1.ACSL4 mediates ferroptosis and its potential role in atherosclerotic cardiovascular disease
Yang GAO ; Hewei QIN ; Dandan LIU
Chinese Journal of Tissue Engineering Research 2025;29(6):1239-1247
BACKGROUND:Ferroptosis is an iron-dependent regulatory form of cell death characterized by iron-dependent lipid peroxidation.Long-chain acyl-coenzyme A synthase 4(ACSL4)is involved in the formation of lipid peroxidation substrates,thereby resulting in ferroptosis.Recent studies have shown that ACSL4-mediated ferroptosis plays a key role in atherosclerotic cardiovascular disease. OBJECTIVE:To summarize the structural function and regulatory mechanism of ACSL4 and its potential molecular mechanism mediating ferroptosis,and to elaborate the application of ACSL4 driving ferroptosis in atherosclerosis,ischemic stroke and myocardial infarction,in order to provide a new therapeutic strategy for the treatment of atherosclerotic cardiovascular diseases. METHODS:Relevant literature was searched in PubMed database from database inception to August 2023 using the keywords of"atherosclerosis,ferroptosis,long-chain acyl-coenzyme A synthase 4,ACSL4,glutathione peroxidase 4,ischemic stroke,myocardial infarction,endothelial cell,smooth muscle cells,foam cell."Finally,76 documents were included for review and analysis. RESULTS AND CONCLUSION:ACSL4 participates in the formation of coenzyme derivatives of polyunsaturated fatty acids and inserts them into phospholipids to provide substrates for lipid peroxidation,the core mechanism of iron death.Among the regulatory factors of ACSL4 expression,integrin α6β4,intracellular vesicular transport factor p115,and zinc lipoprotein A20 negatively regulate its expression.Meanwhile,multiple miRs down-regulate its expression by binding to 3'-UTR.On the contrary,up-regulation of ACSL4 is mostly regulated by transcription factors.ACSL4-dependent production of phospholipids containing polyunsaturated fatty acids is an essential prerequisite for lipid peroxidation and ferroptosis.Moreover,ACSL4 and glutathione peroxidase 4 are mutually dependent as positive and negative regulators of ferroptosis,and their specific mechanisms remain to be further studied.ACSL4-mediated ferroptosis is involved in the pathological mechanism of atherosclerosis,ischemic stroke,and myocardial infarction.Endothelial cell injury in atherosclerosis is closely related to ACSL4-mediated ferroptosis,but there are no reports on the involvement of ACSL4 in foam cell formation,smooth muscle cell phenotype transformation,and calcification.ACSL4 has become a research hotspot as a biomarker and potential target of ferroptosis.Targeting ACSL4 to inhibit ferroptosis may become a new direction for the treatment of atherosclerotic cardiovascular diseases.However,there are few studies on drugs inhibiting ACSL4,and further studies are needed in the future.
2.Retrospective Study on Tongue Image Characteristics of Patients with Glucolipid Metabolism Disorders with Different Traditional Chinese Medicine Syndromes
Shi LIU ; Yang GAO ; Tao JIANG ; Zhanhong CHEN ; Jialin DENG ; Jiatuo XU
Journal of Traditional Chinese Medicine 2025;66(8):826-833
ObjectiveTo explore the distribution pattern of tongue image characteristics in patients with glucolipid metabolic disorders and its main syndromes. MethodsA total of 841 patients with glucolipid metabolic disorders (disease group), and 380 healthy subjects (control group) were included. The disease group was classified into three syndrome types: 283 cases of liver depression and spleen deficiency syndrome, 311 cases of phlegm-dampness obstruction syndrome, and 247 cases of qi stagnation and blood stasis syndrome. Tongue image data were collected using the TFDA-1 Tongue Diagnosis Instrument, and the TDAS V3.0 software was used to analyze the color, texture, and morphological features of the tongue body (TB) and tongue coating (TC) in patents with different syndromes of disease group (including lightness (L), red-green axis (a), yellow-blue axis (b), luminance (Y), difference between red signal and brightness (Cr), difference between blue signal and brightness (Cb), contrast (CON), angular second moment (ASM), entropy (ENT), mean value (MEAN), tongue coating area/tongue surface area (perAll), and tongue coating area/non-coated area (perPart)). Logistic regression analysis was conducted to identify influencing factors for different syndrome types of glucolipid metabolic disorders. ResultsThe tongue body indicators TB-L, TB-Y, and TB-Cb in the disease group were significantly higher than those in the control group, while TB-a, TB-b, and TB-Cr were significantly lower. The tongue coating indicators TC-L, TC-Y, TC-Cb, perAll, and perPart in the disease group were significantly higher than those in the control group, while TC-a, TC-b, and TC-Cr were significantly lower (P<0.05). Comparing with the different syndromes in disease group, the TB-L and TB-Y of the liver depression and spleen deficiency syndrome, and the phlegm-damp obstruction syndrome were higher than those of the qi stagnation and blood stasis syndrome; the TB-a and TB-Cr of the phlegm-damp obstruction syndrome were lower than those of the qi stagnation and blood stasis syndrome; the perAll of the phlegm-damp obstruction syndrome was higher than that of the qi stagnation and blood stasis syndrome (P<0.05). In the analysis of the morphological characteristics of tongue signs, more spotted tongue in disease group compared with control group, more teeth-marked tongue in liver depression and spleen deficiency syndrome than the other two syndromes, more greasy coating in phlegm-damp obstruction syndrome, and more stasis spots of tongue in qi stagnation and blood stasis syndrome (P<0.05). Logistic regression analysis identified that greasy coating, spotted tongue, stasis spots of tongue, tooth-marked tongue, perAll, and TB-Cb are the influencing factors of liver depression and spleen deficiency syndrome; greasy coating, tooth-marked tongue, TC-Cb, and TC-Cr are the influencing factors of phlegm-damp obstruction syndrome; cracked tongue, stasis spots of tongue, tooth-marked tongue, and TB-Y are the influencing factors of qi stagnation and blood stasis syndrome (P<0.05). ConclusionCompared to healthy individuals, patients with glycolipid metabolic disorder have darker tongue color and thicker, greasy tongue coating. Glycolipid metabolic disorder patients of liver depression and spleen deficiency syndrome exhibit a reddish tongue with finer textures and more tooth marks; patients of phlegm-damp obstruction syndrome have lighter tongue coating with a coarser texture and a higher prevalence of greasy coating; patients of qi stagnation and blood stasis syndrome display lower tongue brightness with a higher prevalence of blood stasis spots.
3.Etiological characteristics and molecular evolution of the first mpox case in Huai’an City of Jiangsu Province
Pengfei YANG ; Fang HE ; Qingli YAN ; Heyuan GENG ; Tong GAO ; Qiang GAO ; Chenglong XIONG ; Haiyan PENG
Chinese Journal of Schistosomiasis Control 2025;37(1):85-92
Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/105. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.
4.Relationship between parenting rearing behaviors and adolescent depression: the mediating role of rumination
Fangfang ZHANG ; Rui GAO ; Haiyan YANG
Sichuan Mental Health 2025;38(2):145-152
BackgroundSeveral studies have confirmed that there is a relationship among parenting rearing behaviors, adolescent depression and rumination, moreover, rumination has been found to mediate the relationship between overall parenting rearing behaviors and adolescent depression, while little is known about the mediating role of rumination in the relationship between each dimension of parenting rearing behaviors and adolescent depression. ObjectiveTo explore the mediating role of rumination in the relationship between each dimension of parenting rearing behaviors and adolescent depression, so as to provide reference for the prevention of adolescent depression. MethodsIn March and April 2022, a stratified random sampling technique was utilized to select 302 students in grades 7 to 12 at a middle school in Ningxian county, Gansu Province as the research subjects. The Beck Depression Inventory-II of Chinese Version (BDI-II-C), short-form Egna Minnen av Barndoms Uppfostran (S-EMBU) and Ruminative Response Scale (RRS) were administered to all subjects. Pearson correlation coefficients were calculated. Amos 24.0 was used to check the presence of mediation effect. ResultsA total of 302 (94.08%) completed valid questionnaires. Correlation analysis indicated that the scores of both father's and mother's emotional warmth dimension in the S-EMBU were negatively correlated with the BDI-II-C scores (r=-0.424, -0.297, P<0.01), RRS total score (r=-0.347~-0.175, P<0.01) and RRS each factor score (r=-0.179~-0.285, P<0.01); the scores of both father's and mother's rejection dimension in the S-EMBU were positively correlated with the BDI-II-C scores (r=0.355, 0.248, P<0.01), RRS total score (r=0.262~0.358, P<0.01) and RRS each factor score (r=0.274~0.339, P<0.01); the scores of both father's and mother's overprotection dimension in the S-EMBU were positively correlated with the BDI-II-C scores (r=0.286, 0.245, P<0.01), RRS total score (r=0.175~0.333, P<0.01) and RRS each factor score (r=0.150~0.255, P<0.01). Rumination might mediated the relationship of father's emotional warmth, father's overprotection, mother's overprotection, and mother's rejection with adolescent depression, the effect value were -0.110, 0.221, -0.121, 0.136, and the effect size were 36.07%, 100.00%, 100.00%, 100.00%. ConclusionRumination may play a mediation role in the relationship of father's emotional warmth, father's overprotection, mother's overprotection, and mother's rejection with adolescent depression. [Funded by Shaanxi Provincial Key Research and Development Program (number, 2024SF-YBXM-078); Reaearch and Development Fund of the First Affliated Hoapital of Xi'an JiaoTong University (number, 2022HL-23)]
5.Association between ambient ozone exposure during pregnancy and risk of preterm birth in Guangdong Province
Peng HU ; Shanshan RAN ; Qingmei LIN ; Yin YANG ; Zilong ZHANG ; Xiaoling GUO ; Yonggui GAO ; Jinde ZHAO ; Hualiang LIN
Journal of Environmental and Occupational Medicine 2025;42(4):379-384
Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O3) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O3 exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O3 concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O3 exposure and preterm birth risk and explore potential exposure threshold of O3. Logistic regression models were used to evaluate the association of O3 exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O3 exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m−3, respectively. We observed J-shaped associations between O3 exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O3 exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m−3, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m−3 increase in O3 concentration above the O3 threshold. No significant association was found between O3 exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O3 exposure during pregnancy, and higher concentrations of O3 exposure during pregnancy are associated with the risk of preterm birth. Above the O3 threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O3 exposure concentrations.
6.Analysis of subjective visual vertical test results in patients with benign paroxysmal positional vertigo at different head deflection angles
Maolin QIN ; Xiaobao MA ; Dekun GAO ; Jiali SHEN ; Qin ZHANG ; Yulian JIN ; Jie WANG ; Jun YANG ; Jianyong CHEN
Chinese Journal of Clinical Medicine 2025;32(2):183-187
Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P=0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P<0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.
7.Concept,Organizational Structure,and Medical Model of the Traditional Chinese Medicine Myocardial Infarction Unit
Jun LI ; Jialiang GAO ; Jie WANG ; Zhenpeng ZHANG ; Xinyuan WU ; Ji WU ; Zicong XIE ; Jingrun CUI ; Haoqiang HE ; Yuqing TAN ; Chunkun YANG
Journal of Traditional Chinese Medicine 2025;66(9):873-877
The traditional Chinese medicine (TCM) myocardial infarction (MI) unit is a standardized, regulated, and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings, offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused, providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI, delivering prevention, treatment, and rehabilitation during the acute, stable, and recovery phases. Additionally, the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management, reduce the incidence of myocardial infarction, and improve quality of life.
8.Effect of Erchen Decoction (二陈汤) on Serum Leptin and Expression of LepR,POMC,and NPY in Hypothalamus of Metabolic Syndrome Model Mice with Phlegm Syndrome
Menghan YANG ; Yuanyuan LI ; Xiujuan ZHENG ; Wenhui XIONG ; Xirui HUANG ; Bizhen GAO
Journal of Traditional Chinese Medicine 2025;66(9):948-954
ObjectiveTo explore the potential mechanism of Erchen Decoction (二陈汤, ECD) in improving metabolic syndrome (MS) with phlegm syndrome. MethodsForty mice were randomly divided into a blank group of 10 mice and a modeling group of 30 mice. The MS model with phlegm syndrome was induced in the modeling group by high-fat diet. Thirty successfully modeled mice were randomly divided into a model group, a ECD group, and a metformin group, with 10 mice in each group. The ECD group was given 0.4 g/(kg·d) of ECD, while the metformin group was intervened with 11.1 g/(kg·d) of metformin solution, and the blank group and the model group were given 0.02 ml/(g·d) of sterilized drinking water, all by gavage, once daily for 4 weeks. Body weight, abdominal circumfe-rence, body length, Lee's index and food intake were recorded. Blood glucose and blood lipid levels including fasting blood glucose, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. ELISA was used to detect serum leptin levels, while HE staining was used to observe liver pathological changes. Western Blot and q-PCR were used to detect protein and mRNA expression of hypothalamic leptin receptor (LepR), pro melanocortin (POMC), and neuropeptide Y (NPY) in the hypothalamus. Immunofluorescence was used to detect fluorescence expression of POMC and NPY in the hypothalamic arcuate nucleus region. ResultsPathological results showed that the mice in the model group had numerous fat vacuoles in hepatocytes and significant liver fat deposition, while the ECD and metformin groups showed reduced fat vacuoles and less liver fat deposition. Compared to those in the blank group, the mice in the model group mice showed liver fat deposition, increased body weight, abdominal circumference, Lee's index and food intake; fasting blood glucose, TG, TC, LDL-C, and serum leptin levels were elevated, while HDL-C was decreased; the expression of LepR, POMC protein levels and their mRNA expression decreased, while the protein level and mRNA expression of NPY increased; the fluorescence expression of POMC in the arcuate nucleus was reduced, while NPY fluorescence expression increased (P<0.05 or P<0.01). Compared to the model group, the ECD group and metformin group showed significant improvements in the above indicators (P<0.05 or P<0.01). Compared to the ECD group, the metformin group showed a reduction in body weight and NPY fluorescence expression, and an increase in HDL-C levels (P<0.05 or P<0.01). ConclusionECD can downregulate serum leptin levels and improve glucose and lipid metabolism in the MS of phlegm syndrome. Its mechanism of action may be to reduce liver fat deposition and thereafter affect the expression of neuropeptides related to feeding activity in the hypothalamus.
9.Analysis of influencing factors for maternal intentions to vaccinate age appropriate girls against human papillomavirus
QIU Xiaofei, KANG Xiao, ZHUANG Wenwen, GAO Riyue, ZHANG Delei, SHAO Yanyan, LI Xuedan, YANG Feng
Chinese Journal of School Health 2025;46(4):519-523
Objective:
To investigate the intentions of mothers of ageappropriate girls in Qingdao to vaccinate their daughters against human papillomavirus (HPV), so as to provide theoretical guidance for targeted health education in the future.
Methods:
A multistage random sampling method was adopted to conduct a crosssectional study among 2 244 mothers of girls aged 12-14 years in Qingdao from March to December 2023. The Mann-Whitney U test was used for group comparisons, and Logistic regression was performed to analyze the factors that influenced maternal intention to vaccinate their ageappropriate daughters against HPV.
Results:
Among the surveyed mothers, 89.22% (n=2 002) intended to vaccinate their daughters against HPV, and 68.58% (n=1 539) had fully vaccinated or had plans to complete it for themselves. The knowledge score of mothers intended to vaccinate their daughters was 10 (8, 11). The multivariate Logistic regression analysis showed that mothers aged >45 years (OR=0.19), those with an annual family income of 60 000-<150 000 yuan (OR=0.65), 150 000-<300 000 yuan (OR=0.58), 300 000-500 000 yuan (OR=0.22), and those with higher knowledge scores (OR=0.90) were more likely to vaccinate their daughters (P<0.05). Mothers with a junior college or undergraduate degree (OR=1.66), those who never or occasionally screened for HPV (OR=1.58), those who were intended to be vaccinated, not planning to complete the fullcourse vaccination, or overaged and unvaccinated (OR=7.13), those who were not concerned about their daughters HPV infection (OR=2.54), and those whose daughters were not in adolescence (OR=1.93) were less intended to vaccinate their daughters (P<0.05). The primary reasons for vaccine hesitancy were vaccine safety concerns (65.06%), followed by the belief of mothers that "the children is to young, and can be vaccinated when they are older" (13.25%).
Conclusions
Mothers of eligible girls in Qingdao have relatively higher intentions to vaccinate their daughters against HPV, and willingness is influenced by factors such as the mothers vaccination status, knowledge level, and daughters development stage. It is recommended to strengthen targeted health education, improve the cognitive level and acceptance of mother, and increase the vaccination rate of HPV vaccines.
10.Effect of Tongxinluo Capsules on TCM Syndrome Elements in Patients with Chronic Coronary Syndrome of Qi Deficiency and Blood Stasis Type: A Multicenter and Prospective Cohort Study
Jia WANG ; Xilun TAN ; Xuesen WANG ; Xiaohe YANG ; Meili GAO ; Yiying LIU ; Chenhao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):170-177
ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine (TCM) syndrome elements and major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor, and the patients were divided into an exposure group (integrated traditional Chinese and western medicine treatment group) and a non-exposure group (western medicine treatment group). The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third, sixth, and twelfth months, and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included, with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group, the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved (P<0.05). Compared with the non-exposure group, the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period (P<0.01) and significantly reduced blood stasis syndrome scores in the sixth month (P<0.05). In the remaining follow-up period, there was no statistically significant difference between the two groups. Compared with that of the non-exposure group, during the treatment period (the third month), the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant (P<0.05, P<0.01). At the end of the follow-up period, patients in the non-exposure group had a MACE probability of 6.90% (4/58), higher than 3.13% in the exposure group (4/58). Compared with patients with angina pectoris who used conventional medicine, patients administered with Tongxinluo Capsules had a relative risk(RR) of 0.45 [95%confidence interval(95%CI) 0.12-1.75, P=0.26]. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term, and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year, the incidence of MACE in the exposure group was lower than that in the non-exposure group.


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