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In medical research,predictive models have been widely used to predict disease progression and identify high-risk populations in advance, especially in the prevention and diagnosis of chronic diseases. In ophthalmology, the predictive and diagnostic models for fundus diseases such as age-related macular degeneration and diabetic retinopathy have demonstrated expert-level accuracy. However, the application of predictive models is still in the exploratory stage as for myopia prevention and control. The establishment of a predictive model is helpful to identify the high-risk myopic children in advance, so that preventive measures such as adequate outdoor activities and reducing near work can be taken in time, which is of great significance to prevent or slow down the occurrence and development of myopia. Because the mechanism of myopia has not been fully elucidated, there are still challenges and limitations in the selection of application objects, predictors and predictive outcomes. This paper reviews the research progress of different types of myopia predictive models in order to provide reference for further development and improvement.
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The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase, which is widely studied in histone methylation modification. It can promote epigenetic gene silencing and mediate the occurrence of tumors through a variety of regulatory mechanisms. The gain-of-function and loss-of-function mutations of EZH2 have been confirmed in many cancers. At present, with the extensive attention paid to the regulatory role of EZH2 in epigenetic mechanism, the exact way in which EZH2 imbalance affects the pathogenesis of hematologic malignancies remains to be clarified. This article reviews the pathogenetic role of EZH2 in hematological tumors, and hope to find new targets for the prevention and treatment of hematological tumors.
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Objective:To evaluate the accuracy and stability of Eye-Monitor, a smart wearable device, in quantifying environmental risks related to myopia.Methods:A diagnostic test study was conducted.Forty-two subjects aged 18-25 years old were recruited from Shandong University of Traditional Chinese Medicine in December 2021.Forty-two Eye-Monitors were selected from 80 devices using the simple random sampling method.Static and dynamic tests were carried out to compare environmental risks related to myopia.The static tests included measurements under different working distances, different head tilt angles when sitting, and different light intensities.The dynamic tests included measurements under different near-work time, different outdoor activity time, different time watching computers, and different phone viewing time.Eye-Monitor with the largest sum of absolute values of total relative error was selected, Spearman rank correlation analysis was used to analyze the correlation between the set values and Eye-Monitor measurements, and the accuracy of the objectively measured values was evaluated by Bland-Altman consistency analysis.The stability of the objectively measured values from Eye-Monitor was evaluated by the coefficient of variation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-KS-2021005KY). Written informed consent was obtained from each subject.Results:There were significant correlations between the measured values and setting values in the working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time viewing phones ( rs=0.999, 0.998, 0.999, 0.998, 0.976, 0.959, 0.992, 0.997; all at P<0.001), with the 95% limits of agreement (LoA) of-1.23-2.32 cm, -1.49-4.24°, -13.90-26.90 lx, -6.46-0.11 minutes, -4.50-1.20 minutes, -4.01-1.34 minutes, -2.54-1.94 minutes and-2.15-0.45 minutes, respectively.More than 95% of dots were within the clinically acceptable LoA.The coefficients of variation of the measured values ranged from 1.23%-2.99%, 2.39%-8.25%, 0.87%-8.03%, 1.49%-12.52%, 6.63%-13.59%, 0.00%-14.15%, 1.20%-8.33 and 1.49%-12.51%, respectively, showing good stability.Eye-Monitor had good accuracy in measuring outdoor light intensity (95% LoA: -336.50-130.00 lx). Conclusions:The smart wearable device Eye-Monitor can be used to objectively monitor working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time watching phones, which are with good accuracy and stability.
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【Objective】 To analyze the clinical characteristics of stone culture and preoperative urine culture of patients with renal calculi in Songjiang area of Shanghai and the relationship with postoperative infection. 【Methods】 The clinical data of 213 patients with kidney stones treated at our hospital during Jan.2020 and Jun.2022 were retrospectively analyzed. All patients underwent preoperative clean midcourse urine culture, drug sensitivity test and stone culture. The gender difference between male and female patients and the difference in postoperative infection between stone/bacterial culture positive and negative patients were analyzed. 【Results】 Among the 213 patients, 47(22.1%) had positive urine culture, and the most common bacterium was Escherichia coli (20 strains, 42.6%). The proportion of Escherichia coli was significantly higher in female patients than in male patients [12 strains (48.0%) vs.8 strains (36.4%), P<0.05], while the proportion of Klebsiella pneumoniae was significantly higher in male patients than in female patients [5 strains (22.7%) vs. 3 strains (12.0%), P<0.05]. Drug sensitivity results showed the main Gram-negative bacteria were highly resistant to ampicillin/sulbactam, cefazolin and cefuroxime, but sensitive to imipenem, kanamycin and piperacillin/tazobactam. The main Gram-positive bacteria were highly resistant to clindamycin, erythromycin and levofloxacin, but sensitive to vancomycin, teicoplanin and linezolid. Stone culture was positive in 31 cases (14.6%), and the most common bacterium was Proteus mirabilis (9 strains, 29.0%). However, there was no significant difference in the main bacterial spectrum between male and female patients. The positive rate of urine culture/stone culture in patients with postoperative fever/urosepsis was significantly higher than that in patients with negative urine culture/stone culture (P<0.05). 【Conclusion】 Escherichia coli is the main urinary spectrum of patients with kidney stones in Songjiang area, which is greatly different from the stone culture results. In clinical practice, etiological detection and antibiotics are necessary to reduce the occurrence of postoperative infection.
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Objective@#To investigate the value of combined stool syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 ( TFPI2) gene methylation testing in the early screening of colorectal cancer.@*Methods @#106 patients with colorectal cancer (colorectal cancer group) ,75 patients with advanced adenoma ( advanced adenoma group) and 35 patients with non-advanced adenoma (non-advanced adenoma group) were selected as study subjects,and 153 patients with other gastrointestinal disorders and 182 patients with negative colonoscopy results during the same period were selected as the control group.The quantitative methylation-specific PCR(qMSP) method was used to detect SDC2 and TFPI2 gene methylation in the stool specimens of all subjects.The sensitivity and specificity of the combined SDC2 and TFPI2 gene methylation assay for the detection of colorectal cancer and adenoma were evaluated using colonoscopy and pathology results as the gold standard. @*Results @#Among 106 patients with colorectal cancer, the sensitivity of combined methylation test was 93. 4% ; among 75 patients with advanced adenoma,the sensitivity of combined methylation test was 62. 7% ; among 35 patients with non-advanced adenoma,the sensitivity of combined methylation test was 34. 3% ; the specificity of the combined SDC2 and TFPI2 gene methylation test for colorectal cancer and adenoma screening was 94. 6%.@*Conclusion@#The combined SDC2 and TFPI2 gene methylation test has high sensitivity for colorectal cancer and its early lesions,and it also maintains high specificity.
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Objective:To present the clinical characteristics and treatment on patients with ectopic adrenocorticotropic hormone(ACTH) syndrome (EAS) caused by the retroperitoneal paraganglioma.Methods:The clinical data of a case of EAS caused by retroperitoneal paraganglioma were analyzed retrospectively, and the related literature at home and abroad was reviewed.Results:The 53-year-old female patient was admitted to endocrinology department due to a fifteen-year history of hypertension, accompanied by fatigue for three months, headache and dizziness for one month. The laboratory data demonstrated severe hypokalemia, high level of serum and urinary cortisol, while the ACTH level remained unsuppressed. The 24 h urinary vanillyl mandelic acid (VMA) and serum free methoxyepinephrine (MNs) level were elevated. The abdominal computed tomographic scan suggested a retroperitoneal mass next to the abdominal aorta. After the retroperitoneal tumor resection was performed, immunohistochemical staining of the tumor revealed Syn (+ ), CgA (+ ), ACTH (focal + ). By the retrospective analysis of 22 similar cases from 16 papers and the case summarized above, we found that most patients with EAS caused by the paraganglioma could demonstrate the typical clinical features of Cushing′s syndrome, while lack of the manifestation of paraganglioma. Therefore, preoperative preparations for paraganglioma were usually neglected.Conclusions:Ectopic ACTH syndrome (EAS) originating from paraganglioma is very rare. To improve the diagnosis rate, examination for catecholamine, MNs and 24 h urinary VMA before surgery in patients with EAS is suggested. Considering surgical resection as the optimal treatment, comprehensive preoperative preparations for both paraganglioma and Cushing′s syndrome are significant. A genetic test for pheochromocytoma/ paraganglioma and lifelong postoperative follow-up are also recommend.
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Objective:To study the amino acid and codon usage profile of HIV-1 Env gene in donors whose serum exhibit highly broad cross-neutralizing activity. Methods:The samples were divided into highly broad cross-neutralizing activity group (hBCN + group) and non-highly broad cross-neutralizing activity group (hBCN - group) based on whether the neutralization breadth was higher than 90% or not. Full-length Env genes were amplified by single genome amplification (SGA) method from patients′ plasma samples, and the characteristics of Env sequences in hBCN + group were compared with hBCN - group. The correspondence analysis (COA) on relative amino acid usage (RAAU), adaptability to host based on similarity index D( A, B) and relative synonymous codon usage (RSCU) values of Env genes (hBCN + and hBCN -) with respect to human host RSCU were analyzed. Results:Correspondence analysis showed that the RAAU data of hBCN + group and hBCN - group were distributed along the two main axes to form two relatively separated clusters, indicating that the Env genes of the two groups had relatively unique amino acid usage patterns; the similarity index calculation results showed that hBCN + group (0.097) was lower than the hBCN - group (0.102), in addition, the Env gene of the hBCN + group had less frequency of similarly selected codons with human host system compared to hBCN - group. Conclusions:Env genes in hBCN + group and hBCN - group may have relatively unique amino acid usage patterns, and virus strains in hBCN + group are less adaptable to the host than those in hBCN - group.
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Objective:To observe the effect of goal-oriented management of continuous monitoring of regional cerebral oxygen saturation (rSO 2) on early postoperative neurocognitive disorders (PND) in elderly spinal surgery patients. Methods:From November 2018 to July 2019, 60 patients undergoing posterior lumbar interbody fusion in the Second Hospital of Shanxi Medical University were selected and randomly divided into control group and intervention group, 30 cases in each group. RSO 2 was recorded before anesthesia induction (T 0), 10 min after anesthesia induction (T 1), 10 min after prone position (T 2), 10 min after spinal decompression (T 3), 30 min after spinal decompression (T 4) and 10 min after extubation (T 5); The basic value of rSO 2, the minimum value of rSO 2 (rSO 2min), the average value of rSO 2 (rSO 2mean) and the maximum percentage of decrease of rSO 2 (rSO 2% max) were recorded. When rSO 2 <55% or rSO 2% max >10% and the duration was longer than 15 s, the intervention group took measures such as adjusting head position, adjusting blood pressure, increasing FiO 2 and respiratory parameters, increasing P ETCO 2 until rSO 2 returned to the required range; The control group did not interfere with the intraoperative rSO 2. Neuropsychological tests were used to evaluate the cognitive function of the two groups 7 days after operation. The patients were followed up 30 days after operation with the revised cognitive function telephone questionnaire (TICS-M). The incidence of postoperative neurocognitive impairment (PND) was recorded. The perioperative data and postoperative adverse reactions of the two groups were recorded. Results:At T 3 and T 4, the rSO 2 of the intervention group was significantly higher than that of the control group ( P<0.01), the intraoperative rSO 2min and rSO 2mean of the intervention group were higher than the control group, and the rSO 2%max was lower than the control group ( P<0.05). The incidence of PND 7 days after surgery, extubation time, postanesthesia care unit (PACU) stay time, hospital stay and postoperative adverse reactions in the intervention group were lower than those in the control group ( P<0.05). There was no significant difference in the incidence of PND 30 days after operation between the two groups ( P>0.05). Conclusions:The goal-oriented management of rSO 2 can reduce the incidence of early postoperative PND in elderly spine surgery patients, which is conducive to the rapid recovery of patients after surgery.
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Objective:To analyze the potential specificity of broad neutralizing antibodies (bNAbs) in one patient (DRVI01) with chronic HIV-1 infection.Methods:Sequences of the envelope glycoprotein (Env) obtained from DRVI01 at different time points were analyzed by comparing with the key amino acids of reported HIV-1 bNAbs in HIV Database. After reverse mutation of key amino acids that had frequently mutated to wild type, the neutralizing sensitivity of autologous plasma against wild-type and mutated Env-pesudoviruses was compared and the potential bNAbs in DRVI01 were speculated.Results:Reported key amino acids of 10 bNAbs classes were detected in 155 Env sequences derived from DRVI01. Frequent mutations were found in key amino acids of two bNAbs classes of gp41 fusion domain and gp120/gp41 interface. Neutralizing sensitivity of the contemporaneous autologous plasma and the plasma collected at the next time point against the mutated pesudoviruses was significantly increased as compared with wild-type pesudoviruses.Conclusions:Potential NAbs with similar key amino acids to those of gp41 fusion domain and gp120/gp41 interface might present in the HIV-1 infected patient with broad neutralizing antibodies.
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Objective To compare the efficacy of sertraline hydrochloride combined with risperidone or quetiapine in the treatment of schizophrenia.Methods Eighty-six patients with schizophrenia in Ningbo Psychiatric Hospital were selected and divided into observation group and control group according to the order of admission.The observation group was treated with sertraline hydrochloride combined with quetiapine , and the control group was treated with sertraline hydrochloride combined with risperidone.The clinical symptoms score,clinical efficacy and adverse reactions were compared between the two groups.Results Before treatment,the negative symptoms,positive symptoms,psychopa-thology,total score between the two groups had no statistically significant differences (all P>0.05).After treatment, the negative symptoms ,positive symptoms,psychopathology and total scores of the observation group were (13.43 ± 1.27)points,(11.26 ±1.05)points,(13.54 ±1.84)points and(46.48 ±4.52)points,respectively,which were significantly lower than those of the control group[(16.87 ±1.98)points,(15.48 ±1.63)points,(18.35 ±2.04)points, (58.25 ±5.76)points](t=9.590,14.272,11.481,10.541,all P<0.05).The total effective rate of the observation group was significantly higher than that of the control group [93.02%(40/43) vs.67.44%(29/43)](χ2=8.871, P<0.05).There was no statistically significant difference between the two groups in the incidence rate of adverse reactions (P>0.05).Conclusion Sertraline hydrochloride combined with quetiapine in the treatment of schizophrenia can improve the clinical symptoms of patients ,the clinical efficacy is good ,with mild adverse reactions.
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Objective To research the changes of bile dynamics and plasma levels of cholecystokinin ( CCK ) and vasoactive intestinal peptide ( VIP ) in post-cholecystectomy patients. Methods Twenty-nine post-cholecystectomy patients were selected as observation group, including 14 patients combined with bile duct dilatation and 15 without bile duct dilatation. Another 17 healthy subjects were enrolled as the control group. They were assessed with quantitative 99mTc-EHIDA hepatobiliary scintigraphy to determine bile dynamics. Plasma levels of CCK and VIP were measured by enzyme-linked immunosorbent assay. Results Scintigraphic analysis demonstrated that the time to maximum counts and half excretion of liver were no significantly different among the three groups ( all P>0. 05). The developing time of common hepatic duct, time of maximum counts of common bile duct, half excretion of common bile duct, developing time of duodenum, hepatic portal and duodenum transit time significantly increased in the bile duct dilatation group compared with those of the control group ( all P<0. 05). Development time of duodenum, hepatic portal and duodenum transit time were significantly less in the non-bile duct dilatation group compared with those in the bile duct dilatation group and control group (all P<0. 05). Fasting plasma levels of CCK and VIP were no significantly different among the three groups ( all P>0. 05 ), while postprandial plasma levels of CCK and VIP were significantly higher in the bile duct dilatation group compared to those in the other two groups ( P<0. 05). Conclusion After cholecystectomy, the flow and velocity of bile in bile duct and intestine increases during the interdigestive period for patients without bile duct dilatation, while for patients with bile duct dilatation, bile remains in common bile duct and is blocked from intestine, with gastrointestinal hormone regulation disorder.
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This article reviews studies on the heredity of personality disorders and family environment factors from the population-based studies, and summarizes the interaction between genetic factors and environmental factors. Studies have shown that there is a genetic basis for personality disorders, including family studies, twin studies, and neurophysiological studies. In addition, environmental factors, including social psychological factors, also play an important role in the development of personality disorder. In sum, the occurrence of personality disorder is the result of interactions between genetic factors and environmental factors. This paper snmmarizes sresearch on personality disorders, and investigates the role of interaction between genetic and environmental factors in the development of personality disorders. Such evidence has implications for effective prevention and intervention of personality disorders.
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Objective To study the clinical effect of sequential therapy by intravenous fat emulsion and hemoperfusion in patients with severe organophosphorus pesticide poisoning. Methods Seventy-two patients with severe organophosphorus pesticide poisoning were selected, and the patients were divided into sequential therapy group (36 cases) and conventional therapy group (36 cases) by random digits table method. All the patients were given conventional therapy including gastrolavage, purgation, fluid infusion, atropine, pralidoxime chloride, anti- infection, breath support and hemoperfusion. The patients in sequential therapy group were given intravenous fat emulsion before hemoperfusion. The clinical effect was compared between 2 groups. Results There were no statistical differences in the serum cholinesterase activity on admission and in the first day after treatment between 2 groups (P>0.05). The serum cholinesterase activities in the second, third and seventh day after treatment in sequential therapy group were significantly higher than those in conventional therapy group: (456.3 ± 45.6) U/L vs. (391.3 ± 39.8) U/L, (862.3 ± 96.2) U/L vs. (614.7 ± 78.5) U/L and (1950.9 ± 366.7) U/L vs. (1543.6 ± 285.9) U/L, and there were statistical differences (P<0.05). The total doses of atropine applied and length of stay in sequential therapy group were significantly less than those in conventional therapy group: (85.4 ± 36.2) mg vs. (104.7 ± 45.3) mg and (10.5 ± 4.2) d vs. (13.6 ± 6.2) d, and there were statistical differences (P<0.05). The recovery rate in sequential therapy group was significantly higher than that in conventional therapy group:97.2%(36/36) vs. 80.6%(29/36), and there was statistical difference (P<0.05). Conclusions Sequential therapy by intravenous fat emulsion and hemoperfusion can improve the serum cholinesterase activity, and decrease the total dose of atropine in patients with severe organophosphate pesticide poisoning.
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Objective To investigate the antibiotic resistance, virulence genes, and sequence types of Enterococcus faecium ( E. faecium) strains isolated from children under 3 years old in Sui county, Henan province. Methods Kirby-Bauer antibiotic testing was performed to analyze the antibiotic sensitivi-ties of E. faecium strains to 15 common antibiotics. PCR analysis was used to detect the virulence genes car-ried by the E. faecium strains. Multilocus sequence typing ( MLST) was performed for the typing of E. faeci-um strains. Results Forty-seven E. faecium strains were isolated from 120 stool samples collected from chil-dren under 3 years old in Sui county, Henan province, of which 95. 7% were antibiotic-resistant strains. Most of the isolated E. faecium strains were resistant to rifampicin, accounting for 91. 5% (43/47) of all isolates, followed by those resistant to erythromycin and tetracycline, which accounted for 68. 1% (32/47). Moreover, high resistance rates to those antibiotics commonly used in clinical treatments of E. faecium infec-tion including β-lactam and aminoglycosides antibiotics were observed. Those strains resistant to more than three kinds of antibiotics belonged to the same clonal complex including 12 strains of clonal complex 17 ( CC17) harboring the virulence gene of hyl. All of the isolated E. faecium strains were susceptible to vanco-mycin, linezolid, chloromycetin and nitrofurantoin. Conclusion The E. faecium strains isolated from chil-dren under 3 years old in Sui county, Henan province were multi-antibiotic resistant. There were drug-resist-ance strains belonging to the CC17 and carrying the virulence gene of hyl.
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BACKGROUND:Systemic lupus erythematosus is an autoimmune disease characterized as an emergence of a variety of autoantibodies in serum and multi-system and multi-organ lesions. Currently, there is a lack of effective treatment options, and umbilical cord mesenchymal stem cel s are a promising therapy for systemic lupus erythematosus based on cel biological roles. OBJECTIVE:To observe the therapeutic efficacy of human umbilical cord mesenchymal stem cel transplantation in the treatment of systemic lupus erythematosus in mice. METHODS:Human umbilical cord mesenchymal stem cel s were isolated and cultured fol owed by labeling with DiR fluorescence. Experimental mice were divided into normal control group (C57BL mice), model control group (C57BL/lpr mice), low-, medium-and high-dose umbilical cord mesenchymal stem cel therapy groups (C57BL/lpr mice), with 10 mice in each group. Mice in the low-, medium-and high-dose groups were respectively injected 0.5×106, 1×106, 2×106 human umbilical cord mesenchymal stem cel s, once a week, for 3 consecutive weeks. At the end of treatment, blood samples were col ected to measure antinuclear antibody, anti-histone antibody, anti-double stranded DNA antibody changes;OPG and Foxp3 gene expression changes were detected by quantitative PCR method. RESULTS AND CONCLUSION:After treatment, the levels of anti-nuclear antibodies, anti-histone antibodies and anti-double stranded DNA antibodies in the peripheral blood of mice were al declined in the low-, medium-and high-dose groups, while the number of peripheral blood CD4+CD25+T cel s was significantly elevated. OPG and Foxp3 gene expression was also increased dramatical y in the low-, medium-and high-dose groups, which was similar to that in the normal control group and significantly different from that in the model control group (P<0.01). Experimental findings demonstrate that after transplantation of human umbilical cord mesenchymal stem cel s, al relevant indicators in C57BL/lpr mice recovered to the normal levels, and the high-dose treatment group had the most obvious effect.
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Objective:To analyze the chicken egg-white extracts were co-cultured with cells whether elevated stem cells protein,whether the cells transformation into stem cell.Methods:Four kinds of cells,making a common culture,a 50% chicken egg-white extract co-cultured for 3 days,cells were collected and frozen at -80 degrees,sending the company to do stem cell protein microarray.Results:C57-BMSC has three proteins occurred statistically significant change , TS-UC-MSC has one proteins occurred a statistically significant change ,293T has one protein occurred a statistically significant change ,and 293T-GFP has one protein occurred a statistically significant change.Conclusion:50% chicken egg-white extract co-cultured cells,the cells occurred the phenomenon of transformation into stem cells.
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Objective To investigate the effect of EST and EPBD on the gallbladder function.Methods Fifty-eight patients who underwent common bile duct lithotomy were divided into three groups,the EST major incision group (21),the EST minor incision group (20) and the endoscopic papillary balloon dilation group (17).Twenty healthy people were involved as the control group.The hepatobiliary dynamic imaging was used to evaluate the gallbladder function,indices including (1) Half time of liver excretion (TEX),(2)Peak time of common bile duct excretion (CBD Tup),(3)Gallbladder imaging time(GBVT),(4) Half time of gallbladder excretion (GBT1/2),(5)Gallbladder excretion fraction at the 30th minute (GBEF30min),(6) Gallbladder excretion rate at the 30th minute (GBER 30 min),(7)Duodenum imaging time (DUT),(8) Peak time of bile flowing in duodenal (DU Tup),(9) Bile ratio in gallbladder at the 30th minute(Fgb),(10)Bile ratio in intestinal at the 30th minute (Fsi).Effects of the three operative methods on the gallbladder function were evaluated.Results Compared with the other two treatment groups and control group respectively,the TEX of the EST major incision group was significantly shorter (P <0.05),CBD Tup,DUT and DU Tup appeared earlier (P <0.05),GBVT was delayed (P <0.001),GBT1/2 was shorter (P <0.001),GBEF 30 min was higher (P <0.001) and GBER 30 min was faster (P <0.001) in this group.Gallbladder and intestines ratio (Fgb,Fsi) at the 30th minute were significantly different (P <0.001) with Fgb reducing while Fsi increasing in this group,compared with others.Compared with the control group respectively,neither the minor incision group nor the EPBD group (P > 0.05) showed significant differences in these indices.Conclusion The storage function of gallbladder has been injured and excretion has been enhanced after EST major incision.Neither minor incision nor the EPBD leads to significant change in the gallbladder function.
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Objective To observe the effects of metformin on expression of Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK),nuclear factor-κB (NF-κB) and transforming growth factor β1 (TGF-β1) in cultured rat glomerular mesangial cells (MCs),and explore its renoprotective mechanisms.Methods MCs were cultured in the medium with normal glucose (group NG,5.6 mmol/L),high glucose (group HG,25mmol/L) and different concentrations of metformin (group M1,M2,M3).After 48 h exposure,the supernatants and MCs were collected.The expression of NF-κB and TGF-β1 mRNA was analyzed by real time-PCR.Total-AMPK,phospho-Thr-172 AMPK (p-AMPK),NF -κB p65 and TGF-β1 were visualized by Western blot.Results The real time-PCR and Western blot result showed MCs could express AMPK,NF-κB and TGF-β1 mRNA and protein.After stimulated by HG,the levels of intracellular NF-κB and TGF-β1 expressions were significantly increased compared with group NG (P < 0.05); The levels of NF-κB and TGF-β1 were significantly decreased in group M1,M2 and group M3 compared with group HG in a dose-dependent manner.After stimulated by HG,the level of intracellular p-AMPK were down-regulated compared with group NG(all P < 0.05); The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend (P < 0.05),while the level of total-AMPK protein was unchanged with exposure to HG or different concentrations of mefformin(P > 0.05).Conclusion Metformin can suppress the expression of NF-κB and TGF-β1 of glomerular MCs induced by HG via AMPK activation,which may partly contribute to its reno-protection.
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<p><b>BACKGROUND</b>The renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist - metformin have not been stated clearly. We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines. The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-β1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).</p><p><b>METHODS</b>MCs were cultured in the medium with normal concentration glucose (group NG, 5.6 mmol/L), high concentration glucose (group HG, 25 mmol/L) and different concentrations of metformin (group M1, M2, M3). After 48-hour exposure, the supernatants and MCs were collected. The expression of NF-κB, MCP-1, ICAM-1, and TGF-β1 mRNA was analyzed by real time polymerase chain reaction. Western blotting was used to detect the expression of AMPK, phospho-Thr-172 AMPK (p-AMPK), NF-κB p65, MCP-1, ICAM-1, and TGF-β1 protein.</p><p><b>RESULTS</b>After stimulated by HG, the expression of NF-κB, MCP-1, ICAM-1, TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG (P < 0.05). Both genes and protein expression of NF-κB, MCP-1, ICAM-1, TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P < 0.05). The expression of p-AMPK increased with the rising of metformin concentration, presenting the opposite trend, while the level of total-AMPK protein was unchanged with exposure to HG or metformin. Conlusion Metformin can suppress the expression of NF-κB, MCP-1, ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.</p>
Asunto(s)
Animales , Ratas , Proteínas Quinasas Activadas por AMP , Metabolismo , Células Cultivadas , Mesangio Glomerular , Biología Celular , Glucosa , Farmacología , Células Mesangiales , Metabolismo , Metformina , Farmacología , FN-kappa B , MetabolismoRESUMEN
Objective To explore the effect of different doses of irbesartan on osteopontin expression and fibrosis in diabetic rat kidney. Methods Sixty-three g-week old male Wistar rat were randomly divided into control group (Ctrl group,n=7),diabetes group (DM group,n=14),30 mg·kg-1d-1 hydralazine administrated group (DM+Hyd group,n=12),25 mg·kg-1·d-1 irbesartan administrated group (DM+Irb25 group,n=10),50 mg·kg-1 ·d-1 irbesartan administrated group(DM+Irb50 group,n=9) and 200 mg·kg-1·d-1 irbesartan administrated group (DM+Irb200 group,n=11).Four weeks after modeling,rats were administered with the corresponding dose of irbesartan.After 12 weeks,urinary albumin excretion rate (UAER),endogenous creatinine clearance rate (Ccr) were measured; morphology and collagen deposition in rat kidney were observed by PAS and Masson staining respectively; Ang Ⅱ content in kidney was measured by ELISA; renal tissue TGF-β1 and OPN mRNA expression were detected by real-time PCR. Results UAER and Ccr in the intervention groups of irbesartan were significantly decreased compared with DM group (P<0.05).UAER and Ccr in DM+Irb200 group were significantly lower than those in DM+Irb25 group and DM + Irb50 group (P<0.05).Glomerular hypertrophy,mesangial matrix expansion,tubular lesions and deposition of collagen fiber were siginficant in diabetic rats compared with Ctrl,and prevented after administration with different doses of irbesartan.Ang Ⅱ protein level and TGF-β1,OPN mRNA expression in renal tissue of diabetic rats were significantly higher than those in Ctrl group.Ang Ⅱ,TGF-β1,and OPN mRNA expression was significantly reduced after administration with different doses of irbesartan,and with the increase of irbesartan,the above indicators were decreased P<0.05).Renal local Ang Ⅱ level was positively correlated with OPN mRNA expression (r=0.74,P<0.01). Conclusion Irbesartan reduces renal TGF-β1,OPN mRNA expression by decreasing kidney local Ang Ⅱ in dose-dependent manner,and eventually reduces tubulointerstitial fibrosis,which plays a role in kidney protection.