Trichinella spiralis nudix hydrolase (TsNd) gene encoding a 46 kDa protein was expressed in Escherichia coli and the potential of recombinant TsNd protein (rTsNd) as an antigen for the serodiagnosis of trichinellosis was investigated by ELISA and compared with those of ELISA with T. spiralis muscle larval excretory–secretory (ES) antigens. The sensitivity of both ELISA was 100% (30/30), for the detection of anti-Trichinella IgG antibodies in sera of the experimentally infected mice, and the specificity of rTsNd-ELISA and ES-ELISA was 100% (54/54) and 98% (53/54), respectively (P>0.05). Serum anti-Trichinella antibodies were firstly detected by rTsNd-ELISA at 14 days post infection (dpi), then continued to increase with a detection rate of 100% at 36 dpi. The anti-Trichinella antibody levels at different times after infection were statistically different (P<0.05). The results showed that the rTsNd might be a potential candidate antigen for specific serodiagnosis of trichinellosis. But, it needs to be further evaluated with sera of the patients with trichinellosis and other helminthiasis.

Objective To explore the dynamic changes and significance of heart rate variability(HRV)during the initial phase after acute exposure to Tibet plateau by combining time,frequency domain and non-linear analysis.Methods Eighty-six healthy young men of Han nationality underwent short-term(5 min)heart rate variability(HRV)monitoring at 560 meter above sea level(plain),then were transported to Tibet plateau(3675-meter above sea level)by airplane.There,all subjects were divided into 3 groups,and A gorup(n=12)underwent HRV monitoring on the 2nd day after arrival,B group(n=48)on the 3rd day,C group(n=26)on the 4th day.Results Compared with the data obtained at plain,the standard deviation of normal to normal intervals(SDNN),high frequency(HF)and total power(TP)decreased significantly(P50 ms(PNN50)and normalized high frequency(HFnu)also decreased obviously(P

Coronary Sinus ; abnormalities ; Humans ; Male ; Middle Aged ; Subclavian Vein ; Vena Cava, Superior

Objective To compare the effect of conventional and hyperoxia management strategy during deep hypothermia in patients with DeBake type 1 aortic dissection or aortic arch aneurysm undergoing total aortic arch replacement.Methods 32 adult patients undergoing total aortic arch replacement were randomly allocated to one of two groups(n=16 each):conventional(C)and hyperoxia group(H).The patients had no history of cerebral vascular disease.Left radial artery and dorsal artery of left foot were cannulated for monitoring of blood pressure of upper and lower limbs.Right internal jugular vein was cannulated for CVP monitoring and administration of drug and fluid.Anesthesia was induced with etomidate 10-15 mg,fentanyl 5-10 ?g?kg~(-1) and pancuronium 0.1 mg?kg~(-1) and maintained with fentanyl(total amount was＜20 ?g?kg~(-1)),isoflurane and pancuronium after tracheal intubation.Intermittent i.v.boluses of diazepam,sodium thiopental or propofol were given during cardiopulmonary bypass(CPB).Another catheter was inserted into right internal jugular vein eephalad until resistance was met.The tip of the catheter was at the level of mastoid process.The hyperoxia management involved the following steps:FiO_2 was gradually reduced with decreasing body temperature(T_0)from 70%(36～ 37℃)to 60%-40%(35.9-34℃),38%-30%(32-26℃),30%(26-24℃)and finally to 21%.When nasopharyngeal T_0 was reduced to 22℃ or 5-10 min before selective cerebral peffusion(SCP),FiO_2 was raised to 60%-100% to maintain PjvO_2＞20 mm Hg or SjvO_2＞60%.FiO_2 was maintained at 60%-100% during SCP until T_0 was rewarmed to 22℃,then reduced to 30%.FiO_2 was then gradually increased to 40%(when T_0 reached 28℃),to 50%-70% (34-37℃)and finally to 80%(T_0＞37℃).Blood samples were taken from jugular venous bulb and arterial port of oxygenator for determination of PjvO_2,SjvO_2 and PaO_2 before skin incision (T_1),at 15 min of CPB(T_2),10 min of SCP(T_3),5 min after descending aorta unclamping(T_4),5 min after left subclavian artery unclamping(T_5),5 min after left common carotid artery unclamping(T_6),anonymous artery unclamping(T_7),when nasopharyngeal To returned to 35℉(T_8)and 10 min after CPB was terminated(T_9).The awakening time and the duration of ICU stay(days)were recorded.Pre- and postoperative neurological examination and brain CT scan were performed.Results All patients survived the operation and were discharged from hospital.No new brain infarction occurred.Transient neurologic dysfunction occurred in 2 patients in group H and 3 patients in group C.There was a positive linear relationship between PaO_2 and PjvO_2 during deep hypothermia in group H (r=0.541,P＜0.01).The PjvO_2 and SjvO_2 were significantly higher in group H than in group C.The awakening time and the ICU stay were significantly shorter in group H than in group C.Conclusion The hyperoxia management strategy can provide clinical prognosis than the conventional management strategy during deep hypothermia for total aortic arch replacement by supplying more dissolved oxygen.

Objective To explore the effect of transplantation of mesenchymal stem cells (MSCs) transfected with the human receptor activity modifying protein 1 (hRAMP1) gene on proliferation and apoptosis of vascular smooth muscle cells (VSMCs) after carotid balloon angioplasty was performed in rabbits with carotid atherosclerosis.Methods Density gradient centrifugation and adherent culture were carried out to obtain MSCs,which were then transinfected with an adenovirus vector carrying the hRAMP1 gene or an empty adenovirus vector.A rabbit model of atherosclerotic stenosis and balloon angioplasty was successfully established.Results were randomly divided into three groups:the hRAMP1-MSCs group,theadipose-derived MSCs (Ad-MSCs) group and the control group.MSCs were transinfected with Ad-EGFP-hRAMP1,Ad-EGFP or PBS by transplantation into the injured carotid arteries.Homing and differentiation were assessed with MSCs harvested at 7 d.With MSCs collected at 28 d,Western blotting was used to measure the expression of the hRAMP1 target gene in the carotid artery; the neointima and media area in the injured carotid arteries were estimated; carotid artery morphology was examined with H&E staining; and the proliferation and apoptosis of VSMCs were determined by immunohistochemistry and TUNEL.Results The expression of CD31 and EGFP was found in proliferating neointima lesions at 7d in the hRAMP1-MSCs group and the Ad-MSCs group.At 28d of MSC transplantation,the level of RAMP1 significantly increased in the hRAMP1-MSCs group,compared with the Ad-MSCs and control groups [(63.0±4.9) vs.(28.3±2.5) and (27.2±7.2),all P＜0.05],but there was no differencein the RAMP1 level between the Ad MSCs group and the control group (P＞0.05).Positive expression of the α-smooth muscle antibody (α-SMA) was found in all three groups at 28 d of MSC transplantation.The thickness of the hyperplastic neointima significantly decreased in the hRAMP1-MSCs group,compared with the other two groups (P＜0.05),and was lower in the Ad-MSCs group than in the control group (P＜0.05).The expression of proliferating cell nuclear antigen (PCNA) was lower in the hRAMP1-MSCs group than in the Ad-MSCs and control groups at 28d of MSC transplantation (P ＜0.05),while the PCNA level was lower in the Ad-MSCs group than in the control group (P＜ 0.05).The VSMC apoptosis rate significantly increased in the hRAMP1-MSCs group,compared with the Ad MSCs and control groups (P＜0.05),and was the lowest in the control group (P＜0.05).Conclusions Gene-modified stem cell therapy can effectively inhibit vascular intimal hyperplasia,thereby reducing restenosis after angioplasty.

Objective To study mutations in the extracellular matrix protein 1 (ECM1) gene in a family with lipoid proteinosis (LP). Methods Bi-directional DNA sequencing was used to detect the ECM1 gene in patients with LP as well as among their parents, siblings and children. Results Sequencing from the affected individuals revealed a new compound heterozygote of missense/nonsense mutations, C220G/R476X, which were not found in the control group. The father was a carrier of the missense mutation C220G and the mother was a carrier of the nonsense mutation R476X, both on one allele. The other siblings, the patients' children and their siblings' children were carriers of either C220G or R476X mutations. Conclusion A new compound heterozygous mutation of ECM1 gene was identified in this LP family.

BACKGROUND: Intravenous transplantation has been regarded as a most safe method in stem cell therapies. There is evidence showing the homing of bone marrow stem cells (BMSCs) into the injured sites, and thus these cells can be used in the treatment of acute myocardial infarction (MI). This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model. METHODS: A total of 60 New Zealand rabbits were randomly divided into three groups: control group, epicardium group (group I) and ear vein group (group II). The BMSCs were collected from the tibial plateau in group I and group II, cultured and labeled. In the three groups, rabbits underwent thoracotomy and ligation of the middle left anterior descending artery. The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead II and III of electrocardiogram suggested successful introduction of myocardial infarction. Two weeks after myocardial infarction, rabbits in group I were treated with autogenous BMSCs at the infarct region and those in group II received intravenous transplantation of BMSCs. In the control group, rabbits were treated with PBS following thoracotomy. Four weeks after myocardial infarction, the heart was collected from all rabbits and the infarct size was calculated. The heart was cut into sections followed by HE staining and calculation of infarct size with an image system. RESULTS: In groups I and II, the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group (P<0.05). However, there was no significant difference in the infarct size between groups I and II (P>0.05). CONCLUSION: Transplantation of BMSCs has therapeutic effect on MI. Moreover, epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.
Animals ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Dyslipidemias ; metabolism ; Energy Metabolism ; drug effects ; Fatty Liver ; chemically induced ; complications ; Female ; Fibroblast Growth Factors ; administration & dosage ; pharmacology ; therapeutic use ; Insulin Resistance ; Lipolysis ; drug effects ; Liver ; metabolism ; pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Sodium Glutamate

Protein-protein interactions (PPIs) are not only crucial for the assembly of protein complexes but also fundamental for maintaining normal biological functions. These interactions are vital for protein structure and biological functionality and play a central role in cellular signaling, metabolic pathways, and regulatory networks. The 14-3-3 protein, highly conserved and widely expressed in eukaryotes, primarily recognizes and binds to its partner proteins to participate in essential life processes such as cell cycle control, signal transduction, and energy metabolism. This review discusses the role of dysregulated PPIs between 14-3-3 proteins and their partner proteins such as estrogen receptor α (estrogen receptor α, ERα), RAF proto-oncogene serine/threonine-protein kinase (C-RAF/RAF-1), and p53 in the onset and progression of tumors, focusing on the research progress of 14-3-3/ERα, 14-3-3/C-RAF, and 14-3-3/p53 molecular glues. These molecular glues, by mimicking or enhancing the phosphorylation sites of serine on partner proteins, form covalent bonds, salt bridges, and hydrogen bonds with 14-3-3 proteins, thereby enhancing the stability of PPIs and effectively intervening in protein activity and signaling under pathological conditions. Additionally, this article explores the potential of this chemical intervention strategy in clinically suppressing tumor progression, providing a theoretical foundation and practical guidance for future research directions.

Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. zhuchuanlong@jsph.org.cn.
Adolescent ; Child ; Female ; Glycyrrhizic Acid ; therapeutic use ; Humans ; Male ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Tablets