New perspective on the treatment of rheumatic arthritis based on“strengthening body resistance(Fú Zhèng)”in the theory of co-inhibitory receptor-regulated T-cell immunity

Co-inhibitory receptors serve as crucial regulators of T-cell function,playing a pivotal role in modulating the delicate balance between immune tolerance and autoimmunity.Initially identified in autoimmune disease models,co-inhibitory receptors,including CTLA-4,PD-1,TIM-3,and TIGIT,were found to be integral to immune regulation.Their blockade or absence in these models resulted in the induction or exacerbation of autoimmune diseases.Additionally,scholars have observed that co-inhibitory receptors on lymphocytes hold the potential to influence the prognosis in the context of chronic inflammation.Consequently,the blocking of co-suppressor receptors has emerged as a novel therapeutic approach for inhibiting refractory inflammatory diseases,particularly rheumatoid arthritis.From the standpoint of traditional Chinese medicine(TCM),the treatment of rheumatoid arthritis based on the“strengthening body resistance(FúZhèng)”theory can be construed as the regulation of co-suppressor receptors to modulate the body’s immune function in combating chronic inflammation.This article provides a succinct overview of the role of co-suppressor receptors in anti-inflammatory processes and explores the research prospects of co-suppressor receptor intervention in the treatment of rheumatoid arthritis.The exploration integrates the“strengthening body resistance(FúZhèng)”theory with relevant Chinese medicine formulations.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Enteric glia mediate neuronal outgrowth through release of neurotrophic factors

Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.

The translational importance of establishing biomarkers of human spinal cord injury

The evaluation of such novel therapies for acute spinal cord injury in clinical trials is extremely challenging.Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patients ineligible for trials because they are not examinable.Furthermore,the difficulty in predicting neurologic recovery based on the early clinical assessment forces investigators to recruit large cohorts to have sufficient power.Biomarkers that objectively classify injury severity and better predict neurologic outcome would be valuable tools for translational research.As such,the objective of the present review was to describe some of the translational challenges in acute spinal cord injury research and examine the potential utility of neurochemical biomarkers found within cerebrospinal fluid and blood.We focus on published efforts to establish biological markers for accurately classifying injury severity and precisely predict neurological outcome.

Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Endovascular retrieval of a prematurely deployed covered stent

Several techniques have been reported to address different endovascular device failures. We report the case of a premature deployment of a covered balloon mounted stent during endovascular repair of a posttraumatic carotid-cavernous fistula(CCF). A 50-year-old male suffered a fall resulting in loss of consciousness and multiple facial fractures. Five weeks later, he developed decreased left visual acuity, proptosis, chemosis, limited eye movements and cranial/orbit bruit. Cerebral angiography demonstrated a direct left CCF and endovascular repair with a 5.0 mm × 19 mm covered stent was planned. Once in the lacerum segment, increased resistance was encountered and the stent was withdrawn resulting in premature deployment. A 3 mm × 9 mm balloon was advanced over an exchange length microwire and through the stent lumen. Once distal to the stent, the balloon was inflated and slowly pulled back in contact with the stent. All devices were successfully withdrawn as a unit. The use of a balloon to retrieve a prematurely deployed balloon mounted stent is a potential rescue option if leaving the stent in situ carries risks.

Inhibition of Axinl in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

Axinl is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined.In the present studies,we determined changes in postnatal bone growth by deletion of Axinl in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1 O5X mice and found that hypertrophic cartilage area was largely expanded in AxinlOSX KO mice.A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1OSX KO mice.Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased,demonstrated by decreased TRAPpositive cell numbers,associated with reduction of MMP9-and cathepsin K-positive cell numbers in Axin1 O5X KO mice.OPG expression and the ratio of O p g to Rankl were significantly increased in osteoblasts of Axinl O5X KO mice.Osteoclast formation in primary bone marrow derived microphage(BMM)cells was significantly decreased when BMM cells were cultured with conditioned media(CM)collected from osteoblasts derived from Axin1OSX mice compared with BMM cells cultured with CM derived from WT mice.Thus,the loss of Axinl in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation,leading to delayed bone growth in postnatal Axin1°sx KO mice.

Neurological recovery and antioxidant effects of resveratrol in rats with spinal cord injury: a meta-analysis

Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as the main search terms,all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed,EMBASE,MEDLINE,Web of Science,Science Direct,China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases by computer.The search was conducted from their inception date to April 2017.No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations.Two reviewers independently selected studies according to the title,abstract and full text.The risk of bias in the included studies was also evaluated.Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso,Beattie,and Bresnahan scale score,inclined plane score and Gale’s motor function score.Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels,malondialdehyde levels,nitric oxide synthase activity,nitric oxide levels,xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor.The results of meta-analysis showed that compared with the control group,resveratrol significantly increased the Basso,Beattie,and Bresnahan scale scores after spinal cord injury(n=300,mean difference(MD)=3.85,95%confidence interval(CI)[2.10,5.59],P<0.0001).Compared with the control group,superoxide dismutase levels were significantly elevated(n=138,standardized mean difference(SMD)=5.22,95%CI[2.98,7.45],P<0.00001),but malondialdehyde levels were significantly diminished(n=84,SMD=–3.64,95%CI[–5.84,–1.43],P=0.001)in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurological recovery and exerted antioxidative effects in rat models of spinal cord injury.The limited quality of the included studies reduces the application of this meta-analysis.Therefore,more high-quality studies are needed to provide more rigorous and objective evidence for the pre-clinical treatment of spinal cord injury.

S-Nitrosoglutathione Administration Ameliorates Cauda Equina Compression Injury in Rats

Lumbar spinal stenosis (LSS) causes ischemia, inflammation, demyelination and results in cauda equina (CE) syndrome, with pain and locomotor functional deficits. We investigated whether exogenous administration of S-nitrosoglutathione (GSNO), an endogenous redox modulating anti-neuroinflammatory agent, hastens functional recovery in a CE compression (CEC) rat model. CEC was induced in adult female rats by the surgical implantation of two silicone blocks within the epidural spaces of L4-L6 vertebrae. GSNO (50 μg/kg body weight) was administered by gavage 1 h after the injury, and the treatment was continued daily thereafter. GSNO induced change in the pain threshold was evaluated for four days after the compression. Tissue analyses and locomotor function evaluation were carried out at two weeks and four weeks after the CEC respectively. GSNO significantly improved motor function in CEC rats as evidenced by an increased latency on rotarod compared with vehicle-treated CEC rats. CEC induced hyperalgesia was decreased by GSNO. GSNO also increased the expression of VEGF, reduced cellular infiltration (H&E staining) and apoptotic cell death (TUNEL assay), and hampered demyelination (LFB staining and g-ratio). These data demonstrate that administration of GSNO after CEC decreased inflammation, hyperalgesia and cell death leading to improved locomotor function of CEC rats. The therapeutic potential of GSNO observed in the present study with CEC rats suggests that GSNO is a candidate drug to test in LSS patients.

Vik: A Chatbot to Support Patients with Chronic Diseases

Background: Chatbots are easy to use and simulate a human conversation through text or voice via smartphones or computers. In the field of health, chatbots can improve patient information, monitoring, or treatment adherence. Method: The objective of this article is to describe how a chatbot dedicated to disease monitoring and support of patients can interact with them and how data are exploited to be safe. Results: Wefight designed a chatbot named Vik to empower patients with cancers or chronic diseases and their relatives via personalized text messages. Natural Language Processing models were used. We built several Vik for each disease. Each Vik has its contents, its own NLP model and interacts its way with the patient. Conclusion: Conversational agents may help patients with minor health concerns without seeing a real physician. If the quality of these softwares is not thoroughly assessed, they could be dangerous. If chatbots are effective and safe, they could be prescribed like a drug to improve patient information, monitoring, or treatment adherence.

Do Multiple Isolated Vertebral Thoracolumbar Transverse Process Fractures Increase the Risk of Ligamentous Injury and Surgical Intervention in the Setting of Trauma?

Background: Isolated thoracolumbar vertebral transverse process fractures (TPF) are often considered a stable injury. However, the use of advanced imaging such as magnetic resonance imaging and spine specialist consultation are often ordered as part of the routine workup of these fractures. The routine ordering of advanced imaging, spine specialist consultation, and delayed mobilization causes unnecessary economic and clinical burdens to patients and the overall healthcare system. Purpose: To determine if a higher number of isolated TPFs (iTPFs) lead to an increase in ligamentous injury to the spine, and whether ligamentous injury—if present—requires surgical intervention. Methods: The retrospective review was performed from 2009 to 2015, using a surgical trauma database to identify patients with greater than 3 isolated TPF (iTPF) to determine if iTPF leads to an increase in ligamentous injury to the spine and if this increase leads to increased surgical intervention. Results: A total of 102 patients were identified with complete follow up at 6 - 8 weeks post injury. The majority of the included patients suffered from blunt trauma. There was a small rate of ligamentous injury (n = 7, 7%) that did not require additional treatment. None of the fractures included were considered unstable. None of the patients included required surgical intervention during their hospital visit or in follow up visits. Conclusion: iTPFs are a stable injury to the thoracolumbar spine. There is a small rate of associated ligamentous injury that does not change the management or require further interventions. Thoracolumbar iTPFs do not automatically need spine specialist consultation and advanced imaging techniques.

Visualizing Recovery of Cognitive Function in Stroke

Hippocrates (460-377 BC) first described stroke over 2400 years ago. Stroke is the 4th leading cause of death in Canada (3rd in the USA) and the primary cause of permanent motor and cognitive disability. The majority of strokes are ischemic. The extent of cerebral dysfunction and thus the severity of stroke are based on the location, severity and duration of ischemia. Stroke management and prognosis encompass early recognition of the onset of stroke and post-stroke determination of the extent of brain injury aided by clinical stroke scores and diffusion-weighted imaging. Cognitive domains most likely to be affected following stroke are memory, orientation, language, attention and executive function. While the vast majority of functional recovery occurs within the first 3 months post-stroke, the neural mechanisms promoting recovery are not well understood. Investigations into the neural plasticity of brain areas after a lesion demonstrate that the adult brain can be shaped by environmental inputs, such as rehabilitation techniques. Many rehabilitation techniques are actively being pursued, including brain-computer interfaces providing sophisticated methods for detecting rehabilitation-associated changes in cerebral physiology. The success of such strategies visualized with functional magnetic resonance imaging and positron emission tomography may provide an objective complement to clinical evaluations.

Potential Biomarkers of Schizophrenia from MEG Resting-State Functional Connectivity Networks: Preliminary Data

Previous studies examining coherence and connectivity deviations in schizophrenia patients relied on standard coherence measures between recording sites (at the sensor level). A coherence source imaging (CSI) methodology where coherence is assessed within imaged brain structures (at the source level) was developed recently by our group and applied successfully for detecting coherent areas in the cortical networks of patients with epilepsy. We applied this Magnetoencephalography (MEG)-CSI technique to measure normal and pathological patterns of brain oscillations (biomarkers) in normal subjects and patients diagnosed with schizophrenia. Twelve patients diagnosed with schizophrenia and twelve healthy control subjects were studied. A ten-minute resting state MEG brain scan was performed with eyes open. MEG-CSI analysis was performed to identify the cortical areas that interacted strongly within the 3 - 50 Hz frequency range. Statistically significant increased regions of coherence were detected in schizophrenia patients compared to controls in the right inferior frontal gyrus (BA 47—pars orbitalis), left superior frontal gyrus (BA9— dorsolateral prefrontal cortex), right middle frontal gyrus (BA 10—anterior prefrontal cortex & BA 46—dorsolateral prefrontal cortex), and right cingulate gyrus (BA 24—ventral anterior cingulate cortex). These areas are involved in language, memory, decision making, empathy, executive and, higher cognitive functioning. We conclude that MEG-CSI can detect imaging biomarkers from resting state brain activity in schizophrenia patients that deviates from normal control subjects in several behaviorally salient brain regions. Analysis with MEG-CSI can provide biomarkers of abnormalities in the resting-state. The findings and procedures described can be used to probe the pathophysiology of schizophrenia and possibly detect subtypes.

Danggui Niantong decoction ameliorates joint inflammation and cardiopulmonary injury in TNF-Tg mice

Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,its beneficial effect on cardiopulmonary complications has not been reported.Methods:Female tumor necrosis factor-transgenic(TNF-Tg)mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications.Methotrexate(MTX)served as a positive control.Histopathological assessment of the joint sections was performed using hematoxylin and eosin(HE),Alcian Blue/Orange G,and tartrate-resistant acid phosphatase staining.Bone mass was assessed by micro-computed tomography,inflammatory infiltrates in the heart and lungs were evaluated by HE staining,cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining,and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin(WGA)staining.Results:DGNTT mitigated the inflammation of the ankle joint synovium,decreased the number of osteoclasts,and increased the area of cartilage and bone mass in TNF-Tg mice.In addition,DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues,accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice.As a positive control drug,MTX attenuated the pathological changes in joints,but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice.Conclusions:DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.

Biomarker-guided classificatio scheme of neurodegenerative diseases

1.The complex spectrum of neurodegenerative diseases Epidemiologic data indicate that neurodegenerative diseases（NDDs）show high prevalence with a trend of a progressively growing incidence,especially in aging societies.This presents an increasing social and economic burden.

用密度梯度离心法富集源于小鼠胚胎干细胞的运动神经元样细胞前体(英文)

目的：我们的目标是从源于胚胎体（EBs）的小鼠胚胎干细胞（mESCs）中分离运动神经元样细胞前体（MNLCPs）,以用于发展针对运动神经元疾病的药物筛选试验和移植疗法。天然Shh蛋白（或Shh通路激动剂）和维甲酸诱导的胚胎体中,MNLCPs和未分化细胞的含量是不确定的。如果不把未分化的细胞从细胞培养中充分去除,其可能会干涉药物筛选试验或在移植后增生。我们开发了一种以密度梯度离心法为基础的富集MNLCPs的方法。方法：我们用Wichterle等人2008年改进的方法,将mESCs（HBG3：eGFP：HB9）扩大和分化。通过化学和酶学的无研磨处理,含有绿色荧光蛋白的MNLCPs和未分化细胞的胚胎体被小心轻轻地离解成单细胞。利用OptiprepTM8%~20%逐步梯度离心技术将MNLCPs回收。拥有绿色荧光蛋白的MNLCPs的含量由流式细胞仪检测。结果：我们的结果表明,在胚胎体形成前,mESCs在明胶包被的培养板上生长,其分化为MNLCPs的能力减少。比较mESCs在明胶,明胶与PMEFs,及PMEFs包被的培养板上的生长发现,mESCs在PMEFs包被的培养板上产生含绿色荧光蛋白的MNLCPs的得率为（54.1±11.0）%（x±s;n=12）,在明胶包被的培养板上的得率为（2.8±1.1）%（x±s;n=9）。用密度梯度离心法获得的含绿色荧光蛋白的MNLCPs的平均含量为（87.7±5.5）%（x±s;n=3）。结论：我们的数据表明,不使用细胞分选器,无研磨解离和密度梯度离心法也能用于富集具有高存活率的MNLCPs。有必要对MNLCPs在体外、体内和表型上进行进一步的生理学意义（如神经轴突的生长及形成神经肌肉接头的能力）上的鉴定。

Reactive oxygen species(ROS)-mediated M1 macrophage-dependent nanomedicine remodels inflammatory microenvironment for osteoarthritis recession

Osteoarthritis(OA)is a common chronic inflammatory disorder.Effective remodeling of inflammatory microenvironment in the joint is a promising strategy to prevent OA.However,current drugs remain unsatisfactory due to a lack of targeted and effective ways for relieving inflammatory conditions in OA joints.Bortezomib(BTZ),a proteasome inhibitor,could effectively inhibit proinflammatory cytokines but with poor accumulation in the inflammatory tissues.To overcome the shortcomings of BTZ delivery and to improve the efficacy of OA therapy,herein,we designed a novel nanomedicine(denoted as BTZ@PTK)by the co-assembly of BTZ and an amphiphilic copolymer(denoted as PTK)with ROS-cleaved thioketal(TK)linkages.The TK units in BTZ@PTK are first cleaved by the excessive ROS at OA sites,and then triggered the controlled release of BTZ,resulting in the accurate delivery and the inflammatory microenvironment remodeling.Accordingly,BTZ@PTK suppressed ROS generation and proinflammatory cytokines while promoting M1 macrophage apoptosis in lipopolysaccharide(LPS)-activated RAW264.7 macrophages or LPS/IFN-γ-treated primary macrophages,which leads to a better effect than BTZ.In OA mice,BTZ@PTK passively accumulates into inflamed joints to attenuate pain sensitivity and gait abnormality.Importantly,BTZ@PTK treatment successfully ameliorates synovitis with the reduction of synovial hyperplasia and synovitis scores by suppressing M1 macrophage polarization and promoting M1 macrophage apoptosis in the synovium,thereby delaying cartilage damage.Collectively,BTZ@PTK can effectively modulate inflammatory microenvironment for OA recession by activating M1 macrophage apoptosis and inhibiting M1macrophage-mediated inflammatory response.

Polyphyllin Ⅰ enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth via downregulating the Wnt/β-catenin pathway

OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.

Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice

Objective: Rheumatoid arthritis(RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction(HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis(CIA) mouse model.Methods: DBA/1J female mice were used to establish the collagen-induced arthritis(CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay(ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors m RNA and protein levels after HGWD intervention in RAW264.7 cells.Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints,reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function.HGWD decreased the expression of m RNA for inflammatory factors and the protein expression levels of p-NF-ΚB and IL-17.Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

Shen(Kidney)-Tonifying Principle for Primary Osteoporosis:to Treat Both the Disease and the Chinese Medicine Syndrome

Primary osteoporosis （POP） is one of the most common diseases in the elderly people resulting in high risk of fracture and poor quality of life. In addition to the pathological changes in bone mass, most of the POP patients also suffer from Chinese medicine （CM） syndromes of Shen （Kidney） essence deficiency. Shen essences are highly related to bone. Shen essence deficiency plays an important part in the development of POP and a better diagnosis of POP could be made by combining CM syndromes with Western medicine risk factors. Treatments of POP should aim at both increasing the bone mass and relieving the syndromes of Shen essence deficiency. Clinical study confirmed that treating POP patients with Shen-tonifying herbs could increase the bone mass and relieve the CM syndromes of POP patients. Basic researches clarified the mechanism by which Shen-tonifying herbs increased bone mass in animal models. The mechanisms by which Shentonifying herbs relieve the CM syndromes are still in investigation.