Objective To analyze the cerebral blood flow changes in patients with newly diagnosed untreated early-onset depression(EOD),using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL),and to explore its relationship with clinical phenotypes.Methods The Hamilton Depression Scale(HAMD),Childhood Trauma Questionnaire(CTQ)scores,3D T1WI,and 3D-pCASL brain images of 65 untreated EOD patients and 55 healthy volunteers(HC group)were collected.SPM 12 and DPABI_V7.0 software were used to preprocess and analyze the whole brain images in two groups.Xjview software was used to analyze the value of cerebral blood flow(CBF)at the whole brain level of the two groups,and SPSS 25.0 software was used to evaluate the correlation of CBF values with HAMD scores and CTQ scores.Results Compared with the HC group,the CBF of the EOD group was reduced significantly[P＜0.05,cluster size＞50,false discovery rate(FDR)correction]in the right opercular inferior frontal gyrus(t=5.89),right temporo-parieto-occipital(TPO)region(t=6.49),and blood perfusion increased significantly(P＜0.05,cluster size＞50,FDR correction)in the left superior frontal gyrus(t=5.31)and left insular lobe(t=4.70).Conclusion The proportion of EOD patients with childhood trauma experience is relatively large.EOD patients have both reduced areas and increased areas in cerebral perfusion.The CBF value of the right TPO area is negatively correlated with HAMD scores;The CBF value of the left superior frontal gyrus is positively correlated with the total score of CTQ and the index of physical neglect score in CTQ,which is different from the result of studies that do not distinguish between early-onset and late-onset depression.

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-κB/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1β（IL-1β） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（P<0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（P<0.05，P<0.01）. The uterine organ ratio were decreased significantly（P<0.01），while the ovarian organ ratio were significantly increased（P<0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（P<0.01）.The relative expression levels of inflammation-related protein IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein signaling pathway were significantly increased（P<0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（P<0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（P<0.05，P<0.01）. The uterine organ ratio were increased（P<0.05），while the ovarian organ ratio were decreased（P<0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（P<0.01）. The expression levels of IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein in the high dose group were significantly decreased（P<0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-κB/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．

Alzheimer's disease(AD) patients in China have been surging, and the resultant medical burden and care demand have a huge impact on the development of individuals, families, and the society. The active component compound of Epimedii Folium, Astragali Radix, and Puerariae Lobatae Radix(YHG) can regulate the expression of iron metabolism-related proteins to inhibit brain iron overload and relieve hypofunction of central nervous system in AD patients. Hepcidin is an important target regulating iron metabolism. This study investigated the effect of YHG on the expression of a disintegrin and metalloprotease-17(ADAM17), a key enzyme in the hydrolysis of β amyloid precursor protein(APP) in HT22 cells, by mediating hepcidin. To be specific, HT22 cells were cultured in vitro, followed by liposome-mediated siRNA transfection to silence the expression of hepcidin. Real-time PCR and Western blot were performed to examine the silencing result and the effect of YHG on hepcidin in AD cell model. HT22 cells were randomized into 7 groups: control group, Aβ25-35 induction(Aβ) group, hepcidin-siRNA(siRNA) group, Aβ25-35 + hepcidin-siRNA(Aβ + siRNA) group, Aβ25-35+YHG(Aβ+YHG) group, hepcidin-siRNA+YHG(siRNA+YHG) group, Aβ25-35+hepcidin-siRNA+YHG(Aβ+siRNA+YHG) group. The expression of ADAM17 mRNA in cells was detected by real-time PCR, and the expression of ADAM17 protein by immunofluorescence and Western blot. Immunofluorescence showed that the ADAM17 protein expression was lower in the Aβ group, siRNA group, and Aβ+siRNA group than in the control group(P<0.05) and the expression was lower in the Aβ+siRNA group(P<0.05) and higher in the Aβ+YHG group(P<0.05) than in the Aβ group. Moreover, the ADAM17 protein expression was lower in the Aβ+siRNA group(P<0.05) and higher in the siRNA+YHG group(P< 0.05) than in the siRNA group. The expression was higher in the Aβ+siRNA+YHG group than in the Aβ+siRNA group(P<0.05). The results of Western blot and real-time PCR were consistent with those of immunofluorescence. The experiment showed that YHG induced hepcidin to up-regulate the expression of ADAM17 in AD cell model and promote the activation of non-starch metabolic pathways, which might be the internal mechanism of YHG in preventing and treating AD.
ADAM17 Protein ; Alzheimer Disease/genetics* ; Amyloid beta-Peptides ; Drugs, Chinese Herbal/pharmacology* ; Hepcidins/genetics* ; Humans ; Pueraria

Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/psychology* ; Family ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/psychology* ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index

To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance. Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 μmol/kg), medium dose group (NM Group, 50μmol/kg) and high dose group (NH Group, 100 μmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (HS) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (P＜0.05), and the content of HS in hippocampus was decreased (P＜0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (P＜0.05), and the contents of HS and MBP in hippocampus of SCA3 mice were also improved in different degrees (P＜0.05). Exogenous NaHS may increase the contents of HS and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.

Objective:To investigate the clinical efficacy of modified Bingtitang in treatment of type 2 diabetes mellitus(T2DM) and its effect on pancreas islet function. Method:A total of 108 patients with T2DM were divided into two groups according to the digital number table method, with 54 cases in each group. The control group were given routine therapy of diabetic diet, proper exercise and blood sugar control, while the treatment group were orally given traditional Chinese medicine (TCM) and modified Bingtitang in addition to the therapy of the control group. The blood sugar, pancreas islet function-related indexes, TCM syndrome score, serum retinol binding protein 4 (RBP4) and Betatrohin levels were compared between two groups before and after treatment. The total effective rate was also compared. Result:After treatment, the fasting blood glucose (FPG), glycated hemoglobin (HbA1c), blood glucose variation coefficient (CV-FPG), insulin resistance index (HOMA-IR) of the treatment group were lower than those of control group (P<0.01), while the ratio of insulin secretion index (HOMA-IS), 30-minute insulin increment (I30) and blood glucose proliferation (G30) to(ΔI30/ΔG30)of treatment group were higher than those of the control group (P<0.01). The TCM score and the serum RBP4 level were lower than those of control group (P<0.01), while Betatrohin level was higher than that of the control group (P<0.01), and the total effective rate was higher than that of control group (P<0.05). Conclusion:In addition to the routine treatment, modified Bingtitang can effectively control blood sugar, improve pancreas islet function, and alleviate TCM syndromes, with a significant effect on T2DM. Its mechanism may be related to the regulation of serum RBP4 and Betatrohin levels.

Drug transporters and drag metabolic enzymes are crucial factors in the process of drug treatment.Rhein,as the main active component of traditional Chinese medicine rhubarb,has a wide range of pharmacological activities.Previous studies have shown that rhein is closely related to drug transporters and metabolic enzymes,and can directly activate or inhibit the functions of a variety of transporters and their protein expression.Furthermore,rhein can inhibit the function and protein expression of cytochrome P450 (CYP450),a drug metabolizing enzyme.Thus,when rhein is combined with other drugs,the drug-drug interaction (DDI) may occur based on pharmacokinetic.This paper focuses on the distribution of drug transporters,metabolic enzymes,and the effects of rhein on transporters and metabolic enzymes.

Objective To study the integrated monitoring program regarding mouse and plague, hemorrhagic fever of renal syndrome(HFRS)and leptospirosis. Methods Integrated monitoring plan was used. A designated office coordinated 5 departments' actions within the Zhejiang Provincial Center for Disease Control and Prevention(CDC). Cage-trapping method was conducted to monitor the density of mice from June to October, respectively. Results Lishui municipal CDC had finished the integrated monitoring program on mouse and mouse-borne disease while the Longyou CDC had finished the field investigation, using the integrated monitoring program.Specimens were sent to provincial CDC. The integrated monitoring program needed more number of personnel and better coordination. Lishui reported 3 leptospirosis cases and 58 HFRS cases in 2009,with the incidence rates as 0.13 and 2.44 per 100 000, respectively. Longyou reported 2 leptospirosis case and 1 HFRS cases in 2009, with the incidence rates as 0.49 and 0.25 per 100 000, respectively.Lishui and Longyou had no plague case. Lishui caught 91 mice in 2009 and the density was 4.17%.Longyou caught 37 mice in 2009, with the density as 1.18 percent. Most mice caught from Lishui were Apodemus agrarius and the next was Mus musculus. In Longyou the Rattus tanezumi ranked the first, followed by Apodemus agrarius. The positive rate of HFRS antigen in Lishui and Longyou were 10.42% and 4.59% respectively. The positive rate of HFRS antibody in Longyou was 3.70%. The culture positive rate of leptospirosis in mouse renal of Lishui and Longyou were 0 and 0.98%respectively. The culture positive rate of leptospirosis in pig renal, duck renal, frog renal and cattle urine of Longyou was 0. The culture positive rate of leptospirosis in duck blood of Longyou was 80%.Conclusion The integrated monitoring program on mouse and mouse-borne disease seemed to be feasible and could promote the integrated surveillance and control program on mouse and mouse-borne diseases in China.

BACKGROUNDRecent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE.

METHODSWe genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls. All subjects were from the Northern part of Chinese Han population. The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples.

RESULTSThere was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls. Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age. The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls. Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls. The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients. There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE.

CONCLUSIONSThe SNP rs7574865 in STAT4 is strongly associated with risk of SLE in the Chinese Northern Han population. The TT genotype and T allele in STAT4 rs7574869 are susceptibility factors for SLE, especially for male SLE patients.

Adult ; Asian Continental Ancestry Group ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; genetics ; Lupus Erythematosus, Systemic ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; STAT4 Transcription Factor ; genetics ; Young Adult