OBJECTIVE: To explore the expression and clinical significance of XPO1 in newly diagnosed adult diffuse large B-cell lymphoma (DLBCL), and further investigate its functional mechanism. METHODS: Immunohistochemical testing was conducted for XPO1 expression in 93 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia. A risk model was construed to find survival related genes in DLBCL patients. Cell proliferation, apoptosis, and cell cycle assays were performed to explore the effect of XPO1 inhibitor (KPT-8602) and XPO1 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes. RESULTS The expression of XPO1 in DLBCL patients was higher than that of the controls. Compared with XPO1 low-expression group, XPO1 high-expression group had a worse prognosis. The constructed risk model indicated that XPO1 and 14 genes in nucleocytoplasmic transport pathway (NTP) might be potential prediction marker of adverse outcome in DLBCL. Moreover, KPT-8602 as well as the XPO1 knockdown could inhibit cell proliferation, promote apoptosis, and induce cell cycle arrest in two DLBCL cell lines, Farage and SU-DHL-4. Based on the gene expression profiling in the datasets of DLBCL, patients were classified into XPO1 high and XPO1 low expression groups, and the MYBL1 was identified as the down-stream effector of XPO1. Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of MYBL1 Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new XPO1/MYBL1 signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Exportin 1 Protein ; Karyopherins/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cell Proliferation ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Clinical Relevance

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Objective To analyze the cellular and histopathological characteristics of underdiagnosed thyroid nodules of Chinese thyroid imaging reporting and data system(C-TIRADS) categories 3 and 4a,thus improving the understanding of these lesions. Methods The data of ultrasound and fine needle aspiration cytology were collected from 683 nodules diagnosed based on pathological evidence in 549 patients undergoing thyroid surgery.The cellular and histopathological characteristics of C-TIRADS 3 and 4a nodules were analyzed. Results Two hundred and sixty-eight nodules were classified as C-TIRADS category 3,including 236 benign nodules,12 low-risk ones,and 20 (7.46%) malignant ones.Two hundred and twenty-one nodules were classified as C-TIRADS category 4a,including 133 benign nodules,7 low-risk ones,and 81 (36.65%) malignant ones.The malignancy rates differed between C-TIRADS 3 and 4a nodules (χ²=58.93,P<0.001),and both were higher than the recommended malignancy rate in the guidelines for malignancy risk stratification of thyroid nodules (C-TIRADS) (both P<0.001).According to the pathological evidence,the underdiagnosed C-TIRADS 3/4a nodules were mainly papillary thyroid carcinoma,especially in patients with Hashimoto thyroiditis.There was not a consistent one-to-one match between each ultrasound result and each cytological classification of low-risk thyroid nodules.Conclusions When the malignant features in preoprative ultrasound imaging are atypical or absent,papillary thyroid carcinoma (especially with Hashimoto thyroiditis),follicular carcinoma,and medullary carcinoma are likely to be underdiagnosed as C-TIRADS 3 or 4a nodules.Therefore,efforts should be made to fully understand the cellular and pathological characteristics of these lesions.
Humans ; Thyroid Nodule/diagnostic imaging* ; Female ; Male ; Middle Aged ; Adult ; Ultrasonography ; Biopsy, Fine-Needle ; Aged ; Young Adult ; Thyroid Neoplasms/diagnostic imaging* ; Adolescent

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

BACKGROUND:Interspinous distraction fusion device BacFuse was used for the management of lumbar degenerative disease and obtained good clinical efficacy in recent years.However,the related biomechanical study was lacking. OBJECTIVE:To explore the related biomechanical characteristics of BacFuse,a novel interspinous distraction fusion device,which was used in lumbar degenerative disease. METHODS:After constructing the goat spinal models(L1-L6),they were grouped into four groups based on different simulated surgeries:the control group,the BacFuse group(L3/4),the screw-rod fixation group(L3/4)and the Topping-off group(L3/4 screw-rod fixation + L2/3 BacFuse fixation).The goat lumbar spine surgical model was assembled into a biomechanical testing system.A biomechanical machine was used for mechanical loading,simulating lumbar spine movement of flexion,extension,lateral flexion and rotation with a 4 Nm moment.A visual tracking system was used for positioning and capturing.Finally,mechanical and optical calibration was completed to calculate the range of motion of the L2/3,L3/4 and L4/5 segments. RESULTS AND CONCLUSION:(1)Compared with the control group,the range of motion of the L3/4 segment in the BacFuse group decreased 27.27%,70%,38.1%and 23.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).The range of motion of L3/4 segment in the screw-rod fixation group decreased 72.73%,80%,71.43%and 73.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).(2)Compared with the control group,the range of motion of the adjacent segment L2/3 increased by 33.33%,25%and 23.81%in the extension,lateral bending and rotation directions,respectively in the BacFuse group(P<0.05),with no significant change in flexion.In the screw-rod fixation group,there was a 50%,44.44%,50%and 58.96%increase in the adjacent segment L2/3 in the flexion,extension,lateral calibration and rotation directions,respectively(P<0.05).(3)Compared with the control group,the BacFuse group showed an increase in range of motion in proximal segment L4/5 in the extension and rotation directions by 27.3%and 17.39%(P<0.05)respectively,with no significant change in flexion or lateral bending.In the screw-rob fixation group,the proximal segment L4/5 demonstrated 38.89%,22.73%and 26.09%(P<0.05)increases in range of motion in the flexion,extension and rotation directions,respectively,with no significant change in lateral bending.(4)In the Topping-off group,the range of motion of L2/3 was reduced by 37.04%,73.08%,56.67%and 38.46%in flexion,extension,lateral flexion and rotation,respectively,compared to the screw-rob fixation group(P<0.05).Compared with the screw-rob fixation group,the Topping-off group showed a 20%reduction in the range of motion of the L4/5 in the flexion direction(P<0.05),with no significant differences seen in extension,lateral bending and rotation.(5)It is concluded that the interspinous distraction fusion device BacFuse significantly reduces the range of motion of the implanted segment and provides some stability.It still retains more mobility and reduces the impact on the adjacent segment compared to screw-rob fixation,while the Topping-off tip,which can be used for intervertebral fusion fixation,significantly reduces the range of motion of the adjacent segment and reduces the risk of adjacent segment degeneration.

A rapid analytical method for simultaneous determination of 32 kinds of multi-residue veterinary drugs in eggs was developed using a modified QuEChERS technique based on a reduced graphene oxide-coated melamine sponge(r-GO@MeS)by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The influences of graphene oxide(GO)concentrations,sponge dosages,and purification modes on drug recoveries were investigated during the purification process.The optimal purification conditions involved using a GO concentration of 0.5 mg/mL,a sponge dosage of 6.0 cm3/mL,and a dynamic purification mode of 5 extrusion cycles.Separation was achieved using an Agilent Eclipse Plus C18 RRHD column(100 mm×2.1 mm,1.8 μm),and quantitative analysis was performed by the external standard method using an electrospray ionization source(ESI)in multiple reaction monitoring(MRM)mode.The results showed that all 32 kinds of veterinary drugs exhibited good linear correlation with coefficients greater than 0.999,and matrix effects(MEs)ranging from?7.8%to 18.9%.The limits of detection(LODs)and quantification(LOQs)ranged from 0.2 to 10.2 μg/kg and from 0.6 to 28.0 μg/kg,respectively.The recoveries for the three spiked levels were in the range of 66.5%?117.5%,with intra-day and inter-day precision(Relative standard deviation)below 13.3%and 16.3%,respectively.The synthetic r-GO@MeS exhibited efficient matrix purification without the need of high-speed centrifugation or strong magnetic field assistance.This significantly shorted the sample pretreatment time and improved the convenience of the matrix purification process.Combined with UPLC-MS/MS,the method was suitable for the rapid determination of multi-residue veterinary drugs in eggs.

Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.