OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Aim To explore how Danzhi Jiangtang cap-sules(DJC)safeguard the mitochondrial activity of vascular smooth muscle cells(VSMCs)by controlling the LncRNA TUG1/β-catenin signaling pathway to de-crease vascular calcification(VC).Methods Vascu-lar smooth muscle cell calcification models were in-duced with β-glycerin and diabetic vascular calcifica-tion rat models were induced with vitamin D3+high-fat diet.Von Kossa staining was applied to detect cal-cification of cells and vascular tissue.Colorimetric method of phthalein complex was used to determine calcium content.P-nitrobenzene phosphate colorimetry was employed to assess alkaline phosphatase(ALP)activity.RT-qPCR was used to analyze the expression of VSMCs'osteoblast transformation related genes bone morphogenetic protein2(BMP2),smooth muscle actin alpha(α-SMA),taurine up-regulated1,LncRNA Tug1(Lnc-RNA TUG1),and β-catenin.Western blotting was utilized to detect the protein expression of BMP2,α-SMA and β-catenin.The mitochondrial membrane potential was detected by JC-1 fluorescence probe.Mitochondrial structure was observed by trans-mission electron microscope.Results DJC reduced LncRNA TUG1 expression,down-regulated β-catenin expression,decreased ALP activity and calcium depo-sition,protected mitochondrial function,restored mem-brane potential,and decreased osteoblastic transforma-tion of VSMCs induced by glycerin phosphate.Impor-tantly,DJC attenuated diabetic lower limb VC by down-regulating the expression of LncRNA TUG1,β-catenin,and elevating the expression of α-SMA.Con-clusions DJC capsules significantly improved VSMCs by protecting mitochondrial function by LncRNA TUG1/β-catenin signaling to reduce VSMCs'osteo-blast transformation.

Objective To investigate the effect of osimertinib combined with aspirin on the survival pe-riod of the advanced lung adenocarcinoma patients with epidermal growth factor receptor(EGFR)mutation.Methods Sixty lung adenocarcinoma patients with EGFR mutation in advanced non-small cell lung cancer(NSCLC)first diagnosed in Banan District Second People's Hospital of from August 2020 to October 2021 were selected as the study subjects and divided into the observation group and control group by the random number table method,30 cases in each group.The observation group adopted osimertinib combined with aspi-rin,and the control used osimertinib merely.The overall response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and the adverse reactions occurrence were compared between the two groups.Results ORR and DCR after 3,6,12 months medication in the observation group were higher than those in the control group,but the differences were not statistically significant(P＞0.05).Compared with the control group,PFS and OS in the observation group were longer,and the differences were statistically significant[14.9(11.8,17.2)m vs.10.5(8.9,12.5)m;24.1(19.5,27.4)m vs.18.1(16.1,21.1)m,P＜0.05].In addition,PFS and OS in male and female patients with brain metastasis,EGER19 and 21 ex-on mutation in the observation group were longer than those in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in overall and≥Ⅲ degree adverse reactions between the two groups(P＞0.05).Conclusion Osimertinib combined with aspirin could prolong PFS and OS of the advanced lung adenocarcinoma patients with EGFR mutation without increasing the risk of adverse reactions.

With the prevalence of myopia in Asia, the prevalence of high myopia is gradually increasing, and high myopia has undoubtedly become a public health problem in Asia and even around the globe. As a relatively common pathological change in the eyes of patients with high myopia, optic disc tilt may also become a risk factor for diseases such as glaucoma and macular degeneration, thereby increasing the risk of visual impairment. However, the mechanism of optic disc tilt in high myopia and the role of optic disc tilt in the aggravation of high myopia complications still needs to be further explored. Therefore, this article collects and organizes relevant literatures on optic disc tilt, and makes a comprehensive discussion on the mechanism of optic disc shape changing caused by high myopia and the impact on various complications, so as to provide a certain basis for clinical diagnosis and treatment of high myopia and its complications.

Objective:To explore the effect of fully automatic image segmentation of adenoid and nasopharyngeal airway by deep learning model based on U-Net network. Methods:From March 2021 to March 2022, 240 children underwent cone beam computed tomography（CBCT） in the Department of Otolaryngology, Head and Neck Surgery, General Hospital of Shenzhen University. 52 of them were selected for manual labeling of nasopharynx airway and adenoid, and then were trained and verified by the deep learning model. After applying the model to the remaining data, compare the differences between conventional two-dimensional indicators and deep learning three-dimensional indicators in 240 datasets. Results:For the 52 cases of modeling and training data sets, there was no significant difference between the prediction results of deep learning and the manual labeling results of doctors（P>0.05）. The model evaluation index of nasopharyngeal airway volume: Mean Intersection over Union（MIOU） s （86.32±0.54）%; Dice Similarity Coefficient（DSC）: （92.91±0.23）%; Accuracy: （95.92±0.25）%; Precision: （91.93±0.14）%; and the model evaluation index of Adenoid volume: MIOU: （86.28±0.61）%; DSC: （92.88±0.17）%; Accuracy: （95.90±0.29）%; Precision: （92.30±0.23）%. There was a positive correlation between the two-dimensional index A/N and the three-dimensional index AV/（AV+NAV） in 240 children of different age groups（P<0.05）, and the correlation coefficient of 9-13 years old was 0.74. Conclusion:The deep learning model based on U-Net network has a good effect on the automatic image segmentation of adenoid and nasopharynx airway, and has high application value. The model has a certain generalization ability.
Child ; Humans ; Adolescent ; Adenoids/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Pharynx ; Cone-Beam Computed Tomography ; Nose

Objective:To evaluate the incidence, clinical characteristics and prognosis of second primary malignancies (SPMs) among patients with hypopharyngeal carcinoma (HPC) in real-world analysis.Methods:A total of 594 HPC patients admitted to Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2010 to 2018 were retrospectively analyzed.The incidence and clinical characteristics of HPC patients complicated with SPMs were analyzed. Clinical efficacy was compared among different groups.Results:With a median follow-up time of 66.9 months, SPMs were present in 36.4% (216/594) of HPC patients: 22.2% (132/594) were synchronous and 14.1% (84/594) were metachronous. The upper aerodigestive tract was the most common involved region. Compared with patients without SPMs, patients with synchronous and metachronous carcinoma in situ had similar 5-year overall survival (OS) of 42.2% vs. 44.5% ( P=0.958) and 62.2% vs. 44.5% ( P=0.240), respectively. Patients with synchronous invasive SPMs had a worse 5-year OS of 27.2% vs. 44.5% in their counterparts without SPMs ( P=0.001). Patients with metachronous invasive SPMs had similar 5-year OS of 50.2% vs. 44.5% in their counterparts without SPMs ( P=0.587). SPMs accounted for 42.5% of total death in metachronous invasive SPMs group. Conclusions:Patients with HPC have a high probability of developing SPMs. Moreover, the incidence of complicated with esophageal/gastric carcinoma in situ or metachronous SPMs exerts no effect on prognosis, while the occurrence of synchronous SPMs significantly affectes the prognosis of patients. However, the incidence of SPMs is still one of the main death causes in metachronous invasive SPMs group.

Previously, we discovered that cells contain a 5-hydroxytryptamine (5-HT) degradation system (5DS), which includes 5-HT_2A receptor (5-HT_2AR), 5-HT synthase, and monoamine oxidase A (MAO-A). Among these, 5-HT_2AR has the ability to regulate the expression of 5-HT synthase and MAO-A, and activation of 5DS causes upregulation of these proteins at the same time, resulting in the production of reactive oxygen species (ROS) in the mitochondria. In this study, we investigated the relationship between interstitial pneumonia (IP) and 5DS activation, as well as the therapeutic effect of inhibiting 5DS on IP. Animal models of bleomycin (BLM)-induced IP in mice and radiation (Rad)-induced IP in rats were established, and the models were treated with the 5-HT_2AR antagonist sarpogrelate hydrochloride (SH), 5-HT synthesis inhibitor carbidopa (CDP), and their combination (SH∶CDP = 2∶1). The animal experiments were carried out in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. In the two IP models, immunohistochemistry staining and Western blot analysis showed that the expression of 5-HT synthase was significantly upregulated in all cells of lung tissue, while the expression of 5-HT_2AR and MAO-A was most significantly upregulated in the macrophages. Treatment with SH or CDP significantly reduced pulmonary interstitial thickening, alveolar atrophy with collapse, massive macrophage infiltration and interstitial fibrosis in the two IP models, as measured by HE and Masson staining, and a combination of both almost eliminated the lung tissue lesions. Moreover, treatment with the combination of SH and CDP almost completely eliminated increased ROS and malondialdehyde levels, decreased superoxide dismutase activity, increased tumor necrosis factor-α and interleukin-1β levels, and upregulated nuclear factor-κB phosphorylation and α‍-smooth muscle actin, matrix metalloproteinase-2, and collagen expression. SH and CDP worked together to create a synergistic effect. The findings suggested that the activation of 5DS, as evidenced by increased 5-HT synthesis in all cells of lung tissue and increased 5-HT synthesis and degradation in macrophages, is probably related to the occurrence of IP and that inhibition of 5DS can effectively treat IP.

AIM:A total of 1 084 preschool children in 4 kindergartens in Xining City were surveyed on their visual acuity and refraction status to find out abnormal vision and refraction beyond the normal range. METHODS: A cross-sectional survey study. The overall sampling method was used on October 2019, a total of 1 084 preschool children aged 3-6 years were selected from a kindergarten in the east, west, south and north of Xining City. The children were checked for uncorrected distance vision and refractive status was checked by using a refractive screener.RESULTS: The detection rate of abnormal vision in preschool children in Xining City was 12.21%, and the detection rate of abnormal vision increased with the increasing age(χ2lineartrend=94.40, P<0.05), and there were differences among different age groups(χ2=293.55, P<0.05). Refractive abnormalities accounted for 6.09% of the total number of examinations. With the increasing age, the proportion of compound hyperopic astigmatism decreased(χ2lineartrend=1.79, P>0.05).CONCLUSION: The abnormal visual acuity of preschool children in Xining City gradually increases with the increasing age; The refractive state is dominated by astigmatism, among which the proportion of mixed astigmatism and pure myopia astigmatism is the highest, followed by pure hyperopic astigmatism and compound hyperopic astigmatism; With the increase of age, the diopter of compound hyperopic astigmatism gradually decreases, which is in line with the law of children's eye refractive development.

ObjectiveTo explore the effect of Gegen Qinliantang （GQL） on vulnerable plaque of atherosclerosis based on the macrophage pyroptosis mediated by nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1 pathway. MethodA total of 12 normal C57BL/6CNC mice were used as the control group， and 60 ApoE^-/- mice of the same line were randomized into 5 groups： model group， low-dose， medium-dose， and high-dose GQL groups （GQL-D， GQL-Z， GQL-G groups， respectively）， and western medicine group. The control group and model group were given （ig） equal volume sterile distilled， and GQL-D， GQL-Z， GQL-G and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. Aortic plaques were observed based on hematoxylin and eosin （HE） staining. Serum levels of interleukin （IL）-1β and IL-18 were detected by enzyme-linked immunosorbent assay （ELISA）， protein levels of macrophage mannose receptor （CD206）/apoptosis-associated speck-like protein containing a CARD （ASC） and CD206/NLRP3 by double-labeling immunofluorescence， and C-terminal gasdermin D （GSDMD）， N-terminal GSDMD， NLRP3， pro-cysteinyl aspartate specific proteinase 1 （pro-Caspase-1） and NF-κB p65 by Western blot. ResultCompared with the control group， model group demonstrated serious pathological changes， rise of the levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and decrease of CD206 level （P<0.05）. As compared with model group， the administration groups showed alleviation of the lesions in aortic wall， decrease in levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and rise of CD206 level， with significant difference between some groups （P<0.05）. ConclusionGegen Qinliantang alleviates vulnerable plaque of atherosclerosis by regulating NF-κB/NLRP3/Caspase-1 pathway and further relieving macrophage pyroptosis.

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.