Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.

Aim To investigate the effect of recombi-nant glycoprotein hormone β5/α2(rCGH)on lipolysis in 3T3-L1 adipocytes,and explore the underlying mechanism.Methods 3T3-L1 preadipocytes were cultured and induced to differentiate into mature adipo-cytes,then treated with different concentrations of rCGH for 24 h in vitro.Cell viability of 3T3-L1 adipo-cytes was evaluated by CCK-8 assay,the levels of in-tracellular triglyceride(TG)and glycerol in the culture supernatant were measured by enzymatic method,and the changes of lipid droplets were observed by oil red O staining.The expression levels of HSL and ATGL lipo-lytic proteins in adipocytes were detected by Western blot.To carry out the intervention experiment with dif-ferent concentrations of rCGH with or without the PKA inhibitor,H89,on the mature 3T3-L1 adipocytes,the cultured cells were divided into the control group,H89 pre treatment group,1 μmol·L-1 rCGH group,and(1 μmol·L-1 rCGH+H89)combined intervention group.The contents of intracellular TG and free glycer-ol were measured by enzymatic method,and the ex-pression of CREB and lipolysis-related proteins was de-tected using Western blot.Results Different concen-trations of rCGH(0.25,0.5,1,and 2 μmol·L-1)had no significant effect on the cell viability of adipo-cytes(P＞0.05).Compared with the control group,the treatment with rCGH significantly decreased the size of lipid droplets and intracellular TG content,while significantly elevated glycerol concentration in cell supernatant.rCGH treatment also stimulated the protein expression of p-HSL,ATGL,and p-PKA.In addition,the addition of a PKA inhibitor,H89,atten-uated the effects of rCGH on free glycerol level,intra-cellular TG content,and the expression of p-HSL,p-PLIN1,and p-CREB.Conclusions rCGH enhances the lipolysis of 3T3-L1 adipocytes by up-regulating the activities of HSL,ATGL and PKA,promoting glycerol release,inhibiting TG synthesis and lipid accumula-tion,and its mechanism of action is related to the acti-vation of cAMP/PKA/CREB signaling pathway.

Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.

Aim To observe the changes in hippocam-pal 2A subunit of N-methyl-D-aspartate receptor(NR2A)before and after the learning and memory training,and then investigate the neuropharmacological effects of NR2A by microinjection of NVP-AAM077(NR2A specific antagonist)into the hippocampal den-teta gyrus,based on the spatial learning and memory behavior paradigm induced by Mirror water maze train-ing.Methods Three-month old SD rats were random-ly divided into the training and non-training group,and the rats in the two groups were randomly divided into control group and NVP-AAM077 group(NVP).The expressions of NR2A,brain-derived neurotrophic factor(BDNF),transcriptional activator 4(ATF4)and eu-karyotic transcription initiation factor 2 α(eIF2α)phosphorylation levels in denteta gyrus were detected by Western blot.Then,integrated stress response in-hibitor ISRIB was microinjected into the dentate gyrus after the NVP,the expression of ATF4 and p-eIF2αlevels,and the spatial memory abilities were detected.Results Compared with non-training,behavioral training promoted the expression of NR2A and BDNF of rats in denteta gyrus,and this effect could be inhibi-ted by NVP,which significantly increased the expres-sion of p-eIF2α and ATF4.Injection of ISRIB into denteta gyrus significantly inhibited the expression of ATF4,and reversed the spatial memory impairment caused by NVP.Conclusion NVP-induced hipp-ocampal dentate gyrus NR2A-mediated spatial learning and memory impairment in rats may be related to hipp-ocampal integrated stress response.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P＜0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P＜0.05),and improve inflammation and de-myelination of spinal cords(P＜0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P＜0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.

Objective To compare the efficacy of renal proximal renal artery denervation(pRDN)and full-length renal artery denervation(fRDN)for treatment of hypertension.Methods Fifty-six hypertensive patients were enrolled and randomly assigned to full-length renal artery denervation group(n=25)and proximal renal artery denervation group(n=31).After the procedure,24-hour ambulatory blood pressure monitoring(24 h-ABPM)at 6 months and office blood pressure at 12 months was recorded for statistical analysis.Results The blood pressure at follow-up reduced significantly in both groups,while there was no significant difference between groups.The baseline office blood pressure in fRDN group and pRDN group was(180±15)/(104±10)mmHg and(180±12)/(103±8)mmHg,respectively,which decreased to(142±9)/(82±7)mmHg and(143±10)/(83±6)mmHg at 12 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).The baseline 24 h-ABPM in the two groups was(162±13)/(95±8)mmHg and(160±12)/(94±8)mmHg,respectively,which decreased to(142±11)/(83±7)mmHg and(141±8)/(81±7)mmHg at 6 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).However,there was no significant difference in the reduction of office blood pressure and ambulatory blood pressure between the two groups.No treatment-related adverse events were observed.Conclusions pRDN has similar antihypertensive effect to fRDN.

The prevalence of Lyme disease in endogenous populations in Urumqi,Xinjiang was investigated.In total,795 serum samples were collected from residents of three townships in the surrounding area of Urumqi City from 2022 to 2023,which included 383 from Lucaogou Town,145 from Shuixigou Town,and,267 from Tori Township.Serum levels of IgG and IgM antibodies were screened with an enzyme linked immunosorbent assay(ELISA)and confirmed by western blot(WB)analysis.Clinical data of WB-positive indi-viduals were collected and comprehensive analysis was con-ducted for case diagnosis.The chi square test was used for statistical analysis of the results and the P＜0.05 was consid-ered statistically significant.In total,110(13.84％)of 795 samples were positive.The positivity rates was higher in females than males[16.26％(73/449)vs.10.69％(37/346),x2=5.076,P=0.024],while there was no significant difference among age groups(x2=2.569,P=0.766).The positivity rates for serum antibodies in Shuixigou Town,Lucaogou Town,and Tuoli Township were 17.98％(48/267),14.48％(21/145),and 10.70％(41/383),respectively,with a significantly higher rate in Tuoli Township than Lucaogou Town(x2=7.041,P=0.008).Of 110 individuals who were initially positive for IgG and IgM antibodies with the ELISA,82(10.31％)were con-firmed positive by WB analysis.In total,20(2.52％)patients were diagnosed with Lyme disease based on clinical manifesta-tions.Lyme disease is epidemic among the population in Urumqi,as the infection rate is higher than the national average.Hence,continued surveillance is recommended for prevention of Lyme disease.

To clarify the structural characteristics of virus communities carried by primates in the Guangdong region,and evaluate the risk of the important zoonotic virus monkeypox virus(MPXV)being introduced into China through artificially do-mesticated primates,this study conducted metagenomic research on artificially domesticated primates and performed screening for MPXV.Primate samples were collected from 20 wildlife rescue centers or zoos in 14 prefecture level cities in Guangdong Province,and the structural characteristics of virus communities carried by artificially domesticated primates were identified through Illumina sequencing.Fluorescence quantitative PCR detection of MPXV excluded the risk of MPXV being introduced through artificially domesticated primates in Guangdong Prov-ince.A total of 489 oral and pharyngeal swabs and feces from primates were collected.High-throughput sequencing indicated that the viral group structure in the feces of artificially domesti-cated primates in the Guangdong region is complex and shows regional differences.Members of Alphaflexiviridae and Vir-gaviridae,followed by members of Parvoviridae and Genomo-viridae,had the highest abundance.Subsequently,fluorescence quantitative PCR results showed that all primates from wildlife rescue centers or zoos in Guangdong Province were MPXV neg-ative.This study provides the first description of the complex viral structure characteristics of artificially domesticated primates in the Guangdong region,and elucidates the differences in vi-ral communities among artificially domesticated primates in different regions.Our findings suggested that the risk of zoonotic diseases caused by artificially domesticated primates in Guangdong Province is extremely low,and the risk of MPXV being in-troduced into China through artificially domesticated primates in Guangdong Province is zero.

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.