1.Relevant Mechanism of Traditional Chinese Medicine in Treatment of Hyperandrogenism in Polycystic Ovary Syndrome: A Review
Wenchen FAN ; Hui MA ; Yongfen DING ; Haotian MA ; Fei GAO ; Qiuyu LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):306-317
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Hyperandrogenism (HA), one of its core pathological features, is closely associated with the clinical manifestations and metabolic complications of the disease. Current western medical treatments for PCOS-HA mainly include anti-androgen therapy and ovulation induction, such as short-acting oral contraceptives like Diane-35 and Yasmin. However, long-term use of these medications may result in adverse reactions like increasing the risk of liver dysfunction and exacerbating lipid metabolism disorders, with unsatisfactory long-term efficacy when used alone. Traditional Chinese medicine offers unique advantages in the treatment of PCOS-HA due to its holistic approach and multi-target regulatory mechanisms. In the view of traditional Chinese medicine, PCOS-HA is classified under the categories such as "delayed menstruation", "amenorrhea", and "infertility", with kidney deficiency as the root, as well as liver stagnation and spleen deficiency as the manifestations. Phlegm and blood stasis are considered to be intertwined throughout the disease course. Modern studies have shown that traditional Chinese medicine is significantly effective in improving the androgen levels, restoring ovulation, and improving insulin resistance in PCOS-HA patients. Representative prescriptions, such as Erxian Tang, Jiawei Xiaoyaosan, Guizhi Fulingwan, and Cangfu Daotantang, exert therapeutic effects through various mechanisms including regulation of the hypothalamic-pituitary-ovarian axis, reduction of ovarian androgen synthase activity, improvement of insulin signaling pathways, and inhibition of inflammation and oxidative stress, which demonstrates the characteristics of comprehensive treatment with traditional Chinese medicine. Based on the perspectives of etiology and pathogenesis of traditional Chinese medicine, modern medical cognition, typical prescriptions, and action mechanisms, this paper reviewed the research progress of traditional Chinese medicine in the treatment of PCOS-HA, aiming to provide a reference for in-depth research and clinical applications in this field.
2.Relevant Mechanism of Traditional Chinese Medicine in Treatment of Hyperandrogenism in Polycystic Ovary Syndrome: A Review
Wenchen FAN ; Hui MA ; Yongfen DING ; Haotian MA ; Fei GAO ; Qiuyu LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):306-317
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Hyperandrogenism (HA), one of its core pathological features, is closely associated with the clinical manifestations and metabolic complications of the disease. Current western medical treatments for PCOS-HA mainly include anti-androgen therapy and ovulation induction, such as short-acting oral contraceptives like Diane-35 and Yasmin. However, long-term use of these medications may result in adverse reactions like increasing the risk of liver dysfunction and exacerbating lipid metabolism disorders, with unsatisfactory long-term efficacy when used alone. Traditional Chinese medicine offers unique advantages in the treatment of PCOS-HA due to its holistic approach and multi-target regulatory mechanisms. In the view of traditional Chinese medicine, PCOS-HA is classified under the categories such as "delayed menstruation", "amenorrhea", and "infertility", with kidney deficiency as the root, as well as liver stagnation and spleen deficiency as the manifestations. Phlegm and blood stasis are considered to be intertwined throughout the disease course. Modern studies have shown that traditional Chinese medicine is significantly effective in improving the androgen levels, restoring ovulation, and improving insulin resistance in PCOS-HA patients. Representative prescriptions, such as Erxian Tang, Jiawei Xiaoyaosan, Guizhi Fulingwan, and Cangfu Daotantang, exert therapeutic effects through various mechanisms including regulation of the hypothalamic-pituitary-ovarian axis, reduction of ovarian androgen synthase activity, improvement of insulin signaling pathways, and inhibition of inflammation and oxidative stress, which demonstrates the characteristics of comprehensive treatment with traditional Chinese medicine. Based on the perspectives of etiology and pathogenesis of traditional Chinese medicine, modern medical cognition, typical prescriptions, and action mechanisms, this paper reviewed the research progress of traditional Chinese medicine in the treatment of PCOS-HA, aiming to provide a reference for in-depth research and clinical applications in this field.
3.An exploratory study on the effect of ultrasonic waves against Aedes albopictus larvae
Shuqing JIN ; Xinyi CAI ; Heyi WEN ; Jian FAN ; Hui CAO ; Tianyu SHA ; Hongxia LIU ; Yuan FANG ; Qiang GAO
Shanghai Journal of Preventive Medicine 2026;38(7):550-555
ObjectiveTo evaluate the larvicidal effect of ultrasonic waves against Aedes albopictus larvae at various exposure parameters (distance and time), and to preliminarily investigate the effects of different containers (water volume and depth) and ultrasonic devices on the larvicidal efficacy, so as to provide experimental evidence for the application of ultrasound-based mosquito control technology. MethodsUnder controlled laboratory conditions, two commercially available ultrasonic devices [40 kHz/300 W and (50±5) kHz/70 W] were used to systematically examine the effects of exposure distance (20, 40, 60, 80, and 100 cm), exposure duration (1, 3, 6, 15 and 60 min), larval instar(Ⅰ‒Ⅱ and Ⅲ‒Ⅳ), and container type on the immediate mortality of Aedes albopictus larvae collected from urban areas of Shanghai. Statistical analysis of the mortality rates of larvae among different experimental groups was performed using the chi-square test. ResultsUltrasonic exposure exerted a detectable larvicidal effect against Aedes albopictus larvae of all instars. For early-instar larvae, exposure time significantly affected mortality at all tested distances (20, 40, 60, 80 and 100 cm), with χ² values ranging from 25.57 to 32.74 ( all P<0.001). No significant distance effect was observed in the first and second instar larvae after short-term exposure (1 and 3 min; P>0.05). However, a distance-dependent effect emerged from 6 min onward (P<0.05). During short-term exposure (1 min and 3 min) at close range (20 cm and 40 cm), the immediate mortality of the third and fourth instar larvae was higher than that of the first and second instar larvae. Conversely, during prolonged exposure (15 min and 60 min), the first and second instar larvae exhibited significantly higher mortality than that of the third and fourth instar larvae. These results indicated that larval mortality was jointly influenced by exposure duration and distance. Preliminary experiments indicated that larvicidal efficacy in shallow water was lower than that in deep water. No significant difference in larvicidal effect was observed between the two ultrasonic devices with different frequencies and power outputs. ConclusionUnder laboratory conditions, ultrasound can effectively kill Aedes albopictus larvae, and the larvicidal effect is jointly influenced by larval instar, exposure distance, and aquatic environment. Compact ultrasonic devices show potential for field application in biological mosquito control.
4.Effect of Yiqi Wenyang Huoxue Lishui Components on Cardiac Function and Mitochondrial Energy Metabolism in CHF Rats
Hui GAO ; Zeqi YANG ; Xin LIU ; Fan GAO ; Yangyang HAN ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):27-36
ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure (CHF) and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction (TAC). Eight of the 50 SD rats were randomly selected as the sham group, and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model, trimetazidine (6.3 mg·kg-1), and Yiqi Wenyang Huoxue Lishui components (60 mg·kg-1 total saponins of Astragali Radix, 10 mg·kg-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma, 190 mg·kg-1 aqueous extract of Lepidii Semen, and 100 mg·kg-1 cinnamaldehyde) groups. The rats were administrated with corresponding agents by gavage, and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide (NT-ProBNP), hypersensitive troponin(cTnI), creatine kinase (CK), lactate dehydrogenase (LD), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA). The colorimetric assay was employed to measure the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta (ATP5D), glucose transporter 4 (GLUT4), and carnitine palmitoyltransferase-1 (CPT-1). The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ, Ⅱ, Ⅲ, and Ⅳ. ResultsCompared with the sham group, the model group showed a loosening arrangement of cardiac fibers, fracture and necrosis of partial cardiac fibers, inflammatory cells in necrotic areas, massive blue fibrotic tissue in the myocardial interstitium, increased collagen fiber area and myocardial fibrosis, destroyed mitochondria, myofibril disarrangement, sparse myofilaments, and fractured and reduced cristae. In addition, the rats in the model group showed declined ejection fraction (EF) and fractional shortening (FS), risen left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs), elevated levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, lowered level of SOD, down-regulated protein levels of GLUT4 and CPT-1, decreased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and declined levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). Compared with the model group, the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue, risen EF and FS, declined LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs, lowered levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, elevated level of SOD, up-regulated protein levels of GLUT4 and CPT-1, increased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and elevated levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function, reduce myocardial injury, regulate glucose and lipid metabolism, optimize the utilization of substrates, and alleviate the damage of mitochondrial structure and function, thus improving the energy metabolism of the myocardium in the rat model of CHF.
5.Four new sesquiterpenoids from the roots of Atractylodes macrocephala
Gang-gang ZHOU ; Jia-jia LIU ; Ji-qiong WANG ; Hui LIU ; Zhi-Hua LIAO ; Guo-wei WANG ; Min CHEN ; Fan-cheng MENG
Acta Pharmaceutica Sinica 2025;60(1):179-184
The chemical constituents in dried roots of
6.Value of FMEA evaluation model in preventing and controlling infection of medical device in hospital
Hui DENG ; Anna ZOU ; Niluo MO ; Fan LIU ; Honglin CAO ; Haoran FAN
China Medical Equipment 2025;22(7):119-123,129
Objective:To construct a failure mode and effects analysis(FMEA)evaluation model for medical devices to manage devices,so as to enhance management efficiency for medical devices.Methods:The FMEA was adopted to construct FMEA evaluation model for medical devices,so as to conduct comprehensive lifecycle management for medical devices.The process of management for equipment was optimized,and the operational risk of medical devices was reduced through failure mode(FM)analysis and the construction of management system for equipment.A total of 47 medical devices in clinical use of The First People's Hospital of Neijiang from January to December 2023 were included.In them,23 devices received conventional management mode during January and June 2023,and 24 devices received FMEA evaluation model(model management mode)during July and December 2023.For each group,2,000 patients'medical records were selected.The control effectiveness of infectious indicators,effect of cleaning and disinfection,and quality scores of infectious control for medical devices were compared between different management modes.A self-designed questionnaire was adopted to investigate the recognition scores of engineers who used and managed devices,operators,physicians,and department administrators for two kinds of management modes.Results:In 2,000 patients'medical records,who adopted model management mode,the infection rate of patients,and infection rate of aseptic surgical incision were respectively 0.15%and 0.05%,both were significantly lower than those in the conventional management mode(x2=5.420,8.358,P<0.05).The cleaning rate,and disinfection qualification rate of 24 medical devices,which adopted model management mode,were respectively 83.33%and 87.50%,all of which were significantly higher than these of conventional management mode(x2=8.080,6.741,P<0.05).The scores of standardized operation,rational use,disinfection and cleaning,and emergency intervention for medical devices in adopting model management mode were significantly higher than those in adopting conventional management mode(t=14.435,16.014,13.049,12.537,P<0.05).The recognition scores of engineers who used and managed devices,operators,physicians,and department administrators for adopting model management mode were significantly higher than those for adopting conventional management mode,and the differences were significant(t=12.219,12.147,17.437,13.420,P<0.05).Conclusion:The FMEA evaluation model for medical devices can real-time monitor the entire management process for medical devices,and reduce clinical infections,and ensure normal operation of devices,and improve clinically operational quality of them,and increase satisfaction of staffs in clinical departments.
7.Clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern
Jia-man YANG ; Tong LIU ; De-hui FAN ; Mei-yi SU ; Ying LIN ; Man-guang LIANG ; Zhi-wen OU ; Shun-cong ZHANG
Chinese Traditional Patent Medicine 2025;47(11):3630-3634
AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P<0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P<0.05),and shortened PT,APTT(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.
8.Effects of intraoperative administration of tranexamic acid on early postoperative inflammatory levels and clinical outcomes in elderly male patients with intertrochanteric femur fractures
Xiangxu CHEN ; Huanyi ZHU ; Wei WU ; Chen RUI ; Liu SHI ; Wenbin FAN ; Cheng ZHANG ; Wenjun XIE ; Yingjuan LI ; Hui CHEN ; Yunfeng RUI
Chinese Journal of Trauma 2025;41(5):489-494
Objective:To compare the effects of intraoperative administration or non-administration of tranexamic acid (TXA) on early postoperative inflammatory response and clinical outcomes in elderly male patients with intertrochanteric femur fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 elderly male patients with intertrochanteric femur fractures admitted to Zhongda Hospital Affiliated to Southeast University from January 2020 to December 2022, aged 62-96 years [(79.9±8.4)years]. According to the modified Evans classification, the fractures were classified as types I-III in 33 patients and types IV-V in 59. All the patients were treated with proximal femoral intramedullary nail fixation. Among them, 46 patients received intraoperative TXA (TXA group), while 46 patients did not (non-TXA group). The operative duration, intraoperative blood loss, length of postoperative hospital stay were compared between the two groups. The serum interleukin-6 (IL-6) levels and visual analogue scale (VAS) scores at 1, 3, 5, and 7 days postoperatively were detected. The complication rate and mortality within 1 year postoperatively were also compared between the two groups.Results:All the patients were followed up for 1-12 months [(10.9±2.8)months]. No significant difference was found in the operative duration between the groups ( P>0.05). The intraoperative blood loss and length of postoperative hospital stay were 150.0(100.0, 200.0)ml and (6.8±1.9)days in the TXA group, less or shorter than those in the non-TXA group [200.0(150.0, 262.5)ml and (7.7±2.0)days] ( P<0.05). At 1, 3, and 5 days postoperatively, the IL-6 levels in the TXA group were 84.5(66.3, 100.1)pg/ml, 48.9(36.8, 61.2)pg/ml, and 27.9(19.4, 37.5)pg/ml, which were all lower than those in the non-TXA group [110.3(83.1, 162.9)pg/ml, 63.7(44.2, 84.2)pg/ml, and 32.7(22.4, 42.9)pg/ml] ( P<0.05). No statistically significant difference in the IL-6 level was observed between the two groups at 7 days postoperatively ( P>0.05). At 1 and 3 days after operation, the VAS scores in the TXA group were (4.3±0.9)points and (2.5±0.9)points, lower than those in the non-TXA group [(6.8±1.2)points and (3.0±1.2)points] ( P<0.05). There were no statistically significant differences in VAS scores between the two groups at 5 and 7 days postoperatively ( P>0.05). The complication rate within one year after operation was 28% (13/46) in the TXA group, significantly lower than 50% (23/46) in the non-TXA group ( P<0.05). No significant difference was observed in the mortality within 1 year postoperatively between the two groups ( P>0.05). Conclusion:Compared with non-administration of TXA, intraoperative administration of TXA can effectively reduce the intraoperative blood loss, shorten the length of postoperative hospital stay, significantly lower early postoperative inflammation levels, reduce early postoperative pain intensity, and decrease the incidence of complications in elderly male patients with intertrochanteric femur fractures, with no significant difference in mortality within 1 year after operation between the two groups.
9.Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures (version 2025)
Bolong ZHENG ; Wei MEI ; Yanzheng GAO ; Liming CHENG ; Jian CHEN ; Qixin CHEN ; Liang CHEN ; Xigao CHENG ; Jian DONG ; Jin FAN ; Shunwu FAN ; Xiangqian FANG ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Yong HAI ; Baorong HE ; Lijun HE ; Yuan HE ; Hua HUI ; Weimin JIANG ; Junjie JIANG ; Dianming JIANG ; Xuewen KANG ; Hua GUO ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Chao MA ; Xuexiao MA ; Renfu QUAN ; Limin RONG ; Honghui SUN ; Tiansheng SUN ; Yueming SONG ; Hongxun SANG ; Jun SHU ; Jiacan SU ; Jiwei TIAN ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Zhengwei XU ; Huilin YANG ; Jiancheng YANG ; Liang YAN ; Feng YAN ; Guoyong YIN ; Xuesong ZHANG ; Zhongmin ZHANG ; Jie ZHAO ; Yuhong ZENG ; Yue ZHU ; Rongqiang ZHANG
Chinese Journal of Trauma 2025;41(9):805-818
Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.
10.Cross-cultural adaptation and validation of the postoperative recovery in children scale for dental treatment under general anesthesia (PRiC-DTGA) in Chinese children
Xiaotong SHI ; Bing LIU ; Ze FAN ; Yao ZHANG ; Tiantian LIU ; Zhenzhen GAO ; Haopeng ZHANG ; Hui ZHANG
Chinese Journal of Stomatology 2025;60(10):1128-1136
Objective:To translate and adapt the postoperative recovery in children (PRiC) scale, developing a Chinese version for children undergoing dental treatment under general anesthesia (PRiC-DTGA) with validated psychometric properties.Methods:The PRiC scale underwent forward-backward translation using Brislin′s model. A convenience sample of DTGA patients from the Department of Anesthesiology, School of Stomatology, The Fourth Mility Force Medical University was enrolled for a cross-sectional survey on postoperative complications. Delphi expert consultation informed cultural adaptation based on survey findings to develop the PRiC-DTGA Chinese version. Psychometric validation included reliability and validity testing in a separate DTGA cohort at the same center (April-October 2024).Results:Results from the cross-sectionalsurvey of 231 children showed that 82.7% (191/231) of them hadat least one postoperative complication within 72 hours, and these complications were mainly mild local symptoms. Additionally, 358 copies of the Chinese version of the PRiC-DTGA scale were distributed; 21 invalid questionnaires with incomplete information were excluded, and a total of 337 cases were included inthe study. The final PRiC-DTGA comprised 22 items across three dimensions including physical comfort, social ability, and negative emotional. Exploratory factor analysis (EFA) confirmed all factor loadings>0.4. Confirmatory factor analysis (CFA) demonstrated adequate fit: χ 2/df=1.665, tucker-Lewis index (TLI)=0.924, comparative fit index (CFI)=0.896, standardized root mean square residual (SRMR)=0.041, and root mean square error of approximation (RMSEA)=0.044 (90% CI: 0.035-0.053). Reliability was strong with Cronbach′s α (total scale)=0.853, subscale α=0.632-0.723, split-half reliability=0.824. Validity indices met standards: scale-content validity index (S-CVI)=0.909, Item-CVI range=0.944-1.000, average variance extracted (AVE)=0.473-0.501, composite reliability (CR)=0.830-0.913. Conclusions:The systematically adapted PRiC-DTGA demonstrates robust reliability and validity, serving as an effective tool for assessing postoperative recovery quality in Chinese children following DTGA.

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