Thyroglobulin(Tg)is a glycoprotein with large molecular weight,which is synthesized and secreted into the bloodstream by thyroid follicular cells.The concentration level of Tg in blood is one of the important biomarkers for diagnosis of thyroid diseases such as differentiated thyroid cancer(DTC),subacute thyroiditis,etc..Radioimmunoassay(RIA),immunoradiometric assay(IRMA),and immunochemiluminescence assay(ICMA)are the main clinical methods for detecting Tg.Recently,for meeting the requirement of detecting low concentration of Tg in blood after thyroid clearance surgery,researchers have developed various high-performance analysis methods for detecting Tg concentration in blood samples,providing new assays for thyroid disease screening and efficacy evaluation.This review summarized the analysis methods of Tg,especially the new progresses in the biosensors for monitoring low concentration of Tg in blood during the past five years.The current technical challenges of these methods in clinical applications were briefly discussed,which might provide useful information for developing new liquid biopsy methods of DTC.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To explore the predictive value of soluble fms-like tyrosine kinase-1(sFlt-1)and leukotriene B4(LTB4)in patients with intracranial aneurysms for cerebral vasospasm(CVS)after interventional embolization.Methods A total of 98 patients with intracranial aneurysms admitted to our hospital from January 2019 to September 2023 were regarded as the observation group,and were divided into the CVS group(32 cases)and the non CVS group(66 cases)according to whether CVS occurred or not within 3 to 5 days after surgery;102 healthy examinees in our hospital were selected as the control group.Enzyme-linked immunosorbent assay was used to detect serum levels of sFlt-1 and LTB4;the influencing factors for CVS after interventional embolization of intracranial aneurysms were analyzed by Logistic regression analysis;the predictive value of serum sFlt-1 and LTB4 levels for the occurrence of CVS after interventional embolization of intracranial aneurysms was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of sFlt-1 and LTB4 of patients in the observation group were obviously higher than those in the control group,and the differences were statistically significant(P<0.05).The serum levels of sFlt-1 and LTB4,and the proportions of patients with postoperative blood pressure fluctuation range≥30 mmHg and Hunt-Hess grade Ⅲ in the CVS group were obviously higher than those in the non CVS group,and the differences were statistically significant(P<0.05).SFlt-1(OR:2.985;95%CI:1.684 to 5.291)and LTB4(OR:2.868;95%CI:1.581 to 5.204)were the independent risk factors for CVS after interventional embolization of intracranial aneurysms(P<0.05).The area under the curve(AUC)of sFlt-1 and LTB4 alone and in combination for predicting the occurrence of CVS after interventional embolization of intracranial aneurysms were 0.839,0.825,and 0.915,respectively,with sensitivity of 84.44%,87.59%,and 81.36%,and specificity of 74.26%,75.87%,and 90.98%,respectively.The AUC of the combination of the two was higher than those of sFlt-1 and LTB4 alone,and the differences were statistically significant(Z=2.150,2.546,P<0.05).Conclusion The serum levels of sFlt-1 and LTB4 in patients with CVS after interventional embolization of intracranial aneurysms are increased,and the combination of the two can serve as the important indicators for predicting CVS.

Objective:To investigate the effect of macrophage polarization mediated by Jumonji domain containing-3(JMJD3)-interferon regulatory factor 4(IRF4)signaling pathway on the malignant biological behavior of multiple myeloma(MM)cells.Methods:THP-1 monocytes were induced to differentiate into macrophages by phorbol myristate acetate(PMA).THP-1 macrophages were divided into control group(normal culture),M2 induction group[added recombinant human interleukin(IL)-4,IL-13 proteins],M2+JMJD3 protein group(added recombinant human IL-4,IL-13 and JMJD3 proteins)and M2+JMJD3 inhibitor group(added recombinant human IL-4,IL-13 proteins and JMJD3 inhibitor),the proportion of CD206+cells was detected by flow cytometry,the levels of IL-10 and transforming growth factor-β(TGF-β)in the culture supernatant were detected by ELISA assay,the expression levels of arginase-1(Arg-1),JMJD3 and IRF4 mRNA were detected by real-time quantitative PCR(qRT-PCR),and the expression levels of Arg-1,JMJD3 and IRF4 proteins were detected by Western blot.Correspondingly,human MM cells U266 were cultured with THP-1 macrophage culture supernatant of each group,Methyl thiazolyl tetrazolium(MTT)method and plate colony formation assay were used to detect cell proliferation,cell apoptosis was detected by flow cytometry,Western blot was used to detect the expression levels of apoptosis-promoting protein Bcl-2-associated X protein(Bax)and cleaved caspase-3 in cells,and Transwell assay was used to detect cell migration and invasion.Results:Compared with the control group,the proportion of CD206+cells in THP-1 macrophages,the mRNA and protein expression levels of Arg-1,JMJD3 and IRF4,and the levels of IL-10 and TGF-β in the cell culture supernatant in M2 induction group were significantly increased(P＜0.001),meanwhile,the proliferation activity and the number of clones of U266 cells were significantly increased(P＜0.01),the apoptosis rate and the expression levels of apoptosis-promoting protein Bax and cleaved caspase-3 were significantly decreased(P＜0.001),the numbers of migrated cells and invasive cells were increased(P＜0.001).Compared with M2 induction group,the proportion of CD206+cells in THP-1 macrophages,the mRNA and protein expression levels of Arg-1,JMJD3 and IRF4,and the levels of IL-10 and TGF-β in the cell culture supernatant in M2+JMJD3 protein group were further increased(P＜0.01),meanwhile,the proliferation activity and the number of clones of U266 cells were further increased(P＜0.05),the apoptosis rate and the expression levels of apoptosis-promoting protein Bax and cleaved caspase-3 were further decreased(P＜0.01),the numbers of migrated cells and invasive cells were further increased(P＜0.001);However,the change trends of the above indexes in M2+JMJD3 inhibitor group were opposite to those in M2+JMJD3 protein group.Conclusion:M2 polarization of macrophages mediated by JMJD3-IRF4 signaling pathway can promote the proliferation,migration and invasion of MM cells,and inhibit cell apoptosis.

Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

Objective: To explore the intraseasonal variation in mortality risk from cold temperature exposure in Shandong Province. Methods: Mortality data in Shandong province from 2013 to 2018 were collected from the cause of death surveillance system of Shandong Center for Disease Control and Prevention. The basic information mainly included the date of death, age, gender, education level, cause of death, home address, etc. The daily meteorological data from China Meteorological Data Network mainly included the grid coordinate data of 0.01°×0.01° latitude and longitude, such as daily average temperature (℃) and daily average relative humidity (%). The cold season was from November to February. The first two months were the early cold season and the last two months were the late cold season. The extreme cold temperature was defined as the 10^th percentile of the temperature range of cold season. Time-stratified case crossover design with distributed lag non-linear model analyzed the association between temperature and mortality and the association between extreme low temperature and mortality in different lag days in the cold season, and compared the intraseasonal differences between early (November-December) and late (January-February) cold season. Results: The temperature ranged from -17.3 ℃ to 18.6 ℃ in Shandong Province during the cold season from 2013 to 2018, and the P₁₀ (extreme low temperature) was -13.7 ℃. The average daily temperature in the early cold season was (3.63±4.66) ℃. The temperature in the late cold season was (-0.09±3.70) ℃. The average daily relative humidity was (63.89±14.75) % in the early cold season and (62.27±14.19) % in the late cold season. This study included 1 473 300 deaths in the cold season in Shandong Province between 2013 and 2018. There were 824 601 (55.97%) males and 349 824 (23.75%) cases aged<65 years. There were 803 691 (54.55%) deaths due to circulatory diseases and 140 415 (9.53%) deaths due to respiratory diseases. The results of DLNM showed that the cumulative OR of extreme low temperature in the four months of cold season was 1.74 (95%CI: 1.63, 1.86) with the optimal temperature of 18.6 ℃ as the reference. The cumulative OR values of early and late cold season were 1.50 (95%CI: 1.32, 1.71) and 2.56 (95%CI: 2.12, 3.09), respectively (P<0.001). The lag effect lasted for 12 d. Conclusion: There is an intraseasonal variation of the association between cold temperature and mortality risk in Shandong Province. The mortality risk related to cold temperature in the late cold season is higher than that in the early cold season.
Female ; Humans ; Male ; China/epidemiology* ; Cold Temperature ; Cross-Over Studies ; Hot Temperature ; Mortality ; Seasons ; Temperature ; Middle Aged ; Aged

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Objective:To investigate epidemiological characteristics of a viral rash caused by enterovirus.Methods:Retrospective epidemiological analysis was carried out on the cases who had infections in a company. Throat swab samples were collected to detect 22 kinds of respiratory pathogenic agents’ nucleic acids. Enterovirus VP1 gene was amplified and sequenced.Results:A total of 14 adult cases with skin rash, fever, conjunctival hyperemia and sore throat were reported from February 14 to February 21, 2019 from different departments of the company. The peak of incidence occurred on February 18. There were 4 cases. The clinical features were. Of the 14 cases, 6 were male and 8 were female, male: female ration was 0.75∶1. The average age was 35 years.VP1 sequencing showed that 6 cases had coxsackievirus A6 (CV-A6) infection.Conclusions:Combined with the result of epidemiological investigation and laboratory tests, it can be concluded that the viral rash was caused by enterovirus coxsackievirus A6.