A dominant negative 14-3-3 mutant in Schizosaccharomyces pombe distinguishes the binding proteins involved in sexual differentiation and check point.

The homothallic fission yeast Schizosaccharomyces pombe undergoes sexual differentiation when starved, but sam (skips the requirement of starvation for mating) mutants such as those carrying mutations in adenylate cyclase (cyr1) or protein kinase A (pka1) mate without starvation. Here, we identified sam3, a dominant negative allele of rad24, encoding one of two 14-3-3 proteins. Genetic mapping and whole-genome sequencing showed that the sam3 mutation comprises a change in nucleotide at position 959 from guanine to adenine, which switches the amino acid at position 185 from glutamic acid to lysine (E185K). We generated the rad24-E185K integrated mutant and its phenotype was similar to that of the sam3 mutant, including calcium sensitivity and UV non-sensitivity, but the phenotype is different from that of the Δrad24 strain. While the UV-sensitive phenotype was observed in the Δrad24 mutant, it was not observed in the sam3 and rad24-E185K mutants. The expression of the rad24-E185K gene in wild type cells induced spore formation in the nutrient rich medium, confirming rad24-E185K is dominant. This dominant effect of rad24-E185K was also observed in Δras1 and Δbyr2 diploid mutants, indicating that rad24-E185K generate stronger phenotype than rad24 null mutants. Ste11, the key transcription factor for sexual differentiation was expressed in sam3 mutants without starvation and it predominantly localized to the nucleus. The Rad24-E185K mutant protein retained its interaction with Check point kinase1 (Chk1), whereas it reduced interaction with Ste11, an RNA binding protein Mei2, and a MAPKKK Byr2, freeing these proteins from negative regulation by Rad24, that account for the sam phenotype and UV non-sensitive phenotype. Glucose depletion in rad24-E185K or Δpka1 Δrad24 double mutation induced haploid meiosis, leading to the formation of spores in haploid. The position of glutamic acid 185 is conserved in all major 14-3-3s; hence, our finding of a dominant negative allele of 14-3-3 is useful for understanding 14-3-3s in other organisms.

Automated unruptured cerebral aneurysms detection in TOF MR angiography images using dual-channel SE-3D UNet: a multi-center research.

OBJECTIVES: Time of flight magnetic resonance angiography (TOF-MRA) is the primary non-invasive screening method for cerebral aneurysms. We aimed to develop a computer-aided aneurysm detection method to improve the diagnostic efficiency and accuracy, especially decrease the false positive rate. METHODS: This is a retrospective multicenter study. The dataset contained 1160 TOF-MRA examinations composed of unruptured aneurysms (n = 1096) and normal controls (n = 166) from six hospitals. A total of 1037 examinations acquired from 2013 to 2019 were used as training set; 123 examinations acquired from 2020 to 2021 were used as external test set. We proposed an equalized augmentation strategy based on aneurysm location and constructed a detection model based on dual channel SE-3D UNet. The model was trained with a 5-fold cross-validation in the training set, then tested on the external test set. RESULTS: The proposed method achieved 82.46% sensitivity on patient-level, 73.85% sensitivity on lesion-level, and 0.88 false positives per case in the external test set. The performance did not show significant differences in subgroups according to the aneurysm site (except ACA), aneurysm size (except smaller than 3 mm), or MRI scanners. The performance preceded the basic SE-3D UNet by increasing 15.79% patient-level sensitivity and decreasing 4.19 FPs/case. CONCLUSIONS: The proposed automated aneurysm detection method achieved acceptable sensitivity while controlling fairly low false positives per case. It might provide a useful auxiliary tool of cerebral aneurysms MRA screening. KEY POINTS: • The need for automated cerebral aneurysms detecting is growing. • The strategy of equalized augmentation based on aneurysm location and dual-channel input could improve the model performance. • The retrospective multi-center study showed that the proposed automated cerebral aneurysms detection using dual-channel SE-3D UNet could achieve acceptable sensitivity while controlling a low false positive rate.

Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance / 国际肿瘤学杂志

Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Mechanical circulation support device as a bridging tool for heart transplantation recipients with refractory heart failure / 中华器官移植杂志

Objective:To explore the clinical outcomes of recipients with refractory heart failure requiring an insertion of mechanical circulation support(MCS)device prior to heart transplantation(HT).Methods:From March 2017 to December 2021, retrospective review is performed for clinical data of 7 recipients with refractory heart failure requiring a bridging placement of MCS.There are 2 males and 5 females with an average age of(39.0±16.3)years(7~56 years)and an average weight of(57.6±19.9)kg(7~56 kg).The primary diseases of recipients are dilated cardiomyopathy(4 cases)severe viral myocarditis(2 cases)and ischemic cardiomyopathy(1 case).All of them develope acute decompensation of congestive heart failure.Before implanting MCS, two or more inotropic drugs are offered at maximal doses ages or IABP device, 6 cases required cardio-pulmonary resuscitation treatment and another patient for Heartcon assistance.All the patients bridge to heart transplatation.Results:Adjuvant therapy of MCS was offered for(20.0±11.5)d(7~34 d).Emergency HT is performed.Two post-HT deaths occurr due to multiple organ failure(1 case)and severe infection(1 case).The remainders recover smoothly during a follow-up period of(6~24 months).Conclusions:MCS device is recommended as a bridging too for HT recipients with refractory heart failure.It is imperative to improve clinical outcomes with MCS support before an onset of multiple organ dysfunction.Despite a perioperative mortality, long-term prognosis is generally satisfactory.

Effect of Xiao Qinglongtang on IL-33/ST2 Signaling Pathway in Mice with Allergic Rhinitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.

Surgical strategy for treatment of type A aortic dissection with small true lumen of the descending aorta / 中华胸心血管外科杂志

Objective:To summarize the results and methods of surgical treatment for type A aortic dissection with small true lumen of the descending aorta.Methods:9 patients underwent surgical treatment for type A aortic dissection with small true lumen of the descending aorta between January 2017 and December 2019 were analyzed retrospectively. There were 7 males and 2 females, mean age of (41.6±9.2) years. Acute dissection were 2 cases, and chronic dissection were 7 cases. Preoerative computed tomography was used to diagnose the dissection and evaluate the true lumen of the descending aorta. This procedure was done in all patients via a median sternotomy under hypothermic CPB with SCP. 4-branched prosthetic graft was used to replace the ascending aorta and aortic arch. The procedures involving the descending aorta: Hybrid surgery using TEVAR. Distal intimal flap fenestration. Implanting the intraoperative stent-graft or prosthetic graft at false lumen for second-step operation.Results:There was no in-hospital mortality. Stroke, Spinal cord, visceral ischemia and lower limbs malfunction were not observed. Reintervention was not found in case with acute dissection during follow-up. One patient who reveived fenestration underwent TEVAR, others with chronic dissection underwent thoracoabdominal aortic replacement 3 months after surgery.Conclusion:Hybrid or staged procedures was a suitable alternative to patients with type A aortic dissection with small true lumen of the descending aorta.

Meta-analysis of the Efficacy and Safety of Ⅹa Factor Inhibitors in the Prevention and Treatment of Venous Thromboembolism in Cancer Patients / 中国药房

OBJECTIVE：To systematicall y evaluate the efficacy and safety of a new oral anticoagulant Ⅹ a inhibitor （apixaban，rivaroxaban，edoxaban）in the prevention and treatment of venous thromboembolism （VTE）in cancer patients ，and to provide evidence-based reference for rational use of drugs in clinic. METHODS ：Retrieved from Cochrane Library ，PubMed， Embase，CBM，CNKI，VIP and Wanfang database ，randomized controlled trials （RCTs）about Ⅹa inhibitor （trial group ）versus routine treatment or placebo （control group ）in the prevention and treatment of VTE in cancer patients were collected. After literature screening ，data extraction and quality evaluation was evaluated by using biasrisk evaluation tool recommended by Cochrane System Evaluator M anual 5.1.0，and Meta-analysis was conducted by using Rev Man 5.3 software. RESULTS ：A total of 7 RCTs were included ，including 5 666 patients. Meta-analysis showed that recurrent rate of VTE in trial group was significantly lower than control group [RR ＝0.58，95％CI（0.47，0.71），P＜0.000 01]；there was no statistical significance in the incidence of major bleeding [RR ＝1.12，95％CI（0.67，1.85），P＝0.67] and clinically relevant non-major bleeding [RR ＝1.06，95％CI（0.72，1.55）， P＝0.77] between 2 groups. CONCLUSIONS ：Ⅹa inhibitors can effectively reduce the recurrent risk of VTE in cancer patients ， safety comparable with routine treatment （placebo）.

Surgical treatment strategy for endograft infection after thoracic endovascular aortic repair / 中华外科杂志

Objective@#To examine the results of surgical treatment for endograft infection after thoracic endovascular aortic repair (TEAVR).@*Methods@#Clinical data of 7 patients underwent surgical treatment for endograft infection after TEAVR at Department of Cardiothoracic Surgery, Changhai Hospital, the Navy Medical University between January 2016 and December 2018 were analyzed retrospectively. There were 6 males and 1 female, aging (51.5±16.7) years (range: 25 to 68 years). The origin of the aortic disease was descending aortic aneurysm in 5 cases, and Stanford B aortic dissection in 2 cases. Abdominal aorta below the level of the diaphragm was not involved in all patients. Two patients received "chimney technology" for left subclavian artery procedures. Time to infection was 5(3) months (M(QR)) (range: 1 to 24 months). Aortic endograft infection was diagnosed with a combination of microbiology (positive blood cultures, except one with mycotic), radiological evidence and clinical evidence of sepsis. Two patients suffered from aorto-esophageal fistula received emergency surgery, others were treated with elective surgery. Extra-anatomic prosthetic graft bypass was used for reconstruction of aorta, infected endogarft and aorta was removed, sac drainage was performed. Aorto-esophageal fistula was procedured according to the degree of lesions. All patients received antibiotics with specialist advice for 6 to 8 weeks.@*Results@#One patient died due to septic shock. In the follow-time (range: 6 to 24 months), 1 patient suffered from thoracic infection in 3 months after surgery, an other patient got iliac abscess after a month.@*Conclusions@#Endograft infection after TEAVR is high risk but may be curative. Appropriate selection of patients for infected endograft explantation could get a satisfied results.

Protective effect of anti-aging Klotho protein on human umbilical vein en-dothelial cells treated with high glucose / 中国病理生理杂志

AIM:To study the protective effect of anti-aging Klotho protein on human umbilical vein endothe-lial cells (HUVECs) treated with high glucose (HG).METHODS:HUVECs were cultured in vitro, and divided into PBS control group, 5.5 mmol/L glucose group, 33.3 mmol/L glucose group, 0.1 μmol/L Klotho +33.3 mmol/L glucose group, 1 μmol/L Klotho+33.3 mmol/L glucose group , and 10μmol/L Klotho+33.3 mmol/L glucose group .The viabili-ty of the HUVECs was measured by MTT assay .The content of malondialdehyde ( MDA) , and the activities of lactate de-hydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) in cell culture supernatants were observed . The production of reactive oxygen species ( ROS) in HUVECs was analyzed by flow cytometry .The levels of nitric oxide ( NO) , endothelin ( ET-1 ) , intercellular adhesion molecule-1 ( ICAM-1 ) in HUVEC culture medium were detected by ELISA.The protein expression of nuclear factor-kappa B (NF-κB) in the HUVECs was determined by Western blot .RE-SULTS:Compared with PBS control group , 33.3 mmol/L glucose significantly decreased the HUVEC viability , increased ROS, LDH and MDA levels , reduced the activities of SOD and GSH , decreased the NO secretion , and induced the ET-1 and ICAM-1 secretion and the protein expression of NF-κB in HUVECs.When HUVECs were treated with Klotho protein at different concentrations combined with 33.3 mmol/L glucose, the cell viability was increased significantly , the ROS, LDH and MDA levels were decreased significantly , the antioxidant SOD and GSH activities were significantly increased , the se-cretion of NO was increased , but ET-1 and ICAM-1 releases and protein expression of NF-κB were significantly reduced . CONCLUSION:Anti-aging Klotho protein promotes the viability of HUVECs treated with HG , reduces the oxidative dam-age and ROS production , and restores the normal secretory function of HUVECs , thus playing a protective role in vascular endothelial cells through reducing the protein expression of NF-κB.

Clinical applications of breast imaging reporting and data system / 中国医学影像技术

Breast imaging reporting and data system (BI-RADS) is a standardized system for reporting breast pathology covered mammography,ultrasound and MRI.BI-RADS improves the standardization in interpretation of medical imaging and reduces the confusion of breast imaging interpretation.It is a widely accepted risk assessment and quality assurance tool in mammography,ultrasound and MRI.The development history,clinical applications,limitations of BI-RADS,as well as the clinical applications combined with other imaging techniques were reviewed in this article.

Self-made single-port and three port retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria / 中国内镜杂志

Objective To explore the clinical safety and efficacy of self-made single-port retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria. Methods From Feb 2013 to Mar 2016, clinical data of 34 patients were collected. Of them, 16 cases underwent self-made single-port retroperitoneoscopic renal pedicle lymphatic disconnection and 18 cases underwent three port retroperitoneoscopic renal pedicle lymphatic disconnection. No significant difference was shown in age, body mass index between the two groups (P > 0.05). Mean operative time, estimated bleeding volume, drainage time, postoperative hospital stay, postoperative pain evaluation, satisfaction scores of incision were compared between the two groups. Results All procedures were successfully performed without conversion to open surgery. Compared with the three port surgery group, results in the single-port group were superior in terms of mean operative time [(102.3 ± 16.1) versus (132.4 ± 21.6) min, P < 0.05], there were no significant differences in estimated blood loss, drainage time, postoperative hospital stay, the date in postoperative pain evaluation, satisfaction scores of incision shown that single-port group was superior to three port group. Conclusion Our initial experience revealed that single-port retroperitoneoscopic renal pedicle lymphatic disconnection was a safe, effective, cost-effective and less-invasive procedure for chyluria with improved postoperative pain and cosmetic results.

Correlation between hepatic fibrosis and anti-neutrophil cytoplasmic anti-bodies(ANCA)in schistosomiasis patients / 中国血吸虫病防治杂志

Objective To investigate the association between hepatic fibrosis and anti-neutrophil cytoplasmic antibodies (ANCA)in the patients with schistosomiasis. Methods Totally 145 schistosomiasis patients confirmed by Jingzhou First Peo-ple's Hospital during the period of February 2014 to June 2016 were randomly selected as an experimental group,and 100 healthy people during the same period were randomly selected as a control group. The serum samples of the two groups were col-lected and the level of ANCA was detected by indirect immunofluorescence,and the levels of hyaluronic acid,laminin,procol-lagen type Ⅲ,and collagen type Ⅳ were detected by radioimmunoassay. The levels of the above indexes of the two groups were compared. Results The positive rate of ANCA was 28.96%(42/145)in the experimental group and 1.00%(1/100)in the healthy control group,and the difference between them was statistically significant(P < 0.05). The levels of hyaluronic acid, laminin,procollagen type Ⅲ and collagen type Ⅳ in the experimental group were significantly higher than those in the control group,and the differences were statistically significant(all P < 0.05),and the proportions of those with abnormal levels of hyal-uronic acid,laminin,procollagen type Ⅲ and collagen type IV in the experimental group were significantly higher than those in the control group,and the differences were statistically significant(all P < 0.05). In the experimental group,among the 42 pa-tients with ANCA positives,the proportions of those with abnormal levels of hyaluronic acid and laminin were significantly high-er than the proportions of those with ANCA negatives,and in the former,the levels of the four indicators of liver fibrosis were all higher than the normal values,and the average levels of hyaluronic acid and laminin in the patients with ANCA positives were significantly higher than those in the patients with ANCA negatives(all P < 0.05). Conclusion The patients with schistosomia-sis hepatic fibrosis could be positive for the autoimmune antibody ANCA,and ANCA may be associated with the autoimmune process of liver fibrosis.

Comparative Study between Low-dose Chemotherapy and Surgery for Isolated Eosinophilic Granuloma Bone Lesions in Children / 中山大学学报(医学科学版)

[Objective]To comprehensively compare the feasibility of three different treatment strategies consisting of low-dose chemotherapy(LDC),surgery and surgery with adjuvant low-dose chemotherapy(SLDC)for children with solitary bone lesions of eosinophilic granuloma(SBL-EG).[Methods]We retrospectively reviewed the records of 149 pediatric patients with SBL-EG at our institutions from 2002 to 2014. Our study included 86 patients who received LDC ,33 patients who received surgery and 30 patients who received SLDC. The duration of hospital stay ,time to symptom relief,recovery time,cost,complications and relapse-free sur-vival(RFS)of each strategy were analyzed.[Results]Hospital stay,time to symptom relief,recovery time and cost in the LDC group were significantly shorter or less than those in the surgery or SLDC group (P 0.05). Chemotherapy-related adverse events in the LDC and SLDC groups included nausea(8.62%),aminotransferase elevation(7.76%),slight hair loss(4.31%), immunity decline (21.55%),growth retardation (10.34%) and moon face (7.76%). LDC and SLDC treatment resulted in a significantly longer RFS (147 months and 126 months ,respectively) than surgery alone (114 months)(P = 0.005 and 0.019 , respectively). However ,there was no statistically significant difference in RFS between the LDC and SLDC groups (P = 0.732).[Conclusions]Compared with surgery or SLDC,LDC appears to promote more rapid recovery,less invasion,increase safety and eco-nomic treatment strategy for pediatric patients with SBL-EG.

Improved Brisson's operation correction for concealed penis after circumcision / 重庆医学

Objective To study the effective correction for concealed penis after being operated by circumcision.Methods A total of 16 concealed penis patients underwent circumcision were corrected by improved Brisson's operation,and the treatment effects were observed.Results Shapes of penis were recovered totally or nearly in 16 cases.Five cases appeared serious edema of the penis,but recovered from 3-6 months.The penises were all developed normal without problem of retraction or curvature in 1-2 years of follow up.Conclusion Improved Brisson's operation for concealed penis is an effective remediation for concealed penis after mistherapy by circumcision.

Anti-aging Klotho protein reduce the hypoxia/reoxygenation injury of neonatal rat myocardial cells / 中国病理生理杂志

[ ABSTRACT] AIM:To study the effects of anti-aging Klotho protein on neonatal rat myocardial cells with hypo-xia/reoxygenation ( H/R) injury.METHODS:The cardiomyocytes of neonatal SD rats were cultured to establish hypoxia/reoxygenation model.The myocardial cells were divided into normal control group, H/R model group, different concentra-tions of Klotho protein (0.1μmol/L, 1μmol/L and 10μmol/L) pretreatment groups.The myocardial cells pulse frequen-cy was observed before and after H/R.The cell viability was measured by MTT assay.The leakages of LDH, CK and AST, the content of MDA and the activity of SOD were detected.The apoptotic rate of the myocardial cells was analyzed by flow cytometry.The mRNA expression of endoplasmic reticulum stress markers and apoptosis-related molecules GRP78, CRT, CHOP and caspase-12 was measured by real-time PCR.The protein levels of CHOP, caspase-12 and phosphorylated Akt in the myocardial cells were determined by Western blot.RESULTS: Compared with normal control group, the pulse fre-quency, cell viability rate and SOD activity of myocardial cells were significantly decreased, the cell apoptotic rate as well as the contents of LDH, CK, AST and MDA were increased in H/R model group.The mRNA expressions of GRP78, CRT, CHOP and caspase-12 as well as the protein levels of CHOP and caspase-12 were increased, whereas p-Akt level was decreased obviously.Compared with H/R model group, the pulse frequency, cell viability rate and SOD activity were in-creased significantly, the cell apoptotic rate as well as the contents of LDH, CK, AST and MDA were decreased in Klotho pretreated group.The mRNA expression of GRP78, CRT, CHOP and caspase-12 as well as the protein levels of CHOP and caspase-12 were decreased, while p-Akt level increased significantly.CONCLUSION:Anti-aging Klotho protein improves the myocardial cell survival and inhibits the apoptosis by increasing the resistance of the cells to oxidative stress and exces-sive endoplasmic reticulum stress response, which is related with the activation of Akt phosphorylation in H/R-injured my-cardial cells.

Ethanol extract of propolis protects macrophages from oxidized low-den-sity lipoprotein-induced apoptosis by inhibiting caspase-12 / 中国病理生理杂志

AIM:To investigate the inhibitory effect of ethanol extract of propolis (EEP) on oxidized low-den-sity lipoprotein ( ox-LDL )-induced macrophage apoptosis and the underlying molecular mechanisms . METHODS:RAW264.7 macrophages were pretreated with EEP (7.5, 15 and 30 mg/L), 4-phenylbutyric acid (PBA, 5 mmol/L) or diphenyleneiodonium ( DPI, 5μmol/L) for 1 h and then treated with ox-LDL (100 mg/L) or tunicamycin ( TM, 4 mg/L) for 24 h.The cell viability and apoptosis were determined by MTT assay and Annexin V-FITC apoptosis detection kit , re-spectively.The activity of superoxide dismutase (SOD), and the levels of reactive oxygen species (ROS) and malondial-dehyde (MDA) in the cells were measured.The protein levels of caspase-12, a proapoptotic molecule under endoplasmic reticulum stress ( ERS) , were examined by Western blot analysis .RESULTS:Like PBA ( an ERS inhibitor ) , EEP pro-tected RAW264.7 macrophages from ox-LDL-induced injury in a dose-dependent manner , as assessed by the increased cell viability and the decreased apoptotic rate .The decrease in cell viability and increase in apoptotic rate induced by TM , an ERS inducer, were also attenuated by EEP .Moreover, EEP suppressed ox-LDL-induced oxidative stress as revealed by the decreased generation of ROS and MDA as well as elevated SOD activity , which were similar to DPI , an oxidative stress in-hibitor.Furthermore, EEP significantly suppressed ox-LDL-or TM-induced activation of caspase-12.Similar results were observed in the cells pretreated with PBA or DPI and then treated with ox-LDL.CONCLUSION: EEP may protect RAW264.7 macrophages from ox-LDL-induced apoptosis and the mechanism is at least partially involved in the ability of EEP to suppress oxidative stress and subsequent activation of caspase -12.

Effect of protein kinase C inhibitor on the level of phosphralated extracellular regulated protein kinases in the spinal trigeminal nucleus of migraine model rats / 中华行为医学与脑科学杂志

Objective To explore the effect of protein kinase C inhibitor on the level of phosphralated extracellular regulated protein kinases in the spinal trigeminal nucleus of migraine model rats.Methods Healthy adult male SD rats were randomly divided into four groups:normal group (group C),sham operation group (group C),migraine model group(group M),and H-7group(H-7group),with 18 rats in each group.Dural blood flow and the extracellular discharge frequency in the spinal trigeminal nucleus was recorded.ERK1/2 phosphorylation was tested.Results (1) Dural blood flow:compared with group C((3.8± 1.0)％),the dural blood flow in M group ((78.0±4.2) ％)increased obviously(P＜0.01) ; compared with M group((78.0±4.2)％),the dural blood flow in H-7 group((-24.8±4.9) ％) decreased obviously(P＜0.01).(2) The percentage of extracellular discharge frequency change:two hours after treatment,the percentage of extracellula discharge frequency change in group M ((325.9 ±47.3)％)was higher than that in group C((107.3±16.4)％).The percentage of discharge frequency change in group H-7((136.0±26.5)％) was lower than that in group M((325.9±47.3)％).There was no significant difference in the percentage of discharge frequency change between group H-7((136.0±26.5) ％) and group C((107.3 ± 16.4)％).(2) ERK1/2 phosphorylation:the ERK1/2 phosphorylation in group M was higher than that in group C.The ERK1/2 phosphorylation in group H-7 was lower than than that in group C and group M.Conclusion ERK1/2 is a downstream PKC signal path and PKC may have indirect activation of ERK1/2.

Neurotransmitter-mediated collective rhythms in grouped Drosophila circadian clocks.

Over the past decades, fly Drosophila melanogaster has being used as a premier model organism to study molecular and genetic bases of circadian rhythms. Here the authors propose a multicellular heterogeneous model for which the network of Drosophila circadian oscillators consists of two groups, the self-sustained lateral neurons (LNs) communicating to each other and the damped dorsal neurons (DNs) receiving neurotransmitters only from the LNs without interaction within this group. By simulating different experimental conditions, the authors find that the proposed model, except for being capable of reproducing some known experimental results well, also can predict some interesting phenomena: 1) The DNs need neuronal projections from the LNs to be rhythmic and to synchronize; 2) the effect of communication on mean amplitude and mean period of two oscillatory groups is different; 3) communication delay can facilitate the network synchronization of the LNs; and 4) only the LNs lose rhythmicity under constant light conditions. These results reveal the mechanism of an integrated pacemaker that would govern behavioral and physiological rhythmicity of the model organism.

Noise-induced Synchronized Switching of a Multicellular System / 生物化学与生物物理进展

Genetic bistable systems are a large class of important biological systems. Bistability, the capacity to achieve two distinct stable steady states in response to a set of external stimuli, arises within biological systems ranging from the ? phage switch in bacteria to cellular signal transduction pathways in mammalian cells. On the other hand, the increasing experimental evidence in the form of bimodal population distribution has indicated that noise plays a very key role in the switching of bistable systems. However, the physiological mechanism underling noise-induced switching behaviors has not been well explored yet. In the previous work, it has been showed that noise can induce coherent switch for a single genetic Toggle switch system. Here the influence of several kinds of noises (including intracellular and extracellular noises) on synchronized switch was investigated for a multicell gene toggle switch network system. It has been found that multiplicative noises resulting from fluctuations of either synthesis or degradation rates and the additive noise within each cell (they altogether are called as intracellular noises) all can induce the synchronized switch, and that there exists an optimal noise intensity such that the synchronized switch is optimally achieved and the amplification factor has the maximal value. On the other hand, the extracellular noises arising from the stochastic fluctuation of the cellular environment, not only brings about the synchronized switch, but also enhances it by suppressing intracellular fluctuations when the intracellular noises are not enough to induce the synchronized switch. Finally, the influence of the diffusive rate of signal molecules affected by noise on the dynamics of the multicellular system was also investigated, showing that the larger the diffusive rate, the better the synchronized switch and the larger the amplification factor.

An experimental study of promoting peripheral nerve regeneration through slow-releasing diaphragm with FK506 after end-to-side neurorrhaphy / 中华显微外科杂志

Objective To explore the effect for nerve regeneration with immunosuppresssant FK506 a-round the cut after end-to-side neurorrhaphy of peripheral nerve. Methods There were 40 adult SD rats and were divided into two groups randomly by means. In the experiment group, the right peroneal nerve of SD rat was cut off,then an 1mm epineural window was created on the neighboring tibial nerve,the distal end of peroneal nerve was sutured to the windowed tibial nerve by means of end-to-side attachment, application of slow-releasing diaphragm which was implanted around the nerve anastomosis with FK506. In the contrast group,there were not the FK506 around the cut after end-to-side neurorrhaphy. The tibial and peroneal nerve trunks were labeled by being in jected with fast blue ( KB) and fluorescence golden ( FG) respectively. The labeled cells in the dorsal root ganglia (DRG) and spinal cord were observed by fluorescence microscopy. Results There were a lot of FB labeled cells in the experiment group than in the contrast group in the DRG and spinal cord. Conclusion Immunosuppresssant FK506 could promote nerve regenerative speed and quality after end-to-side neurorrhaphy of peripheral nerve.