Objective To investigate the current status of symptom burden and psychological distress among lung cancer patients in the diagnostic phase, and to explore the chain mediating role of social support and resilience between symptom burden and psychological distress. Methods The patients with lung cancer in the diagnostic phase who were treated in the Department of Thoracic Surgery of the Second Xiangya Hospital of Central South University from October 2022 to June 2023 were investigated by a general information questionnaire using the MD Anderson Symptom Inventory, the Social Support Rating Scale, the Connor-Davidson Resilience Scale, and the Distress Thermometer. The chain mediating role of social support and resilience between symptom burden and psychological distress was analyzed. Results A total of 413 lung cancer patients were enrolled, including 173 males and 240 females, aged (54.69±10.82) years. The detection rate of psychological distress among lung cancer patients in the diagnostic phase was 48.18%, and the average score was (3.84±2.50) points. Psychological distress was positively correlated with symptom burden (P<0.01), and negatively correlated with social support and resilience (P<0.01). The mediating effect of resilience between symptom burden and psychological distress was significant. The chain mediating effect of social support and resilience between symptom burden and psychological distress was also significant. Conclusion Lung cancer patients in the diagnostic phase have a high detection rate of psychological distress. Symptom burden can directly impact psychological distress, and can affect psychological distress through the indirect path of resilience as well as the chain mediating path between social support and resilience among lung cancer patients in the diagnostic phase.

Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans ; Arthritis, Rheumatoid/metabolism* ; Machine Learning ; Male ; Female ; Middle Aged ; Aged ; Synovial Fluid/immunology* ; Osteoarthritis, Knee/metabolism* ; Knee Joint/metabolism* ; ROC Curve ; Diagnosis, Differential

OBJECTIVE: To investigate the effects of liriodendrin on the intestinal flora and the ferroptosis signaling pathway in renal tissue of rats with sepsis-induced acute kidney injury (AKI). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), sepsis model induced by cecal ligation and puncture group (CLP group), and liriodendrin intervention group (CLP+LIR group), with 10 rats in each group. The CLP+LIR group was given 0.2 mL of 100 mg/kg liriodendrin by gavage 2 hours before modeling; Sham group and CLP group were given the same volume of normal saline by gavage. The samples were collected after anesthesia 24 hours after modeling. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. The levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6) were detected by enzyme linked immunosorbent assay (ELISA). The levels of renal function indicators such as creatinine (Cr), and urea nitrogen (UREA) in peripheral blood, and the content of malondialdehyde (MDA) and Fe²⁺ in renal tissue were detected. Western blotting was used to detect the expressions of nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) in renal tissues. The changes of intestinal flora were detected by 16S rDNA high-throughput sequencing. RESULTS: Compared with the Sham group, the CLP group showed significantly enlarged glomeruli, noticeable renal interstitial edema, disorganized kidney tissue, and significantly increased pathological scores. The contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue were significantly increased. The protein expressions of Nrf2, GPX4, and HO-1 in renal tissue were significantly down-regulated. The species richness of intestinal flora decreased significantly, and the relative abundances of pathogenic bacteria such as Morganella, Citrobacter, Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus increased significantly, while the relative abundances of beneficial bacteria such as Butyricimonas, Veillonella, Prevotella, Lactobacillus, Bifidobacterium, and Ruminococcus decreased significantly. Compared with the CLP group, CLP+LIR group could significantly reduce the pathological damage of renal tissue, the pathological score significantly decreased (1.80±0.84 vs. 4.20±1.30, P < 0.05), and improve the composition of intestinal flora, reduce the relative abundances of pathogenic bacteria such as Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus, and significantly increase the relative abundances of Lactobacillus, Bifidobacterium, and Ruminococcus, significantly reduce the contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue [blood TNF-α (ng/L): 191.31±7.23 vs. 254.90±47.89, blood IL-1β (ng/L): 11.15±4.04 vs. 23.06±1.67, blood IL-6 (ng/L): 163.20±17.83 vs. 267.69±20.92, blood Cr (μmol/L): 24.14±4.25 vs. 41.17±5.43, blood UREA (mmol/L): 4.59±0.90 vs. 8.01±1.07, renal MDA (μmol/g): 9.67±0.46 vs. 16.05±0.88, renal Fe²⁺ (mg/g): 0.71±0.07 vs. 0.93±0.04, all P < 0.05], and increase the protein expressions of Nrf2, GPX4, and HO-1 (Nrf2/GAPDH: 1.21±0.01 vs. 0.39±0.01, GPX4/GAPDH: 0.74±0.04 vs. 0.48±0.04, HO-1/GAPDH: 0.91±0.01 vs. 0.41±0.02, all P < 0.05). CONCLUSIONS Liriodendrin has an obvious protective effect on sepsis-induced AKI. The mechanism may involve regulating the intestinal flora, increasing the activation of the Nrf2/HO-1/GPX4 signaling pathway in renal tissue, and reducing ferroptosis.
Animals ; Acute Kidney Injury/microbiology* ; Rats, Sprague-Dawley ; Sepsis/complications* ; Male ; Ferroptosis/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Signal Transduction ; Kidney/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

The microbiological quality of laboratory animals is crucial for the validity and reproducibility of scientific research data,as well as human health and animal welfare.Currently,individual ventilation cages(IVC)have become the mainstream feeding system for rodent laboratory animals.The most commonly used pathogen monitoring method for this feeding system is soiled bedding sentinels(SBS).This method monitors the microbial carrying status of mouse colony through indirect contact and delayed feedback.It can effectively monitor pathogens transmitted via the fecal-oral route,such as mouse hepatitis virus and reovirus.However,this method has difficulty detecting pathogens mainly transmitted through aerosols or direct contact,such as Sendai virus and Pasteurella pneumotropica.The exhaust air dust(EAD)-PCR monitoring method involves swab sampling in the IVC exhaust ducts to monitor the corresponding racks of the ducts;swab sampling before the prefiltration of the host to monitor the entire IVC rack;and EAD collection device sampling to monitor all racks connected to the same host.Different IVC manufacturers have developed corresponding EAD collection devices for their respective IVC systems,making operations convenient and standardization easy.Compared with the SBS method,the EAD-PCR method significantly improves detection rate and timeliness,with the fastest detection possible after one week of exposure.It can serve as a supplement or replacement for the SBS method.Currently,increasing evidence supports that EAD-PCR testing is a more reliable,sensitive,and cost-effective monitoring method,and is more beneficial to animal welfare.This article reviews the application progress of these two methods for monitoring pathogens,analyzes the existing limitations of the EAD-PCR method,and proposes solutions based on its implementation in our laboratory and examination units.The EAD-PCR method helps reduce the number of live sentinel animals used in pathogen monitoring,in order to better maintain the"3Rs"principle of laboratory animal welfare.

The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019. With e-cigarettes becoming more and more popular, smokers have more options other than conventional cigarettes. Under these circumstances, a comprehensive evaluation of the general safety of new tobacco and tobacco-related products, represented by e-cigarettes, to human health is necessary. In this review, we summarize the current research on potential negative impacts of e-cigarette exposure on human health. In particular, studies detailing the relationship between e-cigarettes and the digestive system are summarized, with mechanisms mainly including hepatic metabolic dysfunction, impaired gut barrier, and worsened outcomes of inflammatory bowel disease (IBD). Although believed to be safer than traditional cigarettes, e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma, cardiovascular disease, and IBD. Moreover, nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes. However, non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.

Objective To analyze the value of systemic inflammatory indicators in diagnosing schizo-phrenia and their correlation with disease condition severity and cognitive dysfunction.Methods A total of 47 patients with schizophrenia visited and treated in this hospital from October 2021 to March 2023 were selected as the study subjects,and 47 healthy volunteers during the same period served as the control group.The morn-ing fasting venous blood was collected in all research subjects,and the blood routine and biochemical indicators were measured.The SII,SIRI,NHR and LHR were calculated.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of SII,SIRI,NHR and LHR in the patients with schizophrenia.The correlation adopted the Pearson correlation analysis.Results The levels of SII,SIRI,NHR and LHR in the schizophrenia group were significantly increased compared with the control group,and the difference was statistically significant(P＜0.05).The ROC curve analysis demonstrated that the area under the curve(AUC)of SII,SIRI,NHR and LHR detection alone in diagnosing schizophrenia were 0.683,0.686,0.774 and 0.766 respectively.AUC of their combination detection was 0.886.SII was positively correlated with the gen-eral symptoms and the positive and negative symptom scale(PANSS)total score,and negatively correlated with the spatial structure,linguistic function and delayed memory(P＜0.05);SIRI was positively correlated with the negative symptoms,general symptom and PANSS total score,and negatively correlated with the im-mediate memory,spatial structure,linguistic function,attention;NHR was positively correlated with the nega-tive symptoms,positive symptoms,general symptoms and PANSS total score,and negatively correlated with immediate memory,linguistic function,attention and delayed memory(P＜0.05).LHR was positively corre-lated with the positive symptoms,general symptoms and PANSS total score,and negatively correlated with the spatial structure,linguistic function,attention and delayed memory(P＜0.05).Conclusion SII,SIRI,NHR and LHR combined detection has higher diagnostic value for the patients with schizophrenia.Further-more,the SII,SIRI,NHR and LHR levels are closely correlated with the disease condition severity and cogni-tive function impairment degree.

Objective To explore the relationship between the levels of peroxidoredoxin(PRDX)1 and chromosome 10 deletion phosphatase-tensin homologous gene(PTEN)and liver function and disease activity in patients with autoimmune liver disease.Methods A total of 83 patients with autoimmune liver disease ad-mitted to the hospital from January 2021 to December 2022 were selected as the study objects.According to the disease activity at admission,they were divided into active group(37 cases)and remission group(46 ca-ses).Clinical data and serum PRDX1 and PTEN levels of the two groups were analyzed.At the same time,Child-Pugh classification of liver function was performed,and the patients were grouped.A total of 100 health-y volunteers who underwent physical examination during the same period were selected as the control group.Multivariate Logistic regression was used to analyze the influencing factors of disease activity in patients with autoimmune liver disease,and the evaluation value of serum PRDX1 and PTEN levels on disease activity in pa-tients with autoimmune liver disease after treatment was analyzed by receiver operating characteristic(ROC)curve and area under the curve(AUC).Results Compared with the grade A group,there were no significant differences in serum PRDX1 and PTEN levels in the grade B group(P＞0.05),while serum PRDX1 level was increased and PTEN level was decreased in the grade C group(P＜0.05).Compared with the grade B group,the serum PRDX1 level was increased and PTEN level was decreased in the grade C group(P＜0.05).Com-pared with the control group,there were no significant differences in serum PRDX1 and PTEN levels in the re-mission group(P＞0.05),while the serum PRDX1 level was increased and PTEN level was decreased in the active group(P＜0.05).Compared with the remission group,the level of serum PRDX1 was increased and the level of PTEN was decreased in the active group(P＜0.05).The AUC of serum PRDX1 and PTEN for evalu-ating the disease activity in autoimmune liver disease patients was 0.750 and 0.854,respectively,and the AUC of the combined detection of serum PRDX1 and PTEN was 0.916.The proportion of patients with hepatic dis-comfort and cirrhosis in the active stage group was higher than that in the remission stage group(P＜0.05).Multivariate Logistic stepwise regression analysis results showed that hepatic discomfort(OR=3.487,95％CI:1.534-7.927),cirrhosis(OR=4.289,95％CI:1.744-10.545),PRDX1 ≥5.22 ng/mL(OR=5.068,95％CI:1.951-13.164),PTEN≤0.31 pg/mL(OR=5.387,95％CI:2.099-13.829)were risk factors for disease activity of autoimmune liver disease(P＜0.05).Conclusion The increase of serum PRDX1 level and the decrease of serum PTEN level are closely related to liver function and disease activity in patients with au-toimmune liver disease,and they have certain clinical evaluation value in patients with autoimmune liver dis-ease.

Abstract: Objective To analyze the genetic evolution and molecular characteristics of the H5N6 avian influenza virus A/Changsha/1/2022(H5N6) in a human infection case in Changsha City, providing insights for the prevention and control of H5N6 avian influenza transmission to humans. Methods The sample underwent whole-genome sequencing on a third-generation sequencing platform. Reference sequences were downloaded from the NCBI and GISAID databases for comparison. The phylogenetic tree was constructed and key amino acid mutation sites were analyzed using MEGA7 software. Results The sequence analysis results revealed that the strain studied belongs to the H5 subtype Clade 2.3.4.4b branch. The PB1 gene shared 99.69% homology with the H5N6 virus A/duck/Hunan/S40199/2021(H5N6) from Hunan Province; PB2 had 98.58% homology with A/Whooper swan/Sanmenxia/Y36/2020(H5N8); and other sequences showed high homology with the strain A/Guangdong/1/2021(H5N6) discovered in Guangzhou in 2021. These results indicate that an infection with a recombinant H5N6 subtype avian influenza virus caused the case. The amino acid composition of the cleavage site was RERRRKR↓GLF, consistent with high-pathogenicity avian influenza characteristics. The HA sequence showed no mutations at the Q226L and G228S sites, indicating the preservation of characteristics binding to avian receptors. However, mutations at the S127P, S137A, T160A, T192R, and A267T sites increased the virus's affinity for humans. A deletion found in positions 59-70 of the NA protein stalk implies enhanced viral virulence in mammals. Mutations were noted in the internal genes; S622G in PB1, K389R and V598T in PB2, N409S in PA, N30D and T215A in M1, and P42S in NS1, which may enhance the virulence of avian influenza virus in infecting mice. Conclusions The H5N6 virus strain detected in a human case in Changsha City in this study is highly pathogenic, prone to bind to avian receptors, but numerous mutations at key amino acid sites facilitate infection in humans. Continuous monitoring and research on H5N6 avian influenza virus should be strengthened

Objective To investigate the effect of Galangin on pyroptosis of bone marrow derived macrophages(BMDMs).Methods BMDMs were cultured in vitro and divided into blank control group,model group and Galangin group with different concentrations.Lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were used to construct the pyroptosis model.The effect of different concentrations of Galangin on the proliferation of BMDMs was detected by cell counting Kit-8(CCK-8).The level of cysteinyl aspartate specific proteinase-1 p10 subunit(caspase-1 p10),interleukin-1β(IL-1β)in supernatant and intracellular nucleotide NOD-like receptor protein 3(NLRP3)were detected by Western blotting.IL-1β in supernatant was detected by enzyme-linked immunosorbent assay(ELISA).The cell death was observed by propidium iodide(PI)staining.High-throughput sequencing was used to compare the gene expression in the model group and Galangin groups at 20 μmol/L.Results There was no statistically significant difference between the 5,10,20,40,60,80 μmol/L Galangin groups on the proliferation level of BMDMs(all P>0.05),indicating that no significant effect of Galangin at 5,10,20,40,60,80 μmol/L was observed on the proliferation of BMDMs.So we selected Galangin at 5,10,20 μmol/L and treatment for 1,2 and 4 hours as the effects of different concentrations and time on the pyroptosis of BMDMs.Compared with blank control group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant in model group were significantly increased(all P<0.05).Compared with model group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant of Galangin at 5,10 and 20 μmol/L were significantly decreased[IL-1β protein expression(gray value):0.155±0.006,0.113±0.006,0.111±0.007 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.207±0.044,0.160±0.008,0.082±0.008 vs.1.000±0.000,IL-1β(μg/L):99.80±10.36,85.21±8.78,26.53±4.56 vs.494.10±35.47,all P<0.05].There was no significant difference between the different concentration groups(all P>0.05),but with the extension of treatment time of Galangin,the inhibitory effect was enhanced.The inhibitory effect of Galangin at 20 μmol/L for 4 hours was the most obvious[IL-1β protein expression(gray value):0.186±0.004 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.247±0.009 vs.1.000±0.000,IL-1β(μg/L):173.80±10.56 vs.653.80±76.02,all P<0.05].Treatment with 20 μmol/L Galangin for 4 hours could reduce the number of pyroptotic cell deaths(number of view:23.00±3.61 vs.67.67±15.63,P<0.05)and inhibited the expression of NLRP3 protein(gray value:0.178±0.025 vs.0.406±0.066,P<0.05).High-throughput sequencing showed that,compared with the model group,Galangin down-regulated the genes of Nlrp3,Nod2,IL-1β and up-regulated genes of Skp2(also known as Fbxl1),Fbxl20,Fbxl4,Fbxo32 and Fbxw7.Conclusion Galangin inhibited pyroptosis mediated by NLRP3 inflammasome in macrophages.