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

Objective To explore the current status and influencing factors of returning to work among breast cancer patients by Meta-analysis.Methods Literatures studies on the current status and influencing factors of returning to work among breast cancer patients were systematically searched in databases.The literature was sorted,screened and evaluated,and a total of 15 articles were included,involving 3975 breast cancer patients after surgery.Results After Meta-analysis,the return-to-work rate among breast cancer patients was 48.49％.Age,treatment method,social support,surgical method,and self-efficacy were influencing factors.Conclusion Clinically,early evaluation and intervention should be carried out for patients with relevant factors to improve the quality of life after breast cancer surgery and improve the level of patients' readiness to return to work.

Objective To explore the levels of Kruppel like factor 5(KLF5)and Dickkopf related protein 1(DKK1)in the serum of patients with primary liver cancer and analyze their diagnostic value.Methods A to-tal of 98 patients with primary liver cancer diagnosed in the hospital from March 2021 to March 2024 were in-cluded as the experimental group,and they were divided into early group(40 cases)and late group(58 cases)according to the severity of the disease.Meantime,101 patients with benign liver disease admitted to the hos-pital during the same period time were selected as the control group,and 100 healthy individuals who under-went the physical examination during the same period were selected as the healthy group.Serum samples were obtained from the groups and general clinical data were collected and organized.Enzyme linked immunosor-bent assay was applied to detect the levels of KLF5 and DKK1,and the differences and changes in serum KLF5 and DKK1 levels among the groups were analyzed.Multivariate Logistic regression was applied to ana-lyze the influencing factors of occurrence of primary liver cancer.Receiver operating characteristic curve was used to analyze the efficacy of serum KLF5 and DKK1 levels in the diagnosis of primary liver cancer.Results The levels of alpha fetoprotein(AFP),carcinoembryonic antigen(CEA),KLF5 and DKK1 in the ex-perimental group were significantly higher than those in control group and healthy group(P＜0.05).The lev-els of serum KLF5 and DKK1 were obviously different in patients with primary liver cancer with or without lymph node metastasis(P＜0.05).The levels of serum KLF5 and DKK1 in late group were higher than those in early group(P＜0.05).AFP,CEA,KLF5 and DKK1 levels were independent risk factors for primary liver cancer(P＜0.05).The area under the curve of the combined diagnosis of serum KLF5 and serum DKK1 was 0.928,with specificity of 93.10％,which was better than that of the individual diagnosis(Z combination-DKK1=2.186,Z combination-KLF5=3.386,P=0.029,P=0.001).Conclusion The levels of KLF5 and DKK1 in the serum of patients with primary liver cancer are obviously elevated and change with changes in the condition of dis-ease.The combined detection of KLF5 and DKK1 is of great significance for the diagnosis of primary liver cancer.

Objective To explore the bronchoscopic manifestations of invasive pulmonary fungal disease(IPFD)and evaluate the safety and efficacy of interventional therapy effect.Methods A retrospective analysis was conducted on the clinical data of 35 patients with IPFD who underwent bronchoscopy from May 12,2018 to May 12,2025 to observe the bronchoscopic manifestations and interventional therapy of IPFD.Results 35 patients' clinical data were collected,including 22 males and 13 females,with an age of(53±14)years.The underlying diseases included:10 cases of hematological malignancies,5 cases of long-term use of glucocorticoids,4 cases of type 2 diabetes,2 cases of lung malignancies,and 1 case of organ transplant patient.Chest CT showed that there were 19 cases of lung lesions involving a single lobe and 16 cases involving multiple lobes.The main manifestations under bronchoscopy were 29 cases with mucosal hyperemia and edema(82.9％),22 cases with necrotic substances blocking the lumen(62.9％),17 cases with a large amount of viscous purulent secretions(48.6％),16 cases with partial bronchial stenosis or occlusion(45.7％),9 cases with mucosal necrosis(25.7％),5 cases with mucosal hemorrhage(14.3％),and 3 cases with fungal globules(8.6％).Among them,32 cases(91.4％)received systemic antifungal treatment,17 cases(48.6％)received local amphotericin B perfusion treatment by bronchoscopy,10 cases(28.6％)had the lesion removed by biopsy forceps,6 cases(17.1％)had the lesion frozen by cryoprobe,and 4 cases(11.4％)received argon plasma coagulation treatment.The clinical symptoms of 28 cases(80.0％)improved significantly,and the lung imaging lesions shrank or regressed.Four cases(11.4％)had stable lesions.Three cases(8.6％)did not complete the treatment.Conclusion IPFD is more common in immunosuppressed hosts,bronchoscopy often presents with necrotic substances blocking the lumen,accompanied by purulent secretions,bronchial lumen stenosis,local mucosal hyperemia,edema or necrosis.Systemic antifungal drugs combined with interventional therapy under bronchoscopy have high safety and good therapeutic effects.

Objective To explore the bronchoscopic manifestations of invasive pulmonary fungal disease(IPFD)and evaluate the safety and efficacy of interventional therapy effect.Methods A retrospective analysis was conducted on the clinical data of 35 patients with IPFD who underwent bronchoscopy from May 12,2018 to May 12,2025 to observe the bronchoscopic manifestations and interventional therapy of IPFD.Results 35 patients' clinical data were collected,including 22 males and 13 females,with an age of(53±14)years.The underlying diseases included:10 cases of hematological malignancies,5 cases of long-term use of glucocorticoids,4 cases of type 2 diabetes,2 cases of lung malignancies,and 1 case of organ transplant patient.Chest CT showed that there were 19 cases of lung lesions involving a single lobe and 16 cases involving multiple lobes.The main manifestations under bronchoscopy were 29 cases with mucosal hyperemia and edema(82.9％),22 cases with necrotic substances blocking the lumen(62.9％),17 cases with a large amount of viscous purulent secretions(48.6％),16 cases with partial bronchial stenosis or occlusion(45.7％),9 cases with mucosal necrosis(25.7％),5 cases with mucosal hemorrhage(14.3％),and 3 cases with fungal globules(8.6％).Among them,32 cases(91.4％)received systemic antifungal treatment,17 cases(48.6％)received local amphotericin B perfusion treatment by bronchoscopy,10 cases(28.6％)had the lesion removed by biopsy forceps,6 cases(17.1％)had the lesion frozen by cryoprobe,and 4 cases(11.4％)received argon plasma coagulation treatment.The clinical symptoms of 28 cases(80.0％)improved significantly,and the lung imaging lesions shrank or regressed.Four cases(11.4％)had stable lesions.Three cases(8.6％)did not complete the treatment.Conclusion IPFD is more common in immunosuppressed hosts,bronchoscopy often presents with necrotic substances blocking the lumen,accompanied by purulent secretions,bronchial lumen stenosis,local mucosal hyperemia,edema or necrosis.Systemic antifungal drugs combined with interventional therapy under bronchoscopy have high safety and good therapeutic effects.

Objective To explore the current status and influencing factors of returning to work among breast cancer patients by Meta-analysis.Methods Literatures studies on the current status and influencing factors of returning to work among breast cancer patients were systematically searched in databases.The literature was sorted,screened and evaluated,and a total of 15 articles were included,involving 3975 breast cancer patients after surgery.Results After Meta-analysis,the return-to-work rate among breast cancer patients was 48.49％.Age,treatment method,social support,surgical method,and self-efficacy were influencing factors.Conclusion Clinically,early evaluation and intervention should be carried out for patients with relevant factors to improve the quality of life after breast cancer surgery and improve the level of patients' readiness to return to work.

BACKGROUND: Biliary tract carcinomas (BTCs) are relatively rare but lethal primary malignant tumors derived from the biliary tract system. The burden of BTCs varies according to sex, age, region, and country, but limited attention has been paid to the burden of BTCs. We sought to explore the up-to-date data from the Global Burden of Disease Study (GBD) and expand findings by accessing the demographic features of BTC disease burden. METHODS: Using the latest data from the GBD 2021, we evaluated and analyzed the distributions and patterns of BTC disease burden in various age groups, sexes, regions, and countries. RESULTS: The number of incident cases, deaths, and disability-adjusted life-years (DALYs) tended to increase and peaked at 216,770 (95% uncertainty interval [UI]: 181,890-245,240), 171,960 (95% UI: 142,350-194,240), and 3,732,100 (95% UI: 3,102,900-4,317,000) person-years, respectively, in 2021. However, the average global age-standardized rates (ASRs) of incident cases, deaths, and DALYs shrunk by -11.46% (95% UI: -21.91 to 3.35%), -24.09% (95% UI: -33.19 to 16.88%), and -26.25% (95% UI: -35.53 to 18.36%), respectively, from 1990 to 2021. Meanwhile, the male/female ratio (male per 100 female) of incidence, deaths, and DALYs changed from 76.40, 75.41, and 74.72 to 86.89, 79.11, and 82.29, respectively. In 2021, the highest number of incident cases, deaths, and DALYs occurred in East Asia. The top three highest incidences, deaths, and DALYs were observed in China, India, and Japan, and the highest ASRs were observed in Chile in 2021. Analysis of the Human Development Index along with disease burden estimates of BTCs also suggests that the burden of the disease is related to the level of comprehensive development of the society. CONCLUSION This study provided a comprehensive comparison of differences in the burden of disease across populations and over time, and further presented evidence concerning the formulation of prevention and control policies and etiologic studies for BTCs and proposed logical hypotheses to investigate.
Humans ; Global Burden of Disease ; Biliary Tract Neoplasms/epidemiology* ; Male ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Incidence ; Aged, 80 and over ; Quality-Adjusted Life Years ; Cost of Illness

AIM:The study aimed to explore the effect of curcumin(Cur)on lipopolysaccharide(LPS)-in-duced RAW264.7 cell-derived osteoclasts,together with its underlying mechanism.METHODS:An osteoclast model was established by treating RAW264.7 cells with LPS.The viability of the cells was assessed by CCK-8 assays and osteo-clast formation was evaluated by tartrate-resistant acid phosphatase(TRAP)activity.The levels of reactive oxygen species(ROS),Fe2+,glutathione(GSH),and malondialdehyde(MDA)were examined by biochemical assays.Mitochondrial morphology was assessed by transmission electron microscopy.The mRNA and protein levels of p53,glutathione peroxi-dase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)were determined by RT-qPCR and Western blot,re-spectively.RESULTS:Treatment with LPS successfully induced osteoclasts formation in RAW264.7 cells.The TRAP results showed that compared with the LPS-treated group,the number of osteoclasts and TRAP activity in the curcumin-treated group decreased dose-dependently(P<0.01).Compared with the control group,the LPS+Erastin group showed significantly increased TRAP activity(P<0.01),while after curcumin treatment,the TRAP activity declined in a dose-de-pendent manner(P<0.01).The results of the biochemical tests showed that compared with the control group,the LPS+Erastin group had significantly elevated levels of ROS,Fe2+,and MDA,while the GSH level was significantly reduced(P<0.01),and compared with the LPS+Erastin group,the ROS,Fe2+,and MDA levels in the curcumin group decreased(P<0.01)and GSH levels increased(P<0.01).These effects were all dose-dependent.Transmission electron microscopy showed that compared with the LPS group,the LPS+Erastin group had reduced mitochondrial cristae and increased mem-brane density,while after treatment with curcumin,both these effects were reversed.The RT-qPCR and Western blot re-sults showed that compared with the control group,the mRNA and protein levels of p53 in the LPS+Erastin group were sig-nificantly increased,while those of of SLC7A11 and GPX4 were significantly reduced(P<0.01).After curcumin treat-ment,the p53 mRNA and protein levels were reduced while the levels of SLC7A11 and GPX4 were increased(P<0.01).CONCLUSION:Curcumin can inhibit lipopolysaccharide-induced differentiation of RAW264.7 cells into osteoclasts,and its mechanism may be related to the inhibition of the p53/SLC7A11/GPX4 signaling pathway.

Objective To explore the risk factors for developing chronic pulmonary heart disease in patients with pneumoconiosis.Methods The medical records of pneumoconiosis patients admitted to an occupational disease hospital in Sichuan Province between January 2012 and November 2021 were collected.Kaplan-Meier(K-M)method,or product-limit method,was used to plot the incidence curves of pulmonary heart disease in the pneumoconiosis patients.Cox proportional hazard regression model was used to analyze the influencing factors associated with chronic pulmonary heart disease in patients with pneumoconiosis.Results A total of 885 pneumoconiosis patients were included in this study.The follow-up time was 12 to 115 months and the median follow-up time was 43 months.A total of 138 patients developed chronic pulmonary heart disease and the incidence density of pulmonary heart disease was 38.50/1000 person-years.Multivariate Cox proportional hazard regression analysis showed that the influencing factors of pneumoconiosis inpatients developing chronic pulmonary heart disease included the following,being 50 and older(hazard ratio[HR]=1.85,95%confidence interval[CI]:1.25-2.74),stage Ⅲ pneumoconiosis(HR=2.43,95%CI:1.48-4.01),resting heart rate≥100 beats/min(HR=2.62,95%CI:1.63-4.21),the complication of chronic obstructive pulmonary disease(COPD)(HR=4.52,95%CI:2.12-9.63),underweight(HR=2.40,95%CI:1.48-3.87),overweight and obesity(HR=0.54,95%CI:0.34-0.86),and triacylglycerol(TG)(HR=0.69,95%CI:0.49-0.99).Conclusion Old age,stage Ⅲ pneumoconiosis,high resting heart rate,low BMI,and the complication of COPD are risk factors for chronic pulmonary heart disease in pneumoconiosis patients,while overweight and obesity and TG are protective factors.Early identification of the risk factors and the adoption of the corresponding prevention measures are the key to preventing chronic pulmonary heart disease in patients with pneumoconiosis.

Objective:To understand the molecular characteristics of the mutant strain of polymerase basic protein 2 (PB2) gene of influenza A (H1N1pdm) in Guangdong province, and to explore its specific molecular sites, so as to provide scientific basis for the prevention and control of influenza virus.Methods:Throat swab samples were collected from 2 cases infected with PB2 gene variant strains for virus isolation, and 23 influenza virus strains were selected from Guangdong province for sequencing analysis. The reference sequences and vaccine strain sequences provided by GISAID were used to perform evolutionary analysis on hemagglutinin (HA) and PB2 genes. Virus strain antigen analysis and neuraminidase (NA) inhibition test were carried out. PB2 protein model was constructed and polymerase activity was analyzed.Results:H399N amino acid mutation occurred in the HA gene of PB2-D701N and PB2-A271S variant strains, both of which belonged to the branch of 6B.1A.5a.2a. They belonged to the same big branch and different small branches as the vaccine strain A/Victoria/4897/2022, and they are all vaccine-like strains. In the three-dimensional structure, the mutations of PB2-D701N and PB2-A271S change charge and hydrophobicity.Conclusions:PB2-D701 and A271 were highly conserved, and PB2 mutant strains were not the dominant strains. The PB2 mutant had high antigenicity with the vaccine. The PB2 mutant strain is sensitive to NA inhibitors. The three-dimensional model predicted that PB2-D701N mutation could enhance virulence and affect transmissibility of influenza virus, while PB2-A271S mutation could affect polymerase activity and polymerase complex synthesis of influenza virus.