Objective: To investigate the trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

To investigate the clinical utilization of Rituximab biosimilar (Rituximab injection) in order to provide references for evaluating its rationality and economic value in clinical application.

Objective To assess the exposure levels of heavy metals,including lead,arsenic,mercury,and cadmium,in the local population in Sichuan and Chongqing,China,to compare and analyze the differences in reference intervals(RIs)obtained from direct and indirect sampling methods,and to explore the interchangeability and limitations of these two sampling methods.Methods RIs were obtained by the direct sampling method and the indirect sampling method.In the direct sample method,the levels of blood arsenic,urinary cadmium,urinary mercury,and blood lead levels of 5562 healthy participants aged 22-50 years in Sichuan and Chongqing,China were measured by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry.Using the human biomonitoring(HBM)data,we established RIs for the population by a nonparametric method.On the other hand,in the indirect sampling method,RIs were established via a nonparametric method based on data from the laboratory information system(LIS)of a local hospital after stratifying healthy individuals using a Gaussian mixture model(GMM).Comparative analysis of the RIs derived from the two sampling methods were then conducted.Results The RI for blood arsenic was 0.11-1.3 μmol/L.The RI for urinary cadmium was 0.51-2.80 μmol/mol creatine for adults aged 22 to under 43 years and 0.66-2.96 μmol/mol creatine for adults aged 43-50 years.The RI for urinary mercury was 0.12-1.10 μmol/mol creatine.The RI for blood lead was 14.00-47.00 pg/L for adults aged 22 to under 41 year,16.00-53.38 pg/L for males aged 41-50 year,and 15.00-51.02 pg/L for females aged 41-50 year.Most of the RIs established by the direct sampling method had a narrower range compared to those established by the indirect sampling method,and the RIs established by both sampling methods were partially biased.Conclusions The RIs for blood arsenic,urine cadmium,urine mercury,and blood lead in healthy individuals aged 22-50 years in Sichuan and Chongqing,China were established using both direct and indirect sampling methods,which contributes to a better understanding of environmental exposure to metals in the general population and provides a reference for metal poisoning.For data from the same lab,the GMM-based indirect sampling method demonstrated relatively consistent performance in establishing RIs compared with the direct sampling method.

Objective To establish an analytical method for the simultaneous determination of 18 perfluoroalkyl compounds(PFCs)in tea leaves using a quick,easy,cheap,effective,rugged,and safe(QuEChERS)method for sample pretreatment combined with ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Methods The target analytes—18 PFCs—included 13 carboxylic acid PFCs(perfluorobutanoic acid[PFBA],perfluoropentanoic acid[PFPeA],perfluorohexanoic acid[PFHxA],perfluoroheptanoic acid[PFHpA],perfluorooctanoic acid[PFOA],perfluorononanoic acid[PFNA],perfluorodecanoic acid[PFDA],perfluoroundecanoic acid[PFUdA],perfluorododecanoic acid[PFTrDA],perfluorotridecanoic acid[PFTeDA],perfluorotetradecanoic acid[PFHxDA],perfluorohexadecanoic acid[PFHpS],and perfluorooctadecanoic acid[PFODA])and 5 sulfonic acid PFCs(perfluorobutanesulfonic acid[PFBS],perfluorohexanesulfonic acid[PFHxS],perfluoroheptanesulfonic acid[PFHpS],perfluorooctanesulfonic acid[PFOS],and perfluorodecanesulfonic acid[PFDS]).The QuEChERS pretreatment parameters were systematically optimized using the response surface methodology.The tea leave samples were extracted with an 80%acetonitrile solution and subsequently purified by adding a mixed absorbent consisting of 20 mg N-propyl-ethylenediamine(PSA),210 mg graphitized carbon black GCB),and 60 mg octadecylsilane(C18).The supernatant was concentrated by nitrogen blowing and subsequently re-dissolved in 50%methanol-2 mmol/L ammonium acetate solution.The re-dissolved solution was injected into the UHPLC-MS/MS for analysis.The target analytes were separated on an ACQUITY UPLC BEH C18 column(2.1 mm×50 mm,1.7 μm).The mobile phases consisted of methanol(phase A)and 2 mmol/L aqueous ammonium acetate(phase B),with a gradient elution procedure.The total running time was 18 min.The mass spectrometry analysis was conducted using an electrospray ionization source in negative ionization mode and multi-reaction monitoring(MRM),with quantification performed using the internal standard curve method.The greenness of the analytical method was assessed using Analytical GREEnness calculator(AGREE)and the Analytical Eco-Scale method(AES).Results Under the optimized conditions,the limits of detection(LODs)and limits of quantification(LOQs)of the method were 0.005 7-1.23 ng/g and 0.019-4.09 ng/g,respectively.The average recoveries of most target compounds were 71.1%-117.9%,with relative standard deviations(RSDs)below 15%.The AGREE index of the method was 0.49,and the AES score was 76.At least one PFC was detected in each of the 132 tea leave samples,and the detection rate of carboxylic acid PFC was higher than that of sulfonic acid PFC.The highest detection rates were observed for PFBA at 97.74%,PFHpA at 93.23%,and PFOA at 92.24%.In contrast,PFHpS,PFUdA,PFDoA,PFHxDA,and PFODA were not detected in the samples.Conclusion The proposed method has the advantages of simplicity,rapidity and sensitivity,and is suitable for the analysis of PFCs in tea leaves.The method has high greenness with minimal impact on the operator and the environment.The widespread presence of PFC contamination in tea leaves available in the market warrants strengthened monitoring and regulatory control.

Objective: To analyze the trends in disease burden of tuberculosis among children under 5 years of age in China from 1990 to 2021, so as to provide insights for future tuberculosis control measures among children in China. Methods: Based on the Global Burden of Disease (GBD) 2021 datasets, the incidence, prevalence, mortality and disability adjusted life year(DALY) of tuberculosis of children under 5 years of age in China and globally were collected from 1990 to 2021. The incidence, prevalence, mortality and DALY rate of tuberculosis were compared by genders and types. In addition,the annual percent change(APC) and the average annual percent change(AAPC) of children s tuberculosis burden in China and globally from 1990 to 2021 were calculated by using the Joinpoint regression model, and the changing trends were analyzed. Results: The numbers of incident, prevalent and dead tuberculosis cases were 9 700, 8 477 800 and 200 among children under 5 years of age in China in 2021, and the DALY due to tuberculosis were 27 100 person years. There were significant reductions in incidence, prevalence, mortality and DALY rate of tuberculosis among children under 5 years of age in China ( AAPC =-5.45%, -1.14%, -12.37%, -11.34 %) and globally( AAPC =-2.38%, -1.41%, -4.66%, -4.56%), and the reductions in the incidence, mortality and DALY rate were more significant in China than globally ( P <0.05).In 1992 and later, the numbers of incident, prevalent and dead tuberculosis cases and the DALY of tuberculosis were higher among male than among female. In addition, the disease burden of drug susceptible tuberculosis appeared a tendency of downward in China from 1990 to 2021, while the incidence and prevalence of extensively drug resistant tuberculosis rose since 2015. Conclusions The disease burden of tuberculosis remarkably reduced among children under 5 years of age in China from 1990 to 2021. However, the burden of disease due to multidrug resistant tuberculosis appeared an upward trend recently. Increased attention is required to be paid to the prevention and control of tuberculosis among children and improved diagnosis and treatment of drug resistant tuberculosis are recommended.

Objective To investigate the clonal rearrangement characteristics and clinical application value of IGH gene in B-cell non-Hodgkin's lymphoma(B-NHL).Methods Demographic and clinical data as well as IGH sequencing results of 55 patients with B-NHL who underwent next-generation sequencing(NGS)testing were collected,and IGH gene clonal rearrangement was detected.The characteristics of IGH gene clonal rearrangement,IGHV gene usage,and the clinical application value of NGS for IGH clonal rearrangement were analyzed.Results Among 55 patients with B-NHL and IGH clonal rearrangement,single dominant clones were mainly detected(85.45%,47/55);a few patients had two(12.73%,7/55)and three dominant clones(1.82%,1/55).In terms of preference for IGHV gene usage,IGHV3 gene had the highest frequency of access in B-NHL,followed by IGHV4.Among the IGHV subtypes,IGHV3-23 had the highest frequency in chronic lymphocytic leukemia/small lymphocytic lymphoma,and IGHV4-34 had the highest frequency in primary central nervous system diffuse large B-cell lymphoma and not otherwise specified diffuse large B-cell lymphoma.Conclusion A preference for IGHV gene usage in clonal rearr-angement of IGH genes is noted in B-NHL patients with different pathological types.Using NGS to detect IGHclonal rearrangement can identify subclones and clonal correlations,and assist in disease diagnosis.

Objective:To enhance comprehension of undifferentiated embryonal sarcoma of the liver(UESL)in children by analyzing ultra-sound,CT,and MRI imaging features.Methods:A retrospective analysis was conducted on 11 cases of UESL in children,confirmed through surgery and pathology,at the Children's Hospital,Affiliated Capital Institute of Pediatrics from December 2009 to December 2021.We ana-lyzed the ultrasound,CT,and MRI imaging features of all patients and summarized their characteristics.Results:All 11 cases presented with solitary hepatic masses ranging from 11.5 to 19.8 cm in diameter.Imaging manifestations of UESL correlated with component proportion and distribution within the masses.Lesions displayed clear boundaries in all cases.CT scans revealed mixed low density in 11 cases,with ir-regular floc soft tissue density shadows observed at the edge of cystic density areas or around partitions in a few cases.Ultrasound images of all six cases showed solid space-occupying masses,with varying sizes of anechoic regions within the solid mass.MRI T1WI showed mixed low intensity signal in three cases and strip/large high intensity signal areas in the lesion.T2WI revealed mixed high intensity signal and strip low intensity signal areas in 3 lesions.In the arterial phase,lesions displayed slightly to moderately heterogeneous strip/patch enhancement,primarily marginal enhancement in nine cases and thickened,tortuous arterial shadows in eight cases.In the delayed phase,lesions showed continuous uneven enhancement,with enhancement at the edge and peripheral-to-central filling observed in eight cases.Additionally,the enhancement range continuously increased in eight cases,with the false capsule sign identified in eight cases in the delayed stage.Conclu-sions:Imaging features of UESL in children exhibit distinct characteristics.Understanding these features,in conjunction with clinical findings,may aid in early diagnosis.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective To explore the correlation between erythrocyte distribution width(RDW),medium molecular fragment of osteocalcin N segment(N-MID OC)/special sequence β carboxy-terminal peptide of collagen I(β-CTX)ratio and the risk of hip fracture in elderly women.Methods A total of 731 female patients over 60 years old who were hospitalized in Sichuan Orthopedics Hospital from January 2021 to December 2021 were selected.There were 375 cases with fracture and 358 cases without fracture.The clinical baseline data were collect-ed.Binary logistic regression model was used to analyze the correlation between RDW-CV,N-MID OC/β-CTX ratio and hip fracture in elderly women.Results Logistic regression analysis showed that age,RDW-CV,N-MID OC/β-CTX,calcium(Ca)and phosphorus(P)levels were risk factors for hip fracture in elderly women.The values of RDW-CV and N-MID OC/β-CTX were divided into three levels in equal proportion after ordering from small to large,and the results showed that the higher the RDW-CV and the lower the N-MID OC/β-CTX ratio,the higher the risk of hip fracture in elderly women(P＜0.05).According to receiver operating characteristic curve(ROC),both single test and combined test may be used to diagnose fracture,but combined test may improve the diagnostic performance,with area under curve(AUC)of 0.729,sensitivity and specificity of 60.53%and 75.42%,respec-tively.Conclusions RDW-CV and N-MID OC/β-CTX ratio are associated with hip fracture in elderly women.