1.Visual acuity and corrected visual acuity of children and adolescents in Shanghai City
Chinese Journal of School Health 2025;46(1):24-28
Objective:
To investigate the visual acuity and correction conditions of children and adolescents in Shanghai, so as to provide a scientific basis for developing intervention measures to prevent myopia and protect vision among children and adolescents.
Methods:
From October to December 2022, a stratified cluster random sampling survey was conducted, involving 47 034 students from 16 municipal districts in Shanghai, covering kindergartens (≥5 years), primary schools, middle schools, general high schools and vocational high schools. According to the Guidelines for Screening Refractive Errors in Primary and Secondary School Students, the Standard Logarithmic Visual acuity Chart was used to examine naked vision and corrected vision of students, and general information was collected. The distribution and severity of visual impairment in different age groups were analyzed, and χ 2 tests and multivariate Logistic regression were used to explore factors associated with visual impairment.
Results:
The detection rate of visual impairment among children and adolescents was 76.2%, with a higher rate among females (78.8%) than males ( 73.8 %), higher among Han ethic students ( 76.2 %) than minority students (71.2%), and higher among urban students (76.7%) than suburban students (75.8%), all with statistically significant differences ( χ 2=162.6, 10.4, 5.5, P <0.05). The rate of visual impairment initially decreased and then increased with age, reaching its lowest at age 7 (53.8%) and peaking at age 17 (89.6%) ( χ 2 trend = 3 467.0 , P <0.05). Severe visual impairment accounted for the majority, at 56.6%, and there was a positive correlation between the severity of visual impairment and age among children and adolescents ( r =0.45, P <0.05). Multivariate Logistic regression showed that age, BMI, gender, ethnicity and urban suburban status were associated with visual impairment ( OR =1.18, 1.01, 1.38 , 0.79, 0.88, P <0.05). Among those with moderate to severe visual impairment, the rate of spectacle lens usage was 62.8%, yet only 44.8 % of those who used spectacle lens had fully corrected visual acuity. Females (64.9%) had higher spectacle lens usage rates than males (60.6%), and general high school students had the highest spectacle lens usage (83.9%), and there were statistically significant differences in gender and academic stages ( χ 2=57.7, 4 592.8, P <0.05).
Conclusions
The rate of spectacle lens usage among students with moderate to severe visual impairment is relatively low, and even after using spectacle lens, some students still do not achieve adequate corrected visual acuity. Efforts should focus on enhancing public awareness of eye health and refractive correction and improving the accessibility of related health services.
2.Overview of the amendments and revisions to the General Technical Requirements adopted by the Volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition
ZHANG Jun ; NING Baoming ; WEI Shifeng ; SHEN Haoyu ; SHANG Yue ; ZHU Ran ; XU Xinyi ; CHEN Lei ; LIU Tingting ; MA Shuangcheng
Drug Standards of China 2025;26(1):034-044
To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines; further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly; replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.
3.Quantification of in vivo biomechanics and analysis of influencing factors in cervical spine fixed-point rotation manipulation
Jiyao LIANG ; Honghai ZHOU ; Guikang WEI ; Shaoting SU ; Longhao CHEN ; Xinyu HE ; Liangpu LIU
Chinese Journal of Tissue Engineering Research 2025;29(3):486-492
BACKGROUND:Fixed-point rotation manipulation of cervical spine is a mechanical operation with high technical requirements,but the biomechanics of fixed-point manipulation of cervical spine still lacks relevant quantitative data.Moreover,the research on the influencing factors of cervical fixed-point rotation manipulation includes many parameters and there are differences,so it is necessary to further analyze its influencing factors to improve its related data. OBJECTIVE:To quantify the biomechanical parameters of cervical spine fixed-point rotation manipulation,explore the correlation between different biomechanical parameters,and the influence of individual characteristics of the subjects on the biomechanical parameters of cervical spine fixed-point rotation manipulation. METHODS:Totally 35 cases of cervical spondylosis were Outpatients from Orthopedic Department of Renai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine and selected as the subjects investigated.Wearable mechanical measuring gloves were used to collect biomechanical parameters of cervical spine fixed-point rotation manipulation,including:thumb preload,thumb maximum thrust,palm preload,palm wrench force,and palm wrench maximum force.Personal characteristic parameters were collected,including age,height,weight,and neck circumference.The key biomechanical parameters in the process of cervical spine fixed-point rotation manipulation were analyzed and different individual characteristics were quantified.The results of biomechanical parameters were analyzed using Spearman correlation analysis.The possible effects of different individual characteristic parameters on biomechanics were analyzed. RESULTS AND CONCLUSION:(1)Compared with bilateral mechanical parameters,there was no significant difference between left manipulation and right manipulation(P>0.05).(2)The average of thumb preload force was(7.21±1.19)N;the average of thumb maximum thrust was(28.40±4.48)N;the average of palm preload was(5.67±2.49)N;the average of palm wrench force was(10.90±5.11)N,and the average of palm wrench maximum force was(16.00±7.27)N.(3)There was a significant positive correlation between palm preload and palm wrench force(Rs=0.812,P<0.01).There was a significant positive correlation between palm preload and palm wrench maximum force(Rs=0.773,P<0.01).There was a significant positive correlation between palm wrench force and palm wrench maximum force(Rs=0.939,P<0.01).(4)The weight was positively correlated with thumb preload,palm preload,palm wrench force and palm wrench maximum force(P<0.05).(5)These findings confirm that there is a certain biomechanical standard value in the operation of cervical spine fixed-point rotation manipulation to treat cervical spondylosis.There is no significant difference between the left and right manipulations,which indicates that the manipulation has good consistency and repeatability.There is consistency and coordination among palm preload force,palm wrench force,and palm wrench maximum force.Their contributions to the therapeutic effect are similar.Body weight is an important factor affecting cervical spine fixed-point rotation manipulation.
4.A network meta-analysis on therapeutic effect of different types of exercise on knee osteoarthritis patients
Jia LI ; Qianru LIU ; Mengnan XING ; Bo CHEN ; Wei JIAO ; Zhaoxiang MENG
Chinese Journal of Tissue Engineering Research 2025;29(3):608-616
OBJECTIVE:The main clinical manifestations of knee osteoarthritis are pain,swelling,stiffness,and limited activity,which have a serious impact on the life of patients.Exercise therapy can effectively improve the related symptoms of patients with knee osteoarthritis.This paper uses the method of network meta-analysis to compare the efficacy of different exercise types in the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Embase,Cochrane Library,Web of Science,Scopus,Ebsco,SinoMed,and UpToDate were searched with Chinese search terms"knee osteoarthritis,exercise therapy"and English search terms"knee osteoarthritis,exercise".Randomized controlled trials on the application of different exercise types in patients with knee osteoarthritis from October 2013 to October 2023 were collected.The outcome measures included visual analog scale,Western Ontario and McMaster Universities Osteoarthritis Index score,Timed Up and Go test,and 36-item short form health survey.Literature quality analysis was performed using the Cochrane Manual recommended tool for risk assessment of bias in randomized controlled trials.Two researchers independently completed the data collection,collation,extraction and analysis.RevMan 5.4 and Stata 18.0 software were used to analyze and plot the obtained data. RESULTS:A total of 29 articles with acceptable quality were included,involving 1 633 patients with knee osteoarthritis.The studies involved four types of exercise:aerobic training,strength training,flexibility/skill training,and mindfulness relaxation training.(1)The results of network meta-analysis showed that compared with routine care/health education,aerobic training could significantly improve pain symptoms(SMD=-3.26,95%CI:-6.33 to-0.19,P<0.05);strength training(SMD=-0.79,95%CI:-1.34 to-0.23,P<0.05)and mindfulness relaxation training(SMD=-0.79,95%CI:-1.23 to-0.34,P<0.05)could significantly improve the function of patients.Aerobic training(SMD=-1.37,95%CI:-2.24 to-0.51,P<0.05)and mindfulness relaxation training(SMD=-0.41,95%CI:-0.80 to-0.02,P<0.05)could significantly improve the functional mobility of patients.Mindfulness relaxation training(SMD=0.70,95%CI:0.21-1.18,P<0.05)and strength training(SMD=0.42,95%CI:0.03-0.81,P<0.05)could significantly improve the quality of life of patients.(2)The cumulative probability ranking results were as follows:pain:aerobic training(86.6%)>flexibility/skill training(60.1%)>strength training(56.8%)>mindfulness relaxation training(34.7%)>routine care/health education(11.7%);Knee function:strength training(73.7%)>mindfulness relaxation training(73.1%)>flexibility/skill training(56.1%)>aerobic training(39.9%)>usual care/health education(7.6%);Functional mobility:aerobic training(94.7%)>mindfulness relaxation training(65.5%)>strength training(45.1%)>flexibility/skill training(41.6%)>routine care/health education(3.2%);Quality of life:mindfulness relaxation training(91.3%)>strength training(68.0%)>flexibility/skill training(44.3%)>aerobic training(34.0%)>usual care/health education(12.3%). CONCLUSION:(1)Exercise therapy is effective in the treatment of knee osteoarthritis,among which aerobic training has the best effect on relieving pain and improving functional mobility.Strength training and mindfulness relaxation training has the best effect on improving patients'function.Mindfulness relaxation training has the best effect on improving the quality of life of patients.(2)Limited by the quality and quantity of the included literature,more high-quality studies are needed to verify it.
5.Effect of balance training with different visual conditions on proprioception in patients with chronic ankle instability
Yihan WU ; Zhongqiang LIU ; Qiaoye WEI ; Mingdong LIU ; Keyi CHEN ; Zhigang LI
Chinese Journal of Tissue Engineering Research 2025;29(5):1050-1057
BACKGROUND:Stroboscopic visual training can force sensory reweighting to restore the original weights by increasing sensitivity to proprioceptive information,which may be an effective method to improve proprioception. OBJECTIVE:To determine the effects of balance training in three conditions,low frequency,high frequency and normal vision,on ankle proprioception in patients with chronic ankle instability. METHODS:Thirty-six patients with chronic ankle instability recruited from the students of Southwest Medical University were randomly assigned to a low-frequency vision training group,a high-frequency vision training group,and a normal vision training group,with 12 subjects in each group.Subjects in the three groups underwent progressive hop stabilization and balance training,in which the low-frequency vision training group and the high-frequency vision training group wore stroboscopic spectacles during the training,with a stroboscopic frequency of 1.75 and 5 Hz,respectively.The training in each group was performed three times a week for 4 consecutive weeks.Assessments,including ankle proprioception,ankle stability self-assessment and dynamic postural stability,were performed before training and within 1 week after the completion of training. RESULTS AND CONCLUSION:There was a significant main effect of time factor in ankle proprioception(P<0.05).Compared with the pre-training period,subjects in the low-frequency vision training group and the high-frequency vision training group showed significant improvement in ankle proprioception after 4 weeks of training(P<0.05);and subjects in the low-frequency vision training group showed a significant improvement in ankle proprioception compared with that of the normal vision training group after 4 weeks of training(P<0.05).There were significant main effects of time factor and group×time interaction in ankle proprioception(P<0.05).Compared with the pre-training period,the ankle stability self-assessment in all three groups was improved after 4 weeks of training(P<0.05).And the ankle stability self-assessment in high-frequency visual training group was higher than that in normal vision training group after 4 weeks of training(P<0.05).Compared with the pre-training period,subjects in the low-frequency vision training group and the high-frequency vision training group showed significant improvements in forward dynamic postural stability,posteromedial dynamic postural stability,and posterolateral dynamic postural stability after 4 weeks of training(P<0.05),while in the normal vision training group,forward dynamic postural stability and posterolateral dynamic postural stability were significantly improved after 4 weeks of training(P≤0.05).To conclude,balance training under stroboscopic visual conditioning improves proprioception,ankle stability self-assessment,and dynamic postural stability in patients with chronic ankle instability regardless of frequency.
6.Pathogenesis and treatment progress of flap ischemia-reperfusion injury
Bo HE ; Wen CHEN ; Suilu MA ; Zhijun HE ; Yuan SONG ; Jinpeng LI ; Tao LIU ; Xiaotao WEI ; Weiwei WANG ; Jing XIE
Chinese Journal of Tissue Engineering Research 2025;29(6):1230-1238
BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.
7.Application of 3D-printing patient-specific instruments combined with customized locking plate in opening wedge high tibial osteotomy
Chi MA ; Ning WANG ; Yong CHEN ; Zhihan WEI ; Fengji LIU ; Chengzhe PIAO
Chinese Journal of Tissue Engineering Research 2025;29(9):1863-1869
BACKGROUND:The use of 3D-printed patient-specific instruments in opening wedge high tibial osteotomy has advantages such as shorter operative time,fewer fluoroscopic exposures,and higher correction accuracy.However,previous studies have reported issues such as significant damage to surrounding soft tissues and improper fixation of the plates. OBJECTIVE:To investigate the clinical efficacy of using 3D-printed patient-specific instruments combined with customized locking plate in opening wedge high tibial osteotomy for the treatment of knee osteoarthritis. METHODS:A total of 20 patients diagnosed with knee osteoarthritis were divided into the 3D group(n=10)and the conventional group(n=10)according to surgical methods.The 3D group underwent opening wedge high tibial osteotomy using 3D-printed patient-specific instruments combined with customized locking plate,while the conventional group underwent opening wedge high tibial osteotomy using conventional methods.The operative time,fluoroscopic exposures,incision length,pre-and postoperative hip-knee-ankle angle,medial proximal tibial angle,posterior tibial slope,the difference between the planned and actual correction angle,preoperative and 1,3,6 months postoperative knee range of motion and Lysholm score,and incidence of complications were analyzed and compared between the two groups. RESULTS AND CONCLUSION:(1)The operative time and fluoroscopic exposures were significantly shorter in the 3D group compared to the conventional group,with a statistically significant difference(P<0.001).(2)Both groups showed a significant improvement in postoperative hip-knee-ankle angle and medial proximal tibial angle compared to preoperative values,with a statistically significant difference(P<0.001),while there was no significant change in posterior tibial slope.In the 3D group,the postoperative hip-knee-ankle angle,medial proximal tibial angle,and posterior tibial slope differed from their respective preoperative planned values by(-0.22±0.72)°,(-0.20±0.73)°,and(0.23±0.37)°,but the differences were not statistically significant.The difference between the planned and actual correction angle of 3D group was significantly smaller than that of conventional group(P<0.05).(3)Both groups showed a gradual increase in knee range of motion and Lysholm scores after surgery(P<0.001).Compared to the conventional group,the 3D group had superior knee range of motion at 1 and 3 months postoperatively,as well as a higher Lysholm score at 1 month postoperatively,with statistically significant differences(P<0.05).There were no statistically significant differences in Lysholm score at 3 months and knee range of motion and Lysholm score at 6 months between the two groups(P>0.05).(4)Complications occurred in neither groups.(5)The above results indicate that both 3D-printed patient-specific instruments combined with customized locking plate and conventional methods have good clinical efficacy.However,the former has a shorter operative time,fewer fluoroscopic exposures,and faster postoperative recovery of knee joint function.Additionally,3D-printed patient-specific instruments can achieve preoperative planning accurately.
8.Combination of effective ingredients of traditional Chinese medicine and bone tissue engineering materials for bone repair
Yaokun WU ; Chenglin LIU ; Jiahao FU ; Wei SONG ; Hao CHEN ; Hongzhong XI ; Xin LIU ; Bin DU ; Guangquan SUN
Chinese Journal of Tissue Engineering Research 2025;29(10):2141-2150
BACKGROUND:How to repair bone defect has been a clinical problem for a long time.The effective ingredients of traditional Chinese medicine have good biological activity and therapeutic effect,and the combination of effective ingredients of traditional Chinese medicine and tissue engineering materials has a broad prospect in the field of bone repair.The combination of different effective ingredients of traditional Chinese medicine and scaffolds has similarities in their functional relationships. OBJECTIVE:To collect the cases of the combinations of effective ingredients of traditional Chinese medicine and scaffolds,then analogize tissue engineering scaffolds and effective ingredients of traditional Chinese medicine into two types of traditional Chinese medicine that generate compatibility relationships based on the inspiration of the compatibility of seven emotions and summarize the relationship between the two based on their functional relationships. METHODS:Relevant articles from January 1998 to January 2024 were searched in PubMed and China National Knowledge Infrastructure(CNKI),using English search terms"traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold"and Chinese search terms"traditional Chinese medicine,effective ingredients of traditional Chinese medicine,traditional Chinese medicine monomers,bone tissue engineering,bone tissue engineering scaffold,scaffold,tissue engineering,bone defect,bone repair."A total of 88 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Both tissue engineering scaffold materials and active ingredients of traditional Chinese medicine have been widely used in the field of bone repair.Although they have obvious advantages in osteogenesis,there are still many shortcomings.Many studies are dedicated to preparing composite materials from the two,hoping to exert a detoxification and synergism through the interaction between the two.(2)Some drugs and materials can promote each other in osteogenesis,antibacterial,and promoting angiogenesis,enhancing their original effects.Inspired by the traditional concept of prescription compatibility,this article summarized it as a"Mutual promotion"relationship and provided examples to support it.(3)Some drugs can enhance the strength of materials,while some materials can achieve sustained release and controlled release effects,increase drug loading and stability,or achieve targeted delivery of drugs loaded on them.The article summarized this unilateral enhancement effect as a"Mutual assistance"relationship.(4)The combination of some traditional Chinese medicine and materials can reduce the toxic side effects of the other party.The article summarizes this detoxification relationship as"Mutual restraint and detoxification."(5)The article provided a new perspective on traditional Chinese medicine composite scaffolds,inspired by the seven emotions compatibility relationship and based on the classification of action relationships.It introduced traditional Chinese medicine concepts into the field of tissue engineering,providing new research ideas for subsequent researchers of composite scaffolds,and providing certain convenience in material selection and matching.
9.Application of Anti-tumor Compatibility Structure of Chinese Medicine
Lanpin CHEN ; Feng TAN ; Xiaoman WEI ; Junyi WANG ; Liu LI ; Mianhua WU ; Haibo CHENG ; Dongdong SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):198-208
Malignant tumors are one of the major diseases that endanger human life and health. Chinese medicine has unique advantages in clinical anti-tumor treatment. However, how to translate the anti-tumor effects of Chinese medicine into clinical practice is the core issue that must be addressed in the process of treating malignant tumors with traditional Chinese medicine (TCM). Unlike modern chemical drugs, the compatibility application of Chinese medicine is the key factor that determines whether Chinese medicine can achieve optimal anti-tumor efficacy and realize the goal of "enhancing efficacy and reducing toxicity". The formulation structure based on this compatibility is the basic form for the safe, efficient, and rational clinical use of anti-tumor Chinese medicine, and it mainly includes three categories: herb pairs, tri-herbal combinations, and compound compatibility. Although herb pairs have the characteristics of a simple structure and strong targeting (enhancing efficacy and reducing toxicity), they often have a single effect and cannot fully address the complex pathogenesis of tumors. As a result, herb pairs are rarely used alone in practice. Compared to herb pairs, tri-herbal combinations broaden the application scope of herbs in clinical treatment, but their therapeutic range remains limited. The traditional "sovereign, minister, assistant, and guide" compound prescription, which includes herb pairs and tri-herbal combinations, improves the efficacy of herbs in treating serious diseases, hypochondriasis, chronic diseases, and miscellaneous disorders. However, due to the limitations of its historical background, it has not been integrated with modern clinical practice and modern pharmacological research, which restricts the development of compound compatibility theory. With the emergence of modern medical technology, it has been combined with traditional compatibility theory of Chinese medicine to create an innovative modern compatibility theory. This includes the "aid medicine" theory derived from modern Chinese medicine pharmacology, which compensates for the inability of the "sovereign, minister, assistant, and guide" theory to accurately apply medicine. Additionally, the "state-targeted treatment based on syndrome differentiation" theory, developed from pharmacology and modern medicine, addresses the deficiency in disease cognition in the "sovereign, minister, assistant, and guide" theory. Under the guidance of these compatibility forms and theories, clinical anti-tumor Chinese medicine can exert its maximum anti-tumor efficacy, which is of great significance for the application of Chinese medicine in clinical tumor treatment.
10.Traditional Chinese Medicine Intervention in Diarrhea-predominant Irritable Bowel Syndrome Based on Gut-brain Axis: A Review
Jinchan PENG ; Jinxiu WEI ; Zhu LIU ; Lijian LIU ; Liqun LI ; Chengning YANG ; Guangwen CHEN ; Jianfeng LI ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):311-319
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common digestive system disease with high prevalence and recurrence rates for years, high treatment costs, and serious impacts on patients' quality of life and economic burden. Therefore, it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex, in which the gut-brain axis is a key factor. The gut-brain axis, a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system, regulates gastrointestinal motility, secretion, and immune responses, playing a key role in the occurrence and development of IBS-D. Up to now, antidiarrheal agents, probiotics, and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease, the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine (TCM) has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However, there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years, this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment, providing new ideas for the treatment of IBS-D.


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