Cell mediated gene therapy: A guide for doctors in the clinic

The recent approval of gene therapy products in Europe and Asia and the upsurge of gene therapy products in clinical trials signal the rebound of this technology not only for many orphan diseases but also for non-life threatening diseases. Following the success of induced pluripotent stem(iP S) cells in research, other modified ex vivo gene therapies are also knocking on the door of the clinic. Historically, gene therapy has experienced many ups and downs and still faces many challenges.During the past 10 years, many new ideas have been tried, and the goal of making this technology a more effective treatment modality through greater safety and control is coming within reach. The first clinical trial of i PS cells has begun, and cell mediated gene therapy products have reached phase Ⅲ in some countries. The potential for tumorigenicity and immunogenicity are still concerns with these products, so physicians should understand the biological aspects of engineered cells in the clinic. In this review article, we attempted to provide a summary update of the current state of knowledge regarding this technology: that is, we reviewed products that have finished clinical trials, are still in clinical trials and/or are at the research stage. We also focused on the challenges, future directions, and strategies for making this technology available in the clinic. In addition, the available measures for making gene therapy products safer are within the scope of this article. It is also important to understand the manufacturing process for gene therapy products, because cell characteristics can change during the cell expansion process. When physicians use gene therapy products in the clinic, they should be aware of the viability, temperature sensitivity and stability of these cells because biologic products are different from chemical products. Although we may not be able to answer all possible questions and concerns, we believe that this is the right time for physicians to increase their interest in and understanding of this evolving technology.     

Research progress of gene therapy for vascularization of tissue engineering北大核心

BACKGROUND: The rapid formation of functional vascular system in large-scale engineered graft is the basic prerequisite for its successful survival in the host. The vascularization of tissue engineering by genetic engineering technology has the advantages of good therapeutic effect, low cost and high safety. It is of great significance to carry out the research on gene therapy for vascularization of tissue engineering for long-term effective tissue repair. OBJECTIVE: To summarize the current research status and main problems of seed cells, target genes and gene vectors of gene therapy in tissue engineering vascularization so as to further explore the application prospect of gene therapy in tissue engineering vascularization,. METHODS: The literature retrieval was conducted on PubMed, Web of Science, and CNKI with the key words of “tissue engineering; vascularization; gene therapy; seed cells; target genes; vectors” in Chinese and English, and 61 articles closely related to this study were selected for the review. RESULTS AND CONCLUSION: Mesenchymal stem cells, vascular endothelial cells and endothelial progenitor cells are the most potential seed cells for vascularization of tissue engineering using gene therapy. They not only have good vascular induction, but also benefit the introduction of many virus and non-viral vectors and the expression of vascularization target genes. Vascular endothelial growth factor, angiopoietin-1, basic fibroblast growth factor, bone morphogenetic protein-2, hypoxia inducible factor-1 α and other vascularization target genes are mainly used to construct efficient and stable vascular network in engineering grafts by means of combination of double/multiple gene, coupling of osteogenesis and angiogenesis, and regulation of upstream gene. Since different viral and non-viral vectors have their own advantages and disadvantages, suitable vectors should be selected according to the efficiency of gene transfection, biological safety, and cost in application. At present, although great progress has been made in the application of gene therapy in tissue engineering vascularization, there are still many key technologies to be broken through for clinical application, such as how to improve the targeted release of target growth factors and reduce the safety risk, which is also the research direction and hot spot of tissue engineering vascularization based on gene therapy in the future. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Application of Laser Speckle Imaging in Infrared Radiation Microcirculation

Objective: Blood vessels and their corresponding blood microcirculation are closely related to life activities. Different blood flow and microcirculation in the organism often correspond to different physiological and pathological conditions. The main function of microcirculation system mainly by the arteries, capillaries and microvascular and other small blood vessels(150 μm) composition, is to provide nutrients and oxygen for the organization at the same time, the removal of carbon dioxide and other metabolic waste. Clinical medicine, by monitoring the changes in blood flow can be achieved on diabetes, hypertension, foot ulcers, atherosclerosis,Alzheimer's disease and tumor diseases such as early diagnosis or follow-up. Therefore,monitoring blood flow in blood vessels is not only important for studying the functional and disease mechanisms of biological tissues, but also one of the important methods for the clinical diagnosis and the evaluation of diseases.Changes in skin blood flow has been a hotspot in microcirculation research. At present, the commonly used method on studying the microcirculation of blood flow changes in spatial resolution is not high enough or need to add exogenous markers, with the passage of time, the marker content will gradually reduce the impact of follow-up measurement accuracy. This study aims to investigate the application and characteristics of laser speckle imaging(LSI) in the infrared microcirculation. Methods: Firstly, prepare a complete set of infrared therapy instrument model and recruit 10 volunteers,and then using the laser speckle imaging system to monitor 10 healthy volunteers(keep hand not moving during measurement)through the infrared therapy instrument heating with the microcirculation changes in the surface of the blood flow velocity and blood flow in real time changes. Results: Infrared thermotherapy methods lead to skin microcirculation(blood flow and vasomotor), skin temperature and body temperature increased significantly. From the laser speckle image can be seen in 10 volunteers compared with the normal state of the hand, infrared stimulation after the image of the red area increased, that is, blood flow has significantly increased. Conclusion: With far infrared effect on the skin, most of the energy can be absorbed by the skin energy into heat, causing skin temperature rise, stimulating the skin heat receptors, through the thalamus reflex, the vascular smooth muscle relaxation,blood vessels, and blood circulation to speed up. On the other hand, due to thermal effects,causing the release of vasoactive substances, decreased vascular tension, shallow arteries,shallow capillaries and superficial vein dilation, blood circulation improved. Through the laser speckle imaging technology can be effectively monitored under the influence of infrared therapy instrument under the microcirculation of blood flow changes. Laser speckle imaging has achieved real-time monitoring of vascular structure and function due to the advantages of high temporal resolution and large field imaging. However, since the imaging depth of the laser speckle imaging system is affected by the penetration depth of the excitation light in human tissue limit, the current laser speckle imaging is limited to the surface of the blood vessels and blood flow imaging. Therefore, how to deepen the blood vessel flow imaging is an important future direction of the development.     

How Much Do We Know about Atopic Asthma： Where Are We Now？

Asthma is a common disease in the worldwide and it affects over 3.5 million adults and children in the UK. Asthma is a chronic disease characterized by airway hyperresponsiveness, airway inflammation, airway remodelling and reversible airway obstruction. Inflammatory cells, cytokines, chemokines, adhesion molecules, and mediators are involved in pathogenesis of asthma. Chronic airway inflammation and remodelling are the major characters in asthma, which result in decreased pulmonary function. The precise processes are far understood at moment. Although corticosteroid therapy plus other exiting drugs （bronchodilators and oral leukotriene receptor antagonists） influences many different inflammatory and structural cell types and continues to be as the ＂gold standard＂ of therapy in asthma, many thousands have chronic, severe diseases and suffer daily symptoms which make their lives a misery. There remains a clear need for novel approaches to therapy, which will be informed by a clearer understanding of disease pathogenesis, particularly in the target organ where airway inflammation and remodelling, the hallmarks of asthma occur. Cellular ＆ Molecular Immunology.     

一种模拟传统艾灸电子温灸仪的研制：应用安全及环保效应

BACKGROUND: An electronic moxibustion apparatus that simulates the mechanism of traditional moxibustion therapy is designed and developed to overcome shortcomings of traditional moxibustion therapy, such as non-standardized treatment, limited body position, and production of "smoke" and "ash" during the treatment. OBJECTIVE:To develop a kind of electronic moxibustion apparatus which simulates the traditional moxibustion therapy and has obtained the patent so as to industrialize and modernize moxibustion therapy. METHODS: Bio-waves launched from far infrared materials are beneficial to the human body. An electronic moxibustion apparatus including time temperature controller and moxibustion head was developed, and the closed loop control technique was used to precisely control the temperature and time. Thermal radiation infrared spectrum that moxibustion head generated could simulate the emission spectrum of moxibustion in combination with wormwood oil coating or drug interval, thereby achieving the therapeutic effect similar to traditional moxibustion. RESULTS AND CONCLUSION:The prototype of DZWJY-1 electronic moxibustion instrument has been developed and its safety and electromagnetic compatibility have been detected in Shanghai Testing & Inspection Institute for Medical Devices, China. Relevant clinical trials are ongoing to verify the efficacy. Preliminary clinical evidence shows that the electronic moxibustion apparatus has the same therapeutic effect to the traditional moxibustion therapy, which realizes the safety and environmental protection of moxibustion therapy and provides objective, standardized and modernized evidence for moxibustion therapy 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Effect of He-Ne Laser on the Expressions of EGF and EGFR in Gastric Mucosa of Chronic Atrophic Gastritis

To investigate the histological change and the expressions of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) in atrophic gastric mucosa in rats so as to appraise the effect of these regulators on the formation of atrophic gastritis, to study the expressions of EGF and EGFR in rats with chronic atrophic gastritis (CAG) after the irradiation of He-Ne laser, and to investigate the relations of He-Ne laser and precancerous lesion or apoptosis. The rats were divided into normal group, model group and laser group. The models of CAG rats were established with enema which was the mixed liquor consisted of sodium salicylate and alcohol, combined with irregular fasting and compulsive sporting as pathogenic factors. He-Ne laser(3.36 J/cm2 ) was used to irradiate CAG rats, once a day for 7 min, 20 days as a course of treatment; the expressions of EGF and EGFR were detected with immunohistochemical method. During the process of antral atrophy, the expressions of EGF and EGFR increased, they were higher in model group than those in normal group (P<0.05). After the irradiation of He-Ne laser, the expressions of EGF and EGFR were obviously lower than those in model group (P<0.05). We draw the conclusion as follows: gastric mucosa of model rat is in a hyper-proliferation status, with high protein expressions of apoptosis suppressor EGF and EGFR. CAG has some correlation with the imbalance between cell proliferation and apoptosis. He-Ne laser (3.36 J/cm2 ) can reduce the expressions of EGF and EGFR, which is an effective physiostimulator to stimulate the gastric mucosa of rat. The appropriate secretions of EGF and EGFR are propitious to the repair and regeneration for the gastric mucosa tissues, thus preventing CAG to canceration.     

The Therapeutic Effectiveness of Hybrid Renal Replacement (HRRT) in Patients with Severe Snakebite

Objective:To investigate the therapeutic effects of hybrid renal replacement therapy (HRRT) in patients with severe snake bite. Methods: 15 patients treated with HRRT from July in 2005 to August in 2009 were involved in the study, all patients were established ascular access by central venous catheter, polysulfone membrane connected absorption hemoperfusion cartridge, the blood flow rate was 200 ml/min, the dialysate flow rate was 300 ml/min, heparin or low molecular heparin was used as anticoagulant, treatment time was 6 to 12 hours. Observe the biochemical indicators and APACHE II score before and after HRRT and clinical outcomes of the patients. Results: The level of serum creatinine, glutamic-oxalacetic transaminease, glutamic-pyruvic transaminease, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before HRRT(P<0.05); the level of cholinesterase was significantly higher than the level before HRRT (P<0.01); the APACHE II score before HRRT was 14.1±3.8, but decreased significantly to 7.9±1.4, 6.2±1.1 and 4.2±0.8 at the first, second and seventh day after HRRT, respectively (P<0.01). There are 3 patients died at the first, third, and fourth HRRT, respectively, the rest 12 patients were cured or improved when discharged, the survival rate was 80%, and the mortality was 20%. Conclusion: HRRT may be an effective treatment method for severe snake bite patients, which can reduce the mortality rate and increase the survival rate.     

鸟苷素家族研究进展

Guanylin family, described in recent 10 years, is a series of small peptides (including guanylin, uroguanylin and lymphoguanylin) with structural and functional similarities to heat- stable entero-toxins (STs) elaborated by various pathogenic bacteria. They are abundance of cysteines and are endogenous activators of guanylyl cyclase - C (GC - C) receptors. Immunoreactive guanylin family peptides are localized in many human organs and tissues, especially in gastrointestinal tract and kidney, and play an important role in regulation of water and salt homeostasis. Recent studies showed that the mRNA levels of guanylin family peptides were down - regulated in colorectal cancers; oral intake of uroguanylin might suppress polyp formation in Apc(Min/ ) mouse, and 111^In-labeled-ST peptide analog might specifically target human colon can-cers. These evidences highlight that guanylin family may have a potential application in diagnosis and therapy effects of colorectal cancers.     

Optimizing of Culture Conditionin Horizontal Rotating Bioreactor

1 IntroductionBioreactor is the most important equipment in tissue engineering. It can mimic the micro-environment of cell growth in vitro. At present, horizontal rotating bioreactor is the most advanced equipment for cell culture in the world. 2 Rotating bioreactors2.1 Working principleThere are two kinds of horizontal rotating bioreactor: HARV(high aspect ratio vessel) and RCCS (rotary cell culture system). It is drived by step motor with horizontal rotation, the culture medium and cell…     

迷走神经电刺激治疗癫痫的现状与展望

Electrical vagus nerve stimulation （VNS） has been approved by FDA and is widely used in recent years for the treatment of epilepsy and possibly other medical conditions such as depression. The current success rate of VNS for epilepsy is about 50%, but there are complications, potential risks and cost concerns. One of the major limitations for this new therapy is that its antiseizure mechanisms are by no means clear. In particular, it is not known whether the therapeutic effect is vagal specific, what types of nerve fibers in the vagus nerve are contributing to the therapeutic effects, or what individual patients would benefit from the use of the expensive and invasive VNS implantation. There are controversies regarding how and where the VNS takes effect on epilepsy in the central nervous system. The poor understanding of VNS has inevitably limited the application and success of the therapy. The current review analyses the pros and cons of VNS for epilepsy in vis-à- vis other available therapies including Chinese medical methods, and explores the possible mechanisms in order to stimulate further improvement of this new technology.     

Principles of Development of Multifunctional Equipment for Low-Intensity Laser and Magnetolaser Therapy

Principles of development of multifunctional equipment for low-intensity laser and magnetolaser therapy were developed for: local and zonal external magnetolaser therapy; internal laser therapy; photoblockage intrajoint and intratissue therapy; intravascular laser therapy using disposable intravenous tips; transcutaneous laser-induced blood therapy; laser-induced acupuncture of biologically active points. The apparatus is based on laser diodes and a collimator. Varying the collimator–diode distance regulates therapeutic efficacy. Internal therapy is based on an optical lightguide.     

Laser treatment of patients with chronic glomerulonephritis]

Helium-neon laser therapy of patients suffering from mixed and nephrotic glomerulonephritis demonstrated hypotensive, diuretic and fibrinolytic activity boosting clinical effects. The use of the new treatment method seems to be justified, since all the patients given laser therapy manifested pronounced resistance to the pathogenetic therapy carried out previously (glucocorticoids, cytostatics, hypotensive and diuretic drugs). The presence of diverse effects and lack of complications suggest a broader-scale use of laser therapy in nephrology. At present the authors are analyzing the ++patho-chemical bases of the therapeutic efficacy of laser therapy of patients suffering from chronic glomerulonephritis. The results will be reported in the next paper.     

Quality assurance for nonradiographic radiotherapy localization and positioning systems: report of Task Group 147

New technologies continue to be developed to improve the practice of radiation therapy. As several of these technologies have been implemented clinically, the Therapy Committee and the Quality Assurance and Outcomes Improvement Subcommittee of the American Association of Physicists in Medicine commissioned Task Group 147 to review the current nonradiographic technologies used for localization and tracking in radiotherapy. The specific charge of this task group was to make recommendations about the use of nonradiographic methods of localization, specifically; radiofrequency, infrared, laser, and video based patient localization and monitoring systems. The charge of this task group was to review the current use of these technologies and to write quality assurance guidelines for the use of these technologies in the clinical setting. Recommendations include testing of equipment for initial installation as well as ongoing quality assurance. As the equipment included in this task group continues to evolve, both in the type and sophistication of technology and in level of integration with treatment devices, some of the details of how one would conduct such testing will also continue to evolve. This task group, therefore, is focused on providing recommendations on the use of this equipment rather than on the equipment itself, and should be adaptable to each user's situation in helping develop a comprehensive quality assurance program.     

数字孪生诊疗系统的研究

患者、医疗设备和治疗方案是现代诊疗系统的三个要素,本研究针对该三要素在状态感知、机理模型、智能算法三方面存在的物理信息融合问题进行了探讨.基于数字孪生理念,本研究提出了数字孪生诊疗系统的概念,以实现物理世界和数字世界的虚实映像与实时映射.从孪生数据、孪生机理模型和智能决策三个方面,给出了建立数字孪生诊疗系统的方法,并探...     

颈椎牵引的研究进展

颈椎病的发病率逐年提高,患者也越来越年轻化,所以对颈椎病的治疗意义重大。颈椎病的治疗以牵引治疗为主,该文主要对牵引治疗的 4 个要素和当下的颈椎牵引器械进行分析,并且对颈椎牵引器械的发展趋势进行了展望。     

Managing the replacement cycle of laser inventory

Medical lasers are quickly moving into the replacement phase of technology management. Barnes Hospital (St. Louis, MO) is using its laser team to define a process of planned laser replacement using the experience gained from traditional medical equipment replacement cycles, quality improvement principles and tools, and other formalized interdisciplinary teams. The process described in this paper has six basic steps: (1) A decision is made to request a replacement laser. (2) An appropriation request form is completed and submitted with the clinical and/or technical justifications. (3) Those requests initiated outside of the Clinical Engineering Department are reviewed by the Clinical Engineer/Medical Laser Safety Officer (CE/MLSO). (4) The CE/MLSO presents the requests to the hospital Laser Committee, and (5) then to the Laser Users' Group. (6) Finally, an Expenditure Authorization Committee reviews all capital expense requests, including those for replacement lasers, and allocates funds for the next fiscal year. This paper illustrates and evaluates the process, using an example from the review process for 1993 equipment purchases at Barnes Hospital.     

Ultraviolet and laser radiation safety

Both ultraviolet radiation and laser radiation occupy pmt of the Spectrum designated "optical radiation". Thus, measurement techniques are similar and the same organs (eyes and skin) are at risk from accidental exposure. However, the equipment used to produce ultraviolet and laser radiation differs substantially and the harm caused by each type of radiation is also different. Another significant difference arises from the fact that ultraviolet radiation is natural with associated general population exposure. Consequently, the present article reviews the current status of both ultraviolet and laser radiation with the material divided into two sections where each hazard is considered separately.     

A review of optical imaging and therapy using nanosized graphene and graphene oxide

Nanosized graphene and graphene oxide (GO) are photoluminescent due to the presence of bandgaps and edges/defects. The excellent photostability of these nanomaterials makes them superior to molecular dyes for biological imaging. They can also produce intensive heat under laser irradiation, enabling them to serve as photothermal agents for cancer treatment. In this work, recent studies on the photoluminescence of these materials, their applications for biological imaging and photothermal cancer therapy are reviewed. Properties of laser, particularly the temporal property (continuous wave or pulsed), affect its interaction with materials. Therefore, the photoluminescence and photothermal effects, as well as their applications under both single (one)-photon (continuous wave laser) and two-photon (pulsed laser) excitation were summarized and analyzed. Synergistic therapy which combines chemotherapy and photothermal therapy using these materials is also reviewed. Finally, critical issues and challenges for further research and in medical applications of these materials are analyzed.     

Immediate cutaneous hypersensitivity after treatment of tattoo with Nd:YAG laser: a case report and review of the literature.

BACKGROUND: To our knowledge this is the first reported case of an immediate cutaneous reaction to Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser tattoo removal. A 26-year-old female presented with two 6-year-old tattoos placed at different times. These were of different colors and had remained entirely asymptomatic since placement. There was a Mardi Gras mask on her thigh and a Tasmanian devil on her chest. With laser treatment of the Tasmanian devil, she experienced no untoward effects. However, with treatment of the Mardi Gras mask tattoo, she developed an extensive urticarial and indurated reaction 30 minutes posttreatment. The identical reaction occurred twice with subsequent laser treatments. Dermatology consulted allergy to provide prophylaxis against possible systemic reaction with subsequent Nd:YAG laser therapy. The patient was treated with 3 days of prednisone, cetirizine, and ranitidine before subsequent laser treatments. Prophylactic treatment suppressed all subsequent reactions to laser therapy. RESULTS: Delayed hypersensitivity to tattoo pigments occurring days to weeks after placement is well documented. There are no previous reports of immediate hypersensitivity during placement or laser removal. However, there are two previous reports of local and systemic delayed reactions after laser therapy. CONCLUSIONS: As far as we know, this is the first case report of immediate hypersensitivity after Nd:YAG laser treatment of a tattoo. Prophylactic treatment with steroids and antihistamines prevented reactions with subsequent laser treatments. Reactions after laser removal are rare, but may increase as popularity of skin art increases with the need for subsequent removal.     

Low-intensity lasers in pediatric oncology

The paper outlines the outcomes of treatment for complications associated with chemo- and radiation therapy in children with malignant neoplasms by using low-intensity laser radiation. The use of this therapy may reduce the duration of treatment of these complications by 1.5-2 times. The use of low-intensity laser radiation in the treatment of other complications that are common in pediatric oncological care is briefly described.