Background: Our genomic understanding of lymphomas, a heterogeneous group of neoplasms, has grown exponentially. The latest World Health Organization (WHO) and International Consensus classifications reflect the importance of genetic assessment in the diagnosis and prognostication of and therapeutic decision making in lymphoid neoplasms. To address this clinical need for routinely available and timely testing, we aimed to validate the Ion AmpliSeq Liverpool Lymphoid Network Panel (IALLNP; Thermo Fisher Scientific, Waltham, MA, USA). Methods: We clinically validated the IALLNP on the Ion Torrent Genexus Sequencer (Thermo Fisher Scientific). The panel detects single-nucleotide variants (SNVs) and insertions/deletions (indels) in 60 clinically relevant genes. The validation set included a commercial control and 54 DNA samples covering the spectrum of clinically aggressive and indolent lymphomas. Results: After optimizing for poor coverage regions, recurrent artifacts, and false-negative calls, the panel showed good performance in terms of depth of coverage, on-target reads, and uniformity. Its sensitivity for SNVs and indels at a lower limit of detection of 5% variant allele frequency (VAF) was 100%. Specificity in variant-negative samples was 100%, and the mean per-sample number of false-positive variants—which were easily identifiable and excluded upon interrogation of raw data—was 0.4. The panel demonstrated 92.8% reproducibility; however, all nonreproducible variants fell below the 5% VAF analytical threshold. Conclusions The IALLNP is an accurate and reproducible next-generation sequencing panel that delivers genetic results for lymphoid neoplasms in a clinically meaningful timeframe.

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Child ; Child, Preschool ; Humans ; China ; Practice Guidelines as Topic ; Dyssomnias ; Child Behavior

Objective （ ） To explore the feasibility of using generalized estimating equation GEE to analyze the influencing - （ ） factors of high frequency hearing loss HFHL among noise exposed workers in an air conditioner manufacturing enterprise. Methods - The noise exposed workers in an air conditioner manufacturing industry who had been tested for pure tone hearing threshold twice or more from 2015 to 2019 were selected as the research subjects using the judgment sampling method. Data ， ， ， ， ， （ ） such as age length of service gender smoking alcohol consumption body mass index BMI and HFHL were collected. The Results influencing factors of HFHL were analyzed using the GEE. The detection rates of HFHL from 2015 to 2019 were ， ， ， ， ， 22.2% 23.8% 24.2% 24.1% and 20.9% respectively. Among them the detection rate of HFHL in 2019 was lower than that （ P ） ， ， in 2017 and 2018 all <0.001 . The GEE analysis results showed that the risks of HFHL in 2015 2016 2017 and 2018 were （ P ）， higher than that in 2019 all <0.01 regardless of interaction effects and after adjusting for confounding factors such as ， ［OR（ CI）］ （ - duration of noise exposure smoking and BMI. The odds ratios and 95% confidence intervals 95% were 1.19 1.07 ）， （ - ）， （ - ） （ - ）， 1.33 1.26 1.13 1.39 1.30 1.18 1.43 and 1.27 1.15 1.39 respectively. The risk of HFHL was higher in males than in （P ）， OR（ CI） （ - ） ， （P ）， OR females <0.01 and 95% was 3.78 3.00 4.77 . The older the age the higher the risk of HFHL <0.01 and （ CI） （ - ） Conclusion - 95% was 1.07 1.05 1.09 . The influencing factors of HFHL among noise exposed workers in the air conditioner industry are age and gender. GEE can be used to analyze the factors influencing the longitudinal data of HFHL in workers with noise exposure.

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.

BACKGROUND: TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL. METHODS: We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons. RESULTS: From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line. CONCLUSIONS TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.

Objective:To compare the standards of intellectual impairment in China based on ICF to provide evidences for standardization of identification and services of intellectual impairment. Methods:The national standards of intellectual impairment or injury from Standard of Identification of Work Capacity: Identification Classification of DisabilityCaused by Work-related Injuries, Occupational Diseases and Classification of Impairment Related to Injury and China Insurance Disability Standard and Code were compared under the framework, terminology, coding and evaluation of ICF. Results:These three standards covered ICF three components, including body structure, body function, activity and participation, but not contextual factors. The terminology and coding system of China Insurance Disability Standard and Code came from ICF. However, there was no standardized terminology and coding system among sectors. The classification and evaluation for intellectual impairment were different among these three standards, that made it difficult to compare the outcome directly. Conclusion:It is proposed to adopt the ICF framework and approach to standardize the definition, terms, coding, and evaluation of intellectual impairment in disability standards in China to promote data exchange of evaluation and service among sectors.

A highly sensitive and selective bioluminescent probe for hydrazine (BPH) was designed, synthesized and evaluated for detection of hydrazine in vitro and in vivo. BPH was designed to include a specific recognition group (acetyl) of hydrazine at an appropriate modification site of the optical reporter hydroxyluciferin (D-luciferin), which showed excellent performance both in selectivity and sensitivity to hydrazine. The results showed that the bioluminescent probe BPH developed in this study is an innovative and widely applicable tool for detecting hydrazine in complex natural environment or in animals.

To explore influence of Xinmailong injection on cardiac function and vascular endothelial func‐tion in advanced aged patients with acute myocardial infarction (AMI) heart failure (HF).Methods : A total of 122 advanced aged AMI‐HF patients treated in our hospital from Mar 2015 to Jul 2017 were selected ,randomly and e‐qually divided into routine treatment group (received routine anti‐HF medication ) and Xinmailong group (received Xinmailong injection based on routine treatment group ) ,both groups were treated for 10d and then followed up for six months .LVEF ,wall motion score index (WMSI) ,serum levels of BNP , hsCRP , cTnI ,nitric oxide (NO) ,en‐dothelin (ET)‐1 and inner diameter of brachial artery were observed and compared between two groups before and after treatment .Results : Compared with before treatment ,there were significant rise in LVEF [routine treatment group : (35.42 ± 5.11)% vs. (44.62 ± 5.88)%;Xinmailong group : (36. 13 ± 5.64)% vs. (49.75 ± 6. 18)%] and serum NO level [routine treatmentgroup : (108. 35 ± 21.67) μmol／L vs. (129.68 ± 25. 83 ) μmol／L ; Xinmailong group : (110.26 ± 22.71) μmol／L vs. (156.82 ± 24. 19) μmol／L] ,and significant reductions in WMSI [routine treatment group : (2.49 ± 0.51) score vs. (1.45 ± 0.34) score ; Xinmailong group : (2.51 ± 0.42) score vs. (1. 12 ± 0.27) score] ,NYHA class (routine treatment group :3.19 ± 0. 44 vs. 2.65 ± 0.36 ;Xinmailong group :3. 21 ± 0.42 vs. 2.11 ± 0.28) ,serum levels of BNP [routine treatment group : (986. 72 ± 245.63 ) pg／ml vs. (764.42 ± 217.33) pg／ml ; Xinmailong group : (989.99 ± 243. 54 ) pg／ml vs. (607. 82 ± 198. 65 ) pg／ml ] , hsCRP [routine treatment group : (24.31 ± 3.82) mg／L vs. (14.52 ± 1. 69 ) mg／L ; Xinmailong group :(24.93 ± 3.74) mg／L vs. (7. 81 ± 0. 96) mg／L] ,cTnI [routine treatment group :(5.29 ± 0.43) μg／L vs. (3.01 ± 0. 27) μg／L ;Xinmailong group :(5.37 ± 0.64) μg／L vs. (1.42 ± 0.33) μg／L ] and ET‐1 [routine treatment group :(95. 67 ± 16. 32) ng／L vs. (76. 34 ± 17.82) ng／L ;Xinmailong group :(96.13 ± 17.21) ng／L vs. (57.29 ± 14. 63) ng／L] in two groups ;and LVEF and serum NO level of Xinmailong group were significantly higher than those of routine treatment group , WMSI ,NYHA class ,serum levels of BNP ,hsCRP ,cTnI and ET‐1 of Xinmailong group were significantly lower than those of routine treatment group , P＝0.001 all.Compared with before treatment ,there were significant rise in reactive hyperemia brachial diameter (Dhyperemia ) , fore brachial artery endothelium dependent diastolic‐systolic function (FMD) in Xinmailong group after treatment , and they were significantly higher than those of routine treatment group , P＜0. 05 or ＜0. 01 .Conclusion : Xinmailong injection can significantly improve cardiac function and vascular endothelial function in AMI‐HF patients ,which is worth extending .