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BACKGROUND@#The efficiency of the target versus sub-target dose of renin-angiotensin system inhibitors (RASIs) in elderly patients with heart failure (HF) with reduced ejection fraction (HErEF) remains unclear.@*METHODS@#PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials (RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients (≥ 60 years) with HErEF. The primary outcome was all-cause mortality. The secondary outcomes were cardiac mortality, HF hospitalization, and the composite endpoint of mortality or HF hospitalization. A meta-analysis was conducted to generate combined hazard ratio (HR) and 95% CI.@*RESULTS@#Seven studies (two RCTs and five observational studies) enrolling 16,634 patients were included. A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality (HR = 0.92, 95% CI: 0.87-0.98, I2 = 21%) and cardiac mortality (HR = 0.93, 95% CI: 0.85-1.00, I2 = 15%) but not reduced rates of HF hospitalization (HR = 0.94, 95% CI: 0.88-1.01, I2 = 0) and the composite endpoint (HR = 1.03, 95% CI: 0.91-1.15, I2 = 51%). However, the target dose of RASIs was associated with a similar primary outcome (HR = 0.85, 95% CI: 0.64-1.14, I2 = 0) in a subgroup of very elderly patients > 75 years of age.@*CONCLUSIONS@#Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs. However, the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients > 75 years of age. Future high-quality and adequately powered RCTs are warranted.
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Yarrowia lipolytica is a non-conventional yeast with unique physiological and metabolic characteristics. It is suitable for production of various products due to its natural ability to utilize a variety of inexpensive carbon sources, excellent tolerance to low pH, and strong ability to secrete metabolites. Currently, Y. lipolytica has been demonstrated to produce a wide range of carboxylic acids with high efficiency. This article summarized the progress in engineering Y. lipolytica to produce various carboxylic acids by using metabolic engineering and synthetic biology approaches. The current bottlenecks and solutions for high-level production of carboxylic acids by engineered Y. lipolytica were also discussed, with the aim to provide useful information for relevant studies in this field.
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Carboxylic Acids/metabolism , Metabolic Engineering , Synthetic Biology , Yarrowia/metabolismABSTRACT
In recent years, adaptive laboratory evolution (ALE) has emerged as a powerful tool for basic research in microbiology (e.g., molecular mechanisms of microbial evolution) and efforts on evolutionary engineering of microbial strains (e.g., accelerated evolution of industrial strains by bringing beneficial mutations). The ongoing rapid development of next-generation sequencing platforms has provided novel insights into growth kinetics and metabolism of microbes, and thus led to great advances of this technique. In this review, we summarize recent advances in the applications of long-term and short-term ALE techniques mainly for microbial strain engineering, and different modes of ALE are also introduced. Furthermore, we discuss the current limitations of ALE and potential solutions. We believe that the information reviewed here will make a significant contribution to further advancement of ALE.
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High-Throughput Nucleotide Sequencing , Laboratories , MutationABSTRACT
Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.
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Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.
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Objective To investigate the significance of superb microvascular imaging (SMI) for the detection of neovascularization in carotid atherosclerotic plaques.Methods SMI detected 28 carotid atherosclerotic plaques in 28 patients who underwent carotid endarterectomy.The SMI grade of carotid plaque neovascularization was assigned based on the following grading system:Grade 0,no neovascularization;grade 1,some neovascularization;grade 2,neovascularization observed in the shoulder of the plaque;and grade 3,widely distributed new blood vessels.SMI was used to evaluate the degree of blood flow,maximum flow velocity,and resistance index of the new vessels in the plaque.Microvascular density was measured with CD31 staining.Results Clear correlations were observed between neovascularization density on histopathological staining of the plaque and the degree of blood flow detected with SMI (rs=0.788,P ＜ 0.001).The classification of neovascular blood flow in the plaque was positively correlated with plaque thickness (rs=0.686,P=0.002).Of the 28 cases,neovascularization was detected in 23;of these 23 cases,the direction of blood flow was from the adventitia to the intima in 17 (75％) cases,while 6 (25％) cases showed an irregular direction of blood flow.The mean neovascular flow velocity was (5.620±0.131) cm/s,and the mean neovascular resistance index was 0.660 ± 0.090.Conclusion SMI is useful for the evaluation of carotid atherosclerotic plaque neovascularization.
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Objective To observe and analyze the clinical effect of noninvasive sputum aspiration combined with atomization inhalation in the treatment of pediatric bronchiolitis. Methods Totally 79 children with bronchiolitis diagnosed from January 2016 to December 2017 were selected. The children were divided into observation group (40 cases) and control group (39 cases) by double blind method of stratified random sampling. The observation group were treated with atomization inhalation after noninvasive sputum aspiration;and the control group were treated with the traditional inhalation of sputum according to the condition of the disease.The improvement effect of the symptoms before and after the treatment of the two groups was compared. Results After treatment, the improvement of symptoms in the two groups included cough, fever, wheezing, shortness of breath, lung rales, daily sputum aspiration and hospital stay were (5.34±1.06) d, (1.82±0.35) d, (2.66±0.85) d, (1.76±0.39) d, (4.37±1.29) d, (6.38± 1.39) times, (6.31 ± 0.82) d in the observation group, (6.25 ± 0.98) d, (2.34 ± 0.41) d, (3.08 ± 0.94) d, (2.56 ± 0.41) d, (5.39 ± 1.33) d, (8.31 ± 1.52) times, (8.25 ± 1.09) d in the control group, the difference was statistically significant( t=2.084-8.954, P<0.05). Respiratory function improvement including arterial oxygen saturation,heart rate,respiratory rate was 0.96±0.03, (110.85±4.16) times/min, (29.49±1.87) times/min in the observation group, 0.92±0.03, (119.34±4.22) times/min, (35.14±1.95) times/min in the control group,the difference was statistically significant(t=5.925, 9.005, 13.146, P<0.05). The effective rate of the observation group was 97.50％ (39/40), which was significantly higher than that of the control group 79.49％(31/39), the difference was statistically significant (χ2=4.688, P<0.05).The satisfaction rate of the family members of the observation group of the nebulization and sputum suction service was 100.00％(40/40), which was significantly higher than that of the control group (87.18％, 34/39), the difference was statistically significant (χ2=13.698, P<0.05). Conclusions Noninvasive sputum aspiration combined with atomization inhalation is effective in the treatment of pediatric bronchiolitis. It can relieve airway obstruction, improve asthma symptoms, shorten the time of hospitalization, and the operation is convenient and safe.
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Objective To observe the change of expression of WNT4/β-catenin signaling pathway and its inhibitory factor secreted frizzled-related protein 1 (SFRP1) in renal tissue in diabetic nephropathy(DN) rats, and to explore its possible role in the development of renal fibrosis. Methods Rats were randomly divided into normal control(NC) group and DN group, and equipped with 8 in each group. The IDDM model was prepared by tail vein injection of STZ 55 mg/kg. Hemotoxyin and eosin、Periodic Acid-Schiff and Masson stain were used to observe the morphological structure and fibrotic lesions in renal tissue;Immunohistochemical analysis was used to observe the protein expression of WNT4 and β-catenin in renal tissue;Western blot was used to detect the protein expression changes of WNT4, SFRP1, β-catenin, p-GSK-3β, GSK-3β, Collagenl, a-SMA, E-cadherin in renal tissue in each group;The mRNA expression of WNT4 and SFRPl in renal tissues of rat was detected by realtime PCR. Results Compared with NC group, renal tissue fibrosis was obvious in DN group. Compared with NC group, the protein and mRNA expressions of WNT4 significantly increased (P＜0.05), the protein expressions of β-catenin, p-GSK-3β, α-SMA and collagen I significantly increased (P < 0.05), the protein expressions of Ecadherin significantly decreased (P＜0. 05), the protein and mRNA expression of SFRPl significantly decreased (P＜0.05). Conclusions In the case of DN, the signal pathway of WNT4/β-catenin is abnormal activation. The expression of SFRPl is decreased, and that may inhibit this pathway and promote the development of renal fibrosis in DN.
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Objective@#To compare the visualization ability for thyroid nodular vascularity among superb micro-vascular imaging (SMI), power Doppler flow imaging (PDFI), and color Doppler flow imaging(CDFI), and determine optimal vascular findings for the diagnosis of thyroid nodules.@*Methods@#A total of 58 thyroid nodules from 50 patients were enrolled, including 27 benign nodules (benign group) and 31 malignant nodules (malignant group). Vascular patterns of these nodules were detected by SMI, PDFI and CDFI, respectively.@*Results@#Thyroid cancer was characterized by type III vascular pattern. "Only central vascularity" performed best in detecting thyroid cancers. When using the criterion, SMI performed a better specificity (96.3%) and sensitivity (77.4%) than PDFI (92.5%, 41.9%) and CDFI (88.9%, 48.3%); and the specificity of SMI was significantly higher than the others (all P<0.01).@*Conclusions@#The sign of only central vascularity is of value in distinguishing malignant thyroid nodules. SMI is better on presenting thyroid nodular vascularity than CDFI and PDFI, and it could be used to differentiate thyroid nodules.
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Objective To summarize the characteristics and molecular genetics of sporadic children /adolescent-onset primary hyperparathyroidism PHPT patients and analyze the difference of characteristics between patients with and without CDC73 gene mutations .Methods Germline mutation analyses of MEN1, CDC73, RET, CDKN1B, and CaSR genes were performed in 22 sporadic children/adolescent-onset PHPT patients .Their clinical data were retrospectively analyzed.Results Four patients were found to carry CDC 73 mutations with the mutation rate of 18%(4/22).Patients with CDC73 gene mutationshad higher rates of parathyroid carcinoma and atypical adenomas than those without ,and the recurrence rate postoperatively was as high as 50%.Conclusions Genetic mutation testing is recommended in spo-radic children/adolescent-onset PHPT patients, especially the CDC73 gene.
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The electrospray ionization-ion mobility spectrometric (ESI-IMS) technique has the potential as an analytical separation tool in analyzing polypeptides and amino acids for fast screening unknown samples in anti-chemical and biological terror attacks. A method for detecting several polypeptides and amino acids was developed based on ESI-IMS using air as drift gas at room temperature. The ion mobility of four amino acids and two polypeptides dissolved in methanol was determined on the system at elution rate of 2 mL/ min. The spectra of these compounds had characteristics of finger-printing maps. The limit of detection of this instrument for Substance P could reach 855 ng / mL in 1 min. The results showed that a small, self-contained ESI-IMS instrument with reservoirs of air could be used to quickly detect and accurately identify polypeptides and amino acids.
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A 65-year-old male presented with recurrent palpitation and fatigue over one year. Lab tests revealed him with hyperinsulinaemic hypoglycemia. Insulin autoimmune antibody was repeatedly negative. Imaging of the pancreas seemed to be normal. Insulin-insulin autoimmune antibody complexes were detected by polyethylene glycol precipitation and gel filtration chromatography, thus the diagnosis of insulin autoimmune syndrome was suggested. By adjusting diet and administration of acarbose, all the symptoms were evidently relieved.
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A 65-year-old male presented with recurrent palpitation and fatigue over one year. Lab tests revealed him with hyperinsulinaemic hypoglycemia. Insulin autoimmune antibody was repeatedly negative. Imaging of the pancreas seemed to be normal. Insulin-insulin autoimmune antibody complexes were detected by polyethylene glycol precipitation and gel filtration chromatography, thus the diagnosis of insulin autoimmune syndrome was suggested. By adjusting diet and administration of acarbose, all the symptoms were evidently relieved.
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Objective To investigate the effects of aspirin and clopidogrel on the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases. Methods 116 cases of patients with upper gastrointestinal bleeding and cardiovascular disease as research subjects. 86 cases of patients used antiplatelet drugs (drug group), 30 cases didn't use antiplatelet drugs (non-drug group). In the drug group, 30 patients with aspirin alone (group A), 24 patients with clopidogrel alone (group B) and 32 patients with aspirin and clopidogrel (group C) . Compared the upper gastrointestinal bleeding in each group of patients. Results The incidence of abdominal pain in the drug group was significantly lower than non-drug group (P<0.05). However, there was no significant difference in the incidence of bloating, nausea, vomiting, acid reflux compared with non - drug group. There were no significant differences in the endoscopic manifestations of gastrointestinal bleeding between the drug group and the non-drug group. The incidence of severe gastrointestinal bleeding in the drug group was 47.67%, significantly higher than that in the non-drug group (26.67%)(P<0.05). A, B, C three groups of patients with severe gastrointestinal bleeding rate and bleeding patterns were no significant difference. There was no significant difference in the total effective rate of gastrointestinal bleeding between the drug group and the non-drug group. Conclusion Antiplatelet drugs may increase the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases, but aspirin and clopidogrel alone or in combination had no significant effect on the degree of gastrointestinal bleeding.
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Objective To investigate the effects of aspirin and clopidogrel on the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases. Methods 116 cases of patients with upper gastrointestinal bleeding and cardiovascular disease as research subjects. 86 cases of patients used antiplatelet drugs (drug group), 30 cases didn't use antiplatelet drugs (non-drug group). In the drug group, 30 patients with aspirin alone (group A), 24 patients with clopidogrel alone (group B) and 32 patients with aspirin and clopidogrel (group C) . Compared the upper gastrointestinal bleeding in each group of patients. Results The incidence of abdominal pain in the drug group was significantly lower than non-drug group (P<0.05). However, there was no significant difference in the incidence of bloating, nausea, vomiting, acid reflux compared with non - drug group. There were no significant differences in the endoscopic manifestations of gastrointestinal bleeding between the drug group and the non-drug group. The incidence of severe gastrointestinal bleeding in the drug group was 47.67%, significantly higher than that in the non-drug group (26.67%)(P<0.05). A, B, C three groups of patients with severe gastrointestinal bleeding rate and bleeding patterns were no significant difference. There was no significant difference in the total effective rate of gastrointestinal bleeding between the drug group and the non-drug group. Conclusion Antiplatelet drugs may increase the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases, but aspirin and clopidogrel alone or in combination had no significant effect on the degree of gastrointestinal bleeding.
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Objective To investigate the value of 18 MHz high-frequency linear array ultrasound probe in the diagnosis of thyroid anterior capsular invasion,and compare it with the conventional high-frequency ultrasound probe.Methods Seventy-three nodules in 68 patients in Peking Union Medical College Hospital from December 2015 to March 2016 underwent conventional and 18 MHz high-frequency probes examination before operation and were compared with pathological results.The accuracy,sensitivity and specificity of the 18 MHz high-frequency linear array probe and the conventional high-frequency probe were determined.The consistency between the gold standard and the diagnosis by using two different frequency probes was measured using Kappa statistics.Additionally,diagnostic accuracy of different frequency probes was further evaluated according to the area under the ROC curve.Results The diagnostic consistency test of the total sample of 73 nodules:capsular abutment as the diagnostic criterion,the diagnostic consistency of 18MHz high-frequency probe was good (Kappa=0.803,P ＜ 0.01).The specificity,positive predictive value and accuracy were superior to the conventional high-frequency probe (90.7％ vs 69.8％,87.1％vs 68.3％,90.4％ vs 79.5％).The area under the ROC curve was 0.903,higher than that of the conventional high-frequency probe (0.816),which demonstrated that the former had better diagnostic accuracy.If the disruption of the perithyroidal echogenic line as another diagnostic criterion,the diagnostic consistency of the 18 MHz and conventional high-frequency probe was general,the Kappa value were 0.677 and 0.518.The sensitivity,positive predictive value,negative predictive value and accuracy of conventional high-frequency probe were inferior to the 18 MHz high-frequency probe (53.3％ vs 70.0％,74.5％ vs 82.0％,88.9％ vs 91.3％,78.1％ vs 84.9％).Conclusions The 18 MHz high frequency probe is a feasible tool for accurate prediction of the distance between tumor and thyroid anterior capsular and anterior capsular invasion,and it is helpful for the diagnosis of the preoperative staging and the prognosis of PTC.
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This study was aimed to select the best preparation form of Aurea Helianthus in order to provide a scientific basis for research and development of anti-myocardial ischemia drugs.The content of effective index components of preparation of Aurea Helianthus was detected using HPLC-PDA.Acute myocardial ischemia rat model introduced by injecting pituitrin was used to investigate the effect of anti-myocardial ischemia.The quality of preparation from Aurea Helianthus was characterized based on pharmacy and efficacy.And the characterized results were given correlation analysis.The results showed that the HPLC method for quantitative determination was verified by methodology.The average recoveries were in the range of 97.04％-102.44％.All three preparations of Aurea Helianthus had the efficacy of anti-myocardial ischemia in varying degrees.The enrichment had the highest effect with lowest extraction rate and the lowest dosage,which was the best form in medicinal-preparation application of Aurea Helianthus.It was concluded that the content of related drug components was higher with unique proportion in enrichment of Aurea Helianthus which was prepared based on drug system proved a high quality medicine.Therefore,the key to the improvement of efficacy was to explore the fittest proportion and improve the content of related pharmaceutical ingredients pertinently according to drug system.
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Objective:To introduce a modified method for umbilical reconstruction after single-incision laparoscopic surgery.Methods:Between June 2012 and June 2015,173 patients underwent single-incision laparoscopic cholecystectomy at our institution.All the patients adopted our modified method for umbilical reconstruction.Results:All the surgeries were successful.The umbilical incision healed well with good cosmetic result.Conclusion:The modified method for umbilical reconstruction can improve cosmesis and decrease the possibility of incision hernia after single-incision laparoscopic surgery.More studies are needed to evaluate definitive clinical advantages of this technique.
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Objective T o explore the m etabolic characteristics of lethal bradycardia induced by m yocardial ischem ia in rat's serum . Methods A rat m yocardial ischem ia-bradycardia-sudden cardiac death (M I-B-SC D ) m odel w as established, w hich w as com pared w ith the sham-operation group. T he m etabolic pro-file of postm ortem serum w as analyzed by gas chrom atography-m ass spectrom etry (G C-M S ), coupled w ith the analysis of serum m etabolic characteristics using m etabolom ics strategies. Results T he serum m etabolic profiles w ere significantly different betw een the M I-B-SC D rats and the control rats. C om pared to the control rats, the M I-B-SC D rats had significantly higher levels of lysine, ornithine, purine, serine, alanine, urea and lactic acid; and significantly low er levels of succinate, hexadecanoic acid, 2-ketoadipic acid, glyceraldehyde, hexendioic acid and octanedioic acid in the serum . T here w ere som e correlations am ong different m etabolites. Conclusion T here is obvious m etabolic alterations in the serum of M I-B-SC D rat. B oth lysine and purine have a high value in diagnosing M I-B-SC D . T he results are expected to provide references for forensic and clinical applications of prevention and control of sudden cardiac death.
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<p><b>OBJECTIVE</b>To study the correlation and consistency of the 2 different methods for detecting coagulation function.</p><p><b>METHODS</b>One hundred and six inpatients of ICU and department of gastroenterology in our hospital were retrospectively analyzed. The clinical data of thromboelastography and coagulation test were collected, and the detection results of 2 different methods were statistically analyzed.</p><p><b>RESULTS</b>The K, MA value and α-Angle in thrombelastometry significantly related with fibrinogen (r=-0.62, 0.36, 0.38, all P<0.01), and the R time significantly related with prothrombin time and activated partial thromboplastin time (r=0.31, 0.35, both P<0.01); the Kappa values of K value, MA value, α-Angle and fibrinogen value were 0.34, 0.46, 0.31 respectively (all P<0.05), and the chi square test values were respectively 1.12, 1.42, 0.14 (P=0.28, 0.21, 0.69); the Kappa values of R time in thrombelastometry with prothrombin time, activated partial thromboplastin time(APTT) were respectively 0.05,0.07 (P=0.88, 0.81), and the chi square tests showed that the Kappa values were respectively 19.57, 9.07 (both P<0.01).</p><p><b>CONCLUSION</b>Thromboelastography and coagulation test show significant correlation, with poor consistency, so the 2 kinds of methods can not be replaced for each other, which still can not be used to better assess the risk of bleeding.</p>