ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction （祛风通窍止咳方， QTCD） in the treatment of upper airway cough syndrome （UACS）. MethodsTwenty-four guinea pigs were randomly divided into blank group， model group， traditional Chinese medicine （TCM） group， and inhibitor group， with six guinea pigs in each group. Except for the blank group， guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection， followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling， the TCM group was administered QTCD 0.9 g/（100 g·d） by gavage， the inhibitor group received the transient receptor potential vanilloid receptor 4 （TRPV4） inhibitor GSK2193874 1 mmol/L， 5 min by nebulisation， and the blank group and model group were given 2 ml/（100 g·d） normal saline by gavage once daily. After 7 days of treatment， a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines， including interleukin-6 （IL-6）， interleukin-8 （IL-8） in serum， bronchoalveolar lavage fluid （BALF）， and nasal lavage fluid （NLF） were detected by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the protein levels of TRPV4， substance P （SP）， and calcitonin gene-related peptide （CGRP） in lung and nasal mucosal tissues. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRPV4， SP， and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group， while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group， the model group showed increased cough frequency， serum IgE level， and IL-6 and IL-8 levels in serum， BALF， and NLF. The protein levels of TRPV4， SP， and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated （P＜0.05 or P＜0.01）. Compared with the model group， the TCM group and inhibitor group showed reduced cough frequency， serum IgE level， and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， reduced IL-6 in BALF， reduced IL-8 in NLF， and decreased TRPV4， SP， and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues （P＜0.05 or P＜0.01）. Compared with the TCM group， the inhibitor group had increased serum IgE， IL-6， and IL-8 levels， increased IL-6 level in BALF， and increased IL-8 levle in NLF， but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues （P＜0.01）. ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway， improving airway neurogenic inflammation， alleviating inflammatory responses， and reducing cough hypersensitivity.

BackgroundObsessive-compulsive disorder （OCD） is a common neuropsychiatric illness and is listed as one of the top ten disabling conditions causing loss of income and reduced quality of life. Psychological distress is an important cause of anhedonia in OCD patients， and is closely related to psychosomatic symptoms. Therefore， exploring the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms is of great significance for optimizing clinical psychological treatment protocols for OCD patients. ObjectiveTo explore the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms in OCD patients， with the aim of providing references for managing psychosomatic symptoms in patients. MethodsA total of 90 patients who met the diagnostic criteria for OCD according to the International Classification of Diseases， tenth edition （ICD-10）， and who visited the Mental Health Center outpatient clinic of General Hospital of Ningxia Medical University from September 2023 to November 2024 were selected as the study objects. The instruments and techniques used for the evaluation were： Dimensional Anhedonia Rating Scale （DARS）， 10-item Kessler Psychological Distress Scale （K10） and Psychosomatic Symptom Scale （PSSS）. Model 4 of the Process for SPSS 26.0 was used to test the mediating role of anhedonia in the relationship between psychological distress and psychosomatic symptoms， with Bootstrapping used to assess the significance of mediating effect. ResultsA total of 84 patients （93.33%） completed the valid questionnaire. K10 score was positively correlated with PSSS total score， psychological symptom score and physical symptom score （r=0.559， 0.460， 0.551， P<0.01）. K10 score was negatively correlated with DARS total score （r=-0.527， P<0.01）. The total score of DARS was negatively correlated with PSSS total score （r=-0.497， P<0.01）. Anhedonia mediated the relationship between psychological distress and psychosomatic symptoms， with an indirect effect value was 0.148 （95% CI： 0.042~0.278）， accounting for 26.48% of the total effect. ConclusionPsychological distress can affect the psychosomatic symptoms in OCD patients both directly and indirectly via anhedonia.

Objective To observe the efficacy of percutaneous mechanical thrombectomy(PMT)for treating different traditional Chinese medicine(TCM)syndrome type lower extremity arterial thromboses.Methods Forty patients with lower extremity arterial thromboses who underwent PMT were retrospectively enrolled and divided into dampness-heat syndrome group(n=18)and blood stasis syndrome group(n=22)according to TCM syndrome types.The technical success rate,ankle-brachial index(ABI),Rutherford grade and vascular patency rate 12 months after PMT were compared between groups.Perioperative complications and adverse events during follow-up were recorded.Results The technical success rate of PMT in dampness-heat syndrome group and blood stasis syndrome group was 94.44%(17/18)and 100%(22/22),respectively.Twelve months after PMT,ABI was 0.45±0.11 and 0.52±0.14,and vascular patency rate was 94.44%(17/18)and 81.82%(18/22)in dampness-heat syndrome group and blood stasis syndrome group,respectively,both not significantly different between groups(all P＞0.05).No significant difference of Rutherford grade before treatment was found between groups(P＞0.05),while 12 months after PMT,Rutherford grade in dampness-heat syndrome group was higher than in blood stasis syndrome group(P＜0.05).During perioperative period,false aneurysm of brachial artery occurred in 1 case in dampness-heat syndrome group,while osteofascial compartment syndrome and atrial fibrillation occurred each in 1 case in blood stasis syndrome group,both relieved after treatments.No serious adverse event such as amputation nor death occurred during follow-up.Conclusion PMT was effective and safe for treating different TCM syndrome type lower extremity arterial thromboses.The prognosis of patients with blood stasis syndrome type lower extremity arterial thromboses was better than that of those with dampness-heat syndrome.

Objective:To explore the relationship between insomnia and osteoporosis.Methods:Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio ( OR) and 95% confidence interval ( CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran′s Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results:The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% ( OR=1.007, 95% CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs ( Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10 -5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results ( P=0.059), and radial MR did not detect any outliers. Conclusion:Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

Background and purpose:Human epidermal growth factor receptor 2(HER2)serves as one of the paramount drivers of breast cancer metastasis,with roughly 20%-30%of breast cancer patients exhibiting high expression of HER2.The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells;however,the manner in which HER2 expression is modulated at the mRNA level remains ambiguous.Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2,and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported.This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression.Methods:In this study,a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells.RNA fluorescence in situ hybridization(FISH)was utilized to detect the subcellular localization of circ-0007766.The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance.Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro.The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments,and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured.Additionally,it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972.A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972.The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment.RIP detection was performed in MDA-MB-231 cells,and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).Western blot was used to detect the protein expressions.Results:Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells,with the preponderance being in the cytoplasm.The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues.The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples.The overexpression(knockdown)of circ-0007766 in HER2-negative breast cancer cells(in HER2-positive breast cancer cells)was capable of promoting(inhibiting)the migration and invasion of breast cancer cells.Circ-0007766 directly bound to miR-1972,which inhibited breast cancer cell migration and invasion,thereby forming an endogenous competitive RNA(ceRNA)regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972.Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972.CircRNAs sequestered miRNAs to function as ceRNAs,thereby regulating gene expression at both the transcriptional and translational levels.Finally,we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples,while the expression levels of miR-1972 and HER2 were negatively correlated.Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression.Conclusion:This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis,offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.

Objective To explore the impact of δ-catenin expression level on resting-state brain function in breast cancer patients.Methods Totally 104 female breast cancer patients were prospectively enrolled and divided into δ-catenin high expression group(DH group,n=51)and δ-catenin low expression group(DL group,n=53)according to δ-catenin expression level,while 36 female healthy volunteers were selected as controls(control group).Neuropsychological tests were performed,and resting-state functional MRI(rs-fMRI)were acquired,then parameters of brain function,including amplitude of low frequency fluctuation(ALFF),fractional ALFF(fALFF),regional homogeneity(ReHo)and functional connectivity strength(FCS)of brain regions with differences among groups were obtained.Spearman correlation analysis was used to evaluate the correlations of function parameters of brain regions with general data and neuropsychological test scores.Results Significant differences of fALFF,ReHo and FCS values were found among 3 groups(familywise error rate[FWE]correction,all P＜0.05).fALFF value of left inferior temporal gyrus in DH and DL groups were both higher than that in control group(FWE correction,both P＜0.05),ReHo value of right inferior temporal gyrus in DH group,as well as of right middle temporal gyrus,right inferior temporal gyrus and right fusiform gyrus in DL group were all lower than that in control group(FWE correction,all P＜0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus,left calcarine fissure surrounding cortex and left inferior temporal gyrus in DH group were all higher than that in DL group(FWE correction,all P＜0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus and left calcarine fissure surrounding cortex in DH group were all higher than that in control group(FWE correction,all P＜0.05),while FSC value of left lingual gyrus,left lenticular nucleus and left putamen were both higher than that in control group(FWE correction,both P＜0.05).In brain regions with different fMRI indexes between DH group and DL group,FSC values were lowly positively correlated with CogPCA results(r=0.313,P＜0.05).In brain regions with different fMRI indexes between DH group and control group,fALFF value were lowly positively correlated with trail making test A(TMT A)and trail making test B(TMT B)(r=0.301,0.310,both P＜0.05),ReHo values were lowly negatively correlated with TMT B(r=-0.307,P＜0.05),FCS values were weakly/lowly positively correlated with TMT A and TMT B(r=0.282,0.309,both P＜0.05)and lowly negatively correlated with results of digital symbol substitution test(DSST)(r=-0.363,P＜0.05).In brain regions with different fMRI indexes between DL group and control group,fALFF values were weakly/lowly negatively correlated with results of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),auditory verbal learning test(AVLT)short-term memory and DSST(r=-0.399,-0.362,-0.344,-0.288,all P＜0.05).Conclusion The expression level of δ-catenin had certain impact on brain function of breast cancer patients,resulted in asymmetry changes of brain network in bilateral hemispheres,as well as memory loss through affecting left inferior temporal gyrus,left lenticular nucleus,left putamen and left fusiform gyrus.

Objective To explore novel methods for efficient respiratory viral infection of organoids by microinjection and polarity inversion techniques.Methods Lung tissue samples were obtained from 8-week-old male C57BL/6 mouse,and respiratory epithelial cells were extracted to establish a transwell organoid culture model.The green fluorescent protein(GFP)labeled influenza virus PR8(GFP-PR8)was quantitatively injected into organoids by improving the traditional microinjection platform,and morphologic changes in organoids and the immunofluorescence staining characteristics of tight junction proteins and microtubule proteins were observed.Polarity inversion apical-out(AO)was induced by suspension culture,and the morphological characteristics of polarity inversion was determined by HE staining.Normal and inverted organoids were infected with PR8,and the infection efficiency and expression differences of key pathway genes under different virus concentrations were observed.Results Ordinary organoids showed a significant increase in volume after microinjection.Following PR8 injection,the efficiency of infection was significantly higher in the apical region of organoids,accompanied by noticeable damage,as evidenced by significant down-regulation of tight junction proteins and microtubule protein expression.After suspension culture of the organoids,the polarity of ciliated cells gradually inverted outward over time,and the proportion of AO organoids stabilized on the 6th day.The efficiency of viral infection significantly increased in the inverted organoids,accompanied by significant cellular damage.After PR8 infection at 0.01 MOI,AO organoids showed significant changes in the inflammatory pathway and differentiation-related genes,with the opposite trend observed after higher concentration of PR8 infection.Conclusion Both polarity inversion and microinjection techniques significantly enhance the efficiency of influenza virus infection in organoids,thereby facilitating organoid widespread application in the field of respiratory tract infections.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective: To investigate the changes in the levels of interleukin-6 (IL-6) and let-7e in rats induced by coal mine dust, so as to provide the basis for the mechanism of coal worker's pneumoconiosis (CWP). Methods: Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group, coal dust group, mixed dust group (mixed coal and silica dust) and quartz group. The rats in the control group were exposed to 1 mL physiological saline by non-exposure tracheal perfusion, and the rats in the dust-exposed groups were exposed to 1 mL dust suspension. Rats were sacrificed by anesthesia after 1 month and 6 months, lung tissue was observed using hematoxylin-eosin staining, the pathological change in the lungs was scored using the Szapiel scoring system, the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay, and the expression of let-7e was determined by quantitative real-time PCR. Results: A month after exposure, a small amount of coal spots and inflammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group. The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum. Six months after exposure, there were more coal spots and slightly thickened alveolar septum in the coal dust group, and hyperplasia of pulmonary interstitial fibers, destruction of alveolar structure and silica nodules were observed in the mixed dust group. In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and silica nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P<0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust-exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05). Conclusions Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.

Age-related macular degeneration(AMD)is a serious threat to the visual health of the elderly,and the dysfunction of retinal pigment epithelial cells(RPE)is a significant etiology risk.Aging process leads to RPE repli-cation senescence,and some environment factors like light exposure and cigarette exposure may lead to RPE stress premature aging,and the decreased lysosomal digestion ability of senescent RPE cells may lead to the accumulation of lipofuscin,triggering the occurrence of early AMD.A series of homeostatic imbalances in aging retina,such as cell senescence-renewal imbalance,oxidative stress-antioxidant imbalance,chronic inflammatory-anti-inflammatory imbalance,intestinal barrier and intestinal microbiota imbalance and pro-angiogenesis-antiangiogenic imbalance all contribute to the development of AMD.