MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6Chigh macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl4-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

An analysis of donor semen quality in Chongqing Human Sperm Bank / 中华男科学杂志

<p><b>Objective</b>To evaluate the quality of the donor semen in Chongqing Human Sperm Bank and the influence of age on semen parameters.</p><p><b>METHODS</b>We collected semen samples from 899 donors in Chongqing Human Sperm Bank and divided them into five groups according to the age of the semen donors: 22－25, 26－30, 31－35, 36－40, and >40 years old. Using the Makler Counting Chamber, we measured the semen volume, percentage of progressively motile sperm (PMS), total motile sperm, sperm concentration, total sperm count per ejaculate, and percentage of morphologically normal sperm (MNS). Then, we compared the semen parameters obtained with the fifth percentile and median reference values published in the WHO Laboratory Manual for the Examination and Processing of Human Semen-5th Ed (WHO 5th Ed) and among different age groups using the Kruskall-Wallis H test.</p><p><b>RESULTS</b>The semen volume (1.8 ml), sperm concentration (25.0 × 10⁶/ml), total sperm count (100.7 × 106/ejaculate) and MNS (4.3%) in the semen samples of the 899 donors were obviously higher than the fifth percentile values published in the WHO 5th Ed, and so were the first three parameters (4.0 ml, 88.0 × 10⁶/ml, and 333.7 × 106/ejaculate) than the WHO median reference values. PMS (31.0%) and total motile (38.0%) were lower than the WHO fifth percentile values and so was MNS (11.6%) than the WHO median reference value. PMS (55.0%) and total motile sperm (61.0%), however, were coincident with the median reference values of WHO 5th Ed. Statistically significant differences were observed among the 22－25, 26－30, 31－35, 36－40 and >40 years old groups in perm concentration (88.0 ［1.0－270.0］ vs 96.0 ［5.0－335.0］ vs 100.0 ［3.0－200.0］ vs 105 ［15.0－225.0］ vs 90.0 ［22.0－159.0］ × 10⁶/ml, P < 0.05), but not in the semen volume, PMS, total sperm motility, total sperm count or MNS (P > 0.05).</p><p><b>CONCLUSIONS</b>The donor semen in Chongqing Human Sperm Bank is generally of high quality. Sperm concentration significantly increases with age but decreases in men aged >40 years.</p>

Bacterial culture of donor semen: Analysis of results / 中华男科学杂志

<p><b>Objective</b>To investigate bacterial infection and the distribution of different bacterial species in the donor semen and the influence of different bacterial counts on semen quality.</p><p><b>METHODS</b>Bacterial colonies in the semen samples from 1 126 donors were counted with the Synbiosis Protocol 3 Automatic Colony Counter and the bacterial species with a colony count ≥10⁴ cfu/ml identified with the VITEK2 Compact Automatic Biochemical Analyzer. The Makler Sperm Counting Board was used to examine the semen quality of the semen samples with a colony count = 0 cfu/ml (n = 22, group A), those with a colony count <10⁴ cfu/ml (n = 22, group B) and those with a colony count ≥10⁴ cfu/ml (n = 22, group C). Univariate analysis was employed for comparison of semen quality among different groups.</p><p><b>RESULTS</b>Among the 1 126 donor semen samples cultured, 5 (0.44%) showed mixed bacterial contamination and 993 (88.58%) showed none but with growth of a certain species of bacteria, 2.22% (22/993) with a colony count ≥10⁴ cfu/ml, mainly including Streptococcus bovis, tiny bacilli, Staphylococcus epidermis, and Staphylococcus aureus, among which gram-positive and gram-negative bacteria accounted for 95.45% (21/22) and 4.54% (1/22), respectively. Compared with group A, groups B and C manifested significantly reduced total sperm count (［567.5 ± 327.6］ vs ［421.9 ± 155.9］ and ［389.9 ± 110.6］ × 106 per ejaculate, P <0.05) and percentage of progressively motile sperm (［65.0 ± 6.5］ vs ［61.0 ± 3.5］ and ［61.6 ± 4.3］ %, P <0.05). There were no statistically significant differences among the three groups in the semen liquefaction time, semen pH value, total sperm motility or percentage of morphologically normal sperm (P > 0.05). Of the 284 randomly selected semen samples, 34 (11.97%) were found positive for Ureaplasma urealyticum (UU) and no significant difference was observed in the semen quality between the UU-positive and UU-negative samples (P> 0.05).</p><p><b>CONCLUSIONS</b>The bacteria-positive rate is high in the donor semen and the bacterial species are varied, mainly including gram-positive bacteria. Semen quality is reduced with the increased number of bacterial colonies.</p>

An intervention effect evaluation on nutrition related knowledge, attitude and behavior among prison police / 预防医学

Objective To evaluate the intervention effect of nutrition related knowledge,attitude and behavior among the prison police in Zhejiang Province . Methods Stratified cluster sampling method was used and investigation on knowledge,attitude and behavior was conducted.Nutrition education was carried out targeted to the problem found in the investigation for 6 months.Intervention effect was evaluated by comparison the scores of KAP before and after the intervention.Results The average score of KAP before the intervention was 70. 27 ±1 0. 90,including the average score for knowledge,attitude and behavior was 27. 38 ±6. 97,1 8. 07 ±3. 24 and 24. 82 ±3. 96,respectively.After the intervention, the average score of KAP was 91 . 1 9 ±4. 1 1 ,including the average score for knowledge,attitude and behavior was 37. 03 ±2. 97,1 9. 71 ±0. 71 and 34. 45 ±2. 74,respectively,higher than that before the intervention (P<0. 01 ).Conclusion Nutrition education could improve the awareness of nutrition among prison police .It was an effective method to develop dietary behavior of prison police.

Analysis of the quality of cryopreserved semen from male cancer patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the semen quality of cancer patients and search for a better way of sperm cryopreservation for them.</p><p><b>METHODS</b>We retrospectively analyzed the quality of the semen from 43 cancer patients under cryopreservation in the Sperm Bank of Zhejiang Province, and compared the semen parameters between the cancer patients and 248 normal donors as well as between the testicular cancer cases (n=22) and non-testicular cancer cases (n=21).</p><p><b>RESULTS</b>The cancer patients exhibited significantly lower semen quality than the normal donors as in sperm concentration (60.90 x 10(6)/ml vs 74.27 x 10(6)/ml), progressive motility (41.07% vs 51.79%), and recovery rate (49.98% vs 57.33%) (all P <0.05). Furthermore, the progressive sperm motility and sperm recovery rate after freezing were significantly decreased in the testicular cancer cases (15.68% and 42.81%) than in the non-testicular cancer cases (28.36% and 57.53%) (both P <0.05).</p><p><b>CONCLUSION</b>Semen quality declines in cancer patients, and therefore early sperm cryopreservation is essential for them. Due to the poor sperm motility and recovery rate of testicular cancer patients after freezing, further investigation is required on the improvement of sperm cryopreservation methods.</p>

Preconditioning of stem cells for the treatment of myocardial infarction / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Poor stem cell survival is one of the obstacles for cell regeneration therapy post myocardial infarction (MI) and responsible for unsatisfactory therapeutic effectiveness. Various approaches to improve the status of these cells and increase cell survival have become research foci. The following article is a mini-review on the utilization of cell preconditioning for stem cell survival.</p><p><b>DATA SOURCES</b>The data used in this review were mainly from the articles in Medline and PubMed published from 1990 to 2010. The search terms included "preconditioning, stem cell and myocardial infarction".</p><p><b>STUDY SELECTION</b>Original articles and critical reviews selected were relevant to the review's theme.</p><p><b>RESULTS</b>The harsh ischemic and inflammatory microenvironment in the infarcted myocardium offers a significant challenge to the transplanted donor stem cells. Survival of stem cells following transplantation is affected by many factors, such as limited blood supply, nutritional deficiency, hypoxia, oxidative stress, and inflammation. Preconditioning methods have potent cytoprotective effects, which enables cells to maintain a "standby state" through programmed initiation of cell survival pathways.</p><p><b>CONCLUSIONS</b>The findings suggest that cell preconditioning can be used as an effective anti-apoptotic strategy and enable cells to withstand and survive the harsh environment after transplantation.</p>

Imaging features of duplication of the internal auditory canal / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore multiple slices computed tomography (MSCT) and magnetic resonance imaging (MRI) features of duplication of the internal auditory canal (DIAC) in order to improve the accuracy of diagnosis.</p><p><b>METHODS</b>Four cases (5 ears) were analyzed and the related documents were reviewed retrospectively. MSCT was performed on all cases, and two cases had MRI scanning at the same time.</p><p><b>RESULTS</b>MSCT has shown that the internal auditory canal were divided into two canals by a bony septum in 5 ears. The superior canal ended in a very narrow connection to the facial canal, the inferior portion ended in connection to the cochlea and vestibule. The bony septums from the 2 ears were found no longer intact. The sum of diameter of the two canals was greater than 2 mm. In addition, 5 ears were found to have an enlarged vestibules and the hypoplasia lateral semicircular canals, and meanwhile, 2 ears of them were combined with ipsilateral microtia. Also 1 case of them was combined with microtia, outer acoustic atresia as well as abnormal middle ear. Multiplanar reconstruction and volume rendering images can entirely show the bony septum and two canals. In this study, the vestibular nerve, cochlear nerve and facial nerve were total hypoplastic in one ear, in the other ear, the vestibular and cochlear nerve were hypoplastic, and however, the facial nerve was intact.</p><p><b>CONCLUSIONS</b>MSCT can clearly depict duplication of the internal auditory canals and concomitant anomalies. MRI can clearly show the neural components and their associated malformation.</p>

Levels of soluble adhesion molecules in patients with various clinical presentations of coronary atherosclerosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was to compare concentrations of soluble forms of adhesion molecules in patients with different clinical presentations of coronary artery disease (CAD).</p><p><b>METHODS</b>One hundred and twenty-eight patients with CAD were divided into three groups; the first group was acute myocardial infarction group (AMI group, n = 45), the second group was unstable angina pectoris group (UAP group, n = 48), the third group was stable angina pectoris group (SAP group, n = 35). We compared them with patients with normal coronary arteries (control group, n = 31). The serum levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were measured in all subjects.</p><p><b>RESULTS</b>The serum level of VCAM-1 in the AMI group was significantly higher than in the UAP, SAP and control groups (P < 0.01). The level in the UAP group was significantly higher than the SAP group and control group (P < 0.01) and the level in the SAP group was significantly higher than in the control group (P < 0.01). The serum ICAM-1 level was significantly elevated in the AMI, UAP and SAP groups as compared to the control group (P < 0.01). The levels of serum E-selectin and P-selectin in the AMI and UAP groups were significantly higher than in the SAP and control groups (P < 0.01).</p><p><b>CONCLUSIONS</b>Increased levels of VCAM-1 and ICAM-1, E-selectin and P-selectin, as markers of inflammation, showed the importance of inflammatory processes in the development of atherosclerosis and clinical expression of CAD. Soluble ICAM-1, VCAM-1, E-selectin and P-selectin concentrations are useful indicators of the presence of atherosclerosis and the severity of CAD clinical presentation.</p>

Biological effects and toxicology studies of melamine and its derivative cyanuric acid / 浙江大学学报·医学版

Melamine (Tripolycyanamide) and its derivatives have recently become a public concern on food safety. To better understand melamine and its major derivative cyanuric acid.literature on their chemical properties, metabolism, biological effects, relevant toxicology studies, and the detection methods is reviewed. Studies indicate that the acute toxicity of melamine and cyanuric acid is low. In mammalian, these compounds are hardly metabolized in vivo and are rapidly eliminated in the urine. When used in large dosage,these compounds demonstrate marked renal toxicity,as well as toxic effect towards heart. The renal toxicity is exemplified by the calculi formation, acute renal failure, and subsequently induced carcinomas of the urinary bladder. Among the tested species, male cats and rats are more prone to be affected by the compounds. The HPLC/MS/MS is becoming the mainstay of the detection methods. Despite of the achieved knowledge on melamine and cyanuric acid, further research is warranted to unveil the mechanism of underlying susceptibility of kidney, to develop better analytic methods,and to explore possible biomarkers for better clinical diagnosis.

Study of carvedilol on plaque stability in carotid atherosclerotic rabbits transfected by p53 gene / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of carvedilol on stabilizing atherosclerosis plaque.</p><p><b>METHODS</b>Forty five male Japanese white rabbits were divided randomly into 5 groups with 9 for each. One group was fed up with normal diet as blank control. In other four groups, the common carotid artery of rabbits fed up with high cholesterol diet were injured by balloon. Three groups of them were transfected by wild-type p53 gene 8 weeks later, and then two groups of them were treated with carvedilol (3 mgxkg(-1)xd(-1)) and metoprolol (6 mgxkg(-1)xd(-1)) respectively, high cholesterol diet should be continued for other 4 weeks. Serum lipid, hypersensitive C-reaction protein (hsCRP), oxidized low density lipoprotein (oxLDL), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured in 0, 8, 12 weeks after experiment. The apoptosis rate of smooth muscle cell (SMC) in endomembrane and the local expression of p53, bcl-2, bax, alpha-actin were examined after experiment, and the carotid arteries were examined by light microscopy and transmission electron microscopy.</p><p><b>RESULTS</b>The typical carotid atherosclerotic plaques were observed in balloon-injured groups. The local expression rates of p53 in groups transfected by wild type p53 gene were higher obviously than them in other two groups (P < 0.01). Compared with the rabbits received simple transfection, the thickness of the fibrous cap in rabbits received carvedilol and metoprolol were all increased, but the change could be observed significantly in carvedilol group (P < 0.05). Compared with metoprolol, carvedilol could reduce the level of serum hsCRP, oxLDL, MDA, and increase the concentration of SOD and GSH-PX significantly (P < 0.05 or 0.01), but two medicines had no obvious influence to serum lipid. The apoptosis rate of SMC in endomembrane, the local expression of bax gene and bax/bcl-2 ratio were decreased, the positive expression rates of alpha-actin and bcl-2 were enhanced in carvedilol group (P < 0.01).</p><p><b>CONCLUSIONS</b>Both carvedilol and metoprolol can improve the stability of the plaque, but carvedilol is superior. Its mechanisms may lie in that carvedilol still has function of anti-inflammation, anti-oxidation, decreasing the apoptosis rate of SMC in addition to its function of blocking beta-receptor.</p>

Effect of valsartan on neointimal proliferation and expression of CD34 after angioplasty in rabbits / 中华急诊医学杂志

Objective To investigate the effect of valsartan (angiotensinⅡtypeⅠreceptor antagonists) on neointimal proliferation and expression of CD34 after angioplasty in rabbits.Method Twenty-four male New Zealand White rabbits were randomly divided into three groups:the control group,fed up with common diet;the model group and the valsartan group,fed up with hypercholesterolemic diet for 4 weeks,f then and ballon angioplasty.At 4 weeks after operation,the model group was fed up with common diet,whereas the valsartan group was fed up with the admixture of valsartan 10 mg?kg~(-1)?d~(-1) and common diet.All the rabbits were killed at the end of the 12th weeks.The abdominal aorta was performed with pathologic and morphologic analysis,and expression of CD34 in endothelial cells was analyzed with immunohistochemical method.Results Compared with the model group,the neointimal thickness and area of the valsartan group decreased by 56.58%and 66.81%, respectively.The expression of CD34 of the valsartan group was significantly higher (P

Germline polymorphisms of Bat26 and its significance in gastric cancer microsatellite instability / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To detect the germline polymorphic variations of Bat26 in Chinese and its significance in microsatellite instability (MSI) study of gastric cancers.</p><p><b>METHODS</b>Bat26 was analyzed by PCR-based denatured polyacrymide gel electrophoresis-silver stain method in peripheral blood from 389 healthy people and 34 gastric cancers with matched normal mucosa. Eleven other microsatellite loci were also detected for gastric cancers.</p><p><b>RESULT</b>(1) No Bat26 variations were identified in 423 genomic DNA from peripheral blood or normal mucosa by polyacrymide gel electrophoresis. (2) Two MSI-H cancers, oth Bat26+, were detected in 34 cases of gastric cancer. The alterations of Bat26 and MSI-H status were identical (P<0.05). (3) Compared with those of RER-cancers, MSI-H (RER+)cancers showed more obvious infiltration of intraepithelial lymphocytes and peri-tumoral lymphocytes, and more pushing borders (P<0.05).</p><p><b>CONCLUSION</b>(1) The germline polymorphisms of Bat26 in Chinese people are quasimonomorphic. Thus, no matched genomic DNA is needed while Bat26 was selected for tumor MSI analysis. (2) Bat26 is an independent indicator of MSI-H gastric cancers with distinct clinicopathological features.</p>