1.Effects of long non-coding RNA KIAA0125 on proliferation and apoptosis of acute myeloid leukemia U937 cells
Huali HU ; Fahua DENG ; Yuancheng LIU ; Siqi WANG ; Jingxin ZHANG ; Tingting LU ; Hai HUANG ; Sixi WEI
Chinese Journal of Tissue Engineering Research 2025;29(19):3983-3991
		                        		
		                        			
		                        			BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.
		                        		
		                        		
		                        		
		                        	
2.The chain mediating role of social support and resilience in the relationship between symptom burden and psychological distress among lung cancer patients in the diagnostic phase
Congyu YIN ; Jina LI ; Man YE ; Yingxia LI ; Wei LI ; Lu KANG ; Yayi ZHANG ; Lingzhi HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):798-804
		                        		
		                        			
		                        			Objective To investigate the current status of symptom burden and psychological distress among lung cancer patients in the diagnostic phase, and to explore the chain mediating role of social support and resilience between symptom burden and psychological distress. Methods The patients with lung cancer in the diagnostic phase who were treated in the Department of Thoracic Surgery of the Second Xiangya Hospital of Central South University from October 2022 to June 2023 were investigated by a general information questionnaire using the MD Anderson Symptom Inventory, the Social Support Rating Scale, the Connor-Davidson Resilience Scale, and the Distress Thermometer. The chain mediating role of social support and resilience between symptom burden and psychological distress was analyzed. Results A total of 413 lung cancer patients were enrolled, including 173 males and 240 females, aged (54.69±10.82) years. The detection rate of psychological distress among lung cancer patients in the diagnostic phase was 48.18%, and the average score was (3.84±2.50) points. Psychological distress was positively correlated with symptom burden (P<0.01), and negatively correlated with social support and resilience (P<0.01). The mediating effect of resilience between symptom burden and psychological distress was significant. The chain mediating effect of social support and resilience between symptom burden and psychological distress was also significant. Conclusion Lung cancer patients in the diagnostic phase have a high detection rate of psychological distress. Symptom burden can directly impact psychological distress, and can affect psychological distress through the indirect path of resilience as well as the chain mediating path between social support and resilience among lung cancer patients in the diagnostic phase.
		                        		
		                        		
		                        		
		                        	
3.Application of left internal mammary artery and bilateral radial arteries in off-pump total arterial coronary artery bypass grafting
Shengzhong LIU ; Dachuang WEI ; Bo XIANG ; Jin TAN ; Lu JIANG ; Tao YU ; Keli HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1159-1165
		                        		
		                        			
		                        			Objective To evaluate the safety and efficacy of total arterial off-pump coronary artery bypass grafting (OPCABG) using a left internal thoracic artery (LITA) combined with bilateral radial arteries (RAs). Methods We retrospectively analyzed the clinical data of patients with severe multi-vessel coronary artery disease who underwent total arterial OPCABG with a LITA and bilateral RAs at Sichuan Provincial People’s Hospital from November 2020 to April 2023. Results  A total of 24 patients were included, comprising 23 males and 1 female, with a mean age of (53.63±4.33) years. The New York Heart Association (NYHA) functional class was Ⅱ to Ⅲ. The mean number of distal anastomoses was 3.17±0.38. A Y-graft was constructed in 12 patients and sequential grafting was performed in 4 patients. Concomitant procedures included coronary endarterectomy in 1 patient, intra-aortic balloon pump (IABP) implantation in 10 patients, and thymoma resection in 1 patient. The mean operative time was (308.13±30.39) min, mechanical ventilation time was (15.42±7.42) h, ICU stay was (46.08±27.32) h, and postoperative hospital stay was (11.71±1.90) d. There were no in-hospital deaths. Postoperative complications included one patient of acute renal failure and one patient of cerebral infarction. Pre-discharge color Doppler echocardiography revealed that the left ventricular end-diastolic diameter was significantly smaller than before surgery (P<0.05), while the left ventricular ejection fraction and fractional shortening were significantly higher (P<0.05). Coronary computed tomography angiography (CTA) showed that all arterial grafts were patent. During a mean follow-up of (14.58±8.75) months, no patients experienced angina recurrence or mortality. Repeat coronary CTA or angiography in 16 patients one year postoperatively confirmed that all arterial grafts remained patent. Conclusion  Total arterial OPCABG using a LITA and bilateral RAs is a safe and effective treatment for patients with severe multi-vessel coronary artery disease. For high-risk patients, intraoperative IABP support is recommended.
		                        		
		                        		
		                        		
		                        	
4.Optimization of simmering technology of Rheum palmatum from Menghe Medical School and the changes of chemical components after processing
Jianglin XUE ; Yuxin LIU ; Pei ZHONG ; Chanming LIU ; Tulin LU ; Lin LI ; Xiaojing YAN ; Yueqin ZHU ; Feng HUA ; Wei HUANG
China Pharmacy 2025;36(1):44-50
		                        		
		                        			
		                        			OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score, the contents of gallic acid, 5-hydroxymethylfurfural (5-HMF), sennoside A+sennoside B, combined anthraquinone and free anthraquinone as indexes, analytic hierarchy process (AHP)-entropy weight method was used to calculate the comprehensive score of evaluation indicators; the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature, simmering time, paper layer number and paper wrapping time as factors; validation test was conducted. The changes in the contents of five anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion), five anthraquinone glycosides (barbaloin, rheinoside, rhubarb glycoside, emodin glycoside, and emodin methyl ether glycoside), two sennosides (sennoside A, sennoside B), gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h, simmered on high heat for 20 min and then simmered at 140 ℃, the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 (RSD<1.0%). After simmering, the contents of five anthraquinones and two sennosides were decreased significantly, while those of 5 free anthraquinones and gallic acid were increased to different extents; a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing, which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.
		                        		
		                        		
		                        		
		                        	
5.Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Yun-Lin HUANG ; Chao SUN ; Ying WANG ; Juan CHENG ; Shi-Wen WANG ; Li WEI ; Xiu-Yun LU ; Rui CHENG ; Ming WANG ; Jian-Gao FAN ; Yi DONG
Ultrasonography 2025;44(2):134-144
		                        		
		                        			 Purpose:
		                        			This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. 
		                        		
		                        			Methods:
		                        			Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. 
		                        		
		                        			Results:
		                        			Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). 
		                        		
		                        			Conclusion
		                        			Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD. 
		                        		
		                        		
		                        		
		                        	
6.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
		                        		
		                        			 Background:
		                        			and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. 
		                        		
		                        			Methods:
		                        			This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. 
		                        		
		                        			Results:
		                        			Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. 
		                        		
		                        			Conclusions
		                        			The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy. 
		                        		
		                        		
		                        		
		                        	
7.Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Yun-Lin HUANG ; Chao SUN ; Ying WANG ; Juan CHENG ; Shi-Wen WANG ; Li WEI ; Xiu-Yun LU ; Rui CHENG ; Ming WANG ; Jian-Gao FAN ; Yi DONG
Ultrasonography 2025;44(2):134-144
		                        		
		                        			 Purpose:
		                        			This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. 
		                        		
		                        			Methods:
		                        			Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. 
		                        		
		                        			Results:
		                        			Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). 
		                        		
		                        			Conclusion
		                        			Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD. 
		                        		
		                        		
		                        		
		                        	
8.Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Yun-Lin HUANG ; Chao SUN ; Ying WANG ; Juan CHENG ; Shi-Wen WANG ; Li WEI ; Xiu-Yun LU ; Rui CHENG ; Ming WANG ; Jian-Gao FAN ; Yi DONG
Ultrasonography 2025;44(2):134-144
		                        		
		                        			 Purpose:
		                        			This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. 
		                        		
		                        			Methods:
		                        			Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. 
		                        		
		                        			Results:
		                        			Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). 
		                        		
		                        			Conclusion
		                        			Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD. 
		                        		
		                        		
		                        		
		                        	
9.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
		                        		
		                        			 Background:
		                        			and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. 
		                        		
		                        			Methods:
		                        			This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. 
		                        		
		                        			Results:
		                        			Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. 
		                        		
		                        			Conclusions
		                        			The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy. 
		                        		
		                        		
		                        		
		                        	
10.Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Yun-Lin HUANG ; Chao SUN ; Ying WANG ; Juan CHENG ; Shi-Wen WANG ; Li WEI ; Xiu-Yun LU ; Rui CHENG ; Ming WANG ; Jian-Gao FAN ; Yi DONG
Ultrasonography 2025;44(2):134-144
		                        		
		                        			 Purpose:
		                        			This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. 
		                        		
		                        			Methods:
		                        			Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. 
		                        		
		                        			Results:
		                        			Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). 
		                        		
		                        			Conclusion
		                        			Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD. 
		                        		
		                        		
		                        		
		                        	
            
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