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This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
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Rats , Animals , Doxorubicin/adverse effects , Nephrotic Syndrome , AMP-Activated Protein Kinases/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , ApoptosisABSTRACT
OBJECTIVE@#To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese.@*METHODS@#Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells.@*RESULTS@#Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC50) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L.@*CONCLUSION@#This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.
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Objective:To determine the median effective dose (ED 50) of esketamine for preoperative sedation in different aged pediatric patients. Methods:Pediatric patients, aged 1-6 yr, of American Society of Anaesthesiologists physical status Ⅰ, with the preoperative parental Separation Anxiety Scale (PSAS) score ≥3, undergoing elective surgery under general anesthesia, were selected.According to the age, the children were divided into 1 yr≤age<4 yr low-age group (group L) and 4 yr≤age< 6 yr high-age group (group H). Esketamine 0.5 mg/kg was intravenously injected in the first child in each group.The dose in the next child was determined according to PSAS scores, and the two consecutive dose gradient was 0.1 mg/kg; when the PSAS score in the previous child was ≥3, the dose in the next child was increased; when the PSAS score in the previous child was< 3, the dose in the next child was decreased until appearance of 7 turning points, and then the experiment was terminated.The ED 50 and 95% confidence interval of esketamine for preoperative sedation were calculated by probit analysis. Results:A total of 54 children were enrolled in this study, including 26 cases in group L and 28 cases in group H. The ED 50 and 95% confidence interval of esketamine were 0.413 (0.314-0.530) mg/kg and 0.282 (0.252-0.318) mg/kg in group L and group H, respectively.Compared with group L, ED 50 of esketamine was significantly decreased in group H ( P<0.05). Conclusions:The ED 50 of esketamine for preoperative sedation is 0.413 mg/kg in pediatric patients of 1 yr≤age<4 yr old and 0.282 mg/kg in those of 4 yr≤age<6 yr old, and the efficacy of esketamine for preoperative sedation increases with age.
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Frailty is the clinical syndrome that occurs due to an increase in personal vulnerability and a decline in the ability to maintain one′s internal balance, which is closely related to the development of bladder cancer in the elderly. The research on frailty of elderly patients with bladder cancer in China is still in its infancy. This article discussed the risks of bladder cancer and frailty, the necessity of preoperative frailty assessment in patients with bladder cancer, commonly used assessment tools, and summarized the limitations of the existing evaluation tools to provide reference for further developing and improving the frailty evaluation tools and applications for bladder cancer patients research provides reference.
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Objective:To report 3 cases of rare subtypes of hereditary epidermolysis bullosa.Methods:Clinical data were collected from the probands and their relatives, whole-exome sequencing was performed to screen disease-causing mutations in the probands, and Sanger sequencing or qPCR was conducted to verify the mutations in patients and their relatives.Results:Case 1 mainly presented with linear red scars on the back, and the proband, her mother with similar clinical manifestations and her asymptomatic daughter all carried a mutation c.4573G>A (p.Gly1525Arg) in the COL7A1 gene. Case 2 presented with generalized reticular pigmentation all over the body and occasional blisters restricted to the hand and foot, and carried a de novo mutation c.74C>T (p.Pro25Leu) in the KRT5 gene. Case 3 presented with pigmentation abnormalities mainly located at the sun-exposed sites and incomplete syndactyly of the left hand, and carried homozygous deletion mutations in exons 2-6 of the FERMT1 gene, which were inherited from her asymptomatic parents. Case 1 was diagnosed with dominant dystrophic epidermolysis bullosa pruriginosa, case 2 was diagnosed with epidermolysis bullosa simplex with mottled pigmentation, and case 3 was diagnosed with Kindler epidermolysis bullosa. Conclusion:The clinical manifestations of epidermolysis bullosa vary greatly, and gene detection is very important for confirmation of diagnosis of its rare types.
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Objective:Effects of pole-specific acupuncture combined with Bobath on upper limb function, daily life ability and nerve function after traumatic brain injury were observed.Methods:A total of 142 patients with cerebral hemiplegia after traumatic brain injury from January 2019 to December 2020, were divided into the Bobath group (47 cases), the pole-specific acupuncture group (47 cases) and combination group (48 cases) by the random number method. Bobath group received Bobath rehabilitation, the pole-specific acupuncture group received pole-specific acupuncture rehabilitation, and combination group was given pole-specific acupuncture rehabilitation and Bobath treatment. The overall rehabilitation efficiency, limb function Fugl-Meyer scale score, Barthel index of daily life ability, nerve function, and other indicators were observed and compared.Results:After treatment, the overall recovery efficiency (86.96%) in combination group was significantly higher than that of the Bobath group (65.96%) and acupuncture group (64.44%)( χ2=5.84, P=0.016). After treatment, the limb function Fugl-Meyer scale (including upper limb and lower limb function scores)( F=19.38, 24.83, all Ps<0.01), daily life ability Barthel index (including cognitive ability situation score, language ability score, self-care ability score, social adaptability score and total score) of combination group were significantly higher than those in the Bobath group and acupuncture group ( F=14.91, 15.87, 18.71, 18.88, 32.62, all Ps<0.001), while the NIHSS score of combination group was significantly lower than that of the Bobath group and acupuncture group ( F=31.71, P<0.01). After treatment, the NE[(58.29±9.82)μg/L vs. (86.29±12.35)μg/L, (88.34±12.87)μg/L, F=33.39], DA[(204.29±20.26)μg/L vs. (278.72±27.56)μg/L, (281.14±27.82)μg/L, F=55.50], 5-HT[(231.27±20.12)μg/L vs. (294.74±29.34)μg/L, (298.19±28.73)μg/L, F=13.86], E[(21.85±3.19)μg/L vs. (28.37±4.07)μg/L, (28.26±4.14)μg/L, F=9.34] of combination group were significantly lower than those in the Bobath group and acupuncture group ( P<0.01). Conclusion:Magnetic pole-specific acupuncture combined with Bobath can improve the function of limbs, daily quality of life and nerve function of the patients with traumatic craniocerebral injury with cerebral palsy.
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Objective:To evaluate the efficacy of scalp nerve block combined with general anesthesia in optimizing anesthesia in the patients with moyamoya disease undergoing revascularization.Methods:A total of 154 patients with moyamoya disease, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective revascularization, were divided into 2 groups ( n=77 each) using a random nunber table method: scalp nerve block combined with general anesthesia group (GN group) and general anaesthesia group (G group). Anesthesia was induced with intravenous midazolam 0.05 mg/kg, sufentanil 0.5-1.0 μg/kg, rocuronium 0.6 mg/kg and etomidate 0.2-0.3 mg/kg.After the patients were tracheally intubated after anesthesia induction, ipsilateral scalp nerve block (2 ml for supraorbital nerve block, 2 ml for supratrochlear nerve block; 3 ml for auriculotemporal nerve block, 3 ml for greater occipital nerve block, 3 ml for less occipital nerve block) was performed with 0.5% ropivacaine in GN group.The equal volume of normal saline was locally injected in G group.Anesthesia was maintained by inhalation of sevoflurane and intravenous infusion of remifentanil 0.05-0.10 μg·kg -1·min -1 and cisatracurium 0.1 mg·kg -1·h -1.The consumption of intraoperative remifentanil, requirement for postoperative rescue analgesia, nausea and vomiting, length of postoperative hospital stay, and early neurological complications were recorded.The modified Rankin Scale scores were evaluated before operation, at discharge and at 6 months after operation. Results:Compared with G group, the consumption of intraoperative remifentanil and requirement for postoperative rescue analgesia were significantly decreased ( P<0.05), and no significant change was found in the incidence of postoperative nausea and vomiting, incidence of neurological complications, length of postoperative hospital stay, and modified Rankin Scale scores at each time point in GN group ( P>0.05). Conclusions:Scalp nerve block combined with general anesthesia can increase the perioperative analgesic efficacy and is helpful in achieving a low-opioid anesthesia mode when used in the patients with moyamoya disease undergoing revascularization.
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Objective:To identify the risk factors for early neurological complications after revascularization in adult patients with moyamoya disease.Methods:The medical records of patients of both sexes with moyamoya disease, aged 18-65 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, who underwent revascularization in our hospital from January 2017 to June 2019, were retrospectively collected.According to the occurrence of early postoperative neurological complications, patients were divided into early postoperative neurological complication group and non-early postoperative neurological complication group.The factors such as patient′s age, gender, preoperative clinical symptoms, previous history of hypertension, history of diabetes, history of coronary heart disease, American Society of Anesthesiologists physical status, methods of anesthesia, type of operation, anesthesia time, time for start of operation, operation time, intraoperative urine volume, times of intraoperative vasoactive drugs used, and time of the post-anaesthesia observation room (PACU) stay were collected.Logistic regression analysis was used to identify the risk factors for postoperative early neurological complications.Results:A total of 510 adult patients with moyamoya disease underwent revascularization were enrolled in this study, and the incidence of early postoperative neurological complications was 9.0%.The results of logistic regression analysis showed that preoperative ischemia, intraoperative use of vasoactive drugs more than 3 times and PACU stay time>90 min were risk factors for postoperative neurological complications ( P<0.05). Conclusion:Preoperative ischemia, intraoperative use of vasoactive drugs >3 times and PACU stay time>90 min are risk factors for early neurological complications after revascularization in the patients with moyamoya disease.
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Objective:To analyze differentially expressed genes (DEGs) and the changes of signal pathways in human retinal pigment epithelium cells (ARPE-19) under hypoxic and normoxic conditions and to explore the biological mechanism of hypoxia-induced ARPE-19 cell damage via transcriptome sequencing (RNA-seq) and bioinformatics technology.Methods:The ARPE-19 cells were divided into the hypoxia treatment group and the normoxia control group treated with 1% and 21% O 2 by volume for 8, 24, 48, 72 hours, respectively.The relative expression levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) mRNA were detected with real-time fluorescent quantitative PCR at different time points.RNA-seq and bioinformatics analysis were performed at 8 hours and 24 hours after hypoxia and normoxia treatment.DEGs were screened out under the conditions of |log 2FC|≥1 and P≤0.05.Then the cluster heat map analysis, Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were also carried out.Real-time fluorescent quantitative PCR was employed at 24 hours after hypoxia to detect the relative mRNA expression of genes that might be related to hypoxia in DEGs.Cell viability kit was used to verify and compare the damage effect of hypoxia on ARPE-19 cells at different time points between the two groups. Results:The relative mRNA expression levels of VEGF at 8, 24, 48 and 72 hours after hypoxia treatment and the relative HIF-1α mRNA expression levels at 8, 24 and 48 hours after hypoxia treatment were significantly higher than those of the normoxia control group (all at P<0.05). There were large differences in the mRNA expression levels at 8-hour and 24-hour treatment between the two groups.A total of 62 significant DEGs were screened between the hypoxia treatment group and the normoxia control group after 8-hour hypoxia treatment, among which 45 genes were significantly up-regulated and 17 genes were significantly down-regulated.A total of 255 significant DEGs were screened out between the hypoxia treatment group and the normoxia control group after 24-hour hypoxia treatment, among which 228 genes were significantly up-regulated and 27 genes were significantly down-regulated.The GO functional analysis of DEGs was mainly enriched in processes such as protein degradation, nucleotide biosynthesis, and material transport.KEGG pathway analysis was mainly enriched in PI3K-Akt, cGMP-PKG, and other signaling pathways closely related to metabolism, cell cycle, cell growth, and apoptosis.The core genes HPCA, MT3 and NOS3 were found by protein-protein interaction network analysis.Real-time fluorescent quantitative PCR test results showed that after 24-hour hypoxia treatment, the mRNA expression levels of hypoxia related genes DEPP1, NPPB, PDZK1, HILPDA, TCEA3, NDRG1 and RORC in ARPE-19 cells were significantly increased and the mRNA expression levels of TFRC and NQO1 were significantly decreased (all at P<0.05). The cell morphology was normal and the growth state was good without dead cells after 8-hour and 24-hour hypoxia treatment in ARPE-19 cells.There were dead cells after 48-hour hypoxia treatment, and the number of dead cells was increased at 72 hours after hypoxia treatment. Conclusions:The PI3K-Akt and cGMP-PKG signaling pathways related to metabolism may be involved in hypoxia-induced injury of ARPE-19 cells.Core genes of HPCA, MT3 and NOS3 can be used as functional target genes and play key roles in hypoxia response of cells.
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Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental retardation disease involving multiple organ and system abnormalities.The main manifestations include broad thumbs and big toes, specific facial characteristics, developmental and mental retardation.In addition, it is also manifested as ocular abnormalities, hearing loss, repeated respiratory infection and dyspnea, gastrointestinal disorders, urogenital system disorders and severe constipation.It can be classified into 2 types: RSTS1 (OMIM#180849) caused by the CREBBP gene mutation and RSTS2 (OMIM#613684) caused by the EP300 gene mutation, and most of them are found in the de novo truncated variation.Up to now, a clear diagnosis criterion for RSTS is lacked, which is mainly based on the comprehensive analysis of clinical and genetic results.The main treatment of RSTS is symptomatic and individualized treatment, while early intervention is helpful to improve the prognosis and the quality of life.This study aims to introduce the disease comprehensively, thus enhancing the recognition in RSTS.
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Bile acids are the end products of cholesterol metabolism and are classified as primary bile acids and secondary bile acids. They can promote nutrition absorption and regulate immune response, glucose/lipid/energy metabolism, and microbiota homeostasis by acting on bile acid nuclear receptors and membrane receptors. Cholestatic liver disease (CLD) is a type of liver disease caused by abnormalities of the hepatobiliary system due to cholestasis, with the initial manifestations of hepatocyte and/or bile duct injury, which further leads to abnormal bile acid synthesis, secretion, and excretion. In-depth studies have gradually revealed the role and mechanism of bile acids in CLD, and drugs targeting the action sites of bile acids are under research and development. This article elaborates on the role and mechanism of bile acid metabolism in CLDand summarizes the research and development of drugs for CLD treatment based on bile acid metabolism, so as to provide a reference for future research on the prevention and treatment of CLD.
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Bile acids are the end products of cholesterol metabolism and are classified as primary bile acids and secondary bile acids. They can promote nutrition absorption and regulate immune response, glucose/lipid/energy metabolism, and microbiota homeostasis by acting on bile acid nuclear receptors and membrane receptors. Cholestatic liver disease (CLD) is a type of liver disease caused by abnormalities of the hepatobiliary system due to cholestasis, with the initial manifestations of hepatocyte and/or bile duct injury, which further leads to abnormal bile acid synthesis, secretion, and excretion. In-depth studies have gradually revealed the role and mechanism of bile acids in CLD, and drugs targeting the action sites of bile acids are under research and development. This article elaborates on the role and mechanism of bile acid metabolism in CLDand summarizes the research and development of drugs for CLD treatment based on bile acid metabolism, so as to provide a reference for future research on the prevention and treatment of CLD.
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CHARGE syndrome is a rare autosomal dominant genetic disease, which involves the structure and function of multiple organs.The clinical manifestations are complex and diverse, it can be hereditary, but most cases was sporadic.While, the representation of disease is too much overlap with other diseases, it can be difficult to make a diagnosis only by clinical data.With the discovery of the pathogenic gene-CHD7, it can be further enhanced the knowledge and diagnosis of disease.Prompt diagnosis and treatment is not only beneficial to reduce mortality, but also can help to the prognosis of the patients.Through reviewing the literature, the progress of diagnosis and treatment of CHARGE syndrome were summarized in order to diagnose and treat the disease.
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CHARGE syndrome is a rare autosomal dominant genetic disease,which involves the structure and function of multiple organs. The clinical manifestations are complex and diverse,it can be hereditary,but most cases was sporadic. While,the representation of disease is too much overlap with other diseases,it can be difficult to make a diag-nosis only by clinical data. With the discovery of the pathogenic gene-CHD7,it can be further enhanced the knowledge and diagnosis of disease. Prompt diagnosis and treatment is not only beneficial to reduce mortality,but also can help to the prognosis of the patients. Through reviewing the literature,the progress of diagnosis and treatment of CHARGE syn-drome were summarized in order to diagnose and treat the disease.
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OBJECTIVE@#To evaluate the prognostic value of the difference between peripheral venous and arterial partial pressure of carbon dioxide in patients with septic shock following early resuscitation.@*METHODS@#This prospective study was conducted among the patients with septic shock treated in our department during the period from May, 2017 to May, 2018. Peripheral venous, peripheral arterial and central venous blood samples were collected simultaneously and analyzed immediately at bedside after 6-h bundle treatment. Arterial blood lactate concentration (Lac) and the arterial (PaCO), peripheral venous (PpvCO) and central venous partial pressure of carbon dioxide (PcvCO) were recorded. The differences between PpvCO and PaCO (Ppv-aCO) and between PcvCO and PaCO (Pcv-aCO) were calculated. Pearson correlation analysis was used to test the agreement between Pcv-aCO and Ppv-aCO. Multivariable logistic regression analysis was performed to analyze the possible risk factors for 28-day mortality, and the receiver-operating characteristic curve (ROC) was plotted to assess the prognostic values of these factors for 28-day mortality.@*RESULTS@#A total of 62 patients were enrolled in this study, among who 35 survived and 27 died during the 28-day period. Compared with the survivor group, the patients died within 28 days showed significantly higher Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score (24.2±6.0 20.5±4.9, =0.011), sequential organ failure assessment (SOFA) score (14.9±4.7 12.2±4.5, =0.027), PcvaCO (5.5±1.6 7.1±1.7, < 0.001), PpvaCO (7.1±1.8 10.0±2.7, < 0.001), and arterial lactate level (3.3±1.2 4.2±1.3, =0.003) after 6-h bundle treatment. Pearson correlation analysis showed that Ppv-aCO was significantly correlated with Pcv-aCO (=0.897, R= 0.805, < 0.001). Multiple logistic regression analysis identified Ppv-aCO (β=0.625, =0.001, OR=1.869, 95% CI: 1.311-2.664) and lactate level (β=0.584, =0.041, OR=1.794, 95%CI: 1.024-3.415) as the independent risk factors for 28-day mortality. The maximum area under the ROC (AUC) of Ppv-aCO was 0.814 (95%CI: 0.696- 0.931, < 0.001), and at the best cut- off value of 9.05 mmHg, Ppv-aCO had a sensitivity of 70.4% and a specificity of 88.6% for predicting 28-day mortality. The AUC of lactate level was 0.732 (95%CI: 0.607-0.858, =0.002), and its sensitivity for predicting 28-day mortality was 70.4% and the specificity was 74.3% at the best cut-off value of 3.45 mmol/L; The AUC of Pcv-aCO was 0.766 (95%CI: 0.642-0.891, < 0.001), and its sensitivity was 66.7% and the specificity was 80.0% at the best cut-off value of 7.05 mmHg.@*CONCLUSIONS@#A high Ppv-aCO after early resuscitation of septic shock is associated with poor outcomes. Ppv-aCO is well correlated with Pcv-aCO and can be used as an independent indicator for predicting 28-day mortality in patients with septic shock.
Subject(s)
Humans , APACHE , Carbon Dioxide , Cardiopulmonary Resuscitation , Lactic Acid , Blood , Organ Dysfunction Scores , Partial Pressure , Pilot Projects , Prognosis , Prospective Studies , ROC Curve , Regression Analysis , Shock, Septic , Blood , MortalityABSTRACT
Objective To analyze the efficiency of perinatal group B streptococcal(GBS)infection preven-tion in the local area.Methods From June 2015 to June 2016,3 667 pregnant women were included.Both pre-natal examinations and deliveries were done in our hospital.The analysis of GBS colonization,risk factors and prevention of early-onset disease were done.Results Among preterm and term pregnant women,the rates of GBS screening were 23.4% and 35.6%,respectively.The positive results of GBS were 10.9% and 8.4%,re-spectively.The percentage of women with 2 risk factors were 22.9% and 0.3%,respectively.GBS screening has a better prediction effect for GBS colonization status of women at labor.There were significant differences in the intrapartum antibiotic prophylaxis(IAP)implementation between preterm and term pregnant women. In the IAP efficiency analysis of preterm,GBS colonization and risk factors,preterm had a high sensitivity (96.1%),while the specialties of GBS carry and risk factors were high(93.2% and 90.3% respectively).Con-clusion preterm pregnant women should be highlighted as an important population in the implementation of IAP.GBS screening strategy is better than the risk factors strategy.
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OBJECTIVE:To systematically evaluate the effectiveness and safety of escitalopram and duloxetine in the treatment of depression, and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed, Wanfang database,VIP,CNKI and CBM,randomized controlled trials (RCTs) about escitalopram (trial group) and duloxetine (control group) in the treatment of depression were collected. Meta-analysis was conducted by using Rev Man 5.3 software after data extraction and quality evaluation according to bias risk assessment tool recommended by system evaluator manual 5.3. RESULTS:Finally 25 RCTs were included,involving 2621 patients. The results of Meta-analysis showed that there was no statistical significance in total response rate between 2 groups after 1,2,4,6,8 weeks of treatment or cure rate between 2 groupsafter 4,6,8 weeks of treatment (P>0.05). There was no statistical significance in total response rate [RR=0.96,95％CI(0.88, 1.05),P=0.42] or cure rate [RR=0.91,95％CI(0.78,1.06),P=0.24] of female patients,as well as total response rate [RR=0.96, 95％CI(0.84,1.11),P=0.61] or cure rate [RR=0.90,95％CI(0.54,1.49),P=0.69] of elderly patients between 2 groups. The incidence of constipation [RR=0.59,95％CI (0.42,0.81),P=0.001],dry mouth [RR=0.65,95％CI(0.51,0.82),P=0.0004], nausea [RR=0.68,95％CI(0.56,0.83),P=0.0002] and decreased appetite [RR=0.74,95％CI(0.55,0.99),P=0.04] in trial group were significantly lower than control group,with statistical significance. CONCLUSIONS:The effectiveness of escitalopram is similar to duloxetine in the treatment of depression,but the safety of escitalopram is better than duloxetine.
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Objective To investigate the value of the difference between peripheral arterial and venous blood gas analysis for the prognosis of patients with septic shock after resuscitation.Methods Patients with septic shock aged 18 to 80 years admitted to intensive care unit (ICU) of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine from May 2016 to December 2017 were enrolled. The peripheral arterial blood and peripheral venous blood gas analysis were measured simultaneously after the early 6 hours resuscitation, including pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), base excess (BE), bicarbonate (HCO3-) and lactate (Lac) level, and the difference values between peripheral arterial and venous blood were calculated. According to the 28-day survival, the patients were divided into survival group and death group. Multiple Logistic regression analysis was used to analyze the risk factors of death, and the receiver operating characteristic curve (ROC) was used to analyze the prognostic value of blood gas analysis parameters for prognosis.Results A total of 65 patients with septic shock resuscitation were enrolled in the study, 35 survived while 30 died during the 28-day period. ① There was no significant difference in gender, age, and mean arterial pressure (MAP), central venous pressure (CVP), central venous oxygen saturation (ScvO2) and norepinephrine (NE) dose between the two groups.② The arterial and venous Lac, the difference of Lac (ΔLac) and PCO2 (ΔPCO2) between arterial and venous blood in death group were significantly higher than those in survival group [arterial Lac (mmol/L): 7.40±3.10 vs. 4.82±2.91, venous Lac (mmol/L): 9.17±3.27 vs. 5.81±3.29, ΔLac (mmol/L): 1.77±0.54 vs. 0.99±0.60, ΔPCO2 (mmHg, 1 mmHg =0.133 kPa): 9.64±5.08 vs. 6.70±3.71, allP < 0.01], and there was no significant difference in the other arterial and venous blood gas analysis index and its corresponding differential difference between two groups. ③ Multiple Logistic regression analysis showed that ΔPCO2 [β = 0.247, odd ratio (OR) = 1.280, 95％ confidential interval (95％CI) = 1.057-1.550,P = 0.011], and ΔLac (β = 2.696,OR = 14.820, 95％CI = 2.916-75.324,P = 0.001) were the independent risk factors for the prognosis of septic shock. ④ It was shown by ROC curve analysis that arterial blood Lac, ΔLac andΔPCO2 had predictive value on prognosis of septic shock, the area under ROC curve (AUC) was 0.792, 0.857, 0.680, respectively (allP < 0.05). When the best cut-off value of arterial Lac was 4.00 mmol/L, the sensitivity was 100％, and the specificity was 62.86％ for predictor of death in 28-day; when the best cut-off value of ΔLac was 1.25 mmol/L, the sensitivity was 93.33％, and the specificity was 68.57％ for predictor of death in 28-day; when the best cut-off value of ΔPCO2 was 4.35 mmHg, the sensitivity was 83.33％, and the specificity was 37.14％ for predictor of death in 28-day.Conclusions Compared to other parameters, the difference between peripheral arterial and venous blood gas analysis, ΔPCO2 and ΔLac had the best correlation with the prognosis of septic shock. The ΔPCO2 and ΔLac are the independent prognostic predictors for 28-day survival.
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We investigated the roles of the crude antigen(CA) of Clonorchis sinensis and excretory secretory products (ESPs) in the polarization of Th1 and Th2 cells.Bone marrow-derived cells were generated from BALB/c mice and isolated into immature DCs;immature DCs were then treated with either CA (CA stimulated group),ESPs (ESPs stimulated group),LPS (positive control group) or PBS (negative control group) for 24 hours.Then the CD4+T cells were isolated from mouse spleen by using anti mouse-CD4 Microbeads,and further cocultured with stimulated DCs for another 72 hours.The purities of DCs and CD4+ T cells were evaluated by flow cytometry and the expressing levels of T-bet mRNA and GATA-3 mRNA were detected by real-time PCR.ELISA was used to detect the levels of IFN-γ and IL-4 cytokines in the supernatant.mRNA levels of T-bet and GATA-3 in the ESPs group were higher than those in PBS-stimulated group (P＜0.05).The concentrations of IFN-γ and IL-4 cytokines in the culture were increased in the ESPs group,compared with PBS stimulated group(P＜0.05).IFN-γ but not IL-4 was increased in CA group (P＜0.05).The results implied that CA might play a role in Th1 type immune response,and ESPs likely play roles in both Th1 and Th2 immune responses.
ABSTRACT
Objective To investigate the effects of GM-CSF (granulocyte-macrophage colony-stimulating factor) as an immune adjuvant on the anti-fertility efficacy of canine zona pellucida glycoprotein 3 (CZP3) DNA vaccine.Methods RT-PCR and quantitative real-time PCR were performed to analyze the effects of GM-CSF on the maturation of antigen presenting cells (APCs) and the enrichment of APCs at injection site.Female BALB/c mice were immunized with CZP3 DNA vaccine pcDNA3-CZP3 alone or in combination with genetic adjuvant pcDNA3-GM-CSF by using the method of electrical impulses.ELISA (enzyme-linked immunosorbent assay) was used to detect the levels of IgG and sIgA (secretory IgA) antibodies in serum samples and genital tracts and the levels of IL-4 and IFN-γ in serum samples.MTT method was used to analyze the proliferation of spleen T cells in mice.The binding ability of serum anti-CZP3 antibody to native mouse oocytes was analyzed by indirect immunofluorescence assay.All of the female BALB/c mice were coupled with male mice of the same age six weeks after the first-dose vaccination.Litter size at birth in each group was counted and the differences between different groups were comparatively analyzed.ResultsImmunizing the mice with pcDNA3-CZP3 and GM-CSF significantly promoted the expression of CD80, CD83 and CD86 (P<0.05) and increased the sIgA antibody level in genital tract and IgG level in serum (P<0.01).Moreover, the levels of IL-4 and IFN-γ in serum samples were significantly up-regulated (P<0.05) and the proliferation of spleen T cells was significantly enhanced (P<0.05).Results of the indirect immunofluorescence assay showed that the fluorescence intensity and density on mouse egg surface were positively correlated with the level of antibody in serum.Results of the anti-fertility test suggested that GM-CSF significantly reduced the litter size in mice immunized with pcDNA3-CZP3 vaccine (P<0.05).Conclusion GM-CSF could be used as an effective adjuvant to enhance the anti-fertility efficacy of CZP3 DNA vaccine.