1.Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullination via the SP3/PAD4 pathway.
Changjun LV ; Minghui SUN ; Yilei GUO ; Wenxin XIA ; Simiao QIAO ; Yu TAO ; Yulai FANG ; Qin ZHANG ; Yanrong ZHU ; Yusufu YALIKUN ; Yufeng XIA ; Zhifeng WEI ; Yue DAI
Acta Pharmaceutica Sinica B 2023;13(4):1600-1615
		                        		
		                        			
		                        			Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.
		                        		
		                        		
		                        		
		                        	
2.Preliminary Recommendations on the Timing of Lung Surgery after Novel Coronavirus Infection in Patients with Pulmonary Nodules and Lung Cancer.
Xin LI ; Ming DONG ; Song XU ; Honglin ZHAO ; Sen WEI ; Zuoqing SONG ; Minghui LIU ; Dian REN ; Fan REN ; Qingchun ZHAO ; Renwang LIU ; Chunqiu XIA ; Gang CHEN ; Jun CHEN
Chinese Journal of Lung Cancer 2023;26(2):148-150
		                        		
		                        			
		                        			In recent years, the corona virus disease 2019 (COVID-19) pandemic has had a huge impact on the global medical, political and economic fields. Since the beginning of the COVID-19 epidemic, our understanding of the impact of COVID-19 has grown exponentially. Recently, the COVID-19 epidemic has changed rapidly in China, and there has been controversy over how to carry out surgical operations for patients with lung neoplastic lesions. Some studies have shown that lung cancer patients undergoing surgery are more likely to experience respiratory failure and perioperative death after contracting COVID-19 than the general population, however, delays in cancer treatment are also associated with increased mortality among these patients. In particular, the novel coronavirus Omikron variant has a higher transmissibility and may escape the immunity obtained through the previous novel coronavirus infection and vaccination. In order to minimize the risk of novel coronavirus infection in surgical patients, it is necessary to develop new treatment guidelines, expert consensus and preventive measures. However, the current rapid change of the epidemic situation has led to insufficient time and evidence to develop guidelines and consensus. Therefore, thoracic surgeons need to evaluate specific patient populations at higher risk of severe complications before surgery and weigh the benefit of surgical treatment against the risk of novel coronavirus infection. We try to give some recommendations on lung surgery during the current domestic epidemic situation based on the guidelines and consensus of oncology and thoracic surgery organizations in different regions on lung surgery.
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		                        			Humans
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		                        			Lung Neoplasms/complications*
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		                        			COVID-19
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		                        			SARS-CoV-2
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		                        			Multiple Pulmonary Nodules
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		                        			Pandemics/prevention & control*
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		                        			Lung
		                        			
		                        		
		                        	
3.Training in a wearable exoskeleton improves the lower limb motor recovery of stroke survivors
Yangan LI ; Zejian CHEN ; Nan XIA ; Minghui GU ; Jiang XU ; Xiaoyu XIE ; Xiaolin HUANG
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(2):109-113
		                        		
		                        			
		                        			Objective:To explore any differential effect of training wearing a unilateral exoskeleton on the lower-limb motor function of stroke survivors.Methods:Forty stroke survivors were randomly divided into an exoskeleton group ( n=20) and a control group ( n=20). The control group performed conventional lower extremity exercise training while the exoskeleton group received exoskeleton-assisted lower-limb physical therapy. Each participant received eighteen 40-minute training sessions over three weeks. Before and after the intervention, the walking ability, lower-limb function, balance and ability in the activities of daily living of both groups were evaluated. Integrated electromyography (iEMG) of the rectus femoris and tibialis anterior of both legs was also recorded during sit-to-stand transitions to assess the activation of the affected muscles and the symmetry of bilateral muscle activation. Results:After the three weeks, significant improvement was observed in all of the measurements in both groups, but with the exoskeleton group scoring significantly better on average in functional ambulation category grading (1.63±0.72). Both groups′ iEMGs had also improved significantly compared with before treatment, but the exoskeleton group′s average result was by that time significantly better than the control group′s average.Conclusions:A wearable exoskeleton can effectively improve the rehabilitation of walking, lower limb movement, balance and skill in the activities of daily living of persons with subacute stroke. It better activates the affected lower limb muscles and improves the symmetry of bilateral lower limb muscle activation.
		                        		
		                        		
		                        		
		                        	
4.Early and mid-term results of surgical treatment for complete atrioventricular septal defect
Fengxiang LI ; Minghui ZOU ; Yanqin CUI ; Li MA ; Xu ZHANG ; Shuliang XIA ; Chunmei HU ; Xinxin CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(7):398-404
		                        		
		                        			
		                        			Objective:To summarize the results of surgical treatment for complete atrioventricular septal defect(CAVSD) in early and middle stages.Methods:147 children with CAVSD in Guangzhou Women and Children’s Medical Center from January 2010 to December 2019 were selected, Males 85, females 62, median age of surgery 5 months(1 months-10 years old), median body mass 5.5 kg(2.4-20.9 kg). Complete atrioventricular septal defect was diagnosed by ultrasonic cardiogram before surgery. All the children underwent atrial ventricular valve formation and underwent simultaneous repair.Outpatient follow-up was planned.Ultrasonic cardiogram and electrocardiogram were performed. SPSS 22 statistical software was used for data analysis.Results:All 147 CAVSD patients underwent one-time surgical correction.Early postoperative death occurred in 7 cases(4.76%). The causes of death were: 3 cases of pulmonary hypertension crisis, 3 cases of severe mitral insufficiency(MI), 1 case of postoperative malignant arrhythmia, and the rest of the children were cured and discharged. Permanent pacemaker was installed in 3 patients due to atrioventricular block(AVB). The follow-up time was 1-10 years old, and 2 patients died in late stage: 1 patient did not seek medical treatment in time due to infection, and 1 patient had unknown cause. Five patients underwent secondary surgery: 4 due to severe mitral/tricuspid insufficiency(MI/TI) and 1 due to delayed AVB. The mid-term follow-up showed 9 cases of severe MI and 4 cases of severe TI. Compared with children with surgical age<3 months and ≥3 months, there were statistically significant differences in postoperative ventilator-assisted ventilation time, severe MI before postoperative discharge and total mortality between the two groups( P<0.05). Mid-term follow-up results showed no difference between the two groups. There were statistically significant differences in surgical age, postoperative CICU stay time and total hospital stay between the children with trisomy 21-syndrome and those without trisomy 21-syndrome( P<0.05), and there was no difference between the two groups in mid-term follow-up results. Residual shunt of 1-3 mm VSD was found in 29 cases, 26 cases were closed during follow-up, and 3 cases had smaller residual shunt. Conclusion:Modified single patch technique treatment of CAVSD has good effect, low mortality and low re-operation rate. But age <3 months group, infant mortality was significantly increased, the duration of postoperative mechanical assisted ventilation was prolonged, and the proportion of early postoperative severe MI was high.Severe MI and TI is easy to occur after CAVSD, which requires long-term follow-up and timely treatment. The children with trisomy 21-syndrome were similar to those with normal chromosome except for longer stay in ICU and total hospital stay.
		                        		
		                        		
		                        		
		                        	
5.Outcomes after surgical repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: a series of 104 cases
Minghui ZOU ; Fan CAO ; Li MA ; Yuansheng XIA ; Shengchun YANG ; Weidan CHEN ; Wenlei LI ; Xinxin CHEN
Chinese Journal of Surgery 2023;61(12):1093-1098
		                        		
		                        			
		                        			Objective:To examine the early and midterm surgical outcome of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCA) using revised surgical strategies.Methods:A retrospective analysis of clinical data, surgical methods, and follow-up results was performed of 104 cases of PA/VSD/MAPCA in Department of Cardiovascular Surgery, Guangzhou Women and Children′s Medical Center from January 2017 to September 2022. There were 55 males and 49 females, aged ( M(IQR)) 33.9(84.0) months (range: 0.5 to 209.6 months) at the first surgical procedures. The anatomical classification included 89 cases of type B and 15 cases of type C. The number of major aortopulmonary collateral arteries was 4.2 (3.0) (range: 1 to 8). The Kaplan-Meier method was used for survival estimation. Results:In the first stage of surgery, 50 patients underwent a complete primary repair, 12 patients underwent partial repair, 32 patients underwent palliative right ventricular-pulmonary artery connection, and only 10 patients chose the Blalock-Taussig shunt. There were 10 cases of early death. In the second stage, 14 patients underwent complete repair and 4 patients underwent partial repair with no early death. The interval between the two surgeries was 19 (10) months (range: 9 to 48 months). Finally, during the 40 (34) months follow-up period, a total of 64 patients were complete repair and the right/left ventricular pressure ratio after complete repair was 0.63±0.16 (range: 0.36 to 1.00). Survival analysis showed that survival rates at 1 and 5 years after first-stage surgery were both 89.4% (95% CI: 83.5% to 95.3%). At 28 (34) months (range: 1 to 67 months) of follow-up after complete repair, the survival analysis showed that the survival rates at 1 and 5 years were both 95.2% (95% CI: 89.9% to 100%). Conclusions:Using combined approaches tailored to individual patients and optimized unifocalization strategy, the complete repair rate at one stage and the cumulative complete repair rate at 5 years improved significantly with a lower right/left ventricular pressure ratio and satisfactory early and intermediate survival.
		                        		
		                        		
		                        		
		                        	
6.Clinical and genetic characteristics of young patients with myeloproliferative neoplasms
Mengyu ZHANG ; Mei BAO ; Dayu SHI ; Hongxia SHI ; Xiaoli LIU ; Na XU ; Minghui DUAN ; Junling ZHUANG ; Xin DU ; Ling QIN ; Wuhan HUI ; Rong LIANG ; Meifang WANG ; Ye CHEN ; Dongyun LI ; Wei YANG ; Gusheng TANG ; Weihua ZHANG ; Xia KUANG ; Wei SU ; Yanqiu HAN ; Limei CHEN ; Jihong XU ; Zhuogang LIU ; Jian HUANG ; Chunting ZHAO ; Hongyan TONG ; Jianda HU ; Chunyan CHEN ; Xiequn CHEN ; Zhijian XIAO ; Qian JIANG
Chinese Journal of Hematology 2023;44(3):193-201
		                        		
		                        			
		                        			Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.
		                        		
		                        		
		                        		
		                        	
7.Outcomes after surgical repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: a series of 104 cases
Minghui ZOU ; Fan CAO ; Li MA ; Yuansheng XIA ; Shengchun YANG ; Weidan CHEN ; Wenlei LI ; Xinxin CHEN
Chinese Journal of Surgery 2023;61(12):1093-1098
		                        		
		                        			
		                        			Objective:To examine the early and midterm surgical outcome of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCA) using revised surgical strategies.Methods:A retrospective analysis of clinical data, surgical methods, and follow-up results was performed of 104 cases of PA/VSD/MAPCA in Department of Cardiovascular Surgery, Guangzhou Women and Children′s Medical Center from January 2017 to September 2022. There were 55 males and 49 females, aged ( M(IQR)) 33.9(84.0) months (range: 0.5 to 209.6 months) at the first surgical procedures. The anatomical classification included 89 cases of type B and 15 cases of type C. The number of major aortopulmonary collateral arteries was 4.2 (3.0) (range: 1 to 8). The Kaplan-Meier method was used for survival estimation. Results:In the first stage of surgery, 50 patients underwent a complete primary repair, 12 patients underwent partial repair, 32 patients underwent palliative right ventricular-pulmonary artery connection, and only 10 patients chose the Blalock-Taussig shunt. There were 10 cases of early death. In the second stage, 14 patients underwent complete repair and 4 patients underwent partial repair with no early death. The interval between the two surgeries was 19 (10) months (range: 9 to 48 months). Finally, during the 40 (34) months follow-up period, a total of 64 patients were complete repair and the right/left ventricular pressure ratio after complete repair was 0.63±0.16 (range: 0.36 to 1.00). Survival analysis showed that survival rates at 1 and 5 years after first-stage surgery were both 89.4% (95% CI: 83.5% to 95.3%). At 28 (34) months (range: 1 to 67 months) of follow-up after complete repair, the survival analysis showed that the survival rates at 1 and 5 years were both 95.2% (95% CI: 89.9% to 100%). Conclusions:Using combined approaches tailored to individual patients and optimized unifocalization strategy, the complete repair rate at one stage and the cumulative complete repair rate at 5 years improved significantly with a lower right/left ventricular pressure ratio and satisfactory early and intermediate survival.
		                        		
		                        		
		                        		
		                        	
8.Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile
Shiwei QUMU ; Weiliang SUN ; Jing GUO ; Yuting ZHANG ; Lesi CAI ; Chaozeng SI ; Xia XU ; Lulu YANG ; Xuanming SITU ; Tianyi YANG ; Jiaze HE ; Minghui SHI ; Dongyan LIU ; Xiaoxia REN ; Ke HUANG ; Hongtao NIU ; Hong LI ; Chang'An YU ; Yang CHEN ; Ting YANG
Chinese Medical Journal 2023;136(4):461-472
		                        		
		                        			
		                        			Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.
		                        		
		                        		
		                        		
		                        	
9.Early and mid-term results of surgical revascularization of pulmonary artery in unilateral absence of a pulmonary artery
Wenlei LI ; Li MA ; Weidan CHEN ; Shuliang XIA ; Minghui ZOU ; Xinxin CHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(10):581-585
		                        		
		                        			
		                        			Objective:To summarize the early and middle terms of the revascularization of remnant pulmonary artery in unilateral absent intrapericardial pulmonary artery.Methods:We retrospectively analyzed the medical records of 14 patients(7 males and 7 females) with unilateral absent pulmonary artery, in which 10 were right and 4 were left, the median age at surgery was 5 months. The patients received operation from January 2009 to December 2020. 14 patients, 2 cases associated with tetralogy of Fallot, and 1 case with aortopulmonary window. The diagnosis was made by enhanced CT scan or pulmonary vein wedge angiography. The median diameter of the affected hilar pulmonary artery remnants was(3.20±0.94)mm, and the Z value was -3.92±1.64. All the patients received single-stage revascularization: group A: tube graft interposition in 3 patients, autologous pericardial roll in 5; group B: direct anastomosis in 2, unifocalization in one and main pulmonary artery flap angioplasty in the rest 3.Results:No hospital death occurred. There were no difference finds in the age and weight at operation, the cardiopulmonary bypass time, the mechanical ventilation time, and the length of intensive care unit stay between the two groups. All the patients took aspirin for anticoagulation for 6 months after the operation. The follow-up period was 1 month to 68 months. Because the neo-PA stenosis at the anastomosis was found in one patient in group B, transcatheter balloon angioplasty was performed at 41 months after surgery. Nonetheless, the results were encouraging, symptoms have improved in all patients. The diameter and Z value of the latest ipsilateral pulmonary artery was(6.25±0.99)mm and -2.34±1.18 respectively, significantly improved when compared to the preoperative value. Residual pulmonary artery hypertension was not found. The Z value of the affected side of the pulmonary artery in group B was significantly improved than that in group A.Conclusion:Early and aggressive pulmonary artery revascularization is effective at restoring normal antegrade flow to the affected lung, resulting in improved diameter of the PA, and UAPA patient’s symptoms. The use of autologous pulmonary artery tissue angioplasty may reach a more satisfying result. However, transcatheter intervention may diminish the new pulmonary artery stenosis temporarily, reoperation is still needed in the long-term follow-up.
		                        		
		                        		
		                        		
		                        	
10.Surgical treatment of severe spontaneous intracerebral hemorrhage in the basal ganglia in young adults: a comparison between transsylvian-transinsular and transcortical-transtemporal approach
Lu WANG ; Dongbo LI ; Congjin LI ; Duogui XIA ; Hao ZHANG ; Minghui LI ; Zhanglin QIAN ; Tao YANG
International Journal of Cerebrovascular Diseases 2022;30(2):109-114
		                        		
		                        			
		                        			Objective:To investigate the difference in efficacy between transsylvian-transinsular approach and transcortical-transtemporal approach for hematoma evacuation in the treatment of severe basal ganglia intracerebral hemorrhage in young adults.Methods:Young adult patients with severe intracerebral hemorrhage in the basal ganglia region underwent craniotomy hematoma removal in Ankang Central Hospital from February 2012 to February 2021 were retrospectively enrolled. The Glasgow Outcome Scale score was used to evaluate the outcome at 6 months after onset. 4-5 were defined as good outcome and 1-3 were defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of the poor outcomes. Results:A total of 51 patients were enrolled. Their median age was 41 (interquartile range 39-43) years, and 29 were men (56.8%). The median Glasgow Coma Scale score at admission was 6.0 (interquartile range 5.5-7.0), and the median baseline hematoma volume was 38.0 ml (34.5-47.5 ml). Twenty-one patients (41.2%) were in the transsylvian-transinsular approach group and 30 (58.8%) were in the transcortical-transtemporal approach group. There were no significant differences in demographics, vascular risk factors and baseline clinical data between the transsylvian-transinsular approach group and the transcortical-transtemporal approach group. Compared with the transcortical-transtemporal approach group, the amount of intraoperative bleeding and hematoma residue in the transsylvian-transinsular approach group were less, the proportion of patients requiring decompressive craniectomy was lower (33.3% vs. 63.3%; χ2=4.449, P=0.035), and the duration of dehydration medication and hospital stay were shorter (all P<0.05). However, there was no significant difference in the good outcome rate between the two groups (66.7% vs. 56.7%; χ2=0.518, P=0.472). Multivariate logistic regression analysis showed that lower scores of Glasgow Coma Scale at admission (odds ratio 0.128, 95% confidence interval 0.017-0.977; P=0.047) and longer hospital stay (odds ratio 1.402, 95% confidence interval 1.065-1.844; P=0.016) were independently associated with the poor outcomes. Conclusion:For young adult patients with severe basal ganglia intracerebral hemorrhage who underwent hematoma removal, although there was no significant difference between the outcomes of patients with transsylvian-transinsular approach and transcortical-transtemporal approach, the former had more advantages.
		                        		
		                        		
		                        		
		                        	
            
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