Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients

BACKGROUND Hypertension usually clusters with multiple comorbidities.However,the association between cardiometabolic multimorbidity(CMM)and mortality in hypertensive patients is unclear.This study aimed to investigate the association between CMM and all-cause and cardiovascular disease(CVD)mortality in Chinese patients with hypertension.METHODS The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors(CONSIDER),which comprised 5006 participants aged 19–91 years.CMM was defined as the presence of one or more of the following morbidities:diabetes mellitus,dyslipidemia,chronic kidney disease,coronary heart disease,and stroke.Cox proportional hazard models were used to calculate the hazard ratios(HR)with 95%CI to determine the association between the number of CMMs and both all-cause and CVD mortality.RESULTS Among 5006 participants[mean age:58.6±10.4 years,50%women(2509 participants)],76.4%of participants had at least one comorbidity.The mortality rate was 4.57,4.76,8.48,and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one,two,and three or more morbidities,respectively.In the fully adjusted model,hypertensive participants with two cardiometabolic diseases(HR=1.52,95%CI:1.09–2.13)and those with three or more cardiometabolic diseases(HR=2.44,95%CI:1.71–3.48)had a significantly elevated risk of all-cause mortality.The findings were similar for CVD mortality but with a greater increase in risk magnitude.CONCLUSIONS In this study,three-fourths of hypertensive patients had CMM.Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients,suggesting more intensive treatment and control in this high-risk patient group.

The Epidemiology, Diagnosis and Prognosis of Long-COVID

INTRODUCTION As of October 26, 2022, more than 625 million confirmed cases of COVID-19 and more than 6.56 million deaths have been reported to the World Health Organization(WHO), and the natural history,clinical course, and long-term consequences of this new disease are still not completely understood.After more than two years of fighting against the SARS-CoV-2 pandemic, the number of patients with long-term persistent COVID-19 symptoms after acute infection is noteworthy.

Space-Time Cluster Analysis of Tuberculosis Incidence in Beijing, China

Tuberculosis is one of the top killer diseases in the globe. The aim of this study was to explore the geographic distribution patterns and clustering characteristics of the disease incidence in terms of both space and time with high relative risk locations for tuberculosis incidence in Beijing area. A retrospective space-time clustering analysis was conducted at the districts level in Beijing area based on reported cases of sputum smear-positive pulmonary tuberculosis (TB) from 2005 to 2014. Global and local Moran’s I, autocorrelation analysis along with Ord (Gi*) statistics was applied to detect spatial patterns and the hotspot of TB incidence. Furthermore, the Kuldorff’s scan statistics were used to analyze space-time clusters. A total of 40,878 TB cases were reported in Beijing from 2005 to 2014. The annual average incidence rate was 22.11 per 100,000 populations (ranged from 16.55 to 25.71). The seasonal incidence occurred from March to July until late autumn. A higher relative risk area for TB incidence was mainly detected in urban and some rural districts of Beijing. The significant most likely space-time clusters and secondary clusters of TB incidence were scattered diversely in Beijing districts in each study year. The risk population was mainly scattered in urban and dense populated districts, including in few rural districts.

Comparisons of different statistical models for analyzing the effects of meteorological factors on COVID-19

Objective:This general non-systematic review aimed to gather information on reported statistical models examing the effects of meteorological factors on coronavirus disease 2019(COVID-19)and compare these models.Methods:PubMed,Web of Science,and Google Scholar were searched for studies on"meteorological factors and COVID-19"published between January 1,2020,and October 1,2022.Results:The most commonly used approaches for analyzing the association between meteorological factors and COVID-19 were the linear regression model(LRM),generalized linear model(GLM),generalized additive model(GAM),and distributed lag non-linear model(DLNM).In addition to these classical models commonly applied in environmental epidemiology,machine learning techniques are increasingly being used to select risk factors for the outcome of interest and establishing robust prediction models.Conclusion:Selecting an appropriate model is essential before conducting research.To ensure the reliability of analysis results,it is important to consider including non-meteorological factors(e.g.,government policies on physical distancing,vaccination,and hygiene practices)along with meteorological factors in the model.

Anticancer effects of sweet potato protein on human colorectal cancer cells

AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro . The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo . RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC 50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo .

Sporamin suppresses growth of xenografted colorectal carcinoma in athymic BALB/c mice by inhibiting liver β-catenin and vascular endothelial growth factor expression

BACKGROUND Colorectal cancer(CRC)is the third most common malignancy of the digestive tract and the fifth leading cause of cancer-related mortality in China.Sporamin,a Kunitz-type trypsin inhibitor isolated from sweet potato,is a potential anti-cancer agent with activities against a number of malignant tumor cells in vitro.The liver secretes a myriad of endocrine factors that may facilitate the growth and transformation of tumors in the development of CRC.AIM To investigate the effects of sporamin on liver morphology and biomarkers of xenografted CRC in the liver of athymic BALB/c mice.METHODS Twenty-seven male BALB/c nude mice were randomly divided into control,vehicle,and sporamin groups.Mice in the latter two groups were intraperitoneally xenografted with LoVo colorectal carcinoma cells and intragastrically infused with saline or sporamin(0.5 g/kg body weight/d),respectively,for 3 wk.Hematoxylin and eosin(HE)staining of the sections was performed to observe morphological changes in hepatic tissue and real-time fluorescent quantitative PCR(qPCR)and enzyme-linked immunosorbent assay(ELISA)were used to measure the expression ofβ-catenin and vascular endothelial growth factor(VEGF)in the liver.RESULTS Sporamin significantly reduced the number and weight of tumor nodules formed in the abdominal cavity.Compared with the vehicle group,the mean tumor weight(±SD)in the sporamin group was significantly reduced(0.44±0.10 g vs 0.26±0.15 g)and the total number of tumors decreased from 93 to 55.HE staining showed that enlargement of the nucleus and synthesis of proteins within hepatocytes,as well as infiltration of inflammatory cells into the liver,were attenuated by sporamin.Immunohistochemical staining and ELISA showed that the concentrations ofβ-catenin and VEGF in the liver were significantly reduced by sporamin.Compared with the vehicle group,the expression ofβ-catenin measured in integrated optical density units per area was reduced in the sporamin group(47.29±9.10 vs 26.14±1.72;P=0.003).Expression of VEGF was also reduced after sporamin intervention from 20.78±2.06 in the vehicle group to 15.80±1.09 in the sporamin group(P=0.021).Compared with the vehicle group,the concentration ofβ-catenin decreased from 134.42±22.04 pg/mL to 109.07±9.65 pg/mL after sporamin intervention(P=0.00002).qPCR indicated that compared to the vehicle group,relative mRNA expression ofβ-catenin and VEGF in the liver of mice in the sporamin-treated group was significantly reduced to 71%±1%(P=0.000001)and 23%±7%(P=0.00002),respectively,of the vehicle group levels.CONCLUSION Sporamin down-regulates the expression and secretion ofβ-catenin and VEGF in the liver,which subsequently inhibits the transcription of downstream genes involved in cancer progression and angiogenesis.

BMI and BMI Changes to All-cause Mortality among the Elderly in Beijing： a 20-year Cohort Study

Objective To explore the association between body mass index(BMI)and all-cause mortality among the elderly in Beijing.Methods This analysis was based on the Beijing multidimensional longitudinal study of aging(BLSA),which included 2,090 subjects over 55 years old and was followed-up from 1992 to 2012.BMI-mortality curves were drawn to find the optimal BMI range with the lowest mortality.Cox proportional hazard models were used to obtain the hazard ratios(HRs)for BMI and BMI changes in the overall population and in specific stratified populations.Results During follow-up,1,164 deaths were recorded;BMI-mortality curve was U-shaped,with the lowest mortality at a BMI of approximately 25 kg/m^2.After adjusting for gender,age,smoking,drinking and some pre-existing diseases,HRs for underweight,overweight and obesity compared with normal weight were 1.372(95%CI:1.154-1.631),0.767(95%CI:0.666-0.884)and 0.871(95%CI:0.830-1.246),respectively.HR for BMI drop was 3.245(95%CI:0.824-12.772)in the underweight group and 1.892(95%CI:0.830-1.246)in the normal weight group,HR for BMI rise was 1.795(95%CI:1.243-2.591)in normal weight group and 1.962(95%CI:1.202-3.203)in the overweight group.Conclusion Keeping BMI in an overweight status and stable is related to a reduced mortality.

Tea Consumption is Associated with Increased Risk of Kidney Stones in Northern Chinese： A Cross-sectional Study

Kidney stones are a common urinary system condition that can progress to kidney disease.Previous studies on the association between tea consumption and kidney stones are inconsistent.A cross‐sectional study to investigate the association between tea consumption and kidney stones was conducted from 2013 to 2014 and recruited 9,078northern Chinese adults.A total of 8,807participants were included in the final analysis.

Awareness of initiative practice for health in the Chinese population:A questionnaire survey based on a network platform

BACKGROUND In 2016,the Chinese government issued the Healthy China 2030 plan,which also produced the initiative practice for health(IPFH)concept.However,people’s knowledge and awareness of the IPFH are unclear.AIM To investigate awareness of IPFH in the Chinese population and explore the relevant influential factors.METHODS An internet-based self-designed questionnaire survey was used to collect respondents’demographic characteristics and awareness of health and the IPFH from March 26 to April 18,2020.IPFH consciousness was assessed by the scores for different related questions.The Student’s t test,the Chi-square test,and multiple logistic regression analysis were performed to analyze the differences and influencing factors.RESULTS A total of 2678 valid questionnaires were collected.Of the respondents,973(36.3%)had heard of the IPFH concept.In addition,89.5% of participants agreed with the view that the IPFH is beneficial to improving quality of life,and over half thought that a regular schedule,a reasonable diet,tobacco and alcohol control,a cheerful mood,specific life goals and plans,taking the initiative to accept health-related education and implement health knowledge,good interpersonal relationships,and regular physical examinations were closely related to the IPFH.The majority of respondents paid attention to their health and usually obtained health-related knowledge via social media and were also willing to promote the IPFH.Most of the participants underestimated the role of hospitals,family doctors,and health managers in promoting the IPFH.Age,monthly income,and medical-related work experience were the influencing factors for IPFH awareness.CONCLUSION The Chinese population has limited knowledge of the IPFH.People with strong IPFH awareness are older,earn more,and have medical-related work experience.

Diagnostic Accuracy of the Malnutrition Screening Tool (MST) in Adult Cancer Patients: a Systematic Literature Review and Meta-Analysis

Objective According to literature,cancer patients have the highest incidence of malnutrition among hospital patients(40%-80%).Despite this high prevalence,this condition is still under-diagnosed.The aim of this study was to conduct a systematic literature review and meta-analysis to assess the diagnostic performance of the Malnutrition Screening Tool(MST),a simple tool that can be applied in a busy setting where a comprehensive assessment at screening would be impractical.Methods PubMed,EMBASE and Cochrane central register of controlled trials were systematically searched to identify records relevant to the research question.The QUADAS-2 was used to assess the quality of each included study and the meta-analysis was conducted using the hierarchical bivariate model in STATA.Results Seven records were included in this study and the overall sensitivity specificity,diagnostic odds ratio(DOR).The pooled sensitivity and specificity generated after the meta-analysis in STATA were 0.78(95%CI:0.64-0.88)and 0.82(95%CI:0.76-0.87),respectively.The corresponding DOR was 16.33(95%CI:7.08-37.67).The positive likelihood ratio(LR+)was+4.39(95%CI:3.02-6.38),and the negative likelihood ratio(LR-)were 0.27(95%CI:0.16-0.47)and the 1/LR-3.72(2.14-6.46).Conclusion These results showed that the MST provides weak diagnostic evidence when used to screen for malnutrition in adult cancer patients.

Salvage irrigation-suction in gracilis muscle repair of complex rectovaginal and rectourethral fistulas

AIM:To evaluate the efficacy of gracilis muscle transposition and postoperative salvage irrigation-suction in the treatment of complex rectovaginal fistulas(RVFs)and rectourethral fistulas(RUFs).METHODS:Between May 2009 and March 2012,11female patients with complex RVFs and 8 male patients with RUFs were prospectively enrolled.Gracilis muscle transposition was undertaken in all patients and postoperative wound irrigation-suction was performed in patients with early leakage.Efficacy was assessed in terms of the success rate and surgical complications.SF-36 quality of life(QOL)scores and Wexner fecal incontinence scores were compared before and after surgery.RESULTS:The fistulas healed in 14 patients after gracilis muscle transposition;the initial healing rate was73.7%.Postoperative leakage occurred and continuous irrigation-suction of wounds was undertaken in 5patients:4 healed and 1 failed,and postoperative fecal diversions were performed for the patient whose treatment failed.At a median follow-up of 17 mo,the overall healing rate was 94.7%.Postoperative complications occurred in 4 cases.Significant improvement was observed in the quality outcomes framework scores(P<0.001)and Wexner fecal incontinence scores(P=0.002)after the successful healing of complex RVFs or RUFs.There was no significant difference in SF-36 QOL scores between the initial healing group and irrigationsuction-assisted healing group.CONCLUSION:Gracilis muscle transposition and postoperative salvage wound irrigation-suction gained a high success rate in the treatment of complex RVFs and RUFs.QOL and fecal incontinence were significantly improved after the successful healing of RVFs and RUFs.

Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population

Objective Traditional epidemiological studies have shown that C-reactive protein(CRP)is associated with the risk of cardiovascular diseases(CVDs).However,whether this association is causal remains unclear.Therefore,Mendelian randomization(MR)was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke,atrial fibrillation,arrhythmia and congestive heart failure.Methods We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken(JENGER),and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables.MR estimates were calculated with the inverse-variance weighted(IVW),penalized weighted median and weighted median.MR-Egger regression was used to explore pleiotropy.Results No significant causal association of genetically determined CRP level with ischemic stroke,atrial fibrillation or arrhythmia was found with all four MR methods(all Ps>0.05).The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure(OR:1.337,95%CI:1.005–1.780,P=0.046),whereas the other three methods did not.No clear pleiotropy or heterogeneity were observed.Conclusions Suggestive evidence was found only in analysis of congestive heart failure;therefore,further studies are necessary.Furthermore,no causal association was found between CRP and the other three cardiovascular outcomes.

Association between 25 Hydroxyvitamin D Concentrations and the Risk of COVID-19: A Mendelian Randomization Study

Coronavirus disease 2019(COVID-19),which is caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a global pandemic[1].Primary prevention,which is aimed at delaying disease onset by modulating modifiable risk factors,has been proposed to address the global challenge posed by COVID-19.

A Self-test Prediction Model to Determine the Probability Risk of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in Asia.Several studies have shown that NAFLD is associated with obesity,insulin resistance,type 2 diabetes,hypertension,hyperlipidemia,and metabolic syndrome(MS)[1].Several studies concluded that indicators such as body mass index(BMI),waist circumference(WC)。

免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联--一项孟德尔随机化研究

既往研究已发现免疫球蛋白G(immunoglobulin G,IgG)N-糖基化与代谢特征之间存在关联,但它们之间是否存在因果关联尚有待研究。本研究使用孟德尔随机化(Mendelian randomization,MR)研究方法整合全基因组关联研究(genome-wide association studies,GWAS)和数量性状基因座(quantitative trait loci,QTL)数据探究IgG N-糖基化与代谢特征之间的双向因果关联。在正向MR分析中,通过整合IgG N-糖基-QTL遗传变异与GWAS数据和代谢特征进行分析,分别发现59个包括影响体质指数(body mass index,BMI)的9个IgG N-糖基(glycan peaks,GP)(GP1和GP6等)和影响空腹血糖(fasting plasma glucose,FPG)的7个IgG N-糖基(GP1和GP5等)以及15个[包括影响BMI的5个IgG N-糖基(GP2和GP11等)和影响FPG的4个IgG N-糖基(GP1和GP10等)]由遗传决定的IgG N-糖基在单样本和两样本MR研究中与代谢特征存在因果关联(全部P<0.05)。相应地,对整合代谢特征-QTL-遗传变异与GWAS结果和IgG N-糖基进行MR分析的结果显示,在单样本和两样本MR研究中,分别发现72个包括影响GP1的1个因果代谢特征[高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)]和影响GP2的5个因果代谢特征[FPG、收缩压(systolic blood pressure,SBP)等]和4个[包括影响GP3的1个因果代谢特征(HDL-C)和影响GP9的1个代谢特征(HDL-C)]由遗传决定的代谢特征与IgG N-糖基之间存在因果关联(全部P<0.05)。值得注意的是,在单样本和两样本的MR分析中均发现了遗传决定的高水平的GP11与BMI水平增高存在因果关联[固定效应模型-Beta(SE):0.106(0.034)和0.010(0.005)]和高水平的HDL-C与GP9水平降低存在因果关联[-0.071(0.022)和-0.306(0.151)],且这一结果在单样本和两样本的meta汇总分析中得到了进一步验证[固定效应模型-Beta(95%置信区间)分别为:0.0109(0.0012,0.0207)和-0.0759(-0.1186,-0.0332)]。综上所述,本研究全面的双向MR分析提供了IgG N-糖基化与代谢特征之间双向因果关联的证据,在一定程度上揭示了IgG N-糖基化与代谢特征之间的生物学机制。

IgG N-糖基心血管年龄独立于真实年龄精准表征心血管事件风险

亚临床动脉粥样硬化和代谢紊乱是心血管健康的重要风险因素,应用免疫球蛋白G(IgG)N-聚糖模式作为炎症指标表征其发病风险已有研究报道。然而,对于IgG N-糖基谱在心血管疾病(CVD)风险分层中的能力仍然未知。本研究旨在利用IgG N-糖基标志物开发追踪心血管疾病风险的年龄指数。本研究基于横断面调查,从Busselton健康和老龄研究中共招募1465名40~70岁之间的个体。使用机器学习递归特征消除和惩罚回归算法逐步筛选特征糖基,并开发IgG N-糖基化心血管年龄(GlyCage)指数,以反映归因于心血管风险的与真实年龄间的偏差。结果显示,对GlyCage指数贡献最大的是具有双分叉N-乙酰葡萄糖胺(GlcNAc)的岩藻糖基化N-聚糖(GP6,FA2B)和具有双分叉GlcNAc的双半乳糖基化N-聚糖(GP13,A2BG2)。GlyCage独立于真实年龄,与较高的Framingham十年心血管风险[优势比(OR)为1.09;95%CI:1.05~1.13]和患心血管疾病概率(OR,1.07;95%CI:1.01~1.13)显著相关。GlyCage大于真实年龄三年及以上的个体,其心血管风险和心血管疾病患病概率增加,调整后的OR值分别为2.22(95%CI:1.41~3.53)和2.71(95%CI:1.25~6.41)。GlyCage指数区分十年心血管风险和事件的ROC曲线下面积(AUC)值分别为0.73和0.65,而真实年龄为0.65和0.63。因此,本研究开发的GlyCage指数利用IgG N-糖基谱追踪心血管健康水平。GlyCage和真实年龄之间的差距能够独立地表征心血管风险,提示IgG N-糖基化在心血管疾病的发病机制中起作用。GlyCage指数对心血管风险的预测能力需要在其他人群中进行外部和纵向验证。

A Nested Case-Control Study to Explore the Association between Immunoglobulin G N-glycans and Ischemic Stroke

Objective This study prospectively investigates the association between immunoglobulin G(IgG)N-glycan traits and ischemic stroke(IS) risk.Methods A nested case-control study was conducted in the China suboptimal health cohort study,which recruited 4,313 individuals in 2013–2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. Ig G N-glycans in baseline plasma samples were analyzed.Results A total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks(GPs) were separated from Ig G N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference,obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men(FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio(OR) = 0.92, 95% confidence interval(CI): 0.87–0.97;G1n: OR = 0.74, 95% CI: 0.63–0.87;G0n: OR =1.12, 95% CI: 1.03–1.22). However, these associations were not found among women.Conclusion This study validated that altered Ig G N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations.

月经周期中免疫球蛋白G N-糖基化的周期性变化

Immunoglobulin G(IgG)is the most abundant plasma glycoprotein and a prominent humoral immune mediator.Glycan composition affects the affinity of IgG to ligands and consequent immune responses.The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system.Although the menstrual cycle is the central sex hormonerelated physiological process in most women of reproductive age,IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated.To fill this gap,we profiled the plasma IgG Nglycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles(every 7 days for 3 months)using hydrophilic interaction ultra-performance liquid chromatography(HILIC-UPLC).We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma.On the integrated cohort level,the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait,with the highest being 1.1%for agalactosylated N-glycans.However,intrapersonal changes were relatively high in some cases;for example,the largest difference between the minimum and maximum values during the menstrual cycle was up to 21%for sialylated N-glycans.Across all measurements,the menstrual cycle phase could explain up to 0.72%of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation.In contrast,up to 99%of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation.In conclusion,the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small;thus,the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.

血清免疫球蛋白GN-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物

免疫球蛋白G(Immunoglobulin G,IgG)的N-糖基化在炎症性疾病的发展中起着重要作用。本研究旨在评价IgG N-糖基在消化道癌症亚型中的诊断效能。从中国医学科学院肿瘤医院招募749名消化道癌症患者,包括食管癌(esophageal cancer,EC)、胃癌(gastric cancer,GC)、结直肠癌(colorectal cancer,CRC)和胰腺癌(pancreatic cancer,PC)患者。采用亲水交互高效液相色谱-超高效液相色谱(hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography,HILIC-UPLC)分析血浆中IgG的N-糖基构成。采用Bio-Plex悬液芯片系统检测方法(Bio-Rad)进行炎症因子检测。采用典型相关分析(canonical correlation analysis,CCA)探索糖基和炎症因子之间的相关性。采用LASSO回归和logistic回归模型,基于检测到的糖基谱建立可用于区分胃肠癌症患者和健康人群诊断模型。与健康对照组相比,EC、GC、CRC和PC患者的唾液酸化和半乳糖基化水平降低,而二等分乙酰葡萄糖胺基化水平在消化道癌症患者中升高。此外,只有胰腺癌患者具有低水平的岩藻糖基化。消化道癌症组的IL-1β、IL-31和sCD40L水平均高于对照组。IgG N-糖基的组成与炎症因子相关(r=0.556)。基于糖基的模型表现出良好的诊断效能,EC、GC、CRC和PC的受试者工作特征曲线下面积(AUC)分别为0.972、0.871、0.867和0.907。这些研究结果表明,IgG N-糖基在调节消化道肿瘤的发病机制中发挥了重要作用。血清IgG N-糖基可以作为潜在的非侵入性辅助消化道癌症临床诊断的方法。