Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Moxibustion for medical personnel with negative emotion and insomnia during COVID-19 pandemic: A randomized, controlled trial

Li Xiying,Li Xiaojuan,Wang Xian,Yin Xuan,Li Shanshan,Wu Junyi,Ren Xiumei,Zhang Wei,Mi Yiqun,Xu Shifen 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.3

Background: We conducted this randomized controlled trial (RCT) to evaluate the effectiveness and safety of moxibustion at Sanyinjiao (SP6) acupoint for treatment of negative mood and sleep quality in healthcare workers during the 2019 coronavirus disease (COVID-19). Methods: A total of 180 participants were divided in a 1:1 ratio into two groups, the treatment group (for moxibustion) and the control group (for no treatment). The treatment group had a 30-minute moxibustion therapy once a day for two weeks, followed by a two-week follow-up. The Hamilton Anxiety Scale (HAMA) was used to assess the degree of the participants' anxiety, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to examine their depressed condition. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to measure the level of burnout among healthcare workers. To determine the severity of insomnia, the Sleep Dysfunction Rating Scale (SDRS) was utilized. At baseline, week 2, and week 4, all scales were evaluated. Results: Compared to the control group, The treatment group improved more significantly in the HAMA at week 2 (MD = -19.01, 95% CI: -21.89 to -16.14; P<0.001) and at week 4 follow-up visits (MD = -8.96, 95% CI: -11.19 to -6.73; P<0.001). A subgroup study of HAMA scores revealed that position and education had significant impact on treatment effectiveness. During the 2-week intervention period, the treatment group showed more significant improvements in depressive symptoms measured by PHQ-9 (13.00±2.41 vs. 15.60±3.65; P<0.001), work burnout symptoms measured by MBI-GS (MD = -11.88, 95% CI, -15.73 to -8.03; P<0.001), and insomnia symptoms measured by SDRS (MD = -2.45, 95% CI, -4.24 to -0.66; P<0.01). There were no significant adverse effects reported. Conclusion: Moxibustion at SP6 may be an effective treatment to improve anxiety, depression, sleep quality, and quality of life for healthcare workers during COVID-19.

Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer

Li, Fang-Xuan,Wei, Li-Juan,Zhang, Huan,Li, Shi-Xia,Liu, Jun-Tian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Purpose: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancerfocussing on platelet counts and gastric cancer progression through different TNM stages. Methods: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, > $400{\times}1000/{\mu}L$) and a control group (1,476 patients, ${\leq}400{\times}1000/{\mu}L$). Results: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. Conclusion: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

Preoperative BRAF Mutation is Predictive of Occult Contralateral Carcinoma in Patients with Unilateral Papillary Thyroid Microcarcinoma

Zhou, Yi-Li,Zhang, Wei,Gao, Er-Li,Dai, Xuan-Xuan,Yang, Han,Zhang, Xiao-Hua,Wang, Ou-Chen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background and Objective: The optimal resection extent for clinically unilateral papillary thyroid microcarcinoma (PTMC) remains controversial. The objective was to investigate risk factors associated with occult contralateral carcinoma, and put emphasis on the predictive value of preoperative BRAF mutation. Materials and Methods: 100 clinically unilateral PTMC patients all newly diagnosed, previously untreated were analyzed in a prospective cohort study. We assessed the T1799A BRAF mutation status in FNAB specimens obtained from all PTMC patients before undergoing total thyroidectomy (TT) and central lymph node dissection (CLND) for PTMC. Univariate and multivariate analyses were used to reveal the incidence of contralateral occult cancer, difference of risk factors and predictive value, with respect to the following variables: preoperative BRAF mutation status, age, gender, tumor size, multifocality of primary tumor, capsular invasion, presence of Hashimoto thyroiditis and central lymph node metastasis. Results: 20 of 100 patients (20%) had occult contralateral lobe carcinoma. On multi-variate analysis, preoperative BRAF mutation (p = 0.030, OR = 3.439) and multifocality of the primary tumor (p = 0.004, OR = 9.570) were independent predictive factors for occult contralateral PTMC presence. However, there were no significant differences between the presence of occult contralateral carcinomas and age, gender, tumor size, capsular invasion, Hashimoto thyroiditis and central lymph node metastasis. Conclusions: Total thyroidectomy, including the contralateral lobe, should be considered for the treatment of unilateral PTMC if preoperative BRAF mutation is positive and/or if the observed lesion presents as a multifocal tumor in the unilateral lobe.

Distinct mutations in MLH1 and MSH2 genes in Hereditary Non-polyposis Colorectal Cancer (HNPCC) families from China

( Wen Qian Wei ),( Fang Qi Liu ),( Lei Liu ),( Zuo Feng Li ),( Xiao Yan Zhang ),( Fan Jiang ),( Qu Shi ),( Xiao Yan Zhou ),( Wei Qi Sheng ),( San Jun Cai ),( Xuan Li ),( Ye Xu ),( Peng Nan ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.5

Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed. [BMB reports 2011; 44(5): 317-322]

Comorbidity Relationship to Outcome of Radical Cystectomy in Chinese: a Single Institution Study with the ACE-27 Comorbidity Index

Xuan, Zhu,Zhong, Zhao-Hui,Zhang, Xuan-Zhi,Zhang, Lei,Zhao, Xiao-Kun,Lv, Chen,Xu, Ran,Ren, Wei-Gang,Li, Song-Chao Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

To determine the relationship between comorbidity and outcome after radical cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27 index. Two-hundred-and-forty-six patients treated with radical cystectomy at the Second Xiangya Hospital of Central South University, Hunan Province, China between 2000 and 2010 were retrospectively analyzed. Medical records were reviewed for age, gender, delayed time of radical cystectomy, urinary diversion type, pelvic lymphadenectomy status, TNM stage, and pathological grade. Comorbidity information was assessed by the ACE-27 index. The outcome measurement was overall survival. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the association between comorbidity and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%) females with a mean age of $62{\pm}11$ years. Median duration of follow-up was $47{\pm}31$ months. A total of 151 (61.38%) patents died during follow-up. Of those, 118 (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128 (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly associated with decreased overall survival. In addition, age ${\geq}70$ years (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to be independent risk factors of overall survival. Increasing severity of comorbidity statistically correlated with decreased overall survival after radical cystectomy.

DNA Methylation in Peripheral Blood: A Potential Biomarker for Cancer Molecular Epidemiology

Li, Lian,Choi, Ji-Yeob,Lee, Kyoung-Mu,Sung, Hyuna,Park, Sue K.,Oze, Isao,Pan, Kai-Feng,You, Wei-Cheng,Chen, Ying-Xuan,Fang, Jing-Yuan,Matsuo, Keitaro,Kim, Woo Ho,Yuasa, Yasuhito,Kang, Daehee Japan Epidemiological Association 2012 Journal of epidemiology Vol.22 No.5

<P>Aberrant DNA methylation is associated with cancer development and progression. There are several types of specimens from which DNA methylation pattern can be measured and evaluated as an indicator of disease status (from normal biological process to pathologic condition) and even of pharmacologic response to therapy. Blood-based specimens such as cell-free circulating nucleic acid and DNA extracted from leukocytes in peripheral blood may be a potential source of noninvasive cancer biomarkers. In this article, we describe the characteristics of blood-based DNA methylation from different biological sources, detection methods, and the factors affecting DNA methylation. We provide a comprehensive literature review of blood-based DNA methylation as a cancer biomarker and focus on the study of DNA methylation using peripheral blood leukocytes. Although DNA methylation patterns measured in peripheral blood have great potential to be useful and informative biomarkers of cancer risk and prognosis, large systematic and unbiased prospective studies that consider biological plausibility and data analysis issues will be needed in order to develop a clinically feasible blood-based assay.</P>

Adenosine A3 Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells

Wei Ye,Jinhui Sun,Chunchao Li,Xuan-Yan Fan,Fan Gong,Xinqia Huang,Mingzhu Deng,Jia-Qi Chu 대한기생충학ㆍ열대의학회 2020 The Korean Journal of Parasitology Vol.58 No.4

Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

Study on the micro-scale simulation of wind field over complex terrain by RAMS/FLUENT modeling system

Li, Lei,Zhang, Li-Jie,Zhang, Ning,Hu, Fei,Jiang, Yin,Xuan, Chun-Yi,Jiang, Wei-Mei Techno-Press 2010 Wind and Structures, An International Journal (WAS Vol.13 No.6

A meteorological model, RAMS, and a commercial computational fluid dynamics (CFD) model, FLUENT are combined as a one-way off-line nested modeling system, namely, RAMS/FLUENT system. The system is experimentally applied in the wind simulation over a complex terrain, with which numerical simulations of wind field over Foyeding weather station located in the northwest mountainous area of Beijing metropolis are performed. The results show that the method of combining a meteorological model and a CFD model as a modeling system is reasonable. In RAMS/FLUENT system, more realistic boundary conditions are provided for FLUENT rather than idealized vertical wind profiles, and the finite volume method (FVM) of FLUENT ensures the capability of the modeling system on describing complex terrain in the simulation. Thus, RAMS/FLUENT can provide fine-scale realistic wind data over complex terrains.

Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer

Li-jun Liang,Chen-xi Hu,Yi-xuan Wen,Xiao-wei Geng,Ting Chen,Guo-qing Gu,Lei Wang,You-you Xia,Yong Liu,Jia-yan Fei,Jie Dong,Feng-hua Zhao,Yiliyar Ahongjiang,Kai-yuan Hui,Xiao-dong Jiang 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed. Results For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.