1.Comparative Study on Effect of Jingui Shenqiwan and Liuwei Dihuangwan on Reproductive Ability and Brain Function of Normal Mice
Hong SUN ; Fan LEI ; Chenggong LI ; Rui LUO ; Shixian HU ; Bin REN ; Juan HAO ; Yi DING ; Lijun DU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):1-14
ObjectiveTo explore the effects of Jingui Shenqiwan (JSW) and Liuwei Dihuangwan (LDW) on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group, the other six groups were as follows: a group of both males and females receiving JSW (3.0 g·kg-1), a group of both males and females receiving LDW (4.5 g·kg-1), a group of males receiving water and females receiving JSW, a group of males receiving water while females receiving LDW, a group of females receiving water while males receiving JSW, and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 (female∶male) ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth, which was followed by the observation of newborn mice, calculation of their average number, and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment, the weights of the thymus and spleen were measured to calculate the organ coefficients, and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems, while novel object recognition test (NOR) was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction (Real-time PCR) assay, and protein expression was analyzed with Western blot. ResultsCompared with the control group, oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together (P<0.05), while LDW showed a trend but no statistical significance. Additionally, compared with the control group, JSW could upregulate the gene expression of gonadotropin-releasing hormone (GnRH) in the thalamus, as well as reproductive stem cell factor (SCF) and tyrosine kinase receptor (c-Kit) in the testes and reproductive stem cell marker mouse vasa homologue (MVH) in the ovaries, upregulate the expression of proteins influencing neuronal functional activity, such as brain-derived neurotrophic factor (BDNF), in hippocampal neurons (P<0.05), and enhance sucrose preference in male mice (P<0.05). Compared with the control group, JSW significantly increased sucrose preference and novel object recognition index in offspring mice (P<0.05), which was related to the upregulation of hippocampal dopamine D1 receptor (D1R) and N-methyl-D-aspartate receptor (Nmdar) gene expression. Compared with the control group, both JSW and LDW could upregulate the protein expression of glucocorticoid receptor (GR), BDNF, and tyrosine kinase receptor B (TrkB) in the hippocampus of offspring mice (P<0.05). ConclusionJSW significantly enhances the reproductive ability of normal mice, which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally, JSW has a certain regulatory effect on the brain function of the offspring mice.
2.Xuefu Zhuyutang in Malignant Tumor Disease: A Review
Jiaqi JI ; Xiaoqing HU ; Yihan ZHAO ; Xuhang SUN ; Dandan WEI ; Junwen PEI ; Shiqing JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):321-330
Cancer has become a significant global public health issue, severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates, drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine (TCM) has demonstrated significant clinical efficacy in cancer treatment and small side effects, making it widely applied in the field of oncology. Xuefu Zhuyutang, derived from Yilin Gaicuo, is known for its abilities to invigorate blood circulation, dispel blood stasis, promote Qi flow, and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang, when combined with conventional Western medications, produces significant effects in the treatment of malignant tumors such as liver cancer, lung cancer, and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments, including radiation esophagitis, radiation encephalopathy, radiation-induced oral mucositis, and edema. Additionally, it alleviates cancer-related pain and fever, blood hypercoagulability, and associated complications such as depression and anxiety, and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms, including the inhibition of Wnt/β-catenin signaling pathway activation, suppression of mitogen-activated protein kinase (MAPK) pathway activation, and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration, induce tumor cell apoptosis, suppress tumor angiogenesis, enhance the cytotoxicity of natural killer cells against tumors, improve the tumor microenvironment, and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects: theoretical exploration, clinical studies, mechanisms of action, and pharmacological basis, aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.
3.Xuefu Zhuyutang in Malignant Tumor Disease: A Review
Jiaqi JI ; Xiaoqing HU ; Yihan ZHAO ; Xuhang SUN ; Dandan WEI ; Junwen PEI ; Shiqing JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):321-330
Cancer has become a significant global public health issue, severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates, drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine (TCM) has demonstrated significant clinical efficacy in cancer treatment and small side effects, making it widely applied in the field of oncology. Xuefu Zhuyutang, derived from Yilin Gaicuo, is known for its abilities to invigorate blood circulation, dispel blood stasis, promote Qi flow, and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang, when combined with conventional Western medications, produces significant effects in the treatment of malignant tumors such as liver cancer, lung cancer, and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments, including radiation esophagitis, radiation encephalopathy, radiation-induced oral mucositis, and edema. Additionally, it alleviates cancer-related pain and fever, blood hypercoagulability, and associated complications such as depression and anxiety, and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms, including the inhibition of Wnt/β-catenin signaling pathway activation, suppression of mitogen-activated protein kinase (MAPK) pathway activation, and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration, induce tumor cell apoptosis, suppress tumor angiogenesis, enhance the cytotoxicity of natural killer cells against tumors, improve the tumor microenvironment, and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects: theoretical exploration, clinical studies, mechanisms of action, and pharmacological basis, aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.
4.Effect of Qingfei Shenshi Decoction (清肺渗湿汤) Combined with Western Medicine on Clinical Effectiveness and Immune Function for Patients with Bronchial Asthma of Heat Wheezing Syndrome
Ying SUN ; Haibo HU ; Na LIU ; Fengchan WANG ; Jinbao ZONG ; Ping HAN ; Peng LI ; Guojing ZHAO ; Haoran WANG ; Xuechao LU
Journal of Traditional Chinese Medicine 2026;67(1):38-44
ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction (清肺渗湿汤) combined with western medicine for patients with bronchial asthma of heat wheezing syndrome, and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group, each group with 43 participants. The control group received conventional western medicine, and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group, 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness; secondary outcome measures included traditional Chinese medicine (TCM) syndrome score, asthma control test (ACT) score, pulmonary function indices such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), serum inflammatory factor levels including interleukin-4 (IL-4), tumour necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP), and immune function indices including CD3+, CD4+, CD8+, CD4+/CD8+. All outcome measures were evaluated before and after treatment. Vital signs were monitored, and electrocardiography, blood routine, urine routine, liver function, and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% (39/40), which was significantly higher than that of the control group (85.0%, 34/40, P<0.05). After treatment, both groups showed decreased TCM syndrome scores, IL-4, TNF-α, hs-CRP, and CD8+ levels, as well as increased ACT scores, CD3+, CD4+, CD4+/CD8+, FEV1, FVC, and PEF levels (P<0.05 or P<0.01). Moreover, the improvements in these indices were more significant in the treatment group than in the control group (P<0.05 or P<0.01). No significant abnormalities in safety indicators were observed in either group, and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms, pulmonary function, and clinical effectiveness, with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.
5.Effects of Yishen paidu formula on renal fibrosis in rats with chronic renal failure by regulating the ROS/TXNIP/NLRP3 pathway
Li FENG ; Bowen PENG ; Bin PENG ; Xue FENG ; Shuangyi ZHU ; Wei XIONG ; Xi HU ; Xiaohui SUN
China Pharmacy 2026;37(2):174-179
OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure (CRF) through the reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. METHODS Rats were randomly divided into control group, model group, Yishen paidu formula low-dose (Yishen paidu formula-L) group, Yishen paidu formula high-dose (Yishen paidu formula- H) group, Yishen paidu formula-H+pcDNA-NC group, and Yishen paidu formula-H+ pcDNA-TXNIP group, with 10 rats in each group. Except for control group, all other rats were fed a diet containing 0.5% adenine to establish a CRF model; the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein, once daily, for 8 consecutive weeks. After the last administration, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), ROS, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were measured in each group. Pathological changes in renal tissue were observed, and the protein expression levels of Collagen Ⅲ, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group, the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr, BUN, ROS, MDA, TNF- α, IL-6 and IL-1β, and the protein expressions of Collagen Ⅲ, α-SMA, TGF-β1, TXNIP and NLRP3 were significantly decreased, while SOD levels were significantly increased (P<0.05). Moreover, the changes were more pronounced in the Yishen paidu formula-H group (P<0.05). Compared with Yishen paidu formula-H+pcDNA-NC group, above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly (P<0.05). CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.
6.YTHDF1 regulation of Fis1 on the activation and proliferation and migration ability of hepatic stellate cells
Lin Jia ; Feng Sun ; Qiqi Dong ; Jingjing Yang ; Renpeng Zhou ; Wei Hu ; Chao Lu
Acta Universitatis Medicinalis Anhui 2025;60(1):49-58
Objective:
To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1).
Methods:
The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential.
Results:
Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05).
Conclusion
YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.
7.Difficulties in the Differentiation and Treatment of Diabetic Kidney Disease and Its Clinical Treatment Model
Weiwei SUN ; Huixi CHEN ; Yuxin HU ; Huijuan ZHENG ; Yaoxian WANG
Journal of Traditional Chinese Medicine 2025;66(6):569-574
Diabetic kidney disease (DKD) is one of the main causes of chronic kidney disease. Both traditional Chinese medicine (TCM) and western medicine have their own advantages in the prevention and treatment of DKD, but there are also many difficulties. By analysis of the difficulties faced by TCM and western medicine in the differentiation and treatment of DKD, based on the theory of "miniature masses in the renal collaterals", combined with long-term clinical practice, "internal heat leading to mass" is proposed as the core pathogenesis of DKD. Therefore, a trinity model of "disease-syndrome-symptom" for differentiation and treatment of DKD based on the core pathogenesis has been proposed. This model highlights the status of the core pathogenesis of "internal heat leading to mass" in DKD, and conducts a three-dimensional identification from the perspectives of disease, syndrome and symptom, so as to inspire clinical practice.
8.Effect of Shenge Bushen Capsules and Its Polysaccharides and Flavonoids on Precocious Puberty in Young Mice
Hong SUN ; Fan LEI ; Chenggong LI ; Shixian HU ; Weihua WANG ; Bin REN ; Juan HAO ; Rui LUO ; Lijun DU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):95-103
ObjectiveTo explore the effect of Shenge Bushen Capsules (SBC) on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part, mice were divided into four groups: The control group and the low, medium, and high-dose SBC groups (234.7, 469.4, 938.7 mg·kg-1, respectively). In the second part, mice were divided into four groups: Control group, Pseudostellariae Radix polysaccharide (PRP) group, total flavonoids group, and SBC group, all receiving a dose of 469.4 mg·kg-1. After 7 days of administration, the vaginal opening of female mice and the descent of testes and scrotum in male mice, as well as the ovarian and testicular organ indices, were observed. After 4 weeks of administration, female and male mice were housed together for 2 days, and the pregnancy rate of females was monitored. After delivery, the pregnant female mice continued receiving the treatment for 4 weeks, and the sexual development of their offspring, including vaginal opening, testicular descent, and organ indices of ovaries and testes, was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group, there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration, the pregnancy rate in the low-dose group was significantly reduced (P<0.05), but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices, and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC, Pseudostellariae Radix polysaccharide, significantly reduced the vaginal opening in female mice after 7 days of administration (P<0.05). After 4 weeks, the serum estradiol levels of non-pregnant female mice were decreased (P<0.05), but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally, there were no significant effects on precocious puberty indicators, such as vaginal opening and testicular descent, in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice, and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.
9.Comprehensive Evaluation of Acupuncture for Secondary Dysmenorrhea Based on Health Technology Assessment
Xue WU ; Zhiran LI ; Jing HU ; Xing LIAO ; Weiwei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):165-174
ObjectiveTo carry out a health technology assessment (HTA) of acupuncture for secondary dysmenorrhea (SD) caused by adenomyosis and endometriosis, in order to provide a reference for relevant medical decision-making. MethodsFrom the perspective of the health system, the assessment covers seven areas, including the technical characteristics, safety, effectiveness, economics, ethical fairness, organizational adaptability, and impact on patients and society. The results are reported accordingly. ResultsThe operational specifications of acupuncture are standardized, and the conditions for its use are clearly defined. Acupuncture has a lower overall incidence of adverse events. The main adverse events are localized pain, subcutaneous bleeding, and dizziness, with most symptoms being mild, all of which have corresponding standard treatments. No reports on occupational or environmental safety were found, and the safety operation specifications are available for reference. Compared with conventional Western medicine, acupuncture demonstrates higher effectiveness. Acupuncture may improve the quality of life scores of patients, though no significant difference was observed. The cost of acupuncture is higher than that of conventional Western medicine, but its overall economic value is greater. The informed consent information is relatively comprehensive. Most patients are aware of the potential benefits and risks of acupuncture and voluntarily opt for it. The treatment process fully respects patient privacy and human rights. The clinical application of acupuncture follows the current acupuncture medical service model, with no special requirements for the level of medical institutions. Patient accessibility and affordability are suitable. Patient satisfaction is high. Most patients indicated they would choose acupuncture again for SD. The main barriers to choosing acupuncture are psychological factors (such as fear of acupuncture), cost, and transportation issues. Nearly 70% of patients receiving acupuncture treatment benefit from medical insurance reimbursement, with reimbursement rates generally above 50%, indicating strong social security support. ConclusionThe implementation of HTA for acupuncture in the treatment of SD, using the standards for traditional Chinese medicine (TCM), is feasible. The implementation steps are clear, the data sources for each evaluation domain are adequate, the analysis methods are practical, and the evaluation results are comprehensive. Experts recommend that the findings be used as a reference for relevant medical decision-making.
10.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.


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