Advanced age is a recognized risk factor for primary Sjögren’s disease (pSjD), suggesting a role for aging-related mechanisms in its pathogenesis. However, whether cellular senescence directly drives autoimmune inflammation and glandular dysfunction remains unclear. Furthermore, the specific role of senescent fibroblasts within the pSjD microenvironment has not been defined. This study investigates the mechanisms underlying fibroblast senescence and its therapeutic potential in pSjD. The senescence landscape of salivary glands was assessed by immunohistochemistry, multiplex immunofluorescence, and single-cell RNA sequencing, coupled with computational trajectory and gene regulatory network inference. In vitro, primary salivary gland fibroblasts (SGFs) were treated with interferon-gamma (IFN-γ). Senescence-associated β-galactosidase staining, reactive oxygen species detection, siRNA knockdown, co-immunoprecipitation, dual-luciferase reporter, and transwell migration assays were conducted to elucidate the underlying mechanisms. In vivo, a non-obese diabetic (NOD) mouse model was utilized to evaluate the efficacy of a senolytic combination (dasatinib and quercetin) on salivary flow rates and lymphocytic infiltration. Integrative analysis of human clinical samples and scRNA-seq revealed a significant accumulation of senescent fibroblasts in pSjD salivary glands. Pharmacological clearance of senescent cells in NOD mice significantly attenuated lymphocytic infiltration and restored salivary function, supporting a pathogenic contribution of fibroblast senescence. Subsequent computational trajectories and in vitro validations identified a senescence-enriched DNAJB1high fibroblast subpopulation. Mechanistically, IFN-γ upregulated DNAJB1 transcription via JUND, which was in turn associated with p21-mediated senescence and enhanced CD4⁺ T cell recruitment. Furthermore, in vivo evaluations confirmed that the senolytic intervention effectively suppressed the glandular JUND-DNAJB1-p21 axis, corroborating the mechanistic findings. These findings indicate that the JUND-DNAJB1-p21 axis contributes to fibroblast senescence and autoimmune pathogenesis in pSjD. Senolytic clearance of senescent cells may represent a potential therapeutic strategy for mitigating glandular dysfunction.

BackgroundTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Drug-resistant tuberculosis (DRTB) includes multidrug-resistant tuberculosis without extensive drug resistance (MDRTB) and extensively drug-resistant tuberculosis (EDRTB). Recently, with the continued rise of DRTB, global TB prevention and control efforts have faced even greater challenges.AimsThis study aimed to quantify the changes in age-standardized incidence rate (ASIR) of two types of DRTB from 1991 to 2021 using the Global Burden of Disease (GBD) database, and to examine the epidemiological differences across various regions and countries and applied the autoregressive integrated moving average (ARIMA) model to predict the epidemiological trends of MDRTB and EDRTB from 2022 to 2030.MethodsData were extracted from the GBD database from 1991 to 2021. Estimated annual percentage changes (EAPC) in DRTB ASIR by regions, were calculated to quantify the temporal trends. ARIMA model was applied to predict ASIR between 2022 and 2030.ResultsFrom 1991 to 2021, the global composition of DRTB shifted, with EDRTB increasing in developed regions and MDRTB remaining dominant in regions like sub-Saharan Africa. The highest ASIRs for MDRTB in 2021 were seen in Somalia, while the highest for EDRTB were in Moldova. Significant regional variations were observed, with East Asia showing a decrease in MDRTB and Oceania experiencing large increases in both MDRTB and EDRTB. Additionally, country-specific trends varied widely, with Slovenia showing the greatest decrease in MDRTB and Papua New Guinea the largest increase in EDRTB.ConclusionThis study highlights the ongoing dominance of MDRTB in low SDI regions and the expected decline of EDRTB in high SDI regions due to improved treatments and diagnostics. Global predictions suggest a reduction in DRTB burden by 2030, with a focus on early diagnosis and treatment optimization.

Alterations in intercellular communication driven by cellular senescence constitute an important factor in skin aging. Migrasome, a newly discovered vesicular organelle, efficiently participates in intercellular communication; however, the relationship between cellular senescence and migrasomes remains unreported. This study aims to explore the possible relationship between cellular senescence and migrasomes formation, and investigate the effects of young fibroblast-derived migrasomes on senescent keratinocytes and wound healing in aged skin. Single-cell RNA sequencing (scRNA-seq) data analysis revealed that fibroblasts exhibited the highest level of transcriptional variability during skin aging, and the degree of fibroblast senescence negatively correlated with the expression level of migrasome-associated markers. Further multiplex Immunohistochemistry (mIHC) results suggested that younger mouse skin contained more migrasomes than older mouse skin. Transmission electron microscopy (TEM) observations demonstrated abundant migrasomes in the skin from young individuals. In vitro experiments indicated that young fibroblasts produced significantly more migrasomes than senescent fibroblasts, as confirmed by wheat germ agglutinin (WGA) staining and scanning electron microscopy (SEM). Importantly, purified migrasomes from young fibroblasts were found to reduce the expression of senescence-associated markers in HaCaT cells. In vivo, using a wound healing model in naturally aged mice, we observed that migrasomes derived from young fibroblasts not only accelerated wound healing but also reduced senescence-associated marker expression in the skin. Migrasomes formation ability reduced during skin aging progress, and young fibroblast-derived migrasomes rejuvenated senescent keratinocytes and promoted wound healing in aged skin. These findings offer new ideas for alleviating skin aging and enhancing wound healing in aged skin.

Upon DNA virus infection, cGAS senses viral DNA and triggers MITA (also called STING)-dependent induction of type I interferons (IFN-Is) and other cytokines/chemokines. IFN-Is further activate STAT1/2 to induce interferon-stimulated genes (ISGs) and the innate antiviral response. How the innate antiviral response is silenced in uninfected cells and efficiently mounts upon viral infection is not fully understood. In this study, we found that FBXW7, a substrate recognition component of the SCF E3 ubiquitin ligase complex, is a multifaceted regulator of the innate immune response to DNA viruses. In uninfected cells, FBXW7 mediates the polyubiquitination and degradation of GSK3α/β-phosphorylated SLC35B2/3 at the Golgi apparatus. This leads to the downregulation of sulfated glycosaminoglycans (sGAGs) in the Golgi apparatus and the inactivation of MITA in uninfected cells. In addition, FBXW7 mediates the degradation of GSK3α/β-phosphorylated MYC, which is a repressor of STAT1/2, leading to proper STAT1/2 levels in uninfected cells. The differential regulation of FBXW7 on MITA and STAT1/2 ensures inactivation but is ready for fast mount of the innate immune response in uninfected cells. Infection with DNA viruses activates the PI3K‒AKT axis, which inactivates GSK3α/β and inhibits FBXW7-mediated polyubiquitination and degradation of SLC35B2/3, leading to increased production of sGAGs, activation of MITA and rapid onset of the innate antiviral response. Consistently, gene disruption experiments indicate that FBXW7 modulates the innate antiviral response in human THP-1 and mouse BMDM cells. These findings suggest that FBXW7 functions as a versatile regulator of the innate immune response to DNA viruses by differentially regulating upstream and downstream components of the type I interferon induction loop.

Background Simulation is widely utilized in medical education. Exploring the effectiveness of high-fidelity simulation of clinical research within medical education may inform its integration into clinical research training curricula, finally cultivating physician-scientist development. Methods Standard teaching scripts for both clinical trial and cross-sectional study simulation were designed. We recruited undergraduates majoring in clinical medicine at 3(th) grade into a pre-post intervention study. Additionally, a cross-sectional survey randomly selected medical undergraduates at 4(th) or 5(th) grade, medical students in master and doctor degree as external controls. Self-assessment scores of knowledge and practice were collected using a 5-point Likert scale. Changes in scores were tested by Wilcoxon signed-rank test and group comparisons were conducted by Dunn's tests with multiple corrections. Multivariable quantile regressions were used to explore factors influencing the changes from baseline. Results Seventy-eight undergraduates involved the clinical trial simulation and reported improvement of 1.60 (95% CI, 1.48, 1.80, P < 0.001) in knowledge and 1.82 (95% CI, 1.64, 2.00, P < 0.001) in practice score. 83 undergraduates involved in the observational study simulation and reported improvement of 0.96 (95% CI, 0.79, 1.18, P < 0.001) in knowledge and 1.00 (95% CI, 0.79, 1.21, P < 0.001) in practice. All post-intervention scores were significantly higher than those of the three external control groups, P < 0.001. Higher agreement on the importance of clinical research were correlated with greater improvements in scores. Undergraduates in pre-post study showed high confidence in doing a future clinical research. Conclusion Our study provides evidence supporting the integration of simulation into clinical research curriculum for medical students. The importance of clinical research can be emphasized during training to enhance learning effect.

Objectives: Osteoarthritis (OA) stands as the prevailing progressive musculoskeletal disease, serving as the primary cause of chronic pain and activity limitations among adults over 40. Flavan-3-ols, common polyphenolic compounds, are believed to harbor anti-inflammatory and anti-aging properties. This study explores the relationship between flavan-3-ol intake and osteoarthritis risk in individuals over the age of 40 in the US. Methods: This study included 7452 participants over the age of 40 from three cycles (2007-2008, 2009-2010, and 2017-2018) of the National Health and Nutrition Examination Survey. Information on OA history was obtained via home surveys. Information on flavan-3-ol monomers intake was obtained using a survey from the Food and Nutrient Database for Dietary Studies. We used a logistic regression model and restricted cubic spline to analyze the relationships between flavan-3-ol monomers and OA. Stratified analyses were also conducted in this study. Results: There were 1056 participants with OA and 6396 without OA. Compared to the first tertile (T1) group, the adjusted odds ratio with a 95% confidence interval (CI) of logistic regression model 2 for the flavan-3-ol T2 group was 1.296 (0.979-1.715) (p = 0.068), the OR for (-)-epigallocatechin was 1.292 (1.025-1.629) (p = 0.032), and the OR for (-)-epicatechin 3-gallate was 1.348 (1.013, 1.793) (p = 0.042). A dose-response curve indicated a non-linear association (p for non-linearity <0.05) between OA and total flavan-3-ol monomers (nadir point: 483.29 mg, 95% CI: 0.61-0.90). No interaction effects were found in the subgroup analysis. Conclusions: In individuals over 40 in the US, the average daily dietary intake of flavan-3-ol monomers manifests a J-shaped relationship with OA risk.

Objective To compare and analyze the characteristics of the teaching evaluation tools for evidence-based medicine(EBM) in recent 5 years, so as to provide suggestions for further design and optimization of curriculum evaluation methods. Methods PubMed, Web of Science, Chinese biomedical literature database, CNKI, Wanfang database were searched from January 1, 2018 to September 16, 2022. Two researchers screened the literature, extracted the objects, focused topics, psychometric indicators, item contents, etc. of the tools, and made a comprehensive analysis of the existing tools. Results 16 articles (involving 14 tools) were finally included, all of which were reliable. Among them, 11 tools focus on the mastery level of the respondents' knowledge and (or) skills related to evidence-based medicine (the number of items ranges from 6 to 24), mostly involving the comprehensive cognition of evidence-based medicine, the understanding of common terms, the judgment of key concepts, the sharing and application of evidence-based practice, etc., and the evaluation criteria are mostly the judgment of right and wrong, self-evaluation, and the objective evaluation of feedback content; 7 tools focus on the true attitude of the respondents to the evidence-based practice (the number of items ranges from 3 to 21), and the evaluation criteria are mostly subjective intention options; 4 tools are used to understand the implementation frequency, time allocation and sharing of key links of evidence-based practice by the respondents (the number of items ranges from 6 to 18). The evaluation criteria are mostly subjective choices of frequency. Conclusion The questionnaire of knowledge/skills and their attitudes and behaviors can be used as an auxiliary tool in the evaluation of EBM courses. However, it is still necessary to further optimize the content and proportion of items according to the teaching characteristics and goals of the teaching objects, and develop monitoring and evaluation tools for the teaching process of evidence-based medicine curriculum.

Upon viral infection, cytoplasmic pattern recognition receptors detect viral nucleic acids and activate the adaptor protein VISA/MAVS- or MITA/STING-mediated innate antiviral response. Whether and how the innate antiviral response is regulated by neuronal endocrine functions is unclear. Here, we show that viral infection reduced the serum levels of the β-adrenergic hormones epinephrine and norepinephrine as well as the cellular levels of their receptors ADRB1 and ADRB2. We further show that an increase in epinephrine/norepinephrine level inhibited the innate antiviral response in an ADRB1-/2-dependent manner. Mechanistically, epinephrine/norepinephrine stimulation activated the downstream kinase PKA, which catalyzed the phosphorylation of MITA at S241, S243 and T263, inhibiting MITA activation and suppressing the innate immune response to DNA virus. In addition, phosphorylation of VISA at T54 by PKA antagonized the innate immune response to RNA virus. These findings reveal the regulatory mechanisms of innate antiviral responses by epinephrine/norepinephrine and provide a possible explanation for increased host susceptibility to viral infection in stressful and anxiety-promoting situations.

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases.

The current view of nucleic acid-mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)-mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK-mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.

Differential diagnosis and management for perforated appendicitis and non-perforated appendicitis are current hot topics. The aim of this study is to demonstrate a new entity of non-perforated appendicitis, “acute hemorrhagic appendicitis” through studying cluster of acute appendicitis among Tibetan students at a high school in central China. Over the 11-year period, there were 120 patients with more female patients (102 of 499, 20.4%) than male patients (18 of 474, 3.8%) among 973 Tibetan students. 117 patients’ clinical data were available. Clinical manifestations were identical to classic appendicitis. However, axilla temperature, white blood cell counts and neutrophil level were elevated mildly in 12 (10.3%), 19 (16.2%) and 12 (10.3%) patients respectively. Pathologically, the resected appendices exhibited focal or diffuse hemorrhages in mucosa and/or submucosa, and infiltration by eosinophil and by lymphocytes. No patients had perforated appendicitis. The median time from the onset to surgery was 3 days (IQR, 2–4). All patients were discharged with full recovery. In conclusion, “acute hemorrhagic appendicitis” represented a new entity of non-perforated appendicitis with unique cause and pathogenesis, which might be treated with antibiotics alone or self-limited. Studying the cluster is a reliable method to find new entity of appendicitis.

目的 评价目标教学法在留学生循证医学全英文教学中的效果.方法 根据培养留学生的创证和用证能力的目标,针对性地开设了理论课和实验课.采用期中和期末考试、问卷调查和科研成果三项指标评价教学效果.结果 多数留学生对课程目标、课程内容和课程效果等内容表示肯定,89％(33/37)的留学生对本课程给予了积极的总体评价,90.2％(55/61)的留学生总成绩在80分以上,每个留学生在英文期刊上发表文章1篇以上.结论 布鲁姆目标教学法能适合留学生循证医学课程全英文教学.

Objective Infectious etiology of acute appendicitis is a current hot topic. The most of study on appendicitis came from sporadic patients and focused on clinical treatment rather than control and prevention of appendicitis in the population. The present study aims to investigate the epidemiological features of cluster of acute appendicitis, risk factors, and evaluate effectiveness of control and prevention in population. Methods We conducted longitudinal study on a cluster of acute appendicitis among Tibetan students at a high school in eastern China, which was divided into three stages: 1. We retrospectively collected epidemiological data and clinical data to explore risk factor and possible transmission route in August of 2005; 2. We conducted targeted measures from August of 2005 and analyzed incidence trend from 2000 to 2010; 3. Since no new patients occurred in 2011, we conducted surveillance from the beginning of 2012 until July 2018. Results Among 973 Tibetan students, there were 120 patients with more female patients (102 of 499, 20.4%) than male patients (18 of 474, 3.8%) from January of 2000 to December of 2010. The 4-year cumulative incidence rates in female students enrolled in 2001, 2002, 2003, 2004, 2005, 2006 were 26.8% (11 of 41), 27.1% (13 of 48), 44.7% (21 of 47), 42.4% (14 of 33), 23.1% (9 of 39), and 19.3% (11 of 57), respectively before their graduation. There was a clustering feature. Mutual contact with patients before the onset of symptoms was an important risk factor (Adjusted OR 4.89, 95% CI: 1.67–14.35). Transmission route may be fecal-oral infection. Before conducting targeted measures, the incidence rate increased from 2000 and peaked in 2005. After conducting targeted measures, the incidence rate decreased year by year until 2010. Under surveillance from January of 2012 to July of 2018, only four sporadic patients occurred at this school. Conclusion This cluster of acute appendicitis had features of an infectious disease in epidemiology, which can be controlled and prevented by targeted measures. Our study may also be used for prevention of sporadic patients and be generalized in general population as cluster of appendicitis occurred in many provinces of China.

Background Clinical research has frequently not been taught in a practical way, often resulting in a very didactic approach rendering it not very accessible for medical undergraduates. Simulation can provide an immersive, interactive, and reflective experience and may be applied to the clinical research curriculum. Methods A 7-step model, modified from Kern’s six-step approach and Khamis’s stepwise model, was used to develop the curriculum. A questionnaire survey on undergraduates’ attitude towards, knowledge and practice of clinical research and simulation education was conducted to generate a targeted needs assessment. The simulation framework was integrated into the development of educational strategies. Experts were consulted to assess the curriculum prior to implementation. Results Talent construction in China needs an innovative capability-enhanced clinical research curriculum. Sixty-six clinical undergraduates in our school completed the survey. 89.39% (59/66) of them hadn’t participated in clinical research, while 93.94% (62/66) would like to conduct clinical trials if possible. 75.76% of respondents didn’t have knowledge of or practical abilities in clinical trials. The mean score for practical ability (2.02 ± 0.92) was lower than that of knowledge (2.20 ± 0.93) ( P < 0.01). The dimension of case report form got the lowest score among the five dimensions. Participating in clinical research ( P = 0.04) and learning for themselves ( P < 0.01) by a few students may have increased the total score. The curriculum was designed to simulate the whole process from protocol writing, registration, ethical approval, implementation, and data analysis to reporting based on one case study, and was divided into two parts to simulate different types of research: randomized controlled trials and observational studies. It was conducted in semesters 5 and 7 respectively, both including 16 sessions. After expert consultation, one session having a 29.01% coefficient of variation was adjusted and replaced. The final simulation class design scenario scripts are provided for reference. Conclusions The targeted needs assessment exposed medical undergraduates’ poor knowledge of and abilities in clinical research. This is the first report of a simulation-based clinical research curriculum developed in China, and adds curriculum development and design details to the limited related published studies.

Evidence-based medicine is the basic requirement of international and Chinese medical education, which aims to cultivate medical talents with critical thinking, innovation and clinical problem solving abilities. Wuhan University has offered an evidence-based medicine curriculum since 2004. It has carried out a comprehensive and systematic exploration of practice, completed the establishment of teaching and research departments, the development of teachers and construction of a curriculum sys-tem, covering all medical students. Evidence-based medicine education has been effectively integrated into the development process of medical students in the new era. This paper introduces the orientation and construction of the curriculum system for evidence-based medicine in Wuhan University. In partic-ular, it summarizes the methods of the "1+4" curriculum teaching mode, evaluation of "teaching" and "learning" in the whole process, and explores teacher’s development and heritage, aiming to provide suggestions for China's evidence-based medicine education, and promote the cultivation of medical tal-ents.

Background Human periodontitis is a highly prevalent inflammatory disease that leads to connective tissue degradation, alveolar bone resorption, and tooth loss. Angiopoietin-like 2 (ANGPTL2) regulates chronic inflammation in various diseases and is functionally involved in maintaining tissue homeostasis and promoting tissue regeneration, but there is limited information about its function in periodontitis. Here we investigated the expression and explicit role of ANGPTL2 in periodontitis. Methods Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to detect the ANGPTL2 expression in periodontal tissues and periodontal ligament cells (PDLCs). A ligature-induced periodontitis model was generated in wild-type and ANGPTL2 knockout mice. qRT-PCR and enzyme-linked immunosorbent assay were used to assess the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in cultured PDLCs. Western blot was performed to detect proteins in relevant signaling pathways. Results Increased ANGPTL2 expression was observed in inflamed periodontal tissues and PDLCs. ANGPTL2 deficiency promoted alveolar bone loss with enhanced osteoclastogenesis and inflammatory reactions in ligature-induced periodontitis. Downregulation of ANGPTL2 remarkably enhanced expression levels of interleukin (IL)-6, IL-8, MMP1, and MMP13 in Porphyromonas gingivalis lipopolysaccharide-induced PDLCs, whereas ANGPTL2-overexpressing PDLCs showed opposite trends. ANGPTL2 downregulation activated STAT3 and nuclear factor-kappa B pathways and blocked Akt signaling under inflammatory environment. Treatment with a STAT3 inhibitor partially suppressed the inflammatory reaction of PDLCs mediated by ANGPTL2 knockdown. Conclusions Our study provides the first evidence of an anti-inflammatory effect of ANGPTL2 in murine periodontitis. The findings demonstrate the critical and protective role of ANGPTL2 in alveolar bone loss and periodontal inflammation.

加强高素质医学人才的培养是临床医学教育的根本目的,也是推动临床医学事业不断发展的根本保障.循证医学的提出与发展为创新临床医学教育开辟了新的方法与思路,也为临床医学实践提供了科学合理的决策模式.经过近三十年的发展,国内许多高校已经系统性的开设了循证医学相关的课程,出版了教材,拥有了一批从事循证医学教育的师资力量,对具备循证思维的医学人才培养起到了积极的作用.然而,囿于多种因素,并非所有的高校均能开设相关课程,且已开设的亦有需要相互借鉴的地方.本文简述循证医学的起源及发展、循证医学教育在推动新型医学人才培养中的应用、我校开设循证医学相关课程的经验、新时代背景下循证医学教育的难点及变革,希望为在临床医学教学中开展循证医学课程教育提供参考.

Periodontitis is a widespread chronic infectious-inflammatory disease associated with multiple systemic diseases. Visfatin is an adipokine-enzyme that can be locally produced by human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs). It can upregulate proinflammatory cytokines and matrix metalloproteinases (MMPs) in various types of cells. However, the effects of visfatin on healthy and inflammatory human periodontal cells as well as the underlying molecular mechanisms remain unclear. This study firstly demonstrated visfatin expression was highly elevated in inflamed human gingiva and Pg LPS-treated hPDLCs. Moreover, recombinant visfatin significantly upregulated the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and prodegradative factors (EMPPRIN, MMP1, MMP3 and MMP13) in hPDLCs. Next, we found the levels of proinflammatory and prodegradative cytokines were significantly increased in visfatin-overexpressing hPDLCs, and decreased in visfatin-silencing inflammatory hGFs (iGFs) when treated with Pg LPS. In the absence of Pg LPS, visfatin silencing failed to affect the expression of these factors in iGFs, and overexpression of visfatin upregulated MMPs but no other factors in hPDLCs. Furthermore, marked NF-κB pathway activation with increased phosphorylation of p65 was observed in visfatin-overexpressing hPDLCs. BAY11-7082, a specific inhibitor of NF-κB, partially reversed the upregulation proinflammatory and prodegradative factors induced by visfatin overexpression. Taken together, this study showed that visfatin critically regulates Pg LPS-induced proinflammatory/prodegradative effects in healthy and inflammatory periodontal cells partially via NF-κB pathway. The findings suggest that visfatin is closely involved in the development of periodontitis, and may serve as a promising novel biomarker and therapeutic target for periodontitis management.

Collagen triple helix repeat containing 1 (CTHRC1), a secreted glycoprotein, is widely expressed in many tissues. It has been recently defined as a novel marker for rheumatoid arthritis (RA), a systemic inflammatory disorder. However, the precise role of CTHRC1 in other chronic inflammatory diseases, like periodontal disease, remains unclear. This research aimed to explore the presence of CTHRC1 in periodontal inflammation, determine the precise role in inflammatory response modulation in periodontal ligament cells (PDLCs), and explore its underlying mechanisms. In vivo gingival crevicular fluid (GCF) and gingivae were obtained from healthy people and chronic periodontitis patients. Maxillary tissues of mice with or without ligature-induced periodontitis were immunostained for CTHRC1. In vitro human PDLCs were treated with tumor necrosis factor alpha (TNF-α) to mimic the inflammatory environment. Small interfering RNA (siRNA) was used to silence CTHRC1. SB203580 was used to inhibit the p38 mitogen-activated protein kinase (MAPK) pathway. CTHRC1 was highly expressed in GCF and gingival tissues of periodontitis patients. Animal models also revealed the same tendency. CTHRC1 knockdown promoted inflammatory cytokine production and activated the p38 MAPK signaling pathway in PDLCs. Inhibiting the p38 MAPK signaling pathway partially attenuated the inflammatory responses. This study revealed that CTHRC1 was highly expressed in periodontitis and suggested that CTHRC1 might play an important role in modulating periodontal inflammation.

方法学质量(偏倚风险)评估是医学研究开始前的重要步骤.因此,准确判断研究类型是前提,选择合适的评价工具也很重要.本综述介绍了用于随机对照试验(包括个体和整群)、动物实验、非随机干预性研究(包括随访研究、有对照组的前后对照研究、前后对照研究、非对照纵向研究、间断时间序列研究)、队列研究、病例-对照研究、横断面研究(包括分析和描述性研究)、观察性病例系列和病例报告、比较效果研究、诊断性研究、卫生经济学评价、预测研究(包括预测变量研究、预测模型影响研究、预后预测模型研究)、质性研究、结果测量工具(包括患者-报告的结果测量发展、内容真实性、结构真实性、内部一致性、跨文化真实性/测量不变性、信度、测量误差、校标真实性、结构真实性假设检验、反应度)、系统评价与Meta分析,以及临床实践指南的方法学质量评价工具.通过本综述,读者可以区分医学研究的类型并选择适当的工具.全面掌握相关知识并多加练习是正确评估方法学质量的基本要求.