Objective To establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.Methods A retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022.General data and serological indicators were collected,and patients were divided into infection group(n=262)and control group(n=1036)based on the occurrence of spontaneous peritonitis.Univariate and LASSO regression analyses were used to screen variables,followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients,leading to the establishment of a nomogram prediction model.Finally,the Hosmer-lemeshow(H-L)goodness of fit test,receiver operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA)and clinical impact curve(CIC)were utilized to evaluate the fit degree,accuracy,calibration,and clinical practicability of the nomogram prediction model.Results Single factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus(PVTT),Child-Pugh grade,China Liver Cancer Staging(CNLC)stage,alcohol consumption history,smoking history,white blood cell count(WBC),neutrophil count(NE),hemoglobin(Hb),fibrinogen(FIB),abnormal prothrombin(PIVKA-Ⅱ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total protein(TP),prealbumin(PA),γ-glutamyltransferase(GGT),alkaline phosphatase(ALP),cholinesterase(CHE),total bile acid(TBA),total cholesterol(TC),low density lipoprotein(LDL),creatinine(Cr),HBV DNA,CD3+T cells count,CD4+T cells count,CD8+T cells count,CD4+T cells/CD8+T cells ratio,procalcitonin(PCT),serum amyloid A(SAA),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),alpha-fetoprotein(AFP),and IL-4(P＜0.05).LASSO regression analysis identified 5 variables:Child-Pugh grade,PVTT,WBC,CHE and hs-CRP.Binary logistic regression analysis indicated that Child-Pugh grade(Grade B:OR=5.780,95％CI 3.271-10.213,P＜0.001;Grade C:OR=14.818,95％CI 7.697-28.526,P＜0.001),PVTT(OR=2.893,95％CI 2.037-4.108,P＜0.001),WBC(OR=1.088,95％CI 1.031-1.148,P=0.002),and hs-CRP(OR=1.005,95％CI 1.001-1.010,P=0.026)were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients.Using these 4 variables,a nomogram prediction model was constructed and evaluated.The P-value of the H-L goodness of fit test was 0.760.Moreover,the area under ROC curve(AUC)was 0.866,with a sensitivity of 0.870 and a specificity of 0.716.The average absolute error of the calibration curve is 0.022.DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.Conclusion The nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients,constructed using Child-Pugh grade,PVTT,WBC and hs-CRP,exhibits a high fitting degree and accuracy,with the prediction probability highly consistent with the actual occurrence probability,and possesses certain clinical practicability.

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

China is facing the double burden of high incidence of lung cancer and tuberculosis epidemic. Lung cancer combined with tuberculosis has a high incidence and complexity in clinical practice. High-risk groups include immunocompromised people, long-term smokers and people with a history of tuberculosis. The coexistence of the two diseases not only increases the difficulty of diagnosis and treatment decision-making, but also increases the risk of treatment-related adverse reactions and drug interactions. The guideline was developed by Committee of Integrated Rehabilitation for Lung Cancer, Chinese Anti-Cancer Association; Chinese and Western Integrated Lung Cancer Committee of Chinese Anti-Cancer Association; Society of Tuberculosis, Chinese Medical Association, aiming to standardize the diagnosis and treatment of lung cancer complicated with pulmonary tuberculosis. The guideline emphasizes the core position of combined diagnosis of multimodal imaging, etiology and pathology. It is proposed that anti-tuberculosis and anti-tumor treatment should be coordinated under the framework of multidisciplinary team, and drug interactions and timing optimization should be paid attention to. For surgical treatment, minimally invasive resection combined with systematic lymph node dissection is recommended after infection control. Systemic therapy requires individualized risk stratification and dynamic monitoring of efficacy and adverse reactions. Based on evidence-based medicine and Chinese clinical practice, combined with the accessibility of drugs and technologies, this guideline proposes a whole-process management pathway covering screening, diagnosis, treatment and follow-up, in order to improve the prognosis and quality of life of patients.

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

The water-sediment interface is an important zone for the migration and transformation of chemical substances,but traditional sampling methods make in situ sampling challenging,thus it is difficult to capture information on environmental processes at the micro-scale.In this study,diffusive gradients in thin films(DGT)probe technique was used as in situ tool to detect 18 kinds of typical per-and polyfluoroalkyl substances(PFAS)in the water-sediment system,elucidating their vertical distribution characteristics and patterns.The results showed that different PFAS exhibited distinct variation patterns with depth in water and sediment.Short-chain PFAS exhibited greater mobility,while the migration of long-chain PFAS was restricted in sediment and pore water due to their strong hydrophobicity and adsorption capacity,resulting in relatively small concentration changes in the sediment column.The PFAS concentrations measured by DGT ranged from 11.2 μg/L to 1305 μg/L.For long-chain PFAS,the concentrations measured by DGT were higher than those obtained from direct measurement of water and pore water,while the opposite results were obtained for short-chain PFAS.The DGT results indicated that although long-chain PFAS exhibited strong adsorption to sediment particles,the adsorbed PFAS were still bioavailable.DGT probe technique,with its advantages of in situ sampling and high spatial resolution,provides deep insights into the complex environmental processes occurring at the microscale in the water-sediment systems.DGT offers important technical support and scientific evidence for assessing the adsorption-desorption behavior,bioavailability,and ecological risks of these emerging pollutants in aquatic environment.

Nitrofurantoin(NFT)is a nitrofuran antibiotic commonly used as a veterinary drug to treat bacterial infections in animals.However,due to the low solubility and bioaccumulation properties,NFT is prone to leave excessive residues in animal-derived foods and water systems,posing serious threats to human health and ecosystems.Therefore,there is an urgent need to develop an efficient and rapid detection method for NFT.In this work,nitrogen-doped carbon nanomaterials with unique bowl-like structures(N-CNBs)were synthesized via a hydrothermal-carbonization method.The morphology,surface structure,and specific surface area of N-CNBs were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and X-ray photoelectron spectroscopy(XPS).The N-CNB modified glassy carbon electrode(N-CNB/GCE)was prepared,and the electrochemical test revealed that the N-CNB/GCE exhibited higher conductivity and larger electrochemical active surface area compared to bare GCE and nitrogen-doped hollow carbon nanosphere-modified electrode(N-HCNS/GCE).Additionally,the N-CNB/GCE demonstrated superior electrocatalytic activity toward NFT.An NFT electrochemical sensor was constructed based on N-CNB/GCE.The detection conditions of the sensor were optimized,and differential pulse voltammetry(DPV)was employed for NFT detection under optimal experimental conditions.The established NFT electrochemical sensor had a wide linear range of 0.4-500 μmol/L,a low detection limit(S/N=3)of 0.015 μmol/L and high selectivity,with excellent stability and reproducibility.The practical feasibility of this sensor was confirmed by analysis of NFT in milk and tap water samples,with spiked recoveries ranging from 94.2%to 108.9%.

Nitrofurazone(NFZ)is an antibiotic that is used as a veterinary drug in aquaculture.NFZ abuse can lead to a series of environmental and health issues,making it crucial to establish a rapid and highly sensitive method for NFZ detection.In this study,platinum nanoparticle(PtNPs)-loaded zeolitic imidazolate framework(ZIF-8)was used as a precursor,and PtNPs functionalized nitrogen doped porous carbon(NC)was obtained through pyrolysis.Pt@NC was combined with multi-walled carbon nanotubes(MWCNTs)and cast onto a glassy carbon electrode(GCE)surface to construct an electroch-emical sensor.Electrochemical tests revealed that Pt@NC/WCNT/GCE exhibited an electrochemical active area of 0.066 cm2 and a heterogeneous electron transfer rate constant(k0)of 2.03×10-3 cm/s,which were higher than other materials.Compared with the electrodes modified by other materials,the NFZ generated the highest peak current of irreversible reduction peak on the Pt@NC/WCNT/GCE electrode.In comparison with Pt@ZIF-8/WCNT/GCE,after pyrolysis and carbonization treatment,the reduction current of NFZ increased by 2.19 times,and the reduction peak potential shifted positively by 19 mV simultaneously.When compared with NC/WCNT/GCE,the PtNPs in the composite material enhanced the NFZ current by 4.25 times.Additionally,the experimental conditions for detecting NFZ using the sensor were optimized,including the carbonization temperature of Pt@ZIF-8,ratio of Pt@NC to CNT,loading amount of the modified material,and electrolyte pH.Under the optimized conditions,the sensor demonstrated a linear detection range for NFZ of 0.20-240 μmol/L,a sensitivity of 9.995 μA/((μmol/L)?cm2)and a limit of detection(LOD)of 0.06 μmol/L.The sensor exhibited excellent anti-interference capability,good reproducibility,and stability,with spiked recoveries for NFZ in water samples ranging from 94.6%to 105.6%.This study provided a novel electrochemical sensing approach for NFZ detection.

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