1.Investigation of radon activity concentration and dose assessment in subways of Nanning City, China
Xiufang LU ; Yilong MA ; Rongzheng HUANG ; Ziyue LI ; Jiajie LEI ; Lanying FENG ; Zhangfan CHEN ; Xinchun ZHAO
Chinese Journal of Radiological Health 2026;35(1):67-73
Objective To investigate the radon activity concentrations in subways of Nanning City and assess the average annual effective doses for subway staff and passengers due to radon exposure. Methods Sixty-three stations across the subway lines 2, 3, and 5 were selected as study sites. Radon activity concentrations were measured using the scintillation counting method with scintillation vials. Results The radon activity concentrations in subway lines 2, 3, and 5 were 7.9-24.4, 12.0-26.2, and 12.6-18.2 Bq/m3, respectively. The average radon activity concentrations for these three lines were (17.4 ± 4.6), (19.1 ± 4.1), and (14.6 ± 1.7) Bq/m3, respectively. Statistical analysis using SPSS 26.0 software revealed a significant difference in radon activity concentrations among these stations (P<0.01). Considering the data in previous research, the average radon activity concentration across all stations in the subway lines of Nanning City was determined to be 17.4 Bq/m3. The estimated average annual effective dose due to radon exposure was 0.131 mSv for subway staff and 0.033 mSv for passengers. Conclusion The radon activity concentrations in the subway lines of Nanning City were significantly lower than the national standard limit (400 Bq/m3). The annual effective doses from radon exposure for both subway staff and passengers were below the limits specified in the Basic Standards for Protection Against Ionizing Radiation and for the Safety of Radiation Sources (GB18871—2002). The health impact of radon and its progeny on subway staff and passengers in the subway lines of Nanning City was extremely low and can be considered negligible.
2.Distribution and characteristics of traditional Chinese medicine syndromes in adenomyosis
Xin WANG ; Xinchun YANG ; Tian HANG ; Meiru BAO ; Ruihua ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):811-820
Objective To explore the distribution and characteristics of traditional Chinese medicine(TCM)syndromes in patients with adenomyosis.Methods A retrospective analysis was conducted on the data collected from patients with adenomyosis between December 2019 and April 2022 based on a cross-sectional survey.Variables included age,body mass index(BMI),disease duration,geographical region,dysmenorrhea,menstrual flow,diagnosis and treatment goals,history of adenomyosis-related surgery,postoperative recurrence,and carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)levels.The distribution pattern of TCM syndromes,including general information of patients with different syndromes,CA125 and CA199 levels,were analyzed.The relationship between syndromes and age,BMI,duration of disease,geographic region,and history of adenomyosis-related surgery were analyzed using the multinomial logistic regression.Results A total of 1,816 patients with adenomyosis were included.The most common TCM syndrome was syndrome of cold coagulation and blood stasis(36.84%).The other four TCM syndromes,ranked by frequency,were syndrome of qi stagnation and blood stasis(25.39%),syndrome of blood stasis due to qi deficiency(17.35%),syndrome of kidney deficiency and blood stasis(15.97%),and syndrome of intermin-gled phlegm and blood stasis(4.46%).Significant differences in age,disease duration,and BMI were observed among patients with different TCM syndromes(P<0.05).Patients with syndrome of cold congelation and blood stasis,syndrome of kidney deficiency and blood stasis,were younger than those with syndrome of qi stagnation and blood stasis.Patients with syndrome of cold congelation and blood stasis had a longer disease duration than those with syndrome of blood stasis due to qi deficiency.Patients with syndrome of blood stasis due to qi deficiency had lower BMI(P<0.05)than those with syndrome of intermin-gled phlegm and blood stasis.The most common symptom in North China,East China,Southwest China,Northwest China,and Northeast China was syndrome of cold congelation and blood stasis,accounting for 45.39%,35.98%,30.33%,41.38%,and 50.00%,respectively.The most common syndrome in Southern and Central China was syndrome of qi stagnation and blood stasis,accounting for 31.34%and 36.23%respectively.Differences in syndrome distribution were observed between patients in East,Southwest,South,and Central China and those in North China(P<0.05).Syndrome distribution also varied significantly across different diagnosis and treatment goals,as well as menstrual conditions(P<0.05).For treatment goals such as pain relief,lesion control,menstrual flow reduction,and recurrence prevention,the dominant syndromes were syndrome of cold congelation and blood stasis(40.67%,37.13%,36.95%,and 43.35%,respectively)and syndrome of qi stagnation and blood stasis(29.35%,26.39%,26.10%,and 25.75%,respectively).Among patients seeking assisted pregnancy,the primary syndromes were syndrome of cold congelation and blood stasis(41.12%)and syndrome of kidney deficiency and blood stasis(18.69%).Patients with dysmenorrhea were mostly diagnosed with syndrome of cold congelation and blood stasis(39.95%)and syndrome of qi stagnation and blood stasis(28.52%).Differences in syndrome distribution were observed between patients with small and large menstrual volume,with a higher proportion of syndrome of kidney deficiency and blood stasis in patients with small menstrual volume(P<0.05).However,no significant difference was noted in the distribution of TCM syndromes in different treatment stages.Additionally,no statistical significance was observed in the CA125 and CA199 levels among patients with various TCM syndromes.Multinomial logistic regression analysis revealed that compared with syndrome of cold congelation and blood stasis,the course of disease was the influencing factor of syndrome of blood stasis due to qi deficiency,BMI was the influencing factor of syndrome of qi stagnation and blood stasis and syndrome of intermin-gled phlegm and blood stasis,and geography was the influencing factor of syndrome of blood stasis due to qi deficiency,syndrome of qi stagnation and blood stasis,syndrome of kidney deficiency and blood stasis,and syndrome of intermin-gled phlegm and blood stasis.Conclusion Syndrome of cold coagulation and blood stasis is the most prevalent TCM syndrome among patients with adenomyosis,and the distribution of TCM syndromes has a specific regularity.The syndromes are independently correlated with region,disease duration,and BMI.
3.Multimorbidity pattern and traditional Chinese medicine syndrome characteristics of patients with adenomyosis:A cross-sectional study
Xin WANG ; Xinchun YANG ; Ruihua ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(5):636-645
Objective To explore the multimorbidity pattern and traditional Chinese medicine(TCM)syndrome characteristics of patients with adenomyosis(AM)and to provide insights and data support for medical treatment and comprehensive AM management.Methods By retrospectively analyzing multi-center,large-sample,nationwide cross-sectional survey data,patients were divided into a single AM group or a multimorbidity group based on whether they had other diseases.The prevalence rates of specific multimorbidity or a combination of multimorbidities were calculated respectively.Single-factor analysis was used to explore the influence of age,course of disease,education level,labor nature,monthly income,production history,abortion history,operation history,region,and TCM syndromes on multimorbidity in patients with AM.The multimorbidity patterns of patients with AM were explored using Apriori association rules,and the distribution characteristics of TCM syndromes in different multimorbidity patterns were explored.Results Among 1,814 patients with AM,1,429 were in the multimorbidity group(prevalence of 78.78%).Compared with the single AM group,the patients in the multimorbidity group had a long disease course,high academic qualifications,jobs that mostly involved sitting,a history of surgery,and were primarily concentrated in the north(P<0.05).The proportion of patients with qi stagnation and blood stasis syndrome decreased,whereas the proportion of patients with kidney deficiency and blood stasis syndrome increased.Ten multimorbidity association rules were sorted according to the confidence level,and the first place of binary association rules was breast nodule to breast hyperplasia,and the first place of ternary association rules was hysteromyoma,breast nodule to breast hyperplasia.Comprehensive support and confidence level,in the binary association rules,the strong association rule was breast nodule to thyroid nodule,and sub-strong association rule was thyroid nodule to breast hyperplasia;In the ternary association rules,the strong association rule was hysteromyoma,breast nodules to breast hyperplasia,and sub-strong association rule was endometriosis,thyroid nodules to breast hyperplasia.There was no significant difference in the distribution of TCM syndromes in AM patients with different binary and ternary multimorbidity patterns.Conclusion Patients with AM have different multimorbidity patterns,and the TCM syndromes of patients with AM under different multimorbidity patterns have different characteristics.The management system of AM multimorbidity should be further developed to ensure more comprehensive and standardized health management for patients with AM.
4.Analysis of the Therapeutic Effect of Huoxue Xiaoyi Decoction Combined with Exercise on Ovarian Endometriosis
Tingyu ZHAO ; Xinchun YANG ; Guang SHI ; Ruihua ZHAO ; Zijin WANG ; Ran XU ; Jumei SHI ; Yu ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(5):1326-1334
Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.
5.Multimorbidity pattern and traditional Chinese medicine syndrome characteristics of patients with adenomyosis:A cross-sectional study
Xin WANG ; Xinchun YANG ; Ruihua ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(5):636-645
Objective To explore the multimorbidity pattern and traditional Chinese medicine(TCM)syndrome characteristics of patients with adenomyosis(AM)and to provide insights and data support for medical treatment and comprehensive AM management.Methods By retrospectively analyzing multi-center,large-sample,nationwide cross-sectional survey data,patients were divided into a single AM group or a multimorbidity group based on whether they had other diseases.The prevalence rates of specific multimorbidity or a combination of multimorbidities were calculated respectively.Single-factor analysis was used to explore the influence of age,course of disease,education level,labor nature,monthly income,production history,abortion history,operation history,region,and TCM syndromes on multimorbidity in patients with AM.The multimorbidity patterns of patients with AM were explored using Apriori association rules,and the distribution characteristics of TCM syndromes in different multimorbidity patterns were explored.Results Among 1,814 patients with AM,1,429 were in the multimorbidity group(prevalence of 78.78%).Compared with the single AM group,the patients in the multimorbidity group had a long disease course,high academic qualifications,jobs that mostly involved sitting,a history of surgery,and were primarily concentrated in the north(P<0.05).The proportion of patients with qi stagnation and blood stasis syndrome decreased,whereas the proportion of patients with kidney deficiency and blood stasis syndrome increased.Ten multimorbidity association rules were sorted according to the confidence level,and the first place of binary association rules was breast nodule to breast hyperplasia,and the first place of ternary association rules was hysteromyoma,breast nodule to breast hyperplasia.Comprehensive support and confidence level,in the binary association rules,the strong association rule was breast nodule to thyroid nodule,and sub-strong association rule was thyroid nodule to breast hyperplasia;In the ternary association rules,the strong association rule was hysteromyoma,breast nodules to breast hyperplasia,and sub-strong association rule was endometriosis,thyroid nodules to breast hyperplasia.There was no significant difference in the distribution of TCM syndromes in AM patients with different binary and ternary multimorbidity patterns.Conclusion Patients with AM have different multimorbidity patterns,and the TCM syndromes of patients with AM under different multimorbidity patterns have different characteristics.The management system of AM multimorbidity should be further developed to ensure more comprehensive and standardized health management for patients with AM.
6.Analysis of the Therapeutic Effect of Huoxue Xiaoyi Decoction Combined with Exercise on Ovarian Endometriosis
Tingyu ZHAO ; Xinchun YANG ; Guang SHI ; Ruihua ZHAO ; Zijin WANG ; Ran XU ; Jumei SHI ; Yu ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(5):1326-1334
Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.
7.Distribution and characteristics of traditional Chinese medicine syndromes in adenomyosis
Xin WANG ; Xinchun YANG ; Tian HANG ; Meiru BAO ; Ruihua ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):811-820
Objective To explore the distribution and characteristics of traditional Chinese medicine(TCM)syndromes in patients with adenomyosis.Methods A retrospective analysis was conducted on the data collected from patients with adenomyosis between December 2019 and April 2022 based on a cross-sectional survey.Variables included age,body mass index(BMI),disease duration,geographical region,dysmenorrhea,menstrual flow,diagnosis and treatment goals,history of adenomyosis-related surgery,postoperative recurrence,and carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)levels.The distribution pattern of TCM syndromes,including general information of patients with different syndromes,CA125 and CA199 levels,were analyzed.The relationship between syndromes and age,BMI,duration of disease,geographic region,and history of adenomyosis-related surgery were analyzed using the multinomial logistic regression.Results A total of 1,816 patients with adenomyosis were included.The most common TCM syndrome was syndrome of cold coagulation and blood stasis(36.84%).The other four TCM syndromes,ranked by frequency,were syndrome of qi stagnation and blood stasis(25.39%),syndrome of blood stasis due to qi deficiency(17.35%),syndrome of kidney deficiency and blood stasis(15.97%),and syndrome of intermin-gled phlegm and blood stasis(4.46%).Significant differences in age,disease duration,and BMI were observed among patients with different TCM syndromes(P<0.05).Patients with syndrome of cold congelation and blood stasis,syndrome of kidney deficiency and blood stasis,were younger than those with syndrome of qi stagnation and blood stasis.Patients with syndrome of cold congelation and blood stasis had a longer disease duration than those with syndrome of blood stasis due to qi deficiency.Patients with syndrome of blood stasis due to qi deficiency had lower BMI(P<0.05)than those with syndrome of intermin-gled phlegm and blood stasis.The most common symptom in North China,East China,Southwest China,Northwest China,and Northeast China was syndrome of cold congelation and blood stasis,accounting for 45.39%,35.98%,30.33%,41.38%,and 50.00%,respectively.The most common syndrome in Southern and Central China was syndrome of qi stagnation and blood stasis,accounting for 31.34%and 36.23%respectively.Differences in syndrome distribution were observed between patients in East,Southwest,South,and Central China and those in North China(P<0.05).Syndrome distribution also varied significantly across different diagnosis and treatment goals,as well as menstrual conditions(P<0.05).For treatment goals such as pain relief,lesion control,menstrual flow reduction,and recurrence prevention,the dominant syndromes were syndrome of cold congelation and blood stasis(40.67%,37.13%,36.95%,and 43.35%,respectively)and syndrome of qi stagnation and blood stasis(29.35%,26.39%,26.10%,and 25.75%,respectively).Among patients seeking assisted pregnancy,the primary syndromes were syndrome of cold congelation and blood stasis(41.12%)and syndrome of kidney deficiency and blood stasis(18.69%).Patients with dysmenorrhea were mostly diagnosed with syndrome of cold congelation and blood stasis(39.95%)and syndrome of qi stagnation and blood stasis(28.52%).Differences in syndrome distribution were observed between patients with small and large menstrual volume,with a higher proportion of syndrome of kidney deficiency and blood stasis in patients with small menstrual volume(P<0.05).However,no significant difference was noted in the distribution of TCM syndromes in different treatment stages.Additionally,no statistical significance was observed in the CA125 and CA199 levels among patients with various TCM syndromes.Multinomial logistic regression analysis revealed that compared with syndrome of cold congelation and blood stasis,the course of disease was the influencing factor of syndrome of blood stasis due to qi deficiency,BMI was the influencing factor of syndrome of qi stagnation and blood stasis and syndrome of intermin-gled phlegm and blood stasis,and geography was the influencing factor of syndrome of blood stasis due to qi deficiency,syndrome of qi stagnation and blood stasis,syndrome of kidney deficiency and blood stasis,and syndrome of intermin-gled phlegm and blood stasis.Conclusion Syndrome of cold coagulation and blood stasis is the most prevalent TCM syndrome among patients with adenomyosis,and the distribution of TCM syndromes has a specific regularity.The syndromes are independently correlated with region,disease duration,and BMI.
8.Study on the Effect of Formononetin on Cardiomyocyte Injury induced by Hypoxia/Reoxygenation
Jinpan WU ; Weiping YANG ; Xinchun ZHAO
Journal of Medical Research 2024;53(10):81-86,98
Objective To examine the protective effect and mechanism of formononetin on rat cardiomyocyte injury induced by hy-poxia/reoxygenation.Methods The H9C2 rat cardiomyocytes were randomly divided into the control group,hypoxia/reoxygenation group,and formononetin group.Cells in the control group were cultured in conventional incubators,and cells in the hypoxia/reoxygenation group were cultured in hypoxia incubators and conventional incubators alternately.Cells in the formononetin group were treated with 35μmol/L formononetin after incubation in the hypoxia/reoxygenation.Cell activity was tested by a cell activity detection kit.The content of oxidative stress and inflammatory response indicators were examined by related test kits.The flow cytometry and polynucleotide chain break detection technology were used to detect apoptosis levels.Western blot was used to detect the levels of apoptosis-related proteins.Results Compared with the control group,cells in the hypoxia/reoxygenation group showed decreased cell activity and increased oxida-tive stress,inflammatory damage,and apoptosis(P<0.05).Compared with the hypoxia/reoxygenation group,cells of the formononetin group showed increased cell activity and decreased oxidative stress,inflammatory damage,and apoptosis(P<0.05).Conclusion For-mononetin may protect against hypoxia/reoxygenation injury by reducing the apoptosis of H9C2 rat cardiomyocytes.
9.Symptom clusters and the bridge symptoms in breast cancer patients undergoing postoperative chemotherapy:a network-based cross-sectional analysis
Xinchun ZHANG ; Yihai WANG ; Ling CHEN ; Bei ZHAO
Modern Clinical Nursing 2024;23(8):11-18
Objective To identify symptom clusters in breast cancer patients undergoing chemotherapy and investigate the bridge symptoms that connect the symptom clusters,therefore to provide a guidance for precise intervention in the symptoms.Methods From October 2022 to October 2023,convenience sampling method was employed to selelct 340 breast cancer patients,who underwent postoperative chemotherapy,for investigation in the related symptom clusters and quality of life by using Anderson symptom assessment scale and breast cancer quality of life scale.Cluster analysis was performed to extract the symptom clusters by R software and the impacts of each symptom cluster on quality of life were analysed by stratified regression.A contemporaneous symptom network was constructed to identify the bridge symptoms.Results All 327 patients had completed the study.Three distinct symptom clusters were extracted:-gastrointestinal,psychological and neurological symptom clusters.The gastrointestinal cluster alone accounted for 10.2%of the variation in quality of life.Network analysis highlighted that distress(rbe=3.927,rbs=3.927,rbc=0.436),fatigue(rbe=3.907,rbs=3.907,rbc=0.434)and lack of appetite(rbe=3.842,rbs=3.842,rbc=0.427)were the bridging symptoms which had high expected influence coefficient,strength and closeness centrality index.Conclusion The gastrointestinal symptom cluster makes notably impact on the quality of life in breast cancer patients undergoing chemotherapy.Fatigue,lack of appetite and distress are the bridge symptoms in symptom management strategies in potentially improving the efficiency of intervention and reducing the costs to patient.
10.Study on effect of Huoxue Xiaoyi Formula on ovarian function and pregnancy outcome in rats with endometriosis
Guang SHI ; Xinchun YANG ; Jingrun CUI ; Yu ZHANG ; Ruihua ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(3):374-382
Objective To explore the effect of Huoxue Xiaoyi Formula on ovarian function and pregnancy outcome in endometriosis rats. Methods One hundred female SD rats were fed adaptively for 7 days. According to body weight, 98 rats with a normal estrous cycle were randomly divided into the blank group (n=14), the sham operation group (n=14), the donor group (n=12), and the receptor group (n=58). A rat model of endometriosis was established using allogeneic endometrial transplantation. After the model was successfully established, according to the body weight, 56 rats in the receptor group were randomly divided into the model group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups, with 14 rats in each group. The Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were given 5.86, 11.72, and 23.44 g/kg of Huoxue Xiaoyi Formula, and the blank group, the sham operation group, and the model group were given distilled water by gavage for 15 consecutive days. According to body weight, six rats were randomly selected to take abdominal aortic blood for determination of serum anti-Mullerian hormone (AMH) content by enzyme-linked immunosorbent assay. According to body weight, six rats were randomly selected in the remaining rats to undergo high-frequency small animal ultrasound examination to measure ovarian volume and ovarian artery blood supply (resistance index and pulsatility index), and follicle count were measured. The female mice were fed with male mice at a ratio of 2:1 to observe the pregnancy rate, live fetus number, still fetus number, and absorbed fetus number. The weights of uterus and fetus were measured, while the placental weight, fetal weight, body length, and tail length were measured for live fetus. Bone and visceral malformations were also detected for live fetus. Results There were no significant differences in serum AMH and ovarian volume among the groups. Compared with the model group, the numbers of follicles in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were increased; compared with the Huoxue Xiaoyi Formula low-dose group, the numbers of follicles in the blank group and the Huoxue Xiaoyi Formula medium-dose group were increased (P<0.05). Compared with the model group, the resistance index and pulsatility index of ovarian artery blood flow in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were decreased(P<0.05). There was no significant difference in pregnancy rate among the groups. Compared with the model group and the Huoxue Xiaoyi Formula low-dose group, the live fetus number and the weight of uterus and fetus in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula medium- and high-dose groups were increased (P<0.05). There were no significant differences in the still fetus number, absorbed fetus number, placental weight, fetal weight, body length and tail length among the groups. No visceral or skeletal malformations were found in the live fetal rats among the groups.Conclusion In endometriosis model rats, the ovarian artery blood flow perfusion is insufficient, and the follicle count is reduced, affecting ovary function, thereby reducing the live fetus number. After applying the Huoxue Xiaoyi Formula, it can improve ovarian blood supply, increase the follicle count, and increase the live fetus number. The effect of increasing the live fetus number with the medium- and high-doses of Huoxue Xiaoyi Formula is more significant, and there is no reproductive toxicity.

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