摘要
AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4%-119.5%with the RSDs of 0.91%-7.94%.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.
摘要
A hydrophilic interaction chromatography tandem mass spectrometry method was developed for simultaneous quantification of 35 components in gualoupi injection. The analytes were separated with an ACQUITY XBridge Amide column using 20 mmol·L-1 ammonium formate aqueous solution (pH 3.0) as mobile phase A and 20 mmol·L-1 ammonium formate (pH 3.0)∶acetonitrile (1∶9) as mobile phase B for gradient elution. Mass spectrometry with dynamic multiple reaction monitoring and external standard method were used for quantitative analysis. A total of 35 components were determined in 10 batches of gualoupi injection. The results showed that the 35 compounds had a good linear relationship within their respective concentration ranges with the correlation coefficients (R2 > 0.998 0), the recoveries ranged from 76.6% to 118.5%. The results showed that γ-aminobutyric acid, trigonelline, alanine, threonine, homoserine, citrulline, and leucine were abundant in gualoupi injection, while nicotinamide, methylsuccinic acid, cytosine and choline account for a low percentege. The present study provides an important reference for elucidation of the effective material basis and the improvement of quality standard of gualoupi injection.
摘要
OBJECTIVE@#To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA.@*METHODS@#The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed.@*RESULTS@#A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034).@*CONCLUSIONS@#Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.
Subject(s)
Humans , Carbapenems/therapeutic use , Pseudomonas aeruginosa , Soft Tissue Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Hematologic Diseases , Survival Analysis摘要
Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.
Subject(s)
Animals , Mice , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Cognition , Disease Models, Animal , Mice, Transgenic , Monocytes/pathology , Polysaccharides/therapeutic use , Proteoglycans摘要
To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.
摘要
BACKGROUND@#Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.@*METHODS@#We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.@*RESULTS@#In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05).@*CONCLUSION@#Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.
Subject(s)
Humans , Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Case-Control Studies , Cognition , Cross-Sectional Studies , Peptide Fragments , tau Proteins摘要
OBJECTIVE@#To evaluate the regulation of VEGF-Notch signaling pathway on proliferation and apoptosis of mesenchymal stem cells (MSC) in the patients with aplastic anemia (AA).@*METHODS@#The bone marrow specimens of AA patients were collected for isolation and identification of BM MSC. Westen blot was used to detect the expression of VEGF-Notch signaling pathway-related proteins (VEGF, VEGFR, Notch 1, Jagged 1, Delta-like 1 and Hes1). The VEGF (100 ng/ml) and DAPT (γ-secretase inhibitor, 10 μmol/L) were respectively added into MSC culture system in oder to activate and inhibit the signaling transduction of VEGF-Notch in BM MSC. The proliferation, apoptosis and cell cycle of MSC in AA patients were detected by CCK8 assay and flow cyfometry. The adipogenic differentiation of BM MSC was detected by oil red O staining.@*RESULTS@#The VEGF-Notch signaling pathway was significantly inhibited in AA BM tissues and AA MSC (P<0.05) detected by Western blot. The intervention of VEGF and DAPT significantly activated and inhibited VEGF-Notch signaling in AA MSC, respectively. CCK8 assay showed that VEGF intervention significantly promoted the proliferation of MSC in AA patients (P<0.05). Flow cytometry showed that VEGF significantly inhibited apoptosis of MSCs by blocking S phase cells (P<0.05).@*CONCLUSION@#The activation of VEGF-Notch can restore the proliferation function of MSC in AA patients.
Subject(s)
Humans , Anemia, Aplastic , Apoptosis , Bone Marrow , Cell Proliferation , Mesenchymal Stem Cells , Signal Transduction , Vascular Endothelial Growth Factor A摘要
<p><b>OBJECTIVE</b>To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders.</p><p><b>METHODS</b>From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed.</p><p><b>RESULTS</b>(1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females).</p><p><b>CONCLUSIONS</b>Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Anemia, Aplastic , Diagnosis , Medicine, Chinese Traditional , Methods , Yang Deficiency , Diagnosis , Yin Deficiency , Diagnosis摘要
<p><b>OBJECTIVE</b>To compare short-term postoperative outcomes between antecolic and retrocolic laparoscopic Roux-en-Y gastric bypass(LRYGB).</p><p><b>METHODS</b>Forty obesity patients were admitted into The First Affiliated Hospital of Jinan University from March 2008 to July 2010. All patients were randomly assigned to undergo antecolic (group A, 20 cases) and retrocolic (group B, 20 cases) gastroenteric anastomosis. Short-term outcomes were compared.</p><p><b>RESULTS</b>LRYGB procedures were successfully performed in all the 40 patients. There were no significant differences between the two groups in estimated blood loss during surgery, time to flatus passage, time to resumption of oral intake, or length of postoperative hospital stay. The operation time was longer in group B than that in group A [(163.4±28.1) min vs.(131.8±22.7) min, P<0.05]. There were no patients developed internal hernia or anastomotic leakage in either group. Comparison of short-term gastrointestinal symptoms after surgery showed no statistical significance.</p><p><b>CONCLUSIONS</b>Although retrocolic procedure may be closer to anatomical structure, antecolic and retrocolic anastomosis have comparable short-term outcomes after surgery. Further study is warranted to investigate long-term outcomes.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Gastric Bypass , Methods , Gastroenterostomy , Methods , Laparoscopy , Obesity, Morbid , General Surgery , Prospective Studies , Treatment Outcome摘要
<p><b>OBJECTIVE</b>To investigate the efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) in the treatment for obesity and type 2 diabetes mellitus (DM).</p><p><b>METHODS</b>Twenty-one cases of obesity and 9 cases of type 2 DM received the LRYGB. Weigh changes, excess body weight lose rate (EWL%) and blood glucose level were measured after surgery and occurrence of complications was observed postoperatively.</p><p><b>RESULTS</b>LRYGB procedures in all the 30 cases were successfully performed with no conversion to open surgery. Average operation time was 168 minutes (110-270 mins), volume of blood loss during the surgery was 24.0 ml (10-75 ml). Twenty-one cases of simple obesity received follow-up from 2 months to 5 years. Body weight and BMI decreased significantly in one month [(85.1+/-10.1) kg vs (97.2+/-15.0) kg, 31.2+/-2.2 vs 35.3+/-3.5, both P<0.01] and to a minimal level in 2 to 3 years [(66.8+/-9.2) kg, 24.3+/-1.1], and then maintained at this level. EWL% was correspondingly higher (all P<0.05). Nine type 2 DM patients were followed up for 3 to 8 months, fasting blood glucose and blood glucose OGTT2 hours decreased significantly [(5.9+/-1.4) mmol/L vs (12.6+/-2.6) mmol/L, (7.8+/-1.4) mmol/L vs (17.8+/-4.1) mmol/L, both P<0.05], of whom 4 patients with obesity decreased in BMI significantly (P<0.05), and 5 patients without obesity had no significant changes in BMI (P>0.05). Five cases (16.7%) had postoperative complications, including 1 case of death due to acute fulminant pancreatitis, 1 case of mesenteric hiatal hernia with obstruction in line for reoperation, and the other 3 cases of healing by conservative therapy.</p><p><b>CONCLUSIONS</b>Treatment of obesity and type 2 DM by LRYGB surgery is feasible with significant short term result. Long term outcome needs further observation.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Diabetes Mellitus, Type 2 , General Surgery , Gastric Bypass , Methods , Laparoscopy , Obesity, Morbid , General Surgery摘要
<p><b>OBJECTIVE</b>To investigate the surgical approach, feasibility and effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery for treating type 2 diabetes mellitus.</p><p><b>METHODS</b>Seven obese patients with type 2 diabetes and 5 type 2 diabetic patients without obesity received LRYGB surgery. The changes of the body mass, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG), C peptide (C-P) and HbA1c% were observed postoperatively.</p><p><b>RESULTS</b>LRYGB procedures were successfully performed in all the 12 patients with no conversion to open surgery. The resolution rate was 85.7% in the obese group and 80% in the non-obese diabetic group.</p><p><b>CONCLUSION</b>LRYGB surgery is feasible for treatment of type 2 diabetes with good short-term result, but the long-term outcome awaits further observation.</p>