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.

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 ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

"Upper deficiency leading to vertigo" is one of the representative discussions on deficiency vertigo in Huang Di Nei Jing, which has laid the foundation for the rich development of the theory of "deficiency causing vertigo" in later generations. The brain lymphatic system can remove metabolic wastes and provide nutrients for the brain, which is involved in the development of many brain diseases. This study believes that the broad definition of "upper deficiency leading to vertigo", that is to say, vertigo is triggered by abnormalities in the local physiological functions of the brain orifices, can be used as a platform for the pathogenesis of vertigo. Based on the findings of modern medicine on the lymphoid system, the authors discussed the possible interactions between the lymphoid system, phlegm, blood stasis, deficiency, and other pathological factors of vertigo. β-amyloid, neurotransmitters, inflammatory mediators and other "toxic pathogenic factors" may also be an important cause of vertigo. This article attempted to explain the pathogenesis of "upper deficiency leading to vertigo" with the help of lymphoid system, in order to provide new thinking direction for the development of TCM clinical diagnosis and treatment of vertigo.

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.

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.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective:To establish HPLC fingerprint spectra and multi-component content determination methods for 20 batches of Mori Ramulus from different origins; To evaluate the quality of Mori Ramulus from different producing areas with similarity evaluation, CA, PCA, PLS-DA and other chemical pattern recognition methods.Methods:The chromatography was performed on Wondasil C18 column (4.6 mm×250 mm, 5 μm) at the detection wavelength of 254 nm, with acetonitrile (A) -0.2% glacial acetic acid (B) as the mobile phase at the flow rate of 0.8 ml/min. The fingerprint was established through the "TCM chromatographic Fingerprint Similarity Evaluation System", the similarity was calculated, and the chemical pattern recognition was carried out by SPSS 26.0 and SIMCA 14.1 software.Results:The similarity calculation results of fingerprint spectra showed that the similarity of the production areas in Fujian, Zhejiang, and Hebei was>0.830, while the similarity of other production areas was>0.900; a total of 14 common peaks were identified, and 8 components of mulberroside A, chlorogenic acid, polydatin, oxyresveratrol, resveratrol, morin, kuwanone G and morusin were identified; CA, PCA analysis divided Mori Ramulus from different producing areas into two categories, extracted four principal components, and the cumulative variance contribution rate was 89.247%. PLS-DA analysis was based on a VIP value greater than 1, and three quality difference criteria of mulberroside A, kuwanone G and morusin were selected.Conclusions:The established HPLC fingerprint and content determination method is simple, reproducible, stable, accurate and reliable. Combined with the chemical stoichiometric analysis methods, the quality evaluation of Mori Ramulus from different origins can be complete, and provide a reference for the quality control of mulberry branches.

Objective:To optimize the technology of Zhangbang wine moistening bran stir-fried Mori Ramulus.Methods:Using the total contents of 8 components including mulberry bark glycoside A, chlorogenic acid, resveratrol, resveratrol glycoside, oxidized resveratrol, mulberry pigment, mulberry ketone G, and mulberry saponin as the examination indicators, single factor investigation of five influencing factors of Zhangbang wine moistening bran stir-fried Mori Ramulus: wheat bran dosage, yellow wine dosage, frying temperature, soaking time, and processing time was conducted. Box Behnken response surface methodology was used for experimental design, to optimize processing technology for Zhangbang wine moistening bran stir-fried Mori Ramulus.Results:The optimal processing technology of the response surface method was: soaking time 116 min, wheat bran amount 19%, rice wine amount 10%, roasting time 7 min, and roasting temperature 237 ℃. Under these conditions, the average total content of eight components in the prepared Mori Ramulus decoction pieces was 787.8 μg/g, and RSD was 0.98%. Conclusion:The optimal processing technology of Zhangbang wine moistening bran stir-fried Mori Ramulus is stable, reliable and repeatable, which can better guarantee the quality of Zhangbang wine moistening bran stir-fried Mori Ramulus.

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.

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.