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OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject， and substance P as positive control， the activation effects of 25， 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase， histamine release， and the contents of inflammatory factors； using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 （MRGPRX2） high-expression human embryonic kidney cell line HEK293 （MRGPRX2/ HEK293 cells） as subject， the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase， and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25， 50， 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells （P＜0.05）， and promote the release of tumor necrosis factor-α， interleukin-8， macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees （P＜0.05）. After knocking down MrgprX2， the effects of 25， 50， 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly （P＜0.05）， resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.
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Objective:To investigate the risk factors that affected pathological diagnosis upgrading after resection of colorectal adenoma.Methods:From January 2017 to December 2022, a total of 1 059 patients who underwent adenoma resection after pathologically diagnosed as adenoma by endoscopic forceps biopsy(EFB)were included in General Hospital of Ningxia Medical University. The patients were divided into the pathologically no difference group (1 003 cases) and the pathologically upgraded group (56 cases) based on the comparison of pathological diagnosis of EFB specimens and the specimens after adenoma resection. Clinical information and endoscopic characteristics of the adenoma were compared between the 2 groups. The clinical information included smoking history, family history of colorectal cancer, and the endoscopic characteristics included maximum diameter, morphological characteristics, surface depression, erosion or ulceration, and surface color of adenoma. Chi-square test and Fisher′s exact test were used for statistical analysis. Multivariate logistic regression model was used to analyze the risk factors for pathological diagnosis upgrading after adenoma resection.Results:The proportions of patients with smoking history, family history of colorectal cancer, concomitant hypertension, and coronary heart disease in the pathologically upgraded group were higher than those in the pathologically no difference group (46.43%, 26/56 vs.26.12%, 262/1 003; 8.93%, 5/56 vs.0.70%, 7/1 003; 46.43%, 26/56 vs.30.11%, 302/1 003; 21.43%, 12/56 vs.9.27%, 93/1 003), and the differences were statistically significant( χ2=11.05, Fisher′s exact test, χ2=6.61 and 8.78; all P<0.05). There were statistically significant differences between the pathologically no difference group and pathologically upgraded group in the maximum diameter (929 cases (92.62%) and 23 cases (41.07%) of < 20 mm, and 74 cases (7.38%) and 33 cases (58.93%) of ≥20 mm, respectively), morphological characteristics (220 cases (21.93%) and 28 cases (50.00%) with pedicle, and 783 cases (78.07%) and 28 cases (50.00%) without pedicle, respectively), surface color (347 cases (34.60%) and 3 cases (5.36%) of near normal mucosa, 613 cases (61.12%) and 50 cases (89.29%) of red surface color, and 43 cases (4.29%) and 3 cases (5.36%) of white surface color, respectively), erosion or ulceration (78 cases (7.78%) and 36 cases (64.29%) had erosion or ulceration, and 925 cases (92.22%) and 20 cases (35.71%) had no erosion or ulceration, respectively), and surface depression (6 cases (0.60%) and 8 cases (14.29%) of depression, and 997 cases (99.40%) and 48 cases (85.71%) of non depression, respectively) ( χ2=155.18, 23.30, 20.58 and 176.31, Fisher′s exact test; all P<0.001). The result of multivariate logistic regression analysis showed that surface depression ( OR=25.198, 95% confidence interval (95% CI) 5.812 to 109.246, P<0.001), erosion or ulceration( OR=9.913, 95% CI 4.652 to 21.124, P<0.001), red surface color ( OR=4.276, 95% CI 1.053 to 17.363, P=0.042), white surface color ( OR=8.803, 95% CI 1.398 to 55.435, P=0.021), maximum diameter≥20 mm ( OR=4.689, 95% CI 2.265 to 9.706, P<0.001), family history of colorectal cancer ( OR=8.764, 95% CI 1.418 to 54.162, P=0.019) and smoking history ( OR=2.713, 95% CI 1.376 to 5.349, P=0.004) were independent risk factors for pathological diagnosis upgrading after adenoma resection. Conclusion:Surface depression, maximum diameter ≥20 mm, erosion or ulceration, white or red surface color, family history of colorectal cancer and smoking history may enhance the heterogeneity of adenomas, interfere with the accuracy of EFB pathology, and lead to an upgrade of pathological diagnosis after adenoma resection.
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The outbreak of COVID-19 as an acute communicable disease has also changed the epidemiological status of diabetes mellitus and other noncommunicable chronic diseases. During the COVID-19 epidemic period, it was observed that there were increased morbidity of diabetes, difficulties in blood sugar control and increased acute complications for diabetic patients. This may be attributed to lifestyle changes during the epidemics, such as the reduced exercise time and increased sedentary time, more snacks and sugary food intake, as well as anxiety and depression. However, it is not known the long-term impact of COVID-19 epidemic on the management of diabetic patients, so it is necessary to closely monitor the exposed diabetic patients in the future.
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Objective:To evaluate the effects of remimazolam on gastrointestinal motor function in the patients undergoing gastrointestinal endoscopy.Methods:A total of 262 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-64 yr, with body mass index of 18-28 kg/m 2, scheduled for elective gastrointestinal endoscopy from May 2022 to August 2022, were divided into 2 groups ( n=131 each) using a random number table method: remimazolam group (group R) and propofol group (group P). The patients in group R received intravenous remimazolam 0.20-0.25 mg/kg, and patients in group P received intravenous propofol 1.5-2.0 mg/kg. The gastrointestinal endoscopy was performed when the patients′ Modified Observer′s Assessment of Alertness/Sedation scores ≤3. During fasting before gastrointestinal preparation, before gastrointestinal endoscopy and while leaving the post-anesthesia care unit (PACU), the concentrations of serum motilin and gastrin were measured by enzyme-linked immunosorbent assay, the intestinal peristalsis rating assessed by the endoscopist during the examination was recorded, the occurrence of hypotension and hypoxemia during the examination and occurrence of abdominal distension, abdominal pain, and nausea and vomiting during stay in PACU were recorded. Results:Compared with group P, the intestinal peristalsis rating was significantly increased, the serum motilin and gastrin concentrations were increased while leaving PACU, the incidence of hypotension and hypoxemia was decreased during the examination, and the incidence of abdominal distention was decreased during stay in PACU in group R ( P<0.05). Conclusions:Remimazolam has a milder inhibitory effect on secretion of gastrointestinal hormones than propofol in the patients undergoing gastrointestinal endoscopy and is helpful for the recovery of gastrointestinal motility.
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COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.
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To enhance the learning stickiness, improve low completion rate of online teaching, and promote teaching quality has become the key to solve the contradiction in online teaching. In this paper, taking the teaching of biochemistry as example, based on the trigger mechanism, maintenance mechanism and migration mechanism of sticky learning, guided by the three-dimensional goal of "knowledge and skills, process and method, emotional attitude and values", the BOPPPS (bridge-in, objective, pre-assessment, participatory-learning, post-assessment, summary) teaching model was combined with online teaching. According to the interactive behavior in the course learning space, the Spearman rank correlation analysis was performed by SPSS 18.0 software to comprehensively evaluate the learning stickiness degree. The research has found that, due to its "micro but refined, compact structure and student-centered" characteristics, BOPPPS combining with online teaching can effectively make up for the time and space limitations of offline teaching and the excessively broad online teaching, bring benefits from the perspectives of "inclusion, attraction and production", promote students' active learning, and practically improve learning stickiness. The research provides a new idea for creating online "golden" courses.
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Objective:To explore the impact of completion rates of 3-hour and 6-hour sepsis bundle therapy on prognosis of patients with septic shock in Prefecture-level grade A hospitals, and analyze the risk factors for prognosis.Methods:A retrospective analysis was conducted to patients with septic shock in the intensive care unit (ICU) of Liaocheng People's Hospital, Shandong Province from January 1, 2020 to December 31, 2021. The data of gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), sites of infection, pathogenic microorganisms, completion rates of 3-hour and 6-hour sepsis bundle therapy, 28-day prognosis were collected. Logistic regression analysis was used to identify risk factors for patients' mortality at 28-day.Results:① Among 159 patients with septic shock, 93 survived and 66 died with 28-day. There were no significant differences in gender and age between the survival group and death group. Compared with the survival group, APACHE Ⅱ score and SOFA score were significantly higher in the death group [APACHE Ⅱ score: 26.85±5.04 vs. 20.67±4.29, SOFA score: 12.86±3.02 vs. 9.37±2.51, both P < 0.05]. ② Sites of infection in the 159 patients: 47 cases were abdominal infection (29.6%), 36 case were bloodstream infection (22.6%), 31 cases were pulmonary infection (19.5%), 16 cases were soft tissue infection (10.1%), 13 cases were urinary tract infection (8.2%), 12 cases were biliary tract infection (7.5%), and 4 cases were other sites infection (2.5%). Pathogens were found in 128 cases and the positive rate was 80.5%, including 90 cases of Gram-negative (G -) bacilli (56.6%), 27 cases of Gram-positive (G +) cocci (17.0%) and 11 cases of fungi (6.9%). The top three pathogenic bacteria were Escherichia coli (49 cases, 30.8%), Klebsiella pneumoniae (21 cases, 13.2%) and Staphylococcus aureus (15 cases, 9.4%). The differences were not statistically significant. ③ Among the 159 patients, 101 cases completed 3-hour sepsis bundle therapy (63.5%), including 67 cases (72.0%) in survival group and 34 cases (51.5%) in death group; 106 cases completed 6-hour sepsis bundle therapy (66.7%), including 70 cases (75.3%) in survival group and 36 cases (54.5%) in death group. The differences between the two groups were statistically significant (all P < 0.05). ④ The factors (APACHE Ⅱ score, SOFA score and completion rate of 3-hour and 6-hour sepsis bundle therapy) affecting the prognosis in the univariate analysis were included in the binary Logistic regression analysis, and the results showed that the APACHE Ⅱ score, SOFA score, completion rate of 3-hour sepsis bundle therapy were independent risk factors affecting mortality within 28-day [odds ratio ( OR) was 1.216, 1.303, 0.402, all P < 0.05]. Conclusions:The higher APACHE Ⅱ score and SOFA score in septic shock, the worse the prognosis. Improving the completion rates of 3-hour and 6-hour bundle therapy especially the completion rate of 3-hour bundle therapy can reduce the mortality of patients and improve the prognosis.
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Objective:To explore the application of full-crew stratified teaching combined with PBL teaching in nursing practice teaching in emergency department.Methods:A total of 86 intern nursing students in the Emergency Department of The First Affiliated Hospital of Air Force Medical University from February 2019 to August 2020 were randomly divided into the control group ( n=43) and the observation group ( n=43). The control group used full-crew stratified teaching, and the observation group adopted full-crew stratified teaching combined with PBL teaching. The learning interest, subjective initiative, and recognition of teaching were compared between the two groups, and the theoretical scores, operational skills, and comprehensive ability were assessed among them. Meanwhile, the nursing quality of the intern nursing students was evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The incidence of total learning interest and total subjective initiative of nursing students in the observation group were better than those in the control group ( P<0.05). The scores of the four dimensions of case analysis, theoretical total score, quality, and operation score in the observation group were higher than those in the control group ( P<0.05). There was no significant difference between the two groups in the scores of the three dimensions of short answer, choice, and skills ( P>0.05). The scores of the four dimensions of reasoning ability, information management ability, goal completion ability, and communication ability in the observation were higher than those in the control group ( P<0.05). The total recognition of teaching in the observation group was 95.35% (41/43), which was higher than that in the control group (79.07%, 34/43). Conclusion:Full-crew stratified teaching combined with PBL teaching in emergency department in nursing teaching can fully stimulate the learning interest of the intern nursing students, improve their subjective initiative, enhance their recognition degree of the nursing teaching, and finally improve the nursing quality.
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We report the diagnosis and treatment of a case of reversible cerebral vasoconstriction syndrome characterized by postpartum thunderclap headache. The patient experienced a thunderclap headache on the second day after delivery, which gradually worsened. On postpartum day 4, she presented with sudden convulsion and hypertension on admission on May 19, 2020, and was initially diagnosed with postpartum eclampsia. We confirmed the diagnosis of reversible cerebral vasoconstriction syndrome based on the results of cranial magnetic resonance angiography (MRA) and other examinations and the consultation with neurologists. After antihypertensive and spasmolytic treatment, the patient's blood pressure returned to normal, and she was discharged on postpartum day 8. Reexamination with cranial MRA at 50 + days after delivery indicated that the cerebral vasospasm was relieved. No severe headaches or convulsions were observed during follow-up till June 2021.
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Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians′ heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.
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Objective:To investigate the value of synthetic MRI quantitative parameters in identifying different molecular types of breast cancer and triple negative breast cancer (TNBC) and non-TNBC.Methods:A retrospective analysis was performed on 208 patients diagnosed with invasive ductal breast cancer in the First Affiliated Hospital of China Medical University from March 2019 to September 2020. All patients underwent synthetic MR examinations and the following quantitative parameters were measured, including tumor diameter, volume, apparent diffusion coefficient (ADC), and corresponding values of T 1, T 2, and proton density (PD). According to the immunohistochemical results, there were 122 cases of progesterone receptor (PR) positive and 86 cases of PR negative, 123 cases of estrogen receptor (ER) positive and 85 cases of ER negative, 79 cases of human epidermal growth factor receptor-2 (HER2) positive and 129 cases of HER2 negative, 149 cases of Ki-67 high expression and 59 cases of Ki-67 low expression; there were 36 cases of TNBC and 172 cases of non-TNBC. Independent samples t test or Mann-Whitney U test were used to compare the quantitative parameters of different molecular types, TNBC and non-TNBC patients. Multivariate logistic regression was used to analyze independent predictors of TNBC, and receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the efficacy of sole and combined parameters in identifying TNBC. Results:T 1 and T 2 values in PR negative breast cancer patients were higher than those in PR positive patients ( t=2.30, Z=2.04, P<0.05); the values of T 1 and T 2 in ER negative patients were higher than those in ER positive patients ( t=2.52, Z=2.48, P<0.05); ADC value and tumor diameter of HER2 positive patients were larger than those in HER2 negative patients ( t=-3.21, Z=-3.22, P<0.05). T 2 value, tumor volume and diameter in patients with Ki-67 high expression were significantly higher than those in patients with Ki-67 low expression ( Z=-3.47, -2.51, -2.84, P<0.05); ADC value in Ki-67 high expression group was less than that in Ki-67 low expression group ( t=3.94, P<0.001). T 1, T 2 values and tumor volume in TNBC patients were higher than those in non-TNBC patients ( t=-3.26, Z=-5.58, Z=-2.02, P<0.05], and ADC value in TNBC patients was lower than that in non-TNBC patients ( t=3.07, P=0.002). Multivariate logistic regression analysis showed that T 2 (OR=1.060, 95%CI 1.028-1.093, P<0.001) and ADC value (OR=0.947, 95%CI 0.911-0.984, P=0.005) were independent predictors of TNBC. The efficacy of each parameter alone and in combination to identify TNBC showed that the T 2 value in the single parameter had the largest AUC (0.759), and there was no significant difference between T 2 value and its combined parameters in the diagnosis of TNBC. Conclusions:The quantitative parameters based on synthetic MRI, especially T 2 value, have value in differentiating different molecular types of breast cancer, TNBC and non-TNBC may be another non-contrast parameter for evaluating tumor aggressiveness beyond ADC value.
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Objective:To analyze the prenatal diagnosis results and pregnancy outcomes of conotruncal defects (CTD) fetuses, and to explore the correlation between the CTD and chromosome diseases.Methods:A total of 297 cases of invasive prenatal diagnosis and chromosome analysis were collected at the Prenatal Diagnosis Center of Guangzhou Women and Children′s Medical Center due to CTD from January 1st, 2011 to December 31th, 2019. According to ultrasonic diagnosis, CTD fetuses were divided into 6 subtypes: tetralogy of Fallot (109 cases), pulmonary atresia (30 cases), transposition of the great arteries (77 cases), double outlet right ventricle (53 cases), truncus arteriosus (14 cases) and interrupted aortic arch (14 cases). According to whether they were combined with intracardiac or extracardiac abnormalities, they were divided into simple group (134 cases), combined with other intracardiac abnormalities group (86 cases), combined with extracardiac abnormalities group (20 cases), combined with intracardiac and extracardiac abnormalities group (37 cases) and only combined with ultrasound soft marker group (20 cases), the last 4 groups were referred as non-simple types. The chromosome test results and pregnancy outcomes of each type and group were analyzed retrospectively.Results:Among the 297 CTD fetuses, the chromosome abnormality rate was 17.5% (52/297). There were 21 cases of abnormal chromosome number, 28 cases of pathogenetic copy number variantions and 3 cases of mosaics. All the 19 cases of micropathogenic fragments smaller than 5 Mb were detected by chromosomal microarray analysis (CMA). Among all the subtypes of CTD, the chromosomal abnormality rate of truncus arteriosus was the highest, at 7/14; while the rate of transposition of the great arteries was the lowest, at 5.2% (4/77). There were significant differences in the rate of chromosomal abnormalities between simple and non-simple types [10.4% (14/134) vs 23.3% (38/163); χ2 =8.428, P=0.004]. In each group, the chromosomal abnormality rate was the highest in the combined with intracardiac and extracardiac abnormalities group, at 37.8% (14/37), and the lowest in the simple group, at 10.4% (14/134). There was no significant difference in the rate of chromosomal abnormalities in all subtypes of simple group (all P>0.05). Among 112 cases of live birth, 1 case was 22q11.2 microdeletion syndrome, 5 cases of postnatal clinical diagnosis and prenatal ultrasound diagnosis were not completely consistent, 5 cases died after birth. Conclusions:The incidence of chromosomal abnormalities is high in fetuses with CTD. CTD fetuses with concurrent extrapardiac malformations are more likely to incorporate chromosomal abnormalities. CMA technology could be used as a first-line genetic detection method for CTD. After excluding chromosomal abnormalities, most of the children with CTD have good prognosis.
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【Objective】 To investigate the clinical and genetic characteristics of hemolytic disease of the newborn(HDN) induced by anti-M complicated with pyruvate kinase deficiency (PKD) disease. 【Methods】 The clinical data of a pregnant woman with unexplained adverse pregnancy outcome in the third trimester were retrospectively analyzed, and neonate anemia status and blood transfusion were followed up. With informed consent, peripheral blood of the neonate and her parents were collected for serological tests and disease-related gene target sequence capture and sequencing. The clinical and genetic characteristics of HDN induced by anti-M or PKD were reviewed. 【Results】 The neonate presented severe anemia, hepatosplenomegalism, hyperbilirubinemia at birth, and was confirmed MN combined with ABO neonatal hemolysis by serological tests. The neonate recovered by receiving blood exchange and phototherapy treatments, but he needed to receive blood transfusion each month because of hemolytic anemia. Genetic analysis showed that the neonate had compound heterozygous mutations (c. 1096C>T; c. 941T>C) of PKLR gene inherited from her parents. 【Conclusion】 The clinical manifestations of PKD are similar to that of HDN caused by anti-M in the early stage of the disease. Clinicians should exclude the metabolic diseases of red blood cells when diagnosing severe HDN caused by anti-M.
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Diabetes mellitus is a chronic metabolic disease, in which the abnormality of glucose and lipid metabolism may cause multisystem damage. Sodium-glucose synergistic transporter 2 (SGLT2) inhibitors are a novel type of hypoglycemic drug that can lower blood sugar level by inhibiting the absorption of glucose through renal tubules. Studies have shown that SGLT2 inhibitors also have a lowering effect on blood pressure, but the mechanism is not fully elucidated. In this article the hypotensive effects of SGLT2 inhibitors and possible mechanisms are reviewed.
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Objective:To evaluate the predictive value of the UK Myeloma Research Alliance Risk Profile(MRP)score based on clinical outcomes in elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:Patients aged ≥65 years with NDMM in our hospital from March 2018 to September 2021 were divided into three groups with low, medium and high risk according to MRP scores.Their therapeutic efficacy, adverse effects, and survival were analyzed.Results:A total of 63 NDMM patients were enrolled with median age of 69 years(65-84 years)and median follow-up of 13.3(1.2-43.4)months.Based on MRP score, there were 22 patients in the low-risk group, 13 cases in medium-risk group, 28 patients in the high-risk group.The median progression-free survival(PFS)time of the three groups was 38.4, 25.1 and 21.2 months respectively, and the estimated 2-year PFS rate was 83.9%, 60.0%, and 45.6%, respectively(all P=0.177). The estimated 2-year overall survival(OS)rate was 100.0%, 90.0%, 74.6%, respectively(all P=0.049). Among patients with grade 2 or above hematological adverse events, there were 20 cases(71.4%), 7 cases(53.8%)and 8 cases(36.4%)in the high-, medium-and low-risk groups, with statistically significant differences( χ2=6.154, P=0.046). Among patients with grade 3 or higher non-hematological adverse events, there were 17 cases(60.7%), 5 case(38.5%)and 5 cases(22.7%)in the high-, medium-and low-risk groups, with statistically statistical significance( χ2=7.389, P=0.025). The patients experiencing interruption, delay or replacement of chemotherapy regimen were 6 cases(46.2%)and 19 cases(67.9%)in the medium-and high-risk groups, which were higher than in the low-risk group(31.8%, χ2=6.543, P=0.038). Conclusions:It is feasible to conduct MRP score in elderly NDMM patients.The MRP score can be used to predict the adverse events of chemotherapy, etc, and has certain value for the prognosis evaluation of patients.
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Objective:To explore the correlation between different types of microcirculation alterations and the prognosis in patients with septic shock.Methods:This research employed a prospective observational study methodology for selecting subjects with septic shock. Side-stream dark field(SDF) was used to monitor the sublingual microcirculation to determine the total vascular density (TVD), perfused vessel density (PVD), the proportion of perfused vessels (PPV), and the microvascular flow index (MFI), heterogeneity index (HI) indicators. At the bedside, patients with microcirculation disorders were divided into four types: stasis, dilution, heterogeneity, and hyperdynamic. The 30-day survival status after enrollment and hemodynamics parameters were recorded.Results:A total of 64 patients with septic shock were selected in the study, including 18 cases of stasis type, 11 of dilution type, 18 of heterogeneous type, and 17 of hyperdynamic type. There were statistical differences in the mean arterial pressure (MAP) [stasis:(77±9) mmHg (1 mmHg=0.133 kPa), dilution:(80±11) mmHg, heterogeneity: (78±12) mmHg, hyperdynamic:(88±12) mmHg], TVD [ stasis:(10.84±3.01) mm/mm 2, dilution:(9.64±1.72) mm/mm 2, heterogeneity:(11.39±2.18) mm/mm 2, hyperdynamic: (11.87±2.67) mm/mm 2 ], PVD [stasis:(5.93±1.94) mm/mm 2, dilution:(6.86±1.48) mm/mm 2, heterogeneity: (8.31±1.78) mm/mm 2, hyperdynamic:(9.68±2.46) mm/mm 2], PPV [stasis:52.45 (46.25, 63.33)%, dilution:73.70 (61.50, 75.20)%, heterogeneity: 71.25 (67.95, 77.00)%, hyperdynamic:80.70 (77.25, 86.45)%], MFI(stasis:1.34±0.45, dilution: 1.70±0.38, heterogeneity:1.82±0.28, hyperdynamic:2.25±0.33), and HI [stasis:0.68 (0.51, 1.87), dilution: 0.57 (0.49, 0.64), heterogeneity:0.70 (0.59, 0.91), hyperdynamic: 0.40 (0.37, 0.52)] of the four types of microcirculation alterations. The cumulative survival rates in stasis, dilution, heterogeneity and hyperdynamic types at 30 day were 7/18, 4/11, 10/18 and 14/17, respectively, which in stasis and dilution types was significantly lower than that of hyperdynamic type (χ2=7.221, P=0.007;χ 2=6.764, P=0.009). Multivariate Cox regression analysis showed the type of microcirculation alterations (stasis: RR=4.551, 95 %CI 1.228-16.864, P=0.023; dilution: RR=4.086, 95 %CI 1.011-16.503, P=0.048), acute physiology and chronic health evaluation Ⅱ ( RR=1.077, 95 %CI 1.006-1.153, P=0.032) were independent prognostic risk factors. Conclusions:Microcirculation alterations are common in patients with septic shock, and it is hard to predict the types of microcirculation alterations with hemodynamics parameters. The prognosis of patients with septic shock is related to the types of microcirculation alterations, suggesting that routine monitoring of microcirculation might be helpful to guide hemodynamic therapy.
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Objective:To evaluate the relationship between phosphorylation of glycogen synthase kinase-3β (GSK-3β) and high glucose-caused abolition of cardioprotection induced by sevoflurane postconditioning.Methods:H9c2 cells were incubated in normal glucose (5.56 mmol/L) DMEM culture medium or high glucose (33 mmol/L) DMEM culture medium.The cells were divided into 8 groups ( n=24 each) using a random number table method: normal control group (group NC), normal glucose-cultured hypoxia/reoxygenation (H/R) group (group NH/R), normal glucose-cultured sevoflurane postconditioning group (group NS), normal glucose-cultured GSK-3β inhibitor SB216763 group (group NSB), high glucose-cultured group (group HC), high glucose-cultured H/R group (group HH/R), high glucose-cultured sevoflurane postconditioning group (group HS) and high glucose-cultured GSK-3β inhibitor SB216763 group (group HSB). The model of cardiomyocyte H/R was established by subjecting cardiomyocytes to 3 h of hypoxia followed by reoxygenation.Immediately after onset of reoxygenation, cardiomyocytes were exposed to 2.4% sevoflurane for 30 min in Ns and HS groups.Before the beginning of reoxygenation, GSK-3β inhibitor SB216763 was added to the culture medium with the final concentration of 10 μmol/L in NSB and HSB groups.At 3 h of reoxygenation, the apoptosis rate was determined by Anexin V-PI flow cytometry, the expression of GSK-3β and phosphorylated GSK-3β (p-GSK-3β) was detected by Western blot, superoxide dismutase (SOD) activity was measured using xanthineoxidase method, and lactic dehydrogenase (LDH) activity and malondialdehyde (MDA) content were determined by colorimetric assay. Results:Compared with group NC, apoptosis rate, LDH activity and MDA content were significantly increased, and SOD activity was decreased in group NH/R and group HC, expression of GSK-3β was up-regulated, and expression of p-GSK-3β was down-regulated in group NH/R, expression of p-GSK-3β was up-regulated in group NS, and expression of p-GSK-3β was down-regulated in group HC ( P<0.05). Compared with group NH/R, apoptosis rate, LDH activity and MDA content were significantly decreased, and SOD activity was increased in group NS and NSB groups, and expression of GSK-3β was down-regulated, and expression of p-GSK-3β was up-regulated in group NS ( P<0.05). Compared with group HC, apoptosis rate, LDH activity and MDA content were significantly increased, SOD activity was decreased, expression of GSK-3β was up-regulated, and expression of p-GSK-3β was down-regulated in group HH/R ( P<0.05). Compared with group HH/R, apoptosis rate, LDH activity and MDA content were significantly decreased, and SOD activity was increased in group HSB ( P<0.05). Conclusion:The mechanism by which high glucose abolishes cardioprotection induced by sevoflurane postconditioning is related to inhibiting phosphorylation of GSK-3β.
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Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.
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Objective:To describe the features of point-of-care cardiopulmonary ultrasound (POCUS) in the critically ill patients and analyze the independent factors associated with treatment changes after POCUS assessment.Methods:This was a prospective multicentric observational study from January to December 2018 in 13 intensive care units (ICU) in China. Consecutive patients admitted to the ICU were enrolled, POCUS were performed within the first 24 h of admission. The POCUS parameters included acute or chronic cardiac abnormality, diameter of inferior vena cava (IVC) at end-expiration, right ventricular systolic function, systolic and diastolic function of left ventricle (LV) and lung ultrasound score. The general features of patients and performers were recorded. Based on the treatment proposed by the performer before and after POCUS assessment, the patients were divided into treatment changed and unchanged groups. Factors associated with treatment changes were identified by multiple logistic regression analysis.Results:Totally 1 913 patients were enrolled including 322 (16.8%) patients with shock, 638 (33.3%) patients with respiratory failure, 139 (7.3%) patients with both shock and respiratory failure and 814 (42.6%) perioperative patients. POCUS had contributed to treatment changes in 1 204 (62.9%) patients, including 867 (72.0%) cases involved fluid management. Univariate analysis showed that there were significant differences in general characteristics of patients, performers and POCUS parameters between groups(all P<0.05). Logistic regression analysis showed that independent factors of treatment changes included ministry of education or university affiliated teaching hospitals (vs.general hospitals, OR=1.891, 95% CI=1.314-2.722, P<0.001 and OR=1.644, 95% CI=1.152-2.347, P=0.006 separately), middle and senior title performers (vs.primary title, OR=2.112, 95% CI=1.358-3.284, P=0.001, OR=3.271, 95% CI=2.129-5.025, P<0.001 separately), mechanical ventilation (vs.without, OR=0.488, 95% CI 0.381-0.626, P<0.001), IVC diameter ≤1 cm (vs.1-2 cm, OR=0.317, 95% CI 0.231-0.434, P<0.001), LV ejecting fraction <50% (vs.≥50%, OR=0.328, 95% CI=0.210-0.512, P<0.001), lung ultrasound score of 6-12 and >12 points(vs.score ≤ 6 points, OR=0.237, 95% CI=0.178-0.315, P<0.001 and OR=0.619, 95% CI=0.457-0.837, P=0.002 separately). Conclusions:POCUS assessment contributes to treatment changes, most of which involves fluid management strategy, in 62.9% critical patients. The independent influencing factors associated with POCUS parameters includes IVC diameter at end-expiratory, LV systolic function and lung ultrasound score. The performers′ title and hospital grade also have a noticeable effect.
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BACKGROUND@#Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.@*METHODS@#The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.@*RESULTS@#The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).@*CONCLUSIONS@#The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.