Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective:To measure the cerebral cortical activity by the functional near-infrared spectroscopy,fNIRS during the bilateral single-leg standing in population with chronic ankle instability(CAI)and healthy controls.Method:Sixteen healthy participants without any sprains and 16 participants with unilateral CAI were recruit-ed.The fNIRS was used to collect the brain function signals during the bilateral single-leg standing task.Based on the concentration of oxyhemoglobin(HbO2),the functional activation(β value)of each brain region of the two groups was calculated,and the differences between the groups during the tasks were compared in nine brain regions,including the dorsolateral prefrontal cortex(DLPFC),primary sensory area(S1),supplemen-tary motor area(SMA),and middle temporal gyrus(MTG).Result:Compared to healthy participants,CAI participants exhibited significantly increased cortical activity based on the β value in right SMA(ch28)and left Wernicke's area(ch51)during the single-leg standing on the injured side.During the single-leg standing on the uninjured side,CAI participants exhibited significantly increased cortical activity in the right side of DLPFC(ch15),S1(ch33)and MTG(ch40).Conclusion:The cerebral cortex activation in patients with CAI is different from that in healthy people,ac-cording to the neural mechanism of posture control.There is a higher activation of DLPFC,S1,MTG,SMA,and Wernicke's area in CAI patients during the state of postural control.

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective:To identify the incidence and prevalence of inflammatory bowel disease (IBD) in the northern Chinese population of Jinan, Shangdong Province, along with its temporal trends from 2005 to 2022.Methods:By utilizing the data from the Jinan basic medical insurance system, a population-based IBD cohort was constructed. This facilitated the computation of both the incidence and prevalence rates of IBD, alongside their temporal trends throughout the 2005 to 2022 timeframe. The 95% confidence intervals were estimated using poisson regression.Results:The overall incidence rate of IBD showed a yearly increasing trend, with age-standardized incidence rates rising from 0.03/100 000 in 2005 to 5.39/100 000 in 2022. The age-standardized incidence rate of ulcerative colitis (UC) increased from 0.03/100 000 in 2005 to 4.97/100 000 in 2022. The age-standardized incidence rate of Crohn's disease (CD) rose from 0.05/100 000 in 2011 to 0.44/100 000 in 2022. The crude prevalence of IBD increased from 0.60/100 000 in 2005 to 32.39/100 000 in 2022. Specifically, the crude prevalence of UC increased from 0.60/100 000 in 2005 to 31.44/100 000 in 2022, while the crude prevalence of CD increased from 0.05/100 000 in 2011 to 1.19/100 000 in 2022.Conclusions:Analysis of recent medical insurance data reveals a continuous uptrend in both the incidence and prevalence of IBD in Jinan, a northern city in China. This underscores the urgent need for enhanced medical resources and healthcare guaruntee to ensure the well-being of individuals afflicted with IBD.

Objective:To investigate changes of CD4+T/CD8+T ratio in children with mycoplasma pneumoniae pneumonia(MPP)at different ages and to predict outcome.Methods:A total of 150 children aged 1～12 with MPP admitted to The Second People's Hospital of Hefei from March 2021 to September 2023 were selected as study group,and were divided into improved group(n=112)and deteriorated group(n=38)according to clinical outcomes after treatment.According to age,patients were divided into in-fant group(≤3 years old)38 cases,preschool group(4～6 years old)57 cases,school age group(>6 years old)55 cases.General information,biochemical test indicators and other related data were collected,CD4+T/CD8+T was calculated,and statistical analysis was performed by SPSS23.0 software.Through univariate and multifactor Logistics regression analysis,changes of CD4+T/CD8+T and other indicators in MPP children of different ages were compared,and independent factors affecting outcome of MPP children were screened.ROC curve was used to analyze efficacy of selected independent influencing factors in predicting outcome of MPP children of different ages.Log-binomial model was used to analyze risk effect of age on CD4+T/CD8+T and different outcomes in MPP children.Dose-response relationship between CD4+T/CD8+T and risk of disease progression in MPP children was analyzed by Logistic regression model combined with restricted cubic spline(RCS)model.P<0.05 was statistically significant.Results:CRP,IgA,IgG,IgM and CD8+T were the highest in infant group,followed by preschool group,the lowest in school-age group(P<0.05),CD4+T and CD4+T/CD8+T were the lowest in infant group,followed by preschool group,and the highest in school-age group(P<0.05).MPP children with≤3 years old accounted for the lowest proportion of improvement(18.76%)and the worst improvement,followed by MPP children with 4～6 years old,MPP children with>6 years old accounted for the highest proportion of improvement(43.75%),and the best im-provement(P<0.001).Improvement of children with disease course≤7 days was significantly better than disease course>7 days(P<0.001).CRP,DD,ESR,LDH,IgA,IgG,IgM and CD8+T levels in children with MPP deterioration were significantly higher than children with MPP improvement(P<0.001),and CD4+T and CD4+T/CD8+T levels were significantly lower than children with MPP im-provement(P<0.001).Multi-factor Logistics regression analysis showed that age,IgA,IgG,IgM and CD4+T/CD8+T were independent influencing factors for outcome of MPP children(P<0.05).ROC curve analysis showed that when cut-off value was 1.50,AUC of CD4+T/CD8+T to predict outcome of MPP children was 0.86(95%CI:0.75～0.94),sensitivity and specificity were 83.76%and 84.60%,respectively.Log-binomial model showed that MPP children with CD4+T/CD8+T≤1.50%had the highest risk of worsening out-come.Risk scores before and after adjustment were 2.05(1.41～3.75),2.07(1.46～3.88)and 2.14(1.50～4.02)times of those in im-provement group.School-age children with CD4+T/CD8+T>1.50%had the lowest risk of worsening,and risk before and after adjust-ment was 1.07(1.00～1.87),1.13(1.04～1.98),1.18(1.07～2.01)times higher than improved group.RCS model analysis of relation-ship between CD4+T/CD8+T and different outcomes in MPP children showed that regardless of whether confounders were adjusted,CD4+T/CD8+T was negatively correlated with outcome of MPP children.Conclusion:CD4+T/CD8+T in MPP children of different ages is significantly different.CD4+T/CD8+T is the lowest in infant group,followed by preschool group,and the highest in school-age group.CD4+T/CD8+T in children with worsening MPP is significantly lower than improved MPP,and CD4+T/CD8+T is negatively correlated with outcome of MPP children,which has certain value in predicting outcome of MPP children.

Objective:To construct a lentiviral interference plasmid targeting collapse response regulatory protein 1(CRMP1)gene,to establish a human neuroblastoma cell line(SH-SY5Y)with stable CRMP1 knockdown,and to investigate its impact on expression of NLRP3 inflammasome protein.Methods:Double-stranded shRNA was designed and synthesized targeting h-CRMP1 mRNA sequence,and cloned into PLKO.1 vector.Recombinant shCRMP1 plasmids were constructed correctly,which was transfected into HEK-293T cells for lentiviral packaging.Obtained lentivirus supernatant was concentrated and then infected into SH-SY5Y cells.The interference effect of shCRMP1 plasmid and protein expressions of NLRP3 inflammasome components in SH-SY5Y cells were detected by Western blot.Results:DNA sequencing results showed that insertion sequences of recombinant interference plasmids pLKO.1-shCRMP1 were consistent with designed sequences,which confirmed successful construction of shCRMP1 lentivirus interfering plasmids and transfected into HEK-293T cells for lentivirus packaging,and protein level of CRMP1 in HEK-293T cells were decreased.SH-SY5Y cells were infected with lentivirus concentrate obtained from packaging and screened with puromycin.Western blot results showed that shCRMP1 recombinant lentiviral plasmids could significantly down-regulate CRMP1 protein expression in SH-SY5Y cells.It was also found that in SH-SY5Y cell line with stable CRMP1 knockdown,inhibition of CRMP1 expression could effectively inhibit NLRP3 inflammasome activation under MPP+induction.Conclusion:pLKO.1-shCRMP1 lentiviral interfering plas-mids have been successfully constructed,and interference with CRMP1 can inhibit activation of NLRP3 inflammasome in MPP+-in-duced SH-SY5Y cells.This study provides guidance for further research on mechanism of CRMP1 in neurodegenerative diseases such as Parkinson's disease.

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.