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1.
Article in Chinese | WPRIM | ID: wpr-912575

ABSTRACT

Objective:The optimal allocation of resources is the focus of hospital administrators, and how to improve efficiency is one of the key problems. This paper aims to establish the new mechanism of hospital equipment sharing to optimize the resource allocation.Methods:Taking large-scale general hospital as an example, set up rules for sharing the scientific research equipment in the hospital, establish information management platform to assure the unify and smart management of large-scale scientific research instruments.Results:Through hospital policy-making, information system construction, reward-punishment mechanism updating, a tailored opening and sharing construction scheme of scientific research instruments and equipment in the hospital was established.Conclusions:The construction of equipment sharing platform plays important role in optimize resource allocation, improves the efficiency of existing equipment, and avoids redundant and inefficient use and repeated purchases, which provides strong support for the sustainable development of scientific research in the whole hospital.

2.
Chinese Journal of Nephrology ; (12): 896-903, 2021.
Article in Chinese | WPRIM | ID: wpr-911910

ABSTRACT

Objective:To investigate the association between cognitive impairment and all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis (HD).Methods:A prospective cohort study was conducted. Patients from 11 HD centers in Beijing between April and June 2017 were enrolled. Baseline data were collected, and a series of neuropsychological batteries covered 5 domains of cognitive function were applied for the assessment of cognitive function. The patients were then classified as normal and cognitive impairment groups according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V) and followed-up until June 2018. The clinical characteristics of the two groups of patients were compared. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the independent influencing factors of all-cause mortality, to determine the relationship between cognitive impairment and different cognitive domain impairments and all-cause death.Results:A total of 613 patients were enrolled, of which 496(80.91%) patients had cognitive impairment. Compared with the normal cognitive function group, the patients in the cognitive impairment group tended to be older, longer dialysis vintage, a higher proportion of diabetes, hypertension, and stroke, increased serum iPTH level, and lower education level and urea clearance index (Kt/V) (all P<0.05). After (49.53±8.42) weeks of follow-up, Kaplan-Meier survival analysis showed that the cumulative survival rate of cognitive impairment group was significantly lower than that of cognitive normal group (Log-rank χ2=8.610, P=0.003). Multivariate Cox regression analysis showed that history of diabetes ( HR=2.742, 95% CI 1.598-4.723, P<0.001), coronary heart disease ( HR=1.906, 95% CI 1.169-3.108, P=0.010), dialysis vintage (every increase of 1 month, HR=1.007, 95% CI 1.003-1.011, P=0.001), serum level of albumin (every increase of 1 g/L, HR=0.859, 95% CI 0.809-0.912, P<0.001), cognitive impairment ( HR=2.719, 95% CI 1.088-6.194, P=0.032) were independently associated with all-cause mortality. Multivariate Cox regression analysis on different cognitive domains also indicated that memory impairment ( HR=2.571, 95% CI 1.442-4.584, P<0.001), executive function impairment ( HR=3.311, 95% CI 1.843-5.949, P=0.001) and three, four, five domains combined impairment ( HR=5.746, 95% CI 1.880-17.565, P=0.002; HR=12.420, 95% CI 3.690-41.802, P<0.001; HR=13.478, 95% CI 3.381-53.728, P<0.001) were independently related to all-cause mortality. Conclusions:Cognitive impairment is an independent risk factor of all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis, and the risk is significantly increased in patients with the impairment of the domains of memory, executive function, or in the combination of three to five cognitive domains.

3.
Chinese Journal of Nephrology ; (12): 632-638, 2021.
Article in Chinese | WPRIM | ID: wpr-911888

ABSTRACT

Objective:To investigate the clinical features and associated influencing factors of cognitive impairment in middle-aged and elderly Chinese adult patients undergoing maintenance hemodialysis (HD).Methods:A cross-sectional study was conducted among HD patients from 11 centers in Beijing city from April 2017 to June 2017. A neuropsychological battery covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied in cognitive function assessment. Patients were classified as normal cognitive function group and cognitive impairment group according to the fifth version of the diagnostic and statistical manual of mental disorders criteria (DSM-V). Multivariate binary logistic regression was used to analyze the independent influencing factors of cognitive impairment. Results:A total of 613 HD patients were included in the study, and the prevalence of cognitive impairment was 80.91% (496/613). Attention impairment (81.05%) and memory impairment (63.51%) were the most common impaired domains, and 79.23% was concomitant impairment across two or more cognitive domains among those with cognitive impairment. Compared with the patients in the normal cognitive function group, the patients in the cognitive impairment group had senior age, longer dialysis vintage, higher proportion of diabetes, hypertension, and stroke, higher level of serum intact parathyroid hormone (iPTH), lower education level, and lower urea clearance index (Kt/V) (all P<0.05). Factors were independently associated with cognitive impairment including increasing age ( OR=1.110, 95% CI 1.072-1.150, P<0.001), education time>12 years (with education time<6 years as reference, OR=0.323, 95% CI 0.115-0.909, P=0.032), history of diabetes ( OR=2.151, 95% CI 1.272-3.636, P=0.004), history of stroke ( OR=2.546, 95% CI 1.244-5.210, P=0.011), increased dialysis vintage ( OR=1.016, 95% CI 1.010-1.022, P<0.001), reduced Kt/V( OR=0.008, 95% CI 0.002-0.035, P<0.001), and increased iPTH level ( OR=1.002, 95% CI 1.002-1.003, P=0.012). Conclusions:The prevalence of cognitive impairment in middle-aged and elderly adult Chinese patients undergoing HD is high. Memory and attention are the most commonly impaired domains. Increasing age, low education level, history of diabetes and stroke, increased dialysis vintage, reduced Kt/V and increased serum iPTH are the independent influencing factors associated with cognitive impairment.

4.
Article in Chinese | WPRIM | ID: wpr-911759

ABSTRACT

Venous leg ulcer (VLU) is the most common chronic ulcer of lower extremity caused by persistent venous hypertension. Although the mortality rate is low, VLU seriously affects the quality of life of patients, and has the potential for infection, deterioration, and amputation. The compression therapy is simple and easy to implement, it can effectively reduce venous hypertension and is the most important conservative therapy for treating and preventing recurrence of VLU. There are various devices and applications of compression therapy, and this article reviews the classification of compression therapy, and its application in treatment and recurrence prevention of VLU.

5.
Article in Chinese | WPRIM | ID: wpr-911271

ABSTRACT

Objective:To determine the median effective dose (ED 50) and the 95% effective dose (ED 95) of remifentanil inhibiting responses to endotracheal intubation without neuromuscular relaxant when combined with dexmedetomidine in patients undergoing thyroid surgery. Methods:American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, with body mass index of 18-28 kg/m 2, scheduled for elective thyroid surgery under intraoperative neuromonitoring, were enrolled in this study.Dexmedetomidine was intravenously injected in a loading dose of 0.8 μg/kg at 10 min before anesthesia induction.Anesthesia was induced by intravenously injecting midazolam 0.1 mg/kg, etomidate 0.4 mg/kg and the preset dose of remifentanil.The dose of remifentanil was determined using up-and-down sequential method.The initial dose was set at 3.7 μg/kg.The dose of remifentanil in the next case was determined according to whether responses to endotracheal intubation occurred, and the ratio between the two successive doses was 1.1.The ED 50, ED 95 and 95% confidence interval (CI) were calculated by Probit analysis. Results:when combined with dexmedetomidine for anesthesia induction, the ED 50 (95% CI) of remifentanil inhibiting responses to endotracheal intubation without neuromuscular relaxant was 3.39 (3.29-3.50) μg/kg, and the ED 95 (95% CI) was 3.52 (3.48-3.64) μg/kg. Conclusion:when combined with dexmedetomidine, the ED 50 of remifentanil inhibiting responses to endotracheal intubation without neuromuscular relaxant is 3.39 μg/kg, and the ED 95 is 3.52 μg/kg.

6.
Article in Chinese | WPRIM | ID: wpr-911198

ABSTRACT

Objective:To evaluate the effect of electroacupuncture (EA) on pyroptosis in renal tubular epithelial cells of rats with acute kidney injury (AKI) induced by endotoxin.Methods:Twenty-four healthy clean-grade Sprague-Dawley rats of either gender, aged 6-8 weeks, weighing 160-182 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), group AKI, EA plus AKI group (group EA), sham EA at non-acupoint plus AKI group (group SEA). The model of endotoxemia was established by intraperitoneally injecting 10 mg/kg lipopolysaccharide.Bilateral 30 min EA stimulation of Zusanli and Shenyu (according to atlas of animal acupoint) was performed starting from 5 days before establishing the model (once a day) and at 30 min before lipopolysaccharide administration on the day of establishing the model, with disperse-dense waves, frequency of 15 Hz, and the needle was kept until 6 h after injection of LPS in group EA.EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenyu in group SEA.At 6 h after LPS injection, blood was taken from the heart, and the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr) were detected by an automatic biochemical analyzer, and the serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.The rats were then sacrificed, and the left renal cortex was obtained for determination of pyroptosis rate of renal tubular epithelial cells (by TUNEL). The right renal cortex was obtained to detect the expression of caspase-1 and IL-1β by Western blot, and the expression of caspase-1 mRNA and IL-1β mRNA was detected by real-time polymerase chain reaction. Results:Compared with group C, the concentrations of BUN, Cr, NGAL, KIM-1, TNF-α, and IL-6 were significantly increased, the pyroptosis rate of renal tubular epithelial cells was increased, the expression of caspase-1 and IL-1β protein and mRNA in the renal cortex was up-regulated in group AKI ( P<0.05). Compared with group AKI, the concentrations of BUN, Cr, NGAL, KIM-1, TNF-α, and IL-6 were significantly decreased, the pyroptosis rate of renal tubular epithelial cells was decreased, the expression of caspase-1 and IL-1β protein and mRNA in the renal cortex was down-regulated in group SEA ( P>0.05). Conclusion:The mechanism by which EA reduces AKI may be related to inhibiting pyroptosis in renal tubular epithelial cells of rats.

7.
Chinese Journal of Urology ; (12): 544-545, 2021.
Article in Chinese | WPRIM | ID: wpr-911067

ABSTRACT

Retrovenal ureter is a type of inferior vena cava mutation. Retrovenal ureter with right double inferior vena cava mutation is rare. We reported a case of retrocaval ureteral with right double inferior vena cava variation, right ureteral calculi and hydronephrosis of the right kidney. Peritoneal laparoscopic ureterolithotomy and right posterior vena cava dissection ureteroplasty were performed. Fourteen months after surgery, B-ultrasound of the urinary system was reexamined, and no hydronephrosis was found in the right renal pelvis and ureter.

8.
Article in Chinese | WPRIM | ID: wpr-906437

ABSTRACT

Objective:To establish a qualitative and quantitative method for the determination of aristolochic acids in <italic>Aristolochia cinnabarina</italic> dried root tubers. Method:The dried root tubers of <italic>A. cinnabarina </italic>was qualitative and quantitative analysis by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS). The analysis was performed on Waters ACQUITY UPLC-BEH C<sub>18</sub> column ( 2.1 mm×100 mm, 1.7 μm) with the mobile phase of 0.1% formic acid aqueous solution (A)-acetonitrile (B) for gradient elution (0-1 min, 10%B; 1-9 min, 10%-30%B; 9-11 min, 30%-50%B; 11-15 min, 50%-90%B). The flow rate was 0.45 mL·min<sup>-1</sup>, column temperature was 35 ℃, and the detection wavelength was 250 nm. Mass spectral data was acquired in positive mode of electrospray ionization (ESI). At the same time, the UPLC fingerprints of aristolochic acids in 21 batches of <italic>A. cinnabarina</italic> dried root tubers were established, and the contents of 5 aristolochic acids in <italic>A. cinnabarina</italic> dried root tubers from different producing areas and different harvesting periods were determined. Result:A total of 17 compounds, including 8 aristolochic acids, 7 aristololactams and 2 4,5-dioxoaporphine alkaloids, were identified from <italic>A. cinnabarina</italic> dried root tubers by mass spectrometry data and bibliographic information. Ten common peaks were identified in the UPLC fingerprint, and they were tuberosinone-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside, aristolactam Ⅰa-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside, aristolochic acid Ⅳa-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside, aristolactam Ⅲa-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside, aristolactam Ⅰ-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside, aristolochic acid Ⅲa, aristolochic acid Ⅳa, aristolochic acid Ⅱ, aristolactam Ⅰ and aristolochic acid Ⅰ. According to the quantitative analysis, the results exhibited that aristolochic acid Ⅲa, aristolochic acid Ⅳa, aristolochic acid Ⅱ, aristolactam Ⅰ and aristolochic acid Ⅰ had good linear relationships in the linear range. The relative standard deviations (RSDs) of precision, stability and reproducibility tests were all less than 3.0%, the recovery was 97.06%-101.84% (RSD<3.0%). The contents of aristolochic acid Ⅰ, aristolochic acid Ⅱ, aristolochic acid Ⅲa, aristolochic acid Ⅳa, and aristolactam Ⅰ in 21 batches of <italic>A. cinnabarina</italic> dried root tubers were 0.938 6-3.567 5, 1.377 6-3.688 1, 0.056 3-0.527 7, 0.108 8-0.305 5, 0.021 0-0.081 7 mg·g<sup>-1</sup>, respectively. Conclusion:The content of aristolochic acids in <italic>A. cinnabarina</italic> dried root tubers has a certain difference, the contents of aristolochic acid Ⅰ and Ⅱ are higher than other aristolochic acids. The established method is rapid, simple, accurate and reliable, which can provide reference for the quality control and evaluation of <italic>A. cinnabarina</italic> dried root tubers.

9.
Article in Chinese | WPRIM | ID: wpr-906119

ABSTRACT

Objective:To identify the transdermal constituents of Euodiae Fructus and predict its molecular mechanism in treating diarrhea by transdermal drug delivery. Method:Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and integrated pharmacology methods were used. The rapid identification of transdermal constituents of Euodiae Fructus was realized by the means of comparison of reference substances, analysis of UNIFI system and mass spectrometry. On this basis, Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0, SymMap, DisGeNET databases and literature were used to collected potential targets of transdermal constituents of Euodiae Fructus and targets for diarrhea-related diseases. The disease targets and drug targets were topologically analyzed to obtain the core targets, which were used for the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, Cytoscape 3.6.0 was used to build up a network of transdermal constituents-core targets-key pathways. Result:A total of 19 chemical constituents were speculatively identified from Euodiae Fructus extract, including quinolone alkaloids, limonins, indole alkaloids, organic acids and sterols. A total of 174 core targets of Euodiae Fructus for treating diarrhea were obtained by a topology analysis, signaling pathways of inflammatory response, cell proliferation, nutrient regulation and energy metabolism, signal transduction, bacterial infection were obtained through the analysis of KEGG enrichment. Conclusion:In this study, the transdermal constituents of Euodiae Fructus are identified for the first time, they can participate in the regulation of intestinal inflammation, maintain the integrity of intestinal mucosa, repaire and adjust the metabolism of the body by acting on Rac protein family, phosphatidylinositol 3-kinase, cytochrome P450 enzymes and aldo-keto reductase, respectively. In general, the molecular mechanism of Euodiae Fructus in the treatment of diarrhea is preliminarily elucidated.

10.
Article in Chinese | WPRIM | ID: wpr-906047

ABSTRACT

Objective:To observe the effects of Scutellariae Radix-Hedyotidis Herba on the proliferation of human lung adenocarcinoma A549 cells and the expression of interleukin-6(IL-6), phosphatidylinositol 3-kinase (PI3K),protein kinase B (Akt), p-protein kinase B (p-Akt), mechanistic target of rapamycin (mTOR), hypoxia-inducible factor-1<italic>α </italic>(HIF-1<italic>α</italic>), and Cyclin D<sub>1</sub> at the cellular level, and to explore their molecular mechanism. Method:Following the set-up of the blank group (complete medium), low-, moderate-,and high-dose (20, 40, and 60 mg·L<sup>-1</sup>) Scutellariae Radix-Hedyotidis Herba groups, and low-, moderate-, and high-dose (5, 10, and 20 mg·L<sup>-1</sup>) cisplatin groups, the cell were treated with the corresponding drugs for 24, 48, and 72 h for detecting their viability by tetrazolium bromide (MTT) colorimetry. A549 cells were then divided into the blank group, Scutellariae Radix-Hedyotidis Herba group, cisplatin group, and combined medication group and intervened with the<sup> </sup>complete medium, 40 mg·L<sup>-1 </sup>Scutellariae Radix-Hedyotidis Herba, 10 mg·L<sup>-1</sup> cisplatin, and 40 mg·L<sup>-1 </sup>Scutellariae Radix-Hedyotidis Herba + 10 mg·L<sup>-1 </sup>cisplatin, respectively, for 24, 48 and 72 h, followed by the measurement of inhibitory effects against the proliferation of A549 cells in each experimental group. The level of IL-6 in cell culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA) after 72 h. The mRNA expression levels of HIF-1<italic>α</italic> and Cyclin D<sub>1</sub> in each group were assayed by real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of PI3K, Akt, p-Akt, mTOR, HIF-1<italic>α</italic>, and Cyclin D<sub>1</sub> by Western blot. Result:After 24 h intervention, Scutellariae Radix-Hedyotidis Herba did not significantly inhibit the proliferation of A549 cells. However, 48 h later, the inhibitory effect in Scutellariae Radix-Hedyotidis Herba groups were significantly enhanced in comparison with that in the blank group (<italic>P</italic><0.05), exhibiting a time-dependent response. After 72 h of action, no significant change was present in the inhibitory effect of each Scutellariae Radix-Hedyotidis Herba group, so the optimal concentration of Scutellariae Radix-Hedyotidis Herba was set at 40 mg·L<sup>-1</sup> for follow-up experiments. As demonstrated by the comparison with the blank group, cisplatin at each concentration inhibited the cell proliferation in a time-dependent manner (<italic>P<</italic>0.05). Considering the cell survival rate, the best concentration of cisplatin was set at 10 mg·L<sup>-1</sup>. Compared with the blank group, Scutellariae Radix-Hedyotidis Herba combined with cisplatin remarkably inhibited the proliferation of A549 cells in a time-dependent manner (<italic>P<</italic>0.05), and the differences between the combined medication group and the other two groups became more significant after 72 h of medication (<italic>P<</italic>0.01). The IL-6 level in each experimental group, especially in the combined medication group, significantly declined in contrast to that in the blank group (<italic>P<</italic>0.01). The mRNA expression levels of HIF-1<italic>α</italic> and Cyclin D<sub>1</sub> in all experimental groups were obviously lower than those in the blank group, with the most significant changes observed in the combined medication group (<italic>P</italic><0.05,<italic>P</italic><0.01). The protein expression levels of PI3K, p-Akt, mTOR, HIF-1<italic>α</italic>, and Cyclin D<sub>1</sub> in each experimental group was significantly down-regulated(<italic>P</italic><0.05,<italic>P</italic><0.01), and the levels in the combined medication group were even lower than those in the cisplatin group (<italic>P<</italic>0.01). Conclusion:Scutellariae Radix-Hedyotidis Herba has an inhibitory effect on the proliferation of A549 cells, which may be related to its inhibition against the expression and secretion of IL-6/PI3K/Akt/mTOR-HIF-1<italic>α</italic> axis.

11.
Article in English | WPRIM | ID: wpr-898095

ABSTRACT

BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

12.
Article in English | WPRIM | ID: wpr-898056

ABSTRACT

Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

13.
Article in English | WPRIM | ID: wpr-890391

ABSTRACT

BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

14.
Article in English | WPRIM | ID: wpr-890352

ABSTRACT

Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

15.
Article in English | WPRIM | ID: wpr-922756

ABSTRACT

Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated β-amyloid (Aβ) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in β-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aβ secretion, which was caused by down-regulation of β-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aβ secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.


Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Aspartic Acid Endopeptidases/metabolism , Down-Regulation , Forkhead Box Protein O1/genetics , Humans , Phosphorylation , STAT3 Transcription Factor/metabolism , Secosteroids
16.
Acta Pharmaceutica Sinica B ; (6): 3655-3664, 2021.
Article in English | WPRIM | ID: wpr-922432

ABSTRACT

Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered

17.
Acta Pharmaceutica Sinica B ; (6): 3567-3584, 2021.
Article in English | WPRIM | ID: wpr-922425

ABSTRACT

Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both

18.
Article in Chinese | WPRIM | ID: wpr-888002

ABSTRACT

According to the records of Chinese materia medica,Coptis chinensis var. brevisepala is an authentic Chinese medicinal plant highly recommended by ancient physicians since its rhizome is like a string of beads and has a good medicinal value. However,its medicinal components and values remain to be studied as it is endangered because of overexploitation. Therefore,this study aims to quantitatively determine its effective components based on UPLC-QTOF-MS,and to compare the contents of isoquinoline alkaloids in C.chinensis var. brevisepala with those in other Coptis species. Meanwhile,molecular methods accurately identified 12 batches of C. chinensis var. brevisepala,9 batches of C. chinensis,4 batches of C. deltoidea,and 1 batch of C. teeta. Gradient elution was performed with Waters CORTECS C18 column( 4. 6 mm× 150 mm,2. 7 μm) and the mobile phase acetonitrile-water with 0. 4% formic acid. Mass spectrometry was conducted in ESI positive mode. The quantitative results showed that 8 main alkaloids had a good linear relationship within the concentration range( R~2>0. 996),with the recovery rate of 95. 18%-105. 0% and the RSD of 0. 28%-3. 7%. Compared with that of other Coptis species,the rhizome of C. chinensis var. brevisepala had the highest contents of berberine and columbamine. The total content of the 8 alkaloids in C. chinensis var. brevisepala was similar to that in C. chinensis but higher than that of the other two species. PCA was performed to compare the alkaloids among the 4 species. Besides,the 8 alkaloids were evaluated in different parts of C. chinensis var. brevisepala. The results indicate that this method is reliable and efficient and can provide a reference for the quality research.


Subject(s)
Alkaloids , Berberine Alkaloids , China , Coptis , Drugs, Chinese Herbal/analysis , Plants, Medicinal
19.
Article in Chinese | WPRIM | ID: wpr-888001

ABSTRACT

Coptidis Rhizoma is a common Chinese medicinal in clinical practice,with the effects of clearing heat,drying dampness,purging fire,and removing toxin. All the medicinal plants of Coptis can be used for clinical treatment,but some species are endangered due to resource destruction and difficulty in planting. The dominant medicinal components in Coptidis Rhizoma are isoquinoline alkaloids. There are various methods for the analysis and detection of alkaloids,such as LC-MS,HPLC,and TLC,among which LC-MS is the most widely applied. Different plants of Coptis vary in the kind and content of alkaloids. C. chinensis,C. deltoidea,C. teeta,C. chinensis var. brevisepala,C. omeiensis,C. quinquefolia,and C. quinquesecta mainly contain berberine,palmatine,coptisine,jatrorrhizine,and columbamine,five effective alkaloid components. Plant isoquinoline alkaloids( PIAs) have strong pharmacological activity but are difficult to prepare. The application of synthetic biology of PIAs will be helpful for the clinical application of PIAs. This paper reviews the research progress on biological resources of Coptis species and structures of alkaloids as well as analysis methods and synthetic biology for isoquinoline alkaloids in the medicinal plants of Coptis in recent years,which will facilitate the protection of Coptis medicinal resources and the application and development of alkaloids.


Subject(s)
Alkaloids , Berberine , Berberine Alkaloids , Coptis , Drugs, Chinese Herbal , Isoquinolines , Rhizome
20.
Acta Pharmaceutica Sinica ; (12): 972-982, 2021.
Article in Chinese | WPRIM | ID: wpr-886986

ABSTRACT

Aristolochic acids (AAs) are widely distributed in Aristolochiaceae, and are important toxic components in medicinal plants of Aristolochiaceae. As one of the most powerful carcinogens in the Carcinogenic Potency Database (CPDB), AAs can induce hepatotoxicity, nephrotoxicity, carcinogenicity, mutagenicity, and other adverse reaction. AAs also can produce a series of metabolites such as AA-DNA adducts in the body, and their specific metabolites can be used as biomarkers for early diagnosis and treatment of related diseases. Thus, the current discovery for technical means that can quickly and accurately detect biomarkers possesses significant research value. AAs can be attenuated by processing, compatibility, molecular breeding, and other methods to improve the clinical safety of Chinese medicine containing AAs. In this review, we report the distribution of AAs, attenuation strategies and biomarker detection. We would like to provide a reference for the quality control of AAs-containing Chinese medicines, as well as for the prevention and control of diseases caused by AAs.

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