1.Ethical Considerations and Countermeasure Analysis of Public Mental Disorders Stigma in China
Chinese Medical Ethics 2024;35(6):654-662
		                        		
		                        			
		                        			Discrimination against patients with mental disorders and the resulting stigma will not only affect patients’ medical treatment, but also bring about community isolation and lack of resources. Mental health problems have become a major public health problem and a prominent social problem. From the perspective of bioethics, the existence of public mental disorders stigma violates the principles of justice and respect. This paper quantitatively described the status quo of public mental disorders stigma in China, and explored its influencing factors through factor analysis and binary logistic regression analysis. The public stigma of mental disorders score was (54.64±11.048). Factor analysis extracted 4 common factors, namely isolation, pain, contact, and empathy, with a cumulative explained variance of 68.948%. The results showed that age and contact history were the main factors affecting the public stigma of mental disorders. It is recommended to reduce discrimination by enhancing understanding and improving empathy. Specifically, it is to implement the personal liability for discrimination through ethical regulation and legal construction, and strengthen the concept of a community of shared future for mankind by creating a tolerant social atmosphere, so as to achieve an appropriate balance between public safety and individual rights and interests.
		                        		
		                        		
		                        		
		                        	
2.Predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor
Li ZHANG ; Yueli TIAN ; Yong HE ; Haiyan LI ; Min WANG ; Ying DING ; Yu LIU ; Yongxue ZHANG ; Xiaoli LAN ; Wei CAO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(2):91-96
		                        		
		                        			
		                        			Objective:To investigate the predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor (GIST). Methods:From March 2014 to June 2020, the 18F-FDG PET/CT imaging and surgical pathological data of 35 patients with GIST (27 males, 8 females; age 44-84 years) from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and Zhongnan Hospital of Wuhan University were analyzed retrospectively. Patients were divided into ring-shaped uptake group and other uptake patterns group according to 18F-FDG PET/CT image feature. Fisher′s exact test was used to analyze the differences of tumor necrosis and National Institutes of Health (NIH) risk classification (short for NIH classification) between different image feature groups. Mann-Whitney U test was used to analyze the differences of SUV max , metabolic parameters at different thresholds (2.5, 40%, 50%) of SUV max (metabolic tumor volume (MTV; MTV 2.5, MTV 40%, MTV 50%) and total lesion glycolysis (TLG; TLG 2.5, TLG 40%, TLG 50%)) between different clinicopathological features (lesion location, tumor diameter, mitotic count, Ki-67, necrosis, image feature, NIH classification) groups. Spearman rank correlation analysis was used to explore the correlation between clinicopathological features and metabolic parameters. ROC curve analysis was used to distinguish NIH classification of different metabolic parameters. Delong test was used to compared differences between different AUCs. Results:Of 35 GIST patients, 11(31.4%) were ring-shaped uptake and 24(68.6%) were other uptake patterns, and the differences of necrosis (7/11 vs 12.5%(3/24); P=0.004) and NIH classification (11/11 vs 25.0%(6/24); P<0.001) between the two groups were significant. There were significant differences of metabolic parameters between different groups of tumor diameter, mitotic count, necrosis, image feature, NIH classification ( z values: from -4.70 to -2.09, all P<0.05), while there were no significant differences of Ki-67 ( z values: from -0.83 to -0.71, all P>0.05). Metabolic parameters were correlated with mitotic count, tumor diameter, necrosis, image feature and NIH classification ( rs values: 0.36-0.81, all P<0.05), while was not correlated with Ki-67 ( rs values: 0.12-0.14, all P>0.05). The differences of AUCs between SUV max and MTV 2.5, TLG 2.5, TLG 40%, TLG 50%were significant (0.752, 0.856, 0.856, 0.882, 0.886; z values: 1.96-2.12, all P<0.05). Conclusions:The NIH classification of GIST with ring-shaped uptake on 18F-FDG PET/CT is higher and more prone to necrosis. The 18F-FDG PET/CT metabolic parameters based on different thresholds of SUV max have certain significance for the prediction of NIH classification of GIST, and may be superior to SUV max.
		                        		
		                        		
		                        		
		                        	
3.Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.
Zekai WU ; Yuan SHI ; Yueli CUI ; Xin XING ; Liya ZHANG ; Da LIU ; Yutian ZHANG ; Ji DONG ; Li JIN ; Meijun PANG ; Rui-Ping XIAO ; Zuoyan ZHU ; Jing-Wei XIONG ; Xiangjun TONG ; Yan ZHANG ; Shiqiang WANG ; Fuchou TANG ; Bo ZHANG
Protein & Cell 2023;14(5):350-368
		                        		
		                        			
		                        			Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			Heart/physiology*
		                        			;
		                        		
		                        			Mammals
		                        			;
		                        		
		                        			Myocardial Infarction/metabolism*
		                        			;
		                        		
		                        			Myocytes, Cardiac/metabolism*
		                        			;
		                        		
		                        			Pericardium/metabolism*
		                        			;
		                        		
		                        			Single-Cell Analysis
		                        			;
		                        		
		                        			Zebrafish/metabolism*
		                        			
		                        		
		                        	
4.Genetic testing and clinical analysis of a patient with Dilated cardiomyopathy due to variant of FLNC gene.
Yanlong REN ; Yahui ZHANG ; Xiaoping ZHANG ; Yueli WANG ; Xuxia LIU ; Jin SHENG ; Shangqiu NING ; Wenxian LIU ; Xiaoyan LI
Chinese Journal of Medical Genetics 2023;40(12):1551-1555
		                        		
		                        			OBJECTIVE:
		                        			To explore the genetic basis for a patient with Dilated cardiomyopathy.
		                        		
		                        			METHODS:
		                        			A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG).
		                        		
		                        			RESULTS:
		                        			DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4).
		                        		
		                        			CONCLUSION
		                        			The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Cardiomyopathy, Dilated/genetics*
		                        			;
		                        		
		                        			Genetic Testing
		                        			;
		                        		
		                        			Genetic Counseling
		                        			;
		                        		
		                        			Computational Biology
		                        			;
		                        		
		                        			Frameshift Mutation
		                        			;
		                        		
		                        			Mutation
		                        			;
		                        		
		                        			Filamins
		                        			
		                        		
		                        	
5.Analysis of surgical results of over-80-year-old patients with unilateral multiple septated chronic subdural hematoma
Mingli MAO ; Yueli ZHANG ; Qijun SUN ; Shangwu WANG
Chinese Journal of Nervous and Mental Diseases 2023;49(1):11-15
		                        		
		                        			
		                        			Objective To study the efficacy and safety of hard channel puncture drainage in the treatment of multiple septated chronic subdural hematoma (CSDH) in the elderly by comparison with drilling drainage. Methods Twenty-one over-80-year-old patients with unilateral multiple septated CSDH were treated with drilling drainage in 9 cases (drilling group) and hard channel puncture drainage in 12 cases (hard channel group). The operation time, hematoma clearance rate in 1 week after operation, postoperative complications and hematoma recurrence in 3 months after operation were compared between the two groups. Results The two groups of patients successfully completed the operation. The operation time ranged from 50 to 95 min with a mean of (78±14) min in the drilling group and 22 to 40 min with a mean of (29±5) min in the hard channel group. The difference was significant (P<0.05); One week after operation, the hematoma clearance rate ranged from 92% to100% with a mean of 96%±3% in the drilling group and 90% to 100% with a mean of 94%±3% in the hard channel group. The difference was not significant (P>0.05). Postoperative complications: there was no epilepsy in the drilling group, and 1 epilepsy in the hard channel group (8.3%). The difference was not significant (P>0.05). There were no other complications such as intracranial space occupying gas, brain parenchyma injury, intracranial infection in both groups. Hematoma recurrence 3 months after operation: there was no recurrence in the drilling group and 3 cases (25%) in the hard channel group. The difference was not significant (P>0.05). Conclusions Hard channel puncture drainage is safe and effective in the treatment of elderly multiple septated CSDH. Compared with drilling drainage, it has shorter operation time, less trauma and is more suitable for patients with important organ diseases.
		                        		
		                        		
		                        		
		                        	
6.Clinical and genetic analysis of cases of progressive familial intrahepatic cholestasis type 3
Yueli SHEN ; Xiantu ZHANG ; Yunhao XUN
Chinese Journal of Hepatology 2023;31(3):307-313
		                        		
		                        			
		                        			Objective:To conduct clinical and genetic analysis in two cases of cholestatic liver disease to determine the specific etiology of cholestasis.Methods:Clinical data and the medical histories in family members of two cases were collected. The gene variation was detected by whole-exome sequencing technology. Sanger sequencing validation and bioinformatics analysis were performed on patients and their parents with suspected pathogenic mutations.Results:Whole-exome sequencing showed that the ABCB4 gene of case 1 (a male, 16 years old) had compound heterozygous mutations of c.646C > T from the father and c.927T > A from the mother, while the ABCB4 gene of case 2 (a female, 17 years old) had a compound heterozygous mutation of c.2784-1G > A from the father and c.646C > T from the mother. New mutation sites that had not been previously reported were c.646C > T, c.927T > A, and c.2784-1G > A.Conclusion:In this study, both cases had progressive familial intrahepatic cholestasis type 3 (PFIC-3) caused by ABCB4 gene mutations, and it also enriched the ABCB4 pathogenic variant spectrum. Whole-exome sequencing technology provides a reliable diagnostic tool for etiological analysis.
		                        		
		                        		
		                        		
		                        	
7.Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua.
Guoping SHU ; Yueli TANG ; Mingyuan YUAN ; Ning WEI ; Fangyuan ZHANG ; Chunxian YANG ; Xiaozhong LAN ; Min CHEN ; Kexuan TANG ; Lien XIANG ; Zhihua LIAO
Acta Pharmaceutica Sinica B 2022;12(3):1500-1513
		                        		
		                        			
		                        			Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.
		                        		
		                        		
		                        		
		                        	
8. Associations of POR*28 polymorphisms with tacrolimus stable dose in Chinese kidney transplantation patients
Shuang WANG ; Yueli ZHANG ; Jia LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(9):991-997
		                        		
		                        			
		                        			 AIM: To investigate the correlation between POR*28 single nucleotide polymorphism (SNP) and tacrolimus stable dose in Chinese kidney transplant patients, and to provide reference for the development of individualized dose adjustment programs in this population. METHODS: A total of 350 Chinese kidney transplant patients were enrolled. CYP3A5*3 and POR*28 genes were detected by Mass ARRAY Analyzer Compac Mass spectrometry in Shenggong Bioengineering (Shanghai) Co., LTD. Serum trough concentration of tacrolimus was determined by ENZYME amplification immunoassay (EMIT). The correlation between the above genotypes and tacrolimus stable dose was analyzed. RESULTS: The frequencies of CYP3A5*3 and POR*28 alleles were consistent with hardy-Weinberg genetic balance. The stable dose in patients with CYP3A5*3 GG genotype was significantly lower than that in patients with AG and AA genotype. Based on stratified analysis of CYP3A5, different POR genotypes were significantly correlated with the stable dose of tacrolimus in CYP3A5 expression and non-expression groups. The mean stable dose of tacrolimus was statistically significant between POR*28 patients with at least one T allele and CC wild-type patients (P = 0.003 7 and P = 0.003 1). Multiple Regression Analysis showed that CYP3A5*3 and POR*28 explained 36.6% and 1.7% of the individual differences in stable doses of Tacrolimus, respectively. CONCLUSION: CYP3A5 *3 and POR*28 genotypes are significantly correlated with tacrolimus stable dose in Chinese kidney transplant recipients, and detection before transplantation will contribute to clinical individualized tacrolimus medication. 
		                        		
		                        		
		                        		
		                        	
9.Ethical Considerations and Countermeasure Analysis of Public Mental Disorders Stigma in China
Chinese Medical Ethics 2022;35(6):654-662
		                        		
		                        			
		                        			Discrimination against patients with mental disorders and the resulting stigma will not only affect patients’ medical treatment, but also bring about community isolation and lack of resources. Mental health problems have become a major public health problem and a prominent social problem. From the perspective of bioethics, the existence of public mental disorders stigma violates the principles of justice and respect. This paper quantitatively described the status quo of public mental disorders stigma in China, and explored its influencing factors through factor analysis and binary logistic regression analysis. The public stigma of mental disorders score was (54.64±11.048). Factor analysis extracted 4 common factors, namely isolation, pain, contact, and empathy, with a cumulative explained variance of 68.948%. The results showed that age and contact history were the main factors affecting the public stigma of mental disorders. It is recommended to reduce discrimination by enhancing understanding and improving empathy. Specifically, it is to implement the personal liability for discrimination through ethical regulation and legal construction, and strengthen the concept of a community of shared future for mankind by creating a tolerant social atmosphere, so as to achieve an appropriate balance between public safety and individual rights and interests.
		                        		
		                        		
		                        		
		                        	
10. Application of ultra-thin oblique posterosuperior auricular fascial flap in the second stage of Nagata microtia reconstruction
Gang LI ; Ruhong ZHANG ; Li YANG ; Xuran ZHU ; Yueli LIU ; Yan JIANG
Chinese Journal of Plastic Surgery 2020;36(1):53-55
		                        		
		                        			 Objective:
		                        			To investigate the effect and safety of ultra-thin oblique posterosuperior auricular fascial flap in the second stage of ear reconstruction.
		                        		
		                        			Methods:
		                        			Fifty-six cases with congenital microtia treated in The Second Affiliated Hospital of Zhengzhou University Medical Cosmetology Department from November 2015 to November 2018 were selected as the research objects. In the first stage, the costal cartilage ear stent was implanted, and in the second stage. The ultra-thin posterior oblique fascia flap was used to cover the stent. And the cranioauricular angle was reconstructed by free skin grafting.
		                        		
		                        			Results:
		                        			48 cases of the 54 cases completely survived, and 8 cases had hemorrhage after operation. The wounds were healed after dressing change. The postoperative cranioauricular angle was close to the healthy side.
		                        		
		                        			Conclusions
		                        			In the second stage of ear reconstruction, the retroauricular ultra-thin fascial flap method has reliable blood supply, small wound, unswollen reconstructed ears, and good outcome. It is a good choice for covering the ear framework. 
		                        		
		                        		
		                        		
		                        	
            
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