OBJECTIVE: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia. METHODS: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001). RESULTS: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion. CONCLUSION Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.
Humans ; Phenotype ; Codon, Initiator/genetics* ; Female ; Male ; Retrospective Studies ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobin A/genetics* ; Adult ; Mutation

Objective:To analyze the echocardiographic features of different subtypes of Takayasu arteritis（TA）complicated with heart failure（HF），and to explore the clinical application value of echocardiography in the assessment of TA-HF.Methods:Comprehensive clinical and echocardiographic data were collected from 328 consecutive patients with TA who were admitted to the First Affiliated Hospital of China Medical University between January 2010 and December 2023. HF was diagnosed and classified according to the criteria outlined in the China guidelines for the diagnosis and treatment of heart failure 2024. A total of 38 TA-HF patients was selected and enrolled. Based on left ventricular ejection fraction（LVEF），they were grouped into preserved LVEF（HFpEF）group（LVEF≥50%， n=22）and the reduced LVEF（HFmr/rEF）group（LVEF<50%， n=16）. Clinical and echocardiographic data were compared between the HFpEF group and the HFmr/rEF group. Multivariate analysis was performed to evaluate the risk factors for the occurrence of heart failure. Results:① The incidence of HF was 11.6% in patients with TA（38/328）. In the patients with TA-HF，Numano Type Ⅴ accounted for 52.6%（20/38）. According to HF classification standard，TA-HF most commonly manifested as HFpEF at 57.9%（22/38），HFmrEF and HFrEF each accounted for 21.05%（8/38）respectively. ②Echocardiographic analysis revealed the following findings in TA-HF patients：34（89.5%）patients exhibited left heart dilation，4（10.5%）patients demonstrated right heart dilation，23（60.5%）patients presented with left ventricular myocardial hypertrophy，18（47.4%）patients had moderate/severe aortic valve regurgitation，9（23.7%）patients showed diffuse left ventricular myocardial wall motion abnormalities，8（21.1%）patients displayed segmental left ventricular myocardial wall motion abnormalities，and 11（28.9%）patients were diagnosed with pulmonary hypertension. ③Intergroup comparisons demonstrated significantly lower levels of erythrocyte sedimentation rate，reduced proportions of patients in clinical active phase，and lower incidence of moderate/severe aortic regurgitation in HFmr/rEF group versus HFpEF group（all P<0.05）. Conversely，HFmr/rEF group exhibited significantly higher rates of myocardial motion abnormalities，left atrial anteroposterior diameter，left ventricular end-systolic anteroposterior diameter，and left ventricular end-systolic volume compared to HFpEF group（all P<0.05）. ④Multivariate regression analysis identified left ventricular wall motion abnormality，pulmonary hypertension，moderate/severe aortic regurgitation and left ventricular myocardial hypertrophy as independent risk factors for TA-HF development. Conclusions:TA-HF exhibits diverse echocardiographic manifestations，with distinct echocardiographic features observed among different subtypes. Echocardiography plays a crucial role in the diagnosis，classification，and risk stratification of TA-HF.

Objective:To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.Methods:A retrospective study was conducted on 7 patients diagnosed by Yangjiang People′s Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People′s Hospital of Yangjiang (Ethics No: 20240001).Results:For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A 2, whilst another had significantly decreased Hb A and Hb A 2, in addition with the appearance of a Hb H band. The content of Hb Bart′s in four neonates was ≥0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c. 2delT, HBA2: c. 1A>G, HBA2: c. 1A>T, and HBA1: c. 2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c. 427T>C (Hb CS) and HBA2: c. 2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c. 1A>G and Southeast Asian type deletion. Conclusion:Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c. 1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

Objective:Using graph theory analysis, this study compares the topological and node attributes of the brain network to explore the differences in gray matter structural and functional network topological properties between bipolar depression (BD) patients with and without obsessive-compulsive symptoms (OCS).Methods:A total of 90 BD patients (27 males, 63 females; median age 19.0(22.0, 25.0) years) were recruited from the psychiatric outpatient and inpatient departments of the First Affiliated Hospital of Jinan University between March 2018 and December 2022. Fifty healthy controls (19 males, 31 females; median age: 23.0 (20.0, 27.0) years) were also enrolled. The BD patients were divided into two groups based on the presence of OCS: 53 with OCS (OCS group) and 37 without OCS (NOCS group). Resting-state structural and functional MRI data were collected for all participants to construct gray matter structural and functional networks. Graph therory analysis was applied to calculate network topological metrics such as small-world properties. The structural and functional network topological properties were compared among the BD-OCS, BD-nOCS, and control groups. Partial correlation analysis was conducted to examine the association between network topological metrics with significant group differences and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Support vector machines (SVM) were used with these metrics as classification feature values to improve diagnostic accuracy through pairwise group classification.Results:Structural network analysis of gray matter: compared to HC group, both OCS group and NOCS group showed increased shortest path length and standardized characteristic path length (shortest path length: 0.78 and 0.80 vs. 0.69; normalized characteristic path length: 0.48 and 0.49 vs. 0.43), and decreased global efficiency (0.21 and 0.21 vs. 0.24) compared to the HC group (permutation test, all P<0.05). Compared to NOCS and HC groups, the OCS group showed increased nodal centrality and betweenness centrality in the right rolandic operculum and left superior occipital gyrus (permutation test, all P<0.05). Functional network analysis of gray matter: compared to the NOCS group, the OCS group showed increased node efficiency and decreased betweenness centrality in the cerebellum ( t=2.15, -3.04; all P<0.05); compared to HC groups, the OCS group showed decreased betweenness centrality in the cerebellum and left inferior frontal gyrus, along with increased node centrality and nodal efficiency in the right transverse temporal gyrus ( t=-2.99, -3.61, 3.06, 3.10; all P<0.05). In the OCS group, betweenness centrality in the left inferior frontal gyrus positively correlated with Y-BOCS scale obsessive thinking score ( r=0.303, P=0.034). Nodal centrality and node efficiency of the right transverse temporal gyrus negatively correlated with Y-BOCS total score ( r=-0.301, -0.311) and Y-BOCS obsessional thinking scores ( r=-0.385, -0.380) separately(all P<0.05). SVM classification: the combined network features achieved an area under the curve of 0.80 in distinguising OCS from NOCS patients. Conclusion:BD-OCS and BD-nOCS patients both exhibit consistent changes in gray matter structural network topology, with the OCS group displaying more pronounced nodal topological abnormalities. Multi-network feature integration demostrates potential for diagnostic classfication.

Objective To evaluate the feasibility and effectiveness of 3D digital holographic imaging combined with intraoperative navigation technology in the context of partial nephrectomy.Methods A total of 46 patients who underwent laparoscopic partial nephrectomy in the Department of Urology at the Second People's Hospital of Hefei City between June 2023 and January 2025 were randomly assigned to either the experimental group or the control group.The experimental group(n=23)utilized preoperative planning and intraoperative real-time navigation based on 3D digital holographic imaging,whereas the control group(n=23)relied on preoperative planning using optimized two-dimensional images obtained via contrast-enhanced CT and MRI scans.Preoperative data—including gender,age,body mass index(BMI),tumor diameter,and RENAL score—were collected.Intra-operative parameters such as total operative time,warm ischemia time,intraoperative blood loss,hemoglobin levels,postoperative hospitalization duration,and time to drain removal were recorded.Renal function changes were assessed by comparing serum creatinine levels and estimated glomerular filtration rates(eGFR)before surgery and one month post-surgery.Additionally,the incidence of intraoperative complications—particularly injury to the renal collecting system—and postoperative complications—including positive surgical margins,bleeding,subcutaneous emphysema,and urinary fistula—was analyzed.Results In this study,holographic images were successfully reconstructed for 23 patients with renal tumors in the experimental group.Each anatomical structure—including the kidney and tumor lesions,collecting system,renal arteries and veins,adrenal glands,and inferior vena cava—was color-coded to enable intuitive visualization.These images were used for preoperative planning and provided real-time spatial orientation to accurately locate and guide resection of the tumor during surgery.In the control group,23 patients underwent preoperative planning based on contrast-enhanced CT and MRI scans acquired using optimized parameters.All 46 patients underwent laparoscopic partial nephrectomy performed by the same qualified surgeon,and postoperative pathological analysis confirmed renal tumors,including 27 cases of clear cell carcinoma,7 cases of chromophobe cell carcinoma,5 cases of papillary cell carcinoma,2 cases of sarcomatoid carcinoma,and 5 cases of angiomyolipoma.No significant differences were observed in baseline clinical characteristics(including age,body mass index,tumor diameter,and RENAL score)between the two groups(P＞0.05).The experimental group showed significantly lower values in total operative time,warm ischemia time,intraoperative blood loss,pre-to postoperative hemoglobin changes,and pre-surgical to one-month post-surgical creatinine changes compared to the control group(P＜0.01).Additionally,the experimental group exhibited smaller changes in hospitalization duration,time to drain removal,and glomerular filtration rate from preoperative to one month post-surgery;however,these differences were not statistically significant(P=0.175,P=0.331,and P=0.273).There were no intraop-erative complications or damage to the collecting system in either the experimental or control groups.Postopera-tively,the control group experienced one case of positive surgical margin,one case of hemorrhage,and one case of subcutaneous emphysema.No statistically significant differences were observed between the groups(P＞0.05).Conclusions 3D digital holographic imaging combined with intraoperative navigation technology,based on the fusion of MRI and CT data,facilitates preoperative planning and precise intraoperative guidance.This approach helps reduce operative time,preserve renal function,and lower perioperative risks while ensuring therapeutic efficacy.

Aiming at the classification and lesion localization of giga-pixel pathology whole slide images of breast cancer,a bidirectional gated recurrent unit attention based multi-instance learning(ABMIL-BiGRU)model is proposed for interpretable prediction of H&E stained breast cancer lymph node metastasis images.The method uses two orthogonal bidirectional gated recurrent units to establish the long-short distance dependencies between the features in the row and column directions of the image block,thereby embedding the spatial position and context information of the image block,and then quantifies the attention score of each feature representation through attention multi-instance pooling,thereby achieving whole slide image-level feature aggregation and generating interpretable heat maps.The results show that ABMIL-BiGRU model has an average accuracy of 0.918 6 and an AUCof 0.9467 on the breast cancer metastasis dataset,realizing high-precision prediction of whole slide images and localization of regions of interest,and also providing human-interpretable features at the image block level.The proposed model solves the"accuracy-interpretability trade-off"problem to a certain extent,and its superior performance provides a new paradigm for the clinical application of computer-aided diagnosis and intelligent systems.

Objective To evaluate the feasibility and effectiveness of 3D digital holographic imaging combined with intraoperative navigation technology in the context of partial nephrectomy.Methods A total of 46 patients who underwent laparoscopic partial nephrectomy in the Department of Urology at the Second People's Hospital of Hefei City between June 2023 and January 2025 were randomly assigned to either the experimental group or the control group.The experimental group(n=23)utilized preoperative planning and intraoperative real-time navigation based on 3D digital holographic imaging,whereas the control group(n=23)relied on preoperative planning using optimized two-dimensional images obtained via contrast-enhanced CT and MRI scans.Preoperative data—including gender,age,body mass index(BMI),tumor diameter,and RENAL score—were collected.Intra-operative parameters such as total operative time,warm ischemia time,intraoperative blood loss,hemoglobin levels,postoperative hospitalization duration,and time to drain removal were recorded.Renal function changes were assessed by comparing serum creatinine levels and estimated glomerular filtration rates(eGFR)before surgery and one month post-surgery.Additionally,the incidence of intraoperative complications—particularly injury to the renal collecting system—and postoperative complications—including positive surgical margins,bleeding,subcutaneous emphysema,and urinary fistula—was analyzed.Results In this study,holographic images were successfully reconstructed for 23 patients with renal tumors in the experimental group.Each anatomical structure—including the kidney and tumor lesions,collecting system,renal arteries and veins,adrenal glands,and inferior vena cava—was color-coded to enable intuitive visualization.These images were used for preoperative planning and provided real-time spatial orientation to accurately locate and guide resection of the tumor during surgery.In the control group,23 patients underwent preoperative planning based on contrast-enhanced CT and MRI scans acquired using optimized parameters.All 46 patients underwent laparoscopic partial nephrectomy performed by the same qualified surgeon,and postoperative pathological analysis confirmed renal tumors,including 27 cases of clear cell carcinoma,7 cases of chromophobe cell carcinoma,5 cases of papillary cell carcinoma,2 cases of sarcomatoid carcinoma,and 5 cases of angiomyolipoma.No significant differences were observed in baseline clinical characteristics(including age,body mass index,tumor diameter,and RENAL score)between the two groups(P＞0.05).The experimental group showed significantly lower values in total operative time,warm ischemia time,intraoperative blood loss,pre-to postoperative hemoglobin changes,and pre-surgical to one-month post-surgical creatinine changes compared to the control group(P＜0.01).Additionally,the experimental group exhibited smaller changes in hospitalization duration,time to drain removal,and glomerular filtration rate from preoperative to one month post-surgery;however,these differences were not statistically significant(P=0.175,P=0.331,and P=0.273).There were no intraop-erative complications or damage to the collecting system in either the experimental or control groups.Postopera-tively,the control group experienced one case of positive surgical margin,one case of hemorrhage,and one case of subcutaneous emphysema.No statistically significant differences were observed between the groups(P＞0.05).Conclusions 3D digital holographic imaging combined with intraoperative navigation technology,based on the fusion of MRI and CT data,facilitates preoperative planning and precise intraoperative guidance.This approach helps reduce operative time,preserve renal function,and lower perioperative risks while ensuring therapeutic efficacy.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.