Objective: To observe the effect of electroacupuncture (EA) pretreatment on the protein expression of c-fos in fastigial nucleus (FN) and lateral hypothalamus area (LHA) in rats with acute myocardial ischemia-reperfusion injury (MIRI), and to explore the role and mechanism of FN and LHA in EA at the Heart Meridian fighting against acute MIRI reaction. Methods: Seventy Sprague-Dawley rats were randomly divided into a sham operation group, a model group, an EA-Heart Meridian group and an EA-Lung Meridian group, with 14 rats in each group; an LHA lesion plus EA-Heart Meridian group (LHA+EA-Heart Meridian group) and a FN lesion plus EA-Heart Meridian group (FN+EA-Heart Meridian group), with 7 rats in each group. Except the sham operation group, the left anterior descending branch of coronary artery was ligated to establish acute MIRI rat models in the other 5 groups. In the three groups with EA-Heart Meridian treatment, Shenmen (HT 7) and Tongli (HT 5) were selected; Taiyuan (LU 9) and Lieque (LU 7) were selected in the EA-Lung Meridian group. All the EA groups received EA stimulation prior to modeling, with 1 mA in current intensity and 2 Hz in frequency, 20 min each time, once a day for a total of 7 d. The sham operation group and the model group did not receive EA stimulation. The electrocardiogram was observed in the rats to analyze the ST-segment deviation and cardiac arrhythmia score. The expression of c-fos protein in FN and LHA was detected by immunohistochemistry method. Results: Compared with the sham operation group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in the FN and LHA increased significantly in the model group (all P<0.05). Compared with the model group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in FN and LHA decreased significantly in the EA-Heart Meridian group (all P<0.05). Compared with the EA-Heart Meridian group, the ST-segment deviation and cardiac arrhythmia score increased significantly in the EA-Lung Meridian group, LHA+EA-Heart Meridian group and FN+EA-Heart Meridian group (all P<0.05); the expression of c-fos in FN increased significantly in the EA-Lung Meridian group and LHA+EA-Heart Meridian group (both P<0.05); the expression of c-fos in LHA increased significantly in the EA-Lung Meridian group and FN+EA-Heart Meridian group (both P<0.05). Conclusion: FN and LHA are involved in the mechanism of EA at Heart Meridian to improve the acute MIRI reactions, and the cerebellum may participate in the improvement of cardiac function by EA through the cerebellum-hypothalamus projection.

To investigate the effect of recombinant human growth hormone (rhGH) on JAK2-STAT3 pathway and the growth of gastric cancer cell lines at different GHR expression status, the eukaryotic expression vector targeting human GHR (pGPU6/GFP/Neo-shGHR and pGPU6/GFP/Neo-scramble) was constructed and transfected into MGC803 cells by Lipofectamine 2000. Stable expressive cell lines were obtained by G418 screening. The expression of GHR was analyzed by Western blotting. After being stimulated with rhGH, cell growth was detected by MTT assay. Cell cycle and apoptosis were examined by flow cytometry. The components of JAK2/STAT3 signaling pathway were detected by Western blotting. There is no significant difference of GHR expression between MGC803 and pGPU6/GFP/Neo-scramble-transfected cells (named as MGC803-NC) (P > 0.05). Compared with MGC803, the GHR expression in pGPU6/GFP/Neo-shGHR-transfected cells (named as MGC803-shGHR) decreased significantly (protein decreased 50%). The cells were treated with rhGH at 0, 150 and 300 ng x mL(-1), the growth rate of MGC803 and MGC803-NC increased significantly, PI and the number of G2/M phase cells all increased significantly, and apoptosis decreased significantly. Western blotting revealed that the expression of pJAK2 and pSTAT3 was up-regulated after being treated with rhGH in MGC803 and MGC803-NC cells. In contrast, similar change was not observed in MGC803-shGHR cells. Knockdown of GHR gene may decrease the sensitivity of gastric cancer cells to rhGH, and down-regulating of components of the expression of JAK2/STAT3 signaling pathway may be the potential mechanisms.
Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Human Growth Hormone ; genetics ; pharmacology ; Humans ; Janus Kinase 2 ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Somatotropin ; genetics ; metabolism ; Recombinant Proteins ; genetics ; pharmacology ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Stomach Neoplasms ; metabolism ; pathology ; Transfection

Worldwide sales of biologic drugs exceeded 100 billion USD in 2011. About 32% is from therapeutic monoclonal antibody (mAb). With many blockbuster biopharmaceutical patents expiring over the next decade, there is a great opportunity for biosimilar to enter the worldwide especially emerging market. Both European Medicines Agency (EMA) and Food and Drug Administration (FDA) have introduced regulatory frameworks for the potential approval of biosimilar mAb therapeutics. Rather than providing a highly abbreviated path, as in the case for small molecule chemical drug, approval for biosimilar mAb will require clinical trial and the details will be very much on a case-by-case basis. Since mAb is the dominant category of biologic drugs, mAb will be the focus of this review. First, the United States (US) and European Union (EU) approved mAb and those in phase 3 trials will be reviewed, then strategies on how to win biosimilar competition will be reviewed.
Animals ; Antibodies, Bispecific ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Biosimilar Pharmaceuticals ; standards ; Clinical Trials, Phase III as Topic ; Drug Approval ; European Union ; Humans ; United States ; United States Food and Drug Administration

Objective To investigate the expression and clinical significance of peripheral blood CD4~+, CD25~+ and CD4~+CD25~+ T subpopulations in patients with systemic lupus erythematosis.Methods The per- centage and fluorescence intensities of peripheral blood CD4~+,CD25~+ and CD4~+CD25~+ subpopulations from 34 SLE and 18 normal controls were measured with flow cytometry assay,then the correlation with clincal data was analyzed.The CD25~+ cells were defined as the CD25~(high) cells if their fluorescence intensity was higher than 10. Results The percentage of CD4~+CD25~+,CD4~+CD25~(high) T lymphocytes in active SLE patients[(4.80?1.21)% and (0.25?0.10)%]was lower than that in normal controls[(8.92?3.21)% and(0.44?0.22)% and non-active SLE patients(11.28?2.09)% and(0.59?0.34)%](P＜0.05).However,as for the CD25~+ cells in the CD4~+ T cells,there was no difference between SLE patients and normal control group.Peripheral blood CD4~+CD25~+,CD4~+CD25~(high) cells in SLE were reversely correlated with SLEDAI(r=-0.74,P=0.004 and r=-0.614,P=0.026),but not with others such as complements,ANA titers etc.Peripheral blood CD4~+ and CD25~+ lymphocytes in active SLE pa- tients were also lower than those in normal controls[(23?7)vs(34?7)and(7.4?1.8)vs(13.9?3.4),P＜0.05]. CD25 fluorescence intensities were higher in the SLE patients those in the normal controls,but CD4 fluores- cence intensities were not.Conclusion CD4~+CD25~+ may play a role in the pathogenesis of SLE.

BACKGROUNDNontuberculous mycobacterium (NTM) had been reported to cause cutaneous infections which are difficult to interpret due to the variability of the clinical manifestations. Among NTM infections, Mycobacterium marinum (M. marinum) are mostly seen to cause skin infection. It is therefore important to establish a rapid approach for detection and identification of M. marinum from lesions of patients with suspected M. marinum infections.

METHODSSpecimens were obtained from 5 patients with swimming pool granuloma. DNA was extracted and polymerase chain reaction (PCR) was performed. PCR products were digested with Hae III and BstE II, then analysed by pattern restriction analysis to detect heat shock protein (hsp) 65 kD gene.

RESULTSThe 65 kD hsp gene was found in all specimens from patients with swimming pool granuloma. PCR restriction analysis (PRA) identified all 5 samples to be M. marinum infections, and the result was consistent with that of routine bacteriological identification. The lesions subsided or markedly improved upon treatment.

CONCLUSIONSPRA is a sensitive, specific and rapid method in identification of mycobacteria. Application of this method will be helpful for early diagnosis of mycobacterial skin infections.

Adolescent ; Adult ; Bacterial Proteins ; genetics ; Chaperonin 60 ; Chaperonins ; genetics ; Female ; Granuloma ; microbiology ; Humans ; Male ; Mycobacterium marinum ; genetics ; isolation & purification ; Polymerase Chain Reaction ; methods ; Skin Diseases, Bacterial ; diagnosis ; Staining and Labeling ; Swimming Pools

OBJECTIVETo investigate the level and significance of interleukin-8 (IL-8), soluble intercellular adhesion molecule (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients peripheral blood (PB) during mobilization for peripheral blood stem cells harvesting.

METHODSThe levels of IL-8, sICAM-1 and sVCAM-1 in patients were dynamically assayed by ELISA during the mobilization procedure and the number of CD(34)(+) cell, white blood cell (WBC) and platelet (BPC) by flow cytometric analysis and hematometry respectively. Colony formation was assayed by using semisolid methycellulose culture.

RESULTSThere was a significant increase in plasma levels of IL-8 and both adhesion molecules [IL-8 (247.4 +/- 84.2) microg/L (P < 0.01); sICAM-1 (530.3 +/- 286.1) microg/L (P = 0.002 7); sVCAM-1 (575.3 +/- 350.4) microg/L (P = 0.001 3)] during the mobilization process; furthermore, IL-8 and sVCAM-1 concentration in the patient's plasma was paralleled to the numbers of CD(34)(+) cell, CFU-GM, WBC and BPC (P < 0.001).

CONCLUSIONThe levels of IL-8, sICAM-1 and sVCAM-1 in the patient's plasma were correlated to the PB number of CD(34)(+) cells, CFU-GM, WBC and BPC during the mobilization process. It suggested that analysis of IL-8, and sVCAM-1 dynamic changes may serve as markers for CD(34)(+) cells.

Adolescent ; Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-8 ; blood ; Male ; Middle Aged ; Treatment Outcome ; Vascular Cell Adhesion Molecule-1 ; blood

Objective: To describe the status quo of overweight and obesity among children aged 3 to 5 in Beijing and Tokyo, and to explore its relationship with lifestyle. Methods: Using the method of cluster stratified random sampling, a sample of 444 children aged 3-5 years from Beijing and Tokyo were selected in Oct. and Nov. of 2019. Height, weight and lifestyle were measured. Overweight and obesity among children in the two cities and its relationship with lifestyle were compared and analyzed. Results: Average level of BMI, rate of overweight and obesity of children in Beijing(25.28%) were higher than those in Tokyo( 18.44 %). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with physical activity before breakfast( χ 2=29.14, 31.18, P <0.05). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with different snack frequency after dinner( χ 2=24.72, 21.93, P <0.05). Logistic regression analysis further showed that children s lack of physical activity before breakfast in Beijing is positively related to overweight and obesity( OR= 1.45, 95%CI =1.10-2.68). Beijing children who often eat snacks after supper ( OR=2.56, 95%CI =1.44-3.57,) and sometimes eat snacks were positively correlated with the occurrence of overweight or obesity ( OR=1.72, 95%CI =1.21-2.72). Conclusion The prevalence of overweight and obesity among preschool children in Beijing is higher than that in Tokyo. Potential risk factors for overweight and obesity among infants in Beijing include lack of physical activity before breakfast and frequent snacking after dinner.

OBJECTIVETo measure the bone mineral density (BMD) of mandible and investigate the relationship between mandible and the whole body skeleton BMD.

METHODSHealthy volunteers were recruited in north China, which were divided into 6 groups by age: > or = 20, > or = 30, > or = 40, > or = 50, > or = 60 and > or = 70 years older, 10 male and 10 female in each group. Dual-energy X-ray absoptiometery (DXA) was used to measure the BMD of the lumbar spine, the mentum of mandible and the mandibular angle. The results were analyzed statistically.

RESULTSThe mineral density (MD) of the mentum was (1.310 9 +/- 0.035 5) g/cm2, the left mandibular angle (1.048 9 +/- 0.013 7) g/cm2, the right mandibular angle (1.0547 +/- 0.014 1) g/cm2, the lumbar spine (L2-L4) (1.121 1 +/- 0.017 2) g/cm2. There was a significant difference in mandibular angle and lumbar MD between men and women (P < 0.05). The MD of mandibular angle and lumbar spine decreased significantly after 50 years of age.

CONCLUSIONSThe normal BMD of the mandibular mentum, mandibular angles and lumbar spine is obtained. The BMD of the mandibular angles is closely related to that of the lumbar spine. Mandible can be an appropriate measurement site in the evaluation of skeleton BMD status for the forecast of osteoporosis.

Adult ; Aged ; Bone Density ; China ; Female ; Humans ; Male ; Mandible ; anatomy & histology ; diagnostic imaging ; Middle Aged ; Radiography ; Young Adult

Objective The aim of the study was to investigate the epidemic situation,clinical symptom,diagnosis and epidemiological characteristics of human Fasciola gigantica infection in Dali,Yunnan province.It will also provide a scientific basis for fasciolosis control and prevention.Methods Epidemic data were collected and patient's clinical signs and symptoms were studied.Serum soluble antigen of Fasciola gigantica of patients and part of family members and health people in the same village was detected using enzyme-linked immunosorbent assay (ELISA) and the eggs of Fasciola gigantica in stool were observed under microscope.Sequencing and PCR amplification of Fasciola gigantica eggs had been done.Sequencing results were analyzed using basic local alignment search tool (BLAST) program of the U.S.National Center for Biotechnology Information (NCBI) and the similarity of the two in the sequence of nucleic acid was compared.Furthermore,patients were experimentally given orally therapeutic doses of Triclabendazole 10 mg·kg-1·d-1 daily for 2 days,and kept in the hospital for observation for one week.Moreover,host and vector were investigated in the surrounding ditches of Dali prefecture and Limnaea peregra snail samples were collected.All the snails were squashed by glass sheet in order to detect the cercarie.Cow dung and sheep manure was collected in the Limnaea peregra distribution environment,and the eggs in the feces were checked by microscope after washing and precipitation.Results All the 26 patients had a continued hyperpyrexia with distinct alimentary system symptoms of nausea,vomiting,stomachache,abdominal distension as well as hepatomegaly,sensitive to percussion,different levels of liver damage detected by CT.All the patients had an eaten history of raw Herba Houttuyniae and other aquatic plants,and the course of the disease was similar,with the same epidemiological characteristics.ELISA detection was used in the 26 patients,family members and other healthy population,the results of all the 26 patients were positive(100.0％,26/26) ; the positive rates of the 57 family members and other health people of the same village were 31.6％ (18/57) and 17.1％ (6/35),respectively.The results of sequencing and BLAST program showed that the pathogen was Fasciola gigantica with the similarity between 99％-100％.PCR amplification also confirmed that the eggs were Fasciola gigantica eggs with an approximately 1000 bp band on agarose gel.After treatment with Triclabendazole,body temperature of the patients dropped to normal and symptoms improved markedly.Moreover,329 Limnaea peregra snails were collected including 5 ones with redia and one-tailed cercariae which were preliminary identified as the larva of Fasciola gigantica.There were also eggs of Fasciola gigantica detected in one stool of cattle and one of goat.Conclusions Eating raw food is the leading cause of the onset of the disease.Triclabendazole is the drug of choice to treat Fasciolasis.Health education should be strengthened by government and disease prevention and control departments in order to make the local residents to understand the potential hazard of eating raw aquatic vegetable and drinking unboiled water,which is the key to prevent the occurrence of the disease.

OBJECTIVETo investigate collagen type I alpha 1 (COL1A1) and alpha 2 (COL1A2) gene polymorphisms in Chinese and their relationship with bone mineral density.

METHODSTotalling 628 residents of Han nationality in Guangzhou aged 53.4-15.9 (range 20-79) years were surveyed for COL1A1 and COL1A2 gene genotypes by polymerase chain reaction-restriction fragment length polymorphism. Bone mineral density of the lumbar vertebrae, greater trochanter, femur neck and Ward's triangle was measured by dual-energy X-ray absorptiometry.

RESULTSCOL1A1 Sp1 polymorphism was not found in these subjects, and the genotype of all samples were type SS. COL1A2 genotyping revealed the distribution of EE genotype in 49.7%, Ee in 40.9% and ee in 9.4% of the subjects. The frequency distribution of EcoR1 alleles followed the Hardy-Weinberg equilibrium. The mean bone mineral density did no significantly differ among these genotype groups (P>0.05 by analysis of variance).

CONCLUSIONCOL1A1 Sp1 binding site polymorphism is absent and COL1A2 EcoR1 site polymorphism is not associated with bone mineral density in Chinese of Han nationality.

Adult ; Aged ; Bone Density ; China ; Collagen ; genetics ; Collagen Type I ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Lumbar Vertebrae ; metabolism ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length