●AIM:To identify early molecular diagnostic biomarkers for optic atrophy(OPA)and explore potential mechanisms mediated by proteins.●METHODS:Gene expression data was sourced from eQTLGen(31684 samples;19960 genes).Th...●AIM:To identify early molecular diagnostic biomarkers for optic atrophy(OPA)and explore potential mechanisms mediated by proteins.●METHODS:Gene expression data was sourced from eQTLGen(31684 samples;19960 genes).The OPA discovery cohort came from FinnGen(629 cases;496621 controls);the validation cohort came from the genome-wide association studies(GWAS)catalog(58 cases;496621 controls).Protein data for mediation analysis was obtained from the deCODE Genetics consortium(35559 samples;4907 proteins).Causal estimates were derived using twosample Mendelian randomization(MR).Inverse-variance weighted(IVW)was the primary analysis method.Sensitivity analyses included MR-Egger intercept,Cochran’s Q test for heterogeneity,and leave-one-out analysis.Colocalization analysis validated identified genes.Additionally,interaction analysis identified potential biomarkers.Finally,mediation analysis assessed potential mediating mechanisms.●RESULTS:Multi-cohort validation revealed that increased expression levels of the SEC61A2 and THNSL2 were causally associated with an elevated risk of OPA.Furthermore,we identified 386 genes potentially associated with OPA.Hormone secretion and immune-related pathways were found to play significant roles in OPA pathogenesis.Mediation analysis indicated that Upper zone of growth plate and cartilage matrix associated(UCMA)potentially mediates the effect of SEC61A2 in increasing OPA risk.●CONCLUSION:SEC61A2 and THNSL2 may serve as early diagnostic biomarkers for OPA.Additionally,SEC61A2 likely increases OPA risk through UCMA.展开更多
BACKGROUND Arteriovenous fistula is a rare cause of refractory heart failure,and corrective measures may lead to dramatic improvement;however,the long-term cardiac remodeling outcomes,particularly after delayed closur...BACKGROUND Arteriovenous fistula is a rare cause of refractory heart failure,and corrective measures may lead to dramatic improvement;however,the long-term cardiac remodeling outcomes,particularly after delayed closure,remain unclear.CASE SUMMARY A 57-year-old man was admitted to the hospital with complaints of exertional dyspnea for more than 10 years.Physical examination revealed wet crackles in the lungs and a continuous machinery murmur in the left lower back and groin area.Asymmetric edema and varicose veins were observed in the lower limbs.Echocar-diography revealed a dilated right ventricle with severe pulmonary hypertension.Computed tomography revealed a left common iliac arteriovenous fistula linked to prior lumbar disc surgery.Surgical repair resolved the symptoms,with echo-cardiography at 4 months showing a reduced right atrium(RA)and ventricular(RV)diameter and tricuspid regurgitation.However,during the 2-year follow-up,gradual RA and RV re-expansion(from 35 mm to 51 mm and from 26 mm to 46 mm,respectively)was observed,despite sustained clinical stability.CONCLUSION This case highlights that delayed arteriovenous fistula closure may result in in-complete right heart reverse remodeling,even after symptomatic relief.Potential mechanisms include persistent hemodynamic stress from subclinical residual shunting or functional impairment due to chronic volume overload.Early inter-vention before irreversible right heart damage is critical for optimal outcomes.展开更多
Recent studies have demonstrated that dihydromyricetin(DHM)exerts a protective effect against central nervous system injury.Building on these findings,the present study aimed to investigate whether DHM could ameliorat...Recent studies have demonstrated that dihydromyricetin(DHM)exerts a protective effect against central nervous system injury.Building on these findings,the present study aimed to investigate whether DHM could ameliorate cognitive deficits in a type 2 diabetes mellitus(T2DM)rat model,and to explore whether this effect involved inhibition of the JNK signaling pathway and suppression of endoplasmic reticulum stress(ERS).To establish the T2DM model,Sprague Dawley(SD)rats were fed a high-fat,high-sugar diet in combination with a single intraperitoneal injection of streptozotocin(STZ).Fasting blood glucose levels were measured from tail vein samples,and cognitive performance was evaluated using the Morris water maze(MWM)and Y-maze tests.Following behavioral assessments,the animals were sacrificed by cervical dislocation,and hippocampal tissues were collected for further analysis.Histological examination using hematoxylin-eosin(H&E)staining was performed to assess hippocampal neuronal damage.Western blotting(WB)analysis was employed to quantify the expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2,while ELISA was conducted to measure levels of phosphorylated tau(p-tau)and amyloid-β(Aβ)in the hippocampus.After 12 weeks of oral administration of DHM(250 mg/kg/d),relevant biomarkers were re-evaluated to determine the compound's impact on cognitive function and hippocampal integrity.Additionally,rats from each group received intracerebroventricular injections of various pharmacological agents,namely,TUDCA(an ERS inhibitor),STZ,SP600125(a JNK inhibitor),and anisomycin(AMY,a JNK activator).WB analysis was further conducted to assess the expression of JNK,phosphorylated JNK(p-JNK),and ERS-associated proteins Bip and p-PERK in hippocampal tissue.The results confirmed that combining a high-fat,high-sugar diet with low-dose STZ injection for 4 weeks effectively established a T2DM model.Compared with the control group,T2DM rats exhibited significant cognitive deficits,increased neuronal apoptosis in the hippocampus,and elevated hippocampal levels of p-tau and Aβ.Notably,DHM treatment markedly reversed these pathological changes in T2DM rats,whereas it had no significant effects on control animals.Moreover,administration of TUDCA and SP600125 similarly mitigated cognitive impairment,neuronal apoptosis,and the accumulation of p-tau and Aβin diabetic rats.Conversely,activation of ERS and JNK signaling using tunicamycin(TUN)and AMY,respectively,resulted in exacerbated cognitive decline,increased neuronal apoptosis,and higher levels of p-tau and Aβ.In conclusion,these findings suggested that DHM effectively alleviated cognitive dysfunction in T2DM rats,potentially through the inhibition of JNK signaling and subsequent attenuation of ERS,thereby reducing neuronal apoptosis and the pathological accumulation of p-tau and Aβin the hippocampus.展开更多
Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethyle...Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.展开更多
Objective:To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis(RA).Methods:A total of 36 patients with RA were selected,peripheral blood mononuclear cell(PBMC)and granulo...Objective:To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis(RA).Methods:A total of 36 patients with RA were selected,peripheral blood mononuclear cell(PBMC)and granulocyte were separated from venous blood.RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patieuts with RA.and detect the mRNA expression of downstream factor IL-1β.The correlation between RA and the expression of NLRP3 aud NLRP1 was analyzed.Normal 30 cases were set as control group.Results:Expression levels of NLRP1.and caspase-1mRNA in PBMC of RA group were significautly lower than those of control group(P0.05);NLRP3,caspase-1,and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group(P0.05);NLRP1,IL-1βmRNA expression level had a negative corrlation with anti-rheunatoid factor antibody(P=0.0332,0.0340).Conclusions:NLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors,and play an important role in RA inflammatory mechanisms.展开更多
AIM:To compare the effects of four Bifidobacteria strains(Bifidobacteria L66-5,L75-4,M13-4 and FS31-12,originated from normal human intestines)on weight gain,lipid metabolism,glucose metabolism in an obese murine mode...AIM:To compare the effects of four Bifidobacteria strains(Bifidobacteria L66-5,L75-4,M13-4 and FS31-12,originated from normal human intestines)on weight gain,lipid metabolism,glucose metabolism in an obese murine model induced by high-fat diet.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into six groups.Control group received standard chow,model group received high-fat diet,and intervention groups received high-fat diet added with different Bifidobacteria strains isolated from healthy volunteers'fresh feces.All rats were executed at the 6th weekend.Body weight(BW),obese indexes,oral glucose tolerance test,serum and liver lipid and serum insulin(INS)were tested.Liver lipid deposition was classif ied pathologically.RESULTS:Compared with the model group,B.M13-4 improved BW gains(264.27±26.91 vs 212.55±18.54,P=0.001)while B.L66-5 induced a decrease in BW(188.47±11.96 vs 212.55±18.54,P=0.043).The rest two strains had no significant change in BW.All the four strains can reduce serum and liver triglyceride and significantly alleviate the lipid deposition in liver.All strains showed a trend of lowing serum and liver total cholesterol while B.L66-5 and B.FS31-12 did so more significantly.In addition,all the four strains showed no significant differences in serum INS and glucose level.CONCLUSION:The response of energy metabolism to administration of Bifidobacteria is strain dependent.Different strains of Bifidobacteria might drive different directions of fat distribution.展开更多
AIM To assess the effects of extract of Buddleja officinalis on tear secretion volume,tear film stability,expressions of TGF-β1,IL-1β,TNF-αin lacrimal gland of castrated rabbits with dry eye.METHODS:A total of 30 v...AIM To assess the effects of extract of Buddleja officinalis on tear secretion volume,tear film stability,expressions of TGF-β1,IL-1β,TNF-αin lacrimal gland of castrated rabbits with dry eye.METHODS:A total of 30 victory rabbits were divided averagely into normal group(A),model group(B),therapy group with tow dose extract of Buddleja officinalis(C),therapy group with high dose extract of Buddleja officinalis(D)and therapy group with genistein(E).The dry eye model was established with orchiectomy on Group B,C,D,E.Group C,D,E were administered intragastrically with corresponding dose extract of Buddleja officinalis or genistein for 30 days.All rabbits were detected with SIT.TGF-B 1,IL-1β,TNF-a were detected with immunohistochemistry and the ultrastructure of lacrimal gland was observed under transmission electron microscope.RESULTS:The SIT value of group C,D,E were respectively 13.167±4.957,14.667±5.279,8.667±0.516,obviously higher than that of group B5.667±2.338(P<0.01).The positive expression of IL-1βin acinar cell and glandular tube cell of group C,D were 0.470±0.048,0.510±0.088,obviously lower than that of group B 0.770±0.118(P<0.01).The positive expression of TNF-aof group C,D were 0.498±0.156,0.435±0.069,obviously lower than that of group B 0.769±0.095 to0(P<0.01).The positive expression of TGF-β1 of group C,D were 0.406±0.171,0.497±0.147,obviously higher than that of group80.222±0.113(P<0.01).Any result of group C,D was positive compared with that of group E(P<0.05).Ultrastructure of the lacrimal gland of group C,D,E was well preserved,especially in D group it was remarkable.CONCLUSION:The extract of Buddleja officinalis can adjust lacrimal gland partial inflammation of dry eye.展开更多
The structure of laminar cooling control system for hot rolling was introduced and the control mode, cooling strategy, segment tracking and model recalculation were analyzed. The parameters of air/water cooling models...The structure of laminar cooling control system for hot rolling was introduced and the control mode, cooling strategy, segment tracking and model recalculation were analyzed. The parameters of air/water cooling models were optimized by regressing the data gathering in situ, and satisfactory effect was obtained. The coiling temperature can be controlled within ±15℃.展开更多
AIM:To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS:Rat hepatic fibrosis was induced by carbontet.achloride(CCI4).Forty Sprague-Dawley rats were divided randomly int...AIM:To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS:Rat hepatic fibrosis was induced by carbontet.achloride(CCI4).Forty Sprague-Dawley rats were divided randomly into 4 groups:control,model,and two treatment(PⅠ,PⅡ)groups.Except for rats in control group,all rats were given subcutaneous injection of 400 mL/L CCI4,twice a wk for 8 wk.Rats in PⅠand PⅡgroups were also treated with pioglitazone of 3 mg/kg,daily via gastrogavage beginning on the 1^st day and at the end of the 2^nd week,administration of CCI4 respectively.Liver functions(ALT,AST),serum fibrotic markers(HA,LN,PCIII)and hepatic hydroxyproline(HP)concentration were determined respectively.Histochemical staining of formalin-fixed liver sections with HE,Masson-Trichrome,and immunohistochemical staining for m-smooth muscle actin(α-SMA)were performed.Modified Knodell and Chevallier semi-quantitative scoring system(SSS)was used to evaluate necroinflammatory activity and fibrosis degree.RESULTS:Compared with model group,pioglitazone significantly reduced the serum levels of ALT,AST,HA,LN and PCⅢ(P<0.05 or<0.01).The HP concentrations in PⅠ(210.90±24.07μg/g),and PⅡ(257.36±30.55μg/g)groups were also lower than those in model group(317.80±36.44)μg/g)(P<0.01).Histologic examination showed that PⅠand PⅡgroups had milder hepatocellular degeneration,necrosis and infiltration of inflammatory cells,and thinner or less fibrotic septa than did model group.The scores for necroinflammation in P(2.80±1.03),and PⅡ(3.00±1.05)groups were significantly reduced as compared with model group(4.88±2.30)(P<0.05 or<0.01);the fibrosis scores in PⅠ(3.40±1.65),and PⅡ(4.60±1.35)groups were also markedly lower than those in model group(7.00±3.21)(P<0.05 or<0.01).Immunohistochemical staining showed that expression ofα-SMA in PⅠand PⅡgroups was ameliorated dramatically compared with model group.CONCLUSION:PPARγ,agonist pioglitazone greatly retards the progression of rat hepatic fibrosis induced by CCI4 through inhibition of HSC activation and amelioration of hepatocyte necroinflammation in rats.展开更多
AIM:To develop a new decellularization method depended upon the natural corneal structure and to harvest an ideal scaffold with good biocompatibilities for corneal reconstruction.METHODS:The acellular cornea matrix(AC...AIM:To develop a new decellularization method depended upon the natural corneal structure and to harvest an ideal scaffold with good biocompatibilities for corneal reconstruction.METHODS:The acellular cornea matrix(ACM)were prepared from de-epithelium fresh porcine corneas(DFPCs)by incubation with 100%fresh human sera and additional electrophoresis at 4℃.Human corneal epithelial cells(HCEs)were used for the cytotoxicity tests of ACM.ACM were implanted into the Enhanced Green Fluorecence Protein(eGFP)transgenic mouse anterior chamber for evaluation of histocompatibility.RESULTS:HE and GSIB4 results showed fresh porcine cornea matrix with 100%human sera and electrophoresis could entirely decellularize stromal cell without reducing its transparency.ACM has no cytotoxic effect ex vivo.Animal test showed there was no rejection for one month after surgery.CONCLUSION:These results provide a decellularizing approach for the study of corneal tissue engineering and had the broader implications for the field of biological tissue engineering in other engineered organ or tissue matrix.展开更多
The spatial-temporal bifurcation for Kadomtsev-Petviashvili (KP) equations is considered. Exact two-soliton solution and doubly periodic solution to the KP-I equation, and two classes of periodic soliton solutions i...The spatial-temporal bifurcation for Kadomtsev-Petviashvili (KP) equations is considered. Exact two-soliton solution and doubly periodic solution to the KP-I equation, and two classes of periodic soliton solutions in different directions to KP-Ⅱ are obtained using the bilinear form, homoclinic test technique and temporal and 1 spatial transformation method, respectively. The equilibrium solution uo =-1/6, a unique spatial-temporal bifurcation which is periodic bifurcation for KP-I and deflexion of soliton for KP-Ⅱ, is investigated.展开更多
Objective: To study the disruption of co- localization of human Daxx(hDaxx) with promyelocytic leukemia protein(PML) at the PML oncogenic domains (PODs) by the interaction of hDaxx with adenovirus(Ad) 12 E1B 55 Kiloda...Objective: To study the disruption of co- localization of human Daxx(hDaxx) with promyelocytic leukemia protein(PML) at the PML oncogenic domains (PODs) by the interaction of hDaxx with adenovirus(Ad) 12 E1B 55 Kilodalton Oncoprotein (Ad12 E1B 55kD). Methods: The direct binding reaction of hDaxx and Ad12 E1B 55kD was analyzed by coimmunoprecipitation and Western blotting in vivo or in vitro. The interaction of hDaxx with Ad12 E1B 55kD was studied using yeast two-hybrid assay. Results: hDaxx bounded directly to Ad12 E1B 55kD in vivo and in vitro. hDaxx interacted with full length Ad12 E1B 55kD. Conclusion: Transcriptional regulator hDaxx directly binds to and interacts with Ad12 E1B 55kD.展开更多
A novel determination method of Ag^+ was established. In acetic acid-sodium acetate buffer (pH 5.0) medium, Ag^+ reacts with SCN^- to form AgSCN in the presence of TritonX-100,which results in an increase of reson...A novel determination method of Ag^+ was established. In acetic acid-sodium acetate buffer (pH 5.0) medium, Ag^+ reacts with SCN^- to form AgSCN in the presence of TritonX-100,which results in an increase of resonance light scattering (RLS)and giving a new RLS spectrum.The maximum RLS peak was at 585 nm,The enhancement of resonance light scattering at 585 nm was proportional to the concentration of Ag^+ ranging from 0.0045-4.00μg mL^-1 (r=9991),and the detection limit was 1.37 ng mL^-1 with the recovery of 97.70%- 104.80%。展开更多
In this paper,by making use of the calculous technique and some results of the impulsive differential inequality,oscillatory properties of the solutions of certain nonlinear impulsive delay hyperbolic partial differen...In this paper,by making use of the calculous technique and some results of the impulsive differential inequality,oscillatory properties of the solutions of certain nonlinear impulsive delay hyperbolic partial differential equations with nonlinear diffusion coefficient are investigated.Sufficient conditions for oscillations of such equations are obtained.展开更多
Objective: To investigate the regulation effects on LPS-mediated cytokine secretion and dexamethasone- induced apoptosis in macrophages by transient overexpression of hDaxx. Methods: An eukaryotic expression vector pE...Objective: To investigate the regulation effects on LPS-mediated cytokine secretion and dexamethasone- induced apoptosis in macrophages by transient overexpression of hDaxx. Methods: An eukaryotic expression vector pEGFP/hDaxx, which could express a fusion protein GFP-Daxx, was transfected into macrophages. The expression and localization of GFP-hDaxx fusion protein was analyzed by fluorescent microscope and western blot. The effects of transient overexpression of GFP-hDaxx fusion protein on the lipopolysaccharide(LPS)-mediated secretion of TNF-α and IL-1β were determined by ELISA. Moreover, the dexamethasone-induced apoptosis was determined morphologically by Giemsa stain. Results: The results observed showed that GFP-hDaxx fusion protein overexpressed in macrophages and localized in nuclei but GFP in cytoplasm under fluorescent microscope. The overexpression of GFP-hDaxx fusion protein could be detected by Western blot with an antibody against C-terminal of hDaxx. In the group with overexpressed GFP-hDaxx fusion protein, the LPS-mediated cytokine secretion decreased remarkably at 1 h, 3 h, 6 h respectively after LPS stimulation, and the dexamethasone- induced apoptosis reduced notably at 6 h, 12 h and 24 h respectively after addition of dexamethasone. There were remarkable difference between pEGFP/hDaxx group and control group (P<0.01) at different time. Conclusion: Transient overexpression of hDaxx down-regulates LPS-mediated cytokine secretion in macrophages and inhibits dexamethasone-induced macrophages apoptosis.展开更多
AIM:To determine the effects of a low dose latrunculin(LAT)-A on dexamethasone(Dex)-induced upregulation of extracellular matrix proteins fibronectin(FN)in cultured human trabecular meshwork(HTM)cells.METHODS:HTM cell...AIM:To determine the effects of a low dose latrunculin(LAT)-A on dexamethasone(Dex)-induced upregulation of extracellular matrix proteins fibronectin(FN)in cultured human trabecular meshwork(HTM)cells.METHODS:HTM cells were cultured to confluent and incubated with 0.4 mu mol/L Dex and/or 0.05 mu mol/L LAT-A.FN expression in HTM cells was evaluated by Western blot and immunofluorescence microscopy.RESULTS:Dex up-regulated FN production in HTM cells,failed to do so when co-incubated with LAT-A.LAT-A decreased production of FN in cultured HTM cells.CONCLUSION:This study indicated that LAT-A may modulate the expression of fibronectin in trabecular meshwork to achieve treatment for steroids and other types of glaucoma.It has an important prospect as an intraocular pressure-lowering drug.展开更多
Mycoplamas are a group of wall-less prokaryotes widely distributed in nature, some of which are pathogenic for humans and animals. There are many lipoproteins anchored on the outer face of the plasma membrane, called ...Mycoplamas are a group of wall-less prokaryotes widely distributed in nature, some of which are pathogenic for humans and animals. There are many lipoproteins anchored on the outer face of the plasma membrane, called lipid-associated membrane proteins (LAMPs). LAMPs are highly antigenic and could undergo phase and size variation, and are recognized by the innate immune system through Toll-like receptors (TLR) 2 and 6. LAMPs can modulate the immune system, and could induce immune cells apoptosis or death. In addition, they may associate with malignant transformation of host cells and are also con-sidered to be cofactors in the progression of AIDS.展开更多
AIM:To isolate and analyze the DNA sequences which are methylated differentially between gastric cancer and normal gastric mucosa. METHODS: The differentially methylated DNA sequences between gastric cancer and normal...AIM:To isolate and analyze the DNA sequences which are methylated differentially between gastric cancer and normal gastric mucosa. METHODS: The differentially methylated DNA sequences between gastric cancer and normal gastric mucosa were isolated by methylation-sensitive representational difference analysis (MS-RDA). Similarities between the separated fragments and the human genomic DNA were analyzed with Basic Local Alignment Search Tool (BLAST). RESULTS: Three differentially methylated DNA sequences were obtained, two of which have been accepted by GenBank. The accession numbers are AY887106 and AY887107. AY887107 was highly similar to the 11th exon of LOC440683 (98%), 3' end of LOC440887 (99%), and promoter and exon regions of DRD5 (94%). AY887106 was consistent (98%) with a CpG island in ribosomal RNA isolated from colorectal cancer by Minoru Toyota in 1999. CONCLUSION: The methylation degree is different between gastric cancer and normal gastric mucosa. The differentially methylated DNA sequences can be isolated effectively by MS-RDA.展开更多
Trace elements were determined in high purity gold by high resolution inductively coupled plasma mass spectrometry(HR-ICP-MS).Sample were decomposed by aqua regia.To overcome some potentially problematic spectra/inter...Trace elements were determined in high purity gold by high resolution inductively coupled plasma mass spectrometry(HR-ICP-MS).Sample were decomposed by aqua regia.To overcome some potentially problematic spectra/interference,measurements were acquired in both medium and high resolution modes.The matrix effects due to the presence of excessive HCl and Au were evaluated.The optimum conditions for the determination was tested and discussed.The standard addition method was employed for quantitative analysis.The detection limits range from 0.01ug/g to 0.28ug/g depending on the elements.The method is accurate,quick and convenient.It has been applied to the determination of trace elements in high purity gold with satisfactory results.展开更多
Current design method for circular sliding slopes is not so reasonable that it often results in slope (sliding.) As a result, artificial neural network (ANN) is used to establish an artificial neural network based inv...Current design method for circular sliding slopes is not so reasonable that it often results in slope (sliding.) As a result, artificial neural network (ANN) is used to establish an artificial neural network based inverse design method for circular sliding slopes. A sample set containing 21 successful circular sliding slopes excavated in the past is used to train the network. A test sample of 3 successful circular sliding slopes excavated in the past is used to test the trained network. The test results show that the ANN based inverse design method is valid and can be applied to the design of circular sliding slopes.展开更多
基金Supported by Natural Science Foundation of Hunan Province(No.2023JJ60373).
摘要●AIM:To identify early molecular diagnostic biomarkers for optic atrophy(OPA)and explore potential mechanisms mediated by proteins.●METHODS:Gene expression data was sourced from eQTLGen(31684 samples;19960 genes).The OPA discovery cohort came from FinnGen(629 cases;496621 controls);the validation cohort came from the genome-wide association studies(GWAS)catalog(58 cases;496621 controls).Protein data for mediation analysis was obtained from the deCODE Genetics consortium(35559 samples;4907 proteins).Causal estimates were derived using twosample Mendelian randomization(MR).Inverse-variance weighted(IVW)was the primary analysis method.Sensitivity analyses included MR-Egger intercept,Cochran’s Q test for heterogeneity,and leave-one-out analysis.Colocalization analysis validated identified genes.Additionally,interaction analysis identified potential biomarkers.Finally,mediation analysis assessed potential mediating mechanisms.●RESULTS:Multi-cohort validation revealed that increased expression levels of the SEC61A2 and THNSL2 were causally associated with an elevated risk of OPA.Furthermore,we identified 386 genes potentially associated with OPA.Hormone secretion and immune-related pathways were found to play significant roles in OPA pathogenesis.Mediation analysis indicated that Upper zone of growth plate and cartilage matrix associated(UCMA)potentially mediates the effect of SEC61A2 in increasing OPA risk.●CONCLUSION:SEC61A2 and THNSL2 may serve as early diagnostic biomarkers for OPA.Additionally,SEC61A2 likely increases OPA risk through UCMA.
基金Supported by the Scientific Research Project of Hunan Provincial Health Commission,No.202203012538。
摘要BACKGROUND Arteriovenous fistula is a rare cause of refractory heart failure,and corrective measures may lead to dramatic improvement;however,the long-term cardiac remodeling outcomes,particularly after delayed closure,remain unclear.CASE SUMMARY A 57-year-old man was admitted to the hospital with complaints of exertional dyspnea for more than 10 years.Physical examination revealed wet crackles in the lungs and a continuous machinery murmur in the left lower back and groin area.Asymmetric edema and varicose veins were observed in the lower limbs.Echocar-diography revealed a dilated right ventricle with severe pulmonary hypertension.Computed tomography revealed a left common iliac arteriovenous fistula linked to prior lumbar disc surgery.Surgical repair resolved the symptoms,with echo-cardiography at 4 months showing a reduced right atrium(RA)and ventricular(RV)diameter and tricuspid regurgitation.However,during the 2-year follow-up,gradual RA and RV re-expansion(from 35 mm to 51 mm and from 26 mm to 46 mm,respectively)was observed,despite sustained clinical stability.CONCLUSION This case highlights that delayed arteriovenous fistula closure may result in in-complete right heart reverse remodeling,even after symptomatic relief.Potential mechanisms include persistent hemodynamic stress from subclinical residual shunting or functional impairment due to chronic volume overload.Early inter-vention before irreversible right heart damage is critical for optimal outcomes.
基金financially supported by the Humanities and Social Sciences Research Planning Fund of the Ministry of Education(Grant No.22YJA880086)the Natural Science Foundation of Hunan Province(Grant No.2025JJ70621)+3 种基金the Hunan Provincial Natural Science and Technology Foundation(Grant No.2021JJ30595)Additional support was provided by the Hunan Provincial Graduate Research Innovation Projects(Grant No.CX20211061 and CX20231065)several grants from Jishou University,including campus-level research projects(Grant No.Jdzd21028,Jdzd21004,Jdzd2211,and Jdy22188)the Graduate Base Opening Project(Grant No.TYBJD202303).
摘要Recent studies have demonstrated that dihydromyricetin(DHM)exerts a protective effect against central nervous system injury.Building on these findings,the present study aimed to investigate whether DHM could ameliorate cognitive deficits in a type 2 diabetes mellitus(T2DM)rat model,and to explore whether this effect involved inhibition of the JNK signaling pathway and suppression of endoplasmic reticulum stress(ERS).To establish the T2DM model,Sprague Dawley(SD)rats were fed a high-fat,high-sugar diet in combination with a single intraperitoneal injection of streptozotocin(STZ).Fasting blood glucose levels were measured from tail vein samples,and cognitive performance was evaluated using the Morris water maze(MWM)and Y-maze tests.Following behavioral assessments,the animals were sacrificed by cervical dislocation,and hippocampal tissues were collected for further analysis.Histological examination using hematoxylin-eosin(H&E)staining was performed to assess hippocampal neuronal damage.Western blotting(WB)analysis was employed to quantify the expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2,while ELISA was conducted to measure levels of phosphorylated tau(p-tau)and amyloid-β(Aβ)in the hippocampus.After 12 weeks of oral administration of DHM(250 mg/kg/d),relevant biomarkers were re-evaluated to determine the compound's impact on cognitive function and hippocampal integrity.Additionally,rats from each group received intracerebroventricular injections of various pharmacological agents,namely,TUDCA(an ERS inhibitor),STZ,SP600125(a JNK inhibitor),and anisomycin(AMY,a JNK activator).WB analysis was further conducted to assess the expression of JNK,phosphorylated JNK(p-JNK),and ERS-associated proteins Bip and p-PERK in hippocampal tissue.The results confirmed that combining a high-fat,high-sugar diet with low-dose STZ injection for 4 weeks effectively established a T2DM model.Compared with the control group,T2DM rats exhibited significant cognitive deficits,increased neuronal apoptosis in the hippocampus,and elevated hippocampal levels of p-tau and Aβ.Notably,DHM treatment markedly reversed these pathological changes in T2DM rats,whereas it had no significant effects on control animals.Moreover,administration of TUDCA and SP600125 similarly mitigated cognitive impairment,neuronal apoptosis,and the accumulation of p-tau and Aβin diabetic rats.Conversely,activation of ERS and JNK signaling using tunicamycin(TUN)and AMY,respectively,resulted in exacerbated cognitive decline,increased neuronal apoptosis,and higher levels of p-tau and Aβ.In conclusion,these findings suggested that DHM effectively alleviated cognitive dysfunction in T2DM rats,potentially through the inhibition of JNK signaling and subsequent attenuation of ERS,thereby reducing neuronal apoptosis and the pathological accumulation of p-tau and Aβin the hippocampus.
摘要Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.
基金supported by National Natural Science Fund of China(31300156)
摘要Objective:To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis(RA).Methods:A total of 36 patients with RA were selected,peripheral blood mononuclear cell(PBMC)and granulocyte were separated from venous blood.RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patieuts with RA.and detect the mRNA expression of downstream factor IL-1β.The correlation between RA and the expression of NLRP3 aud NLRP1 was analyzed.Normal 30 cases were set as control group.Results:Expression levels of NLRP1.and caspase-1mRNA in PBMC of RA group were significautly lower than those of control group(P0.05);NLRP3,caspase-1,and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group(P0.05);NLRP1,IL-1βmRNA expression level had a negative corrlation with anti-rheunatoid factor antibody(P=0.0332,0.0340).Conclusions:NLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors,and play an important role in RA inflammatory mechanisms.
摘要AIM:To compare the effects of four Bifidobacteria strains(Bifidobacteria L66-5,L75-4,M13-4 and FS31-12,originated from normal human intestines)on weight gain,lipid metabolism,glucose metabolism in an obese murine model induced by high-fat diet.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into six groups.Control group received standard chow,model group received high-fat diet,and intervention groups received high-fat diet added with different Bifidobacteria strains isolated from healthy volunteers'fresh feces.All rats were executed at the 6th weekend.Body weight(BW),obese indexes,oral glucose tolerance test,serum and liver lipid and serum insulin(INS)were tested.Liver lipid deposition was classif ied pathologically.RESULTS:Compared with the model group,B.M13-4 improved BW gains(264.27±26.91 vs 212.55±18.54,P=0.001)while B.L66-5 induced a decrease in BW(188.47±11.96 vs 212.55±18.54,P=0.043).The rest two strains had no significant change in BW.All the four strains can reduce serum and liver triglyceride and significantly alleviate the lipid deposition in liver.All strains showed a trend of lowing serum and liver total cholesterol while B.L66-5 and B.FS31-12 did so more significantly.In addition,all the four strains showed no significant differences in serum INS and glucose level.CONCLUSION:The response of energy metabolism to administration of Bifidobacteria is strain dependent.Different strains of Bifidobacteria might drive different directions of fat distribution.
基金National Natural Science Foundation of China(No.30772824)Special Fund from Doctoral Program in Colleges and Universities Affiliated to Ministry of Education,China(No.200805410004)+2 种基金Natural Science Fund of Hunan Province of China(No.07JJ3049)Science&Technology Department of Hunan Province fund of China(No.2009FJ3001)Graduate student's innovative fund of Hunan Province of 2008,China(2008 No.68)
摘要AIM To assess the effects of extract of Buddleja officinalis on tear secretion volume,tear film stability,expressions of TGF-β1,IL-1β,TNF-αin lacrimal gland of castrated rabbits with dry eye.METHODS:A total of 30 victory rabbits were divided averagely into normal group(A),model group(B),therapy group with tow dose extract of Buddleja officinalis(C),therapy group with high dose extract of Buddleja officinalis(D)and therapy group with genistein(E).The dry eye model was established with orchiectomy on Group B,C,D,E.Group C,D,E were administered intragastrically with corresponding dose extract of Buddleja officinalis or genistein for 30 days.All rabbits were detected with SIT.TGF-B 1,IL-1β,TNF-a were detected with immunohistochemistry and the ultrastructure of lacrimal gland was observed under transmission electron microscope.RESULTS:The SIT value of group C,D,E were respectively 13.167±4.957,14.667±5.279,8.667±0.516,obviously higher than that of group B5.667±2.338(P<0.01).The positive expression of IL-1βin acinar cell and glandular tube cell of group C,D were 0.470±0.048,0.510±0.088,obviously lower than that of group B 0.770±0.118(P<0.01).The positive expression of TNF-aof group C,D were 0.498±0.156,0.435±0.069,obviously lower than that of group B 0.769±0.095 to0(P<0.01).The positive expression of TGF-β1 of group C,D were 0.406±0.171,0.497±0.147,obviously higher than that of group80.222±0.113(P<0.01).Any result of group C,D was positive compared with that of group E(P<0.05).Ultrastructure of the lacrimal gland of group C,D,E was well preserved,especially in D group it was remarkable.CONCLUSION:The extract of Buddleja officinalis can adjust lacrimal gland partial inflammation of dry eye.
基金ItemSponsored by National Natural Science Foundation of China (50104004)
摘要The structure of laminar cooling control system for hot rolling was introduced and the control mode, cooling strategy, segment tracking and model recalculation were analyzed. The parameters of air/water cooling models were optimized by regressing the data gathering in situ, and satisfactory effect was obtained. The coiling temperature can be controlled within ±15℃.
摘要AIM:To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS:Rat hepatic fibrosis was induced by carbontet.achloride(CCI4).Forty Sprague-Dawley rats were divided randomly into 4 groups:control,model,and two treatment(PⅠ,PⅡ)groups.Except for rats in control group,all rats were given subcutaneous injection of 400 mL/L CCI4,twice a wk for 8 wk.Rats in PⅠand PⅡgroups were also treated with pioglitazone of 3 mg/kg,daily via gastrogavage beginning on the 1^st day and at the end of the 2^nd week,administration of CCI4 respectively.Liver functions(ALT,AST),serum fibrotic markers(HA,LN,PCIII)and hepatic hydroxyproline(HP)concentration were determined respectively.Histochemical staining of formalin-fixed liver sections with HE,Masson-Trichrome,and immunohistochemical staining for m-smooth muscle actin(α-SMA)were performed.Modified Knodell and Chevallier semi-quantitative scoring system(SSS)was used to evaluate necroinflammatory activity and fibrosis degree.RESULTS:Compared with model group,pioglitazone significantly reduced the serum levels of ALT,AST,HA,LN and PCⅢ(P<0.05 or<0.01).The HP concentrations in PⅠ(210.90±24.07μg/g),and PⅡ(257.36±30.55μg/g)groups were also lower than those in model group(317.80±36.44)μg/g)(P<0.01).Histologic examination showed that PⅠand PⅡgroups had milder hepatocellular degeneration,necrosis and infiltration of inflammatory cells,and thinner or less fibrotic septa than did model group.The scores for necroinflammation in P(2.80±1.03),and PⅡ(3.00±1.05)groups were significantly reduced as compared with model group(4.88±2.30)(P<0.05 or<0.01);the fibrosis scores in PⅠ(3.40±1.65),and PⅡ(4.60±1.35)groups were also markedly lower than those in model group(7.00±3.21)(P<0.05 or<0.01).Immunohistochemical staining showed that expression ofα-SMA in PⅠand PⅡgroups was ameliorated dramatically compared with model group.CONCLUSION:PPARγ,agonist pioglitazone greatly retards the progression of rat hepatic fibrosis induced by CCI4 through inhibition of HSC activation and amelioration of hepatocyte necroinflammation in rats.
基金National Natural Science Foundation of China(No.81160118,81100648,81101858,81100649)Natural Science Foundation of Jiangxi Province,China(No.20114BAB215029)+3 种基金Technology Foundation of Jiangxi Province,China(No.20111BBG70026-2)Health Department Science and Technology Foundation,China(No.20121026)Education Department Youth Scientific Research Foundation,China(No.JJJ12158)National High Technology Research of China(863 project)(No.2006AA02A131)
摘要AIM:To develop a new decellularization method depended upon the natural corneal structure and to harvest an ideal scaffold with good biocompatibilities for corneal reconstruction.METHODS:The acellular cornea matrix(ACM)were prepared from de-epithelium fresh porcine corneas(DFPCs)by incubation with 100%fresh human sera and additional electrophoresis at 4℃.Human corneal epithelial cells(HCEs)were used for the cytotoxicity tests of ACM.ACM were implanted into the Enhanced Green Fluorecence Protein(eGFP)transgenic mouse anterior chamber for evaluation of histocompatibility.RESULTS:HE and GSIB4 results showed fresh porcine cornea matrix with 100%human sera and electrophoresis could entirely decellularize stromal cell without reducing its transparency.ACM has no cytotoxic effect ex vivo.Animal test showed there was no rejection for one month after surgery.CONCLUSION:These results provide a decellularizing approach for the study of corneal tissue engineering and had the broader implications for the field of biological tissue engineering in other engineered organ or tissue matrix.
基金Supported by the National Natural Science Foundation of China under Grant Nos 10361007 and 10661002, the Yunnan Natural Science Foundation (No 2004A0001M), and The IMS, CUHK.
摘要The spatial-temporal bifurcation for Kadomtsev-Petviashvili (KP) equations is considered. Exact two-soliton solution and doubly periodic solution to the KP-I equation, and two classes of periodic soliton solutions in different directions to KP-Ⅱ are obtained using the bilinear form, homoclinic test technique and temporal and 1 spatial transformation method, respectively. The equilibrium solution uo =-1/6, a unique spatial-temporal bifurcation which is periodic bifurcation for KP-I and deflexion of soliton for KP-Ⅱ, is investigated.
基金This work was supported by grants from Ministry of Education of P.R. China (No. 2000-65).
摘要Objective: To study the disruption of co- localization of human Daxx(hDaxx) with promyelocytic leukemia protein(PML) at the PML oncogenic domains (PODs) by the interaction of hDaxx with adenovirus(Ad) 12 E1B 55 Kilodalton Oncoprotein (Ad12 E1B 55kD). Methods: The direct binding reaction of hDaxx and Ad12 E1B 55kD was analyzed by coimmunoprecipitation and Western blotting in vivo or in vitro. The interaction of hDaxx with Ad12 E1B 55kD was studied using yeast two-hybrid assay. Results: hDaxx bounded directly to Ad12 E1B 55kD in vivo and in vitro. hDaxx interacted with full length Ad12 E1B 55kD. Conclusion: Transcriptional regulator hDaxx directly binds to and interacts with Ad12 E1B 55kD.
摘要A novel determination method of Ag^+ was established. In acetic acid-sodium acetate buffer (pH 5.0) medium, Ag^+ reacts with SCN^- to form AgSCN in the presence of TritonX-100,which results in an increase of resonance light scattering (RLS)and giving a new RLS spectrum.The maximum RLS peak was at 585 nm,The enhancement of resonance light scattering at 585 nm was proportional to the concentration of Ag^+ ranging from 0.0045-4.00μg mL^-1 (r=9991),and the detection limit was 1.37 ng mL^-1 with the recovery of 97.70%- 104.80%。
基金Supported by the Natural Science Foundation of China(10471086)Supported by the Science Research Foundation of Department of Education of Hunan Province(07C164)
摘要In this paper,by making use of the calculous technique and some results of the impulsive differential inequality,oscillatory properties of the solutions of certain nonlinear impulsive delay hyperbolic partial differential equations with nonlinear diffusion coefficient are investigated.Sufficient conditions for oscillations of such equations are obtained.
基金This work was supported by a grant from theEducation Committee of Hunan Province(No.02C391)
摘要Objective: To investigate the regulation effects on LPS-mediated cytokine secretion and dexamethasone- induced apoptosis in macrophages by transient overexpression of hDaxx. Methods: An eukaryotic expression vector pEGFP/hDaxx, which could express a fusion protein GFP-Daxx, was transfected into macrophages. The expression and localization of GFP-hDaxx fusion protein was analyzed by fluorescent microscope and western blot. The effects of transient overexpression of GFP-hDaxx fusion protein on the lipopolysaccharide(LPS)-mediated secretion of TNF-α and IL-1β were determined by ELISA. Moreover, the dexamethasone-induced apoptosis was determined morphologically by Giemsa stain. Results: The results observed showed that GFP-hDaxx fusion protein overexpressed in macrophages and localized in nuclei but GFP in cytoplasm under fluorescent microscope. The overexpression of GFP-hDaxx fusion protein could be detected by Western blot with an antibody against C-terminal of hDaxx. In the group with overexpressed GFP-hDaxx fusion protein, the LPS-mediated cytokine secretion decreased remarkably at 1 h, 3 h, 6 h respectively after LPS stimulation, and the dexamethasone- induced apoptosis reduced notably at 6 h, 12 h and 24 h respectively after addition of dexamethasone. There were remarkable difference between pEGFP/hDaxx group and control group (P<0.01) at different time. Conclusion: Transient overexpression of hDaxx down-regulates LPS-mediated cytokine secretion in macrophages and inhibits dexamethasone-induced macrophages apoptosis.
基金National Natural Science Foundation of China(No.30772379)Education Department Project of Hunan Province,China(No.04A049)
摘要AIM:To determine the effects of a low dose latrunculin(LAT)-A on dexamethasone(Dex)-induced upregulation of extracellular matrix proteins fibronectin(FN)in cultured human trabecular meshwork(HTM)cells.METHODS:HTM cells were cultured to confluent and incubated with 0.4 mu mol/L Dex and/or 0.05 mu mol/L LAT-A.FN expression in HTM cells was evaluated by Western blot and immunofluorescence microscopy.RESULTS:Dex up-regulated FN production in HTM cells,failed to do so when co-incubated with LAT-A.LAT-A decreased production of FN in cultured HTM cells.CONCLUSION:This study indicated that LAT-A may modulate the expression of fibronectin in trabecular meshwork to achieve treatment for steroids and other types of glaucoma.It has an important prospect as an intraocular pressure-lowering drug.
基金Project (No. 30570093) supported by the National Natural ScienceFoundation of China
摘要Mycoplamas are a group of wall-less prokaryotes widely distributed in nature, some of which are pathogenic for humans and animals. There are many lipoproteins anchored on the outer face of the plasma membrane, called lipid-associated membrane proteins (LAMPs). LAMPs are highly antigenic and could undergo phase and size variation, and are recognized by the innate immune system through Toll-like receptors (TLR) 2 and 6. LAMPs can modulate the immune system, and could induce immune cells apoptosis or death. In addition, they may associate with malignant transformation of host cells and are also con-sidered to be cofactors in the progression of AIDS.
基金The Key Project Fund of the Science and Technology Program of Hunan Province, No. 04SK1004the Scientific Research Fund of Educational Department, Hunan Province, No. 99C195
摘要AIM:To isolate and analyze the DNA sequences which are methylated differentially between gastric cancer and normal gastric mucosa. METHODS: The differentially methylated DNA sequences between gastric cancer and normal gastric mucosa were isolated by methylation-sensitive representational difference analysis (MS-RDA). Similarities between the separated fragments and the human genomic DNA were analyzed with Basic Local Alignment Search Tool (BLAST). RESULTS: Three differentially methylated DNA sequences were obtained, two of which have been accepted by GenBank. The accession numbers are AY887106 and AY887107. AY887107 was highly similar to the 11th exon of LOC440683 (98%), 3' end of LOC440887 (99%), and promoter and exon regions of DRD5 (94%). AY887106 was consistent (98%) with a CpG island in ribosomal RNA isolated from colorectal cancer by Minoru Toyota in 1999. CONCLUSION: The methylation degree is different between gastric cancer and normal gastric mucosa. The differentially methylated DNA sequences can be isolated effectively by MS-RDA.
基金Funded by the Hunan Provincial Natural Science Foundation of China(No.05JJ40017)Hunan Provincial Education Department of China(No.07C029,08C260)
摘要Trace elements were determined in high purity gold by high resolution inductively coupled plasma mass spectrometry(HR-ICP-MS).Sample were decomposed by aqua regia.To overcome some potentially problematic spectra/interference,measurements were acquired in both medium and high resolution modes.The matrix effects due to the presence of excessive HCl and Au were evaluated.The optimum conditions for the determination was tested and discussed.The standard addition method was employed for quantitative analysis.The detection limits range from 0.01ug/g to 0.28ug/g depending on the elements.The method is accurate,quick and convenient.It has been applied to the determination of trace elements in high purity gold with satisfactory results.
摘要Current design method for circular sliding slopes is not so reasonable that it often results in slope (sliding.) As a result, artificial neural network (ANN) is used to establish an artificial neural network based inverse design method for circular sliding slopes. A sample set containing 21 successful circular sliding slopes excavated in the past is used to train the network. A test sample of 3 successful circular sliding slopes excavated in the past is used to test the trained network. The test results show that the ANN based inverse design method is valid and can be applied to the design of circular sliding slopes.