1.Effect modification of amino acid levels in association between polycyclic aromatic hydrocarbon exposure and metabolic syndrome: A nested case-control study among coking workers
Jinyu WU ; Jiajun WEI ; Shugang GUO ; Huixia XIONG ; Yong WANG ; Hongyue KONG ; Liuquan JIANG ; Baolong PAN ; Gaisheng LIU ; Fan YANG ; Jisheng NIE ; Jin YANG
Journal of Environmental and Occupational Medicine 2025;42(3):325-333
Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnvOHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P50), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P75) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.
2.Correlation between the expression of serum LCN2, CMKLR1 and CCL11 and the severity of disease in patients with type 2 diabetes mellitus and dry eye
Guoying LIU ; Jiangping HOU ; Huan WU ; Yi JIANG
International Eye Science 2025;25(5):813-818
AIM: To investigate the correlation between the expression of serum lipocalin 2(LCN2), chemokine like receptor 1(CMKLR1), and C-C motif chemokine ligand 11(CCL11)and the severity of disease in patients with type 2 diabetes mellitus(T2DM)and dry eye(DE).METHODS:A prospective selection of 97 patients(194 eyes)diagnosed with T2DM and DE at our hospital from May 2022 to May 2024 was made as the DE group, which was further divided into mild(47 cases, 94 eyes), moderate(34 cases, 68 eyes), and severe(16 cases, 32 eyes)subgroups based on the severity of dry eye. Additionally, 97 patients(194 eyes)of T2DM without DE were selected as non-DE group, and 97 healthy volunteers(194 eyes)who underwent physical examination during the same period were chosen as control group. Serum levels of LCN2, CMKLR1, and CCL11 were measured in all participants. Spearman correlation analysis was used to assess the relationship between serum levels of LCN2, CMKLR1, and CCL11 and the severity of DE in T2DM patients; multivariate Logistic analysis was used to analyze the factors affecting the severity of T2DM patients with DE. The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum LCN2, CMKLR1 and CCL11 levels for moderate to severe dry eye in T2DM patients.RESULTS: Serum levels of LCN2, CMKLR1, and CCL11 increased progressively from the control group to the non-DE group and then to the DE group(all P<0.05). Within the DE group, these levels also increased progressively from the mild to moderate and then to the severe subgroups(all P<0.05). Spearman correlation analysis showed that serum levels of LCN2, CMKLR1, and CCL11 were positively correlated with the severity of disease(rs=0.604, 0.591, 0.559, respectively; all P<0.05). Stepwise forward multivariate Logistic analysis showed that Schirmer's test(SⅠt), tear break-up time(BUT), serum levels of LCN2, CMKLR1 and CCL11 were the factors affecting the severity of T2DM patients with DE; ROC curve analysis indicated that the combined diagnosis of serum LCN2, CMKLR1, and CCL11 for the progression of T2DM with DE to moderate-to-severe stages had an area under curve(AUC)value of 0.896, which was significantly higher than that of individual diagnoses of LCN2, CMKLR1, and CCL11(Z=2.925, 2.704, 3.483, respectively; P=0.003, 0.007, <0.001).CONCLUSION: Serum LCN2, CMKLR1 and CCL11 levels are increased in T2DM patients with DE, and are positively correlated with the severity of DE. The combination of the three has a high diagnostic value for moderate to severe DE.
3.Sodium arsenite influences proliferation and apoptosis in normal thyroid cells via modulation of ER-PI3K/AKT signaling pathway
Zhihong JIANG ; Hongyun LI ; Xiaowei MA ; Yuanyan LAI ; Jun WU
Journal of Environmental and Occupational Medicine 2025;42(4):467-474
Background Recent advances in understanding the toxic effects of inorganic arsenic have revealed that arsenic exposure impacts multiple endocrine organs, thereby altering their functions. However, the mechanisms underlying arsenic-induced thyroid injury remain unclear. Objective To investigate the mechanisms by which sodium arsenite (NaAsO₂) affects the proliferation and apoptosis of normal thyroid cells (Nthy-ori3-1) through the estrogen receptor (ER)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Nthy-ori3-1 cells were cultured in vitro and divided into the following groups: a control group (complete medium without drugs, 0 μmol·L−1), and NaAsO₂-treated groups at 1, 2, and 4 μmol·L−1. Additionally, 1 μmol·L−1 of the ER inhibitor ICI182780 was used to intervene in the NaAsO₂ exposure groups, resulting in the following combinations: 1 μmol·L−1 NaAsO₂ + ICI182780, 2 μmol·L−1 NaAsO₂ + ICI182780, and 4 μmol·L−1 NaAsO₂ + ICI182780. The median lethal concentration of NaAsO₂ was determined using cell viability assay. Cell viability was assessed at 24, 36, and 48 h using Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was evaluated via plate cloning assay. Apoptosis was detected using Hoechst
4.Value of three-dimensional inversion-recovery with real reconstruction sequence using an ultralong repetition time for endolymphatic hydrops
Menglong ZHAO ; Huaili JIANG ; Shujie ZHANG ; Zhuang LIU ; Kai LIU ; Di WU ; Xinsheng HUANG ; Mengsu ZENG
Chinese Journal of Clinical Medicine 2025;32(2):200-206
Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P < 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P < 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.
5.Application of three-dimensional fluid-attenuated inversion recovery sequence using artificial intelligence-assisted compressed sensing technique in intravenous gadolinium contrast-enhanced magnetic resonance imaging of inner ear
Kai LIU ; Jian WANG ; Huaili JIANG ; Shujie ZHANG ; Di WU ; Xinsheng HUANG ; Mengsu ZENG ; Menglong ZHAO
Chinese Journal of Clinical Medicine 2025;32(2):212-217
Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P<0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P<0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P<0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P<0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.
6.Alleviation of Ulcerative Colitis by Shaoyaotang via Inhibiting Glycolysis Through SIRT6/HIF-1α Pathway
Yiling XIA ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Erle LIU ; Yiwen WANG ; Shaijin JIANG ; Yiqian YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):10-19
ObjectiveTo investigate the role of silent information regulatory protein (SIRT6)/hypoxia-inducible factor-1α (HIF-1α) pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis (UC) and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group, a model group, a Mesalazine group (0.42 g·kg-1), a Shaoyaotang group (31.08 g·kg-1), an inhibitor group (OSS-128167, 50 mg·kg-1), and an inhibitor + Shaoyaotang group (50 mg·kg-1 OSS-128167 + 31.08 g·kg-1 Shaoyaotang). A UC model was established by the administration of 2.5% dextran sulfate sodium (DSS) solution for mice in other groups for 7 d, except for the blank group. The mice in each group were treated with saline, Mesalazine, Shaoyaotang, inhibitor, and inhibitor + Shaoyaotang, respectively, for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region, and colon tissue was taken. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect serum interleukin (IL)-10, IL-17, and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A (LDHA) levels. Immunohistochemistry (IHC) was employed to detect IL-22 and transforming growth factor-β1 (TGF-β1) levels in colon tissue, and Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect relative protein and mRNA expressions of SIRT6, HIF-1α, and LDHA. ResultsCompared with those of the blank group, disease activity index (DAI) scores of mice in the model group and inhibitor group were significantly increased (P<0.01). The length of colon tissue was significantly shortened, and colon tissue was congested and eroded. The pathohistological scores were significantly increased (P<0.01). The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated, and the levels of IL-10 were significantly decreased (P<0.01). The protein expressions of IL-22 and TGF-β1 were significantly reduced in colon tissue (P<0.01). The relative protein and mRNA expressions of SIRT6 were significantly decreased (P<0.01), and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated (P<0.01). The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group (P<0.01). Compared with the model group, the Mesalazine group, the Shaoyaotang group, and the inhibitor + Shaoyaotang group showed reduced colonic injury, significant decrease in serum IL-17 and IL-6, significant increase in IL-10 (P<0.01), significant increase in the protein expressions of IL-22 and TGF-β1 in colon tissue (P<0.01), significant increase in the protein expressions of SIRT6 and the relative mRNA expressions (P<0.01), and significant reduction in the protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate (P<0.01). Compared with those in the Shaoyaotang group, the serum IL-17 and IL-6 were significantly increased, and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group (P<0.01). The protein expressions of IL-22 and TGF-β1 in colon tissue were significantly decreased (P<0.01). The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased (P<0.01). The protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate were significantly elevated (P<0.01). However, the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway, and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.
7.Alleviation of Ulcerative Colitis by Shaoyaotang via Inhibiting Glycolysis Through SIRT6/HIF-1α Pathway
Yiling XIA ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Erle LIU ; Yiwen WANG ; Shaijin JIANG ; Yiqian YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):10-19
ObjectiveTo investigate the role of silent information regulatory protein (SIRT6)/hypoxia-inducible factor-1α (HIF-1α) pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis (UC) and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group, a model group, a Mesalazine group (0.42 g·kg-1), a Shaoyaotang group (31.08 g·kg-1), an inhibitor group (OSS-128167, 50 mg·kg-1), and an inhibitor + Shaoyaotang group (50 mg·kg-1 OSS-128167 + 31.08 g·kg-1 Shaoyaotang). A UC model was established by the administration of 2.5% dextran sulfate sodium (DSS) solution for mice in other groups for 7 d, except for the blank group. The mice in each group were treated with saline, Mesalazine, Shaoyaotang, inhibitor, and inhibitor + Shaoyaotang, respectively, for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region, and colon tissue was taken. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect serum interleukin (IL)-10, IL-17, and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A (LDHA) levels. Immunohistochemistry (IHC) was employed to detect IL-22 and transforming growth factor-β1 (TGF-β1) levels in colon tissue, and Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect relative protein and mRNA expressions of SIRT6, HIF-1α, and LDHA. ResultsCompared with those of the blank group, disease activity index (DAI) scores of mice in the model group and inhibitor group were significantly increased (P<0.01). The length of colon tissue was significantly shortened, and colon tissue was congested and eroded. The pathohistological scores were significantly increased (P<0.01). The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated, and the levels of IL-10 were significantly decreased (P<0.01). The protein expressions of IL-22 and TGF-β1 were significantly reduced in colon tissue (P<0.01). The relative protein and mRNA expressions of SIRT6 were significantly decreased (P<0.01), and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated (P<0.01). The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group (P<0.01). Compared with the model group, the Mesalazine group, the Shaoyaotang group, and the inhibitor + Shaoyaotang group showed reduced colonic injury, significant decrease in serum IL-17 and IL-6, significant increase in IL-10 (P<0.01), significant increase in the protein expressions of IL-22 and TGF-β1 in colon tissue (P<0.01), significant increase in the protein expressions of SIRT6 and the relative mRNA expressions (P<0.01), and significant reduction in the protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate (P<0.01). Compared with those in the Shaoyaotang group, the serum IL-17 and IL-6 were significantly increased, and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group (P<0.01). The protein expressions of IL-22 and TGF-β1 in colon tissue were significantly decreased (P<0.01). The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased (P<0.01). The protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate were significantly elevated (P<0.01). However, the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway, and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.
8.Current Situation, Trend, and Opportunity of Applying Blockchain to the Supply Chain of Orphan Drugs
Wenyan LI ; Yile YOU ; Jindong WU ; Xinrui LI ; Yunyun JIANG ; Shengfeng WANG
JOURNAL OF RARE DISEASES 2025;4(1):14-21
The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.
9.Dynamic Sequential Diagnosis and Treatment of Pediatric Nephrotic Syndrome Based on the "Sweat Pore-Qi and Liquid-Kidney Collaterals"
Zhenhua YUAN ; Mingyang CAI ; Yingying JIANG ; Jingjing WU ; Wenqing PAN ; Zichao DING ; Shuzi ZHANG ; Xianqing REN
Journal of Traditional Chinese Medicine 2025;66(10):1007-1010
Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals", it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure, qi and liquid imbalance, and kidney collaterals impairment, and it is proposed that the treatment principle is to nourish the sweat pore, regulate qi and fluid, and supplement the kidney and unblock the collaterals. In clinic, guided by sequential therapy and according to the different disease mechanism characteristics of the four stages, including early stage of the disease, hormone induction stage, hormone reduction stage, hormone maintenance stage, the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency, modified Zhenwu Decoction (真武汤) was applied to warm yang and drain water; for hormone induction stage with yin deficiency resulting in effulgent fire, modified Zhibai Dihuang Pill (知柏地黄丸) plus Erzhi Pill (二至丸) was used to enrich yin and reduce fire; for hormone reduction stage with qi and yin deficiency, modified Shenqi Dihuang Decoction (参芪地黄汤) was used to boost qi and nourish yin; for hormone maintenance stage, modified Shenqi Pill (肾气丸) was used to supplement yin and yang. Meanwhile, the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals, so as to providing ideas for clinical treatment.
10.Expression and clinical significance of TLR4 and NF-κB in conjunctival epithelial cells and tears of patients with dry eye
Guoying LIU ; Jiangping HOU ; Huan WU ; Yi JIANG
International Eye Science 2025;25(6):975-979
AIM: To investigate the expression and clinical diagnostic value of toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: From January 2023 to June 2024, 104 dry eye patients(104 eyes, disease group)who visited our hospital and 100 healthy individuals(100 eyes, control group)who underwent physical examination were selected. The changes of TLR4 and NF-κB in conjunctival epithelial cells and tears were analyzed. Pearson analysis was applied to analyze the correlation between TLR4 and NF-κB expression in conjunctival epithelial cells and tears. Logistic analysis was applied to analyze the factors that affected dry eye. ROC was applied to analyze the diagnostic value of TLR4 and NF-κB expression in conjunctival epithelial cells and tears for dry eye.RESULTS: The differences in the use of eye drops, tear film break-up time(BUT), Schirmer's test(SⅠt), tear film thickness(TFT), and corneal fluorescein staining(CFS)scores between the disease group and the control group were statistically significant(all P<0.01). The expression levels of TLR4 and NF-κB in conjunctival epithelial cells and tears in the disease group were significantly higher than those in the control group(all P<0.01). There was a positive correlation between TLR4 and NF-κB in conjunctival epithelial cells and tears(r=0.392, 0.348, all P<0.05). Frequent use of eye drops, CFS score, TLR4, and NF-κB were risk factors for dry eye(OR=2.153, 3.183, 1.578, 2.452, all P<0.05), while BUT, SⅠt, and TFT were protective factors for dry eye(OR=0.654, 0.755, 0.276, all P<0.05). The sensitivity, specificity, and AUC of TLR4 combined with NF-κB in conjunctival epithelial cells in the diagnosis of dry eye were 86.54%, 81.00%, and 0.889, respectively. The combination of TLR4 and NF-κB had higher diagnostic value for dry eye than uncombined diagnosis(Zcombination-TLR4=3.506, P=0.001; Zcombination-NF-κB=3.165, P=0.002). The sensitivity, specificity, and AUC of TLR4 combined with NF-κB in tears for diagnosing dry eye were 82.69%, 70.00%, and 0.818, respectively. The combination of TLR4 and NF-κB in tears had higher diagnostic value for dry eye than uncombined diagnosis(Zcombination-TLR4=3.117, P=0.002; Zcombination-NF-κB=2.363, P=0.018).CONCLUSION: The expression levels of TLR4 and NF-κB in conjunctival epithelial cells and tears of patients with dry eye are elevated. TLR4 and NF-κB are related to the development of dry eye, and that elevated levels of both are associated with an increased risk of dry eye disease. The combination of TLR4 and NF-κB has a certain diagnostic significance for dry eye.

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