ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

AIM: To analyze the changes in binocular visual function before and after small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:A prospective non-randomized controlled study was conducted. A total of 94 patients(188 eyes)who visited the refractive outpatient department of the ophthalmology department of the General Hospital of the PLA from June 2022 to June 2023 and voluntarily chose SMILE were consecutively included. They were grouped according to the degree of myopia, including 24 cases(48 eyes)in the low myopia group(-3.00 D

Objective To compare the long-term prognosis of elderly patients with stageⅠnon-small cell lung cancer (NSCLC) after lobectomy or segmentectomy. Methods Data of elderly patients with stageⅠNSCLC between 2010 and 2020 were collected from the SEER database. According to the resection method, patients were divided into a lobectomy group and a segmentectomy group. The overall survival (OS) and lung cancer-specific survival (LCSS) of the two groups were compared by propensity score matching (lobectomy : segmentectomy=2 : 1). Results A total of 9990 patients were included, including 5840 (58.46%) females and 4150 (41.54%) males, with an average age of (70.48±6.47) years. Among them, 9029 patients were in the lobectomy group and 961 patients were in the segmentectomy group. After propensity score matching, a total of 2883 patients were matched, including 1 922 patients in the lobectomy group and 961 patients in the segmentectomy group. There was no statistical difference in baseline data between the two groups (P>0.05). The 10-year OS rate and LCSS rate of the lobectomy group were higher than those of the segmentectomy group (OS: 51.15% vs. 38.35%, P<0.01; LCSS: 79.68% vs. 71.52%, P<0.01). Subgroup analysis showed that the survival advantage of lobectomy was found in patients aged 60-<70 years and ≥80 years; for patients 70-<80 years, there was no statistical difference in OS or LCSS between the two surgical methods (P>0.05). In addition, for patients with tumor diameter ≤2 cm (stages ⅠA1-ⅠA2), lymph node dissection number≥10, and receiving adjuvant radiotherapy/chemotherapy, segmentectomy could also achieve a similar prognosis as lobectomy. Conclusion Overall, for elderly patients with stage ⅠNSCLC, lobectomy can achieve better OS and LCSS. However, individual differences, tumor characteristics, and perioperative treatment plans should be considered comprehensively to determine the surgical method for elderly patients with stageⅠNSCLC.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Aim To explore the effect of berberine (B E) on RSV infected HEp-2 cells and the related mechanism. Methods HEp-2 cells were infected with RSV and treated with BE. Cell viability was assessed using the CCK-8 assay. Protein expression levels of NLRP3, ASC, caspase-1, PINK1, Parkin, Beclinl, p62, LC3 I,LC3 II,and BNIP3 in HEp-2 cells were detected by Western blot. The secretion level of IL-1 p in HEp-2 cells was measured using ELISA. Apoptosis rate and mitochondrial membrane potential of HEp-2 cells were examined by flow cytometry. Mitochondrial ROS (mtROS) in HEp-2 cells was detected through MitoSOX staining. Colocalization of mitochondria and autophagosomes in HEp-2 cells was investigated using immunofluorescence staining. Cyclosporin A was used for validation experiments. Results BE could significantly improve the activity of RSV-infected HEp-2 cells,reduce the apoptosis rate (P < 0. 05), and decrease the activation level of NLRP3 inflammasomes and IL-lp level (P <0. 05); BE improved mitochondrial function by increasing mitochondrial membrane potential and ATP levels,and reduced mtROS. BE significantly promoted the colocalization of mitochondria-autophagosome in RSV infected cells, inducing PINK1/ Parkin and BNIP3 to mediate mitochondrial autophagy; cyclosporine A aggravated RSV infection. Conclusions BE has protective effects on HEp-2 cells infected by RSV. The mechanism may be related to the inhibitory effect of BE on the production of mtROS and the activation of NLRP3 inflammasomes by inducing PINK1/ Parkin and BNIP3-mediated mitochondrial autophagy.

Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.

Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

The conversion of carbon dioxide into high value-added energy has become a research hotspot.In this study,by using Ti3AlC2 and CuCl2·2H2O as precursors,accordion-like two-dimensional Cu0/Cu2+-Ti3C2Tx catalysts modified with Cu0 nanoparticles and Cu2+ self-intercalation were successfully prepared for electrocatalytic reduction of CO2.The performance of the material was tested,and the results showed that in a CO2-saturated 0.5 mol/L KHCO3 electrolyte solution,compared with the original Ti3AlC2,the initial potential of the electrocatalytic conversion of CO2 to C2H4 over Cu0/Cu2+-Ti3C2Tx catalyst decreased from ?0.65 V(vs RHE)to?0.01 V(vs RHE).The maximum current density increased from 0.19 mA/cm2 to 2.5 mA/cm2,the double layer capacitance(Cdl)value increased from 2.61 mF/cm2 to 55.06 mF/cm2.The material showed higher catalytic activity and faster electron transfer rate(Charge transfer resistance(Rct)value was only 16.9 Ω).Moreover,the material showed high electrochemical active area and excellent stability.This research provided a promising method for designing and preparing elcetrocatalytic reduction(ECR)catalysts in the future.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

BACKGROUND:Combining seed cells with 3D bioprinting technology enables the specific construction of various tissues and organs to meet the demands of tissue repair.However,further research is needed on the promotion of angiogenesis in damaged tissues. OBJECTIVE:By cultivating a 3D scaffold structure of methacrylated gelatin loaded with fibroblasts,obtaining the supernatant,and mixing it in different proportions with a complete culture medium to simulate the cellular microenvironment during tissue repair,this study aimed to explore the role of various cellular microenvironments in promoting angiogenesis in endothelial cells. METHODS:A methacrylated gelatin scaffold structure loaded with fibroblasts was prepared using an extrusion-based 3D bioprinting process.Hydrogel scaffold extract was prepared and mixed with a complete culture medium in ratios of 1:1,1:2,and 1:4 to obtain conditioned medium.Mouse embryonic fibroblasts BALB3T3 and human umbilical vein endothelial cells were co-cultured with complete medium(control group)and hydrogel scaffold extract,respectively.Cell proliferation was assessed using the CCK-8 assay and cell viability was analyzed using live/dead staining.Three kinds of conditioned medium and complete medium(control group)were used to co-culture with human umbilical vein endothelial cells for tube formulation assay,vascular genetic testing,and immunofluorescence staining of CD31. RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the methacrylated gelatin scaffold exhibited a porous structure,and rheological results demonstrated excellent mechanical properties of the hydrogel.CCK-8 assay and live/dead cell staining showed that the hydrogel scaffold extract had no obvious cytotoxicity.(2)Tube formulation assay indicated that the hydrogel showed the total length of cell tubules in 1:1 conditioned medium group was smaller than that in the control group(P<0.05).There were no statistical differences among the four groups in the number of vascular branches formed by endothelial cells(P>0.05).(3)qRT-PCR results showed that for vascular endothelial growth factor mRNA expression,the 1:2 conditioned medium group was lower than the 1:1 conditioned medium group on day 1(P<0.01).On day 3,the expression level of vascular endothelial growth factor in the 1:2 conditioned medium group was higher than that in the control group(P<0.01).On day 5,the cytokine expression level in the 1:2 conditioned medium group was significantly higher than that in the other three groups(P<0.01 or P<0.000 1).The expression in the 1:1 conditioned medium group was significantly lower than that in the other three groups(P<0.05 or P<0.01).On day 1,the expression level of basic fibroblast growth factor in the 1:1 conditioned medium group was significantly higher than that in the control group and 1:4 conditioned medium group(P<0.01,P<0.05).The expression was higher in the 1:2 conditioned medium group than that in the control group(P<0.05).On day 3,the expression levels of cytokines in the 1:4 conditioned medium group was higher than that in the control group(P<0.05).(4)On day 3,the expression of CD31 in the 1:2 conditioned medium group was higher than that in the control group and the 1:4 conditioned medium group(P<0.05).(5)The results indicate that the resulting conditioned media can simulate the microenvironment of vascular regeneration after tissue damage,promoting the vascularization process of endothelial cells.The best promotion of vascularization in endothelial cells was observed when the ratio of supernatant to complete culture medium was 1:2.