1.Key Information Research and Modern Clinical Application of Xiaofengsan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Ningli WANG ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):238-249
Employing bibliometric methods and adhering to principles of textual research, this study systematically investigated prescription source, formula name, composition evolution, dose evolution, origin, processing, ancient and modern applications of Xiaofengsan. Xiaofengsan, also known as Renshen Xiaofengsan and Chantui Xiaofengsan, was first recorded in the Taiping Huimin Hejijufang(hereafter referred to as Jufang) of the Southern Song dynasty. The formula composition included Schizonepetae Spica, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoptery Rhizoma et Radix, Bombyx Batryticatus, Saposhnikoviae Radix, Poria, Cicadae Periostracum, Pogostemonis Herba, Ginseng Radix et Rhizoma, Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium, a total of 12 medicinal materials. In terms of the evolution of formula composition, formulas across dynasties largely aligned with those recorded in Jufang, with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages:Schizonepetae Spica of 82.6 g, Glycyrrhizae Radix et Rhizoma of 82.6 g, Chuanxiong Rhizoma of 82.6 g, Notoptery Rhizoma et Radix of 82.6 g, Bombyx Batryticatus of 82.6 g, Saposhnikoviae Radix of 82.6 g, Poria of 82.6 g, Cicadae Periostracum of 82.6 g, Pogostemonis Herba of 82.6 g, Ginseng Radix et Rhizoma of 82.6 g, Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g, the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder(pass through the No.5 sieve), and 8.26 g was taken for each dose, which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily, 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat, eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases, predominantly affecting the upper body, especially the head and face. The diseases involved in modern applications were mostly dermatological diseases, including urticaria, eczema, atopic dermatitis and others. In this paper, by combing the relevant ancient literature, the key information of Xiaofengsan was textual researched, in order to provide reference for the modern application and development of this formula.
2.Professor WU Rongzu's Clinical Experience in Treating Irritable Bowel Syndrome with Constipation Using Fuyang Tongmi Decoction (扶阳通秘汤)
Yihao YANG ; Junran ZHU ; Wendi WU ; Liyun JIANG ; Yueqiu DONG ; Yueqing CAI ; Ruibin ZHOU ; Yunjiao XU ;
Journal of Traditional Chinese Medicine 2026;67(10):1049-1051
This paper introduces professor WU Rongzu's clinical experience in using Fuyang Tongmi Decoction (扶阳通秘汤, FTD) to treat irritable bowel syndrome with constipation (IBS-C). It is believed that yang qi depletion, water cold, earth dampness, and wood constraint are the key pathogenesis.The treatment principle is warming water, drying the earth and venting wood, with the basic formula FTD adjusted according to the symptoms. This approach aims to transport the qi movement of the middle jiao (焦) and support the recovery of intestinal function of directing turbidity downward, providing a treatment strategy for IBS-C caused by yang deficiency.
3.Historical Evolution and Modern Clinical Application of Huoxiang Zhengqisan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Congcong LI ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):156-167
In this study, bibliometric methods were used to systematically investigate the name and origin, the evolution of prescription composition, dose evolution, origin and processing method, decoction method, ancient application, modified application, modern application and other information of Huoxiang Zhengqisan. After research, Huoxiang Zhengqisan, also known as Huoxiang Zhengqitang, was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium, 41.3 g of Angelicae Dahuricae Radix, 41.3 g of Perilla frutescens(actually Perillae Folium), 41.3 g of Poria, 82.6 g of Pinelliae Rhizoma, 82.6 g of Atractylodis Macrocephalae Rhizoma, 82.6 g of Citri Reticulatae Pericarpium(actually Citri Exocarpium Rubbum), 82.6 g of Magnoliae Officinalis Cortex, 82.6 g of Platycodonis Radix, 123.9 g of Pogostemonis Herba, and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula, Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products, Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products, and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose, take 8.26 g of the powdered formula, add 300 mL of water, along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus, and decoct until reduced to 140 mL. The decoction should be administered hot, with three times daily. To induce sweating, the patient should be kept warm under a quilt, and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness, regulate Qi and harmonize the middle, which is mainly used to treat a series of diseases of digestive and respiratory systems. However, potential adverse reactions, including allergies, purpura and disulfiram-like reactions, should be considered during clinical use. Huoxiang Zhengqisan features a rational composition, extensive clinical application, and strong potential for further research and development.
4.Historical Evolution and Modern Clinical Application of Huoxiang Zhengqisan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Congcong LI ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):156-167
In this study, bibliometric methods were used to systematically investigate the name and origin, the evolution of prescription composition, dose evolution, origin and processing method, decoction method, ancient application, modified application, modern application and other information of Huoxiang Zhengqisan. After research, Huoxiang Zhengqisan, also known as Huoxiang Zhengqitang, was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium, 41.3 g of Angelicae Dahuricae Radix, 41.3 g of Perilla frutescens(actually Perillae Folium), 41.3 g of Poria, 82.6 g of Pinelliae Rhizoma, 82.6 g of Atractylodis Macrocephalae Rhizoma, 82.6 g of Citri Reticulatae Pericarpium(actually Citri Exocarpium Rubbum), 82.6 g of Magnoliae Officinalis Cortex, 82.6 g of Platycodonis Radix, 123.9 g of Pogostemonis Herba, and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula, Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products, Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products, and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose, take 8.26 g of the powdered formula, add 300 mL of water, along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus, and decoct until reduced to 140 mL. The decoction should be administered hot, with three times daily. To induce sweating, the patient should be kept warm under a quilt, and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness, regulate Qi and harmonize the middle, which is mainly used to treat a series of diseases of digestive and respiratory systems. However, potential adverse reactions, including allergies, purpura and disulfiram-like reactions, should be considered during clinical use. Huoxiang Zhengqisan features a rational composition, extensive clinical application, and strong potential for further research and development.
5.Textual Research on Lianggesan from Ancient Literature and Its Modern Clinical Application
Weilu NIU ; Chengqi LYU ; Mengjie YANG ; Shunxi WANG ; Jingkang QIAO ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Jianwei LI ; Gang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):223-234
Lianggesan was first recorded in Taiping Huimin Heji Jufang, which was composed of Rhei Radix et Rhizoma, Natrii Sulfas, Gardeniae Fructus, Forsythiae Fructus, Scutellariae Radix, Glycyrrhizae Radix et Rhizoma(GRR), Menthae Haplocalycis Herba, Lophatheri Herba and Mel. It was clinically applied to treat fire-heat syndrome in the upper and middle Jiao, and the curative effect was positive. In this study, the bibliometric method was used to conduct a detailed textual research on the formula name, medicinal composition, dosage evolution, origin and processing, functional indications and other aspects of Lianggesan. Research revealed that Lianggesan has six other names, such as Lianqiao Yinzi, Lianqiao Jiedusan, Jufang Lianggesan, Jiegu Lianggesan, Hejian Lianggesan and Qingji Lianggesan. Based on the edition of Taiping Huimin Heji Jufang, an analysis of the evolution of its formula composition revealed that the missing Chinese medicines were predominantly bamboo leaves and honey, while the added Chinese medicines were primarily supplements introduced to address changes in disease manifestations. After textual research, the dosage for one dose of Lianggesan from Taiping Huimin Heji Jufang was as follows:826 g of Rhei Radix et Rhizoma, 826 g of Natrii Sulfas, 826 g of GRR, 413 g of Gardeniae Fructus, 413 g of Menthae Haplocalycis Herba, 413 g of Scutellariae Radix, and 1652 g of Forsythiae Fructus. Decocting method was as following:Grinding the Chinese medicines into coarse powder(2-4 mm), taking 8.16 g per dose, adding 300 mL of water, along with 2 g of Lophatheri Herba and 5 g of Mel, and decocting to 140 mL. The residue was removed and taken warmly 30 min after meals. It was recommended to take it three times daily until improvement was achieved. The origins of the 9 Chinese medicines were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. Except for GRR, which required single frying(stir-frying), the remaining medicines were all raw products. The description of the function of this formula in ancient books was summarized as purging fire and promoting bowel movements, clearing heat from the upper body and purging the lower body, and the main syndromes included facial redness, tongue swelling, red eyes, etc. In modern applications, the formula is primarily used for respiratory and digestive system diseases, including acute lung injury, chronic obstructive pulmonary disease, herpetic angina and aphthous stomatitis, covering 142 types of diseases. In summary, this paper can provide a basis for further research and development of Lianggesan through the literature review and key information combing.
6.Key Information Research and Modern Clinical Application of Famous Classical Formula Yanghetang
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Shunxi WANG ; Ziwen WANG ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):238-246
Through data collection and collation combined with bibliometrics, this study conducted a series of textual research on Yanghetang, such as the name and origin, the evolution of prescription composition and modern clinical application. Yanghetang was first recorded in Bencao Yidu of WANG Ang in the Qing dynasty. In addition to Yanghetang, there were 3 bynames of Jiawei Yanghetang, Quanshengji Yanghetang and Zhenjun Yanghetang. Regarding the composition of the formula, a total of 4 versions of Yanghetang were collected. The first version is the 5 medicines version of Cervi Cornus Colla, Rehmanniae Radix Praeparata, Cinnamomi Cortex, Zingiberis Rhizoma and Ephedrae Herba in Bencao Yidu. The second version is the 7 medicines version of Waike Zhengzhi Quanshengji, changing Zingiberis Rhizoma to Zingiberis Rhizoma Praeparatum Carbonisata(ZRPC) and adding Sinapis Semen and Glycyrrhizae Radix et Rhizoma(GRR) on the basis of Bencao Yidu, and most of the Yanghetang is of this version. The third version is the 6 medicines version of Wushi Yifang Huibian, that is, on the basis of Bencao Yidu, Zingiberis Rhizoma is changed into ZRPC, and Sinapis Semen is added. The fourth version is the 6 medicines version in Yifang Jiedu, that is, on the basis of Bencao Yidu, Zingiberis Rhizoma is changed into Zingiberis Rhizoma Praeparatum, and GRR Praeparata cum Melle is added. Regarding the dose of Yanghetang, the doses of the medicines in Waike Zhengzhi Quanshengji was converted into the modern doses as follows:37.3 g of Rehmanniae Radix Praeparata, 1.87 g of Ephedrae Herba, 11.19 g of Cervi Cornus Colla, 7.46 g of Sinapis Semen, 3.73 g of Cinnamomi Cortex, 3.73 g of GRR, and 1.87 g of ZRPC. The origins of the above medicines are consistent with the 2020 edition of Chinese Pharmacopoeia. The processing specification of Rehmanniae Radix Praeparata is steaming method, ZRPC is ginger charcoal, Sinapis Semen is the fried products, and the rest of the medicines are raw products. The decoction method was verified by the decoction method in Chonglou Yuyao, which is similar in the time, and it is recommended that the above medicines should be added with 600 mL of water, decocted to 100 mL, and taken warmly 30 min after meal. For each dose, it is recommended to use 1-3 doses per day according to the doctor's advice in combination with clinical practice. The diseases involved in the ancient applications involved 42 diseases in 11 departments, including orthopedics, dermatology and gynecology, which were dominated by Yin-cold syndrome. However, the diseases involved in modern research also include 148 related diseases in 10 departments, such as orthopedics, obstetrics and gynecology, which is consistent with the ancient books. In recent years, the research hotspots of Yanghetang have focused on more than 10 fields, including osteoblasts, malignant tumors, wound healing, traditional Chinese medicine fumigation and so on, which are widely used. It is suitable for comprehensive research and development because of its rational formula composition, clear origin, processing and decoction method, and wide clinical application.
7.Influenza vaccination on preventing the respiratory tract infection in preschool children
Mei LYU ; Zhen WANG ; Yu' ; e WANG ; Liyun FANG ; Yang YANG
Journal of Public Health and Preventive Medicine 2025;36(4):73-76
Objective To explore the effect of influenza vaccination on the prevention of respiratory tract infection in preschool children. Methods The clinical data of 400 preschool children (1-6 years old) who were diagnosed with respiratory tract infection for the first time in department of pediatrics of Xi'an Third Hospital and second department of respiratory medicine of Xi'an Children's Hospital were retrospectively analyzed from January 2023 to December 2023, including acute bronchitis, upper respiratory tract infection and pneumonia. According to the actual influenza vaccination status, the patients were divided into vaccination group (n=210) and non-vaccination group (n=190). The incidence of respiratory tract infection was compared between both groups. The fever duration, average course of disease, hospitalization rate, clinical symptoms scores (fever, cough, nasal congestion, sore throat), inflammation indicators [C-reactive protein (CRP), white blood cell count (WBC), neutrophil percentage (NE%)] and recurrence rate after 6 months of follow-up were compared. Results The incidence of respiratory tract infection in the vaccination group was significantly lower than that in the non-vaccination group (21.43% vs 43.16%, P<0.05), and the hospitalization rate was significantly lower compared with that in the non-vaccination group (P<0.05). The scores of fever, cough, nasal congestion and sore throat were lower in the vaccination group than those in the non-vaccination group (P<0.05), and the CRP, WBC and NE% were significantly lower compared to the non-vaccination group (P<0.05). After 6 months of follow-up, the recurrence rate in the vaccination group was 11.11% (5/45), which was significantly lower than 26.83% (22/82) in the non-vaccination group (χ2=0.038, P=4.288<0.05). Conclusion Influenza vaccination can effectively reduce the incidence of respiratory tract infection in preschool children, relieve the symptoms and shorten the disease course after infection. Its preventive effect on influenza is particularly significant, suggesting the importance of strengthening influenza vaccination in preschool children.
8.Clinical value of the prognostic nutritional index in predicting the prognosis of patients with advanced liver cancer treated with transarterial chemoembolization combined with ablation therapy
Wenjing YANG ; Lingyi ZHU ; Chaoming HUANG ; Qi HUANG ; Zijian ZHU ; Yeyu ZHANG ; Shiji FANG ; Liyun ZHENG ; Zhongwei ZHAO ; Jiansong JI
Journal of Interventional Radiology 2025;34(5):512-517
Objective To assess the clinical value of prognostic nutritional index(PNI)in predicting the prognosis of patients with advanced liver cancer treated with transarterial chemoembolization(TACE)combined with ablation therapy.Methods A total of 112 patients with advanced liver cancer,who received TACE combined with ablation at the Lishui Municipal Central Hospital of China from January 2020 to January 2024,were enrolled in this study.The general data,survival status,and survival time were collected.The Youden index of PNI was calculated using the receiver operating characteristic(ROC)curve model,and the optimal cutoff value was determined.Based on the optimal cutoff value,the patients were divided into low-PNI group and high-PNI group.The progression-free survival(PFS)and overall survival(OS)time were compared between the two groups,and the independent risk factors affecting PFS and OS were analyzed.Results The Youden index for PNI was 0.43,and the optimal cutoff value of PNI was 43.95.The low-PNI group included 65 patients,and the high-PNI group included 47 patients.There were no statistically significant differences in the baseline data between the two groups.The median PFS and the median OS in the high-PNI group were 13.21 months(95%CI=4.37-22.03)and 40.80 months(95%CI=31.55-50.05)respectively,which were longer than 9.20 months(95%CI=6.58-11.82)and 21.37 months(95%CI=16.56-26.17)respectively in the low-PNI group,the differences were statistically significant(both P<0.05).The 6-month,one-year and 2-year PFS in the high-PNI group was 56.95%,47.25%and 33.87%respectively,which were higher than 43.95%,32.56%and 16.31%respectively in the low-PNI group.The one-year,2-year and 3-year cumulative survival rates in the high-PNI group were 80.77%,66.66%and 39.40%respectively,which were higher than 63.79%,34.31%and 27.75%respectively in the low-PNI group.Multivariate regression analysis indicated that the number of nodules,metastasis and PNI significantly affected OS,and metastasis and PNI strikingly affected PFS.High PNI was a protective factor for both PFS and OS.Conclusion For patients with advanced liver cancer treated with TACE combined with ablation therapy,PNI is an effective indicator for predicting the prognosis.
9.Research progress on the relationship between the photobiomodulation and amblyopia
Shuxian HU ; Mei LIU ; Jingjing DONG ; Yang YANG ; Li LIU ; Xuan MA ; Liyun GUO
International Eye Science 2025;25(9):1431-1435
Amblyopia is a common visual development disorder and is the main cause of monocular vision impairment in children and adults. Photobiomodulation(PBM), a non-invasive treatment method, has gradually gained attention in the field of ophthalmology. This paper begins with the macroscopic manifestation of light on the animal model of amblyopia. Additionally, it discusses the pathological changes of the amblyopic retina and the human eye's central nervous system, as well as the influence and mechanism of PBM on the visual perception and processing system and its chemical effect on the visual system through dopamine and melatonin. It examines its mechanism of action, current clinical application status, and future development direction in order to provide new ideas and theoretical foundation for amblyopia treatment.
10.Multi-center clinical study on the efficacy and safety of combined lienal polypeptide injection therapy in children with Mycoplasma pneumoniae pneumonia
Qi CHENG ; Yunxiao SHANG ; Han ZHANG ; Jiujun LI ; Ning CHEN ; Lishen SHAN ; Nan YANG ; Lihua NING ; Xuemei BAI ; Jianhua LIU ; Yuling HAN ; Jichun WANG ; Jing LI ; Yong FENG ; Liyun LIU ; Li CHEN ; Si LIU ; Qinzhen ZHANG ; Jia ZHENG ; Fengchao LI ; Sukun LU ; Yun ZHANG ; Xiaoyi CHAI
International Journal of Pediatrics 2025;52(3):204-210
Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia(MPP)in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized,controlled,multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1,2023 to January 31,2024 were included.According to the severity of pneumonia,they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP(SMPP/RMPP)group with 160 cases,and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1,using the random number table method.After screening,subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin,while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT,length of hospital stay,duration of fever,cough score,whether mild cases developed into severe or refractory cases,duration of hormone use,use of intravenous immunoglobulin(IVIG),bronchoscopy treatment,and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication,vital signs,blood routine,urine routine,liver function,myocardial enzymes,renal function,and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals,including 118 cases in the experimental group and 113 cases in the control group.Main observation index:the rate of lung CT aggravation in the experimental group was lower than that in the control group(2.6% vs 15.3%, P<0.01),and the difference was statistically significant.Secondary indexes:there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).However,the rate of cases of plastic bronchitis(PB)found under bronchoscopy in the experimental group was lower than that in the control group(0 vs 18.8%, P=0.03),and the difference was statistically significant.Among the mild MPP(72 cases),there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and the improvement rate of lung CT between the two groups(all P>0.05).However,compared with the control group,the rate of cases developing into SMPP/RMPP in the experimental group was less(24.3% vs 48.6%, P=0.03),and the difference in IgG before and after treatment was small[0.53(-0.04,1.18)g/L vs 1.33(0.48,2.25)g/L, P=0.01].Among the SMPP/RMPP cases(159 cases),the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group(0 vs 20%, P=0.04),and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group(1.3% vs 19.5%, P<0.01),and the improvement rate of lung CT in the experimental group was higher than that in the control group(88.8% vs 75.3%, P=0.03),with statistically significant differences.There were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).Two cases in the experimental group developed rashes,which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine,liver function,myocardial enzymes,renal function,electrocardiogram,and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP,reduce the rate of aggravation of the image findings,promote the absorption of lung inflammation,reduce the rate of PB found under bronchoscopy,and has good safety.


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