1.Mechanism of action of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Wei LI ; Tinghui JIANG ; Yongqiang ZHU ; Yan LIU
Journal of Clinical Hepatology 2025;41(3):588-593
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.
2.Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Tinghui JIANG ; Wei LI ; Yongqiang ZHU ; Yan LIU
China Oncology 2025;35(10):952-958
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.
3.Application of ipsilateral high-frequency rTMS combined with biofeedback-based air swallowing training in patients with post-stroke dysphagia
Panpan GAO ; Qian ZHANG ; Tinghui LIU ; Jie SUN
The Journal of Practical Medicine 2025;41(8):1105-1110
Objective To investigate the impact of high-frequency repetitive transcranial magnetic stimula-tion(rTMS)combined with biofeedback-assisted dry swallowing training on treating dysphagia following a stroke.Methods A total of 152 patients with dysphagia after stroke,admitted to the hospital from January 2022 to January 2024,were randomly divided into four groups using a random number table,with 38 cases in each group.The biofeedback group received biofeedback-assisted dry swallowing training,the magnetic stimulation group received high-frequency rTMS on the unaffected side,the combined group received both biofeedback-assisted dry swallowing training and high-frequency rTMS on the unaffected side,and the placebo group received conventional swallowing training and sham rTMS.All interventions lasted for 4 weeks.Clinical efficacy was recorded,and pre-and post-treatment assessments of the upper esophageal sphincter(UES)opening time,opening degree,and pharyngeal contraction duration were performed using multifunctional esophageal manometry.Additionally,swallowing func-tion,nutritional status,neurological function,and quality of life were compared.Results The clinical efficacy of the combined group was higher than that of the biofeedback and magnetic stimulation groups.Post-treatment UES opening time,opening degree,and pharyngeal contraction duration were(205.33±29.01)ms,(1.14±0.34)cm,and(559.19±63.48)ms,respectively,which were significantly better than those in the other 3 groups(P<0.05).The swallowing function scores of the combined group were(6.04±0.83)and(20.03±3.26)points,and significant improvements were observed in swallowing function,nutritional status,neurological function,and quality of life(P<0.05).Conclusion High-frequency rTMS combined with biofeedback-based dry swallowing training signifi-cantly improves the efficacy in the treatment of dysphagia after stroke.
4.Application of ipsilateral high-frequency rTMS combined with biofeedback-based air swallowing training in patients with post-stroke dysphagia
Panpan GAO ; Qian ZHANG ; Tinghui LIU ; Jie SUN
The Journal of Practical Medicine 2025;41(8):1105-1110
Objective To investigate the impact of high-frequency repetitive transcranial magnetic stimula-tion(rTMS)combined with biofeedback-assisted dry swallowing training on treating dysphagia following a stroke.Methods A total of 152 patients with dysphagia after stroke,admitted to the hospital from January 2022 to January 2024,were randomly divided into four groups using a random number table,with 38 cases in each group.The biofeedback group received biofeedback-assisted dry swallowing training,the magnetic stimulation group received high-frequency rTMS on the unaffected side,the combined group received both biofeedback-assisted dry swallowing training and high-frequency rTMS on the unaffected side,and the placebo group received conventional swallowing training and sham rTMS.All interventions lasted for 4 weeks.Clinical efficacy was recorded,and pre-and post-treatment assessments of the upper esophageal sphincter(UES)opening time,opening degree,and pharyngeal contraction duration were performed using multifunctional esophageal manometry.Additionally,swallowing func-tion,nutritional status,neurological function,and quality of life were compared.Results The clinical efficacy of the combined group was higher than that of the biofeedback and magnetic stimulation groups.Post-treatment UES opening time,opening degree,and pharyngeal contraction duration were(205.33±29.01)ms,(1.14±0.34)cm,and(559.19±63.48)ms,respectively,which were significantly better than those in the other 3 groups(P<0.05).The swallowing function scores of the combined group were(6.04±0.83)and(20.03±3.26)points,and significant improvements were observed in swallowing function,nutritional status,neurological function,and quality of life(P<0.05).Conclusion High-frequency rTMS combined with biofeedback-based dry swallowing training signifi-cantly improves the efficacy in the treatment of dysphagia after stroke.
5.Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma
Xue YU ; Tianhao SHEN ; Cheng ZHOU ; Yu LIU ; Tinghui JIANG ; Wei LI ; Yongqiang ZHU ; Yan LIU
China Oncology 2025;35(10):952-958
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.
6.Clinical effect of 125I seeds implantation combined with arterial infusion chemotherapy for patients with advanced pancreatic cancer
Cheng ZHOU ; Tianhao SHEN ; Tinghui JIANG ; Xue YU ; Yan LIU
Journal of Interventional Radiology 2024;33(8):878-884
Objective To evaluate the clinical efficacy of 125I seeds implantation combined with transcatheter arterial infusion(TAI)in treating advanced pancreatic carcinoma(PC).Methods By using envelope sealing method,76 patients who met enrollment criteria were divided into observation group and control group.Finally,a total of 67 patients were enrolled in this study.The observation group had 31 patients and the patients received 125I seeds implantation combined with TAI therapy,and the control group had 36 patients and the patients received TAI therapy.After 3 courses of treatment,the clinical efficacy,pain score,incidence of obstructive jaundice(OJ),and survival time were compared between the two groups.Results In the observation group and the control group,the objective response rate(ORR)was 48.4%and 25.0%respectively,and the difference was statistically significant(P<0.05);the disease control rate(DCR)was 83.9%and 66.7%respectively,and the difference was not statistically significant(P>0.05).In both groups,the postoperative one-month and 3-month pain scores were decreased obviously when compared with the preoperative values(P<0.05),but the reduction of pain score in the observation group was more obvious than that in the control group(P<0.05).In the observation group and the control group,the pain relief rates were 23.06%and 13.4%respectively,and the difference was statistically significant(P=0.0252);the incidences of OJ were 19.4%and 50.0%respectively,and the difference was statistically significant(P<0.05);the median survival time was 7.9 months and 5.1 months respectively,and the difference was statistically significant(P<0.05).In both groups,the postoperative one-month and 3-month CA199 levels were decreased,and the difference was statistically significant(P<0.05).No statistically significant difference in the incidences of adverse reactions such as nausea,vomiting,diarrhea and leukopenia existed between the two groups(P>0.05).Conclusion 125I seeds implantation combined with TAI therapy can effectively relieve cancer pain,prolong survival time in patients with advanced PC,and it is clinically safe.Therefore,this therapy is worthy of clinical promotion.
7.Biomechanical Effects of Jumping Distance on Stress Distributions of Anterior Dental Implant with Socket-Shield Technique
Qian WANG ; Jingheng SHU ; Tinghui SUN ; Haidong TENG ; Bingme SHAO ; Zhan LIU
Journal of Medical Biomechanics 2023;38(3):E594-E600
Objective To study the biomechanical effect of jumping distance on dental implants with socket-shield technique (SST), so as to provide references for clinical standards of jump distance. Methods Based on clinical characteristics, four groups of three-dimensional (3D) SST implant system models with 0, 0. 5, 1 and 1. 5 mm jumping distance were established, and the corresponding material parameters were assigned. The peak stress and stress distributions on models were simulated under specific occlusal condition. Results When the jumpingdistance was non-zero, namely, the implant was not in contact with the retained root fragment, the stress of the implant and abutment increased with the increase of jumping distance, and the peak stress in root fragment and periodontal membrane decreased with the increase of jumping distance. When the jumping distance was zero, the peak stress of the implant, abutment, root fragment and periodontal membrane reached the maximum, far exceeding that of the other groups. Conclusions The jumping distance has a significant effect on the SST implant system. It is recommended to take a larger jumping distance in clinical practices. The edge of the root fragment should be rounded, and the size of the lower edge should not be too small.
8.Influence of severe neck angulation on hemodynamic and clinical outcomes following endovascular aneurysm repair: a hemodynamic analysis and a retrospective cohort study
Yang LIU ; Ming QING ; Jichun ZHAO ; Bin HUANG ; Yi YANG ; Tinghui ZHENG ; Ding YUAN
Chinese Medical Journal 2022;135(21):2577-2584
Background::For patients with severe neck angulation (SNA), hemodynamic and clinical outcomes following endovascular aneurysm repair (EVAR) are still unclear. This study aimed to explore the influence of SNA on hemodynamic and clinical outcomes following EVAR.Methods::This study included a hemodynamic analysis and a retrospective cohort study from West China Hospital of Sichuan University between January 2011 and December 2020. The Cox regression model, inverse probability of treatment weighting (IPTW) analysis, sensitivity analysis, and subgroup analysis were applied. Primary outcome was type IA endoleak (T1AEL).Results::In this hemodynamic analysis, nine non-severe neck angulation (nSNA) and 16 SNA idealized models were constructed. We found a significant difference in drag force between SNA and nSNA models (7.016 ± 2.579 N vs. 4.283 ± 1.460 N, P = 0.008), and proximal neck angles were significantly associated with the magnitude of drag force (F = 0.082 × α-0.006 × β + 2.818, α: 95% confidence interval [CI] 0.070-0.094; P = 0.001; β: 95% CI -0.019 to 0.007; P = 0.319). In our cohort study, 514 nSNA patients (71.5 ± 8.5 years; 459 males) and 208 SNA patients (72.5 ± 7.8 years; 135 males) were included, with a median follow-up duration of 34 months (16-63 months). All baseline characteristics were well balanced after IPTW matching. We found that SNA was associated with a significant risk of adverse limb event (hazard ratio [HR] 2.18, 95% CI 1.09-3.12), yet was not associated with T1AEL, overall survival, or reintervention. In patients without proximal or distal additional procedures (DAP), subgroup analyses suggested a significant risk of T1AEL (Proximal: HR 5.25, 95% CI 1.51-18.23; Distal: HR 5.07, 95% CI 1.60-16.07) and adverse limb event (Proximal: HR 2.27, 95% CI 1.01-5.07; Distal: HR 2.91, 95% CI 1.30-6.54) in SNA patients. However, no noticeable difference was observed in patients with proximal or DAP. Conclusions::SNA has a critical influence on hemodynamic and clinical outcomes following EVAR. Appropriate additional procedures may be of great benefit to SNA patients.
10.Application of esketamine in combination with butorphanol in endotracheal intubation guided by fiberoptic bronchoscopy with spontaneous breathing
Wanmin PEI ; Jian LIU ; Tinghui DAI ; Dan XIAO
Journal of Chinese Physician 2022;24(11):1683-1686
Objective:To observe the effects of esketamine combined with butorphanol in endotracheal intubation guided by fiberoptic bronchoscopy with spontaneous breathing.Methods:Forty patients suspected of having difficult airways during elective general anesthesia operations in Hunan Provincial People′s Hospital were prospectively selected and divided into control group and observation group by random number table. Propofol plus sufentanil, esketamine plus butorphanol were used for intravenous general anesthesia respectively. At the same time, they were assisted with cricothyroid puncture and surface anesthesia of nasopharynx and larynx, and then trachea intubation with spontaneous breathing was performed through the nose under the guidance of fiberoptic bronchoscope. The changes of heart rate (HR), mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO 2), and the levels of serum cortisol, norepinephrine and adrenaline before and after endotracheal intubation were compared between the two groups. The number of body motions and coughing at the completion of endotracheal intubation was compared between the two groups. Results:In the control group, the HR and MAP at the completion of intubation were higher than those before intubation, and the PaO 2 was lower than those before intubation (all P<0.05); In the observation group, there was no significant difference in HR, MAP and PaO 2 at the completion of intubation and before intubation (all P>0.05). The HR and MAP at the end of intubation in the observation group were lower than those in the control group, and the PaO 2 was higher than that in the control group (all P<0.05). The number of body motion and coughing in the observation group was significantly less than that in the control group at the completion of endotracheal intubation (all P<0.01). At the end of endotracheal intubation, the serum cortisol, norepinephrine and epinephrine level in the observation group were significantly lower than those in the control group (all P<0.01). Conclusions:Esketamine combined with butorphanol has advantages over propofol combined with sufentanil in the application of fiberoptic bronchoscopy guided tracheal intubation in difficult airways that retain spontaneous breathing, and can better control the stress response caused by tracheal intubation.

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