CMTR1 promotes colorectal cancer cell growth and immune evasion by transcriptionally regulating STAT3.

CMTR1, also called IFN-stimulated gene 95 kDa protein (ISG95), is elevated by viral infection in a variety of cells. However, the functions of CMTR1 in colorectal cancer (CRC), especially its roles in tumorigenesis and immune regulation, remain unclear. Here, we first identified CMTR1 as a novel oncogene in colorectal cancer. Based on The Cancer Genome Atlas (TCGA) database exploration and human tissue microarray (TMA) analysis, we found that CMTR1 expression was markedly higher in CRC tissues than in adjacent normal tissues. High CMTR1 expression was correlated with poor prognosis in CRC patients. Knockdown (KD) of CMTR1 significantly suppressed cell proliferation and tumorigenicity both in vitro and in vivo, whereas overexpression of CMTR1 resulted in the opposite effects. KEGG pathway analysis revealed differential enrichment in the JAK/STAT signaling pathway in colorectal cancer cells with CMTR1 KD. Mechanistically, suppression of CMTR1 expression inhibited RNAPII recruitment to the transcription start site (TSS) of STAT3 and suppressed STAT3 expression and activation. Furthermore, the efficacy of PD1 blockade immunotherapy was prominently enhanced in the presence of CMTR1 KD via increased infiltration of CD8 + T cells into the tumor microenvironment. Overall, it appears that CMTR1 plays a key role in regulating tumor cell proliferation and antitumor immunity.

Effects of C3aR and receptor for advanced glycation end products on bone metabolism in APP/PS1 mice models of Alzheimer′s disease / 中华内分泌代谢杂志

Objective:To investigate the effects of complement C3a receptor(C3aR) and receptor for advanced glycation end product(RAGE) on bone metabolism in APP/PS1 mice model of Alzheimer′s disease.Methods:Alzheimer′s disease model APP/PS1 mice was hybridized with C3aR knockout mice(C3aR -/-), RAGE knockout mice(RAGE -/-) to generate APP/PS1-C3aR -/- and APP/PS1-RAGE -/-, respectively. In vivo, micro computed tomography(Micro-CT) scan, bone tissue osteocalcin immunohistochemical staining, tartrate-resistant acid phosphatase(TRAP) staining and Goldner′s trichrome staining were used to understand the variabilities of bone metabolism between different genotypes of mice; In vitro, bone marrow-derived osteoblast and osteoclast induction cultures were used to understand the effects of C3aR and RAGE on osteoblast and osteoclast differentiation. Results:In in vivo experiments, APP/PS1-C3aR -/- and APP/PS1-RAGE -/- mice showed increased bone mass, increased bone formation, decreased bone resorption, and increased osteoid compared to APP/PS1 mice( P<0.05). In in vitro experiments, bone marrow mesenchymal stem cells(BMSCs) derived from APP/PS1-C3aR -/- and APP/PS1-RAGE -/- mice showed enhanced osteoblast differentiation and elevated expression levels of alkaline phosphatase(ALP) and runt-related transcription factor 2(RUNX2), diminished osteoclast differentiation, and reduced positive TRAP staining( P<0.05). Conclusions:Both C3aR and RAGE are involved in regulating the process of APP/PS1 bone metabolism. Knockout of C3aR and RAGE can improve osteoporosis in APP/PS1, providing a new target for the clinical treatment of Alzheimer′s disease combined with osteoporosis.

Clinical observation on electroacupuncture plus Yi Jin Jing (Sinew-transforming Qigong Exercises) for knee osteoarthritis / 针灸推拿医学（英文版）

Objective: To observe the efficacy of electroacupuncture (EA) plus Yi Jin Jing (Sinew-transforming Qigong Exercises) for knee osteoarthritis (KOA). Methods: A total of 60 patients with KOA were divided into an observation group and a control group according to the random number table method, with 30 cases in each group. Patients in the observation group received the treatment of EA plus Yi Jin Jing (Sinew-transforming Qigong Exercises), while patients in the control group only received EA treatment. Both groups were treated for 5 weeks. The changes of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores in the two groups were observed after treatment. Results: After treatment, the total effective rate in the observation group (92.3％) was significantly higher than that in the control group (70.0％), (P<0.05); the WOMAC and VAS scores in both groups were significantly lower than those before treatment, showing statistical significance (all P<0.01); there were significant differences in the post-treatment changes in the WOMAC and VAS scores between the two groups (P<0.05, P<0.01). Conclusion: EA plus Yi Jin Jing (Sinew-transforming Qigong Exercises) is clinically effective for KOA. This combined treatment can alleviate clinical symptoms.

Management of Data Sharing of Human Genetic Resources and Its Enlightenment to China / 中国医学科学院学报

Human genetic resources are valuable for life science research and pharmaceutical industry.Competitions for human genetic resources and the relevant techniques and industries have increasingly become intense among countries with the the implementation of precision medicine strategy and the maturity of gene editing technology.In the context of scientific progress and efficiency,the Organisation for Economic Co-operation and Development,the most important international economic organization,has proposed solutions to technological development and research paradigm changes from the perspective of national and global public interests.The United States,Japan,the United Kingdom,and some other developed countries have also released their policies and guidelines on the sharing of genetic resource data.In this article we analyzed these policies and guidelines,with an attempt to further improve the administration of human genetic resource sharing in China and promote the legal sharing and effective use of these resources.

APP promotes osteoblast survival and bone formation by regulating mitochondrial function and preventing oxidative stress.

Amyloid precursor protein (APP) is ubiquitously expressed in various types of cells including bone cells. Mutations in App gene result in early-onset Alzheimer's disease (AD). However, little is known about its physiological function in bone homeostasis. Here, we provide evidence for APP's role in promoting bone formation. Mice that knocked out App gene (APP-/-) exhibit osteoporotic-like deficit, including reduced trabecular and cortical bone mass. Such a deficit is likely due in large to a decrease in osteoblast (OB)-mediated bone formation, as little change in bone resorption was detected in the mutant mice. Further mechanical studies of APP-/- OBs showed an impairment in mitochondrial function, accompanied with increased reactive oxygen species (ROS) and apoptosis. Intriguingly, these deficits, resemble to those in Tg2576 animal model of AD that expresses Swedish mutant APP (APPswe), were diminished by treatment with an anti-oxidant NAC (n-acetyl-l-cysteine), uncovering ROS as a critical underlying mechanism. Taken together, these results identify an unrecognized physiological function of APP in promoting OB survival and bone formation, implicate APPswe acting as a dominant negative factor, and reveal a potential clinical value of NAC in treatment of AD-associated osteoporotic deficits.

Application and development of block chain technology in health field / 中华医学图书情报杂志

Block chain, as a decentralized, trustless database technology program with an intact information trans-parency and a privacy protection function, can be use to construct a highly effective and reliable transmission sys-tem and promote the Internet to become an infrastructure in building the society-trusted network. Block chain is of significant advantages in optimizing the business processes, reducing the operation cost and improving the synergis-tic efficiency in financial industry, and is thus rapidly applied in other industries. The construction of health and medical big data is faced with the challenge of both information security and privacy protection in health field. Block chain is characterized by high fault tolerance, unaltered infrastructure and privacy protection function, and has thus a large room for its application in medical treatment, pharmaceutical industry, medical insurance and ge-nomics.

Development and Validation of the Production Process of Parecoxib Sodium Freeze-dried Preparation Based on Quality by Design / 中国药学杂志

OBJECTIVE: To prepare parecoxib sodium freeze-dried preparation, evaluate and validate the feasibility of the production process and quality reliability of the preparation. METHODS: Risk assessment of the production process of parecoxib sodium freeze-dried preparation was performed based on the method of quality by design (QbD).The key steps and key process parameters were identified.The critical quality attributes (CQAs)of the intermediates and final product were clarified, the validation protocol and acceptable standard were accordingly developed, and the production process was validated. RESULTS: The production process of parecoxib sodium freeze-dried preparation met the GMP requirements, and the intermediate and final products met the quality standards. CONCLUSION: The established production process of parecoxib sodium freeze-dried preparation is feasible and the product quality is controllable.

High frequency key words co-occurrence cluster-based analysis of hotspots in studies of telemedicine / 中华医学图书情报杂志

Objective To provide the reference for researchers to understand the current situation in telemedicine by studying its hotspots with visual representation.Methods The cluster of Web of Science(WOS)-covered papers on telemedicine in the past 10 years was analyzed by bibliographic co-occurrence analysis combined with the dual cluster software gcluto.Results The hotspots in studies of telemedicine at present were centralized on system con-struction,evaluation analysis and data output.Conclusion Telemedicine,an important means for the rational allo-cation of medical resources,needs its researchers to integrate their study and new technologies,improve their medi-cal service level and promote the equality of medical service.

Clinical experience of Qin's eight scalp needles for treatment of Parkinson's disease / 中国针灸

The eight scalp needles, founded by Professor QIN Liang-fu, and its clinical experience for treatment of Parkinson's disease (PD) are introduced. Based on his years of clinical experience, it is proposed by Professor QIN that the Governor Vessel is mainly for miscellaneous disease and disease of limbs. Combined with distribution of cephalic motor region and meridian, an acupuncture treatment plan that is full of innovativeness is proposed, which is called Qin's eight scalp needles. It includes bilateral Fengchi (GB 20), Shuaigu (GB 8), Toulinqi (GB 15) as well as Yintang (GV 29) and Baihui (GV 20), mainly for treatment of nervous system diseases, such as PD and multiple sclerosis and so on. Besides, some outpatient cases are introduced to explain that eight scalp needle could alleviate the progression of PD, improve patients' motor, cognitive and affective disorders, reduce the suffering of patients, and improve the patient's quality of life.

Swedish mutant APP suppresses osteoblast differentiation and causes osteoporotic deficit, which are ameliorated by N-acetyl-L-cysteine.

Reduced bone mineral density and hip fracture are frequently observed in patients with Alzheimer's disease (AD). However, mechanisms underlying their association remain poorly understood. Amyloid precursor protein (APP) is a transmembrane protein that is ubiquitously expressed in bone marrow stromal cells (BMSCs), osteoblasts (OBs), macrophages (BMMs), and osteoclasts (OCs). Mutations in the APP gene identified in early-onset AD patients are believed to cause AD. But little is known about APP's role in bone remodeling. Here, we present evidence for Swedish mutant APP (APPswe) in suppression of OB differentiation and function in culture and in mouse. APP expression in BMSCs increases during aging. Ubiquitous expression of APPswe in young adult Tg2576 transgenic mice (under the control of a prion promoter) recaptured skeletal "aging-like" deficits, including decreased OB genesis and bone formation, increased adipogenesis and bone marrow fat, and enhanced OC genesis and bone resorption. Remarkably, selective expression of APPswe in mature OB-lineage cells in TgAPPswe-Ocn mice (under the control of osteocalcin [Ocn] promoter-driven Cre) also decreased OB genesis and increased OC formation, resulting in a trabecular bone loss. These results thus suggest a cell-autonomous role for APPswe in suppressing OB formation and function, but a nonautonomous effect on OC genesis. Notably, increased adipogenesis and elevated bone marrow fat were detected in young adult Tg2576 mice, but not in TgAPPswe-Ocn mice, implying that APPswe in BMSCs and/or multicell types in bone marrow promotes bone marrow adipogenesis. Intriguingly, the skeletal aging-like deficits in young adult Tg2576 mice were prevented by treatment with N-acetyl-L-cysteine (NAC), an antioxidant, suggesting that reactive oxygen species (ROS) may underlie APPswe-induced osteoporotic deficits. Taken together, these results demonstrate a role for APPswe in suppressing OB differentiation and bone formation, implicate APPswe as a detrimental factor for AD-associated osteoporotic deficit, and reveal a potential clinical value of NAC in the treatment of osteoporotic deficits. © 2013 American Society for Bone and Mineral Research.

Effect of fluoride on the function of osteoblast bone formation / 中华风湿病学杂志

Objective To observe the effects of different concentration of NaF on osteoblasts function of bone formation and dose effect relationship.Methods Osteoblasts were obtained from the calvaria of 24 hour newborn SD rats by enzymic degestion and cultuered in the medium with 10 -7 ～5? 10 -4 mol/L NaF.The ALP activity and osterocalcin were examined by biochemical assay and radioimmunologic assay (RIA) respectively.Results Results showed that the effect of NaF on ALP activity was in a double phase manner,e.g. low concentration NaF(10 -7 ,10 -6 ,10 -5 mol/L) increased ALP activity ( P

Experimental Study on the Influence of NaF on the Proliferation and Differentiation of Osteroblasts / 华中科技大学学报(医学版)

The effects of different concentrations of NaF on the proliferation and differentiation of osteroblasts were observed. Osteroblasts were obtained from the calvaria of 24-h newborn Sprague Dawley (SD) rat by using enzymic degestion method and cultured in the medium containing 10-7 mol/L to 10-5( 10-4 mol/L NaF. The rate of cell proliferation, ALP activity and osterocalcin were examined by the methods of MTT, biochemical assay and radioimmunologic assay (RIA) respectively. The results showed that the effect of NaF on the proliferation of osteroblasts was regulated in a double-phase manner: low doses of NaF (10-7 mol/L, 10-6 mol/L,10 5 mol/L) increased cell proliferation by 11. 3 o, 10. 9 % and 10. 6 % (P＜0. 05) respectively, vice versa at high doses (10-4 mol/L, 5×10-4 mol/L). As compared with control group, high doses of NaF decreased the proliferation rate by 9. 6 %, 9. 7 % respectively. The response of cell differentiation to NaF was varied. The influence of NaF on ALP activity was similar to that of cell proliferation. However, all concentrations of NaF used stimulated the secretion of osterocalcin with the highest secreting rate being up to 67. 14 % at 5×10 4 mol/L NaF. It was concluded that the influence of NaF on the proliferation of rat calvarial osteroblasts regulated in a double-phase manner, but the action on cell differentiation was varied.