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@#Objective To explore the clinical effect of hemoperfusion (HP) in cardiopulmonary bypass (CPB) on postoperative inflammation in patients with acute type A aortic dissection (AAD). Methods Adult patients with AAD who planned to undergo total aortic arch replacement from July 2020 to November 2021 were continuously enrolled in our heart center. Patients were randomly divided into a HP group and a control (C) group. The HP group was treated with disposable HP device (Model: HA380, Zhuhai Jafron Biomedical, China) in CPB during the operation. Results Finally, 70 patients were included with 59 males and 11 females at an age range of 21-67 years. There were 35 patients in both groups. In this study, 3 patients died within 3 days after surgery, 2 in the HP group and 1 in the C group, and the remaining 67 patients survived to the follow-up end point (30 days after surgery). There was no statistical difference in preoperative baseline data, operative method, CPB time, block time, or other intraoperative data between the two groups. Blood product dosage, intubation time, hospital stays, and hospitalization expenses were similar between the two groups. Intraoperative hemoglobin (82.70±2.31 g/L vs. 82.50±1.75 g/L, P=0.954] and platelet concentration [(77.87±7.99)×109/L vs.(89.17±9.99)×109/L, P=0.384] were not statistically different between the HP group and C group. In the HP group, postoperative (ICU-12 h) interleukin-6 (IL-6) [338.14 (128.00, 450.70) pg/mL vs. 435.75 (180.50, 537.00) pg/mL, P=0.373], IL-8 [35.04 (18.02, 40.35) pg/mL vs. 43.50 (17.70, 59.95) pg/mL, P=0.383], and IL-10 [21.19 (6.46, 23.50) pg/mL vs. 43.41 (6.34, 50.80) pg/mL, P=0.537] were slightly lower than those in the C group, and the difference was not statistically different. The incidences of pulmonary infection (0.00% vs. 11.76%, P=0.042) and liver injury (2.94% vs. 20.58%, P=0.027) in the HP group were significantly lower than those in the C group, and the incidence of other postoperative complications, such as arrhythmia, nervous system complications and urinary system complications, showed no statistical difference between the two groups. Conclusion HP therapy in CPB is safe, but its effect on reducing postoperative inflammatory factors, postoperative inflammatory reactions and postoperative complications in the patients with AAD is limited, and it may be of application value to some high-risk patients with lung and liver injury.
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Objective:To investigate the factors for serious complications within 30 days after surgery in elderly patients with advanced epithelial ovarian cancer(EOC)who undertook primary debulking surgery(PDS).Methods:The clinical data of International Federation of Gynecology and Obstetrics(FIGO)stage ⅢC/Ⅳ EOC patients aged≥60 years who received PDS in gynecological department of National Cancer Center and National Center of Gerontology between January 2014 and December 2018 were retrospectively analyzed.Clavien-Dindo scoring system was applied to grade the complications within 30 days after surgery.The serious early postoperative complications were those of grade Ⅲ or above occurred within 30 days after surgery.Multivariate Logistic regression analysis was used to screen the independent risk factors of serious complications within 30 days after surgery.Results:A total of 133 patients were included in this study and serious complications rated 11.3%(15/133). The mean age of patients in severe complication group was significantly higher than that in the control group[(69.80±6.56) vs.(65.87±5.14), t=2.699, P=0.008]. The proportion of patients with preoperative ECOG score≥2 was significantly higher in the severe complication group than that in the control group[26.7%(4/15) vs.5.9%(7/118), χ2=4.985, P=0.026], and the proportion of preoperative hypoalbuminemia(<35 g/L)was significantly higher in the severe complication group[20.0%(3/15) vs.3.4%(4/118), χ2=4.897, P=0.027]. However, there was no significant difference in intraoperative bleeding, R0 resection rate as well as surgical complexity( χ2=1.964, 0.330, 4.637, all P>0.05)between the two groups.Multivariate Logistic regression analysis showed that the independent factors for serious early postoperative complications were age≥70 years( OR=4.345, P=0.028), ECOG score≥2( OR=25.619, P=0.008)and preoperative albumin <35 g/L( OR=6.733, P=0.040). Conclusions:In the elderly ovarian cancer patients, individualized perioperative management should be strengthened for the patients with factors associated with serious early postoperative complications, in order to reduce severe complications and improve the prognosis.
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Objective:To investigate the effects and potential mechanism of vitamin D supplementation on testicular function in aging rats induced by D-galactose.Methods:The aging rats were induced by D-galactose with subcutaneous injection. The animals were randomly divided into 6 groups: aging rats (DG), aging rats with low-dose vitamin D supplementation (LD), aging rats with high-dose vitamin D supplementation (HD), normal control rats(NC), normal rats with low-dose vitamin D supplementation(LN), normal rats with high-dose vitamin D supplementation (HN). The body weight, testicular weight, serum testosterone concentrations and sperm quality of the rats in each group were measured. The testis morphological changes were detected using light microscopy. The activity of superoxide dismutase (SOD) and level of malondialdehyde(MDA) were determined with spectrophotometer. The expression levels of Nrf2, GCLC, SOD2 and VDR in testis were detected by western blot.Results:At baseline, compared with NC group, testicular weight, serum testosterone level, SOD activity, Nrf2, GCLC and SOD2 expression levels were significantly decreased in DG group, while MDA level was significantly increased. After vitamin D supplementation, testicular weight, testosterone levels and SOD activity in both of HD and LD groups were significantly increased, while the MDA level was significantly decreased. The expression levels of Nrf2, GCLC, SOD2 and VDR were significantly increased.Conclusion:Vitamin D supplementation may enhance the testicular antioxidant capacity through activating Nrf2-ARE signaling pathway, and improve the testicular function in D-galactose-induced aging rats.
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Objective:To analyze the risk factors for postoperative one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment (MDT) by intramedullary nailing.Methods:The clinical data were retrospectively analyzed of the 158 elderly patients with femoral intertrochanteric fracture who had undergone MDT by proximal femoral intramedullary nailing between January 2018 and August 2020 at Department of Orthopedics, Trauma Center, Zhongda Hospital Affiliated to Southeast University. There were 41 males and 117 females with an average age of 82.5 years (from 65 to 95 years). By the modified Evans classification, there were 15 cases of type Ⅰ, 16 cases of type Ⅱ, 35 cases of type Ⅲ, 81 cases of type Ⅳ, and 11 cases of type Ⅴ. The one-year mortality was documented in the patients after surgery. To screen for risk factors, univariate analysis was conducted of gender, age, body mass index (BMI), modified Evans classification of fractures, time from injury to operation, American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI) and comorbidities, as well as preoperative hemoglobin (Hb), serum albumin (ALB) and total lymphocyte count (TLC). The factors with P<0.05 were included in the multivariate logistic regression model analysis to determine the risk factors. Results:A total of 13 patients died within one year after surgery, yielding a mortality of 8.2% (13/158). Univariate analysis showed significant differences in age, body mass index, modified Evans classification of fractures, CCI and Hb between the surviving and dead patients ( P<0.05). Multivariate logistic regression analysis showed that age >85 years ( OR=0.122, 95% CI: 0.018 to 0.834, P=0.032), BMI>23.9 kg/m 2 ( OR=0.083, 95% CI: 0.013 to 0.510, P=0.007), CCI≥3 points ( OR=0.051, 95% CI: 0.090 to 0.275, P=0.001) and preoperative Hb<90 g/L ( OR=4.733, 95% CI: 1.036 to 21.624, P=0.045) were the independent risk factors for postoperative one-year mortality in the elderly patients with intertrochanteric fracture following MDT by proximal femoral intramedullary nailing. Conclusions:After MDT by proximal femoral intramedullary nailing of femoral intertrochanteric fractures, the geriatric patients with an age >85 years, BMI>23.9 kg/m 2, CCI≥3 points and Hb<90 g/L are likely to die. Therefore, special care should be taken for them.
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OBJECTIVE@#To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells.@*METHODS@#Human glioma U251 cells were treated with 8.0 μmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway.@*RESULTS@#AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P < 0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P < 0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P < 0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05).@*CONCLUSION@#AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.
Subject(s)
Humans , Apoptosis , Atorvastatin/pharmacology , Cell Line, Tumor , Cell Proliferation , Glioma/pathology , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal TransductionABSTRACT
Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.
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Objective:To observe the expression of molecular chaperone-mediated autophagy in hippocampal neurons and its relationship with brain injury after recurrent-status seizures.Methods:Seven-day-old SD rats were divided into two groups according to simple randomization: the control group (NS group, 6 rats) and the recurrent-seizure group (RS group, 39 rats). Rats in the RS group were subjected to recurrent seizures after repeated inhalation of flurothyl, with 30 minutes once each day for consecutive 7 days.A total of 30 convulsive models were successfully established (9 rats that failed to establish models were discarded), and they were further divided into 0 h, 1.5 h, 3 h, 12 h and 24 h after the last seizure according to simple randomization, with 6 rats in each group.Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were adopted for the observation of the expression of molecular chaperone-mediated autophagy markers [heat shock cognate protein 70 (Hsc70), lysosome-associated membrane protein type 2a (LAMP-2a), heat shock protein 40(HSP40) and heat shock protein 90(HSP90)] in hip-pocampal neurons, and apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL).Results:(1) RT-PCR and Western blot showed that, compared with the NS group, the expression of Hsc70, as a molecular chape-rone, started to increase at 1.5 h and continued until 24 h after the last seizure in the RS group ( P<0.05). HSP90 increased immediately after the last seizure and lasted until 24 h after the seizure ( P<0.01); the expression of HSP40 and LAMP-2a also showed high expression after the last seizure episode ( P<0.05). (2) The TUNEL method showed that the number of apoptotic cells in the hippocampal CA1 region increased significantly at 3 h (36.33±5.16)/40 field, 12 h (44.83±4.83)/40 field and 24 h (54.83±7.16)/40 field after the last seizure compared with NS group(15.16±2.48)/40 field ( P<0.01). (3) Pearson correlation analysis showed that the level of apoptosis in hippocampal CA1 region of rats after recurrent seizures was positively correlated with the expression of molecular chaperone marker molecules (Hsc70: r=0.734, P=0.001; LAMP2a: r=0.790, P<0.001). Conclusions:After recurrent seizures in developmental rats, the presence of increased expression of multiple molecular chaperone-mediated autophagy, which may positively correlate with apoptosis, may be involved in the process of brain injury.
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BACKGROUND@#Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service (EMS). This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China.@*METHODS@#A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally. Four status of awareness and annual income were identified: unaware and low-income, unaware-only, low-income-only, and aware and regular income. The outcomes were whether they intended to call EMS or not. The regional distribution of each status and their associations with not calling EMS were presented.@*RESULTS@#The status of unaware and low-income, unaware-only, and low-income-only accounted for 6.3% (11,806/187,673), 11.9% (22,241/187,673), and 21.5% (40,289/187,673) of the total sample, respectively. Not calling EMS was significantly associated with the status of unaware and low-income (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 3.07-3.35), unaware-only (OR: 2.38, 95% CI: 2.31-2.46), and low-income-only (OR: 1.67, 95% CI: 1.63-1.71), compared with the aware and regular income status. The Midwest regions had higher percentages of people in the unaware and low-income status; the East, South, and Central had higher percentages of unaware-only status; the North and Northeast regions had a higher percentage of low-income-only status, compared with other regions.@*CONCLUSION@#The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.
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Humans , China , Emergency Medical Services , Odds Ratio , Socioeconomic Factors , StrokeABSTRACT
Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.
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Objective:To explore the effects of scout scanning parameters (projection angle and tube potential) on image quality and radiation dose in chest CT and to provide guidance for the selection of scanning parameters in clinical practice.Methods:Different parameter combinations were selected to acquire the scout view of the anthropomorphic adult chest phantom. Fifteen scout views were obtained under parameter combinations of the projection angle (0/90/180 degrees), tube potential (70/80/100/120/140 kV) and tube current (25 mA). And then, chest spiral scans were performed according to the scout views. The other parameters were Assist kV, smart mA (maximum range), 80 mm detector width, 0.992∶1 pitch, 0.5 s rotation time, 330 mm scanning length, 5 mm thickness, NI (noise index) 10. The radiation dose modulation index (ASiR-V) was 30%, and the iterative level was 50%. Volume CT dose index (CTDI vol) and tube current at 4 body levels (pulmonary apex, trachea bifurcation, mammary level and diaphragmatic dome) were recorded. The thermoluminescent dosimeters (TLDs) were used to measure the organ dose of the breast glandular. Regions of interest (ROIs)were selected at the trachea bifurcation and diaphragmatic dome to calculate the contrast noise ratio (CNR). Results:The tube potential of the spiral scanning was automatically selected as 80 kV when the projection angle was 0 degree. The changing of the tube potential for the scout had little influence on the tube current at the four body levels, and the variation range was 0-2% (5/230). The tube potential in the spiral scanning was automatically selected as 100 kV when the projection angles were 90 and 180 degrees. The changing of the tube potential for the scout had a great influence on the tube current at the slice of trachea bifurcation and the variation range was from 14%(29/210)to 44%(93/210). According to the angle projection, there were statistical differences in CTDI vol( P< 0.017), organ dose of the breast glandular, and CNR at the slices of trachea bifurcation and at diaphragmatic dome ( F=13.027, 24.727, 10.630, P< 0.05). According to the tube potential in the scout scanning, there were no significant differences in CTDI vol, organ dose of the breast glandular and CNR at both levels ( P> 0.05). Conclusions:In chest CT, the influence of the projection angle in scout scanning on the image quality and radiation dose was more significant than that of the tube potential.
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Objective:To explore the application value of overall nursing intervention in PET/MR imaging in children with epilepsy.Methods:A total of 48 pediatric epilepsy patients who underwent PET/MR imaging in the Nuclear Medicine Department of the First Medical Center of the PLA General Hospital from July 2018 to October 2019 were enrolled. Among them, 24 patients with overall nursing intervention were used as the experimental group, and 24 patients were routine nursing intervention patients, who were served as the normal control group, and the examination time, Self-Rating Anxiety Scale (SAS) scores and patient satisfaction scores (filled in by the patient′s guardian) of the experimental group and the control group were collected and compared.Results:The inspection time of the experimental group was (15.1±0.5) min, significantly lower than (24.8±1.3) min of the control group ( tvalue was 32.940, P<0.01); the SAS score of the experimental group was (35.7±4.2) points, lower than(43.8±3.3) points of the control group ( tvalue was 7.357, P<0.01), and the patient satisfaction score was (92.8±5.5) points, higher than (69.8±11.1) points of the control group ( tvalue was 9.088, P<0.01 or 0.05). Conclusion:Overall nursing intervention in PET/MR imaging of pediatric patients with epilepsy can significantly cut down the examination time, reduce the anxiety of patients′ family members and improve the satisfaction of nursing care. It lays the foundation for clinicians to further accurately diagnose epilepsy foci and has important application value.
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The abundance of proteins in human urine is low and easily to be masked by high-abundance proteins during mass spectrometry analysis. Development of efficient and highly selective enrichment methods is therefore a prerequisite for achieving deep coverage of urine protein markers. Notably, different experimental methods would affect the urine protein enrichment efficacy and the coverage of urine proteome. In this study, ultrafiltration, nitrocellulose membrane enrichment and saturated ammonium sulfate precipitation were used to process 10 mL urine samples from five healthy volunteers and five bladder cancer patients. The urine proteins were enriched and separate by SDS-PAGE to compare the purification efficiency of different methods. Moreover, the peptide identification effects of different purification methods were analyzed by mass spectrometry to determine the best method for enriching urine protein histones. Saturated ammonium sulfate precipitation method outperformed the ultrafiltration and the nitrocellulose membrane enrichment methods in terms of the protein enrichment efficacy and quality. The interference of highly abundant albumin was reduced, whereas the amount of low-abundance protein was increased, and the sensitivity of mass spectrometry identification was increased. The saturated ammonium sulfate precipitation method may be applied for large-scale urine processing for screening clinical diagnostic markers through proteomics.
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Humans , Histones , Mass Spectrometry , Proteome , Proteomics , UrinalysisABSTRACT
In this article, based on z-curve theory and position weight matrix (PWM), a model for nucleosome sequences was constructed. Nucleosome sequence dataset was transformed into three-dimensional coordinates, PWM of the nucleosome sequences was calculated and the similarity score was obtained. After integrating them, a nucleosome feature model based on the comprehensive DNA sequences was obtained and named CSeqFM. We calculated the Euclidean distance between nucleosome sequence candidates or linker sequences and CSeqFM model as the feature dataset, and put the feature datasets into the support vector machine (SVM) for training and testing by ten-fold cross-validation. The results showed that the sensitivity, specificity, accuracy and Matthews correlation coefficient (MCC) of identifying nucleosome positioning for were 97.1%, 96.9%, 94.2% and 0.89, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.980 1. Compared with another z-curve method, it was found that our method had better identifying effect and each evaluation performance showed better superiority. CSeqFM method was applied to identify nucleosome positioning for other three species, including , and . The results showed that AUCs of the three species were all higher than 0.90, and CSeqFM method also showed better stability and effectiveness compared with iNuc-STNC and iNuc-PseKNC methods, which is further demonstrated that CSeqFM method has strong reliability and good identification performance.
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The major challenge in the development of recombinant biologics lies in generating and isolating rare high-producing stable single clone in a short period of time. The selection marker is an essential component of the plasmid vector, it plays an important part in the generation and screening of producing cell lines. Engineering the selection marker to enhance the stringency of selection for high producing cells is one of the most effective approaches to improve the cell line development process. Here, using Chinese hamaster overy (CHO) cells as an example, we introduce the application of selection marker for generation of recombinant biologics producing mammalian cell lines, methods of engineering the selection markers to enhance the selection stringency, and propose considerations on cell substrate stability and selection marker safety, in order to provide references for high-efficiency development of recombinant biologics.
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Adolescent , Adult , Humans , Middle Aged , Young Adult , Age Distribution , Betacoronavirus , Physiology , China , Epidemiology , Coronavirus Infections , Epidemiology , Virology , Disease Outbreaks , Health Behavior , Masks , Pandemics , Pneumonia, Viral , Epidemiology , Virology , Social Media , Surveys and QuestionnairesABSTRACT
BACKGROUND@#Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1 (HTRA1) gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.@*METHODS@#We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1, 2020. CARASIL probands with genetic diagnosis reported to date were also reviewed. The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.@*RESULTS@#Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included. Compared with typical CARASIL, HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors (P < 0.001), a later onset age (P < 0.001), and a relatively slower clinical progression. Alopecia and spondylosis can be observed, but less than those in the typical CARASIL. Thirty-five heterozygous mutations in HTRA1 were reported, most of which were missense mutations. Amino acids located close to amino acids 250-300 were most frequently affected, followed by these located near 150∼200. While amino acids 250∼300 were also the most frequently affected region in CARASIL patients, fewer mutations precede the 200th amino acids were detected, especially in the Kazal-type serine protease domain.@*CONCLUSIONS@#HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL. The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.
Subject(s)
Humans , Cerebral Infarction , Cerebral Small Vessel Diseases/genetics , Heterozygote , High-Temperature Requirement A Serine Peptidase 1/genetics , Leukoencephalopathies/genetics , Mutation/geneticsABSTRACT
Objective:This study mainly discussed the clinical characteristics, autoimmune status and lymphocyte subsets of patients with Takayasu arteritis (TA) without hormone and immunosuppressive therapy, in order to provide guidance for immunotherapy.Methods:Using cross-sectional study, twenty-nine patients with TA admitted to the Department of Rheumatology and the Department of Vasculitis of Beijing Anzhen Hospital from January 2018 to November 2019 were selected, including 28 females and 1 male, with the middle age of 39 year. These patients met the diagnostic criteria of American Society of Rheumatology for TA, and were not treated with hormone and immunosuppressant. Clinical data of these patients were collected, and the immunological indexes and lymphocyte subsets of peripheral blood were detected simultaneously. At the same time, the immunological indexes and peripheral blood lymphocyte subsets of 21 healthy normal people were detected as control. Chi square test, independent sample t test and nonparametric test were used for analysis. Results:Among the 29 patients with TA, 28 were female, 26 were in the active stage of disease; the main manifestations of systemic symptoms were malaise (62.07%) and headache (41.38%), the main manifestations of vascular symptoms were bruits and pulse weakening (68.97%), and the most of Numano type was V type (79.31%). The absolute value of total T (CD3) lymphocytes [(1 337.14±312.46)μl vs (1 139.95±340.96)μl, t=2.120, P=0.039], the percentage [46.29%±6.55% vs 36.55%±7.42%, t=4.903, P<0.000 1] and the absolute value [(815.52±194.11)μl vs (571.44±187.55)μl, t=4.450, P<0.000 1] of helper T (CD4) lymphocytes, the ratio of CD4/CD8 [1.83 (1.41-2.30) vs 1.32 (1.03-1.39), Z=3.401, P=0.001] were higher compared with those of healthy controls, while the percentage of natural killer (NK) cells (CD56) [10.71%(6.45%-14.30%) vs 14.57%(10.87%-18.47%), Z=2.408, P=0.016] decreased. The complement C3 [1.16 (1.02-1.31) g/L vs 1.05 (0.93-1.15) g/L, Z=2.383, P=0.021] in patients with TA was higher than those in healthy controls and immunoglobulin (Ig) G [11.97 (8.74-14.43) g/L vs 14.37 (13.11-15.47) g/L, Z=3.017, P=0.003] in patients with TA was lower than those in healthy controls. Compared with the control group, the ESR [19.31 (9.50-28.50) mm/h vs 3.71 (2.00-5.00) mm/h, Z=5.338, P<0.000 1], hs-CRP [6.52 (0.32-8.62) mg/L vs 0.73 (0.35-1.07) mg/L, Z=2.983, P=0.003] and Q-CRP [8.73 (1.03-7.72) mg/L vs 0.57 (0.08-0.98) mg/L, Z=4.263, P<0.000 1] of patients with TA were all increased. Conclusions:The autoimmunity of patients with TA without hormone or immunosuppressant treatment is in active state, and the total T-lymphocytes and helper T-lymphocytes in peripheral blood are significantly increased in order to cope with the inflammatory response of the systemic artery vessels.
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Objective:To investigate risk factors for severe hematological toxicity of adjuvant chemotherapy and prognostic factors in elderly patients with ovarian cancer.Methods:We retrospectively analyzed 117 ovarian cancer patients aged 60 years and older who underwent surgery followed by adjuvant chemotherapy between January 2006 to December 2016 at Beijing Hospital.Risk factors for grade Ⅲ-Ⅳ hematological toxicity were assessed by using multivariate logistic regression analysis.Prognostic factors influencing progression-free survival(PFS)were evaluated by univariate and multivariate Cox regression analysis.Results:The mean age of patients was(69.3±7.9)years.After surgery, 67.3% patients(70/104)had a satisfactory tumor reduction, and 83.5%(86/103)received a standard treatment.Multivariable logistic regression analysis showed that risk factors for severe hematological toxicity included albumin level<40 g/L( OR=3.434, 95% CI: 1.074~10.968)and age>75( OR=3.676, 95% CI: 1.032~13.093). Progression-free survival for patients was 20.4 months(95% CI: 19.4~26.0). Univariate Cox regression analysis showed that FIGO(the International Federation of Gynecology and Obstetrics)staging, pelvic lymphadenectomy, tumor burden, transfusion therapy and residual tumor size were risk factors influencing 3-year PFS.Multivariate Cox regression analysis showed that low tumor burden was the only independent risk factor for 3-year PFS( HR=2.067, 95% CI: 1.174~4.424, P=0.023). Conclusions:Age ≥75 and albumin levels have effects on the incidences of complications during adjuvant chemotherapy, which in turn affect whether patients can complete standard adjuvant therapy and the clinical outcome of patients with ovarian cancer after surgery.To maximize the efficacy of treatment and reduce the side effects of adjuvant therapy, individualized treatment plans should be formulated for elderly patients with poor prognostic factors.
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Objective:To investigate the infection status and the infection rate of age stratification of human papillomavirus (HPV) subtypes in women at some areas of Beijing, who were diagnosed with no intraepithelial lesions and canceration, low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL), based on the diagnosis of women′s thinprep cytologic test(TCT).Methods:From January 2019 to December 2019, the cervical exfoliated cells of women who presented in Department of Gynaecology and Obstetrics of Beijing Anzhen Hospital Affiliated to Capital Medical University were collected, and the high-risk HPV typing nucleic acid test kit (fluorescence quantitative PCR) was used for genotyping.The results were retrospectively analyzed.Meanwhile, the patients who were tested by TCT at the same time were screened.According to the TCT pathological diagnosis, these patients were divided into three groups: no intraepithelial lesions and canceration (hereinafter referred to as the control group), low-grade squamous intraepithelial lesions (TCT-LSIL) and high-grade squamous intraepithelial lesions (TCT-HSIL). The chi square test was used for the statistical analysis.Results:In control group (561 cases), 68 cases were infected by at least one subtype of HPV, with a total positive rate of 12.12%.In TCT-LSIL group (385 cases), 288 cases were infected by at least one subtype of HPV, with a total positive rate of 74.81%.In TCT-HSIL group (170 cases), 128 cases were infected by at least one subtype of HPV, with a total positive rate of 75.29%.The highest positive rate was type 52 in the control group, while the highest positive rate was type 16 in the TCT-LSIL and TCT-HSIL groups.The infection rate of the three groups increased with the increase of cervical pathological grade.The infection rates of type 16, 18, 31, 33, 39, 45, 51, 52, 56, 58 and 68 were significantly different among the three groups (all P<0.05). The infection rate of HPV16 in the TCT-HSIL group was significantly higher than that in the control group and the TCT-LSIL group(P′<0.017). After all the subjects were stratified by age, only type 16 had statistical difference in infection rate among different age groups (all P<0.05). After age stratification of three groups, within the age<31 years old, the infection rates of 16, 18, 31, 33, 39, 45, 51, 52, 56 and 58 types were statistically different among the three groups (all P<0.05). In the age range of ≥31-<41 years old, the infection rates of 16, 18, 39, 51, 52, 56 and 58 types were statistically different among the three groups (all P<0.05). In the age range of ≥41-<51 years old, the infection rates of 16, 18, 35, 52, 56 and 58 types were statistically different among the three groups (all P<0.05). In the age≥51 years old, the infection rates of 16, 18, 31, 33, 51, 52 and 58 types were statistically different among the three groups (all P<0.05). After the age stratification of TCT-LSIL group, the infection rates of 16 and 45 types were statistically different among in the four groups of<31, ≥31-<41, ≥41-<51 and ≥51 years old (all P<0.05). However, there was no significant difference in the infection rate of each subtype in the control group and the TCT-HSIL group(all P>0.05). Conclusion:HPV subtypes 16, 18, 51, 52, and 58 are the main infection types in high grade squamous intraepithelial lesion patients, which are the main types of HPV caused cervical lesions.In addition, the infection rates of HPV in patients with cervical high-grade squamous intraepithelial lesionsare similar in different age groups.
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BACKGROUND@#Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily.@*METHODS@#A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude.@*RESULTS@#The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave.@*CONCLUSIONS@#Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.