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Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.
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ObjectiveTo study the chemical constituents of the seeds of Sophora tonkinensis. MethodThe chemical constituents were isolated and purified by chromatography with MCI resin， silica gel， Sephadex LH-20， and semi-preparative high performance liquid chromatography. Their structures were identified by physicochemical properties， spectral data as well as relevant references. Meanwhile， the antibacterial activities against Helicobacter pylori of these compounds were screened by agar dilution method. ResultA total of 22 compounds were isolated from the methanol extract of the seeds of S. tonkinensis， and characterized as 4′，7-dihydroxy-6-methoxy isoflavone （1）， daidzein （2）， wighteone （3）， dalparvone （4）， 5，7-dihydroxy-4′-methoxyisoflavone （5）， prunetin （6）， formononetin （7）， genistein （8）， 5-methoxydaidzein （9）， ononin （10）， 7，4′-dihydroxyflavone （11）， liquiritigenin （12）， bayin （13）， 2，4-dihydroxybenzoate （14）， methyparaben （15）， 4-hydroxyacetophenone （16）， p-anisaldehyde （17）， methyl indole-3-carboxylate （18）， 4-［β-D-apiofuranoyl-（1→6）-O-β-D-glucopyranosyloxy］ phenylacetonitrile （19）， （-）-methyl dihydrophaseate （20）， methyl canavaliol ester （21）， vomifoliol 3′-O-β-D-apiofuranosyl-（1→6）-β-D-glucopyranoside （22）. ConclusionCompounds 1， 5， 6， 9 and 16 are isolated from S. tonkinensis for the first time， compounds 4， 14， 17-22 are isolated from the genus of Sophora for the first time. In addition， compounds 10 and 13 display moderate antibacterial activities against H. pylori.
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OBJECTIVES@#To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission.@*METHODS@#A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points.@*RESULTS@#On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism.@*CONCLUSIONS@#The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.
Subject(s)
Humans , Infant, Newborn , Ascorbic Acid , Cysteine , Metabolomics , Methionine , Neonatal Sepsis , Pyruvates , SepsisABSTRACT
This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.
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Animals , Humans , Rats , Glucocorticoids/pharmacology , Human Umbilical Vein Endothelial Cells , Neovascularization, Pathologic/metabolism , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolismABSTRACT
@#Adoptive cellular immunotherapy has been widely recognized in recent years due to its remarkable results, especially the success of CD19-specific chimeric antigen receptor (CAR) autologous T cell therapy for malignant hematoma. Previous studies have found the existence of tumor immune microenvironment, heterogeneous targets, and immunosuppressive receptors in solid tumors, which has led to the shortcomings of CAR-T treatment of solid tumors. This article proposes the methods to improve CAR-T cells to increase T cell infiltration, co-expression of cytokines and enzymes and modification of related receptors in order to enhance the anti-solid tumor activity of CAR-T, laying a theoretical foundation for the follow-up CAR-T cell treatment of solid tumors.
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Objective:To explore the effects and mechanism of PR-957 on hypoxic-ischemic brain damage(HIBD) of newborn rats.Methods:A total of 54 rats aged seven days were recruited and randomly divided into sham operation group, HIBD group and PR-957 intraperitoneal group.HIBD model was established according to modified Rice method.PR-957 group was given intraperitoneal injection PR-957(20 mg/kg) after hypoxic-ischemic.Model group was intraperitoneally injected with equal volume of DMSO.Ligation or hypoxic treatment were not given in sham operation group.HE staining was applied to observe inflammation in cortex.Immunohistochemical analysis was adopted to observe the expression of interleukin(IL)-17 and IL-10 in brain tissue.Western blot was carried out to test the protein level of low molecular poly peptide 7 (LMP7), forkhead box P3(FOXP3), and retinoic acid-recepter-related orphan receptor gamma t(RORγt). The proportion of T helper cells 17(Th17)/Treg was detected by flow cytometry.Results:HE staining displayed that sham operation group brain structure was basically normal, HIBD group revealed significant inflammation in the left cerebral cortex, while some pathological improvement was observed in PR-957 group.Immunohistochemistry: IL-10 positive cells in left cortex of HIBD group [(12.11±3.73)%] were lower than sham operation group[(29.12±3.95)%] and PR-957 group[(22.61±6.59)%], and the differences were statistically significant (all P<0.05). IL-17 positive cells in the left cortex of HIBD group [(35.55±4.85)%] were higher than sham operation group [(8.48±2.58)%] and PR-957 group [(19.16±4.31)%], and the differences were statistically significant (all P<0.05). Western blot: the expression of LMP7 and RORγt in HIBD group (1.01±0.12, 0.71±0.10) were higher than those in sham operation group (0.50±0.10, 0.34±0.07) and PR-957 group (0.65±0.13, 0.54±0.07), and the differences were statistically significant ( P<0.05). The expression of FOXP3 in HIBD group (0.44±0.10) was lower than sham operation group (0.93±0.07) and PR-957 group (0.68±0.09), and the differences were statistically significant (all P<0.05). The flow cytometry of peripheral blood: the Th17/Treg ratio of HIBD group (0.66±0.24) was higher than sham operation group (0.20±0.09) and PR-957 group (0.45±0.18), and the differences were statistically significant (all P<0.05). Conclusion:PR-957 can regulate the immune balance of Th17/Treg cells and reduce the inflammatory in the brain tissues of HIBD newborn rats.
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Objective:To study the effect of melatonin (MEL) on the pyroptosis of hippocampus in neonatal rats with hypoxic-ischemic brain damage (HIBD), and the related mechanism.Methods:The animal model of HIBD was established by the modified Rice method.According to the random number table, a total of 105 Sprague-Dawley (SD) rats aged 7 days were divided into 7 groups (15 rats in each group): sham operation (Sham) group, model (HIBD) group, MEL treatment group (5, 10 and 20 mg/kg), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway inhibitor (LY294002) treatment group and MEL+ LY294002 group.The hippocampus neuronal morphology and the changes of nissl bodies were observed through HE staining and nissl staining.The mRNA expression levels of Nod-like receptor family 3 (NLRP3), apoptosis-associated speck-like protein containing a card (ASC), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the left hippocampus of rats were detected by real-time fluorescence quantitative PCR.The protein expression level of the above indexes and the level of phosphorylated Akt (p-Akt) were measured by Western blot.Results:Compared with the Sham group, the number of cell layers in hippocampal CA1 region in the HIBD group decreased, the cell arrangement was irregular, and there were less nissl bodies.Besides, the mRNA expression levels of NLRP3 (1.98±0.08 vs.0.86±0.13), ASC (1.40±0.12 vs.0.81±0.07), Caspase-1 (1.46±0.10 vs.0.75±0.09), GSDMD (1.35±0.10 vs.0.81±0.10), IL-18 (1.23±0.08 vs.0.23±0.04), IL-1β (1.83±0.09 vs.0.57±0.08) and p-Akt (1.12±0.12 vs.0.54±0.07) in the HIBD group were significant higher than those in the Sham group (all P<0.05). Compared with the HIBD group, there were more cell layers in hippocampal CA1 region of the MEL group (10 mg/kg), the arrangement of cells was more regular, and the number of nissl bodies increased.The mRNA expression levels of NLRP3 (1.04±0.10), ASC (0.91±0.06), Caspase-1 (0.63±0.06), GSDMD (1.01±0.09), IL-18 (0.65±0.05) and IL-1β (0.63±0.10) in the MEL group were statistically significantly lower than those in the HIBD group (all P<0.05). Compared with the MEL group (10 mg/kg), the arrangement of cells in hippocampal CA1 region of the MEL+ LY294002 group was relatively disordered, the nissl bodies declined, the p-Akt protein level (0.87±0.09 vs.1.99±0.27) decreased significantly, and the Caspase-1(p20) protein level (0.85±0.09 vs.0.58±0.09) increased significantly (all P<0.05). Conclusions:MEL may inhibit the hippocampal pyroptosis in neonatal rats with HIBD by activating the Akt signaling pathway, thereby protecting the brain.
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A review of the basic and clinical researches on the traditional Chinese medicine (TCM) for pancreatic cancer. Current researches show that the treatment of pancreatic cancer with traditional Chinese medicine can inhibit tumor cell proliferation, invasion and angiogenesis, induce cell apoptosis, reverse tumor multidrug resistance and inhibit tumor angiogenesis. There are a mount of therapeutic TCM treatment, which can improve the clinical symptoms, reduce the adverse reactions of chemotherapy drugs, improve the quality of life and chemotherapy effect.
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A series of novel pyrano[2, 3-d]trizaole compounds were synthesized and their α-glucosidase inhibitory activities were evaluated by in vitro enzyme assay. The experimental data demonstrated that compound 10f showed up to 10-fold higher inhibition (IC74.0 ± 1.3 μmol·L) than acarbose. The molecular docking revealed that compound 10f could bind to α-glucosidase via the hydrophobic, π-π stacking, and hydrogen bonding interactions. The results may benefit further structural modifications to find new and potent α-glucosidase inhibitors.
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OBJECTIVE@#To observe the effect of early acupoint electrical stimulation on the decline of lower limbs muscle strength in patients with intensive care unit-acquired weakness (ICU-AW) caused by septic shock.@*METHODS@#A total of 58 patients with ICU-AW caused by septic shock were randomly divided into an observation group (28 cases, 1 case dropped off ) and a control group (30 cases, 2 cases dropped off ). Patients in both groups received routine basic treatment. In the observation group, acupoint electric stimulation therapy was added at Huantiao (GB 30), Futu (ST 32), Zusanli (ST 36), Xuanzhong (GB 39) and Taichong (LR 3). Unilateral point with electrodes were applied, the SDZ-Ⅱ electronic instrument (discontinuous wave, frequency in 2 Hz, strength in 5 mA) was connected and changed to the other side after 30 min of unilateral treatment.The treatment was given 2 times daily, continued for 7 d or until the medical research council (MRC) score being 54 points or more. The changes of lower limb muscle strength MRC score, modified Rankin scale (MRS) score, bilateral quadriceps thickness and gastrocnemius pinnate angle of both groups were observed before treatment and on discharge. The time of admission to ICU, time of hospitalization, mortality during hospitalization, and mortality 28 d after discharge were compared between the two groups. The MRS scores of the two groups were followed up 28 d after discharge.@*RESULTS@#The MRC scores of lower limb muscle strength in the two groups on discharge were higher than those before treatment (@*CONCLUSION@#Early acupoint electrical stimulation can improve the lower extremity muscle decline in patients with ICU-AW caused by septic shock.
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Humans , Acupuncture Points , Electric Stimulation , Lower Extremity , Muscle Strength , Shock, Septic/therapyABSTRACT
This article reported a case of nemaline myopathy caused by KLHL40 gene complex heterozygous mutations. This baby girl presented with shortness of breath, low myodynamia, and low muscle tension immediately after birth. However, her symptoms became worse after conventional treatment. Physical examination found lower muscle strength and muscle tone in four limbs and no primitive reflexes. The biochemistry test showed increased serum creatine kinase (CK). A muscle biopsy was not performed. The second-generation gene test confirmed the KLHL40 gene complex heterozygous mutations, which was a known mutation c.932G>T (p.R311L) and a de novo mutation c.1487T>A (p.M496K), inherited from the father and mother, respectively. Nemaline myopathy is a rare congenital muscular disease characterized by nemaline bodies in muscle fibers. Pathological and genetic diagnoses are the gold standards for the diagnosis of this disease.
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Objective: To investigate the safety and efficacy of regional transport to percutaneous coronary intervention(PCI) hospitals from non-PCI hospitals after thrombolysis in patients with acute ST-segment elevation myocardial infarction(STEMI) in northwest China. Methods: In this retrospective study, 1 062 STEMI patients who were transferred from non-PCI hospitals within 24 hours from symptom onset, during January 2015 and January 2019 in the First Hospital of Lanzhou University, were included. According to the treatment strategy, they were divided into two groups, namely intravenous thrombolysis combined with PCI group(n=240), and primary PCI group(n=822). Observation endpoint were in-hospital adverse cardiovascular and cerebrovascular events and bleeding events, Including all-cause death, ischemic stroke, malignant arrhythmia, intracranial hemorrhage and hemorrhage with hemoglobin decrease≥50 g/L. Results: A total of 1 062 STEMI patients were included(age was (61±12) years old), with 905 males (85.2%). The proportion of grade 0 TIMI blood flow in the primary PCI group before operation was significantly higher than that in the thrombolysis combined with PCI group(63.0%(518/822) vs. 36.3%(87/240)， P<0.001). Compared with primary PCI group, the time from symptom onset to first medical contact(2.11(1.00, 4.00)hours vs.3.00(1.13, 7.07)hours, P<0.001) and reperfusion in thrombolysis combined with PCI group(3.07(1.83, 4.87)hours vs. 6.92(4.07, 11.15) hours, P<0.001) were significantly shorter. The proportion of all-cause death was significantly higher in the primary PCI group than that in the thrombolysis combined with PCI group (1.8%(15/822) vs. 0, P=0.03). There was no significant difference in hemorrhage, ischemic stroke and malignant arrhythmia between the two groups(all P>0.05). Conclusions: For STEMI patients initially hospitalized in non-PCI hospitals, regional transport combined with PCI is feasible and effective. It does not significantly increase the risk of bleeding and cardiovascular and cerebrovascular events, with shorter time from symptom onset to myocardial reperfusion.
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Aged , Humans , Male , Middle Aged , Angioplasty, Balloon, Coronary , China , Myocardial Infarction , Percutaneous Coronary Intervention , Retrospective Studies , ST Elevation Myocardial Infarction/therapy , Thrombolytic Therapy , Treatment OutcomeABSTRACT
A female infant, aged 43 days, had shortness of breath, cyanosis, groan, and dyspnea since birth. Physical examination showed cyanosis of lips and three-concave sign, and multiple lung imaging examinations showed diffuse ground-glass opacities in both lungs. The girl was given anti-infective therapy and continuous mechanical ventilation but there were no significant improvements in symptoms. Gene testing confirmed a compound heterozygous mutation, c.1890C>A(p.Tyr630Ter)+c.3208G>A(p.Ala1070Thr), in the ABCA3 gene, with the former from her father and the latter from her mother. Pathological examination of the lungs indicated pulmonary interstitial disease. The girl was diagnosed with infantile diffuse pulmonary interstitial disease caused by mutations in the ABCA3 gene. When full-term neonates experience shortness of breath and dyspnea after birth, pulmonary imaging suggests diffuse ground-glass changes, and conventional treatment is not effective (ventilator-dependent), congenital pulmonary surfactant metabolism defects needs to be considered. Gene testing, which can provide a basis for early intervention, prognostic evaluation, and genetic counseling, should be performed as early as possible.
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Female , Humans , Infant , Dyspnea , Lung , Lung Diseases, Interstitial , Mutation , Pulmonary SurfactantsABSTRACT
Background@#Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome, which is an autosomal dominant disorder caused by mutation of the folliculin (FLCN) gene. This study was established to investigate the mutation of the FLCN gene and the phenotype in a family with PSP.@*Methods@#We investigated the clinical and genetic characteristics of a large Chinese family with recurrent spontaneous pneumothorax. Genetic testing was performed by Sanger sequencing of the coding exons (4-14 exons) of the FLCN gene.@*Results@#Among ten affected members in a multi-generational PSP kindred, with a total of 18 episodes of spontaneous pneumothorax, the median age for the initial onset of pneumothorax was 42.5 years (interquartile range: 28.8-57.2 years). Chest computed tomography scan of the proband showed pulmonary cysts and pneumothorax. A novel nonsense mutation (c.1273C>T) in exon 11 of FLCN gene that leads to a pre-mature stop codon (p.Gln425*) was identified in the family. The genetic analysis confirmed the diagnosis of BHD syndrome in this family in the absence of skin lesions or renal tumors.@*Conclusions@#A novel nonsense mutation of FLCN gene was found in a large family with PSP in China. Our results expand the mutational spectrum of FLCN gene in patients with BHD syndrome.
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Objective@#To investigate the clinical application values of computed tomography (CT), ischemic modified albumin (IMA) and D-dimer (D-D) levels in the disease assessment of patients with acute pulmonary embolism (APE).@*Methods@#From June 2015 to June 2018, 100 suspected APE patients in our hospital were selected as the study subjects, after the CT " gold standard" inspection, the 80 patients diagnosed with APE were as APE group, including 38 cases in high-risk group and 42 cases in low-risk group: 20 non APE cases and 60 healthy volunteers at the same time were selected as control group. The serum IMA level was detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the plasma D-D level was detected by immunoturbidimetry. Receiver operating characteristc (ROC) curve was used to analyze the diagnostic values of IMA and D-D for APE disease.@*Results@#The levels of IMA and D-D in APE group were significantly higher than those in non APE group and control group (P<0.05); the levels of IMA and D-D in non APE group were significantly higher than those in control group (P<0.05), while those in high-risk group were significantly higher than those in low-risk group (P<0.05); CT examination after admission was as the gold standard for diagnosing APE disease; ROC curve showed that, the area under curve (AUC) of D-D and IMA in diagnosing APE was 0.875 and 0.763, respectively, with corresponding sensitivity 90.01% and 93.87%, specificity 52.21% and 95.65% respectively; the AUC of IMA combined D-D level in diagnosing APE was 0.834, the sensitivity was 95.87%, and the specificity was 78.69%; the AUC of D-D and IMA in diagnosing high-risk APE was 0.950 and 0.914, respectively, with the corresponding sensitivity 97.21% and 93.98%, specificity 31.58% and 76.98%, respectively. The AUC of IMA combined D-D level in diagnosing high-risk APE was 0.958, with sensitivity 96.39%, specificity 76.87%. Compared with CT results, in the 80 patients diagnosed with APE, there were 4 patients with negative IMA and 6 patients with negative D-D, and the control group samples test showed negative IMA and D-D levels were all negative. The consistency of CT combine with D-D ( Kappa=0.734, P=0.000), and CT combine with IMA (Kappa=0.819, P=0.000) were good.@*Conclusions@#According to the results of CT examination, IMA combined with D-D level has a good sensitivity and specificity in the diagnosis of APE, which can effectively improve the diagnostic rate of APE diseases, and provide an important basis for clinical rapid and reliable detection and treatment of APE diseases.
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Objective To investigate the clinical application values of computed tomography (CT),ischemic modified albumin (IMA) and D-dimer (D-D) levels in the disease assessment of patients with acute pulmonary embolism (APE).Methods From June 2015 to June 2018,100 suspected APE patients in our hospital were selected as the study subjects,after the CT " gold standard" inspection,the 80 patients diagnosed with APE were as APE group,including 38 cases in high-risk group and 42 cases in low-risk group:20 non APE cases and 60 healthy volunteers at the same time were selected as control group.The serum IMA level was detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA),and the plasma D-D level was detected by immunoturbidimetry.Receiver operating characteristc (ROC) curve was used to analyze the diagnostic values of IMA and D-D for APE disease.Results The levels of IMA and D-D in APE group were significantly higher than those in non APE group and control group (P ＜ 0.05);the levels of IMA and D-D in non APE group were significantly higher than those in control group (P ＜ 0.05),while those in high-risk group were significantly higher than those in low-risk group (P ＜ 0.05);CT examination after admission was as the gold standard for diagnosing APE disease;ROC curve showed that,the area under curve (AUC) of D-D and IMA in diagnosing APE was 0.875 and 0.763,respectively,with corresponding sensitivity 90.01％ and 93.87％,specificity 52.21％ and 95.65％ respectively;the AUC of IMA combined D-D level in diagnosing APE was 0.834,the sensitivity was 95.87％,and the specificity was 78.69％;the AUC of D-D and IMA in diagnosing high-risk APE was 0.950 and 0.914,respectively,with the corresponding sensitivity 97.21％ and 93.98％,specificity 31.58％ and 76.98％,respectively.The AUC of IMA combined D-D level in diagnosing high-risk APE was 0.958,with sensitivity 96.39％,specificity 76.87％.Compared with CT results,in the 80 patients diagnosed with APE,there were 4 patients with negative IMA and 6 patients with negative D-D,and the control group samples test showed negative IMA and D-D levels were all negative.The consistency of CT combine with D-D (Kappa =0.734,P =0.000),and CT combine with IMA (Kappa =0.819,P =0.000) were good.Conclusions According to the results of CT examination,IMA combined with D-D level has a good sensitivity and specificity in the diagnosis of APE,which can effectively improve the diagnostic rate of APE diseases,and provide an important basis for clinical rapid and reliable detection and treatment of APE diseases.
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Objective To explore the effect of goal-directed therapy bundle based on pulse-indicated continuous cardiac output (PiCCO) parameters to the prevention and treatment of acute kidney injury (AKI) in patients after cardiopulmonary bypass cardiac operation. Methods A prospective observational study was conducted. The adult patients with selective cardiopulmonary bypass cardiac operation admitted to the Third People's Hospital of Chengdu from December 2015 to January 2018 were enrolled. All patients were divided into two groups based on informed consent for PiCCO monitor at the time of admission to the intensive care unit (ICU): regular monitoring and treatment group (group A) and goal-directed therapy group based on PiCCO parameters (group B). In group A, the restrictive capacity management strategy was implemented to maintain the mean arterial pressure (MAP) > 65 mmHg (1 mmHg = 0.133 kPa) and the central venous pressure (CVP) between 8 mmHg and 10 mmHg. In group B, volume and hemodynamic status were optimized depending on PiCCO parameters to a goal of cardiac index (CI) > 41.68 mL·s-1·m-2, global end diastolic volume index (GEDVI) > 700 mL/m2 or intrathoracic blood volume index (ITBVI) > 850 mL/m2, extravascular lung water index (EVLWI) < 10 mL/kg, and MAP > 65 mmHg. Then the changes in hemodynamics and different prognosis of the patients in two groups were observed. Risk factors affecting the AKI were analyzed by Logistic regression. Results 171 cases were included, with 68 in group A and 103 in group B. There were no significant differences in gender, age, pre-operative scores by European system for cardiac operative risk evaluation (EuroScore), operation ways, operation time, cardiopulmonary bypass time, intraoperative dominant liquid equilibrium quantity, the use of intra-aortic balloon counterpulsation (IABP) during operation, and serum creatinine (SCr) level at the time of admission to ICU between the two groups. There were no significant differences in CVP within 24 hours after admission to ICU between the two groups. MAP in group B was significantly higher than that in group A at 8 hours and 16 hours after ICU admission (mmHg: 68.9±6.3 vs. 66.7±5.1, 69.0±4.9 vs. 67.0±5.3, both P < 0.05). Sequential organ failure assessment (SOFA) score in group B was significantly lower than that in group A at 24 hours after ICU admission (5.7±2.2 vs. 6.9±2.8, P < 0.05). Dominant liquid equilibrium quantity in group B was significant higher than that in group A at 24 hours after ICU admission (mL/kg: 7.1±6.2 vs. -0.1±8.2, P < 0.01), but there was no significant difference of that between groups at 48 hours and 72 hours after ICU admission. Compared with group A, incidence of combination with AKI during 72 hours after ICU admission was significantly decreased in group B [48.5% vs. 69.1%; odds ratio (OR) =0.422, 95% confidence interval (95%CI) = 0.222-0.802, P < 0.05], and incidence of moderate to severe AKI was also significantly decreased in group B (19.4% vs. 35.3%; OR = 0.442, 95%CI = 0.220-0.887, P < 0.05). There was no significant difference in usage of continuous renal replacement therapy (CRRT) after ICU admission between both groups (group A was 4.4%, group B was 4.9%, P > 0.05). It was shown by correlation analysis that only MAP and CI at 8 hours after ICU admission were significantly negatively correlated with AKI (MAP and AKI: r = -0.697, P = 0.000;CI and AKI: r = -0.664, P = 0.000). It was shown by Logistic regressive analysis that the MAP and CI at 8 hours after ICU admission were independent risk factors that influence the incidence of AKI at 72 hours after ICU admission (MAP:OR = 0.736, 95%CI = 0.636-0.851, P = 0.000; CI: OR = 0.006, 95%CI = 0.001-0.063, P = 0.000). There were no significant differences in the duration of mechanical ventilation, the length of ICU stay, the post-operation complications (except AKI), 7-day and 28-day mortality between the two groups. Conclusions Goal-directed therapy bundle based on PiCCO parameters reduced the incidence of AKI in patients after cardiopulmonary bypass cardiac operation and improved the severity of systemic disease. However, it did not reduce the duration of mechanical ventilation, length of ICU stay, the incidence of complications (except AKI), short-term mortality. The MAP and CI at 8 hours after ICU admission were independent risk factors that influence the incidence of AKI in patients after cardiopulmonary bypass cardiac operation.
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BACKGROUND@#Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome, which is an autosomal dominant disorder caused by mutation of the folliculin (FLCN) gene. This study was established to investigate the mutation of the FLCN gene and the phenotype in a family with PSP.@*METHODS@#We investigated the clinical and genetic characteristics of a large Chinese family with recurrent spontaneous pneumothorax. Genetic testing was performed by Sanger sequencing of the coding exons (4-14 exons) of the FLCN gene.@*RESULTS@#Among ten affected members in a multi-generational PSP kindred, with a total of 18 episodes of spontaneous pneumothorax, the median age for the initial onset of pneumothorax was 42.5 years (interquartile range: 28.8-57.2 years). Chest computed tomography scan of the proband showed pulmonary cysts and pneumothorax. A novel nonsense mutation (c.1273C>T) in exon 11 of FLCN gene that leads to a pre-mature stop codon (p.Gln425*) was identified in the family. The genetic analysis confirmed the diagnosis of BHD syndrome in this family in the absence of skin lesions or renal tumors.@*CONCLUSIONS@#A novel nonsense mutation of FLCN gene was found in a large family with PSP in China. Our results expand the mutational spectrum of FLCN gene in patients with BHD syndrome.
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OBJECTIVE@#To observe the effect of ultrasound-guided acupoint electrical stimulation on the patients with diaphragmatic dysfunction associated with mechanical ventilation in ICU.@*METHODS@#Fifty-two patients were randomly divided into an observation group (26 cases, 3 cases dropping) and a control group (26 cases). Conventional treatment was given to all patients. On the basis of conventional treatment, acupoint electrical stimulation therapy was applied at Zhangmen (LR 3), Dabao (SP 21), Pishu (BL 20), Shenshu (BL 23), etc. In the observation group, the treatment was given for 30 min each time, 3 times a day for 7 days. Diaphragm thickening fraction (TFdi) was used as an index to guide the individualized setting of stimulation intensity and judge the effect, and the difference of mechanical ventilation time, ICU time, total hospitalization time, hospital mortality and reintubation rate between the two groups were observed.@*RESULTS@#The mechanical ventilation time in the observation group was shorter than that in the control group (0.05). During hospitalization, 2 patients died in the observation group and 3 patients died in the control group, there was no significant difference in hospital mortality (>0.05). One patient in the observation group was reintubated and 8 patients in the control group (<0.05). The use of acupoint electrical stimulation was a factor in shortening the mechanical ventilation time and reducing the reintubation events (<0.05).@*CONCLUSION@#Ultrasound-guided acupoint electrical stimulation can relieve ventilator-induced diaphragmatic dysfunction, reduce ventilator support time and reintubation events.
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Humans , Acupuncture Points , Diaphragm , Electric Stimulation , Electric Stimulation Therapy , Respiration, ArtificialABSTRACT
Objective@#To establish a real-time PCR (RT-PCR) assay for detecting mRNA expression of killer cell immunoglobulin-like receptor (KIR) 2DS1 gene( KIR2DS1 ) on the surface of natural killer (NK) cells, and evaluate its performance. @*Methods@#A total of 57 recipient-donor pairs of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) were enrolled in this study. The specific primers and probe of KIR2DS1 gene were designed for Taqman-MGB fluorescence quantitative PCR detection system. The performance parameters of the detecting system, such as coincidence rate, repeatability, sensitivity, scope of application of the instrument and reproducibility of operation technicians were evaluated and validated. @*Results@#The KIR-SSO Genotyping Test was used as the gold standard. The results of 35 samples showed the accuracies of self-built method were all 100% for both of positive and negative KIR2DS1 . Three samples with high, median and low value of Ct values were used to verify the repeatability. The coefficients of variation of intra-assay and inter-assay were ranged from 0.09% to 0.46% and 0.71% to 1.13% respectively. The sensitivity of the established method was up to 10 2 copies/μL at least. The coefficients of variation of the three samples with sensitivity of 10 2 copies/μL were 5.37%, 2.71% and 5.51% in five repeated tests respectively. The regression analysis for the samples measured by ABI-7500 and LC-480 fluorescence quantitative PCR instrument showed regression equation was Y=0.973 6X+0.118 3 (R 2 =0.961 9, R 2 ＞0.95). The reproducibility of 10 samples with positive KIR2DS1 operated by two technicians showed that the biases were all less than ±5%. @*Conclusion@#A TaqMan-MGB real-time PCR assay for detection of mRNA expression of KIR2DS1 gene was established successfully with fine performance.