Liver cancer (LC) remains one of the most prevalent tumors globally. Despite considerable advancements in its clinical treatment in recent years, the global burden of this disease is projected to increase. According to World Health Organization statistics, the number of LC deaths worldwide in 2022 was 760,000, ranking third among all cancers. Therefore, there is an urgent need to delve deeper into the realms of LC diagnosis, prognosis, and treatment. Proteomics, as an emerging technology leveraging mass spectrometry (MS)-based protein identification, liquid chromatography separation, and bioinformatics-driven data integration, enables the systematic characterization of proteome dynamics to address critical challenges in LC research. These challenges include the discovery of diagnostic and prognostic biomarkers as well as therapeutic targets. By scrutinizing the expression of specific proteins in both normal and cancerous tissues through high-throughput protein microarrays, researchers can uncover novel biomarkers. The use of these biomarkers alone or in combination with established ones holds the potential to significantly advance the fields of LC diagnosis, prognosis, and treatment. In general, the application of proteomics has significantly promoted the development of LC research. In this review, we summarized the latest advancements in the application of proteomics in LC, with a particular focus on diagnosis, prognosis, and treatment. We also concluded selected protein markers, aiming to offer guidance for further applications and present additional therapeutic targets for LC.

Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Background Noise-induced hearing loss (NIHL) is a prevalent occupational health problem in workplace settings, with non-steady noise exposure being particularly widespread. Although kurtosis-adjusted equivalent sound level (\begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}) methods based on linear regression are available to assess hearing damage, the complexity of kurtosis effects necessitates introducing new metrics through nonlinear regression to improve predictive accuracy for hearing loss from non-steady noise exposure. Objective To examine the adjustment terms [\begin{document}$ \mathrm{lg}(\beta _{N}/{\beta }_{G}) $\end{document}] and coefficients (λ) of \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} using nonlinear regression and evaluate the method’s effectiveness in assessing occupational hearing loss associated with non-steady noise exposure. Methods A cross-sectional study design was employed, enrolling 1034 manufacturing workers and evaluating noise exposure to estimate hearing loss metrics. Quantile regression analysis quantified the proportional contributions of influencing factors for noise-induced permanent threshold shift at 3, 4, and 6 kHz frequencies (NIPTS₃₄₆). \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} was computed using multiple linear regression and nonlinear least squares optimization. Paired t-tests analyzed predictive efficacy before and after kurtosis adjustment to evaluate its impact on ISO 1999 NIPTS₃₄₆ predictions. Chow tests compared the similarity of logistic regression curves for high-frequency noise-induced hearing loss (HFNIHL) incidence between non-steady noise (\begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}) and steady noise (\begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document}), thereby validating the effectiveness of \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}. Results The quantile regression analysis showed that kurtosis was a significant indicator of occupational hearing loss risk from non-steady noise (contribution rate was 27.5%, P<0.05). The linear regression and nonlinear least squares methods obtained six different combinations of coefficients (λ) and adjustment terms [\begin{document}$ \mathrm{lg}(\beta _{N}/{\beta }_{G}) $\end{document}]. Incorporating these \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} adjustments into the ISO 1999 predictive model significantly reduced NIPTS underestimation (from 14.2 dB HL with \begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document} to 11.5–5.6 dB HL with \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}, P < 0.001). The model \begin{document}$ {{{L'}}_{\text{EX,}\text{8}\text{ h}\text{,6}}=L}_{\mathrm{E}\mathrm{X},8\;\mathrm{h}}+7.9\mathrm{lg}({{\beta }_{N}}/{10}) $\end{document} achieved the most significant improvement, reducing underestimation by 8.7 dB HL. The logistic curve analysis further demonstrated that all \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} dose-response relationships for non-steady noise aligned more closely with the steady noise group than \begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document}, with \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}\text{,6}} $\end{document} showing the smallest divergence (difference: 4.1%). Conclusions \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} demonstrates superior efficacy in assessing the risk of occupational hearing loss induced by non-steady noise exposure. The \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} metric, constructed by calculating adjustment terms and coefficients through nonlinear regression analysis, exhibits greater effectiveness than linear regression methods in evaluating occupational hearing loss associated with non-steady noise exposure.

Background Temporal kurtosis (without frequency weighting, i.e., Z-weighted kurtosis) can evaluate noise-induced hearing loss (NIHL). However, few studies have considered the function of frequency weighting (A- or C-weighted) kurtosis on NIHL. Objective To study the significance of A- and C-weighted kurtosis adjustment for equivalent sound level (L'_{EX,8 h}) in evaluating occupational hearing loss. Methods A cross-sectional survey was used to select 973 noise-exposed workers in seven industries as the subjects. The noise exposure of all workers was assessed by distributions of A-, C-, and Z-weighted kurtosis (e.g., K_A, K_C, and K_Z) and respective adjusted equivalent sound level (e.g., L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z). The significance of A- and C-weighted kurtosis in evaluating NIHL was evaluated by correlations between three types of L'_{EX,8 h} and NIHL, and improvement of noise-induced permanent threshold shift (NIPTS) underestimation predicted by the ISO prediction model (Acoustics—Estimation of noise-induced hearing loss, ISO 1999-2013). Results The median K_A, K_C, and K_Z were 68.33, 28.22, and 19.82, respectively. The binary logistic regression showed that L_{EX, 8 h}-K_A, L_{EX, 8 h}-K_C, and L'_{EX, 8 h}-K_Z were risk factors for NIHL (OR>1, P<0.001). The receiver operating characteristic (ROC) curve showed that when the outcome variable was noise-induced hearing impairment (NIHI), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.625, 0.628, and 0.625, respectively. When the outcome variable was high-frequency noise-induced hearing loss (HFNIHL), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX, 8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.624, 0.623, and 0.622, respectively (P<0.05). The order of underestimation improvement values predicted by L'_{EX,8 h} for NIPTS₁₂₃₄ was: L'_{EX,8 h}-K_A (4.68 dB HL)>L'_{EX,8 h}-K_C (4.38 dB HL)>L'_{EX,8 h}-K_Z (4.28 dB HL) (P<0.001). The order of underestimation improvement values predicted by L'_{EX,8 h}-K for NIPTS₃₄₆ was: L'_{EX,8 h}-K_A (7.20 dB HL)>L'_{EX,8 h}-K_C (6.83 dB HL)>L'_{EX,8 h}-K_Z (6.71 dB HL) (P<0.001). Conclusion The adjustment of A- and C-weighted kurtosis to equivalent sound level L_{EX,8 h} can effectively improve the accuracy of the ISO 1999 prediction model in NIPTS prediction, and compared with the C-weighted, the A-weighted kurtosis can improve the result of the ISO 1999 prediction model in terms of underestimating NIPTS.

Social robots play an important role in the field of medical companionship， providing services such as companion communication， drug monitoring， and rehabilitation guidance for the elderly and other subjects. However， social robots also pose the risk of deceiving medical users. Although certain forms of social robots’ deception can be used for therapeutic purposes， unethical deception can have adverse consequences for patients， doctors， and even society. These risks include causing patients to develop attachment disorders， violating their privacy， endangering their health， and even undermining the credibility of the healthcare system. Faced with the deception problem of social robots， starting from relational theory， medical artificial intelligence developers can conduct ethical regulation from the following two paths. First， social robots should be ethically programmed， including embedding programs for limiting benevolent lies， implementing informed consent principles， and ensuring information accuracy. Second， the deceptive behaviors of social robots should be controlled， requiring developers to take full-process supervision responsibility， design medical social robots that can supervise each other， and participate in formulating quality standards and evidence mechanisms for deception issues.

Objective To investigate the epidemiological trends,temporal and spatial distribution characteristics of pulmonary tuberculosis in Lanping County.Methods Based on tuberculosis management data and basic information systems from the"China Disease Prevention and Control Information System,"pulmonary tuberculosis data from Lanping County for 2018-2023 were obtained.Descriptive epidemiology,concentration method,circular distribution method,and spatial autocorrelation analysis were used to conduct epidemiological and spatial analyses of the pulmonary tuberculosis data.Results A total of 2836 TB cases were reported in Lanping County from 2018 to 2023,with an average annual incidence rate of 233.26 per 100000,showing a declining trend.The male-to-female ratio was 1.95∶1,with the highest incidence among individuals aged 60 and above(932 cases,32.86%).Cases were predominantly among farmers(91.01%)and the Lisu ethnic group(52.68%).TB incidence showed weak seasonality with a bimodal distribution,with primary peak occurring from October to March and secondary peak from June to August.Tu'e Township(324.74 per 100,000),Shideng Township(307.42 per 100000),and Jinding Town(260.98 per 100,000)had the highest incidence rates,accounting for 1,284 cases or 45.28%of the county's total cases.In 2020,the incidence of pulmonary tuberculosis in Lanping County showed a spatial clustering distribution(global Morans's I value<0,P value<0.05),with Shideng Township consistently showing high-low aggregation characteristics.Conclusion Between 2018-2023,while the tuberculosis incidence rate in Lanping County has declined,it still falls short of Yunnan Province's tuberculosis prevention and control targets,and the prevention and control work continues to face significant challenges.Strengthening screening of high-risk populations and providing medical support to remote areas will be key measures for future prevention and treatment.

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*

Objective:To discuss the effect of microRNA-34a-5p(miR-34a-5p)on the neuron apoptosis in hippocampus tissue of the rats with temporal lobe epilepsy,and to clarify its mechanism.Methods:Fifty-two male SD rats were randomly divided into control group,model group,miR-34a-5p inhibitor group,and inhibitor negative control group,and there were 13 rats in each group.The PONEMAH 6.X experimental animal telemetry platform was used to record the electroencephalogram(EEG)of the rats in various groups;real-time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression levels of miR-34a-5p in hippocampus tissue of the rats in various groups;HE staining was used to observe the morphology of hippocampus tissue of the rats in various groups;TUNEL method was used to detect the apoptotic rates of neurons in hippocampus tissue of the rats in various groups;immunohistochemistry method was used to determine the positive expression rates of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in various group;Western blotting method was used to detect the expression levels of cyclin-dependent protein kinase 6(CDK6),phosphorylated retinoblastoma protein(p-Rb),and E2F transcription factor 1(E2F1)proteins in hippocampus tissue of the rats in various groups.Results:No abnormalities were observed in the rats in control group;the rats in model group,miR-34a-5p inhibitor group,and inhibitor negative control group exhibited varying degrees of drooling,trembling,bloody tears,staring,chewing tremors,followed by nodding and blinking,and finally forelimb convulsions,standing upright,and falling.Compared with control group,the total duration of epileptic seizures of the rats in model group was significantly prolonged(P<0.01);compared with model group,the total duration of epileptic seizures of the rats in miR-34a-5p inhibitor group was shortened(P<0.01);compared with miR-34a-5p inhibitor group,the total duration of epileptic seizures of the rats in inhibitor negative control group was prolonged(P<0.01).The RT-qPCR results showed that compared with control group,the expression level of miR-34a-5p in hippocampus tissue of the rats in model group was increased(P<0.01);compared with model group,the expression level of miR-34a-5p in hippocampus tissue of the rats in miR-34a-5p inhibitor group was increased(P<0.05);compared with miR-34a-5p inhibitor group,the expression level of miR-34a-5p in hippocampus tissue of the rats in inhibitor negative control group was increased(P<0.01).The HE staining results showed that compared with control group,the cell arrangement in model group was disordered;compared with model group,the cell arrangement in miR-34a-5p inhibitor group was orderly;compared with miR-34a-5p inhibitor group,the cell morphology in inhibitor negative control group was irregular.The TUNEL staining results showed that compared with control group,the apoptotic rate of neurons in CA1 region of hippocampus tissue of the rats in model group was increased(P<0.01);compared with model group,the apoptotic rate of neurons in CA1 region of hippocampus tissue of the rats in miR-34a-5p inhibitor group was decreased(P<0.05);compared with miR-34a-5p inhibitor group,the apoptotic rate of neurons in CA1 region of hippocampus tissue of the rats in inhibitor negative control group was increased(P<0.05).The immunohistochemistry results showed that compared with control group,the positive expression rates of CDK6,p-Rb and E2F1 proteins in hippocampus tissue of the rats model group were increased(P<0.05 or P<0.01);compared with model group,the positive expression rates of CDK6,p-Rb and E2F1 proteins in hippocampus tissue of the rats in miR-34a-5p inhibitor group were decreased(P<0.05);compared with miR-34a-5p inhibitor group,the positive expression rates of CDK6,p-Rb and E2F1 proteins in hippocampus tissue of the rats in inhibitor negative group were increased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in model group were increased(P<0.01);compared with model group,the expression levels of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in miR-34a-5p inhibitor group were decreased(P<0.05 or P<0.01);compared with miR-34a-5p antagomir group,the expression levels of CDK6,p-Rb,and E2F1 proteins in hippocampus tissue of the rats in inhibitor negative control group were increased(P<0.05 or P<0.01).Conclusion:The expression of miR-34a-5p is upregulated in the hippocampal tissue of temporal lobe epilepsy rats,and hippocampal neuron apoptosis is increased.Inhibition of miR-34a-5p expression can reduce the hippocampal neuron apoptotic rate,and its mechanism may be related to the regulation of CDK6,p-Rb,and E2F1 protein expressions in the hippocampus tissue by miR-34a-5p.

Objective:To investigate the preventive and therapeutic effects and mechanisms of Dachaihu decoction(DCD)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and liver injury in mice,as well as the association between DCD benefits and gut microbiota modulation.Methods:Mice were treated with DCD(20.10 and 10.05 g/kg)for 2 weeks,with free access to drinking water containing 3%DSS in the second week to induce UC.Histopathological examination,RT-qPCR and 16S rRNA sequencing were used to investigate the effect of DCD on UC mice.Results:DCD pretreatment significantly alleviated weight loss,bloody diarrhea with mucus,histopathological abnormalities of the colon,and colon shortening in mice with DSS-induced UC.In addition,DCD pretreat-ment significantly upregulated the levels of Occludin,ZO-1,and MUC-2 in the colon and protected the intestinal barrier of mice.DCD pretreatment also alleviated inflammatory cell infiltration in the colon and the liver and significantly reduced the expression levels of the proinflammatory factors such as IL-1β,IL-6,TNF-α,iNOS,COX-2,and NLRP3,thereby exerting a protective effect against UC and liver injury.It should be noted that DCD corrected gut micro-biota imbalance in UC mice by enriching probiotic bacteria such as Lactobacillus and Bifidobacterium and reducing harmful bacteria such as Norank_f_Desulfovibrionaceae and Escherichia-Shigella.Conclusion:DCD can alleviate DSS-induced UC and exert a liver-protecting effect by protecting intestinal barrier,inhibiting inflam-mation,and regulating gut microbiota.

Objective:To establish a nomogram prediction model for severe postpartum hemorrhage in subsequent pregnancies after multiple cesarean sections.Methods:A retrospective analysis was performed for the clinical and imaging data of 395 pregnant and par-turient women with multiple cesarean section who were hospitalized for delivery from January 2021 to December 2023.Univariate analysis and multivariate logistic regression analysis were used to investigate the risk factors for severe postpartum hemorrhage in sub-sequent pregnancies after multiple cesarean sections.A nomogram prediction model was established and validated in terms of specific-ity,accuracy,and clinical decision-making utility.Results:Among the 395 patients,131 experienced severe postpartum hemorrhage,accounting for 33.16%.The univariate analysis showed that times of pregnancy,times of vaginal delivery,grade of hospitals for previ-ous surgeries,number of prenatal checkups during this time of pregnancy,pregnancy-induced hypertension,gestational diabetes,pla-centa previa,location of placenta,association between placenta and uterus,and whether emergency cesarean section was performed were risk factors for severe postpartum hemorrhage in subsequent pregnancies after multiple cesarean sections(P<0.05).The multivari-ate logistic regression analysis showed that times of pregnancy,number of prenatal checkups,gestational diabetes,position of placenta,and whether emergency cesarean section was performed were independent risk factors for severe postpartum hemorrhage in subsequent pregnancies after multiple cesarean sections(P<0.05).A nomogram prediction model was established based on these independent risk factors,which had an area under the ROC curve of 0.783(95%CI=0.732-0.834),and there was a good consistency between the pre-dicted probability curve and the observed frequency curve.When the probability of severe postpartum hemorrhage predicted by the nomogram model was within the range of 0.15-1.0,the model has a good value of clinical decision-making.Conclusion:The incidence rate of severe postpartum hemorrhage in this population can be re-duced by attending regular prenatal checkups,controlling preg-nancy complications,and reducing the rate of emergency cesarean section and the number of deliveries.The nomogram prediction model established in this study has certain clinical application prospects.