ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Objective To investigate the effects of varying durations of overwork on cardiomyocyte pyroptosis in mice.Methods A total of 24 SPF KM mice were randomly divided into four groups(n=6)using a random number table:control group,2-week overwork(W2)group,4-week overwork(W4)group,and 6-week overwork(W6)group.Mice in control group were normally raised,while those in W2,W4,and W6 groups were forced to stand in water for 8 h and then restrained for 3 h daily for 2,4,6 weeks,respectively.The general condition and weekly weight changes of the mice were observed.After modeling,blood samples were collected,and hearts were excised.Myocardial histopathological changes were assessed using hematoxylin and eosin(HE)staining.The localization of gasdermin D(GSDMD)protein in myocardial tissue was detected through immunohistochemical staining,and the expression levels of pyroptosis-related proteins[NOD-like protein receptor 3(NLRP3),Caspase-1,GSDMD]in myocardial tissue were analyzed using Western blotting.The contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in serum and myocardial tissues were measured using ELISA.Results(1)The weight of control group mice increased steadily within 2 weeks.In W2 group,there was no significant weight change within 2 weeks,while in W4 and W6 groups,the body weights were higher than their initial values from the 2nd to 6th week.Compared with control group,the body weights of W2,W4,and W6 groups were lower than those of control group in the 1st and 2nd week,with statistically significant differences(P<0.05).The activity levels of the mice in W2,W4,and W6 groups initially increased and then decreased,with their fur becoming dull and falling out,and their mental state deteriorating.(2)In control group,cardiomyocytes were neatly arranged,and the nuclear morphology was normal.Compared with control group,in W2 group,cardiomyocyte arrangement was less regular,and capillary congestion was increased.In W4 group,the vascular congestion in the myocardium was significantly increased,the interstitial tissue was hyperplastic,and vacuolization appeared around the nuclei.In W6 group,the myocardial interstitium was loose,fat infiltration was increased,vacuolization around the nuclei was increased,and myocardial fibers were swollen,and the arrangement was disordered.(3)GSDMD was mainly located in the cytoplasm of cardiomyocytes.Compared with control group,the expression levels of NLRP3,Caspase-1,and GSDMD proteins in W2,W4,and W6 groups were significantly increased,and the expression levels were in the order of W6 group>W4 group>W2 group,with significant differences(P<0.05).(4)Compared to control group,the levels of IL-1β in serum and myocardial tissues of W2,W4,and W6 groups were significantly increased.In serum,the level of IL-1β in W6 group was higher than those in W2 and W4 groups,and in myocardial tissue,the levels in W4 and W6 groups were higher than those in the W2 group,with significant differences(P<0.05).There were no significant differences in IL-1β levels in serum among W2 and W4 groups,nor were there significant differences in myocardial tissue between W4 and W6 groups(P>0.05).Compared with control group,the levels of IL-18 in serum and myocardial tissue of W4 and W6 groups were significantly increased(P<0.05).In serum,the levels of IL-18 in W4 and W6 groups were higher than that in W2 group,and in myocardial tissue,the level in W6 group was higher than those in W2 and W4 groups,with the differences being statistically significant(P<0.05).Conclusions Overwork can cause structural damage to mouse myocardial tissue,increase the expression of pyroptosis proteins NLRP3,Caspase-1,GSDMD,and aggravate myocardial inflammatory responses in overworked mice.Cardiomyocyte pyroptosis may be one of the factors contributing to sudden cardiac death induced by overwork.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Mitochondrial diabetes mellitus(MDM)is a genetically heterogeneous disorder caused by mitochondrial DNA(mtDNA)or nuclear DNA mutations,characterized by multi-system involvement and diverse clinical phenotypes.We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus.Systematic evaluation revealed concurrent bilateral sensorineural hearing loss,bilateral basal ganglia calcification,and electroencephalographic abnormalities.A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion.Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084.This case re-port is complemented by a literature review focusing on the pathogenesis,genetic characteristics,and therapeu-tic approaches of mitochondrial diabetes,with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations.Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Objective To analyze the relationship of miRNA-146a gene polymorphisms and ischemic post-stroke depression(PSD).Methods The SNP rs2910164 in the miRNA-146a gene in 200 ischemic PSD patients(case group)and 200 ischemic non-PSD patients(control group)was analyzed using the SNaPshot technique.The relative expression levels of miRNA-146a in the peripheral blood of two groups were determined.Results The case group showed significantly different allele and genotype frequencies of the SNP rs2910164 as compared with the control group(G vs.C:P=0.003;GG+CG vs.CC:P=0.012).Meanwhile,the case group presented a significantly lower level of miRNA-146a relative expression(P<0.05).Within the control group,additionally,the subgroup of GG+CG genotypes demonstrated a significantly lower level of miRNA-146a relative expression compared with the subgroup of CC genotypes(P<0.05).Conclusion SNP rs2910164 in the miRNA-146a is associated with the susceptibility to ischemic PSD,and G allele may play a role in the ischemic PSD.

Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and γ-aminobutyric acid (GABA) in the hippocampus of model mice decreased significantly, while acetylcholine (ACh), tryptophan (Try), and glutamic acid (Glu) levels increased significantly. Treatment with Danzhi Xiaoyao San led to varying degrees of restoration in the aforementioned neurotransmitters. In terms of predictive validity, the antidepressant paroxetine effectively ameliorated depressive behaviors in the model mice, and the classic formula Danzhi Xiaoyao San demonstrated varying degrees of improvement in depression-related indicators. In conclusion, this study has established a novel animal model of liver-stagnation with the fire depression, thereby expanding the repertoire of traditional Chinese medicine depression models. This development contributes to the diversification of melancholic syndrome models in Chinese medicine, offering a broader spectrum of options for scientific exploration, efficacy evaluation, and drug screening in the future prevention and treatment of depression with traditional Chinese medicine. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 20230313040).