BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

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Objective:To explore the dosimetric differences of different dose accumulation method for brachytherapy combined with external beam radiation therapy (EBRT) of cervical cancer and establish clinical prediction models for radiation-induced late rectal injury (RLRI) after radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of patients who received radical concurrent chemoradiotherapy (CCRT) for cervical cancer in the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College from January 1, 2020 to November 30, 2021. EBRT combined with brachytherapy was employed for the patients, and dose assessment was performed in two means: the direct accumulation using equivalent dose in 2-Gy fractions (EQD2) and deformable image registration (DIR)-based dose accumulation of 3D planning images. The toxicity criteria of the Radiation Therapy Oncology Group were adopted as the RLRI grading criteria. The prediction models of RLRI using both dose assessment method were constructed. The areas under the receiver operating characteristic (ROC) curves were calculated to assess the predictive accuracy of the different dose assessment method.Results:In the case of brachytherapy, the D95% and D90% EQD2 doses to high-risk clinical target volumes (HR-CTVs) were 2.18 and 2.92 Gy higher respectively and the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 1.74, 2.28, and 2.26 Gy higher, respectively compared to DIR-based dose accumulation ( t = 3.82, 5.21, 4.58, 5.17, 2.05, P < 0.05). For EBRT combined with brachytherapy, the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 6.22, 7.61, 9.56 Gy higher than DIR-based doses, respectively, and the dosimetric differences were statistically significant ( t = 9.40, 10.59, 7.87, P < 0.001). The joint prediction model yielded an area under the ROC curve of 0.788. The sensitivity and specificity of the optimal cut-off value were 0.850 and 0.660, respectively. Furthermore, the Hosmer-Lemeshow goodness-of-fit tests indicated high goodness-of-fit ( P > 0.05). The prediction model for DIR-based dose accumulation of traditional predictors yielded areas under the ROC curves for D2 cm 3 and D1 cm 3 to the rectal of 0.784 and 0.763, respectively. The sensitivities of the optimal cut-off values were 0.850 and 0.750, respectively, and the specificities were 0.679 and 0.717, respectively. Conclusions:There are dosimetric differences between the direct dose accumulation using EQD2 and DIR-based dose accumulation of 3D planning images for brachytherapy combined with EBRT. Both the joint prediction model and the DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal are effective in predicting RLRI. Given the complex calculation of the joint prediction model, it is recommended that RLRI should be predicted through DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal clinically.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Objective To compare the efficacy of renal proximal renal artery denervation(pRDN)and full-length renal artery denervation(fRDN)for treatment of hypertension.Methods Fifty-six hypertensive patients were enrolled and randomly assigned to full-length renal artery denervation group(n=25)and proximal renal artery denervation group(n=31).After the procedure,24-hour ambulatory blood pressure monitoring(24 h-ABPM)at 6 months and office blood pressure at 12 months was recorded for statistical analysis.Results The blood pressure at follow-up reduced significantly in both groups,while there was no significant difference between groups.The baseline office blood pressure in fRDN group and pRDN group was(180±15)/(104±10)mmHg and(180±12)/(103±8)mmHg,respectively,which decreased to(142±9)/(82±7)mmHg and(143±10)/(83±6)mmHg at 12 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).The baseline 24 h-ABPM in the two groups was(162±13)/(95±8)mmHg and(160±12)/(94±8)mmHg,respectively,which decreased to(142±11)/(83±7)mmHg and(141±8)/(81±7)mmHg at 6 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).However,there was no significant difference in the reduction of office blood pressure and ambulatory blood pressure between the two groups.No treatment-related adverse events were observed.Conclusions pRDN has similar antihypertensive effect to fRDN.

Objective:To investigate the levels of serum IgM, IgG, IgA and neutralizing antibodies (NAbs) in convalescing patients infected with the novel coronavirus and their diagnostic significance.Methods:Five hundreds and eighty one infected patients and 219 non-infected patients were detected by chemiluminescence method . The positive rate of antibody and antibody level were statistically analyzed for statistical significance. The correlation between the antibodies was compared, and the ability of each antibody to identify breakthrough infection in the vaccinated population was evaluated by combining ROC curve.Results:The antibody titers of IgM, IgG, NAbs and IgA in infected patients were higher than those in uninfected individuals. The antibody positive rate and antibody level of infected persons who were vaccinated and not vaccinated, with different ages, different doses of vaccines, and different intervals of vaccination were statistically significant ( P<0.05); IgA antibody levels were positively correlated with IgG and NAbs, and NAbs is positively correlated with IgG antibody; In breakthrough infection analysis, IgG, IgA and NAbs antibodies were good at identifying infected persons in the vaccinated population. Conclusions:The positive rate of IgM antibody is low in the convalescence period, which is of little significance for monitoring the course of COVID-19 and evaluating the efficacy of vaccines. In addition, the antibody level and positive rate can be significantly improved by the booster injection of COVID-19 vaccine. Differences in IgG, IgA, and NAbs antibody levels can be used to identify breakthrough infection cases from vaccinated populations.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.
Animals ; Humans ; Mice ; Antigens, CD19 ; Burkitt Lymphoma/drug therapy* ; Cell- and Tissue-Based Therapy ; Follow-Up Studies ; Immunotherapy, Adoptive ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Receptors, Chimeric Antigen

Objective To study the efficacy and safety of bronchial artery embolization(BAE)with tris-acryl gelatin microspheres(TAGM)combined with platinum spring coil with fiber(microcoils)in the treatment of acute severe hemoptysis caused by bronchiectasis.Methods A retrospective analysis of 48 patients with bronchiectasis was performed.After the lesion vessels were confirmed by angiography,the distal capillary bed was embolized with TAGM(300-500 μm),the middle blood flow was embolized with microcoils according to the diameter of the small artery,and then the proximal vessels were embolized with TAGM(500-700 μm)again.In patients with pulmonary artery/vein fistula,appropriate TAGM(500-700 μm)was selected according to the size of the fistula and the blood flow velocity,followed by dense embolization with multiple microcoils.The complete occlusion of the lesion vessel was confirmed again by arteriography after embolization.Results The overall success rate of operation was 95.83％.There were 36 patients with immediately stopped bleeding,6 cases with effective treatment,4 cases with improved treatment,1 case with invalid treatment due to the leakage of the responsible blood vessel,which was improved after the second embolization.There was 1 case died in surgery due to sudden massive hemoptysis,choking and suffocation.During the 3-51 months follow-up,1 patient died due to sudden massive hemoptysis;4 patients had recurrent hemoptysis due to poor control of infection and collateral circulation,which were controlled after reemboliza-tion,and 1 patient with bronchiectasis and pulmonary tuberculosis had repeated hemoptysis caused by multiple pulmonary lesions and severe pulmonary infection,performing on four times embolization.There was no patient with recurrent hemoptysis occurring recanalization of primary embolized vessel.During the follow-up,the overall survival rate was 97.87％,and the hemoptysis control rate was 87.23％.Conclusion TAGM combined with microcoils is safe and effective in the treatment of acute massive hemoptysis,which has good short-term effect and long-term prognosis.