Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.

Objective:To analyze the epidemiological information of oral leukoplakia and explore the relationship between clinical characteristics and different degrees of epithelial dysplasia.Methods:A total of 430 patients with oral leukoplakia confirmed by pathology in the Department of Oral Medicine, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from February 2013 to May 2021 were enrolled. Epidemiological information was recorded, and univariate and multivariate Logistic regression analysis were performed on age, gender, smoking, drinking, lesion size, lesion site and lesion type to evaluate the correlation between the risk factors and the degree of epithelial dysplasia in oral leukoplakia.Results:A total of 430 valid samples were included in this study, among which 23 patients were diagnosed with oral leukoplakia with concurrent cancer. The age of all patients was (52.9±12.9) years (22-85 years); 213 were male and 217 were female. One hundred and seventy-six cases (40.9%) had lesions on the lateral and ventral tongue, and 254 cases (59.1%) had lesions in other locations. Three hundred and two cases (70.2%) had homogeneous lesions, and 128 cases (29.8%) had heterogeneous lesions. The degrees of epithelial dysplasia included none [11.9% (51/430)], mild [51.9% (223/430)], moderate [24.4% (105/430)], severe [6.5% (28/430)], and concurrent cancer [5.3% (23/430)]. Smoking, drinking, and gender were correlated with the degree of epithelial dysplasia in some binary classification systems, while tongue (border and ventral) and non-homogeneous damage were significantly correlated with higher degrees of epithelial dysplasia in all binary classification systems ( P<0.05). Conclusions:Lesions on the lateral or ventral tongue and heterogeneous lesions are significantly associated with higher degrees of dysplasia, suggesting that clinicians should pay more attention to these types of oral leukoplakia during the follow-up monitoring process.

Objective:To analyze the epidemiological information of oral leukoplakia and explore the relationship between clinical characteristics and different degrees of epithelial dysplasia.Methods:A total of 430 patients with oral leukoplakia confirmed by pathology in the Department of Oral Medicine, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from February 2013 to May 2021 were enrolled. Epidemiological information was recorded, and univariate and multivariate Logistic regression analysis were performed on age, gender, smoking, drinking, lesion size, lesion site and lesion type to evaluate the correlation between the risk factors and the degree of epithelial dysplasia in oral leukoplakia.Results:A total of 430 valid samples were included in this study, among which 23 patients were diagnosed with oral leukoplakia with concurrent cancer. The age of all patients was (52.9±12.9) years (22-85 years); 213 were male and 217 were female. One hundred and seventy-six cases (40.9%) had lesions on the lateral and ventral tongue, and 254 cases (59.1%) had lesions in other locations. Three hundred and two cases (70.2%) had homogeneous lesions, and 128 cases (29.8%) had heterogeneous lesions. The degrees of epithelial dysplasia included none [11.9% (51/430)], mild [51.9% (223/430)], moderate [24.4% (105/430)], severe [6.5% (28/430)], and concurrent cancer [5.3% (23/430)]. Smoking, drinking, and gender were correlated with the degree of epithelial dysplasia in some binary classification systems, while tongue (border and ventral) and non-homogeneous damage were significantly correlated with higher degrees of epithelial dysplasia in all binary classification systems ( P<0.05). Conclusions:Lesions on the lateral or ventral tongue and heterogeneous lesions are significantly associated with higher degrees of dysplasia, suggesting that clinicians should pay more attention to these types of oral leukoplakia during the follow-up monitoring process.

Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.

Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.

Objective To investigate the effects of long-term occupational exposure to high-frequency noise in specific frequency bands on auditory function of the inner ear,and to evaluate the mechanisms of auditory threshold damages due to high-frequency noise exposure utilizing bone conduction audiometry and acoustic physical models.Methods The study subjects included factory workers and airport ground staff working in high-noise environments for a long period.Two groups(an exposure group and a control group)were established,and the exposure group was further divided into 3 subgroups according to exposure duration:5-9 years,10-14 years,and over 15 years.Bone conduction audiometry was used to assess auditory threshold changes in different frequency bands(4,6,8 kHz),while a sound level meter was employed to record noise exposure intensity.The impact of noise on the cochlea was simulated using an acoustic physical model.Multivariable regression analysis,controlling for confounding factors such as age and gender,was used to further analyze the independent effects of exposure duration and intensity on auditory damage.Results The auditory thresholds of exposure group were significantly higher than those of control group in the high-frequency bands,particularly in 8 kHz frequency band(P＜0.001).With increasing exposure duration,auditory damage in exposure group progressively worsened,and the most significant auditory threshold changes was found in the group exposed for over 15 years.The predictions made by the acoustic physical model closely matched the actual measurements,and the high model fitting degree(R2:0.85-0.90)in the long-term exposure group indicated a strong predictive capability for the cumulative effects of cochlear damage.Conclusion Long-term exposure to high-frequency noise in specific frequency bands results in significant cumulative damage to auditory function of the inner ear.Exposure duration and intensity are the primary independent risk factors.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.