, L)) and the calcium-activated transient outward chloride current (I(Cl, Ca)), and the repolarization characteristic of action potential in phase 1 under isoprenaline (ISO) stimulation in atrium myocytes of rabbit.</p><p><b>METHODS</b>Atrium myocytes were obtained by enzymatic dissociation from a section of atrial free wall. The membrane currents and action potential were recorded by the whole-cell patch-clamp technique.</p><p><b>RESULTS</b>After recording I(Ca, L), atrium myocytes were perfused with ISO (1 micromol/L) immediately. Five minutes later, a transient outward current (I(to)) was significantly induced, and the peak of I(to) was gradually increased while I(Ca, L) gradually decreased with increasing in clamp voltage. The I(to) was resistant to 4-AP (3 mmol/L) but sensitive to DIDS (150 micromol/L, Cl(-) channel blocker). This current was blocked by CdCl(2) (200 micromol/L, Ca(2+) channel blocker). The elicited rate of I(to) was 91.67% (P < 0.05). (2) The shape of AP was like an inverse triangle with no plateau in Phase 2 after ISO (1 micromol/L) perfusion. Moreover, compared to the parameters of control group, APD(50) and APD(90) were significantly shortened from (65.4 +/- 4.2) ms and (95.8 +/- 3.8) ms to (12.8 +/- 3.8) ms and (27.0 +/- 4.7) ms, and reduced to 80.46% and 71.87%, respectively (P < 0.01, n = 12). 4-AP (3 mmol/L) had on obvious effect on the shape of AP, however, the plateau of AP in phase 2 was recovered by DIDS (150 micromol/L) perfusion, APD(50) and APD(90) were (41.1 +/- 4.5) ms and (79.6 +/- 3.4) ms respectively. Compared to the parameters of control group, there were no significant differences (P > 0.05, n = 12). These results indicated that ionic transport were changed by ISO perfusion in atrium myocytes and I(to) played an important role in the phase 1 repolarization of AP.</p><p><b>CONCLUSIONS</b>Before ISO administration, we could only observe I(Ca, L) in atrium myocytes of rabbit. After isoproterenol intervention, certain intracellular ionic consistency and membrane ionic channels were changed. Calcium activated chloride channel and I(to2) revealed obvious predominance which shorten APD significantly. Action potential showed a triangle with no plateau, suggesting an electrical remodeling in atrium myocytes. The remodeling of ionic channel is related possibly with the opening of Ca(2+)-activated Cl(-) current, which maybe the electrophysiological base of reentrant atrial tachycardia.</p>

The distribution of gene polymorphisms in the intron 2 and exon 2 of interleukin-1 receptor antagonist and their correlation with the serum lipoprotein level / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the distribution of variable numbers of tandem repeat (VNTR) polymorphism in the intron 2 and the single nucleotide polymorphism (SNP) at position +8006 in the exon 2 of IL-1RN in healthy Chinese Han Population of Wuhan province and to analyze their correlation with the serum lipoprotein level.</p><p><b>METHODS</b>IL-1RN (VNTR) and IL-1RN (+8006) polymorphisms were detected by PCR and PCR-RFLP methods in 251 healthy Chinese Han Population of Wuhan, and the levels of serum lipoprotein, IL-1 and IL-1Ra were inspected simultaneously.</p><p><b>RESULTS</b>In IL-1RN (VNTR), allele I appeared most common, then allele II, and allele IV was rare. At the position of IL-1RN (+8006), allele T was most commonly seen followed by allele C. Allele II of IL-1RN (VNTR) always existed with allele C of IL-1RN (+8006). The levels of serum lipoprotein, IL-1 and IL-1Ra were not different among the different genotypes of the two polymorphisms.</p><p><b>CONCLUSION</b>There were two gene polymorphisms in the intron 2 and exon 2 of IL-1RN, which were not correlated with the levels of serum lipoprotein, IL-1 and IL-1Ra. However, there seemed to be a linkage disequilibrium between IL-1RN (VNTR) and IL-1RN (+8006).</p>

Therapeutic effect of levamisole plus HBV vaccine and dipyridamole on patients chronically infected by HBV with precore mutation / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the incidence of precore mutation in HBeAg negative HBV infected patients and the therapeutic effect of the immune therapy (levamisole + HBV vaccine + dipyridamole) on patients chronically infected by HBV with precore mutation.</p><p><b>METHODS</b>The precore region of HBV from the HBeAg (-) chronic hepatitis patients was sequenced and the patients suffered from HBV with precore mutation were treated with immune therapy.</p><p><b>RESULTS</b>The precore mutation rate was 10/12. The therapeutic effect of the immune therapy on the precore mutation patients (5/7) was better than that on the HBsAg(+), HBeAg(+) patients (2/11), P less than 0.05.</p><p><b>CONCLUSION</b>The precore mutation rate was quite high in the HBsAg(+), HBeAg(-) patients we studied. The immune-therapy has some therapeutic effects on the patients with precore mutation. But the number of cases was too small, further study is needed.</p>

Differential clinical diagnostic parameters of acute hepatitis B and flare of chronic HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate useful clinical diagnostic parameters for differentiating acute hepatitis B and flare of chronic HBV infection.</p><p><b>METHODS</b>Using PCR method to detect viral level in the patient's serum, HBV marker was detected by ELISA kit. Liver function was also detected.</p><p><b>RESULTS</b>The patient can be diagnosed as acute hepatitis B if a patient has one of the following parameters: (1)HBV-DNA negative on admission. (2) When the patient's ALT was lower than 400 IU/L, HBV-DNA was negative or HBsAg became negative or HBeAg/HBeAb seroconverted.</p><p><b>CONCLUSION</b>The viral DNA level, HBV marker and ALT can help differentiate acute hepatitis B and flare of chronic HBV infection.</p>