Objective On the basis of the theory of the tumor metastatic state, this work aims to explore the metastasis trajectories and peripheral immune response patterns in patients with non-small cell lung cancer (NSCLC) receiving vital qi-strengthening and toxin-eliminating therapy (Fuzheng Juandu) and reveal the value of peripheral immunity in assessing vital qi deficiency during metastasis. Methods A retrospective study design was adopted. Patients with NSCLC admitted from January 1, 2018, to October 31, 2025 were enrolled. Data on metastasis status and peripheral immune indices were collected at the follow-up time points of one, two, three, and five years. Group-based trajectory modeling was used to fit metastasis trajectories, and the independent predictors of trajectory grouping were analyzed through multifactor and multiclassification logistic regression. Results A total of 184 patients with NSCLC were included, and three different groups of metastasis trajectories were identified, namely, the low-risk stable (46.74%, n=86), low-risk rising (13.59%, n=25), and high-risk stable (39.67%, n=73) groups. Univariate analysis revealed substantial differences in peripheral immune indices among the three trajectory groups. Multivariate analysis showed that TNM stage, absolute neutrophil count, lymphocyte count, absolute monocyte count, platelet volume, SAA:CRP ratio, and NLR were independent predictors of the low-risk rising group, whereas TNM stage, absolute monocyte count, basophil count, SII, and NLR were independent predictors of the high-risk stable group. Conclusion Under Fuzheng Juandu therapy, patients with NSCLC exhibit three distinct metastasis trajectories, each corresponding to a specific peripheral immune response pattern. Elucidating these peripheral immune response patterns may facilitate the objective quantification of the degree of vital qi deficiency, prediction of future metastasis risk, and providing an important reference for the individualized clinical implementation of Fuzheng Juandu therapy.

Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P＜0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P＜0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.

AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.

AIM To investigate the effects of Wenyang Jiedu Tongluo Recipe(WYJDTLR)on macrophage recruitment and polarization function in a mouse model of diabetic kidney disease(DKD).METHODS 50 db/db mice were randomly divided into the model group,the valsartan group(10.29 mg/kg)and the high-dose,medium-dose and low-dose WYJDTLR groups(26.52,13.26 and 6.63 g/kg),with 10 mice in each group,in contrast to another 10 db/m mice of the blank group.After 8 weeks of administration,the mice had their levels of fasting blood glucose,24-hour urinary protein quantity(24h-UTP),serum creatinine(Scr)and blood urea nitrogen(BUN)observed;their morphological changes of renal tissues observed by HE staining;their degree of renal glycogen deposition observed by PAS staining;their degree of renal fibrosis observed by Masson staining;their levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1 β in renal tissue detected by ELISA;their renal protein expressions of VCAM-1 and ICAM-1 detected by IHC and Western blot;and their renal expressions of CD86 and CD206 detected by IF.RESULTS Compared with the model group,the WYJDTLR groups displayed decreased levels of fasting blood glucose,24h-UTP,Scr and BUN(P＜0.05,P＜0.01);improved degree of glomerular hypertrophy,mild proliferation of mesangial cells,dilatation of renal tubular,vacuolar degeneration of renal tubular epithelial cells,deposition of glomerular glycogen,and fibrosis of renal tissues(P＜0.01);decreased levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1β in renal tissue(P＜0.05,P＜0.01);decreased renal protein expressions of VCAM-1 and ICAM-1(P＜0.05,P＜0.01),thus reduced the recruitment of macrophages to the kidney;decreased renal CD86 protein expression(P＜0.01);and increased CD206 protein expression(P＜0.01),thus inhibited M1-type polarization of macrophages and promoted M2-type polarization of macrophages.CONCLUSION WYJDTLR can delay the DKD progression in mice by reducing the occurrence of inflammatory reactions through reducing the level of macrophage recruitment factor,inhibiting the M1-type polarization,and promoting the M2-type polarization.

Objective To analyze the literature in the field of body fluid identification collected in the Web of Science Core Collection(WoSCC)database from 2000 to 2023,and explore the research sta-tus,hotspots and development trends in this field.Methods The CiteSpace software was utilized to conduct a visual analysis of the literature in the field of body fluid identification included in the WoSCC database from 2000 to 2023.Meanwhile,a bibliometric analysis of the annual publication vol-ume,journal distribution,national contribution,research institutions,author collaboration,and keywords of the literature was conducted.Results A total of 715 papers on forensic body fluid identification were included,and the annual publication volume showed a continuous and stable growth.Among the 55 countries(regions)that published papers,the United States ranked first with 174 papers,followed by China with 107 papers.In terms of journal distribution,Forensic Science International:Genetics had the largest number of papers,which accounted for 20%of the total papers.In terms of author collaboration,a total of 2 079 authors participated in body fluid identification research,and the author collaboration network showed a clearly clustered distribution.The keywords analysis revealed that re-search hotspots focused on traditional methods,specific RNA molecular markers,DNA methylation,spectroscopy,and the application of microbiomics.Conclusion Research in the field of forensic body fluid identification is thriving,and research institutions and teams should strengthen their collaboration.Establishing unified result interpretation standards and systems and exploring the multiple biomarkers combined application methods will be the research hotspots and important directions for future research in this field.

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Objective:To carry out differential study for clinical application of the domestic and imported electrode of plasma surgery by using real world data,so as to provide data support for clinical selection of electrode products in plasma surgery.Methods:An observational study was adopted,and a total of 384 patients who underwent adenoidectomy by using domestic electrode of plasma surgery(domestic electrode)or imported electrode of plasma surgery(imported electrode)at Children's Hospital,Zhejiang University School of Medicine between March and October 2024 were selected.The data of patients who received domestic or imported electrode were recorded,respectively.The indicators of safety and effectiveness,and economic indicator of surgeries adopted respectively two kinds of electrodes for patients were compared,and the differences of clinical application of the two kinds of electrodes were analyzed.Results:The average hospitalization cost of patients who adopted imported electrode was(11,300±2,500)CNY,which was higher than(7,600±1700)CNY,and the difference was statistically significant(t=-17.546,P<0.05).The surgical duration,postoperative heart rate,postoperative hypotension and hypertension of patients who adopted domestic electrode to conduct adenoidectomy were higher than those of patients who adopted imported electrode,while there were not significant differences between them(P>0.05).The incidences of damage and infection of eustachian cushion of patients who adopted domestic electrode to conduct adenoidectomy were higher than those of patients who adopted imported electrode,and the incidence of bleeding was lower than that of patients who adopted imported electrode,while the differences were not significant(P>0.05).Conclusion:Domestically plasma surgical electrode can effectively save patients'medical costs,which is safe and reliable in clinical use,and it can be mutually replaceable with the imported plasma surgical electrode..

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.