Background As one of the most severe occupational diseases in China, pneumoconiosis is significantly burdened by its complications, which adversely affects patients' quality of life. Objective To identify the influencing factors of complications in pneumoconiosis and to construct an early prediction model for pneumoconiosis complications, providing theoretical guidance for clinical diagnosis, treatment, and rehabilitation. Methods A case-control study was conducted using data from the Chongqing 5G Pneumoconiosis Rehabilitation Management Information Platform. A total of 1872 pneumoconiosis patients with complications, who received rehabilitation at various rehabilitation stations in Chongqing from January 2021 to December 2024, were enrolled as the case group. Concurrently, 2348 patients without complications from the same platform and period were included as the control group. Univariate analysis, LASSO regression, and logistic regression were employed to identify influencing factors for complications. An extreme gradient boosting (XGBoost) model was trained using ten-fold cross-validation to predict pneumoconiosis complications. The SHapley Additive exPlanations (SHAP) method was applied for model visualization. Results The analysis of influencing factors revealed that increased age, silicosis type, advanced stage of pneumoconiosis, dependence in activities of daily living, abnormal muscle strength, increased dyspnea index, presence of cough, viscous sputum, impaired cardiac function, severe abnormality in the 6-minute walk test (6MWT), and increased Borg score were risk factors for complications (P<0.05). The XGBoost model demonstrated an area under the curve (AUC) of receiver operating characteristic of 0.718, and a Brier score of 0.211 for the calibration curve. Decision curve analysis demonstrated a superior net benefit within the threshold probability range of 0.2 to 1.0 compared to "all-patient intervention" and "no-patient intervention" strategies, indicating good predictive performance and significant clinical utility. SHAP visualization identified the top six important features as Borg score, age, 6MWT, muscle strength, pneumoconiosis stage, and cough symptoms. Conclusion Multiple factors influence the occurrence of complications in pneumoconiosis patients. Clinical attention should be focused on elderly patients with decreased cardiopulmonary reserve, pronounced respiratory symptoms, and diminished muscle strength. The XGBoost model demonstrates satisfactory discrimination, calibration, and clinical applicability in predicting pneumoconiosis complications and may serve as a useful reference for clinical decision-making.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Objective To investigate the distribution characteristics of Oncomelania hupensis snails in Yunnan Province fol-lowing interruption of schistosomiasis transmission, so as to provide the evidence for assessing the risk of schistosomiasis transmission and scientifically formulating the schistosomiasis surveillance program. Methods According to the requirements of the National Schistosomiasis Surveillance Scheme (2020 Edition), O. hupensis snail surveillance data were collected from 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province from 2020 to 2024, including area of snail survey, area of snail habitats, area of re-emerging snail habitats, number of frames surveyed, number of frames with O. hupensis snails, number of O. hupensis snails captured, and number of living snails, and the occurrence of frames with snails and mean density of living snails were calculated. Changes in snail status over the 5-year period from 2020 to 2024 and the differences in snail distributions specified by epidemic intensity, environmental type, and vegetation type were analyzed. Results The areas of snail survey increased from 1 727.96 hm² in 2020 to 3 894.45 hm² in 2024 (peak) across 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province during the period from 2020 through 2024. The areas of snail habitats increased from 70.36 hm² in 2020 to a peak in 2023 (172.04 hm²), followed by a reduction to 132.36 hm² in 2024, and the areas of re-emerging snail habitats increased from 42.71 hm² in 2020 to a peak in 2022 (78.43 hm²), followed by a reduction to 40.21 hm² in 2024. The occurrence of frames with snails and mean density of living snails increased from 1.24% (3 025/244 404) and (0.033 2 ± 0.038 7) snails/0.1 m² in 2020 to peaks at 2.03% (6 231/307 563) and (0.066 9 ± 0.068 4) snails/0.1 m² in 2023, followed by reductions to 1.04% (5 829/559 941) and (0.032 6 ± 0.057 7) snails/0.1 m² in 2024, respectively. There was a significant difference in the occurrence of frames with snails over the 5-year study period (χ² = 1 962.95, P < 0.05), and the occurrence of frames with snails reduced by 48.71% in 2024 relative to in 2023 (χ² = 1 411.05, P < 0.005); however, there was no significant difference in the mean density of living snails over the 5 years (H = 5.310, P > 0.05). There were significant differences in the occurrence of frames with snails (χ² = 481.27, P < 0.05) and mean density of living snails (H = 6.872, P < 0.05) in schistosomiasis-endemic areas with different epidemic intensities. The occurrence of frames with snails (χ² = 25.32 and 38.70, both P values < 0.017) and mean density of living snails (Z = 28.55 and 49.96, both P values < 0.017) were higher in schistosomiasis transmission-interrupted and eliminated areas with snails than in schistosomiasis-eliminated areas without snails, and the occurrence of frames with snails (χ² = 453.54, P < 0.017) and mean density of living snails (Z = −56.97, P < 0.017) were higher in schistosomiasis-eliminated areas with snails than in schistosomiasis transmission-interrupted areas with snails. O. hupensis snails were mainly distributed in paddy fields, dry farmlands and ditches; however, the occurrence of frames with snails (13.40%, 424/3 164) and mean density of living snails [(0.252 8 ± 0.158 7) snails/0.1 m²] were higher in ponds/weirs than in other types of environments (both P values < 0.05). Rice, dry farmland crops and weeds were main vegetations in which O. hupensis snails were distributed, and the occurrence of frames with snails (2.29%, 7 111/310 140) and mean density of living snails [(0.072 3 ± 0.018 9) snails/0.1 m²] were higher in weeds than in other types of environments (both P values < 0.05). Conclusions O. hupensis snails have been effectively controlled in Yunnan Province following implementation of integrated schistosomiasis control measures; however, there are still risk factors for schistosomiasis transmission, including reduced attention to schistosomiasis control and snail re-emergence. Improved control efforts and surveillance system construction and timely identification of risk factors of snail status and timely management are recommended to ensure the achievement of the target of schistosomiasis elimination as scheduled.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Objective To investigate the correlation between peripheral blood CD14+CD16+monocytes and IgG N-glycosyl levels and disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 109 SLE patients admitted to Xingtai Cental Hospital from August 2021 to November 2024 were retrospectively selected as the study objects.According to SLE disease activity index(SLE-DAI),the patients were divided into active group(n=52)and stable group(n=57).In addition,56 patients who underwent physical examination during the same period were selected as the control group.Clinical data of patients were collected,CD14+CD16+mononuclear cells were detected by flow cytometry(FCM),and IgG N-glycosyl levels were detected by hydrophilic interaction chromatography-mass spectrometry.Logistic regression analysis was performed to analyze the influencing factors of SLE-DAI,and multicollinearity test[variance inflation factor(VIF)]was performed for independent variables.The prediction model of disease activity was constructed.The effectiveness of the predictive model was evaluated by describing the recviver operator characteristic(ROC)curve and calculating the area under the curve(AUC)value.Hosmer-Lemeshow goodness-of-fit test predicted the calibration degree of the model.Results The levels of WBC,Hb,PLT,ALB,complement C3 and complement C4 in control group were higher than those in SLE group(t=8.917～22.171),and the levels of CRP were lower than those in SLE group(t=-17.359),with differences were statistical significance(all P<0.05).The CRP level and the proportion of CD14+CD16+mononuclear cells in the active group were higher than those in the stable group,and the differences were statistically significant(t=5.449,11.112,all P<0.05).The IgG glycosylation characteristics of galactosylation,sialylation and N-acetylglucosamine modification were lower than those in the stable group,and the differences were statistical significance(Z=-2.432～-0.158,all P<0.05).Spearman correlation analysis showed that the proportion of CD14+CD16+monocytes was significantly negatively correlated with IgG galactosylation,sialylation level and bisection N-acetylglucosamine modification(r=-0.656,-0.531,-0.608,all P<0.01).CD14+CD16+monocyte ratio was positively correlated with SLE-DIA(r=0.581,all P<0.01).IgG galactosylation,sialylation levels and bisection N-acetylglucosamine modification were negatively correlated with SLE-DIA(r=-0.645,-0.609,-0.503,all P<0.01).Logistic regression analysis showed that CRP>8.21mg/L,CD14+CD16+≥16.17%,sialylation<22.05%and isotropic N-acetylglucosamine modification<16.53%were independent risk factors for disease activity in SLE patients(Wald χ2=4.471～12.811,all P<0.05).The VIF values of the above independent variables were all less than 10.By establishing the Logistic regression prediction model and drawing the ROC curve,the AUC value for diagnosing SLE disease activity was 0.821(95%CI:0.733～0.905),the sensitivity,specificity and the Yodon index were 85.37%,75.67%,0.677,respectively.and the P values of Hosmer-Lemeshow goodness-of-fit test models were 0.568,respectively.Conclusion The proportion of CD14+CD16+monocytes in peripheral blood of SLE patients increase significantly,and the level of IgG glycosylation characteristics decrease,both of which are correlated with SLE-DIA.The predictive model constructed based on the two had a good ability to distinguish SLE-DIA from inactive state,with high sensitivity and moderate specificity conducive to early clinical recognition,and the model fitting effect is good.SLE-DIA can be evaluated more accurately.

Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

Depression is a heterogeneous mental disorder in which the interaction between genetic susceptibility and environ-mental factors plays a key role in its pathogenesis.Although the specific mechanisms of the disease still need to be thoroughly studied and elucidated,there is now a broad consensus that epi-genetic markers have a central influence on its mechanism of ac-tion.DNA methylation of brain-derived neurotrophic factor(BD-NF)is not only regarded as a promising epigenetic biomarker of pathology,but may also help predict the efficacy of antidepres-sants.In this paper we reviewed the gene structure of BDNF and its DNA methylation regulation mechanism,and also analyzed the changes of DNA methylation of this factor in depression pa-tients and animal models,aiming to provide new ideas and theo-retical support for clinical research.

Objective:To investigate the dynamic cerebral oxygen metabolism characteristics in drug-naive patients with primary insomnia (PI), and analyze the association between the cerebral oxygen metabolism and insomnia symptoms.Methods:A total of 31 drug-naive patients with PI and 36 healthy controls were recruited from July 2024 to February 2025. Insomnia symptoms were assessed by the Pittsburgh sleep quality index (PSQI). Functional near infrared spectroscopy (fNIRS) technique was employed to collect 180 s resting-state oxygenated hemoglobin concentration changes from dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex, temporal lobe (TL), parietal lobe (PL) and occipital lobe. Sliding time window analysis and K-means clustering algorithm were applied to cluster the oxygenation data into K temporal categories. Statistical analysis, including t-test, Wilcoxon rank-sum test, chi-square test, Pearson/Spearman correlation analysis, and multiple linear regression were performed using SPSS 26.0 software. Results:Clustering analysis revealed 4 characteristic temporal categories (K=4) during the 180 s resting-state. Compared to healthy controls, drug-naive PI patients exhibited higher oxygenation levels in bilateral TLs during the second temporal category(left TL(18.19±6.18)mmol/dL, (16.82±4.47)mmol/dL; right TL(18.20±8.97)mmol/dL, (16.17±5.64)mmol/dL), but lower levels during the third temporal category(left TL(16.54± 5.09)mmol/dL, (17.98±5.34)mmol/dL; right TL(15.82±7.29)mmol/dL, (17.84±5.94)mmol/dL), and exhibited lower oxygenation level in right PL during the second category((16.16±6.56)mmol/dL, (17.60±5.84)mmol/dL) (all P<0.05). Oxygenation levels in the right DLPFC during the first temporal category ( β=0.44, t=2.52, P=0.018), in the left DLPFC during the second temporal category( β=-0.47, t=-2.82, P=0.009), and in the right PL during the second temporal category( β=-0.46, t=-2.78, P=0.010) were influencing factors for the PSQI score. Conclusions:The bilateral TLs and right PL in drug-naive PI patients exhibit phase-specific abnormalities in oxygen metabolism, potentially attributable to the insomnia-induced dysregulation of endogenous neural oscillations. The oxygen concentration changes in bilateral DLPFCs and right TL are associated with insomnia symptoms.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.