Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Objective To explore clinical efficacy of osteoplasty combined with percutaneous vertebroplasty(PVP)and percutaneous kyphoplasty(PKP)alone in treating osteoporosis vertebral compression fractures(OVCFs).Methods The clini-cal data of 80 patients with single-level OVCFs treated from January 2021 to June 2022 were retrospectively analyzed,and were divided into treatment group and control group according to different surgical methods,40 patients in each group.In treatment group,there were 24 males and 16 females,aged from 60 to 83 years old with an average of(70.43±7.31)years old;bone min-eral density ranged from-3.30 to-2.50 SD with an average of(-2.84±0.24)SD;1 patient with T10,4 patients with T11,11 pa-tients with T12,7 patients with L1,7 patients with L2,5 patients with L3,3 patients with L4,2 patients with L5;bone setting tech-nique combined with PVP were performed.In control group,there were 27 males and 13 females,aged from 60 to 82 years old with an average of(68.98±6.94)years old;bone mineral density ranged from-3.40 to-2.50 SD with an average of(-2.76±0.23)SD;2 patients with T10,3 patients with T11,13 patients with T12,11 patients with L1,5 patients with L2,3 patients with L3,2 patients with L4,1 patient with L5;simple PKP were peformed.Visual analogue scale(VAS)and lumbar Oswestry disability in-dex(ODI)were compared between two groups before operation,3 days,3 and 12 months after operation.The changes of local kyphotic angle,vertebral wedge angle and vertebral anterior margin height ratio were compared between two groups before op-eration,3 days and 12 months after operation.Results All patients were successfully completed operation.Treatment group were followed up from 13 to 22 months with an average of(16.82±2.14)months,and control group were followed up from 13 to 23 months with an average of(16.45±2.56)months.Three patients were occurred bone cement leakage in treatment group,while 1 patient were occurred bone cement leakage and 1 patient occurred sensory disturbance of lower limb skin in control group;there were no significant difference in complications between two groups(P＞0.05).There were no significant difference in preoperative VAS and ODI between two groups(P＞0.05).At 3 days after operation,VAS of treatment group 3.68±0.62 was significantly higher than that of control group 4.00±0.72(P＜0.05).There were no significant difference in VAS and ODI be-tween two groups at 3 and 12 months after operation(P＞0.05).There were no significant difference in local kyphotic angle,vertebral wedge angle and vertebral anterior margin height between two groups at 3 days and 12 months after operation(P＞0.05).Conclusion Compared with PKP,bone setting manipulation combined with PVP for the treatment of OVCFs has advan-tages in early postoperative pain relief.In terms of vertebral height recovery,bone setting manipulation combined with PVP and PKP alone have similar clinical effects.

Objective:To analyze the efficacy and influencing factors of cyclosporine(CsA)alone in the treatment of children with acquired aplastic anemia(AA).Methods:The clinical data of children diagnosed with AA and treated with CsA alone from January 1,2016 to December 31,2020 in the Children's Hospital of Chongqing Medical University were collected,and the efficacy and influencing factors of CsA treatment were evaluated.Results:Among the 119 patients,there were 62 male and 57 female,with a median age of 7 years and 1 month.There were 45 cases of very severe AA(VSAA),47 cases of severe AA(SAA),and 27 cases of non-severe AA(NSAA).At 6 months after treatment,the efficacy of VSAA was lower than that of SAA and NSAA,and there was a statistical difference(P＜0.01).6 cases died early,16 cases relapsed,2 cases progressed to AML and ALL.The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA,while high PLT count was a protective factor(P=0.008,P=0.002).The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5 × 109/L,68.5％,respectively.Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST(P=0.020,OR=0.062),and high PLT count was a protective factor(P=0.044,OR=1.038).At 3 months of treatment,CsA response and NSAA were the risk factor for recurrence(P=0.001,0.031).Conclusion:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone.A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA,and a high proportion of bone marrow lymphocyte was an unfavorable factor.CsA response at 3 months and NSAA were risk factors for recurrence.

Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length,and the shorter the telomere,the longer the disease course,the more prone to relapse,the lower the overall survival rate,and the higher the probability of clonal evolution.The regulation of telomere length is affected by many factors,including telomerase activity,telomerase-related genes,telomere regulatory proteins and other related factors.Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia.This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.

Objective:To investigate the feasibility of a three-dimensional no new U-Net (3D nnU-Net) deep learning (DL) network for the automatic segmentation of colorectal cancer (CRC) based on abdominal CT images.Methods:This was a cross-sectional study. From January 2018 to May 2023, a total of 2180 primary CRC patients, confirmed by pathology at the Guangdong Provincial Hospital of Traditional Chinese Medicine (center 1, n=777), Nanfang Hospital, Southern Medical University (center 2, n=732), and Sun Yat-sen Memorial Hospital (center 3, n=671), were enrolled in this retrospective study. The baseline abdominal CT examination of each patient was conducted using CT equipment from 7 different models across 4 vendors, at the 3 centers, encompassing both the arterial phase (AP) and venous phase (VP). Two radiologists manually delineated the volume of interest to circumscribe the entire tumors in dual-enhanced phase CT images. The CT data of CRC patients from center 1 and center 3 were merged and divided into a training set ( n=1 159) and a validation set ( n=289) using a weighted random method with a ratio of 4∶1. The patients from center 2 were used as an independent external test set ( n=732). The 3D nnU-Net segmentation model was trained and tested. Using manually annotated label data as the benchmark, segmentation performance of the model was evaluated based on different phases and tumor locations. The segmentation coverage rate (SCR), Dice similarity coefficient (DSC), recall (REC), precision (PRE), F1-score, and 95% Hausdorff distance (HD 95) were calculated. The mean manual segmentation time and the mean automatic time were compared using independent samples t-test. Results:In the independent external test set, the performance of the 3D nnU-Net model based on the AP CT images was superior to that based on the VP CT images. On the AP images, the SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.865, 0.714, 0.716, 0.736, 0.714, and 27.228, respectively; on the VP images, they were 0.834, 0.679, 0.710, 0.675, 0.679, and 29.358, respectively. The model achieved the best performance on right-sided colon cancer, with SCR, DSC, REC, PRE, F1-score, and HD95 on the AP CT images at 0.901, 0.775, 0.780, 0.787, 0.775, and 21.793, respectively. Next were left-sided colon cancer and rectal cancer, while the segmentation performance for transverse colon cancer was the worst (SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.731, 0.631, 0.641, 0.630, 0.631 and 38.721, respectively). The automatic segmentation time on a single phase was (1.0±0.3) min, while the manual segmentation time was (17.5±6.0) min ( t=128.24, P<0.001). Conclusions:After training and validating on a dataset from multiple centers with various CT scanner vendors, the 3D nnU-Net DL model demonstrates the capability to automatically segment CRC based on abdominal CT images, while also showcasing commendable robustness and generalization ability.

Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.
Humans ; Prognosis ; Apoptosis ; Regulated Cell Death ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Tumor Microenvironment

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: To propose the an optimal screw placement scheme to prevent femoral neck shortening, finite element analysis was used to evaluate the biomechanical outcome of different numbers formed by full threaded screws at different positions in the treatment of femoral neck fractures of Pauwels type Ⅱ. METHODS: Recruited for this study was a 55-year-old female volunteer with a weight of 70 kg and a height of 165 cm. CT scan data of her right femur was collected. The models of femoral of Pauwels typeⅡ and fully threaded screw(FTS) and partially threaded screw(PTS) were constructed in three-dimensional modeling software. All these screw placement schemes were divided into eight groups simulated the inverted triangular configuration:three PTSs, an anterosuperior FTS and two PTSs, a posterosuperior FTS and two PTSs, an inferior FTS and two PTSs, an anterosuperior PTS and two FTSs, a posterosuperior PTS and two FTSs, an inferior PTS and two FTSs and three FTSs. All fracture internal fixation models were processed in finite element analysis software. Parameters of postoperative femoral neck length, displacement distribution and peak displacement of screws and VonMises stress distribution and peak stress of screws, the proximal femur and fracture section were collected. RESULTS: The maximum VonMises stress of screws was 239.71, 213.44, 199.37, 230.82, 201.63, 215.72, 185.65 and 192.64 MPa, respectively, which was concentrated in the inferior screw near the fracture line. The maximum Von Mises stress of the proximal femur was 269.48, 241.62, 249.43, 269.69, 271.60, 346.64, 236.97 and 439.62 MPa, respectively, which was concentrated in the inferior medial area of subtrochanteric femur. The maximum Von Mises stress of fracture section was 149.12, 143.04, 140.47, 139.63, 139.81, 130.07, 117.77 and 57.89 MPa, respectively, which was concentrated around the partially threaded screw channel instead of the fully threaded screw channel. The maximum displacement of screws was 5.52, 5.43, 5.32, 5.17, 5.05, 5.13, 5.28 and 5.04 mm, respectively, which was along the axis of the femoral neck, and the displacement distribution was concentrated on the tip of the screw. The length of postoperative femoral neck length was 74.69, 74.72, 74.70, 74.70, 74.72, 74.70, 74.72 and 74.74 mm, respectively. CONCLUSION The placement of one anterosuperior partially threaded screw and two fully threaded screws with an inverted triangular distribution can not only meet the sliding compression effect to promote femoral neck healing and ensure the stability of the proximal femur, but also reduce the degree of postoperative femoral neck shortening and reduce the incidence of hip joint dysfunction. This study provides a new optimal screw placement solution for the treatment of femoral neck fractures.
Female ; Humans ; Middle Aged ; Bone Screws ; Femoral Neck Fractures/surgery* ; Femur Neck ; Finite Element Analysis ; Software ; Fracture Fixation, Internal

OBJECTIVE: To establish a culture system for human nasal mucosal organoids with controllable differentiation to reproduce the structure and function of the source tissue through staged expansion-differentiation culture. METHODS: Fresh samples of surgically resected middle turbinate and nasal polyp tissues were collected, from which the nasal mucosa epithelial cells were isolated by enzymatic digestion and filtration for continuous culture at the air-liquid interface for expansion (EO group) or staged culture for expansion and differentiation (DO group). Immunohistochemical staining was used to characterize the structure, cellular composition and ciliary function of nasal mucosal organoids in the two groups. The secretion function of the differentiated nasal mucosal organoids in DO group was evaluated using PAS staining. RESULTS: Both of the two organoid culture systems yielded vacuolar or solid spherical 3D organoids, and their diameters increased progressively with time. On day 16 of culture, more vacuolar organoids occurred in DO group, while more solid spherical organoids were seen in EO group, and the proportion of vacuoles was significantly greater in DO group than in EO group [(54.67±13.26)% vs (21.67±8.57)%, P < 0.05]. Short tandem repeat (STR) test of the nasal mucosal organoids and the source tissue showed a 100% match between them. On day 21 of culture, scanning and transmission electron microscopy of the nasal mucosal organoids identified ultrastructure of cilia in DO group and short villi structure in most of the organoids in EO group. Immunohistochemical staining showed positivity for P63 (basal cells), β-tubulin (ciliated columnar cells), and MUC5AC (goblet cells) in the organoids. Compared with those in EO group, the organoids in DO group showed significantly greater percentages of ciliated cells [(7.95±1.81)% vs (27.04±5.91)%, P < 0.05] and goblet cells [(14.46±0.93)% vs (39.85±5.43)%, P < 0.05) with a similar percentage of basal cells [(56.91±14.12)% vs (53.42±15.77)%, P > 0.05]. The differentiated nasal mucosal organoids in DO group were positively stained for glycogen. CONCLUSION The staged expansion-differentiation culture method allows more stable and prolonged growth of the cultured cells in vitro to produce organoids with controllable differentiation closely resembling the morphological structure and functions (ciliary function and secretory function) of the source tissue.
Cell Differentiation ; Cells, Cultured ; Epithelial Cells ; Humans ; Nasal Mucosa ; Organoids