1.Epidemiology and pathogenesis of the link between rheumatoid arthritis and periodontitis.
Huiya FANG ; Jin LIN ; Yiwu QIU ; Zijian CHENG ; Weiqian CHEN
Journal of Zhejiang University. Science. B 2025;26(5):448-460
Rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation of synovial tissue, is divided into two subtypes-anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. While the pathogenic mechanisms of ACPA-positive RA are well-understood, the etiology of ACPA-negative RA remains largely unknown. The association between RA and periodontitis (PD) has been observed since the early 1900s, with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue. However, the associations between PD and the two subtypes of RA differ. This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD, explore potential pathogenic mechanisms linking the two diseases, and highlight the key distinctions between the subtypes of RA and their respective associations with PD. We also discuss the possibility of early intervention or the treatment of the two diseases. Ultimately, this review aims to provide valuable insights for future research in this field.
Humans
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Arthritis, Rheumatoid/complications*
;
Periodontitis/complications*
;
Anti-Citrullinated Protein Antibodies/immunology*
;
Risk Factors
2.Repetitive transcranial magnetic stimulation improves learning memory and enhances drainage efficiency of intracerebral glymphatic system in cerebral amyloid angiopathy model mice
Sijing LI ; Feng YANG ; Guijuan ZHOU ; Limin DENG ; Xuanwei WEN ; Shudong LIN ; Jingming KUANG ; Zijian XIAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):111-117
Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on learning memory and abnormal Aβ deposition in cerebral amyloid angiopathy(CAA) model mice, and further to investigate whether the mechanism involves the transport function of glymphatic system.Methods:Eight-month-old SPF grade Tg-SWDI mice were randomly divided into the CAA group and the rTMS group according to the random number table method with 7 in each group.Seven wild-type mice of the same genetic background and age served as the control group. The mice in rTMS group received two weeks of high-frequency rTMS intervention, and the mice in CAA group and control group were only restrained without rTMS intervention.Learning and memory functions were evaluated using the Morris water maze test.Amyloid-beta deposition, glymphatic system clearance, and aquaporin-4(AQP4) polarization were assessed using immunofluorescence, and AQP4 expression levels were measured by Western blot.Statistical analysis of the data was conducted using SPSS 25.0 and GraphPad Prism 9.5 softwares.Repeated-measures ANOVA was used for data on escape latency, and one-way ANOVA was used for comparisons between multiple groups for other data.Results:(1)In the novel object recognition test, there were statistically significant differences in recognition indices among the three groups of mice ( F=22.59, P<0.05). Compared with the control group, the mice in the CAA group showed a significant decrease in the new object recognition index ( P<0.05).Compared with the CAA group, the mice in the rTMS group showed a significant increase in the new object recognition index ( P<0.05).(2)In the Y-maze, there were statistical differences in the spontaneous alternation rates among the three groups ( F=5.00, P<0.05). Compared with the control group, the spontaneous alternation rate in the CAA group was significantly lower ( P<0.05).And compared with the CAA group, the spontaneous alternation rate in the rTMS group was significantly higher ( P<0.05).(3)In the Morris water maze test, there were significant interactions in escape latency among the three groups ( F=4.05, P=0.02), significant main effects of time ( F=713.22, P<0.01), and significant main effects of group ( F=421.55, P<0.01). There was no significant statistical difference in swimming speed among the three groups ( F=0.19, P>0.05), while the difference of the number of entries into the inner zone and the proportion of time spent were statistically significant( F=71.67, 294.14, both P<0.05).Compared with the control group, the CAA group mice significantly decreased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).(4)Compared with the CAA group, the rTMS group significantly increased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).The result of immunofluorescence test showed that there was a statistically significant difference in the levels of Aβ in the cerebral vessels among the three groups( F=385.76, P<0.01).The levels of Aβ in the cerebral vessels of the CAA group (62.00±2.65) were significantly higher than those in the control group (9.00±1.00, P<0.01).The levels in the rTMS group (51.33±3.21) were significantly lower than those in the CAA group (62.00±2.65, P<0.01). Using the residual fluorescence tracer levels of the control group as a baseline, there were statistically significant differences in the tracer intensities in the corpus callosum and cerebral cortex( F=258.97, 46.44, both P<0.05), the tracer intensities in the corpus callosum (3.57±0.21) and cerebral cortex (4.96±0.79) of the CAA group mice were significantly higher than those in the rTMS group (1.45±0.14, 1.78±0.47, P<0.01). The polarization of AQP4 in the cerebral cortex of rTMS group (0.51±0.07) was significantly higher than that in the CAA group (0.30±0.02, P<0.01). Conclusion:rTMS can alleviate learning memory and abnormal Aβ deposition in CAA model mice by modulating AQP4 polarisation and promoting transport function of glymphatic system.
3.Repetitive transcranial magnetic stimulation improves learning memory and enhances drainage efficiency of intracerebral glymphatic system in cerebral amyloid angiopathy model mice
Sijing LI ; Feng YANG ; Guijuan ZHOU ; Limin DENG ; Xuanwei WEN ; Shudong LIN ; Jingming KUANG ; Zijian XIAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):111-117
Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on learning memory and abnormal Aβ deposition in cerebral amyloid angiopathy(CAA) model mice, and further to investigate whether the mechanism involves the transport function of glymphatic system.Methods:Eight-month-old SPF grade Tg-SWDI mice were randomly divided into the CAA group and the rTMS group according to the random number table method with 7 in each group.Seven wild-type mice of the same genetic background and age served as the control group. The mice in rTMS group received two weeks of high-frequency rTMS intervention, and the mice in CAA group and control group were only restrained without rTMS intervention.Learning and memory functions were evaluated using the Morris water maze test.Amyloid-beta deposition, glymphatic system clearance, and aquaporin-4(AQP4) polarization were assessed using immunofluorescence, and AQP4 expression levels were measured by Western blot.Statistical analysis of the data was conducted using SPSS 25.0 and GraphPad Prism 9.5 softwares.Repeated-measures ANOVA was used for data on escape latency, and one-way ANOVA was used for comparisons between multiple groups for other data.Results:(1)In the novel object recognition test, there were statistically significant differences in recognition indices among the three groups of mice ( F=22.59, P<0.05). Compared with the control group, the mice in the CAA group showed a significant decrease in the new object recognition index ( P<0.05).Compared with the CAA group, the mice in the rTMS group showed a significant increase in the new object recognition index ( P<0.05).(2)In the Y-maze, there were statistical differences in the spontaneous alternation rates among the three groups ( F=5.00, P<0.05). Compared with the control group, the spontaneous alternation rate in the CAA group was significantly lower ( P<0.05).And compared with the CAA group, the spontaneous alternation rate in the rTMS group was significantly higher ( P<0.05).(3)In the Morris water maze test, there were significant interactions in escape latency among the three groups ( F=4.05, P=0.02), significant main effects of time ( F=713.22, P<0.01), and significant main effects of group ( F=421.55, P<0.01). There was no significant statistical difference in swimming speed among the three groups ( F=0.19, P>0.05), while the difference of the number of entries into the inner zone and the proportion of time spent were statistically significant( F=71.67, 294.14, both P<0.05).Compared with the control group, the CAA group mice significantly decreased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).(4)Compared with the CAA group, the rTMS group significantly increased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).The result of immunofluorescence test showed that there was a statistically significant difference in the levels of Aβ in the cerebral vessels among the three groups( F=385.76, P<0.01).The levels of Aβ in the cerebral vessels of the CAA group (62.00±2.65) were significantly higher than those in the control group (9.00±1.00, P<0.01).The levels in the rTMS group (51.33±3.21) were significantly lower than those in the CAA group (62.00±2.65, P<0.01). Using the residual fluorescence tracer levels of the control group as a baseline, there were statistically significant differences in the tracer intensities in the corpus callosum and cerebral cortex( F=258.97, 46.44, both P<0.05), the tracer intensities in the corpus callosum (3.57±0.21) and cerebral cortex (4.96±0.79) of the CAA group mice were significantly higher than those in the rTMS group (1.45±0.14, 1.78±0.47, P<0.01). The polarization of AQP4 in the cerebral cortex of rTMS group (0.51±0.07) was significantly higher than that in the CAA group (0.30±0.02, P<0.01). Conclusion:rTMS can alleviate learning memory and abnormal Aβ deposition in CAA model mice by modulating AQP4 polarisation and promoting transport function of glymphatic system.
4.Digital Intelligence Drives the High-Quality Development of the Healthcare Service System:Development Mechanisms and Implementation Pathway
Jie PAN ; Tianfeng ZHANG ; Yumeng ZHANG ; Xiaojun LIN ; Weiwei LI ; Chao SONG ; Hongyu LAI ; Xiang YAN ; Xiuli WANG ; Xing QU ; Zijian DENG ; Xin CHEN ; Liming QUAN ; Qijun ZHAO ; Yucheng DONG ; Wei ZHANG ; Kui WU ; Xuefeng TANG
Journal of Sichuan University (Medical Sciences) 2024;55(5):1055-1062
The rapid development of digital intelligence technologies is providing a powerful boost to the high-quality development of the healthcare system.Considering the current state of our healthcare services and guided by General Secretary Xi Jinping's insights on new quality productive forces and the directives from Third Plenary Session of Communist Party of China's 20th Central Committee,the high-quality development of the healthcare service system should focus on digital intelligence technologies such as cloud computing,big data,privacy computing,blockchain,Internet of Things(IoT),mobile computing,and AI.The key measures should include the optimization of production factors,services,and governance.Emphasis should be placed on enhancing the efficient and intensive development of the development model,ensuring the high-quality and continuous integration of the supply model,and transitioning to scientific and modern management methods.Herein,we analyzed the"factor optimization—service optimization—governance optimization"development mechanism driven by digital intelligence and proposed corresponding implementation pathways,intending to provide references for establishing a high-quality and efficient healthcare service system with Chinese characteristics.
5.Luteolin suppresses oral carcinoma 3 (OC3) cell growth and migration via modulating polo-like kinase 1 (PLK1) expression and cellular energy metabolism.
Pengfei GAO ; Wentao ZHANG ; Yujie LIN ; Ruijie LU ; Zijian LOU ; Gang LU ; Ruolang PAN ; Yunfang CHEN
Journal of Zhejiang University. Science. B 2023;24(12):1151-1158
Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).
Humans
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Mouth Neoplasms/pathology*
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Carcinoma, Squamous Cell/metabolism*
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Luteolin/therapeutic use*
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Squamous Cell Carcinoma of Head and Neck/drug therapy*
;
Head and Neck Neoplasms/drug therapy*
;
Cell Line, Tumor
6.Effects and mechanism of Elafibranor on the proliferation, migration and apoptosis of human prostate cancer
Junjie AI ; Zijian WANG ; Wei NI ; Xiaojuan LIN
Journal of Modern Urology 2023;28(9):813-817
【Objective】 To investigate the effects and molecular mechanism of Elafibranor (ELA) on the proliferation, migration and apoptosis of human prostate cancer (PCa) cells. 【Methods】 After PCa DU145 cells were treated with culture media containing different dosages of ELA, the proliferation, migration and apoptosis were determined with MTT assay, wound healing assay and Transwell assay, respectively. The expressions of genes related to lipid metabolism were detected with real-time quantitative polymerase chain reaction (real-time qPCR). 【Results】 The relative cell proliferation rate at 48 h was 100% in the blank control group, (86.9±7.8)% in the low-dose (5 μmol/L) group and (58.5±9.4)% in the high-dose (15 μmol/L) group;the wound healing rate at 24 h was (74.7±3.2)%, (61.8±2.9)% and (53.2±3.3)%;the relative percentage of migrated cells at 24 h was 100%, (32.4±11.2)% and (15.4±3.2)%;the cell apoptosis rate at 48 h was (9.3±1.4)%, (11.3±0.3)%, and (15.2±4.5)%, respectively, all P<0.05. After ELA treatment for 48 h, the genes related to fatty acid intake (SCPX, PLTP) and fatty acid oxidation (PDK1, ACOX2) were significantly down-regulated in the high-dose group, while the gene related to fatty acid deposition (PLIN2) was significantly up-regulated, indicating that the lipid metabolism pathway of DU145 cells was seriously interfered by the ELA treatment. 【Conclusion】 ELA can inhibit the proliferation and migration, and promote the apoptosis of prostate cancer cells by interfering in the lipid metabolism pathway, which exhibits remarkable potential of clinical translation in the field of anti-tumor chemotherapy.
7.Exploration of risk factors and establishment of nomograms model for postoperative adjuvant chemotherapy in stage Ⅰ gastric cancer
Li LI ; Yunhe GAO ; Benlong ZHANG ; Zijian WANG ; Qiying SONG ; Hao CUI ; Zhi QIAO ; Lin CHEN
International Journal of Surgery 2023;50(5):306-311,C1
Objective:To identify the risk factors associated with postoperative adjuvant chemotherapy in patients with stage I gastric cancer and establish nomograms model based on risk factors.Methods:In this retrospective case-control study, 161 cases with stage Ⅰ primary gastric adenocarcinoma were included who underwent gastrectomy at the Department of General Surgery of the First Medical Center of Chinese PLA General Hospital from January to December in 2020, including 129 male cases and 32 females cases, with the average age of (59.90±0.80) years. Among them, 41 cases were treated with postoperative adjuvant chemotherapy (chemotherapy group), while 120 cases who did not receive postoperative adjuvant chemotherapy (no chemotherapy group). Univariate and multivariate Logistic regression analyses were used to identify the risk factors of adjuvant chemotherapy in stage Ⅰ gastric cancer patients and establish the nomograms predictive model. ROC curve and calibration curve were used to evaluate the performance of the model.Results:Multivariate analysis revealed that primary tumor site, tumor size, T stage, N stage lymph-vascular tumor embolus or perineural invasion were the independent risk factors of postoperative adjuvant chemotherapy for stage Ⅰ gastric cancer( P<0.05). The ROC curve indicated that area under the curve (AUC) of the multivariate model was 0.91(95% CI: 0.86-0.97). The calibration curve showed that probability predicted by nomograms was consistent with the actual situation(C-index: 0.91). Conclusions:The tumor located in the proximal stomach, tumor size>2 cm, T 2, N 1, lymph-vascular tumor embolus or perineural invasion maybe be the risk factors for chemotherapy decision in stage Ⅰ gastric cancer patients. The established model has good predictive ability for postoperative chemotherapy of stage Ⅰ gastric cancer patients, which might provide reference for the selection of clinical decisions in this part of patients.
8.Research status of abnormal lipid metabolism associated with pancreatic cancer
Ning MAO ; Zhongchao CAO ; Zhitao LIN ; Zijian HUANG ; Bei SUN ; Gang WANG
Chinese Journal of Digestive Surgery 2022;21(8):1112-1116
In recent years, with the continuous studies on tumor metabonomics, more and more results have shown that changes of metabolism play important roles in the occurrence and development of malignant tumor. Carcinogenic factors can destroy the metabolic balance of human body, induce metabolic reprogramming, and then mediate a variety of biological behaviors to partici-pate in the proliferation and invasion of cancer cells. Lipids provide the body with the necessary energy and essential fatty acids, and a variety of lipid molecules and metabolites are involved in cell signal transduction. Lipid metabolism is an important link in the metabolic system of the body, and the relationship between the occurrence and development of pancreatic cancer and lipid metabo-lism is not clear. The purpose of this paper is to reveal the changes of lipid metabolism in pancreatic cancer, summarize some preclinical studies and clinical trials, and deeply explain the research status of abnormal lipid metabolism associated with pancreatic cancer, so as to provide new ideas for the study of pancreatic cancer pathogenesis and accurate treatment.
9.Current status of the application of translational medicine in the early diagnosis of pancreatic cancer
Ning MAO ; Zijian HUANG ; Zhitao LIN ; Bei SUN ; Gang WANG
Chinese Journal of Digestive Surgery 2021;20(4):466-470
Pancreatic cancer is a rapidly progressive and highly malignancy of the digestive system. In recent years, the diagnosis and treatment of pancreatic cancer has been in a slow stage of development, and the 5-year survival rate of patients remains very low. The main objective of translational medicine is to remove the barriers between basic medical research and clinical medical applications, to achieve practical integration between laboratory and clinic, and to accelerate the translation of the results obtained from basic research into clinical diagnosis, evaluation and treatment of diseases, thus promoting the development of life sciences. With the rapid development of the concept and technology of translational medicine, its application in the early diagnosis of pancreatic cancer can bring new hope for effectively improving the overall prognosis of patients. The authors comprehensively analyzed the latest research progress of translational medicine in the early diagnosis of pancreatic cancer in order to improve the early diagnosis and long-term survival of pancreatic cancer patient.
10.The effects of clostridium butyricum and butyrate on acute necrotizing pancreatitis with acute liver injury in rats and the mechanism
Qingqing YAN ; Lin JIA ; Zijian HE ; Yaoxing HUANG ; Weidong LI
Chinese Journal of Pancreatology 2021;21(2):94-98
Objective:To observe the protective effects of Clostridium butyricum and butyrate on pancreas, liver and intestinal mucosa in rats with acute necrotizing pancreatitis (ANP), and to explore the possible mechanism.Methods:Forty Sprage-dawley rats were randomly divided into control group, ANP group,Clostridium butyricum treated group(CB group) and butyrate treated group(SB group), with 10 rats in each group by random number method. The ANP rat models were prepared by retrograde injection of sodium taurocholate into the biliopancreatic duct. Rats in CB and SB group were given intragastic administration of Clostridium butyricum 1×10 9 CFU or sodium butyrate (100 mg/kg) in 10 days once a day before modeling. Serum amylase (SAMY), lypase, ALT, AST, TBil, tumor necrosis factor alpha(TNF-α), IL-6 and HMGB1were measured after 24 h. Protein from intestinal mucosa was extracted and Western Blotting was used to measure expression of tight-junction proteins ZO-1, claudin-1 and occludin. Pancreas and liver tissues were stained with hematoxylin-eosin and scored by pathology. Results:The levels of amylase [(9365.1±716.5), (5947.3±512.0), (6517.7±269.6)U/L], lipase[(8343.7±1041.4), (6600.4±899.7), (6754.4±1046.4)U/L], AST[(560.5±72.7), (432.0±76.2), (429.8±40.5)U/L], ALT[(499.9±65.2), (385.7±46.0), (395.8±45.8)U/L], TBil[(134.2±56.2), (74.3±65.2), (81.3±35.3)U/L], TNF-α[(162.0±14.4), (100.4±6.3), (119.2±12.5)ng/L], IL-6[(161.4±26.0), (104.8±15.2), (105.5±12.7)ng/L], HMGB1[(100.1±6.7), (58.0±7.7), (63.4±7.2)ng/L] in ANP group, CB group and SB group were detected; and the pathological scores of pancreas[(11.2±1.08),(9.45±1.06), (9.04±0.89)] and liver[(2.89±0.73), (2.09±0.49), (2.12±0.52)] in ANP group,CB group and SB group were higher than those in control group[(100.6±5.20)U/L, (966.5±301.9)U/L,(30.2±6.3)U/L, (27.6±5.9)U/L, (2.4±0.6)U/L, (29.5±4.8)ng/L,(36.9±7.6)ng/L,(35.5±5.7)ng/L,(1.18±0.05),(0.56±0.09)]. However, those indexes in CB group and SB group were lower than those in ANP group, and the difference was statistically significant (all P<0.05). The expression of ZO-1 in control group, ANP group, CB group and SB group was 1.83, 0.79, 1.25 and 1.16. The expression of claudin-1 in control group, ANP group, CB group and SB group was 0.58, 0.13, 0.43 and 0.37. The expression of occludin in control group, ANP group, CB group and SB group was 1.06, 0.38, 0.82 and 0.79. The expression of TJ proteins in ANP group was significantly lower than that in other groups and the difference was statistically significant (all P<0.05). Conclusions:Clostridium butyricum and metabolites butyrate can alleviate the inflammatory response in ANP rats with liver injury, maintain the function of intestinal mucosal barrier and prevent the liver injury.

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