1.Neuroplasticity Mechanisms of Exercise-induced Brain Protection
Li-Juan HOU ; Lan-Qun MAO ; Wei CHEN ; Ke LI ; Xu-Dong ZHAO ; Yin-Hao WANG ; Zi-Zheng YANG ; Tian-He WEI
Progress in Biochemistry and Biophysics 2025;52(6):1435-1452
		                        		
		                        			
		                        			Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection. 
		                        		
		                        		
		                        		
		                        	
2.Effectiveness of acceptance and commitment therapy in improving depression, anxiety, psychological flexibility and return-to-school rate among adolescents with school absenteeism
Yanshan ZHANG ; Zhifang CHEN ; Ke ZHENG ; Guobang WU ; Fushan XU ; Maorong HU
Sichuan Mental Health 2025;38(3):198-203
		                        		
		                        			
		                        			BackgroundThe issue of school absenteeism due to school refusal in adolescents has become increasingly prominent. Acceptance and Commitment Therapy (ACT) has been applied successfully to improve depression, anxiety, and psychological flexibility in adolescents, while few studies have tested the effect of ACT intervention on above-mentioned psychological aspects and return-to-school rate in adolescents with school absenteeism. ObjectiveTo explore the effect of ACT on depression, anxiety, psychological flexibility and return-to-school rate in school absenteeism adolescents, and to provide a broader evidence base for clinical interventions. MethodsFrom May to June 2024, a sample of 50 adolescents with Shenzhen school registration who had been suspended from school for more than a consecutive month for school refusal were recruited based on Wechat official account platform. The adolescents were divided into study group and control group by random number table method. Both groups received psychological education with the theme of 'Causes and Coping Strategies of School Refusal', and study group added a 6-week ACT intervention with weekly 1-hour sessions. At baseline and after treatment, Patients’ Health Questionnaire Depression Scale-9 item (PHQ-9), Generalized Anxiety Disorder Scale-7 item (GAD-7) and Comprehensive assessment of Acceptance and Commitment Therapy processes (CompACT) were used for the clinical evaluation. ResultsA total of 45 (90.00%)adolescents completed the study, including 25 in study group and 20 in control group. Analysis revealed that study group scored higher on PHQ-9 and GAD-7, while lower on total CompACT score, openness dimension and awareness dimension compared with control group, with statistical significance (F=7.786, 10.334, 12.922, 14.374, 3.075, P<0.05 or 0.01). After intervention, the rate of return-to-school was higher in study group than in control group (40.00% vs 10.00%, χ²=5.114, P<0.05). ConclusionACT intervention for adolescents with school absenteeism may alleviate depression and anxiety, improve their psychological flexibility and increase return-to-school rate.[Funded by the "14th Five Year Plan" for Social Sciences Project in Jiangxi Province (number, 24JY41D); Science and Technology Planning Project of Shenzhen Municipality (number, 20210617155253001)] 
		                        		
		                        		
		                        		
		                        	
3.Plasma miRNA testing in the differential diagnosis of very early-stage hepatocellular carcinoma: a multicenter real-world study
Jie HU ; Ying XU ; Ao HUANG ; Lei YU ; Zheng WANG ; Xiaoying WANG ; Xinrong YANG ; Zhenbin DING ; Qinghai YE ; Yinghong SHI ; Shuangjian QIU ; Huichuan SUN ; Qiang GAO ; Jia FAN ; Jian ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):350-354
		                        		
		                        			
		                        			Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
		                        		
		                        		
		                        		
		                        	
4.Investigation of an occupational acute carbon monoxide poisoning incident caused by nitrogen generator failure
Xianbang CAO ; Youhui HE ; Weifeng ZHENG ; Dan XU
China Occupational Medicine 2025;52(2):237-241
		                        		
		                        			
		                        			Objective To analyze the characteristics and causes of an occupational acute carbon monoxide poisoning incident caused by a nitrogen generator malfunction. Methods The workers and the workshop from an electronic component manufacturing company in Guangzhou City, which had an occupational acute carbon monoxide poisoning incident, were selected as the research subjects using the retrospective investigation method. Relevant data of worksite survey of occupational health, clinical records of poisoning patients, and occupational disease diagnosis data were collected for analysis. Results A total of 15 workers who experienced discomfort in this incident, were from the final inspection workshop using high-purity nitrogen (purity of 99.999%). The short-term exposure concentration of carbon monoxide in the workplace air at three oven operating posts using high-purity nitrogen was 64.1, 581.0, and 142.0 mg/m³, respectively, while the concentration in the workplace air at the oven operating posts using regular nitrogen and the nitrogen-generating room was <0.1 mg/m³. Carboxyhemoglobin saturation levels in the 15 patients ranged from 2.000%-17.300%. Occupational acute mild carbon monoxide poisoning was diagnosed in nine patients, occupational acute carbon monoxide exposure reactions was diagnosed in six patients. This poisoning incident was caused by machine malfunction and improper operation, leading to occupational acute carbon monoxide poisoning. Conclusion Companies using nitrogen production machine should enhance their ability to identify carbon monoxide risks, strengthen training and management of workers, establish emergency response plans for nitrogen production and use, ensure proper maintenance of production equipment, and optimize operational procedures to prevent acute poisoning incidents. 
		                        		
		                        		
		                        		
		                        	
5.Changes in coordination of departments for major epidemic prevention and control in China before and after the outbreak of COVID-19: an analysis on official documents
Zhonghui HE ; Peiwu SHI ; Qunhong SHEN ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Zhi HU ; Anning MA ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Qingyu ZHOU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):446-450
		                        		
		                        			
		                        			ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination. 
		                        		
		                        		
		                        		
		                        	
6.A systematic evaluation of the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces
Huayi ZHANG ; Qingyu ZHOU ; Huihui HUANGFU ; Peiwu SHI ; Qunhong SHEN ; Chaoyang ZHANG ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Anning MA ; Zhaohui GONG ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Chao HAO ; Zhi HU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):451-457
		                        		
		                        			
		                        			ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal. 
		                        		
		                        		
		                        		
		                        	
7.Analysis of pollution of PM 2.5 in children s bedrooms caused by using solid fuels and the influencing factors
ZHENG Ping, SHI Chunli, XIN Shuzhi, CHEN Shunqiang, SHEN Yue, ZHANG Bei, XU Ning, WANG Qiang
Chinese Journal of School Health 2025;46(7):932-936
		                        		
		                        			Objective:
		                        			To investigate the indoor fine particulate matter (PM 2.5 ) pollution and its influencing factors in children s bedrooms using solid fuel, so as to provide evidence for effective strategy to reduce PM 2.5  pollution.
		                        		
		                        			Methods:
		                        			From December 2019 to November 2020, 198 households (108 in the north, 90 in the south) from two pilots in the north(Jiamusi in Heilongjiang Province) and south of China (Mianyang in Sichuan Province) were selected, and status of solid fuels using were obtained through home visits, dynamic changes in PM 2.5  concentrations in children s bedrooms were monitored by using real time online instruments, and the influencing factors of PM 2.5 pollution were analyzed by using a mixed effects model.
		                        		
		                        			Results:
		                        			During the monitoring period, the daily PM 2.5  concentrations in the northern and southern pilot were 78.33 (40.50, 154.80) and 38.54(26.20, 58.46) μg/m 3, respectively, exceeding standard rates of 44.57% and 33.22%. During the heating period, the daily PM 2.5  concentrations in the northern and southern pilot were 212.50(133.60,244.10) and 104.42(73.97, 134.90) μg/m 3, respectively, with over standard rates of 96.75% and 86.96%. The mixed effects model analysis results showed that children s bedroom PM 2.5  concentrations were associated with solid fuel usage duration, window opening time, room layout (shared entrance door between kitchen and bedroom), indoor smoking, indoor humidity, and solid fuel use in the bedroom ( β =0.19, -0.05, 1.20, 0.43, 0.02, 0.35, all  P <0.05).
		                        		
		                        			Conclusion
		                        			Solid fuel combustion significantly comtributes to PM 2.5  pollution in children s bedrooms, with more pronounced impacts observed in northern China compared to southern regions.
		                        		
		                        		
		                        		
		                        	
8.Effect of Mori Folium-Ginseng Radix et Rhizoma on Glucose and Lipid Metabolism and Mechanism in Mouse Model of Type 2 Diabetes Mellitus
Congyi LIU ; Ning WANG ; Jingjing XU ; Tingting WANG ; Na ZHENG ; Zimeng HUANG ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):20-28
		                        		
		                        			
		                        			ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma (HMG) on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses (1.56, 3.12 g∙kg-1, respectively) or metformin (0.26 g∙kg-1) by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test (OGTT) was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)], liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], non-esterified fatty acids (NEFA), glycosylated serum protein (GSP), serum glucose (GLU), fasting insulin (FINS), and renal function indicators [creatinine (Crea) and blood urea nitrogen (BUN)] were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma (PPARγ), acetyl coenzyme A carboxylase (ACC), and sterol regulatory element-binding protein-1 (SREBP-1) were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group, the model group presented increased body weight, elevated levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, GSP, and HDL-C, up-regulated protein levels of ACC and SREBP-1, and down-regulated protein level of PPARγ (P<0.01). Meanwhile, the model group presented a large amount of lipid droplets and steatosis in the liver, as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group, the high- and low-dose HMG groups showed decreased body weight, declined levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, and GSP, and elevate level of HDL-C (P<0.05, P<0.01). Moreover, the two groups showcased reduced lipid droplets and steatosis in the liver, as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ (P<0.01). ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ, SREBP-1, and ACC. 
		                        		
		                        		
		                        		
		                        	
9.Effect of Mori Folium-Ginseng Radix et Rhizoma on Glucose and Lipid Metabolism and Mechanism in Mouse Model of Type 2 Diabetes Mellitus
Congyi LIU ; Ning WANG ; Jingjing XU ; Tingting WANG ; Na ZHENG ; Zimeng HUANG ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):20-28
		                        		
		                        			
		                        			ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma (HMG) on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses (1.56, 3.12 g∙kg-1, respectively) or metformin (0.26 g∙kg-1) by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test (OGTT) was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)], liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], non-esterified fatty acids (NEFA), glycosylated serum protein (GSP), serum glucose (GLU), fasting insulin (FINS), and renal function indicators [creatinine (Crea) and blood urea nitrogen (BUN)] were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma (PPARγ), acetyl coenzyme A carboxylase (ACC), and sterol regulatory element-binding protein-1 (SREBP-1) were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group, the model group presented increased body weight, elevated levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, GSP, and HDL-C, up-regulated protein levels of ACC and SREBP-1, and down-regulated protein level of PPARγ (P<0.01). Meanwhile, the model group presented a large amount of lipid droplets and steatosis in the liver, as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group, the high- and low-dose HMG groups showed decreased body weight, declined levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, and GSP, and elevate level of HDL-C (P<0.05, P<0.01). Moreover, the two groups showcased reduced lipid droplets and steatosis in the liver, as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ (P<0.01). ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ, SREBP-1, and ACC. 
		                        		
		                        		
		                        		
		                        	
10.Progress in clinical application of anti-CD20 monoclonal antibody in refractory nephrotic syndrome in children
Jinbo XIANG ; Guanguo SHEN ; Zheng LI ; Xiaoyan HU ; Tingting CAO ; Ziran XU ; Ting DING ; Jingbo LI
China Pharmacy 2025;36(16):2078-2084
		                        		
		                        			
		                        			Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome (RNS) in children. The first- generation rituximab is the most widely used in clinical practice; it shows definite efficacy in children with RNS, is recommended by guidelines, particularly for achieving a high remission rate in minimal change nephrosis, and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab, while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However, there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions, and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS, but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use, clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.
		                        		
		                        		
		                        		
		                        	
            

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