Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored...Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.展开更多
In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an ...In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.展开更多
AIM： To explore effects of huoxiangzhengqi liquid （HXZQ） on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea （BSD）. METHODS： BSD was induced in Balb/...AIM： To explore effects of huoxiangzhengqi liquid （HXZQ） on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea （BSD）. METHODS： BSD was induced in Balb/c mice by oral administration with Bacillus dysenteriae and Salmonella typhimurium. HXZQ was administrated from the day of diarrhea induction at dosages of 5.21 g/kg and 0.52 g/kg, respectively. The onset of diarrhea and lasting time were recorded. Peyer＇s patches and peripheral lymphocytes were prepared for flow cytometry, and levels of TNF-α in peripheral blood and enteric tissue homogenates were determined with ELISA. Student＇s t test was employed for statistics. RESULTS： Mice in BSD group started showing continuous diarrhea on the day of induction until the fourth day when they were sacrificed. Diarrhea in the mice of HXZQ high and low dose groups lasted for 36 and 54 h, respectively. There were more CD4^＋ and CD8^＋ cells in peripheral blood, fewer CD4^＋ cells in Peyer＇s patches in BSD mice compared to normal mice. Fewer CD4^＋ and CD8^＋ cells was shown in the mice in HXZQ high group compared to BSD mice. In Peyer＇s patch, there were more CD8^＋ cells in mice in HXZQ high and low dose groups and more CD4^＋ in mice in HXZQ high group. Higher levels of TNF-α in peripheral blood and intestinal tissue homogenates in BSD group were observed. Mice in HXZQ high group showed decreased levels of TNF-α in peripheral blood and enteric tissue homogenates. CONCLUSION： The immune regulation of CD4^＋ and CD8^＋ cells in Peyer＇s patch and suppression of TNF-α levels in enteric homogenates may partially explain the effect of HXZQ on improvement of BSD.展开更多
The Wumeng Mountain area is located at the juncture of Sichuan,Guizhou,and Yunnan provinces in China.In terms of geotectonic setting,it lies in the suture part of two giant tectonic domains,namely the Tethys-Himalayan...The Wumeng Mountain area is located at the juncture of Sichuan,Guizhou,and Yunnan provinces in China.In terms of geotectonic setting,it lies in the suture part of two giant tectonic domains,namely the Tethys-Himalayan sedimentary zone and Circum-Pacific Ocean tectonic domain.There are 38 counties in the Wumeng Mountain area(Fig.1),with a total area of 107×10^3 km^2 and a population of about 23×10^6.The maximum altitude in this area is 4017 m,with the elevation difference between various landforms being up to more than 2000 m.This area suffers frequently occurring natural disasters,severe rocky desertification,unevenly distributed water resources,rare agricultural land per capita,and fragile ecological environment.As a result,it has long been a difficult problem for the local poverty-stricken people to get rich.展开更多
In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the...In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the revision process.展开更多
We propose an optimal approach to solve the problem of multi-degree reduction of C-Brzier surfaces in the norm L2 with prescribed constraints. The control points of the degree-reduced C-Brzier surfaces can be explicit...We propose an optimal approach to solve the problem of multi-degree reduction of C-Brzier surfaces in the norm L2 with prescribed constraints. The control points of the degree-reduced C-Brzier surfaces can be explicitly obtained by using a matrix operation that is based on the transfer matrix of the C-Brzier basis. With prescribed boundary constraints, this method can be applied to piecewise continuous patches or to a single patch with the combination of surface subdivision. The resulting piecewise approximating patches are globally G1 continuous. Finally, numerical examples are presented to show the effectiveness of the method.展开更多
Background:Brucellosis was a common human and livestock disease caused by Brucella strains,the category B priority pathogens by the US Center for Disease Control(CDC).Identified as a priority disease in human and live...Background:Brucellosis was a common human and livestock disease caused by Brucella strains,the category B priority pathogens by the US Center for Disease Control(CDC).Identified as a priority disease in human and livestock populations,the increasing incidence in recent years in China needs urgent control measures for this disease but the molecular background important for monitoring the epidemiology of Brucella strains at the national level is still lacking.Methods:A total of 600 Brucella isolates collected during 60 years(from 1953 to 2013)in China were genotyped by multiple locus variable-number tandem repeat analysis(MLVA)and the variation degree of MLVA11 loci was calculated by the Hunter Gaston Diversity Index(HGDI)values.The charts and map were processed by Excel 2013,and cluster analysis and epidemiological distribution was performed using BioNumerics(version 5.1).Results:The 600 representative Brucella isolates fell into 104 genotypes with 58 singleton genotypes by the MLVA11 assay,including B.melitensis biovars 2 and 3(five main genotypes),B.abortus biovars 1 and 3(two main genotypes),B.suis biovars 1 and 3(three main genotypes),and B.canis(two main genotypes)respectively.While most B.suis biovar 1 and biovar 3 were respectively found in northern provinces and southern provinces,B.melitensis and B.abortus strains were dominant in China.Canine Brucellosis was only found in animals without any human cases reported.Eight Brucellosis epidemic peaks emerged during the 60 years between 1953 and 2013:1955-1959,1962-1969,1971-1975,1977-1983,1985-1989,1992-1997,2000-2008 and 2010-2013 in China.Conclusions:Brucellosis has its unique molecular epidemiological patterns with specific spatial and temporal distribution according to MLVA.Trial registration:IDOP-D-16-00101.展开更多
Dysfunctional megakaryopoiesis hampers platelet production,which is closely associated with thrombocytopenia(PT).Macrophages(MΦs)are crucial cellular components in the bone marrow(BM)microenvironment.However,the spec...Dysfunctional megakaryopoiesis hampers platelet production,which is closely associated with thrombocytopenia(PT).Macrophages(MΦs)are crucial cellular components in the bone marrow(BM)microenvironment.However,the specific effects of M1 MΦs or M2 MΦs on regulating megakaryocytes(MKs)are largely unknown.In the current study,aberrant BM-M1/M2 MO polarization,characterized by increased M1 MΦs and decreased M2 MΦs and accompanied by impaired megakaryopoiesis-supporting abilities,was found in patients with PT post-allotransplant.RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MΦs of PT patients.Moreover,in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MΦs from PT patients.Furthermore,we found M1 MΦs suppress,whereas M2 MCDs support MK maturation and platelet formation In humans.Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MΦs,as indicated by decreased MK count,colony-forming unit number,high-ploidy distribution,and platelet count.Importantly,genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MΦs both in vitro and in a MO-specific PI3K-knockdown murine model,indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 M(Ds.Furthermore,our preliminary data indicated that TGF-β released by M2 MΦs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs.Taken together,our data reveal that M1 and M2 MΦs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner,which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.展开更多
Background:The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly,with confirmed cases distributed across 31 counties.However,the epidemiology of brucellosis transmission has not ...Background:The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly,with confirmed cases distributed across 31 counties.However,the epidemiology of brucellosis transmission has not been fully elucidated.To characterize the infecting strains isolated from humans,multiple-locus variable-number tandem repeats analysis(MLVA)and whole-genome single-nucleotide polymorphism(SNP)-based approaches were employed.Methods:Strains were isolated from two males blood cultures that were confirmed Brucella m elitensis positive following biotyping and MLVA.Genomic DNA was extracted from these two strains,and whole-genome sequencing was performed.Next,SNP-based phylogenetic analysis was performed to compare the two strains to 94 B.melitensis strains(complete genome and draft genome)retrieved from online databases.Results:The two Brucella isolates were identified as B.melitensis biovar 3(QH2019001 and QH2019005)following conventional biotyping and were found to have differences in their variable number tandem repeats(VNTRs)using MLVA-16.Phylogenetic examination assigned the 96 strains to five genotype groups,with QH2019001 and QH2019005 assigned to the same group,but different subgroups.Moreover,the QH2019005 strain was assigned to a new subgenotype,llj,within genotype II.These findings were then combined to determine the geographic origin of the two Brucella strains.Conclusions:Utilizing a whole-genome SNP-based approach enabled differences between the two B.m elitensis strains to be more clearly resolved,and facilitated the elucidation of their different evolutionary histories.This approach also revealed that QH2019005 is a member of a new subgenotype(Hj)with an ancient origin in the eastern Mediterranean Sea.展开更多
Background:The Qinghai-Tibet Plateau(QTP)of China is an extensive pastoral and semi-pastoral area,and because of poverty and bad hygiene conditions,Brucella is highly prevalent in this region.In order to adequately pr...Background:The Qinghai-Tibet Plateau(QTP)of China is an extensive pastoral and semi-pastoral area,and because of poverty and bad hygiene conditions,Brucella is highly prevalent in this region.In order to adequately prevent this disease in the QTP region it is important to determine the identity of Brucella species that caused the infection.Methods:A total of 65 Brucella isolates were obtained from human,livestock and wild animals in Qinghai,a Chinese province in east of the QTP.Two molecular typing methods,MLVA(multi-locus variable-number tandem-repeat analysis)and MLST(multi locus sequence typing)were used to identify the species and genotypes of these isolates.Findings:Both MLVA and MLST typing methods classified the 65 isolates into three species,B.melitensis,B.abortus and B.suis,which included 60,4 and 1 isolates respectively.The MLVA method uniquely detected 34(Bm01~Bm34),3(Ba01~Ba03),and 1(Bs01)MLVA-16 genotypes for B.melitensis,B.abortus and B.suis,respectively.However,none of these genotypes exactly matched any of the genotypes in the Brucella2012 MLVA database.The MLST method identified five known ST types:ST7 and ST8(B.melitensis),ST2 and ST5(B.abortus),and ST14(B.suis).We also detected a strain with a mutant type(3-2-3-2-?-5-3-8-2)of ST8(3-2-3-2-1-5-3-8-2).Extensive genotype-sharing events could be observed among isolates from different host species.Conclusions:There were at least three Brucella(B.melitensis,B.abortus and B.suis)species in Qinghai,of which B.melitensis was the predominant species in the area examined.The Brucella population in Qinghai was very different from other regions of the world,possibly owing to the unique geographical characteristics such as extremely high altitude in QTP.There were extensive genotype-sharing events between isolates obtained from humans and other animals.Yaks,sheep and blue sheep were important zoonotic reservoirs of brucellosis causing species found in humans.展开更多
Background:Brucellosis is an infectious-allergic zoonotic disease caused by bacteria of the genus Brucella.Early diagnosis is the key to preventing,treating,and controlling brucellosis.Fluorescence polarization immuno...Background:Brucellosis is an infectious-allergic zoonotic disease caused by bacteria of the genus Brucella.Early diagnosis is the key to preventing,treating,and controlling brucellosis.Fluorescence polarization immunoassay(FPA)is a new immunoassay for relatively rapid and accurate detection of antibodies or antigens based on antigen-antibody interaction.However,there is no report on FPA-based detection of human brucellosis in China.Therefore,this study is to evaluate the value of FPA for the diagnosis of human brucellosis in China.展开更多
Background:The association between free triiodothyronine(FT3)and long-term prognosis in dilated cardiomyopathy(DCM)patients has not been evaluated.The purpose of this study was to determine whether the level of FT3 co...Background:The association between free triiodothyronine(FT3)and long-term prognosis in dilated cardiomyopathy(DCM)patients has not been evaluated.The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM.Methods:Data of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014.FT3 was measured by fluoroimmunoassay.Other biochemical markers,such as free thyroxin(FT4),thyroid-stimulating hormone,red blood cell,hemoglobin,blood urea nitrogen,and serum creatinine,were tested at the same time.Follow-up was performed every 3 months.The primary endpoint was all-cause mortality.Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’prognosis.The association of long-term mortality in DCM and FT3 was compared using Cox hazards model.Results:Data of 176 patients diagnosed with DCM were collected.Of them,24 patients missed FT3 values and six patients were lost to follow-up.Altogether,data of 146 patients were analyzed.During the median follow-up time of 79.9(53.5-159.6)months,nine patients lost,61 patients died(non-survival group),and 85 patients survived(survival group).FT3 was significantly lower in non-survival group than that in survival group(3.65±0.83 pmol/L vs.4.36±1.91 pmol/L;P=0.003).FT3 also showed a significantly positive correlation with red blood cell and hemoglobin,negatively correlated with age,blood urea nitrogen and serum creatinine(P<0.05),respectively.Patients in the group of lower FT3 levels(FT3≤3.49 pmol/L)suffered from a higher risk of all-cause mortality(P for log-rank=0.001).In multivariate Cox regression analysis,FT3 level was significantly associated with all-cause mortality(hazard ratio:0.70,95%confidence interval 0.52-0.95,P for trend=0.021).Conclusion:Low levels of FT3 were associated with increased all-cause mortality in patients with DCM.展开更多
Objective：We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease （CAVD） in patients with normal or mildly impaired rena...Objective：We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease （CAVD） in patients with normal or mildly impaired renal function. Methods：We measured serum levels of calcium, phosphate, alkaline phosphatase （AKP）, intact parathyroid hormone （iPTH）, 25-hydroxyvitamin D （25-OHD）, and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis （AVSc） （n=164） or stenosis （AVS） （n=96） and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results：Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels （al P〈0.001）. Similarly, osteocalcin, procol agen I N-terminal peptide, andβ-isomerized type I col agen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS （al P〈0.001）. In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding varia-bles, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were in-dependently associated with the presence and severity of CAVD. Conclusions： This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism.展开更多
Background:Human brucellosis is a neglected public health issue in China and reports of HIV-infected individuals complicated with brucellosis are rare.This report describes the case of an HIV-infected patient complica...Background:Human brucellosis is a neglected public health issue in China and reports of HIV-infected individuals complicated with brucellosis are rare.This report describes the case of an HIV-infected patient complicated with brucellosis.We want to raise awareness of clinical diagnosis of brucellosis among clinicians.Furthermore,we should be more concerned about cases with pyrexia of unknown origin,especially in non-epidemic areas of brucellosis in China.Case presentation:We encountered the case of a 31-year-old HIV-infected male with a CD4+T lymphocyte count of approximately 300.On May 1,2019,the patient had onset of non-specific caustic irregular fever with body temperature reaching 41.0°C.He was admitted to two medical institutions in Yunnan with pyrexia of unknown origin.Finally,on day 7 of hospitalization in the Public Health Clinical Medical Center in Chengdu City,he was diagnosed as having brucellosis infection based on blood culture results.Conclusions:This is the first reported case of brucellosis concomitant with HIV infection in China.Laboratories in infectious disease hospitals and category A level III hospitals in the southern provinces of China should be equipped with reagents for clinical diagnosis of brucellosis and to strengthen the awareness of brucellosis diagnosis in China.Secondly,in provinces with a high incidence of AIDS and brucellosis such as Xinjiang and Henan,it is recommended to implement a joint examination strategy to ensure the early detection,diagnosis,and treatment of this infection.展开更多
To acquire data of Brucella cellular fatty acids(CFAs)and probe into the possibility of utilizing CFAs information in typing Brucella,19 reference strains were subjected to CFAs study.After all strains were inoculated...To acquire data of Brucella cellular fatty acids(CFAs)and probe into the possibility of utilizing CFAs information in typing Brucella,19 reference strains were subjected to CFAs study.After all strains were inoculated on Brucella Agar plates,the cells were harvested,saponificated,methylated and extracted to provide fatty acid methylesters for gas chromatography(GC)analysis.Based on the CFAs data matrix,a dendrogram of 19 reference strains was generated by SPSS11.5 software package.The results showed that 19 reference strains were divided intofive clusters:cluster 1 included B.suis(bv.1,2,3,5)and B.ovis;cluster 2 included B.abortus(bv.3,4,5,6)and B.melitensis(bv.1,2,3);cluster 3 included B.abortus(bv.1,2,7,9)and B.neotomae;cluster 4 was B.suis(bv.4);and cluster 5 was B.canis.Typing Brucella by GC analysis of CFAs is a good method to reflect drug resistance of Brucella,and the classification is beneficial for clinical therapy.It also provides a new result of typing and demonstrates that the traditional classification is not completely reasonable.CFAs analysis may identify B.suis(bv.4)and B.canis.展开更多
Deepwater offshore area,with rich oil and gas resources,has currently become the hot area for oil and gas exploration and the main battlefield where global oil majors compete with each other.This article summarizes th...Deepwater offshore area,with rich oil and gas resources,has currently become the hot area for oil and gas exploration and the main battlefield where global oil majors compete with each other.This article summarizes the current situation of deepwater oil and gas exploration and development overseas from the perspectives of exploration history,exploration achievements and technical progress,and analyzes the difficulties and challenges faced by the industry,such as low level understanding of hydrocarbon accumulation conditions,global security and environmental challenges.And then,several feasible implementation strategies have been proposed on how to actively deal with the challenges,promote Chinese oil companies' overseas exploration,and realize efficient exploration and development of deepwater oil and gas fields overseas.These strategies consist of three aspects:profit-oriented operation principle,exploration ideas supported by theory and technology,and exploration strategy that puts safety first.In the era of low oil prices,Chinese oil companies must build up confidence,seize the opportunity and face the challenge while taking efforts to innovate technologies and theories,updates strategic ideas,and cultivate deepwater talents so as to be in an active position in global deepwater exploration and development industry in the future.展开更多
基金supported by projects from the National Natural Science Foundation of China(81370977,81570796 and 81370018)by the Shanghai Science and Technology Committee(14411960900)
文摘Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.
基金supported by a grant from the NIH:DK32333supported by the National Natural Science Foundation of China (81070693 and 81200647)
文摘In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism （PHPT） changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT con- tinues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.
基金Supported by the National ‘863’ Project, No.2003AA2Z3245 and E-institute of Shanghai Municipal Education Commission, No. E03008
文摘AIM： To explore effects of huoxiangzhengqi liquid （HXZQ） on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea （BSD）. METHODS： BSD was induced in Balb/c mice by oral administration with Bacillus dysenteriae and Salmonella typhimurium. HXZQ was administrated from the day of diarrhea induction at dosages of 5.21 g/kg and 0.52 g/kg, respectively. The onset of diarrhea and lasting time were recorded. Peyer＇s patches and peripheral lymphocytes were prepared for flow cytometry, and levels of TNF-α in peripheral blood and enteric tissue homogenates were determined with ELISA. Student＇s t test was employed for statistics. RESULTS： Mice in BSD group started showing continuous diarrhea on the day of induction until the fourth day when they were sacrificed. Diarrhea in the mice of HXZQ high and low dose groups lasted for 36 and 54 h, respectively. There were more CD4^＋ and CD8^＋ cells in peripheral blood, fewer CD4^＋ cells in Peyer＇s patches in BSD mice compared to normal mice. Fewer CD4^＋ and CD8^＋ cells was shown in the mice in HXZQ high group compared to BSD mice. In Peyer＇s patch, there were more CD8^＋ cells in mice in HXZQ high and low dose groups and more CD4^＋ in mice in HXZQ high group. Higher levels of TNF-α in peripheral blood and intestinal tissue homogenates in BSD group were observed. Mice in HXZQ high group showed decreased levels of TNF-α in peripheral blood and enteric tissue homogenates. CONCLUSION： The immune regulation of CD4^＋ and CD8^＋ cells in Peyer＇s patch and suppression of TNF-α levels in enteric homogenates may partially explain the effect of HXZQ on improvement of BSD.
文摘The Wumeng Mountain area is located at the juncture of Sichuan,Guizhou,and Yunnan provinces in China.In terms of geotectonic setting,it lies in the suture part of two giant tectonic domains,namely the Tethys-Himalayan sedimentary zone and Circum-Pacific Ocean tectonic domain.There are 38 counties in the Wumeng Mountain area(Fig.1),with a total area of 107×10^3 km^2 and a population of about 23×10^6.The maximum altitude in this area is 4017 m,with the elevation difference between various landforms being up to more than 2000 m.This area suffers frequently occurring natural disasters,severe rocky desertification,unevenly distributed water resources,rare agricultural land per capita,and fragile ecological environment.As a result,it has long been a difficult problem for the local poverty-stricken people to get rich.
文摘In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the revision process.
基金Project supported by the National Natural Science Foundation of China （Nos. 11401373, 61402281, and 11601322） and the Zhejiang Provincial Natural Science Foundation, China （No. LY16F020020）
文摘We propose an optimal approach to solve the problem of multi-degree reduction of C-Brzier surfaces in the norm L2 with prescribed constraints. The control points of the degree-reduced C-Brzier surfaces can be explicitly obtained by using a matrix operation that is based on the transfer matrix of the C-Brzier basis. With prescribed boundary constraints, this method can be applied to piecewise continuous patches or to a single patch with the combination of surface subdivision. The resulting piecewise approximating patches are globally G1 continuous. Finally, numerical examples are presented to show the effectiveness of the method.
基金This study was supported by grants from the Chinese National Programs for High Technology Research and Development:Lab Infectious Materials and Biological Risk Source Key Technology and Product Research(No.2014AA021404)the National Nature Science Foundation(No.81271900).
文摘Background:Brucellosis was a common human and livestock disease caused by Brucella strains,the category B priority pathogens by the US Center for Disease Control(CDC).Identified as a priority disease in human and livestock populations,the increasing incidence in recent years in China needs urgent control measures for this disease but the molecular background important for monitoring the epidemiology of Brucella strains at the national level is still lacking.Methods:A total of 600 Brucella isolates collected during 60 years(from 1953 to 2013)in China were genotyped by multiple locus variable-number tandem repeat analysis(MLVA)and the variation degree of MLVA11 loci was calculated by the Hunter Gaston Diversity Index(HGDI)values.The charts and map were processed by Excel 2013,and cluster analysis and epidemiological distribution was performed using BioNumerics(version 5.1).Results:The 600 representative Brucella isolates fell into 104 genotypes with 58 singleton genotypes by the MLVA11 assay,including B.melitensis biovars 2 and 3(five main genotypes),B.abortus biovars 1 and 3(two main genotypes),B.suis biovars 1 and 3(three main genotypes),and B.canis(two main genotypes)respectively.While most B.suis biovar 1 and biovar 3 were respectively found in northern provinces and southern provinces,B.melitensis and B.abortus strains were dominant in China.Canine Brucellosis was only found in animals without any human cases reported.Eight Brucellosis epidemic peaks emerged during the 60 years between 1953 and 2013:1955-1959,1962-1969,1971-1975,1977-1983,1985-1989,1992-1997,2000-2008 and 2010-2013 in China.Conclusions:Brucellosis has its unique molecular epidemiological patterns with specific spatial and temporal distribution according to MLVA.Trial registration:IDOP-D-16-00101.
基金This work was supported by the National Key Research and Development Program(2017YFA0104500 and 2019YFC0840606)National Natural Science Foundation of China(82070188,81870139,81930004)+1 种基金the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the Science and Technology Project of Guangdong Province of China(2016B030230003).
文摘Dysfunctional megakaryopoiesis hampers platelet production,which is closely associated with thrombocytopenia(PT).Macrophages(MΦs)are crucial cellular components in the bone marrow(BM)microenvironment.However,the specific effects of M1 MΦs or M2 MΦs on regulating megakaryocytes(MKs)are largely unknown.In the current study,aberrant BM-M1/M2 MO polarization,characterized by increased M1 MΦs and decreased M2 MΦs and accompanied by impaired megakaryopoiesis-supporting abilities,was found in patients with PT post-allotransplant.RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MΦs of PT patients.Moreover,in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MΦs from PT patients.Furthermore,we found M1 MΦs suppress,whereas M2 MCDs support MK maturation and platelet formation In humans.Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MΦs,as indicated by decreased MK count,colony-forming unit number,high-ploidy distribution,and platelet count.Importantly,genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MΦs both in vitro and in a MO-specific PI3K-knockdown murine model,indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 M(Ds.Furthermore,our preliminary data indicated that TGF-β released by M2 MΦs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs.Taken together,our data reveal that M1 and M2 MΦs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner,which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.
基金supported by National Key R&D Program of China(Grant No.2020YFA0907101)Major Infectious Diseases such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects(2018ZX10201002)the National Natural Scientific Foundation of China(81860588).
文摘Background:The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly,with confirmed cases distributed across 31 counties.However,the epidemiology of brucellosis transmission has not been fully elucidated.To characterize the infecting strains isolated from humans,multiple-locus variable-number tandem repeats analysis(MLVA)and whole-genome single-nucleotide polymorphism(SNP)-based approaches were employed.Methods:Strains were isolated from two males blood cultures that were confirmed Brucella m elitensis positive following biotyping and MLVA.Genomic DNA was extracted from these two strains,and whole-genome sequencing was performed.Next,SNP-based phylogenetic analysis was performed to compare the two strains to 94 B.melitensis strains(complete genome and draft genome)retrieved from online databases.Results:The two Brucella isolates were identified as B.melitensis biovar 3(QH2019001 and QH2019005)following conventional biotyping and were found to have differences in their variable number tandem repeats(VNTRs)using MLVA-16.Phylogenetic examination assigned the 96 strains to five genotype groups,with QH2019001 and QH2019005 assigned to the same group,but different subgroups.Moreover,the QH2019005 strain was assigned to a new subgenotype,llj,within genotype II.These findings were then combined to determine the geographic origin of the two Brucella strains.Conclusions:Utilizing a whole-genome SNP-based approach enabled differences between the two B.m elitensis strains to be more clearly resolved,and facilitated the elucidation of their different evolutionary histories.This approach also revealed that QH2019005 is a member of a new subgenotype(Hj)with an ancient origin in the eastern Mediterranean Sea.
基金supported by the Science and Technology Plan of Qinghai Province(NO.2013-Z-749)the Youth Innovation Promotion Association of Chinese Academy of Sciences(NO.2015352).
文摘Background:The Qinghai-Tibet Plateau(QTP)of China is an extensive pastoral and semi-pastoral area,and because of poverty and bad hygiene conditions,Brucella is highly prevalent in this region.In order to adequately prevent this disease in the QTP region it is important to determine the identity of Brucella species that caused the infection.Methods:A total of 65 Brucella isolates were obtained from human,livestock and wild animals in Qinghai,a Chinese province in east of the QTP.Two molecular typing methods,MLVA(multi-locus variable-number tandem-repeat analysis)and MLST(multi locus sequence typing)were used to identify the species and genotypes of these isolates.Findings:Both MLVA and MLST typing methods classified the 65 isolates into three species,B.melitensis,B.abortus and B.suis,which included 60,4 and 1 isolates respectively.The MLVA method uniquely detected 34(Bm01~Bm34),3(Ba01~Ba03),and 1(Bs01)MLVA-16 genotypes for B.melitensis,B.abortus and B.suis,respectively.However,none of these genotypes exactly matched any of the genotypes in the Brucella2012 MLVA database.The MLST method identified five known ST types:ST7 and ST8(B.melitensis),ST2 and ST5(B.abortus),and ST14(B.suis).We also detected a strain with a mutant type(3-2-3-2-?-5-3-8-2)of ST8(3-2-3-2-1-5-3-8-2).Extensive genotype-sharing events could be observed among isolates from different host species.Conclusions:There were at least three Brucella(B.melitensis,B.abortus and B.suis)species in Qinghai,of which B.melitensis was the predominant species in the area examined.The Brucella population in Qinghai was very different from other regions of the world,possibly owing to the unique geographical characteristics such as extremely high altitude in QTP.There were extensive genotype-sharing events between isolates obtained from humans and other animals.Yaks,sheep and blue sheep were important zoonotic reservoirs of brucellosis causing species found in humans.
文摘Background:Brucellosis is an infectious-allergic zoonotic disease caused by bacteria of the genus Brucella.Early diagnosis is the key to preventing,treating,and controlling brucellosis.Fluorescence polarization immunoassay(FPA)is a new immunoassay for relatively rapid and accurate detection of antibodies or antigens based on antigen-antibody interaction.However,there is no report on FPA-based detection of human brucellosis in China.Therefore,this study is to evaluate the value of FPA for the diagnosis of human brucellosis in China.
基金funded by grants from the National Key Research and Development Program of China(No.2016YFE0117000)the National Natural Science Foundation of China(Nos.81901410,81871113)+2 种基金Qinghai Provincial Natural Science Fund(No.2017-ZJ-769)333 project of Jiangsu Province(No.BRA2017544)Changzhou Science and Technology Bureau(No.CJ20190102)。
文摘Background:The association between free triiodothyronine(FT3)and long-term prognosis in dilated cardiomyopathy(DCM)patients has not been evaluated.The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM.Methods:Data of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014.FT3 was measured by fluoroimmunoassay.Other biochemical markers,such as free thyroxin(FT4),thyroid-stimulating hormone,red blood cell,hemoglobin,blood urea nitrogen,and serum creatinine,were tested at the same time.Follow-up was performed every 3 months.The primary endpoint was all-cause mortality.Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’prognosis.The association of long-term mortality in DCM and FT3 was compared using Cox hazards model.Results:Data of 176 patients diagnosed with DCM were collected.Of them,24 patients missed FT3 values and six patients were lost to follow-up.Altogether,data of 146 patients were analyzed.During the median follow-up time of 79.9(53.5-159.6)months,nine patients lost,61 patients died(non-survival group),and 85 patients survived(survival group).FT3 was significantly lower in non-survival group than that in survival group(3.65±0.83 pmol/L vs.4.36±1.91 pmol/L;P=0.003).FT3 also showed a significantly positive correlation with red blood cell and hemoglobin,negatively correlated with age,blood urea nitrogen and serum creatinine(P<0.05),respectively.Patients in the group of lower FT3 levels(FT3≤3.49 pmol/L)suffered from a higher risk of all-cause mortality(P for log-rank=0.001).In multivariate Cox regression analysis,FT3 level was significantly associated with all-cause mortality(hazard ratio:0.70,95%confidence interval 0.52-0.95,P for trend=0.021).Conclusion:Low levels of FT3 were associated with increased all-cause mortality in patients with DCM.
基金Project supported by the Science and Technology Commission of Shanghai Municipality(No.114119a8800),China
文摘Objective：We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease （CAVD） in patients with normal or mildly impaired renal function. Methods：We measured serum levels of calcium, phosphate, alkaline phosphatase （AKP）, intact parathyroid hormone （iPTH）, 25-hydroxyvitamin D （25-OHD）, and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis （AVSc） （n=164） or stenosis （AVS） （n=96） and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results：Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels （al P〈0.001）. Similarly, osteocalcin, procol agen I N-terminal peptide, andβ-isomerized type I col agen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS （al P〈0.001）. In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding varia-bles, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were in-dependently associated with the presence and severity of CAVD. Conclusions： This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism.
基金This study was funded by Major Infectious Diseases such as AIDS and Viral Hepatitis Prevention and Control technology major projects grants(No.2018ZX10101002)Major Infectious Diseases such as AIDS and Viral Hepatitis Prevention and Control technology major projects grants(No.2018ZX10201002).
文摘Background:Human brucellosis is a neglected public health issue in China and reports of HIV-infected individuals complicated with brucellosis are rare.This report describes the case of an HIV-infected patient complicated with brucellosis.We want to raise awareness of clinical diagnosis of brucellosis among clinicians.Furthermore,we should be more concerned about cases with pyrexia of unknown origin,especially in non-epidemic areas of brucellosis in China.Case presentation:We encountered the case of a 31-year-old HIV-infected male with a CD4+T lymphocyte count of approximately 300.On May 1,2019,the patient had onset of non-specific caustic irregular fever with body temperature reaching 41.0°C.He was admitted to two medical institutions in Yunnan with pyrexia of unknown origin.Finally,on day 7 of hospitalization in the Public Health Clinical Medical Center in Chengdu City,he was diagnosed as having brucellosis infection based on blood culture results.Conclusions:This is the first reported case of brucellosis concomitant with HIV infection in China.Laboratories in infectious disease hospitals and category A level III hospitals in the southern provinces of China should be equipped with reagents for clinical diagnosis of brucellosis and to strengthen the awareness of brucellosis diagnosis in China.Secondly,in provinces with a high incidence of AIDS and brucellosis such as Xinjiang and Henan,it is recommended to implement a joint examination strategy to ensure the early detection,diagnosis,and treatment of this infection.
基金supported by a grant from the National High Technology Research and Development Program of China(863 Program)(No.2007AA02Z410).
文摘To acquire data of Brucella cellular fatty acids(CFAs)and probe into the possibility of utilizing CFAs information in typing Brucella,19 reference strains were subjected to CFAs study.After all strains were inoculated on Brucella Agar plates,the cells were harvested,saponificated,methylated and extracted to provide fatty acid methylesters for gas chromatography(GC)analysis.Based on the CFAs data matrix,a dendrogram of 19 reference strains was generated by SPSS11.5 software package.The results showed that 19 reference strains were divided intofive clusters:cluster 1 included B.suis(bv.1,2,3,5)and B.ovis;cluster 2 included B.abortus(bv.3,4,5,6)and B.melitensis(bv.1,2,3);cluster 3 included B.abortus(bv.1,2,7,9)and B.neotomae;cluster 4 was B.suis(bv.4);and cluster 5 was B.canis.Typing Brucella by GC analysis of CFAs is a good method to reflect drug resistance of Brucella,and the classification is beneficial for clinical therapy.It also provides a new result of typing and demonstrates that the traditional classification is not completely reasonable.CFAs analysis may identify B.suis(bv.4)and B.canis.
文摘Deepwater offshore area,with rich oil and gas resources,has currently become the hot area for oil and gas exploration and the main battlefield where global oil majors compete with each other.This article summarizes the current situation of deepwater oil and gas exploration and development overseas from the perspectives of exploration history,exploration achievements and technical progress,and analyzes the difficulties and challenges faced by the industry,such as low level understanding of hydrocarbon accumulation conditions,global security and environmental challenges.And then,several feasible implementation strategies have been proposed on how to actively deal with the challenges,promote Chinese oil companies' overseas exploration,and realize efficient exploration and development of deepwater oil and gas fields overseas.These strategies consist of three aspects:profit-oriented operation principle,exploration ideas supported by theory and technology,and exploration strategy that puts safety first.In the era of low oil prices,Chinese oil companies must build up confidence,seize the opportunity and face the challenge while taking efforts to innovate technologies and theories,updates strategic ideas,and cultivate deepwater talents so as to be in an active position in global deepwater exploration and development industry in the future.
