Polymorphisms of some cytokines and chronic hepatitis B and C virus infection

AIM： To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus （HBV） and hepatitis C virus （HCV） infection. METHODS： Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked imrnunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction （PCR）. Hepatocellular injury, as revealed by alanine aminotransferase （ALT） and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-γ＋874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR.RESULTS： Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele. CONCLUSION： These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage.

TREATMENT OF MUCOUS MEMBRANE DISEASES OF THE DIGESTIVE TRACT WITH JING liE LIAN OIAO TANG——Therapeutic Effect in 168 Cases

From October 1985 to October 1987,weused Jing Jie Lian Oiao Tang(荆芥连翘汤)totreat 168 patients of mucous membrane diseasesof the digestive tract with good therapeutic ef-fect.CLINICAL DATASelection of CasesIn this series,all 168 cases are inpatientswith diseases of the mucous membrane from themouth to the colon,the diagnosis being con-firmed with endoscopy when necessary.41

A Clinical Analysis on the Therapeatic Effects of 360 Cases Acute High Altitude Pulmonary Edema Treated on the Spot in High Altitude Regions

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Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.

Regenerative medicine in China:main progress in different fields

Regenerative medicine(RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells,tissue engineering,active molecules and gene therapy.Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma,burns,diseases of aging and nerve regeneration.The products Activ Skin and bone repair scaffolds have been approved and are applied in the clinic,and similar products are being studied.About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic.Gene therapy,therapeutic cloning and xenotransplantation are some of the strategies being studied.However,China needs to develop standards,regulations and management practices suitable for the healthy development of RM.Aspects that should be strengthened include sound administrative systems,laws,and technical specifications and guidelines;conservation of stem cell resources;emphasis on training and retention of talented stem cell researchers;and reasonable allocation of resources,diversification of investment and breakthroughs in key areas.Finally,broad and deep international cooperation is necessary.

Relationship Between Red Cell Hemorrheologic Characteristic Change and Its Immune Function in Early Hemorrhagic Shock Rabbits Under Hypoxia

In order to clarify the pathogenesis and rules of high altitude hemorrhagic shock, the relationship between the red cell hemorrheologic change and its immune function in early hemorrhagic shock rabbits under hypoxia was observed, so as to explore the pathogenesis of high altitude hemorrhagic shock furtherly. Fortyfive male grey rabbits were used in the experiment and devided them randomly into 3 groups: control group,

Machine Learning-Based Scoring System for Early Prognosis Evaluation of Patients with Coronavirus Disease 2019

Background The global spread of coronavirus disease 2019(COVID-19)continues to threaten human health security,exerting considerable pressure on healthcare systems worldwide.While prognostic models for COVID-19 hospitalized or intensive care patients are currently available,prognostic models developed for large cohorts of thousands of individuals are still lacking.Methods Between February 4 and April 16,2020,we enrolled 3,974 patients admitted with COVID-19 disease in the Wuhan Huo-Shen-Shan Hospital and the Maternal and Child Hospital,Hubei Province,China.(1)Screening of key prognostic factors:A univariate Cox regression analysis was performed on 2,649 patients in the training set,and factors affecting prognosis were initially screened.Subsequently,a random survival forest model was established through machine analysis to further screen for factors that are important for prognosis.Finally,multivariate Cox regression analysis was used to determine the synergy among various factors related to prognosis.(2)Establishment of a scoring system:The nomogram algorithm established a COVID-19 patient death risk assessment scoring system for the nine selected key prognostic factors,calculated the C index,drew calibration curves and drew training set patient survival curves.(3)Verification of the scoring system:The scoring system assessed 1,325 patients in the test set,splitting them into high-and low-risk groups,calculated the C-index,and drew calibration and survival curves.Results The cross-sectional study found that age,clinical classification,sex,pulmonary insufficiency,hypoproteinemia,and four other factors(underlying diseases:blood diseases,malignant tumor;complications:digestive tract bleeding,heart dysfunction)have important significance for the prognosis of the enrolled patients with COVID-19.Herein,we report the discovery of the effects of hypoproteinemia and hematological diseases on the prognosis of COVID-19.Meanwhile,the scoring system established here can effectively evaluate objective scores for the early prognoses of patients with COVID-19 and can divide them into high-and low-risk groups(using a scoring threshold of 117.77,a score below which is considered low risk).The efficacy of the system was better than that of clinical classification using the current COVID-19 guidelines(C indexes,0.95 vs.0.89).Conclusions Age,clinical typing,sex,pulmonary insufficiency,hypoproteinemia,and four other factors were important for COVID-19 survival.Compared with general statistical methods,this method can quickly and accurately screen out the relevant factors affecting prognosis,provide an order of importance,and establish a scoring system based on the nomogram model,which is of great clinical significance.

Innovative and propagable translational research model established for cell-based therapy at Chinese PLA General Hospital

The use of translational medicine in Chinese hospitals ap- pears to have become easier over the last decade. Products developed in the laboratory can sometimes be applied in the clinic under life-saving circumstances. Arteannuin is one of the most successful examples of translation during the past decade in China, having been used to treat more than one million patients with malaria. However, several approaches developed in the laboratory, with proven benefits to patients,

PRENATAL DIAGNOSIS OF THALASSEMIAS BY USING POLYMERASE CHAIN REACTION (PCR)

DNA analysis has become the method of choice for diagnosis of many genetic disorders. In 1978 Kan and Dozy described the first useful restriction fragment length polymorphism (RFLP) in the β globin gene cluster which was found to be in disequilibrium strongly associated with the sickle cell anemia gene (Hb S). Based on that, they did the linkage analysis for Hb S gene and successfully made prenatal diagnosis. From then on, as genetic markers, RFLPs have been widely used for the linkage analysis and the diagnosis of genetic disorders. In 1983 oligonucleotide hy-

PRODUCTION AND CHARACTERIZATION OF MONOCLONAL ANTIBODY TO THE α-CHAIN OF THE FOURTH COMPONENT OF HUMAN COMPLEMENT

It has been found that the fourth component of human complement （C4） is a β1E globulin with a sedimentation coefficient of 10S and its average concentration in human serum is 430 μg/ml. The molecular weight of native C4 was estimated to be 202,000 and is composed of three disulfide-linked polypeptide chains, α, β and γ,

Regenerative medicine in China:demands, capacity,and regulation

Regenerative medicine(RM)is an emerging interdisciplinary field of research.Its clinical application focuses on the repair,replacement,and regeneration of cells,tissues,and organs by approaches including cell reprogramming,stem cell transplantation,tissue engineering,activating factors,and clone treatment.RM has become a hot point of research in China and other countries.China's main and local governments have attached great importance to RM and given strong support in relevant policies and funding.About 3.5 billion RMB has been invested in this field.Since 1999,China has established about 30 RM centers and cooperates with many advanced countries in RM research and benefits from their cooperation.However,China needs to develop standards,regulations,and management practices suitable for the healthy development of RM.In this review,we focus on its great demand,capacity,and relative regulations.

CART trials are going ahead

For a long time,unresectable tumors were mainly controlled by chemotherapy,radiation therapy or kinase inhibitors,with which complete and durable remission was infrequent despite great advances achieved.Until recently,together with checkpoint inhibitors,chimeric antigen receptor modified T(CART)therapies have made immunotherapy percolated into the mainstream of cancer treatment due to astonishing clinical results.

Dynamic microenvironment and multiple damaged tissue regeneration in a de novo and synchronized manner

Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects, age, diseases, or serious damage （Cheng et al., 2016a; Cheng et al., 2016b）. Regenerative medicine strategies in- clude the transplantation of bioactive factors, stem cells, or biomaterials, even the induced regeneration in a de novo, depending on the application （Fu, 2014a; Huang and Fu, 2014）. However, there are several limitations to the use of regenerative medicine in the clinic with respect to using stem cells and biomaterials.

Nerve transfer with 3D-printed branch nerve conduits

Background:Nerve transfer is an important clinical surgical procedure for nerve repair by the coaptation of a healthy donor nerve to an injured nerve.Usually,nerve transfer is performed in an end-to-end manner,which will lead to functional loss of the donor nerve.In this study,we aimed to evaluate the efficacy of 3D-printed branch nerve conduits in nerve transfer.Methods:Customized branch conduits were constructed using gelatine-methacryloyl by 3D print-ing.The nerve conduits were characterized both in vitro and in vivo.The efficacy of 3D-printed branch nerve conduits in nerve transfer was evaluated in rats through electrophysiology testing and histological evaluation.Results:The results obtained showed that a single nerve stump could form a complex nerve network in the 3D-printed multibranch conduit.A two-branch conduit was 3D printed for transferring the tibial nerve to the peroneal nerve in rats.In this process,the two branches were connected to the distal tibial nerve and peroneal nerve.It was found that the two nerves were successfully repaired with functional recovery.Conclusions:It is implied that the two-branch conduit could not only repair the peroneal nerve but also preserve partial function of the donor tibial nerve.This work demonstrated that 3D-printed branch nerve conduits provide a potential method for nerve transfer.