1.Effect of 3% diquafosol sodium eye drops on the tear film homeostasis of patients wearing orthokeratology lenses
Jiahong HAN ; Jianjun LIU ; Qinbin BAO ; Xu YANG
International Eye Science 2025;25(10):1667-1671
AIM:To investigate the effect of 3% diquafosol sodium eye drops on tear film homeostasis in patients wearing overnight orthokeratology lenses.METHODS:Retrospective study. A total of 340 patients(564 eyes)fitted with night-worn orthokeratology lenses from June to December 2022 were respectively divided into a diquafosol sodium group(200 cases, 323 eyes, treated with 3% diquafosol sodium eye drops)and a sodium hyaluronate group(140 cases, 241 eyes, treated with sodium hyaluronate eye drops). The uncorrected visual acuity(LogMAR), ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), meibomian gland infrared imaging score, and corneal epithelial fluorescein staining were analyzed and compared between the two groups.RESULTS:Compared to baseline, both groups showed significant improvements in uncorrected visual acuity(LogMAR)at 1 wk, 1, and 3 mo after lens wear(all P<0.01). However, no statistically significant difference in uncorrected visual acuity(LogMAR)was observed between the two groups at any time point(all P>0.05). No significant differences in NIBUT or OSDI scores were found between the groups before and at 1 wk after lens wear(all P>0.05). At the 1- and 3 mo follow-ups, the 3% diquafosol sodium group demonstrated significantly longer NIBUT(all P<0.001)and lower OSDI scores(all P<0.001)compared to the sodium hyaluronate group. After wearing lens for 3 mo, the meibomian gland infrared imaging scores were significantly better in the diquafosol sodium group(P<0.001), whereas no significant intergroup difference was observed in corneal fluorescein staining(P>0.05). Furthermore, the incidence of adverse events during the study period did not differ significantly between the two groups(P>0.05).CONCLUSION:Compared with sodium hyaluronate, 3% diquafosol sodium eye drops were more effective in maintaining tear film homeostasis in patients wearing overnight orthokeratology lenses.
2.Intermittent hypoxia aggravates asthma inflammation via NLRP3/IL-1β-dependent pyroptosis mediated by HIF-1α signalling pathway.
Ling ZHOU ; Huojun ZHANG ; Lu LIU ; Fengqin ZHANG ; Lingling WANG ; Pengdou ZHENG ; Zhenyu MAO ; Xiaoyan ZHU ; Guisha ZI ; Lixiang CHEN ; Xiaojing CAI ; Huiguo LIU ; Wei LIU
Chinese Medical Journal 2025;138(14):1714-1729
BACKGROUND:
Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved.
METHODS:
A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro .
RESULTS:
In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation.
CONCLUSIONS
Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Humans
;
Asthma/metabolism*
;
Animals
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Pyroptosis/physiology*
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Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
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Mice
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Signal Transduction/physiology*
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Male
;
Hypoxia/metabolism*
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Female
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Interleukin-1beta/metabolism*
;
Adult
;
Inflammation/metabolism*
;
Middle Aged
;
Mice, Inbred C57BL
3.Combined analysis of transcriptome and metabolome on the effect of virulence protein Mp1p from Talaromyces marneffei on macrophages
LIU Yuxuan ; WEI Wudi ; BAO Xiuli ; CHEN Lixiang ; ZHANG Baili ; HE Xiaotao ; YE Li ; JIANG Junjun ; LIANG Hao
China Tropical Medicine 2024;24(3):265-
Objective To explore the effect of Mp1p on host macrophages through transcriptomics combined with metabolomics. Methods Firstly, a THP-1 macrophage strain (THP-1-Mp1p+) stably expressing Mp1p was constructed using lentivirus. Secondly, using high-throughput RNA sequencing (RNA Seq) technology, the expression level of intracellular mRNA was detected in transcriptomics analysis to determine differentially expressed genes; In metabolomics analysis, metabolite identification was performed through database comparison, and pathway analysis was performed on differential metabolites to reveal potential mechanisms of action. Finally, the results of metabolomics and transcriptomics were combined for analysis, and differential metabolites and genes were analyzed to further elucidate the mechanism of action of Mp1p on macrophages. Results Transcriptome analysis showed that, compared with the negative control group, the THP-1-Mp1p+ group had a total of 1 180 differentially expressed genes (DEGs), with 345 upregulated genes and 835 downregulated genes. GO enrichment analysis of DEGs showed that there were 135 differentially expressed genes, including 105 in biological processes (BP), 28 in cellular components (CC), and 2 in molecular functions (MF). The KEGG analysis results showed that the effect of Mp1p on THP-1 macrophages was highly correlated with the TNF pathway. The metabolomic analysis found that both the blank control group and the THP-1-Mp1p+ macrophage group achieved good separation between QC samples in both positive and negative ion modes. The threshold for significant differential metabolites was set at: VIP≥1 and T-test P<0.05, resulting in the identification of 488 differential metabolites, with 230 in the positive ion mode and 258 in the negative ion mode. Pathway enrichment analysis of the identified metabolites pointed to significant enrichment in metabolic pathways. The combined analysis confirmed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway were important metabolic pathways involved. Conclusions The virulence factor Mp1p may affect host macrophages by modulating the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway. The findings contribute to a better understanding of the mechanisms of action of Mp1p and may offer potential directions for the selection of relevant diagnostic and therapeutic targets in the future.
4.Psychological problems in breast cancer patients should be taken seriously
Lijuan HOU ; Liyuan LIU ; Fei WANG ; Lixiang YU ; Zhigang YU
Chinese Journal of Surgery 2024;62(2):110-115
With the transformation of the biopsychosocial medical model, psychological problems and related interventions for breast cancer patients have received more and more attention. Patients often have various psychological problems, in diagnosis, treatment, and even in the state of disease-free survival, such as anxiety and depression, which not only seriously reduces the quality of life, but also affects the follow-up treatment and increases the risk of recurrence and metastasis. Therefore, physicians should perform routine psychological screening and appropriate intervention for patients. In recent years, psychological intervention has gradually become an important part of comprehensive breast cancer treatment, in which cognitive behavior therapy can alleviate patients′ anxiety and sleep disorders, mindfulness therapy can treat patients′ anxiety, depression and fear of cancer recurrence, and psychoeducational support is mainly used to address patients′ mood disorders and sexual dysfunction. Improving patients′ compliance with treatment and quality of life is the main goal of psychological intervention for breast cancer patients.
5.An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor
Liang LI ; Zequn FENG ; Lianfang ZHANG ; Ruiqing WANG ; Xiaoxia ZHANG ; Liyuan LIU ; Lixiang YU ; Zhigang YU ; Zhongcheng GAO
Chinese Journal of Surgery 2024;62(2):135-140
Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.
6.DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis:Perspective of Different Water Iodine Exposure
Chen YAO ; Liu JINJIN ; Qu MENGYING ; Ren BINGXUAN ; Wu HUAIYONG ; Zhang LI ; Zhou ZHENG ; Liu LIXIANG ; Shen HONGMEI
Biomedical and Environmental Sciences 2024;37(9):1044-1055
Objective This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT),focusing on the influence of varying water iodine exposure levels. Methods Participants were divided into categories based on median water iodine (MWI) concentrations:iodine-fortified areas (IFA,MWI<10 μg/L),iodine-adequate areas (IAA,40 ≤ MWI ≤ 100μg/L),and iodine-excessive areas (IEA,MWI>300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89,40,and 47 pairs for IFA,IAA,and IEA,respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget? and QRT-PCR for 176/176 paired samples. Results KLRC1,KLRC3,and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed,whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore,KLRC1 was hypomethylated and highly expressed in both IFA and IEA. Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally,DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.
7.Psychological problems in breast cancer patients should be taken seriously
Lijuan HOU ; Liyuan LIU ; Fei WANG ; Lixiang YU ; Zhigang YU
Chinese Journal of Surgery 2024;62(2):110-115
With the transformation of the biopsychosocial medical model, psychological problems and related interventions for breast cancer patients have received more and more attention. Patients often have various psychological problems, in diagnosis, treatment, and even in the state of disease-free survival, such as anxiety and depression, which not only seriously reduces the quality of life, but also affects the follow-up treatment and increases the risk of recurrence and metastasis. Therefore, physicians should perform routine psychological screening and appropriate intervention for patients. In recent years, psychological intervention has gradually become an important part of comprehensive breast cancer treatment, in which cognitive behavior therapy can alleviate patients′ anxiety and sleep disorders, mindfulness therapy can treat patients′ anxiety, depression and fear of cancer recurrence, and psychoeducational support is mainly used to address patients′ mood disorders and sexual dysfunction. Improving patients′ compliance with treatment and quality of life is the main goal of psychological intervention for breast cancer patients.
8.An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor
Liang LI ; Zequn FENG ; Lianfang ZHANG ; Ruiqing WANG ; Xiaoxia ZHANG ; Liyuan LIU ; Lixiang YU ; Zhigang YU ; Zhongcheng GAO
Chinese Journal of Surgery 2024;62(2):135-140
Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.
9.The preliminary application of cinematic rendering reconstruction technology in acute aortic dissection
He ZHANG ; Zhongxiao LIU ; Meng YU ; Miao YU ; Ziyou WANG ; Wenbei XU ; Xiaonan SUN ; Shenman QIU ; Lixiang XIE ; Yanchun ZHANG ; Yankai MENG ; Cunjie SUN ; Kai XU
Journal of Practical Radiology 2024;40(10):1620-1624
Objective To analyze the clinical application value of cinematic rendering(CR)reconstruction technology in acute aortic dissection(AAD),and to compare the imaging quality between CR and volume rendering(VR)reconstruction.Methods Patients with suspected A AD who underwent aortic computed tomography angiography(CTA)were analyzed retrospectively.All images were uploaded to Siemens Syngo.via post-processing workstation for VR and CR three-dimensional reconstruction,respectively.The optimized view angle,staining and transparency were selected and segmented by a radiologist to display the lesion to the full extent.All subjective evaluations of post-processing images were randomly evaluated on Siemens Syngo.via post-processing workstation by two radiologists.The two radiologists reached a consensus after consultation,and the results without consensus were evaluated by another senior radiologist.The 3-point scale was used in the subjective evaluation of post-processing images.The scores of rupture,endometrium,and true and false cavity were recorded.The diagnostic confidence was also recorded.Results A total of 21 ADD patients were enrolled,11 patients(52.3%)were Debakey Ⅲ type.The scores of rupture in CR and VR reconstruction were 2.952 points and 2.619 points,respectively,which had significant difference(P=0.016).For the endometrium of AAD,the score of all 21 patients in the CR reconstruction was 3 points,while only 7 patients(33.3%)in the VR reconstruction had 3 points,which showed significant difference between the both(P<0.001).For the true and false cavity of AAD,only 1 patient(4.8%)in the VR reconstruction was 3 points,while all 21 patients in the CR reconstruction had 3 points(P<0.001).The scores of CR reconstruction on the diagnostic confidence were significantly higher than those of VR reconstruction(P<0.001).Conclusion CR reconstruction can provide photorealistic anatomical post-processing images,and can improve the display and evaluation of AAD.
10.Predictive value of the differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on therapeutic response in patients with papillary thyroid cancer
Junyu ZHANG ; Di FAN ; Zhiyong SHI ; Tiane LUO ; Zhifang WU ; Hongliang WANG ; Keyi LU ; Suyun YANG ; Lixiang WU ; Tingting HU ; Yuanyuan MOU ; Sijin LI ; Haiyan LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):730-735
Objective:To investigate the predictive value of differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on the therapeutic response to 131I treatment in patients with papillary thyroid cancer (PTC). Methods:A retrospective study was conducted on 46 PTC patients (16 males, 30 females, age 20-77 years) who underwent total thyroidectomy and received 131I treatment between January 2021 and August 2021 in First Hospital of Shanxi Medical University. Peripheral blood lymphocyte subsets (T, B, CD4 + T, CD8 + T, natural killer (NK), helper T (Th)1, Th2, Th17, and regulatory T (Treg) cells) were measured 1-2 d before and 30 d after 131I treatment. Based on serological and imaging evidence, therapeutic response at 6-12 months post- 131I therapy was categorized as either excellent response (ER) or non-excellent response (NER). Differences of preablative stimulated thyroglobulin (psTg) and clinical baseline characteristics between two groups were assessed by using independent-sample t test, paired t test, or Mann-Whitney U test. Predictive value of lymphocyte subsets before and after 131I treatment for therapeutic response was assessed through logistic regression analysis, ROC curve analysis, and decision curve analysis (DCA). Results:In ER group ( n=33) and NER group ( n=13), most lymphocyte subsets showed different degrees of reduction 30 d after 131I treatment compared to before 131I treatment, such as T, B, CD4 + T and Th1 cells in ER group, as well as T, B, CD4 + T, Th1, Th2, Th17, and Treg cells in NER group ( t values: 2.41-9.57, all P<0.05). Before 131I treatment, NER group had significantly higher levels of psTg, Th2, Th17, and Treg cells compared to the ER group ( t values: from -3.32 to -2.48, U=29.00, all P<0.05). After 131I treatment, most of lymphocyte subsets in NER group (T, B, CD4 + T, CD8 + T, Th1 and Treg cells) showed higher trend than those in ER group but without statistical significances ( t values: from -1.12 to -0.06, all P>0.05). Th2 cells before 131I treatment (odds ratio ( OR)=25.00, 95% CI: 1.36-459.10, P=0.030) was identified as a risk factor for NER. ROC curve analysis indicated that AUCs of psTg and Th2 cells for predicting therapeutic response were 0.932 and 0.790, respectively, which was 0.958 for the combined psTg and Th2 cells. DCA showed that within the threshold probability range of 10%-60%, the curves for psTg, Th2 cells, and the combined psTg and Th2 cells were all higher than the extreme curve, suggesting good effect. Conclusions:Most lymphocyte subsets decrease to varying degrees, and NER group shows a significant decrease 30 d after 131I treatment. Th2 cells may be a risk factor for poor response to 131I treatment, providing a certain value in predicting the therapeutic response to 131I treatment.

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