Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10 8/kg, and the number of CD34 + cells was 3.29 (2.53-6.10) ×10 6/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

Objective:To compared the changes of macular microvascular architecture in early stage familial exudative vitreoretinopathy (FEVR) patients with inner retinal layer (IRL) persistence and without IRL persistence.Methods:A retrospective clinical study. From 2017 to 2022, 94 patients with stage 1 FEVR with or without IRL residue and 45 age- and sex-matched healthy volunteers with 45 eyes (normal control group) who were confirmed by ophthalmology examination in Hangzhou Hospital of Optometry Affiliated to Wenzhou Medical University and Zhejiang Provincial People's Hospital were included in the study. According to whether there was IRL residue, the patients were divided into IRL group and non-IRL group, with 22 patients (22 eyes) and 72 patients (72 eyes), respectively. Best corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) were performed in all eyes. Superficial vessel density (SCP) and deep vessel density (DCP) of whole image, fovea and parafovea, the area and perimeter of fovea avascular area (FAZ), A-circularity index (AI, perimeter/standard circle perimeter with equal area) and vessel density around the 300 μm width of the FAZ (FD), central macular thickness (CMT) on macular 3 mm × 3 mm scan on OCTA were measured.Results:SCP and DCP of whole image ( F=10.774, 4.583) and parafovea ( F=10.433, 3.912), CMT ( F=171.940) in IRL group and non-IRL group on macular 3 mm × 3 mm scan on OCTA were significantly lower than that in normal persons ( P<0.05). There were significant differences among three groups of the area of FAZ ( F=4.315), AI ( F=3.413), FD-300 ( F=13.592) ( P<0.05). BCVA were worst in IRL group ( P<0.05). Conclusions:Blood flow density decreased in macular area of FEVR patients. CMT is significantly thicker than normal population. The FAZ area of the foveal IRL residual eyes is small and irregular, with worse BCVA and lower macular blood density.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To investigate the prevalence of anxiety and depression in patients undergoing thoracic tumor radiotherapy, preliminarily evaluate the nutritional risk of patients, and analyze the possible influential factors of anxiety and depression and their correlation with nutritional risk, providing a theoretical basis for further formulating a personalized psychological nursing plan for patients undergoing thoracic tumor radiotherapy.Methods:A total of 121 patients who underwent thoracic tumor radiotherapy between April 2019 and March 2020 in Cancer Hospital of The University of Chinese Academy of Sciences were selected for this study. We evaluated patients' psychological statuses using the Hospital Anxiety and Depression Scale and patients' nutritional risk using the Nutrition Risk Screening. We performed univariate analysis, unconditional logistic regression analysis, and contingency analysis to analyze the factors that affected the psychological status of patients undergoing thoracic tumor radiotherapy and correlate patients' psychological status with nutritional risk.Results:Among 121 patients, 99 (81.8%) patients undergoing thoracic tumor radiotherapy would develop or had developed anxiety, and 42 (34.7%) patients were at the boundary of depression or had depression. Correlation analysis revealed that nutritional risk was correlated with the prevalence of anxiety and depression. Logistic regression analysis showed that surgery, first radiotherapy, and nutritional risk were the factors that affected the prevalence of anxiety. Marital status, location of tumors, surgery, first radiotherapy, and nutritional risk affected the prevalence of depression.Conclusion:Patients undergoing thoracic tumor radiotherapy have serious psychological problems. Nutritional risk is positively correlated with the prevalence of anxiety and depression. Surgery and first radiotherapy are the factors that affect the prevalence of anxiety and depression.

Objective:To investigate the risk factors associated with failure of trial of labor in primiparous women with preeclampsia (PE) and to establish a risk prediction model.Methods:Primiparae with PE who underwent trial of labor in the Department of Obstetrics of Suzhou Ninth People's Hospital from February 2018 to July 2020 were retrospectively selected as the modeling set, and divided into two groups: the success group and the failure group. Various parameters were compared between the two groups and those data with statistically significant difference were analyzed with multivariate logistic regression analysis. Those factors related to vaginal delivery failure in primiparous women with PE were identified. Based on the results, a risk prediction model was established using R language. Its performance was assessed with receiver operating characteristic (ROC) curve and goodness-of-fit test. This study also retrospectively enrolled primiparae with PE who underwent trial of labor in the same hospital from August 2020 to December 2021 as the validation set. Bootstrap method was used for verification and a calibration chart was created.Results:A total of 312 PE patients were selected as the modeling set with 89 in the failure group and 223 in the success group. Another 146 primiparae with PE were selected as the validation set. Logistic regression analysis showed that older age ( OR=1.609, 95% CI: 1.251-2.483), higher body fat rate in early pregnancy ( OR=1.456, 95% CI: 1.209-2.159) and higher ratio of umbilical artery systolic to diastolic flow velocity within a week before delivery ( OR=1.799, 95% CI: 1.372-2.794) were risk factors for vaginal delivery failure in primiparae with PE, while more maternal education during pregnancy ( OR=0.233, 95% CI: 0.054-0.672) and higher Bishop score ( OR=0.395, 95% CI: 0.258-0.756) were protective factors. A nomogram model to predict the risks of vaginal delivery failure was constructed based on the above five factors. The area under the ROC curve (AUC) of the modeling set was 0.921 (95% CI: 0.847-0.963) with the cut-off value of 0.213, and the corresponding sensitivity and specificity were 0.871 and 0.852, respectively;goodness-of-fit test showed that the observed values matched with those expected ( χ2=7.69, P=0.464); and the calibration curve indicated that the consistency of the prediction model was good. The AUC of the validation set was 0.903 (95% CI: 0.835-0.942) with the sensitivity and specificity of 0.892 and 0.796, respectively; the discrepancy between the observed values and those expected was not significant as indicated by goodness-of-fit test ( χ2=6.82, P=0.512); calibration curve of the validation set showed that the predicted values of the model was consistent with the actual values. Conclusions:The failure of vaginal delivery in primiparae with PE is associated with maternal age, prenatal body fat percentage, ratio of fetal umbilical artery systolic to diastolic flow velocity within a week before delivery, maternal education during pregnancy and Bishop score. The nomogram model based on these five risk factors for prediction of vaginal delivery failure performs well.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Objective: To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center. Methods: Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed. Results: A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade Ⅲ-Ⅳ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups. Conclusions The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.

Objective To evaluate the efficacy of follicular unit extraction (FUE) in the repair of scarring eyebrow loss.Methods A total of 30 patients with scarring eyebrow loss were treated with FUE technique in the Department of Plastic Surgery of Zhengzhou First People's Hospital,including 18 females and 12 males with 41 eyebrow defects.Fine soft hairs with a length of 5-10 mm were extracted from the back of the ear and temporal region of the patients,and then were split into individual follicular units under a microscope at 6 × magnification.The transplant density ranged from 20 to 30 FU/cm2.Results During the 3-18 months of follow-up after the surgery,eyebrows in the recipient areas grew in a natural direction and showed good appearance.The survival rate of hair grafts was up to 90％,and the patients were satisfied with the results.Conclusion FUE may be an ideal method for the treatment of scarring eyebrow loss with less injury and high survival rate of hair grafts.

Purpose To investigate the diagnostic value of p16/Ki-67 dual stain cytology for detection of cervical precancerous lesions as a novel option for cervical lesions screening.Methods A total of 295 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) from thinprep cytologic test (TCT) were selected.Double staining of p16/Ki-67 cytology,vaginal biopsy,biopsy and pathological examination were applicated,p16/Ki-67 dual stain cytology was compared with that of biopsy and pathological examination.At the same time,The sensitivity and specificity of p16/Ki-67 dual stain cytology between ASC-US and LSIL was analyzed.Results The positive rate of p16/Ki-67 dual stain cytology were 37.42％ and 36.36％ in ASC-US and LSIL,respectively.The positive rate of cervical intraepithelial neoplasia 2/3 (CIN2/3) were 25.77％ and 25.76％.The sensitivity and specificity of the p16/Ki-67 test for detecting CIN2/3 was 83.33％ and 78.51％.The sensitivity and the specificity of the p16/Ki-67 test for detecting CIN2/3 was 85.30％ and 80.61％ in LSIL group.Conclusion p16/Ki-67 double stain cytology detection can improve the sensitivity of CIN2/3 and the specificity of human papilloma virus (HPV).p16/Ki-67 double stain detection can effectively triage the high grade cervical lesions in TCT and improve the accuracy of cervical cancer screening.