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The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.
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Rats , Animals , NF-kappa B/metabolism , Spleen , Gastrointestinal Microbiome , Toll-Like Receptor 4 , Polysaccharides/pharmacology , Astragalus Plant/metabolism , Immune System Diseases/drug therapy , Body WeightABSTRACT
【Objective】 To analyze the causes and preventive measures of lipemic blood in voluntary blood donors. 【Methods】 Data of 12 000 voluntary blood donors donated at our blood station from January 2018 to June 2020 were retrospectively analyzed. The incidence, discarding rate and causes of lipemic blood were investigated, and preventive measures were formulated. 【Results】 384(3.20%) out of the 12 000 blood samples were lipemic blood, while mild, moderate and severe lipemic blood constituted 181, 148 and 55 cases, respectively. The incidence of lipoemia in males(4.22%) was higher than that in females(1.52%). The incidence of lipoemia in 26~45 and 36~45 age population was 4.75%, which was higher than that in 18~25 age group(0.62%). The incidence of lipoemia was the lowest in donors with mass index(kg/m2) <18.5, followed by 18.5~24.9 and >30 (P<0.05). The incidence of lipemic blood among first-time blood donors(4.38%) was higher than that in repeated donors(2.31%), higher in blood donation collected during 13: 00 to 17: 00(3.54%) than 9: 00 to 12: 00 a. m.(2.73%), also higher in group blood donors(4.01%) than street blood donors(1.56%)(P<0.05). The free Hb of red blood cells in moderate and severe group was higher than that in mild group immediate after preparation and 7 days after preparation (P<0.05). 【Conclusion】 There was a significant tendency for the incidence of lipemic blood in voluntary blood donors, which causes blood discarding. The publicity of blood donation, pre-donation consultation and advice on reasonable diet should be boosted to reduce the discarding rate of lipemic blood and improve the use of blood.
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Objective:To evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) on sedation in healthy volunteers.Methods:Forty-six healthy volunteers of both sexes, with the Sleep Self-Rating Scale score 10-30, aged 22-28 yr, with the body mass index 18.5-23.0 kg/m 2, were selected and divided into 2 groups ( n=23 each) using a random number table method: TEAS group (E group) and control group (C group). Bilateral Neiguan and Shenmen acupoints were stimulated for 30 min in group E, while the stimulator was only connected, and no current was given in group C. The bispectral index (BIS)value, heart rate, oxygen saturation and mean arterial pressure were recorded at 10 min in the supine position (T 0) during the quiet period, at 10 min intervals during stimulation (T 1, 2) and at 5 min intervals within 15 min after the end of electrical stimulation (T 3-5). Then the condition whether the patient had fallen asleep was observed, and the patients were followed up on the second day for sleep status and related complications. Results:Compared with the baseline at T 0, the BIS value was significantly decreased at T 2-5 in group E ( P<0.05). The BIS value was significantly lower at T 3, 4 in group E than in group C ( P<0.05). There was no significant difference in sleep status during stimulation and at the night of the trial between the two groups ( P>0.05). Heart rate, oxygen saturation and mean arterial pressure were in the normal range at each time point, and no trial-related complications occurred in the two groups ( P>0.05). Conclusion:TEAS can produce certain sedative effect on healthy volunteers.
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Objective@#This study collected and analyzed data from patients with microtia in multiple clinical centers to obtain the incidence characteristics of microtia in Chinese.@*Methods@#Data from 746 patients with microtia were collected from six hospitals, including theThird Hospital of Hebei Medical University, Hunan Provincial People′s Hospital, the Second Hospital of Hebei Medical University, Weihai Municipal Hospital, West China Hospital Sichuan University, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2017. These data included the results of physical examination and the results of auxiliary examination such as electrocardiogram, chest CT, and abdominal ultrasound. Then, the accompanying malformations of the microtia were statistically analyzed and discussed. Data were entered and processed using SPSS 19.0 statistical software. The relationship between microtia deformities and associated malformations was analyzed by Pearson χ2 test. P<0.05 was considered statistically significant.@*Results@#A total of 746 patients with microtia were included, including 513 males and 233 females, aged 5-27 years old. There were 678 cases of unilateral microtia, 68 cases of bilateral microtia; 128 cases of Ⅰ degree, 564 cases of Ⅱ degree, and 54 cases of Ⅲ degree. In addition, 336 cases (45%) were associated with dysplasia of other systems. Detected anomalies were 321 cases of the ear, face, and neck, 261 cases of musculoskeletal system and 76 cases of cardiovascular system, 30 cases of anomalies of the urogenital system, eye, 27 cases of respiratory system, 7 cases of central nervous system, 5 case of digestive system and 1case of diaphragmatic hernia. The proportion of male and female with microtia was 47.0% (241/513) and 40.8% (95/233), respectively, and there was no significant difference in between (χ2=2.493, P=0.114); The composition ratios of unilateral and bilateral associated malformations were 45.7% (310/678) and 38.2% (26/68 ), and there was no significant difference in between (χ2=1.400, P=0.237); The composition ratios of Ⅰ, Ⅱ, Ⅲ degree-associated malformations were 39.8% (51/128), 42.6% (240/564), and 83.3% (45/54), and the difference was statistically significant (χ2= 34.794, P<0.001).@*Conclusions@#Microtia has significant clinical heterogeneity with a higher proportion of associated malformations. A higher incidence of associated deformities in patients with severe microtia was observed. Systematic examination is required, which will be helpful to clinical therapy and etiology analysis.
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Objective@#To understand the infection rate and genotype distribution of high risk-human papillomavirus (HR-HPV) and the detection rate of different grades of cervical lesions in Han and Mongolian women in China and provide evidence for the development of screening and vaccination strategies for the prevention and control of cervical cancer in different ethnic groups.@*Methods@#In June 2017, a multicenter, population-based study for cervical cancer screening in low-resource settings in China was conducted in three rural areas: Xiangyuan and Yangcheng counties in Shanxi province, and Etuoke county in Inner Mongolia Autonomous Region. A total of 9 517 women aged 30-65 years were included in the study, and two cervical and vaginal secretion samples were collected from them for HPV and PCR-based HPV DNA tests. The positive samples in any of two tests were used for PCR-based HPV genotyping test by using Sansure-pioneered One-Step Fast Release technology. Women with positive results in any the HPV tests were referred for colposcopy and punch biopsy was given if cervical intraepithelial neoplasia lesion (low-grade lesion or worse) was suspected in colposcopy evaluation. Endocervical curettage was performed if women had an unsatisfactory colposcopy exam (the squamocolumnar junction was not completely visible). Pathological detection result was used as the golden standard of diagnosis.@*Results@#HR-HPV infection rates in Han and Mongolian women were 21.83% (1 842/8 438) and 24.93% (269/1 079), respectively. There were statistical differences in HPV infection rates between the two ethnic groups (χ2=5.328, P=0.021). The detection rate of cervical intraepithelial neoplasia grade 1 in Mongolian women (2.83%) was higher than that in Han women (0.87%), and the difference was statistically significant (χ2=33.509, P<0.001). There were no significant differences in cervical intraepithelial neoplasia grade 2 or worse detection rate between the two ethnic groups [Mongolian woman: 1.04% (11/1 059), Han Woman: 0.95% (80/8 378), χ2=0.069, P=0.793]. Among Han and Mongolian women with cervical intraepithelial neoplasia grade 2 or worse, the three most common HR-HPV types were HPV16, HPV52 and HPV58. There was no significant difference for multiple infection rate between Han and Mongolian women (41.37% vs. 44.35%, χ2=0.764, P=0.382).@*Conclusions@#The results show that HPV infection rate in Mongolian women was higher than that in Han women. Close attention should be paid to HPV16, 52 and 58 in the prevention and control of cervical cancer in Han and Mongolian women.
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Objective To evaluate the efficacy of intermittent positive pressure ventilation (IPPV,1 ml/kg) of the operated lungs in preventing hypoxemia during one-lung ventilation (OLV) in elderly patients undergoing radical resection of esophageal cancer.Methods Sixty American Society of Anesthsiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 65-75 yr,with body mass index of 18.5-24.0 kg/m2,were divided into 2 groups (n =30 each) using a random number table method:convention group and IPPV group.In convention group,ventilator settings were adjusted with the tidal volume of 6-8 ml/kg,respiratory rate of 15 breaths/min,inspiratory/expiratory ratio of 1 ∶ 2,and fraction of inspired oxygen 70％ during OLV.In IPPV group,ventilator settings were adjusted with the tidal volume of 1 ml/kg,respiratory rate of 15 breaths/min,and fraction of inspired oxygen 70％ on the operated side during OLV,and the ventilator settings on the other side were consistent with those previously described in convention group.Before anesthesia induction (T0),at 10 min of two-lung ventilation (T1),at 15,30 and 45 min of OLV (T2,4) and at 10 min after the end of OLV (T5),blood samples were collected from the radial artery for blood gas analysis.The partial pressure of arterial oxygen (PaO2) and alveolar to arterial partial pressure of oxygen were recorded.Respiratory index (RI) and oxygenation index (OI) were calculated.The occurrence of PaO2 ＜ 60 mmHg,RI＞ 1.0 and OI＜ 200 mmHg was recorded during OLV.Results Compared with convention group,the RI was significantly decreased at T4,the PaO2 and OI were increased,and the incidence of PaO2＜60 mmHg,RI＞ 1.0 and OI ＜ 200 mmHg was decreased in IPPV group (P＜ 0.05).Conclusion IPPV (1 ml/kg) of the operated lungs can prevent the occurrence of hypoxemia during OLV in elderly patients undergoing radical resection of esophageal cancer.
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Objective@#To explore the role of HPV viral loads in random biopsy under normal colposcopy.@*Methods@#908 atypical squamous cells of undetermined significance (ASC-US) and HPV positive women, recruited in cluster sampling in 9 provinces including 5 urban areas and 9 rural areas in China from 1999 to 2008 and meeting the inclusion and exclusion criteria were included in this analysis. According to relative light units/cutoff (RLU/CO) value, subjects were stratified as low (286 cases), intermediate (311 cases) and high (311 cases) viral load groups. Risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among different viral load groups were compared with linear trend Chi-square test.@*Results@#Detection rate of CIN3+ in low, intermediate and high viral load groups were 2.1% (6 cases), 2.6% (8 cases) and 6.8% (21 cases) (Chi-square test for trend χ2=8.91, P=0.003) and were 60.3, 74.0 and 201.3 times higher than ASC-US and HPV negative women, respectively. Among 908 subjects, 27.0% (245 cases) were abnormal under colposcopy and 68.6% (623 cases) diagnosed as normal. Under normal colposcopy, detection rate of CIN3+ in low, intermediate and high viral load groups were 0.9% (2 cases), 0.9% (2 cases) and 3.8% (7 cases) (χ2=6.42, P=0.040).@*Conclusion@#HPV viral loads display satisfactory risk stratification ability among ASC-US and HPV positive women under normal colposcopy. Women with high HPV viral loads show a significantly increased detection rate of existing CIN3+ and could be recommended to perform random biopsy for histologic diagnosis.
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Objective@#To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+).@*Methods@#We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups.@*Results@#Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ2=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ2=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ2=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting.@*Conclusion@#Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.
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Diabetes is a common disease,the complications caused by hyperglycemia have a serious impact on the quality of life of patients.The wound healing after skin injury in diabetic patient is affected by many factors.This article reviews various factors related to angiogenesis and wound healing in diabetes,including insulin,endogenous hydrogen sulfide,hypoxia inducible factor-1α and tumor necrosis factor-α.These findings may provide a new theoretical basis for the treatment of diabetic wound healing,foot ulcer and other complications.
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BACKGROUND:There are a lot of adipose-derived stem cel s in the vascular stroma. These cel s are shown to play a very important role in the fat granule transplantation. OBJECTIVE:To explore the role of adipose-derived stem cel s in the fat granule transplantation. METHODS:Normal adipose tissues were obtained from 10 male BALB/C mice, SPF grade. Adipose-derived stem cel s and fat granules were extracted from the abdominal fat tissues. Another 24 nude mice acted as recipients and were assigned into control, fat granule transplantation or mixed transplantation (adipose-derived stem cel s+fat granules) groups. In the latter two groups, fat granule suspension and suspension of fat granules and adipose-derived stem cel s were injected into the shoulder of rats, respectively. In the control group, the same volume of cel medium was injected. Four weeks later, separated plasma and grafts were taken out for indicator measurement. RESULTS AND CONCLUSION:Compared with the fat granule transplantation group, the mixed transplantation could remarkably increase the weight of grafts, while reduce the absorption of grafted fat tissues (P<0.01). After transplantation, the highest level of vascular endothelial growth factor in the plasma was obtained in the mixed transplantation group fol owed by fat granule transplantation group and control group (P<0.01). Level of basic fibroblast growth factor and microvessel density were significantly higher in the mixed transplantation group than the fat granule transplantation group (P<0.01). Better cel morphology and higher number of fat droplets were found in the mixed transplantation group compared with the fat granule transplantation group. Al these results indicate that adipose-derived stem cel transplantation can remarkably promote the expression of basic fibroblast growth factor, improve graft microcirculation, and improve morphology and function of fat granules.
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Objective To explore the mechanism of radio-resistance of breast cancer stem cells by investigating the effects of ionzing radiation on the reactive oxygen species (ROS),apoptosis and cycle distribution.Methods The breast cancer MCF-7 cells were suspension cultured in serum-free medium containing a variety of growth factors. There were MCF-7 (breast cancer cells),MCF-7-S (breast cancer stem cells),MCF-7+8 Gy and MCF-7-S+8 Gy groups in the experiment. 4-24 h after 8 Gy irradiation, the ROS levels, percentages of apoptotic cells and percentages of the cells at each cycle phage were measured by FCM with 2′, 7′-dichlorodihydrofluorescin diacetate (DCFH-DA ), Annexin Ⅴ-FITC/PI and PI staining, respectively. Results The breast cancer stem cell microsphere accumulated hundreds of cells were obtained successfully at 7 d after suspension culture with serum-free medium containing a variety of growth factors;the FCM results showed that CD44+CD24- phenotype breast stem cells were up to 75.20%.With the time prolongation,the ROS levels and apoptosis in MCF-7 group and MCF-7-S group showed increasing trendency, and reached for the maximum values at 12 and 24 h;the ROS levels in MCF-7-S group were significantly lower than those in MCF-7 group at 4,8,12 and 24 h (P<0.05 or P<0.01), and the percentage of apoptotic cells in MCF-7-S group was significantly higher than that in MCF-7 group only at 8 h(P<0.05);the ROS levels (4,8,12 and 24 h)and percentage of apoptotic cells(12 h)were significantly increased in MCF-7+8 Gy group (P<0.05),and the percentages of apoptotic cells (4,8,12 and 24 h)in MCF-7-S +8 Gy group were significantly decreased (P<0.05 or P<0.01),but the ROS levels had no obvious change in MCF-7-S+8 Gy.At 12 h,as compared with MCF-7 group,the percentages of the cells at G0/G1 phase and G2/M phase in MCF-7-S group were significantly decreased (P<0.05),and the percentage of the cells at S phase was significantly increased (P<0.05 );the percentage of the cells at G2/M phase in MCF-7+8 Gy group was significantly increased (P<0.05 ), but there were no significant changes in MCF-7-S+ 8 Gy group. Conclusion Ionizing irradiation can cause the increasing of ROS level and apoptosis and G2/M phase arrest in breast cancer cells,but has no obvious effects on the breast cancer stem cells;it indicates that radio-resistance might be related to ROS level,apoptosis and G2/M phase arrest.
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Objective To observe the changes of MMP-1 and TIMP-1 expression in the pathological scar tissue after scar-skin replantation and to explore the mechanism of treating pathological scars with scar-skin replantation through a rabbit ear model.Methods Rabbit ears were used to establish the hypertrophic scar animal model in this study.Specimens were taken for three times:normal skin,hypertrophic scar and scar-skin replantion separately.We then performed HE staining,Masson staining and immunohistochemical staining to observe the expression of MMP-1 and TIMP-1 in these three groups of specimens.Results The expression of both MMP-1 and TIMP-1 significantly increased in the hypertrophic scar tissue after scar-skin replantation compared with the control group (P＜0.01).The expression of MMP-1 increased more significantly than that of TIMP-1 (P＜0.01).Conclusions The mechanism of scar-skin replantation's effect in the treatment for hypertrophic scar is relevant to the imbalance in the interaction between MMP-1 and TIMP-1 in the scar tissue.
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Objective To investigate the difference between simple continued traction and areola dermal flap filling in inverted nipple correction surgery.Methods There were 60 nipples of 32 patients in simple continuous traction group and 62 nipples of 32 patients in dermal flap filling group.Follow-up was conducted for 12 months.The surgical results were compared with statistical analysis.Results Wound healing,nipple shape,blood supply,feeling and breast-feeding function in simple continuous traction group were better than those of the dermal flap filling group.There was no statistically significant difference in diameter and height of nipple,nipple retraction and relapse rate between the two groups.Conclusions Simple continuous traction is superior to dermal flap filling.Both methods are safe and effective for the treatment of various types of inverted nipple and two groups of patients have improved in symptoms and appearance.
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Objective To treat axillary osmidrosis by using three procedures (small incision apocrine curettage,cut-off operation and aspiration surgery),to observe the postoperative complications,efficacy and the pathological changes of skin,and to explore the advantages of these three procedures.Methods Seventy-five cases of evere bilateral axillary osmidrosis were involved in this study,totally 150 axillary surgery area,which was randomly divided into different group:Group A (curettage group); Group B (cut-off group) and Group C (aspiration group).Different surgical treatment was conducted in the three groups of operation area.Results Incidence of complications was 28.30 ％ and total effective rate was 94.34 ％ in Group A; in Group B,incidence of complications was 6.38 ％,and total effective rate was 97.87 ％ ; in Group C,incidence of complications was 4.00 ％ and total effective rate was 78.00 ％.The incidence of complications was significantly different between Groups A and B and between Groups A and C,but not significant difference between Groups B and C.The cure rate and efficiency were not significant difference between Groups A and B groups,but significant difference was found between Groups A and C and Groups B and C.HE staining results showed that the dermal tissues were partially destroyed in Group A and B,and no apocrine sweat glands were not seen within the dermis and subcutaneous tissues; in Group C,the dermal tissue was rarely destroyed,and a lot of apocrine sweat glands were reserved within the dermis and subcutaneous tissues.Conclusions Efficacy of curettage and cut-off procedures is better,but that of aspiration is worse in the treatment of axillary asmidrosis.The complications of cut-off surgery and aspiration are less,but urettage has more complications.Therefore,the efficacy of cut-off operation is the best with least complications among the three procedures.
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Objective To compare the effects of fentanyl,sufentanil and remifentanil on the immune function of dendritic cells in human umbilical cord blood.Methods Human umbilical cord blood mononuclear cells were obtained by density gradient centrifugation and seeded in 24-well plates with a density of 1 × 106/ml (2ml/hole).The cells were randomly divided into 7 groups (n =15 each):control group (group C),fentanyl 1.0 ng/ml group (group F1),fentanyl 5.0 ng/ml group (group F5),sufentanil 0.1 ng/ml group (group S1),sufentanil 0.5 ng/ml group (group S5),remifentanil 1.0 ng/ml group (group R1),and remifentanil 5.0 ng/ml group (group R5).The cells were incubated for 10 days in serum-free culture medium containing 50 ng/ml recombinant human granulocyte colony stimulating factor,10 ng/ml recombinant human interleukin-4 or the corresponding concentration of fentanyl,sufentanil or remifentanil,and then 50 ng/ml recombinant human tumor necrosis factor alpha was added to the culture medium and the cells were incubated for another 4 days in the seven groups.Three holes in each group were chosen and the cell morphology was examined with inverted microscope.Six holes in each group were chosen for determination of the concentration of IL-12 in the supernatant and expression of CD80/CD86.Six holes in each group were chosen for measurement of the cell viability.Results Compared with group C,the concentration of IL-12 and cell viability were significantly decreased and the expression of CD80/CD86 was down-regulated in groups F5,S1,S5,R1 and R5 (P ＜ 0.05).The concentration of IL-12,cell viability and expression of CD80/CD86 were significantly lower in groups S1 and R1 than in group F1 (P ＜ 0.05).Compared with group F5,the concentration of IL-12 was significantly decreased in group S5,and the concentration of IL-12 and cell viability were significantly decreased and the expression of CD80/CD86 was down-regulated in group R5 (P ＜ 0.05).The concentration of IL-12 and cell viability were significantly lower in group R1 than in group S1 (P ＜ 0.05).The concentration of IL-12,cell viability and expression of CD80/CD86 were significantly lower in group R5 than in group S5 (P ＜ 0.05).Conclusion Remifentanil has stronger inhibitory effect on the immunological function of dendritic cells in human umbilical cord blood than sufentanil,and the inhibitory effect of sufentanil is stronger than that of fentanyl.
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The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45γ [corrected], revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45γ [corrected] identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that: (1) dimerization of Gadd45γ [corrected] is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.
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Animals , Humans , Mice , Amino Acid Motifs , Apoptosis , Radiation Effects , CDC2 Protein Kinase , Cell Cycle , Cell Survival , Crystallography, X-Ray , Cyclin B , Metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Cyclin-Dependent Kinases , HeLa Cells , Intracellular Signaling Peptides and Proteins , Chemistry , Genetics , Metabolism , Mutagenesis, Site-Directed , Mutation, Missense , Proliferating Cell Nuclear Antigen , Metabolism , Protein Binding , Protein Interaction Domains and Motifs , Protein Multimerization , Protein Structure, Quaternary , Ultraviolet RaysABSTRACT
YKL-40 (human cartilage glycoprotein 39) is a newly discovered inflammatory cytokine, which belongs to the member of 18 glycosyl hydrolase of mammal family. Previous studies have indicated that YKL-40 is associated with the acute or chronic inflammatory diseases and tumors. Studies in recent years have suggested that YKL-40 may be involved in the occurrence and development of atherosclerotic plaques, and it is correlated with the plaque instability. The physiological function and the mechanisms of YKL-40 are not fully understood. It may have the roes of promoting vascular smooth muscle migration and proliferation, promoting cell adhesion and proliferation, as well as regulating extracellular matrix remodeling The detection of YKL-40 may have some significance in the aided diagnosis, predicting prognosis, prevention of cardiocerebrovascular diseases, and even the establishment of new therapeutic strategies.
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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can be induced in ischemia and other pathological states and mediate neuronal apoptosis after cerebral ischemia.Understanding the upregulation mechanism of TRAIL in ischemic brain tissue is promising to develop new treatment for stroke.
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Objective To investigate the effect of malignant tumor on neuromuscular block of cisatracurium. Methods Sixty ASA Ⅰ or Ⅱ patients with head and neck neoplasms (15 cases with benign tumor, 45 with malignant tumor), aged 18-64 yr, were randomly divided into 4 groups ( n = 15 each): Ⅰ benign tumor group (group B,3 × ED95 ); Ⅱ -Ⅳ different dose cisatracurium group (group C1 (2 × ED95 ), C2 (3 × ED95 ) and C3 (4 ×ED95)). Neuromuscular block was assessed with accelerograph F (TOF-watch SX). Single stimulation of ulnar nerve was used. Anesthesia was induced with TCI of propofol (target plasma concentration 3 μg/ml) and remifentanil (target effect-site concentration 3 ng/ml). Tracheal intubation was facilitated with cisatracurium 0.15 mg/kg in group B, and with cisatracurium 0.10, 0.15 and 0.20 mg/kg in group C1, C2 and C3 respectively. The onset time, clinical duration, time for recovery of T/Tc to 75 % and recovery index were recorded. Results The clinical duration, time for recovery of T/Tc to 75 % and recovery index were significantly longer in group C2 than in group B (P ＜ 0.05). The onset time was significantly shorter, while the clinical duration and time for recovery of T/Tc to 75% were significantly longer in group C2 and C3 than in group C1 , and in group C3 than in group C2 ( P ＜0.05) .Conclusion The duration of action and recovery times of cisatracurium were prolonged in patients with malignant tumor.
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Objective To investigate the effects of sufentanil,remifentanil and fentanyl oH cellular immune function in patients undergoing radical resection of esophageal cancer.Methods Forty-five ASA Ⅰ or Ⅱpatients aged 45-64 yr undergoing radical resection of esophageal cancer were randomly divided into 3 groups(n=15 each):sufentanil group(SF);remifentanil group(RF)and fentanyl group(F).The patients were premedicated with iv atropine 0.5 mg.Anesthesia was induced with midazolam 0.04 mg/kg,propofol TCI(CT=3μg/ml)and TCI of sufentanil,remifentanil or fentanyl(CT=0.5,5 and 5 ng,ml respectively in the 3 groups).Endobronchial intubation was facilitated with vecuronium 0.1 mg/kg.The patients were mechanically ventilated.PETCO2 was maintained at 30-40 mm Hg.Anesthesia was maintained with inhalation of sevoflurane(0.7-1.5 MAC)and TCI of sufentanil,remifentanil or fentanyl(CT=0.5,5 and 5 ng/ml respectively).Venous blood samples were taken from peripheral vein before anesthesia(T0,baseline),60 min after skin incision(T1),immediately(T2),24 h(T3)and 72 h(T4)after the end of operation for determination of the expression of CD3+,CIM+,CD8+on T cells and CD3-CD16+CD56+on natural killer cells by flow cytometry,CD4+/CD8+ratio,serum concentrations of IL-2 and IL-10 by ELISA.Results Compared with the baseline values,the CD4+T-lymphocytes and CIM+/CD8+ratio were significantly decreased at T2,while the CD3-CD16+CD56+NK cells were significantly increased in all 3 groups.The CD3+T-lymphocytes were significantly decreased at T2 as compared to the baseline value at T0 in SF and RF groups.The CIM+and CD3+T-lymphocytes were significantly decreased at T3 as compared with the baseline value in all 3 groups.Serum IL-2 concentration was significantly higher at T3 in SF group than in RF group.Serum IL-10 concentration was sismficantly higher at T4 in RF group than in SF group.Conclusion Sufentanil,remifentanil and fentanyl can depress cenular immune function to some extent in patients undergoing radical resection of esophageal cancer.