Vγ9Vδ2 T cells are immune effector cells capable of killing multiple myeloma (MM) cells and have been tested in clinical trials to treat MM patients. To enhance the MM cell killing function of Vγ9Vδ2 ...T cells, we introduced a BCMA-specific CAR into ex vivo expanded Vγ9Vδ2 T cells through electroporation of the CAR-encoding mRNA. The modified Vγ9Vδ2 T cells displayed a high cytolytic activity against BCMA-expressing MM cell lines in vitro, while sparing BCMA-negative cells, including normal B cells and monocytes. Subsequently, we intravenously injected KMS-11 human MM cells to generate a xenograft mouse model. The treatment of the tumor-bearing mice with Zometa and anti-BCMA CAR- Vγ9Vδ2 T cells resulted in a significant reduction of tumor burden in the femur region, as well as the overall tumor burden. In association with the decrease in tumor burden, the survival of the MM cell-inoculated mice was markedly prolonged. Considering the potential of Vγ9Vδ2 T cells to be used as off-the-shelf products, the modification of these cells with a BCMA-specific CAR could be an attractive option for cancer immunotherapy against bone marrow cancer MM.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The highly restricted expression of B-cell maturation antigen (BCMA) on plasma cells makes it an ideal target for chimeric antigen receptor (CAR) immune cell therapy against multiple myeloma (MM), a ...bone marrow cancer. To improve the infiltration of ex vivo expanded human natural killer (NK) cells into the bone marrow, we electroporated these cells with mRNA encoding the chemokine receptor CXCR4. The CXCR4-modified NK cells displayed increased in vitro migration toward the bone marrow niche-expressing chemokine CXCL12/SDF-1α and augmented infiltration into the bone marrow compartments in mice. We further modified the CXCR4-NK cells by electroporation of mRNA encoding a CAR targeting BCMA. After the intravenous injection of the double-modified NK cells into a xenograft mouse model of MM, we observed significantly reduced tumor burden in the femur region of the living mice and the extended survival of the tumor-bearing mice. Collectively, this study provides the experimental evidence that the co-expression of CXCR4 and anti-BCMA CAR on NK cells is a possible effective way to control MM progression.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Peer education has become a strategy for health promotion among high-risk groups for HIV infection worldwide. However, the extent to which peer education could have an impact on HIV prevention or the ...long-term effect of this impact is still unknown. This study thus quantifies the impact of peer education over time among high-risk HIV groups globally.
Following the PRISMA guidelines, a systematic review and meta-analysis was used to assess the effects and duration of peer education. A thorough literature search of PubMed, Web of Science, Embase and Cochrane Library was performed, and studies about peer education on high-risk HIV groups were reviewed. Pooled effects were calculated and the sources of heterogeneity were explored using meta-regression and subgroup analysis.
A total of 60 articles with 96,484 subjects were identified, and peer education was associated with 36% decreased rates of HIV infection among overall high risk groups (OR: 0.64; 95%CI: 0.47-0.87). Peer education can promote HIV testing (OR = 3.19; 95%CI:2.13,4.79) and condom use (OR = 2.66, 95% CI: 2.11-3.36) while reduce equipment sharing (OR = 0.50; 95%CI:0.33,0.75) and unprotected sex (OR = 0.82; 95%CI: 0.72-0.94). Time trend analysis revealed that peer education had a consistent effect on behavior change for over 24 months and the different follow-up times were a source of heterogeneity.
Our study shows that peer education is an effective tool with long-term impact for behavior change among high-risk HIV groups worldwide. Low and middle-income countries are encouraged to conduct large-scale peer education.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Promising progress has been made in adoptive transfer of allogeneic natural killer (NK) cells to treat relapsed or refractory acute myeloid leukemia (AML). In this regard, chimeric antigen receptor ...(CAR)-modification of NK cells is considered as a compelling approach to augment the specificity and cytotoxicity of NK cells against AML. Using a non-viral piggyBac transposon technology and human peripheral blood-derived primary NK cells, we generated CAR-NK cells to target NKG2D ligands and demonstrated their in vitro activity in lysing cancer cells expressing the ligands and in vivo efficacy in inhibiting tumor growth in a xenograft KG-1 AML model. We further generated CAR-NK cells co-expressing transgenes for the NKG2D CAR and interleukin-15 (IL-15). The ectopic expression of IL-15 improved the in vitro and in vivo persistence of NKG2D CAR-NK cells, leading to enhanced in vivo tumor control and significant prolongation of mouse survival in the KG-1 AML model. Collectively, our findings demonstrate the ectopic expression of IL-15 as an important means to improve the antileukemic activity of NKG2D CAR-NK cells. Our study further illustrates the feasibility of using the piggyBac non-viral platform as an efficient and cost-effective way for CAR-NK cell manufacturing.
Display omitted
With a non-viral piggyBac transposon system, IL-15 armored NKG2D CAR-NK cells were generated from human PBMCs. These cells displayed superior persistence and anti-AML activity both in vitro and in vivo as compared with NKG2D CAR-NK cells without IL-15.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hand, foot, and mouth disease (HFMD) has caused a substantial burden of disease in China, especially in Guangdong Province. Based on notifiable cases, we use the time series ...Susceptible-Infected-Recovered model to estimate the basic reproduction rate (R0) and the herd immunity threshold, understanding the transmission and persistence of HFMD more completely for efficient intervention in this province. The standardized difference between the reported and fitted time series of HFMD was 0.009 (<0.2). The median basic reproduction rate of total, enterovirus 71, and coxsackievirus 16 cases in Guangdong were 4.621 (IQR: 3.907-5.823), 3.023 (IQR: 2.289-4.292) and 7.767 (IQR: 6.903-10.353), respectively. The heatmap of R0 showed semiannual peaks of activity, including a major peak in spring and early summer (about the 12th week) followed by a smaller peak in autumn (about the 36th week). The county-level model showed that Longchuan (R0 = 33), Gaozhou (R0 = 24), Huazhou (R0 = 23) and Qingxin (R0 = 19) counties have higher basic reproduction rate than other counties in the province. The epidemic of HFMD in Guangdong Province is still grim, and strategies like the World Health Organization's expanded program on immunization need to be implemented. An elimination of HFMD in Guangdong might need a Herd Immunity Threshold of 78%.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The association between the incidence of hand, foot, and mouth disease (HFMD) and ambient temperature has been well documented. Although the severity of symptoms is an important indicator ...of disease burden and varies significantly across cases, it usually was ignored in previous studies, potentially leading to biased estimates of the health impact of temperature. Methods We estimated the disability-adjusted life year (DALY) by considering the severity of symptoms for each HFMD case reported during 2010-2012 in Guangdong and used distributed lag-nonlinear models to estimate the association between the daily average temperature and daily DALY of HFMD cases at the city-level. We investigated the potential effect modifiers on the pathway between temperature and DALY and pooled city-specific estimates to a provincial association using a meta-regression. The overall impact of temperature was further evaluated by estimates of DALYs that could be attributed to HFMD. Results The overall cumulative effect of daily mean temperature on the DALY of HFMD showed an inverse-U shape, with the maximum effect estimated to be beta = 0.0331 (95%CI: 0.0199-0.0463) DALY at 23.8°C. Overall, a total of 6.432 (95%CI: 3.942-8.885) DALYs (attributable fraction = 2.721%, 95%CI: 1.660-3.759%) could be attributed to temperature exposure. All the demographic subgroups had a similar trend as the main analysis, while the magnitude of the peak of the temperature impact tended to be higher among the males, those aged greater than or equal to3yrs or from the Pear-River Delta region. Additionally, the impact of temperature on DALY elevated significantly with the increasing population density, per capita GDP, and per capita green space in parks. Conclusions Temperature exposure was associated with increased burden of HFMD nonlinearly, with certain groups such as boys and those from areas with greater population density being more vulnerable.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been ...specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia.
This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40-75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day,
= 80) or placebo (
= 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial.
A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%;
= 0.005), low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01,
= 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17;
= 0.02), and apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01;
= 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers.
The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings.
•Higher all-cause mortality was attributed to greater PM1, PM2.5 and PM10 exposure.•The risk from PM1 tends to be 1.1% and 1.3% greater than that from PM2.5 and PM10.•The elderly, unmarried and less ...educated ones were more vulnerable to the impact of PMs.•Participants generally at low PM exposures were more susceptible than others.
The association between long-term particulate matter (PM) exposure and all-cause mortality has been well-documented. However, evidence is still limited from high-exposed cohorts, especially for PM1 which is smaller while more toxic than other commonly investigated particles. We aimed to examine the potential casual links of long-term PMs exposure with all-cause mortality in high-exposed areas.
A total of 580,757 participants in southern China were enrolled during 2009–2015 and followed up to 2020. The annual average concentration of PM1, PM2.5, and PM10 at 1 km2 spatial resolution was assessed for each residential address through validated spatiotemporal models. We used marginal structural Cox models to estimate the PM-mortality associations which were further stratified by sociodemographic, lifestyle factors and general exposure levels.
37,578 deaths were totally identified during averagely 8.0 years of follow-up. Increased exposure to all 3 PM size fractions were significantly associated with increased risk of all-cause mortality, with hazard ratios (HRs) of 1.042 (95 % confidence interval (CI): 1.037–1.046), 1.031 (95 % CI: 1.028–1.033), and 1.029 (95 % CI: 1.027–1.031) per 1 μg/m3 increase in PM1, PM2.5, and PM10 concentrations, respectively. We observed greater effect estimates among the elderly (age ≥ 65 years), unmarried participants, and those with low education attainment. Additionally, the effect of PM1, PM2.5, and PM10 tend to be higher in the low-exposure group than in the general population.
We provided comprehensive evidence for the potential causal links betweenlong-term PM exposureand all-cause mortality, and suggested stronger links for PM1compared to large particles and among certain vulnerable subgroups.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Hand, foot, and mouth disease (HFMD) is a major public health issue in China while temperature and humidity are well-documented predictors. However, evidence on the combined effect of ...temperature and humidity is still limited. It also remains unclear whether such an effect could be modified by the enterovirus 71 (EV71) vaccination. Methods Based on 320,042 reported HFMD cases during the summer months between 2012 and 2019, we conducted a study utilizing Distributed Lag Non-Linear Models (DLNM) and time-varying DLNM to examine how China’s HFMD EV71 vaccine strategy would affect the correlation between meteorological conditions and HFMD risk. Results The incidence of HFMD changed with the Discomfort Index in an arm-shaped form. The 14-day cumulative risk of HFMD exhibited a statistically significant increase during the period of 2017–2019 (following the implementation of the EV71 vaccine policy) compared to 2012–2016 (prior to the vaccine implementation). For the total population, the range of relative risk ( RR ) values for HFMD at the 75th, 90th, and 99th percentiles increased from 1.082–1.303 in 2012–2016 to 1.836–2.022 in 2017–2019. In the stratified analyses, Han Chinese areas show stronger relative growth, with RR values at the 75th, 90th, and 99th percentiles increased by 14.3%, 39.1%, and 134.4% post-vaccination, compared to increases of 22.7%, 41.6%, and 38.8% in minority areas. Similarly, boys showed greater increases (24.4%, 47.7%, 121.5%) compared to girls (8.1%, 28.1%, 58.3%). Additionally, the central Guizhou urban agglomeration displayed a tendency for stronger relative growth compared to other counties. Conclusions Although the EV71 vaccine policy has been implemented, it hasn’t effectively controlled the overall risk of HFMD. There’s been a shift in the main viral subtypes, potentially altering population susceptibility and influencing HFMD occurrences. The modulating effects of vaccine intervention may also be influenced by factors such as race, sex, and economic level.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hand, foot, and mouth disease (HFMD) is an epidemic infectious disease in China. Relationship of neighborhood greenness with human health has been widely studied, yet its association with severe HFMD ...has not yet been established.
Individual HFMD cases that occurred in Guangdong province in 2010 were recruited and were categorised into mild and severe cases. Residential greenness was assessed using global land cover data. We used a case-control design (i.e., severe versus mild cases) with logistic regression models to assess the association between neighborhood greenness and HFMD severity. Effect modification was also examined.
A total of 131,606 cases were included, of whom 130,840 were mild cases and 766 were severe cases. In an unadjusted model, HFMD severity increased with higher proportion of neighborhood greenness (odds ratio, OR = 1.029, 95%CI: 1.009-1.050). The greenness-HFMD severity association remained (OR = 1.031, 95%CI: 1.006-1.057) after adjusting for population density, demographic variables and climate variables. Both population density (Z = 4.148, P < 0.001) and relative humidity (Z = -4.297, P < 0.001) modified the association between neighborhood greenness and HFMD severity. In the stratified analyses, a protective effect (OR = 0.769, 95%CI: 0.687-0.860) of greenness on HFMD severity were found in the subgroup of population density being lower than and equal to 5 ln(no.)/km
. While in both the subgroups of population density being higher than 5, the greenness had hazard effects (subgroup of > 5 & ≤7: OR = 1.071, 95%CI: 1.024-1.120; subgroup of > 7: OR = 1.065, 95%CI: 1.034-1.097) on HFMD severity. As to relative humidity, statistically significant association between greenness and HFMD severity was only observed in the subgroup of being lower than and equal to 76% (OR = 1.059, 95%CI: 1.023-1.096).
Our study found that HFMD severity is associated with the neighborhood greenness in Guangdong, China. This study provides evidence on developing a prevention strategy of discouraging the high-risk groups from going to the crowded green spaces during the epidemic period.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
