Objective:To investigate the predictive value of pregnancy-associated plasma protein A(PAPP-A),fasting blood glucose(FPG),body mass index(BMI)and age in gestational diabetes mellitus(GDM)during the first trimester.Methods:A retrospective analysis was performed on 792 pregnant women who underwent pre-natal examination and delivered in Sichuan Provincial Maternal and Child Health Care Hospital from December 2021 to June 2022.They were divided into GDM group(232 cases)and control group(560 cases)according to whether they had GDM.The clinical data,serum PAPP-A median multiple(PAPP-A MoM)in early pregnancy and FPG levels were compared between the two groups.The indicators with statistical significance in univariate analy-sis were included in multivariate Logistic regression analysis to analyze the related factors affecting the occurrence of GDM.The receiver operating curve(ROC)and area under the curve(AUC)of different indexes were plotted to compare the efficacy of GDM prediction.Results:①The age,pre pregnancy BMI,early pregnancy FPG and the proportion of assisted reproductive technology in GDM group were higher than those in control group,and the differences were statistically significant(P＜0.05).The early pregnancy PAPP-A MoM level in GDM group was lower than that in control group,and the difference was statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that older age,lager pre-pregnancy BMI and lager FPG in the first trimester were in-dependent risk factors for GDM occurrence(OR＞1,P＜0.05),while an increase of PAPP-A MoM in the first tri-mester was a protective factor(OR＜1,P＜0.05).③ROC showed that the combination of PAPP-A MoM in early pregnancy,FPG in early pregnancy,BMI in pre-pregnancy and age had the highest AUC(0.752)when predicting GDM,with a sensitivity of 55.6％and a specificity of 84.3％.Conclusions:The combined screening of serologi-cal(PAPP-A +FPG)and clinical data(pre-pregnancy BMI +age)in early pregnancy has a high clinical application prospect and can be popularized.

Even though retinal images of objects change their locations following each eye movement, we perceive a stable and continuous world. One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information. There have been several proposals on how this may be done, including eye-position modulation (gain fields) of retinotopic receptive fields (RFs) and craniotopic RFs. In the present study, we investigated coordinate systems used by RFs in the lateral intraparietal (LIP) cortex and frontal eye fields (FEF) and compared the two areas. We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation. The same recording and analysis procedures were applied to the two brain areas. We found that, in both areas, RFs were distributed from retinotopic to craniotopic representations. There was no significant difference between the distributions in the LIP and FEF. Only a small fraction of neurons was fully craniotopic, whereas most neurons were between the retinotopic and craniotopic representations. The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts. These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF, and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.
Animals ; Macaca ; Visual Fields ; Frontal Lobe/physiology* ; Eye Movements ; Brain

Objective:To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse ( HR=3.91, 95% CI 1.96-7.79; HR=4.15, 95% CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse ( HR=6.50, 95% CI 2.58-16.34; HR=5.19, 95% CI 1.78-15.16), with ETV6::RUNX1 ( HR=0.23, 95% CI 0.07-0.74) and HSCT after relapse ( HR=0.24, 95% CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions:Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

ObjectiveAlthough expression of the TEAD1 protein in preadipocytes has been established, its function remains unclear. In this study, we sought to detect transcripts of TEAD1 in chicken and to examine the effects of this protein on the proliferation, migration, apoptosis, and differentiation of immortalized chicken preadipocyte cell lines (ICP1). MethodsThe full-length sequence of the TEAD1 gene was cloned and the two transcripts were subjected to bioinformatics analysis. The subcellsular localization of TEAD1 transcripts was determined based on indirect immunofluorescence. The effects of TEAD1 transcripts overexpression on the proliferation of ICP1 cells were examined by RT-qPCR, CCK-8, and EdU assays; the effects of TEAD1 transcripts on ICP1 cells migration were examined based on the scratch test; and the effects of TEAD1 transcripts overexpression on ICP1 cells apoptosis were analyzed using apoptosis-Hoechst staining and RT-qPCR. The expression of TEAD1 transcripts in different tissues, cells lines, and ICP1 at different periods of differentiation was analyzed by RT-qPCR. The effects of TEAD1 transcripts overexpression on lipid droplet accumulation and adipogenic-related gene expression in ICP1 cells were analyzed based on Oil Red O and BODIPY staining, RT-qPCR, Western blot, and dual-luciferase reporter gene assays. Finally, the content of triglyceride (TG) was measured in TEAD1 overexpressed ICP1 cells. ResultsThe full-length TEAD1 was cloned and two TEAD1 transcripts were identified. The TEAD1-V1 protein was found to be localized primarily in the cell nucleus, whereas the TEAD1-V2 protein is localized in the cell cytoplasm and nucleus. The overexpression of both TEAD1-V1 and TEAD1-V2 significantly inhibited the proliferation of ICP1 cells. Whereas the overexpression of TEAD1-V1 promoted ICP1 cell migration, the overexpression of TEAD1-V2 had no significant effects on ICP1 migration; the overexpression of both TEAD1-V1 and TEAD1-V2 significantly promoted the apoptosis of ICP1 cells. We found that the different transcripts of TEAD1 have similar expression pattern in different tissues and cells lines. During induced preadipocyte differentiation, the expression of these genes initially declined, although subsequently increased. Overexpression of TEAD1-V1 promoted a significant reduction in lipid droplet formation and inhibited C/EBPα expression during the differentiation of ICP1 cells (P<0.05). However, the overexpression of TEAD1-V2 had no significant effect on lipid droplet accumulation or the expression of adipogenic-related proteins (P>0.05). Overexpression of TEAD1-V1 significantly decreased triglyceride content in ICP1 cells (P<0.05), while overexpression of TEAD1-V2 had no effect on triglyceride content in ICP1 cells (P>0.05). ConclusionIn this study, for the first time, identified two TEAD1 transcripts. Overexpressed transcripts TEAD1-V1 and TEAD1-V2 both inhibited the proliferation of chicken preadipocytes and promoted apoptosis of chicken preadipocytes. TEAD1-V1 inhibited the differentiation of preadipocytes and promoted the migration of preadipocytes, while TEAD1-V2 had no effect on the differentiation and migration of preadipocytes.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To establish a cell line stably expressing the transient receptor potential melastatin 2(TRPM2)channel for screening TRPM2 inhibitors based on PiggyBac transposition system.Methods:A plasmid PiggyBac-human TRPM2(pPB-hTRPM2)eukaryotic expression vector was constructed using PiggyBac transposition system.The plasmid and a helper plasmid were co-transfected into HEK293T cells to express TRPM2,which was identified by fluorescence and patch-clamp assays.The high throughput screening performance was assessed with the Z'factor.Calcium imaging and patch clamp techniques were employed to assess the initial activity of eleven compound molecules,confirming the inhibitory effects of the primary molecules on TRPM2.The protective effect of the screened compounds on damaged cells was validated using the oxygen-glucose deprivation/reperfusion(OGD/R)injury model and CCK-8 kit.The level of cellular reactive oxygen species(ROS)was detected by flow cytometry.The neuroprotective effects of the compounds were evaluated using a transient middle cerebral artery occlusion(tMCAO)mouse model.Results:The HEK293T cells transfected with pPB-hTRPM2-EGFP showed high TRPM2 expression.Puromycin-resistant cells,selected through screening,exhibited robust fluorescence.Whole-cell patch results revealed that induced cells displayed classical TRPM2 current characteristics comparable to the control group,showing no significant differences(P＞0.05).With a Z'factor of 0.5416 in calcium imaging,the model demonstrated suitability for high-throughput screening of TRPM2 inhibitors.Calcium imaging and electrophysiological experiments indicated that compound 6 significantly inhibited the TRPM2 channel.Further experiments showed that 1.0 μmol/L of compound 6 enhanced cell viability(P＜0.05)and reduced the level of ROS(P＜0.05)of SH-SY5Y under OGD/R injury.0.3 and 1.0 mg/kg of compound 6 reduced the cerebral infarction volume in tMCAO mice(both P＜0.05).Conclusions:A stable TRPM2 gene expressing cell line has been successfully established using PiggyBac gene editing in this study.TRPM2 channel inhibitors were screened through calcium imaging and patch clamp techniques,and an inhibitor compound 6 was identified.This compound can alleviate cell damage after OGD/R by reducing cellular ROS levels and has a protective effect against cerebral ischemia-reperfusion injury in mice.

Objective To study the changes in related parameters after secondary preparation of blood components,in order to further improve the quality of blood components.Methods Different centrifugation conditions were selected for the preparation of primary blood component red blood cells in additive solution leukocytes reduced,and the quality was tested.Then,using the red blood cells in additive solution leukocytes reduced as the initial blood for secondary preparation,and the red blood cells were washed through the Haemonetics ACP 215 device,and the quality was tested.The preparation pa-rameters of blood components were observed,compared and optimized.Results Under comparable centrifugation effects of different centrifugation conditions,the quality control items,which of primary blood components of red blood cells in additive solution leukocytes reduced and frozen plasma prepared by the separation,such as volume,hemoglobin,hematocrit and re-sidual white blood cells met the relevant national standards.And the quality control items of secondary blood components of washed red blood cells such as the hemoglobin and superalbumin content both met the relevant national standards,while vol-ume exceeded the standard by 7-14 mL,which can be operated to the standard range.In addition,the recovery rate of red blood cells and the clearance rate of plasma protein could reach 75%and 99%respectively.Conclusion There is a certain correlation between primary and secondary preparation of blood components,but the relevant parameters of secondary prepa-ration of blood components can be flexibly adjusted according to the actual situation to ensure that the quality of prepared blood component products meet the national standards,thus ensuring clinical treatment effect and safety.