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Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P<0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136~2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102~1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.
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BACKGROUND@#Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGFb1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. @*METHODS@#An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. @*RESULTS@#Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and a-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-b1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of profibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. @*CONCLUSION@#Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.
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Objective:To investigate the clinical efficacy of recombinant human epidermal growth factor combined with sodium hyaluronate eye drops in the treatment of cataracts after multifocal intraocular lens implantation and its effect on inflammation factors in tears and tear film stability.Methods:A total of 86 patients with cataracts who underwent multifocal intraocular lens implantation at Jinan 2 nd People's Hospital from July 2020 to January 2023 were included in this randomized controlled study. These patients were randomly divided into a control group and a combined group, with 43 patients in each group. Patients in the control group were administered sodium hyaluronate eye drops postoperatively, while patients in the combined group received a combination of recombinant human epidermal growth factor and sodium hyaluronate eye drops. All patients were treated for 1 month. Before and after treatment, the levels of inflammatory factors in tears, tear film stability-related indicators, and corneal endothelial cells were measured and compared between the two groups. Additionally, any adverse reactions experienced by the patients were recorded throughout the treatment period. Results:After treatment, the levels of interleukin-6 and tumor necrosis factor-α in the tear fluid of the combined group were (17.91 ± 2.45) μg/L and (72.14 ± 8.43) μg/L, respectively. These values were significantly lower than those in the control group, which were (24.63 ± 3.05) μg/L and (86.97 ± 9.85) μg/L, respectively ( t = 11.26, 7.50, both P < 0.001). Additionally, the fluorescein staining score for corneal damage in the combined group was (2.34 ± 0.37) points. This was significantly lower than the score of (3.42 ± 0.48) points observed in the control group ( t = 11.69, P < 0.001). Tear break-up time and Schirmer I Test in the combined group were (8.68 ± 0.96) seconds and (9.31 ± 1.04) mm/5 minutes, respectively. These values were significantly higher than those in the control group, which were (7.81 ± 0.89) seconds and (7.14 ± 0.86) mm/5 minutes, respectively ( t = -4.36, -10.54, both P < 0.001). Furthermore, the corneal endothelial cell density and the proportion of hexagonal cells in the combined group were (2 514.09 ± 259.31) counts/mm 2 and (41.67 ± 5.05)%, respectively. These values were significantly higher than those in the control group, which were (2 244.82 ± 253.37) counts/mm 2 and (36.75 ± 4.96)% in the control group ( t = -4.87, -29.45, both P < 0.001). The incidence of adverse reactions in the combined group was 11.63% (5/43), which was significantly higher than 6.98% (3/43) in the control group ( χ2 = 0.55, P > 0.05). Conclusion:The combination of recombinant human epidermal growth factor with sodium hyaluronate eye drops following multifocal intraocular lens implantation in patients with cataracts effectively decreases the levels of inflammatory factors in tear fluid. This treatment regimen also enhances tear film stability, promotes the repair of injured corneal tissue, and is highly safe.
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Antibody-drug conjugates (ADCs) are conjugated by a linker between an antibody drug targeting a specific antigen and a payload, such as a small cytotoxic drug. ADCs combine the potent killing effect of traditional small cytotoxic drugs with the tumor targeting property of antibody drugs. As of February 2022, the U.S. Food and Drug Administration (FDA) had approved 12 ADC antitumor agents. Based on the analysis of clinical pharmacology review reports of approved ADC drugs combined with relevant guidelines, it is found that in the development of ADC, in addition to the general research in clinical pharmacology, there are special considerations in dose selection and dose modification for special population due to the special anti-tumor mechanism of ADC. It is hoped that this paper will be enlightening to domestic researchers when developing ADC.
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Objective:To investigate the effect of mind mapping on the discharge readiness of patients undergoing first coronary stent implantation, so as to provide basis for seeking effective discharge guidance in clinical practice.Methods:One hundred patients who were hospitalized in the Department of Cardiology, the Second Affiliated Hospital of Dalian Medical University from December 2019 to August 2020 and who underwent coronary stent implantation for the first time were selected as the study objects. They were divided into the control group and the experimental group with 50 cases in each group by the random number table method. The control group was given routine discharge guidance, and the experimental group was given discharge guidance using mind mapping. Readiness for Hospital Discharge Scale and Quality of Discharge Teaching Scale were used to compare the differences of discharge readiness and discharge guidance quality between the two groups after intervention.Results:The personal status, adaptability, predictive support and the total score of discharge readiness in the experimental group were (25.18 ± 3.79), (45.24 ± 3.63), (36.62 ± 3.63), (107.04 ± 8.92) points, which were all higher than those in the control group (23.34 ± 3.04), (41.68 ± 3.62), (35.14 ± 2.14), (100.16 ± 7.36) points, with statistically significant differences ( t values were -4.91--2.48, all P<0.05). The actual acquired content, guiding skills and results, total scores of discharge guidance quality of patients in the experimental group were (56.66 ± 6.06), (94.46 ± 4.33), (151.12 ± 8.26) points, which were all higher than those in the control group (45.38 ± 9.19), (89.44 ± 10.87), (134.82 ± 14.31) points, with statistically significant differences ( t values were -7.25, -3.03, -6.97, all P<0.05). Conclusions:Mind mapping can effectively improve the discharge preparation degree and discharge guidance quality of patients undergoing coronary stent implantation for the first time, and it is a simple and practical discharge guidance tool.
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Objective:To understand the level of thirst distress in heart failure and analyze its influencing factors, in order to provide a theoretical basis for implementing the intervention measures to alleviate patients′ thirst distress.Methods:A total of 187 patients with heart failure who met the inclusion criteria from the First Affiliated Hospital and the Second Affiliated Hospital of Dalian Medical University from November 2019 to October 2020 were selected as the research objects. The General Information Questionnaire, Thirst Distress Scale-Heart Failure, Generalized Anxiety Disorder 7-item Scale, Patient Health Questionaire-9 and Brief Illness Perception Questionnaire were used to investigate heart failure patients. Multiple linear regression was used to explore the influencing factors of heart failure patients′ thirst distress.Results:The score of thirst distress in heart failure patients was (23.95 ± 4.21), multiple stepwise linear regression analysis showed that heart function grade, diuretic usage, anxiety, depression and disease perception were the influencing factors of thirst distress in patients with heart failure, which explained 41.9% of the thirst distress in heart failure patients.Conclusions:The thirst distress of heart failure patients is in the middle level, and its thirst distress is affected by many factors, clinical medical staff should pay attention to the severity of thirst distress in patients with heart failure, actively develop different intervention measures to reduce patients′ thirst sensation, and explore effective schemes to alleviate thirst distress in patients with heart failure.
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Antidepressants are mainly used to treat mental illnesses. Traditional antidepressants mainly target monoamine neurotransmitters, but these drugs are slow to be effective and cannot meet clinical needs. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis and focus on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in clinical practice. This article mainly summarizes the research mechanisms and treatment programs of new antidepressants, and briefly reviews common rapid-acting antidepressants.
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Objective:To investigate the significance of Th1/Th2 cytokines in prognostic stratification of acute myeloid leukemia (AML).Methods:A total of 83 patients with newly diagnosed AML from June 2017 to April 2019 in the First People's Hospital of Yunnan Province were collected. According to the Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia (non-acute promyelocytic leukemia) (2017 edition), AML patients were divided into poor prognosis group (45 cases), moderate prognosis group (19 cases), and good prognosis group (19 cases); moderate prognosis plus poor prognosis was treated as the not good prognosis. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the expression differences of Th1/Th2 cytokines in peripheral blood of different prognosis groups; cytokines with statistical differences among different prognosis groups were selected, and the cut-off value of AML patients with different prognostic stratification distinguished by cytokines was determined by using receiver operating characteristic (ROC) curve. Finally, patients were divided into ≥ cut-off value group and <cut-off value group according to the cut-off value, and then the association of both groups with the prognostic stratification in guideline was also analyzed. Results:The median expression level of tumor necrosis factor (TNF)-β of patients in moderate prognosis group [3.80 pg/ml (2.75 pg/ml, 15.32 pg/ml)] was higher than that of patients in poor prognosis group [2.78 pg/ml (1.28 pg/ml, 3.36 pg/ml)] and good prognosis group [1.61 pg/ml (0.83 pg/ml, 3.04 pg/ml)] ( U=216, P=0.02; U = 312, P < 0.05); the median expression level of TNF-β in good prognosis group was lower than that in poor prognosis group ( U = 562, P = 0.048). There were no statistically significant differences in the expression levels of Th1/Th2 cytokines of AML patients with different prognostic stratification (all P>0.05).The cut-off value of TNF-β was 3.23 pg/ml in good prognosis group and moderate prognosis group, the area under the ROC curve was 0.866 (95% CI 0.753-0.978, P < 0.05); among 26 patients with TNF-β≥ 3.23 pg/ml, 25 (96.2%) patients had not good prognosis. The cut-off value was 3.62 pg/ml for distinguishing between moderate prognosis group and poor prognosis group, the area under the ROC curve was 0.747 (95% CI 0.610-0.884, P = 0.02); 18 (100%) patients with TNF-β≥ 3.62 pg/ml had not good prognosis. The cut-off value was 2.19 pg/ml for distinguishing between good prognosis group and not good prognosis group, the area under the ROC curve was 0.719 (95% CI 0.595-0.842, P = 0.04); among 53 patients with TNF-β≥2.19 pg/ml, 46 (86.8%) patients had not good prognosis. Conclusions:The high expression of TNF-β may indicate that the prognosis of AML patients is not good. When the level of TNF-β was equal or greater than 3.62 pg/ml, it may contribute to the prognostic stratification of AML patients.
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The clinical trial of OBCA (OCALIVA) in the treatment of primary biliary cirrhosis (PBC) shows its efficacy. As it is difficult to conduct sufficient clinical studies in moderate and severe hepatic impairment population, the applicant and the FDA theorem have different opinions based on the same model, such as population PK, exposure-response and physiologically-based PK (PBPK). The applicant considers that the increase in the exposure of drug in liver tissue is limited, and there is no need for dose adjustment, that is, 5 mg, once a day. FDA believes that the influencing factors of the PBPK model have not been fully taken into account and the validation of the PBPK is not robust with a wide variability, and there is also a risk of high blood drug exposure in patients. It is recommended to significantly reduce the dose, that is, 5 mg, once a week, no more than 10 mg, per week at least 3 days interval, and accordingly written into the medication instructions. After approval many patients with hepatic impairment did not take medicine according to the instructions, therefore overdosed, resulting in death. The results fully prove that the original considerations and decisions of FDA have been verified, and the experience and lessons of this example once again suggest that modeling and simulation need bold assumptions and careful verification.
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Objective To explore the risk factors and early intervention methods of obesity in children aged 5-14 years in Xuzhou. Methods Children from 3 urban areas were randomly selected from Xuzhou City for physical measurement. The children were divided into obese group and normal group based on 2 standard deviations of WHO standard weight. A questionnaire survey was used to assess the risk factors for obesity in children aged 5 to 14, and early intervention measures were put forward. Results The detection rate of obese children in this group was 53.00%. Single factor analysis showed that breastfeeding, supplementary food addition at 4 and 6 months, fast eating, preference for dessert, drinks and fried foods, sleep time <8h/d, dislike of sports, daily TV watching time ≥ 2h / d, obesity of father and mother, mother's education level, and parents' obesity cognition were related to obesity in children aged 5-14 (P <0.05) . Logistic regression analysis revealed that artificial feeding, fast eating, deep frying, sweet drinks, mother's education, father's obesity and mother's obesity were high risk factors of children's obesity. Conclusion The incidence of obesity in children aged 5-14 years old in Xuzhou was high. Early feeding mode, children's preference for fried desserts, parents' obesity and mother's education level were the main risk factors for children's obesity. It is suggested that communities promote more health education on children’s obesity.
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Objective@#To study the prevalence of high-risk HPV (HR HPV) in women who accepted cervical cancer screening in Beijing and its distribution in cervical precancerous lesions.@*Methods@#From January 2014 to March 2015, all women aged 35-64 years old and received free screening in institutions of cervical cancer in Beijing were recruited. Stratified cluster random sampling method was used in selecting 31 091 women for gynecological examination and genotyping of HR-HPV. Those positive for HR-HPV (except for HPV 16/18) were examined for cervical cell. For those atypical squamous cells of uncertain significance (ASCUS) and above, who were positive for HPV 16/18 and with uncertain results for cervical cell, were transferred for colposcopy examination. For those with suspicious or abnormal results for colposcopy, were transferred for histopathology. The prevalence of HR-HPV, cervical cancer and precancerous lesions among the participants were analyzed.@*Results@#Totally 31 091 women aged from 35-year-old to 64-year-old, with 44.3% (13 780 women) in the 35-49 age group and 55.7% (17 311 women) in the 50-64 age group. 66.1% (20 536 women) were rural women. The infection rate of HR-HPV was 7.4%(2 305 cases) among the women. High-risk infection rates of HPV except HPV 16/18 were 5.7% (1 758 cases), and multi-infection rate was 1.5% (477 cases). The highest infection rate was 7.9% (1 044 cases) among the 45-49 year-old and 50-54 year-old age groups (χ2=14.07, P=0.015). The rate in rural women was significantly higher than that of the urban women (6.2%, 507 cases; 7.9%, 1 798 cases) (χ2=25.75, P<0.001). The proportion of HPV16, HPV18, HPV52, HPV51, HPV58 was 17.0% (391 cases), 6.9% (161 cases), 8.6% (20 cases), 5.2% (12 cases) and 7.7% (18 cases), respectively. The detection rate of cervical cancer and precancerous lesions in the population was 395.6/100 000 (123 cases). In high-grade squamous intraepithelial lesions (HSIL), HPV16 and 18 infections accounted for 60.5% (72 cases) of all. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old group which were 1.5% (107 cases) and 25.2% (30 cases) (χ2=11.54, P=0.042).@*Conclusion@#Top five types of HR-HPV infection in women who accepted cervical cancer screening in Beijing were HPV16, 18, 52, 51 and 58. The infection rate of HPV16 and 18 increased significantly in HSIL women. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old age group.
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Objective To understand the cognition and acceptability of females on cervical cancer screening and preventive human papilloma virus(HPV) vaccine and to analyze the related influencing factors.Methods A total of 695 female outpatients were selected and conducted the investigation.Then the investigation data were statistically analyzed.Results The females knowing the cervical cancer screening accounted for 44.32% (308/695),the females receiving cervical cancer screening before accounted for 43.73% (297/695),the females knowing the HPV vaccine accounted for 17.70% (123/695) and the females willing to inoculating HPV vaccine accounted for 48.00%(59/123).TV and network were the main pathways for obtaining the information.The age,educational degree,and cognition on cervical cancer screening were the important factors affecting HPV vaccine cognition.Conclusion The females have high cognition and acceptability on cervical cancer screening,while have low cognition rate on HPV vaccine,but its acceptability is high.It is necessary to strengthen the health education and propaganda of preventing cervical cancer knowledge to boost the implementation of cervical cancer prevention and control work.
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Objective To investigate effects of diabetes mellitus (DM) on pharmacokinetics (PK) of cephradine (CED).Methods DM model was induced by iv.alloxan 60 mg·kg-1.A reversed phase HPLC internal standard method was developed for measurement of CED plasma concentration.After blood collection,rats were sacrificed to collect kidneys for calculating kidney index(KW/BW).DM and normal control (CTL) rats were randomly assigned to receive iv.or ig.CED at a dose of 180 or 90 mg·kg-1.The 3p97 program was used to calculate PK parameters.Results The developed HPLC method was validated to have high specificity,precision,recovery and good storage stability,and met requirements for PK study of CED.The CED in rats of both DM and CTL groups showed the iv.two-compartment PK and ig.one-compartment PK and followed the first-order kinetics.Following iv.dosing,a remarkably decreased t1/2β and MRT,increased CLt were evident in DM group as compared with CTL group (P < 0.05).After ig dosing,a significant decrease in t1/2k and t a remarkable increase in CLt and Cm=were observed for DM group as compared with CTL group (P < 0.05).The DM rats showed a trend of decreased t1/2ka vs CTL rats.There was no significant difference in the oral bioavailability between the two groups (P > 0.05).KW and KW/BW in DM group were increased remarkably compared with CTL group (P < 0.05).Conclusion The DM vs CTL results in faster absorption and elimination of CED in rats,but does not have significantly affect in oral bioavailability.The compensatory hypertrophy and hyperfunction of early-stage diabetic kidneys may constitute one of causes of quick elimination of CED in rats with DM.
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Objective To study the effect of the treatment of epiglottis cyst by Nd:YAG laser combined with clamp under electronic laryngoscope. Methods Under superficial anesthesia, ninety cases of epiglottis cyst complicated with a series of pharyngeal clinical symptoms which were treated by Nd:YAG laser combined with clamp guided under electronic laryngoscope. Results Eight patients were not reexamined, and the rest 82 patients were followed up after one month, the body sensation and laryngeal obstruction disappeared or relieved signiifcantly. After further conifrmation by laryngoscope, the cysts of 79 cases were disappeared, and 3 cases were considered residual, the cysts was clamped out and treated by biopsy forceps Laser, further checked after 2 months by laryngoscope, the cysts disappeared! 100%recovered. Conclusion Treatment of epiglottis cyst by Nd:YAG laser combined with clamp under electronic laryngoscope has many advantages such as clear vision, accurate positioning, less hemorrhage, less postoperative complications, less recurrence rate and less pain. Treatment is effective and worthy of clinical promotion.
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Objective To compare the clinical efficacy of nedaplatin and cisplatin combined with docetaxel in the treatment of cervical cancer.Methods 80 patients with cervical cancer were selected as the research subjects.According to different chemotherapy regimens,they were divided into observation group(40 cases)and control group(40 cases).The observation group adopted nedaplatin combined with docetaxel chemotherapy regimen,while the control group used cisplatin plus docetaxel chemotherapy regimens.The clinical curative effect,adverse reaction of chemotherapy,hospitalization related indicators,etc were compared between the two groups.Results The total effective rate of the observation group was 85.0%,which of the control group was 77.5%,the difference was not statistically significant(x2=0.739,P=0.739).The incidence rate of gastrointestinal reaction(Ⅰ-Ⅳ)in the observation group was 25.0%,which was lower than 82.5% in the control group(x2=26.560,P=0.000).The incidence rate of renal toxicity(grade Ⅰ-Ⅱ)of the observation group was 2.5%,which was lower than 17.5% of the control group(x2=5.000,P=0.025).The length of hospital stay of the observation group was(2.93 ±0.39)days,which was shorter than(4.97 ±0.81)days of the control group(t=14.352,P=0.000).The incidence rate of bone marrow inhibition(grade Ⅰ-Ⅱ)of the observation group was 43.0%,which was significantly higher than 25.0% of the control group(x2=4.381,P=0.036).1 year overall survival(OS),no local recurrence rate(LRF)and no distant metastasis survival rate(DMF)between the two groups had no statistically significant differences(all P>0.05).Conclusion Efficacy of nedaplatin or cisplatin combined with docetaxel in adjuvant chemotherapy of cervical cancer has similar prognosis,nedaplatin has less toxicity,and can shorten the time of hospitalization,patients are more likely to accept,it is worthy of clinical promotion.
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Objective To observe the effects of high-fat feeding on growth and the expression of insulin-like growth factor 1 (IGF-1),insulin receptor substrate 1 (IRS-1) in adolescent rats'liver with non-alcoholic fatty liver disease,and to elucidate the relationship between growth failure in adolescent rats with non-alcoholic fatty liver disease and IGF-1,IRS-1 turbulence.Methods Thirty-six Sprague-Dawley (SD) young rats of 21 days were randomly divided into normal control group(NC group,n =18) and high-fat feeding group(HF group,n =18).Non-alcoholic fatty liver disease(NAFLD) model was induced by feeding the SD rats with high-fat food.Immunohistochemistry was applied to detect the expression levels of IGF-1 and IRS-1 in liver tissue.The expressions of mRNA of IGF-1 and IRS-1 were measured by RT-PCR.Results Compared with NC group,the serum alanine amino transferase (ALT),total cholesterol (TC),triglyceride (TG) of HF group in the 6th,8 th,12th week were gradually increased.The serum ALT [(194.67 ± 11.15) U/L],TC [(1.81 ± 0.09) mmol/L],TG [(0.34 ± 0.05) mmol/L] contents of HF group at 8th week were higher than those at 6th week [(166.00 ± 22.01) U/L,(1.52 ± 0.22) mmol/L,(0.41 ±0.12) mmol/L,respectively],and the serum ALT[(213.0 ±27.67) U/L],TC[(2.15 ±0.37) mmol/L],TG[(0.38 ±0.15)mmol/L] contents of the 12th week were significantly increased compared with 6th week and 8th week.The constitution and body length of the HF group were lower than those of the normal control group.With time extended,the liver tissue steatosis,inflammation,the balloon like change of the liver tissue pathology of HF group in 6,8,12th week gradually increased.Immunohistochemistry results showed that HF group IRS-1 [(1.46 ± 0.23),(0.74 ± 0.17),(0.85 ± 0.31)],IGF-1 [(0.92 ± 0.02),(0.83 ± 0.02),(0.77 ± 0.03)] expression gradually decreased,the difference was statistically significant(F =36.024,P < 0.05).IGF-1 and IRS-1 mRNA expressions in HF group were consistent.Conclusion The liver tissue IGF-1 and IRS-1 are correlated with the weight and body length.The growth failure of young rats induced by high-fat feeding may be related to the decreased expression of IGF-1 and IRS-1.
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Objective To explore the protective role of lipoxin A4 (LXA4) during early process of atherosclerosis formation in rats with juvenile metabolic syndrome (MS).Methods Rat models of juvenile MS were established with 3-week Sprague-Dawley (SD) rats fed on high-carbonhydrates and high-fat diet for 6 weeks.The other qualified ones were randomly grouped into model group,LXA4 low-dose group,LXA4 middle-dose group,and LXA4high dose group,and a control group fed with normal forage.The low,middle,high-dose groups were injected different doses of LXA4 daily,while the model group and control group were injected with the same dose of isotonic NaCl solution for 2 consecutive weeks.After 2-week medication,the visceral adipose tissue were isolated by laparotomy and heart blood collected by thoracotomy under anesthesia,followed the fixation of thoracic and abdominal aortas in the immobilized rats.The mRNA expression level of inflammation cytokines interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),C-reactive protein (CRP) in the adipose tissue were determined by semi-quantitative reverse transcription PCR (RT-PCR),respectively.Secretions of IL-6,and TNF-α in serum were determined by enzyme linked immunosorbent assay (ELISA).Immunocytochemistry was used to label endomembrane and middle-membrane of thoracic aorta,and endothelial cell layer in each group and the ratios of thickness of endomembrane and middle-membrane were compared.Results Compared with the control group,weight,body length and abdominal circumference of juvenile MS rats increased significantly (all P < 0.05),and levels of fasting plasma glucose (FPG),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and insulin in models increased significantly (P < 0.05).RT-PCR showed that the mRNA expressions of inflammatory cytokines IL-6,TNF-α and CRP in adipose tissue in model rats were upexpressed (all P < 0.05).Compared with model rats,mRNA of IL-6,TNF-oα,and CRP in mid,high-dose rats were downexpressed (all P < 0.05),mRNA of TNF-α in low-dose rat downexpressed (all P < 0.05),and there were no significant differences between mRNA expressions of IL-6,CRP in low-dose and model rats according to statistics (all P >0.05).Compared with control group,inflammatory cytokines IL-6,TNF-α secreted in serum of model rats were increased significantly (all P < 0.05),and inflammatory cytokines secreted in serum of intervention rats were decreased significantly compared with model rats (P < 0.05).Pathological changes were as follows:HE staining:compared to model group,aortic tunica intima of model rats were remarkably thickened and endothelial cell layer was fragmented and incomplete,which was attenuated in each intervention group.The ratios of endomembrane and middle-membrane in rats:at the end of consecutive medication for 2 weeks,the ratios of endomembrane and middle-membrane in model rats were significantly greater than those of control group (P < O.05),and the ratios of endomembrane and middle-membrane in high-dose intervention rats were significantly smaller than those of the model group (P < 0.05),but still greater than control group,while there were no statistical differences between the ratios in low,middle-dose intervention rats and model rats (P > 0.05).Conclusions The increasing inflammatory cytokines are involved in early process of atherosclerosis formation in rats with juvenile MS.LXA4 by reducing the expression of inflammatory factor level in adipose tissue,thereby reducing the inflammatory cytokines in serum,alleviate the damage of arterial wall.
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Objective To discusse the effect of edaravone for brain tissue oxidative damage after cerebral hemorrhage through observing the hemorrhage rats back edema and the change of lipid peroxidation.Methods 150 healthy and clean male SD rats, were randomly divided to sham operation group,control group,treatment group,50 cases in each group,each group choose five time points,post operative 0.5 day,1 day,2 days,3 days, 4 days,observed different 10 rats at each time point.The intracerebral hemorrhage model was made by using the method of stereotactic autologous blood injection.The changes of water content, the content of MDA and the activity of superoxide dismutase were monitored in three groups at different time points.Results Surrounding the hematoma in the brain tissue around the hematoma after intracerebral hemorrhage in sham operation group,treatment group of postoperative day 1-4 days each time hematoma surrounding brain tissue water content was significantly lower than that in control group(P<0.05);Control group after 2 days of cerebral edema and reached the highest value;Sham operation group and treatment group of postoperative half of the day to 4 days each time the content of MDA were significantly lower than in control group ( P <0.05 );Sham operation group and treatment group postoperative half of the day to 4 days each time the brain tissue SOD activity was significantly higher than control group(P<0.05).Conclusion The effect is obvious that edaravone for cerebral hemorrhage rats brain tissue around hematoma edema, reduce cerebral hemorrhage rat tissue oxidative damage.
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The cyclization of 2,3-oxidosqualene is the key branch point of ergosterol and triterpenoid biosynthesis. Downregulation of 2,3-oxidosqualene metabolic flux to ergosterol in Saccharomyces cerevisiae may redirect the metabolic flux toward the triterpenoid synthetic pathway. In our study, primers were designed according to erg7 gene sequence of S. cerevisiae. Three fragments including 5' long fragment, 5' short fragment and erg7 coding region fragment were amplified by PCR. 5' long fragment consists of the promoter and a part of erg7 coding region sequence. 5' short fragment consists of a part of promoter and a part of erg7 coding region sequence. These fragments were inserted reversely into pESC-URA to construct antisense expression plasmids. The recombinant plasmids were transformed into S. cerevisiae INVSc1 and recombinant strains were screened on the nutritional deficient medium SD-URA. The erg7 expression level of recombinant strains, which harbored antisense expression plasmid of erg7 coding region, was similar to that of INVScl by semi-quantitative PCR detection. But erg7 expression level of recombinant strains, which harbored 5' long antisense fragment and 5' short antisense fragment, was significantly lower than that of the control. The results of TLC and HPLC showed that the ergosterol content of recombinant strains, which harbored 5' long antisense fragment, decreased obviously. The ergosterol contents of the others were almost equal to that of INVSc1. Lanosterol synthase gene expression was downregulated by antisense RNA technology in S. cerevisiae, which lays a foundation for reconstructing triterpenoid metabolic pathway in S. cerevisiae by synthetic biology technology.
ABSTRACT
<p><b>OBJECTIVE</b>To study the cytomorphologic features of anaplastic lymphoma kinase (ALK)-rearranged pulmonary adenocarcinoma.</p><p><b>METHODS</b>The morphologic features in 153 pulmonary adenocarcinoma cytology specimens encountered during the period from September, 2011 to April, 2015 in Shanghai Cancer Hospital were retrospectively reviewed. Fluorescence in-situ hybridization (FISH) and/or immunohistochemistry (Ventana D5F3) for ALK gene rearrangement were carried out. The samples studied included 34 pleural effusion specimens, 40 endobronchial ultrasound-guided transbronchial needle aspirates (EBUS-TBNA) and 79 fine needle aspirates of palpable masses on body surface.</p><p><b>RESULTS</b>Thirty-nine cases (25.5%) of ALK-rearranged samples were identified by FISH and/or immunohistochemistry, including 3 cases diagnosed by FISH and 36 cases by both technologies. The median age of the ALK-positive group was 50 years, significantly younger than that of the ALK-negative group (60 years old, P = 0.002). Only 4 of the ALK-positive patients were smokers, which was significantly less than that of the ALK-negative group (P < 0.01). In ALK-positive group, 3 cases showed cribriform pattern with prominent nucleoli, 3 cases showed cribriform pattern with mucin-rich cells and 8 cases showed extracellular mucus with mucin-rich cells. The above cytomorphologic patterns were significantly less common in ALK-negative tumors (P < 0.01).</p><p><b>CONCLUSIONS</b>ALK-rearranged lung adenocarcinoma is associated with certain distinctive morphologic patterns, including cribriform architecture, presence of prominent nucleoli, mucin-rich cells and extracellular mucus, which can be observed in cytology specimens (including conventional smears and cell block sections). These findings, when combined with clinical features, may give clues to detection of ALK-positive cases.</p>