Yunnan sudden death syndrome (YSDS) is an abruptly fatal disease of unknown etiology, found mostly in central or northwestern mountain area (with altitude between 1 815 and 2 225 meters ) of Yunnan province from June to September every year. It occurs mostly in young female adults, with high incidences in Lisu, Yi and Miao ethnics and high familial aggregation. The clinical manifestation of YSDS is changeful and the pathological characteristic is lack of specificity. The pathogenesis may be at-tributed to several factors including poor hygiene and lower socioeconomic conditions, lack of Selenium or Chromium, infection of Coxsackie B virus, mushroom consumption and special geological conditions. This article reviews the epidemiologic features, clinical manifestations, pathological features, etiology and hypothesis in order to provide clues for the research of YSDS.

AIM To investigate the effects of Wuzi Yanzong Prescription (Lycii Fructus,Cuscutae Semen,Rubi Fructus,Plantaginis Semen and Schisandrae chinensis Fructus) on DNA damage of testis cells in adult male mice induced by cyclophosphamide (CTX).METHODS Forty out of fifty adult male Balb/C mice were injected intraperitoneally with CTX and then were randomly and equally divided into model control group (normal saline),Wuzi Yanzong Prescription low-,medium-and high-dose groups (100,200 and 400 mg/kg),and the other ten mice served as normal control group (normal saline).All mice were anesthetized by inhalation of ether,and then were sacrificed by cervical dislocation.The sperm count,sperm motility and malformation rate of sperm were tested.The content of 8-hydroxy-deoxyguanosine (8-OHdG) in serum was measured using ELISA;the DNA damage degree of cells in testis was detected by single cell gel electrophoresis;the protein expressions of p-P53 and γ-H2AX in testis were examined by Western blot.RESULTS Compared with the model control group,Wuzi Yanzong Prescription groups showed significant increase in the sperm count,sperm motility and significantly decreased malformation rate of sperm,the level of 8-OHdG in serum,and the protein expressions of p-P53 and γ-H2AX in testis were also significantly decreased.CONCLUSION Wuzi Yanzong Prescription can significantly alleviate the DNA damage of testis cells in mice induced by CTX through down-regulating protein expressions of p-P53 and γ-H2AX.

Yunnan sudden death syndrome (YSDS) is an abruptly fatal disease of unknown etiology, found mostly in central or northwestern mountain area (with altitude between 1,815 and 2,225 meters) of Yunnan province from June to September every year. It occurs mostly in young female adults, with high incidences in Lisu, Yi and Miao ethnics and high familial aggregation. The clinical manifestation of YSDS is changeful and the pathological characteristic is lack of specificity. The pathogenesis may be attributed to several factors including poor hygiene and lower socioeconomic conditions, lack of Selenium or Chromium, infection of Coxsackie B virus, mushroom consumption and special geological conditions. This article reviews the epidemiologic features, clinical manifestations, pathological features, etiology and hypothesis in order to provide clues for the research of YSDS.
Adult ; China ; Death, Sudden/pathology* ; Female ; Humans ; Syndrome

OBJECTIVETo study the expression of alpha5beta1 integrin in the abnormal scars and its role and significance in the formation and development of abnormal scars.

METHODSThe expression of alpha5beta1 integrin was observed in hypertrophic scar (15 samples), keloid (15 samples) and normal skin (10 samples) with SP immunohistochemical method and colloidal gold immuno-electron microscopic technique. The data were semi-quantitatively analyzed.

RESULTSThe expression levels of alpha5beta1 integrin in the fibroblasts of keloids and hypertrophic scars were higher than normal skin; the expression of alpha5beta1 integrin in the fibroblasts of keloids was higher than hypertrophic scars (P < 0.01).

CONCLUSIONThe alpha5beta1 integrin appears to have close relation to the formation and development of abnormal scars. To find a way to decrease the expression level of alpha5beta1 integrin in fibroblasts may be a new approach to inhibit scar hypertrophy.

Cicatrix ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Integrin alpha5beta1 ; analysis ; metabolism ; Keloid ; metabolism ; pathology ; Microscopy, Immunoelectron ; Skin ; chemistry ; pathology ; ultrastructure

Objective To study the effects of two stimulators of the innate immune system, polyinosine-polycytidylic acid [Poly (I:C)] and R848, on the activation of microglia in rat spinal cord. Methods Thirty male Lewis rats (6 to 8 weeks old) were divided into Poly(I:C) group (n=12), R848 group (n=15) and control group (n=3). According to the killing time, the Poly(I:C) group and R848 group were divided into 4 and 5 sub-groups, respectively, with 3 rats in each sub-group. The rats in the subgroups received intraperitoneal injection of a single bolus of Poly(I:C) (5 mg/kg) or R848 (1 mg/kg) accordingly, and in the control group, the same volume of phosphate-buffered saline (PBS) was administered. Activated microglia were observed using immunohistochemistry for ED-1, AIF-1, EMAP Ⅱ, OX6, and P2X4R, and BrdU staining was used to identify the proliferating cells. Results Compared with the control group, both Poly (I:C) and R848 groups showed a significant but transient increase of ED-1-positive spinal cord microglia 4 days after the injection, while no significant differences were found in the microglial markers AIF-1, EMAP Ⅱ, OX6, P2X4 receptor (P2X4R), indicating that the microglia were not fully activated. Tracing of the cell proliferation by BrdU revealed that only a small fraction of the proliferating cells were microglia (less than 5%). Conclusion Poly(I:C) and R848 have definite effects on the innate immune system of the spinal cord and modulate the immune activity in the spinal cord, suggesting the value of these agents in modulating local regenerative processes in injured spinal cord.

By using the cell density, cell viability, size distribution of cell aggregates,specific consumption rate of glucose (q_ glc ), specific production rate of lactate (q_ lac ), lactate transform rate (Y_ lac/glc ) and amino acids utilization as the evaluation indexes, the growth and metabolism of HEK293 cells under carrier-free immobilization culture mode were examined and compared with those of HEK293 cells cultured in static tissue flasks. It was found that HEK293 cells grown as suspended cell aggregates in spinner flasks maintained the basic growth and metabolism characteristics of HEK293 cells in stationary anchored culture, and HEK293 cells under carrier-free immobilization culture mode as suspended aggregates in stirred bioreactor facilitate perfusion performance and increase unit productivity. Cultivation of HEK293 cells in carrier-free immobilization culture mode has potential for further improving mammalian cells culture technique.

BACKGROUNDRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation at the synovial membrane. Although great progress has been made recently in exploring the etiology and pathogenesis of RA, its molecular pathological mechanism remains to be further defined and it is still a great challenge in determining the diagnosis and in choosing the appropriate therapy in early patients. This study was performed to screen candidate RA-associated serum proteins by comparative proteomics to provide research clues to early diagnosis and treatment of RA.

METHODSSera isolated from 6 RA patients and 6 healthy volunteers were pooled respectively and high-abundance proteins were depleted by Plasma 7 Multiple Affinity Removal System. The protein expression profiles between the two groups were then compared by two-dimensional gel electrophoresis (2-DE) and the proteins over/under-expressed by more than 3-fold were identified by mass spectrometry analysis. To validate the differential expression levels of the identified proteins between the two groups, ELISA was performed in two of the identified proteins in individual sera from 32 RA patients and 32 volunteers.

RESULTSEight proteins which over/under-expressed in sera of RA patients were identified. Among them, chain A of transthyretin (TTR) was under-expressed, while serum amyloid A protein, apolipoprotein A (ApoA)-IV, ApoA-IV precursor, haptoglobin 2, ceruloplasmin (Cp), immunoglobulin superfamily 22 and HT016 were over-expressed. ELISA test confirmed that Cp expressed remarkably higher while TTR obviously lower in RA group compared with volunteer group.

CONCLUSIONThere were 8 identified proteins differentially expressed between RA group and volunteer group, which might be candidate RA-associated proteins and might be promising diagnostic indicators or therapeutic targets for RA.

Adult ; Apolipoproteins A ; blood ; Arthritis, Rheumatoid ; blood ; Blood Proteins ; analysis ; Ceruloplasmin ; analysis ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Prealbumin ; analysis ; Proteomics ; Serum Amyloid A Protein ; analysis

By using the size distribution of cell aggregates, viable cell density, cell viability, specific consumption rate of glucose (q(glc)), specific production rate of lactate (q(lac)) and lactate transform rate (Y(lac/glc)) as the evaluation indexes, the effects of hydrodynamic on aggregates formation, growth and metabolism of HEK293 cells in suspension culture were examined in 250mL spinner-flasks by setting the agitation rates at 25, 50, 75 and 100r/min, respectively. It was found that agitation plays an important role in HEK293 cell aggregates formation and cell aggregates size distribution. After 7d cultivation in spinner-flasks operated at 50r/min and 75r/min, the average diameter of HEK293 cell aggregates was 201 microm and 175 microm, respectively, with the fraction of aggregates larger than 225 microm less than 10%. The cell viability was kept above 90% with the metabolic indexes, including q(glc), q(lac) and Y(lac/glc) kept constant. These results demonstrated that hydrodynamic derived from the proper agitation play a decisive role in controlling the formation and size distribution of HEK293 cell aggregates, and provided sufficient mass transfer to support the normal growth and metabolism of HEK293 cells in suspended aggregates.
Bioreactors ; Cell Aggregation ; Cell Culture Techniques ; instrumentation ; Cell Line ; Cell Proliferation ; Humans ; Kinetics

The present study utilized LC-MS and HPLC approaches to characterize the metabolites of neferine in rat liver after an oral administration of 20 mg x kg(-1), and investigated the involvement of CYP450 isoforms in the metabolism of neferine by their selective inhibitors in vitro, separately. In positive ionization mode, besides neferine, four metabolites (M1-M4) were detected. M2 (the major metabolite) and M4 were identified as liensinine and isoliensinine by comparison with reference substances. Moreover, according to the analysis of metabolic rule of parent drug (neferine), M1 and M3 may be desmethylliensinine and desmethyl-isoliensinine, respectively. Furthermore, the metabolism of neferine in rat liver microsomes showed that the percentage inhibition of the major metabolism (liensinine) formation was 80.5% by quinidine (10 micromol x L(-1), selective CYP2D1 inhibitor) and 25.7% by ketoconazole (1 micromol x L(-1), selective CYP3A1 inhibitor). Neferine was mainly metabolized by CYP2D1 or CYP3A1 to liensinine, isoliensinine, desmethyl-liensinine and desmethyl-isoliensinine.
Administration, Oral ; Alcohol Oxidoreductases ; antagonists & inhibitors ; Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Benzylisoquinolines ; administration & dosage ; isolation & purification ; metabolism ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP3A ; Cytochrome P450 Family 2 ; Isoquinolines ; metabolism ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; metabolism ; Nelumbo ; chemistry ; Phenols ; metabolism ; Plants, Medicinal ; chemistry ; Quinidine ; pharmacology ; Rats ; Seeds ; chemistry ; Spectrometry, Mass, Electrospray Ionization

Objective To analyze the comparation of national early warning score (NEWS), rapid emergency medicine score (REMS) and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score in predicting prognosis of critically ill patients in emergency department (ED). Methods A retrospective study was conducted. Critically ill patients, aged > 16 years, hospitalized > 24 hours, and admitted to the ED of Nanhua Hospital Affiliated to South China University from January 2016 to June 2017 were enrolled. NEWS, REMS and APACHE Ⅱ score were calculated based on the worst value of each index within 24 hours after emergency admission. The primary endpoint was 28-day mortality. The relationship between the three scoring systems and the prognosis of patients was analyzed. The predictive value of three scoring systems for the prognosis of critically ill patients in ED was analyzed by receiver operating characteristic curve (ROC). Results A total of 119 emergency severe patients were enrolled in the study, and the 28-day mortality was 21.0%. The scores of NEWS, REMS and APACHE Ⅱ in the death group were significantly higher than those in the survival group (NEWS score: 9.40±3.19 vs. 5.72±2.35, REMS score: 12.64±4.46 vs. 7.97±3.28, APACHE Ⅱscore: 26.64±6.92 vs. 16.19±5.48, all P < 0.01). With the increase of NEWS, REMS and APACHE Ⅱ score, the 28-day mortality of patients gradually increased [28-day mortality of NEWS < 5, 5-6, ≥ 7 was 3.03% (1/34), 13.33% (4/34), 64.25% (20/51); 28-day mortality of REMS < 12, 12-16, ≥ 17 was 10.99% (10/91), 50.00% (11/22), 66.67% (4/6); 28-day mortality of APACHE Ⅱ < 15, 15-24, ≥ 25 was 2.33% (1/43), 15.09% (8/59), 69.57% (16/23), respectively, all P < 0.01]. The ROC curve analysis showed that the areas under the ROC curve (AUC)of NEWS, REMS and APACHE Ⅱ score for predicting the prognosis of emergency critically ill patients were 0.830 [95% confidence interval (95%CI) = 0.737-0.923], 0.782 (95%CI = 0.671-0.892) and 0.878 (95%CI = 0.800-0.956), respectively (all P = 0.000), and the accuracy of prediction was 57.4%, 48.6%, 65.4%, respectively. Conclusions The scores of NEWS, REMS and APACHE Ⅱ were useful in predicting prognosis of critically ill patients, with the highest accuracy of APACHE Ⅱ forecast, followed by NEWS, and the lowest of REMS. After comprehensive consideration of cost-effectiveness, NEWS is more reliable in ED.