1.Electro-acupuncture for Vascular Cognitive Impairment:A Visualized Data Mining Analysis
Hai-Zhen GUO ; Han WU ; Mei-Kang YAO ; Jiang-Wei SHI ; Tao YU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):161-168
		                        		
		                        			
		                        			Objective To summarize the acupoints and parameters commonly used in the treatment of vascular cognitive impairment(VCI)by electro-acupuncture(EA)through the visual data mining technique to provide a reference basis for clinical treatment.Methods The clinical studies of EA on the treatment of VCI were searched in CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases.The literature is managed by Note Express and the database is established by Excel.The frequency of selected acupoints,frequency,meridian tropism,parameter frequency and frequency of used acupoints are counted.Factor analysis is carried out by SPSS 21.0 software.SPSS Modeler 18.3 software is used to analyze association rules and co-occurrence network,and the analysis results are visualized by Cytoscape 3.9.1 software.Results Finally,155 papers were included,containing 155 acupoint prescriptions and 157 parameter prescriptions.Acupoint prescriptions involved 100 acupoints with a total frequency of 856 times;parameter prescriptions involved 33 parameters with a total frequency of 788 times.Conclusion At present,there is a big difference between the clinical studies,and there is no recognized acupoint and parameter for EA treatment of VCI.By further summarizing the law of EA acupuncture point and parameter,the study has sorted out the law of commonly used acupoints,meridian tropism,compounding and parameter selection for EA treatment of VCI.It was concluded that the selection of acupoints mainly started from the three aspects of deficiency,phlegm and stasis,focusing on the combination of local and distal selection of acupoints,through the identification of internal organs and meridians,to achieve the simultaneous regulation of the heart,spleen and kidney,and to take into account both the symptoms and the root cause,and to play the roles of opening the orifices to wake up mind,calming mind and benefiting intellect,strengthening the spleen and tonifying the kidneys,and invigorating blood circulation to remove stasis.The parameters of EA are recommended to be sparse and dense wave,low frequency,as tolerated by the patient,30 minutes/times,1 time/day,5 times/week as the main combinations,which can provide a certain reference basis for clinical decision-making.
		                        		
		                        		
		                        		
		                        	
2.Clinical Observation on the Thumb-tack Needling for Subcutaeous Embedding Combined with Joint Mobilization in the Treatment of Post-stroke Shoulder-Hand Syndrome
Jing-Xia CHEN ; Xiao-Han YUAN ; Hong-Xing LIU ; Bo-Wen LI ; Mei-Yu JIANG ; Ya-Nan ZHAO ; Wen-Feng SONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):689-695
		                        		
		                        			
		                        			Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P<0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P<0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P<0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P<0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P<0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P>0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.
		                        		
		                        		
		                        		
		                        	
3.A multicenter retrospective cohort study on the attributable risk of patients with Acinetobacter baumannii sterile body fluid infection
Lei HE ; Dao-Bin JIANG ; Ding LIU ; Xiao-Fang ZHENG ; He-Yu QIU ; Shu-Mei WU ; Xiao-Ying WU ; Jin-Lan CUI ; Shou-Jia XIE ; Qin XIA ; Li HE ; Xi-Zhao LIU ; Chang-Hui SHU ; Rong-Qin LI ; Hong-Ying TAO ; Ze-Fen CHEN
Chinese Journal of Infection Control 2024;23(1):42-48
		                        		
		                        			
		                        			Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
		                        		
		                        		
		                        		
		                        	
4.Influencing factors for intestinal colonization and secondary infection of CRKP in neonates
Yu ZHAI ; Qing-Rong LI ; Jiang LI ; Wei HE ; Ping-An HE ; Mei LYU ; Xu YANG
Chinese Journal of Infection Control 2024;23(2):133-141
		                        		
		                        			
		                        			Objective To analyze the influencing factors for intestinal colonization and secondary infection of car-bapenem-resistant Klebsiella pneumoniae(CRKP)in neonates,and provide a basis for formulating prevention and control strategies for CRKP infection.Methods Neonates who were admitted to the neonatal ward of a hospital from January 2021 to October 2022 were selected as the study subjects,and the first screening of CRKP was con-ducted within 48 hours after admission.In addition,active anal swab screening for carbapenem-resistant Ente-robacterales(CRE)was performed weekly during hospitalization,and the infection status of CRKP strains was mo-nitored.Clinical data of neonates in the colonization group,non-colonization group,and infection group were ana-lyzed.Intestinal colonized strains and the non-repetitive CRKP strains isolated from clinical specimens of neonates with secondary infection after colonization were performed carbapenemase gene detection,multilocus sequence ty-ping(MLST)and pulsed-field gel electrophoresis(PFGE)analysis.Results A total of 1 438 neonates were active-ly screened for CRE,174 were CRKP positive,CRKP colonization rate was 12.1%.Among 174 neonates,35 were with secondary infection,with the incidence of 20.1%.The independent risk factors for neonatal CRKP intestinal colonization were cesarean section(OR=2.050,95%CI:1.200-3.504,P=0.009),use of cephalosporins(OR=1.889,95%CI:1.086-3.288,P=0.024),nasogastric tube feeding(OR=2.317,95%CI:1.155-4.647,P=0.018).Protective factors were breast-feeding(OR=0.506,95%CI:0.284-0.901,P=0.021),oral probiotics(OR=0.307,95%CI:0.147-0.643,P=0.002),and enema(OR=0.334,95%CI:0.171-0.656,P=0.001).Independent risk factors for secondary infection after intestinal colonization of neonatal CRKP were carbapenem anti-biotic use(OR=19.869,95%CI:1.778-222.029,P=0.015)and prolonged hospital stay(OR=1.118,95%CI:1.082-1.157,P<0.001).The detection results of drug resistance genes showed that carbapenemase-producing genes of CRKP strains were all blaKPC-2,all belonged to type ST11.Homologous analysis showed that intestinal CRKP colonization was highly homologous with the secondary infection strains after colonization.Conclusion CRKP intestinal colonization during neonatal hospitalization may increase the risk of CRKP infection.Risk and pro-tective factors of neonatal intestinal colonization and secondary infections after colonization should be paid attention,and corresponding preventive and control measures should be taken,so as to reduce the occurrence and transmission CRKP healthcare-associated infection.
		                        		
		                        		
		                        		
		                        	
5.Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China
Yun SONG ; Ying HE ; Xin Xue LU ; Mei Xiao ZHANG ; Lin XIAO JIANG ; Qing SONG ; Yong Xue HUANG ; Xia Hong MA ; Cheng Peng YU ; Yang Wu ZHU
Biomedical and Environmental Sciences 2024;37(2):178-186
		                        		
		                        			
		                        			Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.
		                        		
		                        		
		                        		
		                        	
6.Observation on the Clinical Efficacy of Dongj ing Tiaoshen Comprehensive Therapy Combined with Computerized Cognitive Behavioral Therapy for Insomnia in the Treatment of Chronic Insomnia of Liver Depression and Spleen Deficiency Type
Tian-Hui TAN ; Yu GUO ; Jie-Lin HUANG ; Jiang-Ning QIU ; Xiao-Min XIE ; Xue-Mei CAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1129-1136
		                        		
		                        			
		                        			Objective To observe the clinical effect of Dongjing Tiaoshen Comprehensive Therapy combined with computerized cognitive behavioral therapy for insomnia(CCBT-I)in the treatment of chronic insomnia patients with liver depression and spleen deficiency syndrome.Methods A total of 60 patients with chronic insomnia of liver depression and spleen deficiency type were randomly divided into observation group and control group,30 cases in each group.Both groups of patients were treated with CCBT-I as the basic treatment,the observation group was additionally treated with Dongjing Tiaoshen Comprehensive Therapy,i.e.,mind-regulating acupuncture therapy combined with regular aerobic exercises and Dantian Qigong exercises,and the control group was additionally treated with cranial electrotherapy stimulation.The course of treatment for the two groups covered 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)score,Self-rating Anxiety Scale(SAS)score and Self-rating Depression Scale(SDS)score in the two groups were observed before and after treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 86.67%(26/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the PSQI scores of the two groups were significantly lower than those before treatment(P<0.05),and the decrease of PSQI scores in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,the SAS and SDS scores of the two groups were significantly lower than those before treatment(P<0.05),and the decrease of SAS and SDS scores in the observation group tended to be superior to that in the control group,but there was no significant difference between the two groups(P>0.05).Conclusion For the treatment of chronic insomnia of liver depression and spleen deficiency type,the combination of Dongjing Tiaoshen Comprehensive Therapy with CCBT-I can significantly improve the sleep quality,relieve anxiety and depression,and improve the quality of life of the patients,which exerts significant efficacy.
		                        		
		                        		
		                        		
		                        	
7.CHEN Bo-Lai's Experience in Treating Low Back Pain of Kidney Deficiency and Phlegm Obstruction Type Based on the Theory of Kidney Being the Root of Phlegm
Wen-Xi SUN ; Qi PENG ; Yu-Fu HUANG ; Jiang-Nan YE ; Hong-Mei LI ; Yong-Peng LIN ; Hong-Shen WANG ; Bo-Lai CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1616-1620
		                        		
		                        			
		                        			The kidney governs water and is the congenital foundation.The kidney plays an important role in the transportation and distribution of body fluid,has the interior-exterior relationship with the waterffu-organ bladder,and has the meridian connection with the stomach,the reservoir of water and food,through the thoroughfare vessel.Therefore,the kidney plays a key role in the formation of phlegm.Professor CHEN Bo-Lai believes that low back pain of kidney deficiency and phlegm obstruction type is characterized by deficiency in the origin and excess in the superficiality.Excess in the superficiality is manifested as phlegm obstruction,and deficiency in the origin is manifested as kidney deficiency.Clinically,the patients with low back pain of kidney deficiency and phlegm obstruction type mainly have the manifestations of lumbosacral dull pain and fixed pain,stiffness in the waist,limb numbness or hemiplegia,accompanied by soreness and weakness of waist and knees,and preference for pressing and kneading.The treatment of low back pain of kidney deficiency and phlegm obstruction type can be based on theory of kidney being the root of phlegm,follows the therapy of tonifying kidney and eliminating phlegm,and can be performed by the modified use of basic prescription of Litan Decoction(mainly composed of Euryales Semen,Pinelliae Rhizoma,Sesami Semen Nigrum,Platycladi Semen,Paeoniae Radix Alba,Citri Reticulatae Pericarpium and Poria)together with the assistance of herbs for strengthening spleen and dispersing lung based on the differentiation of the complicated symptoms.The thoughts of Professor CHEN Bo-Lai for the differentiation and treatment of low back pain of kidney deficiency and phlegm obstruction type can be used as a reference for the treatment of low back pain with Chinese medicine.
		                        		
		                        		
		                        		
		                        	
8.Clinical Study on Yiqi Huatan Tongluo Prescription Combined with Drug-Coated Balloon in the Treatment of Coronary Heart Disease of Qi Deficiency and Phlegm Stasis Obstructing Collateral Type
Mei-Chun HUANG ; Yu-Peng LIANG ; Pei-Zhong LIU ; Sheng-Yun ZHANG ; Se PENG ; Chuang-Peng LI ; He-Zhen ZHANG ; Tian-Wei LAI ; Chang-Jiang AI ; Qing LIU ; Ai-Meng ZHANG ; Shao-Hui LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2656-2662
		                        		
		                        			
		                        			Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68%(47/53),and that of the control group was 75.47%(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P<0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P>0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P<0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P<0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87%(10/53),and that in the control group was 20.75%(11/53).There was no significant difference between the two groups(P>0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.
		                        		
		                        		
		                        		
		                        	
9.Influencing factors and the Nomogram model to predict early hematoma expansion of intracranial hemorrhage
Fa WU ; Yu-Lin YANG ; Ting-Ting WU ; Rui JIANG ; Jie WU ; Peng WANG ; Fei-Zhou DU ; Hong-Mei YU ; Jian-Hao LI
Medical Journal of Chinese People's Liberation Army 2024;49(5):504-510
		                        		
		                        			
		                        			Objective To investigate factors influencing the occurrence of early haematoma expansion(HE)in patients with spontaneous intracerebral hemorrhage(sICH),to develop a predictive model and evaluate its predictive efficacy.Methods A retrospective cohort of 238 patients with sICH,admitted to General Hospital of Western Theater Command between January 2017 and December 2022,was analyzed.Patients were categorized into two groups based on the criteria of HE exceeding 33%in relative volume or 6 ml in absolute volume:HE group(n=62)and non-haematoma expansion(NHE)group(n=176).Clinical characteristics,laboratory findings,Non-contrast Computed Tomography(NCCT)imaging,and Glasgow Coma Scale(GCS)scores were compared between the two groups.Multifactorial logistic regression analysis was employed to identify risk factors for HE and to model the probability of its occurrence.The R language rms package was utilized to construct a nomogram model for predicting HE in sICH patients,Additionally,the related clinical,NCCT,and GCS models were constructed.The predictive efficacy of each model for HE in sICH patients was evaluated using area under Receive Operative Characteristic(ROC)curve(AUC),and the clinical application value of each model was assessed using accuracy,sensitivity,specificity,and Jordon's index.The Delong test was applied to analyze differences in the predictive values of the models.Results Significant differences in satellite sign,vortex sign,and history of anticoagulant treatment were observed between two groups(P<0.05).Multifactorial logistic regression analysis revealed independent risk factors for HE in sICH patients,including the first CT examination time,homogeneity,history of anticoagulant medication,volume,maximal diameter,hypodensity sign,island sign,satellite sign,and vortex sign(P<0.05).The AUCs for the constructed clinical model,NCCT model,GCS model and nomogram model in predicting the occurrence of HE in sICH patients were 0.672,0.706,0.518 and 0.754,respectively.The nomogram model demonstrated higher accuracy,sensitivity,Jordon's index and AUC compared with those in the clinical and NCTT models.Conclusions The first CT examination time,homogeneity,history of anticoagulant treatment,volume,maximum diameter,hypodensity sign,island sign,satellite sign,and vortex sign are independent predictors of early HE in sICH patients.The nomogram model,constructed with the above parameters,demonstrated high predictive efficacy for HE and holds potential for clinical application.
		                        		
		                        		
		                        		
		                        	
10.Clinical characterization and prediction modeling of lung cancer patients with high energy metabolism
Jiang-Shan REN ; Jun-Mei JIA ; Ping SUN ; Mei PING ; Qiong-Qiong ZHANG ; Yan-Yan LIU ; He-Ping ZHAO ; Yan CHEN ; Dong-Wen RONG ; Kang WANG ; Hai-Le QIU ; Chen-An LIU ; Yu-Yu FAN ; De-Gang YU
Medical Journal of Chinese People's Liberation Army 2024;49(9):1004-1010
		                        		
		                        			
		                        			Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.
		                        		
		                        		
		                        		
		                        	
            
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