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1.
Blood ; 143(2): 124-138, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-37748139

ABSTRACT

ABSTRACT: Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity. The molecular mechanisms behind this phenomenon are not fully understood. Here, we observed that the expression of FUS is increased in aged HSCs, and enforced FUS recapitulates the phenotype of aged HSCs through arginine-glycine-glycine-mediated aberrant FUS phase transition. By using Fus-gfp mice, we observed that FUShigh HSCs exhibit compromised FUS mobility and resemble aged HSCs both functionally and transcriptionally. The percentage of FUShigh HSCs is increased upon physiological aging and replication stress, and FUSlow HSCs of aged mice exhibit youthful function. Mechanistically, FUShigh HSCs exhibit a different global chromatin organization compared with FUSlow HSCs, which is observed in aged HSCs. Many topologically associating domains (TADs) are merged in aged HSCs because of the compromised binding of CCCTC-binding factor with chromatin, which is invoked by aberrant FUS condensates. It is notable that the transcriptional alteration between FUShigh and FUSlow HSCs originates from the merged TADs and is enriched in HSC aging-related genes. Collectively, this study reveals for the first time that aberrant FUS mobility promotes HSC aging by altering chromatin structure.


Subject(s)
Aging , Hematopoietic Stem Cells , Mice , Animals , Aging/physiology , Phenotype , Hematopoietic Stem Cells/metabolism , Chromatin/metabolism , Glycine/metabolism
2.
J Viral Hepat ; 30(6): 489-496, 2023 06.
Article in English | MEDLINE | ID: mdl-36807422

ABSTRACT

In 2020, China conducted a nationwide, sero-epidemiological, cross-sectional survey of viral hepatitis. The stratified multi-stage cluster random sampling method was used to select the permanent population aged 1-69 years, followed by questionnaire survey and sample collection and detection of the serological markers of hepatitis B (HBV) and hepatitis C viruses (HCV). A total of 4747 individuals aged 1-69 years were investigated in Zhejiang Province. The positive rates of hepatitis B surface antigen and anti-HCV were 4.3% and 0%, respectively. Compared to a similar sero-epidemiological survey in 1992, the 2020 survey showed that the HBV infection rate in Zhejiang Province decreased by 56.5%. In both surveys, HBV infection rate increased with age (in 1992, χ2  = 185.866, p = .000; in 2020, χ2  = 1383.836, p = .000). Compared with 1992, the positive anti-HCV rate in those aged 1-69 years in 2020 decreased by 100.0%. This result showed that the HBV vaccine and blood screening to prevent HBV and HCV infection significantly decreased the infection rate of HBV and HCV in the younger generation of Zhejiang province. However, the rate of HBV carriers aged 30-69 years was still high, which underscores the need to strengthen the management and treatment of chronic HBV infection. Hence, Zhejiang province can eliminate the public health threat of viral hepatitis.


Subject(s)
Hepatitis B , Hepatitis C , Humans , Seroepidemiologic Studies , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Hepacivirus , Hepatitis B virus , China/epidemiology , Prevalence , Surveys and Questionnaires , Cross-Sectional Studies , Male , Female , Adolescent , Adult , Middle Aged , Aged , Infant , Child, Preschool , Child
3.
Haematologica ; 108(10): 2677-2689, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37165848

ABSTRACT

Aged hematopoietic stem cells (HSC) exhibit compromised reconstitution capacity and differentiation-bias towards myeloid lineage, however, the molecular mechanism behind it remains not fully understood. In this study, we observed that the expression of pseudouridine (Ψ) synthase 10 is increased in aged hematopoietic stem and progenitor cells (HSPC) and enforced protein of Ψ synthase 10 (PUS10) recapitulates the phenotype of aged HSC, which is not achieved by its Ψ synthase activity. Consistently, we observed no difference of transcribed RNA pseudouridylation profile between young and aged HSPC. No significant alteration of hematopoietic homeostasis and HSC function is observed in young Pus10-/- mice, while aged Pus10-/- mice exhibit mild alteration of hematopoietic homeostasis and HSC function. Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. Taken together, this study for the first time evaluated the role of PUS10 in HSC aging and function, and provided a novel insight into HSC rejuvenation and its clinical application.


Subject(s)
Intramolecular Transferases , RNA , Animals , Mice , Intramolecular Transferases/genetics , Intramolecular Transferases/metabolism , Hematopoietic Stem Cells/metabolism , Aging
4.
J Viral Hepat ; 29(4): 280-288, 2022 04.
Article in English | MEDLINE | ID: mdl-35075747

ABSTRACT

To evaluate the cost-effectiveness of the post-vaccination serologic testing (PVST) plus active-passive immunoprophylaxis of infants born to hepatitis B surface antigen (HBsAg)-positive mothers, a Markov model was constructed by R 4.0.1 to compare the current strategy (three-dose HepB plus HBIG) and the PVST strategy (post-vaccination serologic testing plus the current strategy) for infants of HBsAg-positive mothers. Costs and utility scores were assessed from a field survey. Other model inputs were extracted from published literature and unpublished data from the Zhejiang provincial center for disease control and prevention (Zhejiang CDC). We calculated the incremental cost-effectiveness ratio (ICER) as the main result within 1-year cycle length with a 81 horizon among 50,000 infants and performed one-way sensitivity analysis and probabilistic sensitivity analysis to explore the reliability of outcome. The ICER was -4130.18 yuan/quality-adjusted life year (QALY) for the PVST strategy compared with the current strategy from the societal perspective. It was estimated that the PVST strategy would save about 3,809,546 yuan and prevent loss of 922.37 QALYs within 81 cycles among 50,000 infants. ICER was most sensitive to the discount rate, and the cost-effectiveness acceptability curves showed that the PVST strategy reached a probability of being 100% cost-effective below willing to pay (107,624 yuan). In conclusion, the PVST strategy had increased the utility and reduced cost among infants born to HBsAg-positive mothers. The PVST strategy is a more cost-effective choice for infants born to HBsAg-positive mothers than the current strategy, and further promotion of the PVST project is recommended.


Subject(s)
Hepatitis B Surface Antigens , Hepatitis B , China , Cost-Benefit Analysis , Female , Hepatitis B/prevention & control , Hepatitis B Vaccines , Humans , Infant , Markov Chains , Mothers , Reproducibility of Results , Vaccination
5.
Blood ; 136(2): 183-198, 2020 07 09.
Article in English | MEDLINE | ID: mdl-32305041

ABSTRACT

Hematopoietic stem cell (HSC) aging correlates with an increasing risk of myeloproliferative disease and immunosenescence. In this study, we show that aging-related inflammation promotes HSC aging through tumor necrosis factor-α (TNF-α)→ERK→ETS1→interleukin27Ra (IL27Ra) pathway. TNF-α, a well-known biomarker of inflammation, increases during aging and induces the expression of IL27Ra on HSCs via ERK-ETS1 signaling. Deletion of IL27Ra rescues the functional decline and myeloid bias of HSCs and also reverses the inhibitory effect of TNF-α on HSCs. Aged IL27Ra-/- mice had a reduced proportion of myeloid-biased HSCs and did not display the biased myeloid differentiation that occurs in aged wild-type mice. IL27Ra+ HSCs exhibit impaired reconstitution capacity and myeloid-bias compared with IL27Ra- HSCs and serve as a myeloid-recovery pool upon inflammatory insult. Inflammation-related genes were enriched in IL27Ra+ HSCs and this enrichment increases with aging. Our study demonstrates that age-induced IL27Ra signaling impairs HSCs and raises the possibility that interfering with IL27Ra signaling can counter the physiologically deleterious effect of aging on hematopoietic capacity.


Subject(s)
Aging/immunology , MAP Kinase Signaling System/immunology , Myeloid Progenitor Cells/immunology , Receptors, Interleukin/immunology , Aging/genetics , Aging/pathology , Animals , Inflammation/genetics , Inflammation/immunology , Inflammation/pathology , MAP Kinase Signaling System/genetics , Mice , Mice, Knockout , Myeloid Progenitor Cells/pathology , Receptors, Interleukin/genetics , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
6.
J Viral Hepat ; 28(10): 1413-1421, 2021 10.
Article in English | MEDLINE | ID: mdl-34310810

ABSTRACT

In 2016, China officially proposed for the first time that infants born to HBsAg-positive mothers should be tested for HBsAg and anti-HBs 1-2 months after their third dose of HepB, also known as the post-vaccination serological testing programme. This study aimed to systematically evaluate the implementation and influencing factors of PVST to further reduce HBV infection risk in infants and improve the protective effect of HepB to the greatest extent. A prospective observational study was conducted to investigate the interruption of MTCT of hepatitis B. Univariate and multivariate analyses were applied to explore factors associated with the PVST follow-up rate among HBsAg-positive mothers and their infants. Additionally, bivariate analysis was performed on HBsAg and anti-HBs results in infants born to HBsAg-positive mothers. Here, the participation rate of PVST was 67.08% among 2120 pairs of positive mothers and infants. The HBsAg-positive rate among participants was 0.77%, whereas the anti-HBs positive rate was 96.84%, and both negative rates were 2.39%. Among infants with double negative results (34), only 15 completed three doses of HepB and PVST again, and 14 (93.33%) of which the antibody test results turned positive. Older mothers with high educational levels who reside in the local area were the most likely to PVST follow-up. The PVST programme is necessary to evaluate the HepB response status of newborns after vaccination. Moreover, revaccination for susceptible infants can effectively improve the MTCT-blocking rate of hepatitis B. Therefore, the scope of PVST projects in Zhejiang and China should be expanded.


Subject(s)
Hepatitis B Surface Antigens , Hepatitis B , Female , Follow-Up Studies , Hepatitis B/prevention & control , Hepatitis B Antibodies , Hepatitis B Vaccines , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Mothers , Prospective Studies , Vaccination
7.
BMC Public Health ; 21(1): 1157, 2021 06 16.
Article in English | MEDLINE | ID: mdl-34134671

ABSTRACT

BACKGROUND: Previous studies have shown that a certain proportion of the population did not seek medical treatment after coughing, and understanding the potential reasons is crucial for disease prevention and control. METHOD: A population-based study was conducted with the probability proportional to population size sampling in Yiwu, Zhejiang, China. A total of 5855 individuals aged ≥15 years lived in Yiwu for more than 6 months were included. All participants completed a laptop-based questionnaire to collect detailed information by a face-to-face interview. Characteristics of individuals were described by categories of health seeking behavior using frequency and percentage. Univariate and multivariate logistic regression analyses were performed to estimate the associations of social-demographic and cough characteristics with health seeking behavior. RESULTS: 19.3% (1129/5855) of participants had a cough in the past month, 40% (452/1129) had sought medical treatment. Of these, 26.5% (120/452) chose hospitals at county level or above. Individuals aged ≥65 years old (OR = 2.25, 95% CI: 1.23, 4.12), female (OR = 1.57, 95% CI: 1.21, 2.06), living in rural areas (OR = 1.30, 95% CI: 1.003, 1.69), persistent cough for 3-8 weeks (OR = 2.91, 95% CI: 1.72, 4.92) and with more accompanying symptoms (P trend < 0.001) were more likely to seek medical treatment, but those coughed for > 8 weeks were not (p > 0.5). Female (OR = 0.33, 95% CI: 0.21, 0.54) and people living in rural areas (OR = 0.57, 95% CI: 0.36, 0.92) were less likely to choose hospitals at county level or above while the higher educated were more likely to (OR = 3.29, 95% CI: 1.35, 8.02). Those who coughed for more than 2 weeks were more likely to choose hospitals at or above the county level. But the number of accompanying symptoms does not show any significant relationship with the choice of medical facility. CONCLUSION: The present study found that age, sex, living areas and features of cough were associated with health seeking behavior. It is worth noting that those who coughed for too long (e.g. > 8 weeks) were less likely to seek medical treatment. Targeted measures should be developed based on the key factors found in this study to guide persons to seek medical treatment more scientifically.


Subject(s)
Cough , Patient Acceptance of Health Care , Aged , China/epidemiology , Cough/epidemiology , Cross-Sectional Studies , Delivery of Health Care , Female , Health Behavior , Humans
8.
J Med Virol ; 92(1): 62-70, 2020 01.
Article in English | MEDLINE | ID: mdl-31475733

ABSTRACT

T follicular helper (TFH) cells, a critical subset of CD4+ T cells, provide help to B cells during the procession of the humoral immune response in the germinal center (GC) and extrafollicular sites. CXCR5+ CD4+ T cells in human circulating blood, referred to herein as peripheral TFH (pTFH) cells, share phenotypes and functional properties with TFH cells in GC. Hepatitis B vaccine protects about 60% of the chronic hepatitis C patients from hepatitis B. The immunological bases that lead to the induction of protective antibody response is not well understood. In the present study, the pTFH cells subsets were determined in 18 healthy controls (anti-HBs ≥ 100 mIU/mL; HC), 21 nonresponders (anti-HBs < 10 mIU/mL; NR), and 23 weak responders (10 mIU/mL ≤ anti-HBs < 100 mIU/mL; WR) of chronic hepatitis patients upon routine hepatitis B vaccination. Though the frequency of the pTFH cell was equivalent in HC, WR, and NR, ICOS+ pTFH cells in HC underwent expansion with increased IL-21 secretion and production of serum anti-HBs response at 4 weeks after a full course of hepatitis B vaccination. These changes were not shown in both NR and WR. Analysis of ICOS+ pTFH cells represents a novel cellular determinant of the hepatitis B vaccine-induced humoral immune response, which may have relevance for design of hepatitis B vaccine.


Subject(s)
Antibody Formation , Hepatitis B Vaccines/immunology , Hepatitis B/immunology , Inducible T-Cell Co-Stimulator Protein/blood , T Follicular Helper Cells/immunology , Adult , Aged , Cytokines/blood , Female , Hepatitis B/prevention & control , Hepatitis B Antibodies/blood , Humans , Immunity, Humoral , Interleukins/blood , Male , Middle Aged , Vaccination
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 47(2): 169-173, 2018 05 25.
Article in Zh | MEDLINE | ID: mdl-30226312

ABSTRACT

OBJECTIVE: To determine measles antibody levels and influencing factors among children aged 6 to 15 years in Zhejiang province. METHODS: Blood samples were collected from 2069 children aged 6 to 15 years in Changxing county (Huzhou) and Liandu district (Lishui) of Zhejiang province. Serum level of measles IgG antibody was measured using ELISA, and 800 mIU/mL was applied as the cut-off point of high antibody level. Chi-square or trend Chi-square test was used to analyze difference in positive rates of high antibody level among children with different characters, and the factors related to high antibody level in the vaccinated children were analyzed using multivariate logistic regression. RESULTS: Among 2069 subjects, positive rate of high measles antibody level was 36.06% (746/2069). Multivariate logistic regression showed that the high measles antibody level was significantly associated with age of children and the age of first measles vaccine inoculation. The positive rate of high measles antibody level decreased with age(OR=0.866, 95%CI:0.830-0.904, P<0.01), and the positive rate in children whose first vaccination at ≥ 12 months of age was higher than those whose first vaccination at 8 months of age(OR=0.633, 95%CI:0.498-0.805, P<0.01). CONCLUSIONS: In order to obtain high measles antibody level and to maintain high levels of population immune barrier, it is suggested that first dose of vaccination can be appropriately delayed in low epidemic areas, and elder children should have timely catch-up vaccination.


Subject(s)
Measles , Adolescent , Antibodies, Viral , Child , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G , Male , Measles Vaccine , Vaccination
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 47(4): 374-380, 2018 02 25.
Article in Zh | MEDLINE | ID: mdl-30511524

ABSTRACT

OBJECTIVE: To evaluate the cost/benefit of different vaccination strategies related to chickenpox vaccine. METHODS: The direct economic cost and indirect economic cost caused by chickenpox were obtained through questionnaire survey. The epidemic characteristics of chickenpox in Zhejiang province were studied by literature review. Dynamic model was set up by Matlab software based on the parameters of chickenpox, to predict the incidence trends of chickenpox with different immunization strategies (no vaccination, 1-dose vaccination, 2-dose vaccination) in future 40 years (2017-2056). A cost-benefit analysis was conducted, and the sensitivities of the main parameters were analyzed. RESULTS: Through the questionnaire survey of 105 cases, the direct and indirect economic cost per case was 506.84 Yuan and 1045.39 Yuan respectively, with the total of 1552.23 Yuan. During the prediction period (40 years), there would be 7.0908 million cases in strategy 2, which was 59.71% less than strategy 1 (17.5989 million cases). Total vaccination costs in strategy 2 were 2.366 billion Yuan, with a total economic gain of 33.741 billion Yuan and benefit/cost ratio (BCR) of 14.26:1. If strategy 3 was adopted, 2.7249 million chickenpox cases would occur, with a decrease of 84.52% compared with strategy 1. Total vaccination costs in strategy 3 was 4.495 billion Yuan, with a total economic gain of 44.309 billion Yuan and BCR of 9.86:1. Analysis showed that the vaccine price was the most sensitive variable, followed by the incidence of chickenpox in the absence of vaccine. CONCLUSIONS: In Zhejiang province, one-dose strategy and two-dose strategy were both cost effective. It is suggested that the chickenpox vaccination should be included in the immunization program in Zhejiang province.


Subject(s)
Chickenpox Vaccine , Chickenpox , Cost-Benefit Analysis , Immunization Programs , Vaccination , Chickenpox/prevention & control , Humans , Immunization Programs/economics , Immunization Programs/methods , Vaccination/economics
11.
BMC Infect Dis ; 16(1): 723, 2016 Nov 30.
Article in English | MEDLINE | ID: mdl-27899091

ABSTRACT

BACKGROUND: In order to control the spread of rubella and reduce the risk for congenital rubella syndrome, an additional rubella vaccination program was set up for all secondary school students since 2008 in Zhejiang, China. METHODS: We conducted a descriptive analysis of rubella incidence among different age groups from 2005 to 2015 and a serosurvey of female subjects aged 15-39 years to understand the possible effects of this immunization program. RESULTS: The average annual rubella incidence rate had decreased from 15.86 per 100,000 population (2005-2007) to 0.75 per 100,000 population (2013-2015) in Zhejiang. The decrease in the rate of rubella incidence in girls aged 15-19 years was more accelerated (from 138.30 to 0.34 per 100,000) than in the total population during 2008-2015 (from 32.20 to 0.46 per 100,000). Of 1225 female subjects in the serosurvey, 256 (20.9%) were not immune to rubella. The proportion of subjects immune to rubella was significantly different among different age groups (Wald χ2 = 22.19, p = 0.000), and subjects aged 15-19 years old had the highest immunity (88.0%). Rubella antibody levels were significantly lower in women aged 25-30 years with 26.7% of them not immune, followed by the group aged 20-24 years (25.0%) and 30-35 years (24.5%). CONCLUSIONS: Rubella vaccine included in the Expanded Program on Immunization together with vaccination activities for secondary school students can help in rubella control, particularly in targeted age groups in the program. Seroprevalence of antibodies to the rubella virus amongst the female population within childbearing age in Zhejiang, China, is still too low to provide immunity. In addition to vaccination programs in the secondary schools, rubella vaccination should also be encouraged in women of childbearing age, which can be done effectively combined with pre-marital examination in China.


Subject(s)
Rubella Syndrome, Congenital/prevention & control , Rubella Vaccine/therapeutic use , Rubella/epidemiology , Rubella/prevention & control , Adolescent , Adult , Antibodies, Viral/blood , China/epidemiology , Female , Humans , Immunization Programs , Rubella Syndrome, Congenital/epidemiology , Rubella Vaccine/immunology , Rubella virus/immunology , Rubella virus/pathogenicity , Schools , Seroepidemiologic Studies , Serologic Tests , Students , Young Adult
12.
Med ; 5(3): 173-175, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38460494

ABSTRACT

We analyzed the potential of HER2-targeted antibody-drug conjugates (ADCs) in treating NSCLC with activating HER2 mutations. We identified specific mutations, notably G776delinsVC, that are associated with higher therapeutic response rates, suggesting a refined approach for precision treatment. Further validation and exploration are crucial for potential breakthroughs in ADC therapy.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Immunoconjugates , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Immunoconjugates/therapeutic use , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Trastuzumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy
13.
Sci Rep ; 14(1): 8345, 2024 04 09.
Article in English | MEDLINE | ID: mdl-38594451

ABSTRACT

With the rapid development of new energy vehicles, the users have an increasing demand for charging piles. It is generally believed that the charging pile is a kind of practical product, and it only needs to realize the charging function. However, as a product, the shape design of the charging pile will directly affect the user experience, thus affecting product sales. Therefore, in the face of increasingly fierce market competition, when designing the shape of charging piles, it is necessary to adopt the traditional evaluation method and human physiological cognitive characteristics to evaluate the shape of charging piles more objectively. From the user's point of view, using the electroencephalogram (EEG) of the user, with the help of the multifractal detrended fluctuation analysis (MF-DFA) method, this paper comprehensively analyzes the differences in emotional cognitive characteristics between two kinds of charging piles, namely, the charging pile with a curved appearance design and the charging pile with square appearance design. The results show that there are significant differences in human physiological cognitive characteristics between two kinds of charging piles with different shapes. And different shapes of charging piles have different physiological cognitive differences for users. When designing charging pile product shapes, human beings can objectively evaluate the product shape design according to the physiological cognition differences of users, so as to optimize the charging pile product shape design.


Subject(s)
Hemorrhoids , Humans , Electroencephalography
14.
Nat Aging ; 4(4): 510-526, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38632351

ABSTRACT

DNA damage contributes to the aging of hematopoietic stem cells (HSCs), yet the underlying molecular mechanisms are not fully understood. In this study, we identified a heterogeneous functional role of microcephalin (MCPH1) in the nucleus and cytoplasm of mouse HSCs. In the nucleus, MCPH1 maintains genomic stability, whereas in the cytoplasm, it prevents necroptosis by binding with p-RIPK3. Aging triggers MCPH1 translocation from cytosol to nucleus, reducing its cytoplasmic retention and leading to the activation of necroptosis and deterioration of HSC function. Mechanistically, we found that KAT7-mediated lysine acetylation within the NLS motif of MCPH1 in response to DNA damage facilitates its nuclear translocation. Targeted mutation of these lysines inhibits MCPH1 translocation and, consequently, compromises necroptosis. The dysfunction of necroptosis signaling, in turn, improves the function of aged HSCs. In summary, our findings demonstrate that DNA damage-induced redistribution of MCPH1 promotes HSC aging and could have broader implications for aging and aging-related diseases.


Subject(s)
DNA Damage , Necroptosis , Animals , Mice , Aging/genetics , DNA Damage/genetics , Genomic Instability , Hematopoietic Stem Cells/physiology , Translocation, Genetic
15.
Nat Aging ; 4(2): 213-230, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38233630

ABSTRACT

Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity and differentiation bias toward myeloid lineages. However, the molecular mechanism behind HSC aging remains largely unknown. In this study, we observed that RNA N1-methyladenosine-generating methyltransferase TRMT6-TRMT61A complex is increased in aged murine HSCs due to aging-declined CRL4DCAF1-mediated ubiquitination degradation signaling. Unexpectedly, no difference of tRNA N1-methyladenosine methylome is observed between young and aged hematopoietic stem and progenitor cells, suggesting a noncanonical role of the TRMT6-TRMT61A complex in the HSC aging process. Further investigation revealed that enforced TRMT6-TRMT61A impairs HSCs through 3'-tiRNA-Leu-CAG and subsequent RIPK1-RIPK3-MLKL-mediated necroptosis cascade. Deficiency of necroptosis ameliorates the self-renewal capacity of HSCs and counters the physiologically deleterious effect of enforced TRMT6-TRMT61A on HSCs. Together, our work uncovers a nonclassical role for the TRMT6-TRMT61A complex in HSC aging and highlights a therapeutic target.


Subject(s)
Hematopoietic Stem Cells , Signal Transduction , Mice , Animals , Cell Differentiation/genetics , Aging/genetics
16.
Hum Vaccin Immunother ; 20(1): 2341454, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38695296

ABSTRACT

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.


Subject(s)
Antibodies, Bacterial , Immunoglobulin G , Pertussis Toxin , Whooping Cough , Humans , Seroepidemiologic Studies , Pertussis Toxin/immunology , Immunoglobulin G/blood , Whooping Cough/epidemiology , Whooping Cough/immunology , Whooping Cough/prevention & control , China/epidemiology , Antibodies, Bacterial/blood , Child , Adult , Young Adult , Adolescent , Child, Preschool , Middle Aged , Pertussis Vaccine/immunology , Pertussis Vaccine/administration & dosage , East Asian People
17.
Hum Vaccin Immunother ; 20(1): 2338505, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38599768

ABSTRACT

The waning of maternal antibodies may cause infants to lose protection against measles before receiving measles-containing vaccine (MCV). The aim of this study is to investigate the changing characteristics and influencing factors of measles antibodies in preterm infants (PT), and to provide scientific basis for optimizing MCV vaccination strategy of the target population. Blood samples were collected from PT and full-term infants (FT) at the chronological age (CA) of 3, 6, and 12 months. Measles antibodies were quantitatively detected by enzyme-linked immunosorbent assay. Demographic and vaccination information were both collected. Kruskal-Wallis rank sum test was used to compare the measles antibodies among different gestation age (GA) groups, and multiple linear regression was performed to identify the correlative factors for the antibodies. Measles antibodies of PT decreased significantly with age increasing before MCV vaccination. The positive rates of antibodies of PT were 10.80% and 3.30% at the age of 3 and 6 months, respectively (p < .001). At 12 months, the measles antibodies and seropositive rate in the infants who received MCV vaccination increased sharply (p < .001). Regression analyzes showed that the younger the GA or the older the age, the lower the antibodies at 3 months(p < .001,p = .018); while the lower measles antibody levels at 3 months and older age predicted the lower antibodies at 6 months(p < .001, p = .029). PT were susceptible to measles due to the low level of maternally derived antibodies before MCV vaccination. More efforts should be considered to protect the vulnerable population during their early postnatal life.


Subject(s)
Infant, Premature , Measles , Infant , Humans , Infant, Newborn , Measles Vaccine , Measles/prevention & control , Measles virus , Antibodies, Viral , China/epidemiology , Vaccination
18.
Thorac Cancer ; 15(14): 1187-1194, 2024 May.
Article in English | MEDLINE | ID: mdl-38576119

ABSTRACT

INTRODUCTION: Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. METHODS: To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross-dimensional real-world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit-risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. DISCUSSION: This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Risk Assessment/methods , Carcinoma, Non-Small-Cell Lung/drug therapy , Antineoplastic Agents/therapeutic use , Patient Selection , China , Eligibility Determination/methods
19.
BMC Infect Dis ; 13: 139, 2013 Mar 18.
Article in English | MEDLINE | ID: mdl-23506461

ABSTRACT

BACKGROUND: A prolonged measles epidemic occurred in Wenzhou City, China after a nationwide measles mass immunization campaign (MMIC) in 2010. We conducted an investigation to identify factors contributing to this epidemic and to provide evidence-based recommendations for measles elimination strategies in China. METHODS: Measles was diagnosed using the national standard case-definitions. We estimated the population vaccination coverage based on the proportion of measles patients that had been vaccinated. In a case-control investigation, all measles patients who received treatment in The Second Affiliated Hospital of Wenzhou Medical College (Hospital S) during November 1 to December 31, 2010 served as cases; controls were randomly selected among all other patients who received treatment in Hospital S during the same time period, frequency matched by month of hospital visit. We reviewed medical records of case- and control-patients to compare their exposure history at Hospital S and to its intravenous rehydration room (IV room) during the incubation period (7-21 days before their illness onset). RESULTS: The attack rate of measles in Wenzhou City was 3.3/100,000 during September 1, 2010 to January 11, 2011. Children aged 8-11 m had the highest attack rate (171/100,000) of all age groups. In children not age-eligible for the MMIC but should have been routinely vaccinated after the MMIC, the vaccination rate was only 52%. In the case-control investigation, 60% (25/42) of case-patients compared with 21% (35/168) of control-patients had visited Hospital S (adjusted ORM-H = 5.5, 95% CI = 2.7-11). Among unvaccinated children who had received treatment in Hospital S, 84% (21/25) of case-patients compared 38% (11/29) of control-patients had visited the IV room (adjusted ORM-H = 9.2, 95% CI = 1.5-59). CONCLUSION: Relaxed routine measles vaccination among children after the MMIC was the main factor responsible for this epidemic. Exposure in the IV room at Hospital S facilitated the epidemic. To reach the goal of measles elimination, the Chinese public health authorities should make greater efforts to improve timely routine measles vaccination, and to reduce nosocomial transmission.


Subject(s)
Epidemics , Measles Vaccine/administration & dosage , Measles/epidemiology , Adolescent , Adult , Analysis of Variance , Case-Control Studies , Child , Child, Preschool , China/epidemiology , Cross Infection/epidemiology , Cross Infection/transmission , Hospitals , Humans , Infant , Mass Vaccination , Measles/prevention & control , Measles/transmission , Middle Aged , Odds Ratio , Risk Factors
20.
Hum Vaccin Immunother ; 19(2): 2252241, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37706316

ABSTRACT

This study aimed to determine the level of viral hepatitis knowledge as well as the self-awareness of hepatitis B virus surface antigen (HBsAg) positive individuals, to provide data support for the next steps in viral hepatitis prevention and control. We conducted a cross-sectional survey to assess the knowledge of viral hepatitis among the general population aged 15-69 years in Zhejiang Province, China. A total of 3,626 individuals were surveyed with 10 questions. The knowledge level of the participants is reflected by the scores from the survey. Adequate knowledge was defined as a score of ≥ 6. The knowledge rate was defined as the ratio of the number of individuals with adequate knowledge to the total number of individuals. The knowledge rate of viral hepatitis among the general population aged 15-69 years in Zhejiang Province was 52.34% (mean score, 5.23). The majority of participants (52.51%) had adequate knowledge of viral hepatitis. Multiple logistic regression analysis showed that medical staff had the best knowledge of viral hepatitis, followed by individuals with university or higher education, those aged 40-49 years, and those with a history of hepatitis B vaccination. 34.16% of HBsAg positive participants were aware of their infection status before. The mean score of knowledge of viral hepatitis was significantly lower among HBsAg-positive than HBsAg-negative individuals. Knowledge of viral hepatitis in Zhejiang Province was still low, especially among HBsAg-positive individuals with no awareness of their infection status. More effort should be needed to improve public awareness of viral hepatitis.


Subject(s)
Hepatitis B Surface Antigens , Humans , Cross-Sectional Studies , China/epidemiology , Universities
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