Rat cardiac fibroblasts inhibit gap junction between cardiomyocytes through increasing matrix metalloproteinase 2 activity / 中国病理生理杂志

AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.

Decision characteristics in adolescents with mood disorders and suicide attempts / 中国心理卫生杂志

Objectives:To analyze the performance and characteristics of adolescent suicide attempters in dif-ferent dimensions of decision making,a computational model was used in this study.Methods:A total of 70 adoles-cent suicide attempters with mood disorders meeting the International Statistical Classification of Diseases and Re-lated Health Problems,Tenth Revision(ICD-10)diagnosis,40 non-suicide attempters with mood disorder,and 49 normal controls were included.By using the MCQ and IGT and through computational model analysis,the adoles-cent suicide attempters'performance and underlying cognitive components in impulsive decision making and value-and learning-based decision making were analyzed.Results:The overall delay discounting rates showed no signifi-cant differences(P＞0.05)among the group of suicide attempters,patient controls,and normal controls in the MCQ.This rate was significantly higher in suicide attempters and non-suicide attempters than in normal controls(P＜0.05);there was no significant difference between the three groups of subjects'decision making performance in the IGT(P＞0.05).Computational model analysis revealed that compared to non-suicide attempters and normal controls,suicide attempters showed reduced sensitivity to the outcome as well as reduced exploratory behavior(Pa-rameter estimate with non-overlapping 80％HDI).Conclusion:Adolescent suicide attempters may not be able to learn from the outcome of the decision and explore more possible options to resolve the crisis,as well as impulsive decision-making impairment may be associated with depressed states rather than suicide attempts.

Evaluation and application of automated quality control of automatic pipeline in clinical biochemical and immunological detection / 中华检验医学杂志

Objective:To assess the applicability of fully automatic pipeline automated testing for internal quality control (automated quality control).Methods:Stability, assay efficiency and implementation costs of 18 biochemical tests, 5 immunoturbidimetric tests and 11 chemical illuminescent tests in the Department of Laboratory Medicine of Peking Union Hospital from January 2019 to July 2022 were evaluated using automated quality control implementation methods. The detailed method is as follows: quality control materials for biochemical, immunoturbidimetric and chemiluminescent tests were stored in the refrigerator in the pipeline which was controlled by the intermediate software, and were automatically retrieved and tested as pre-set followed by documenting and storing. The quality control setup for the biochemical tests included refreshing quality control materials daily and weekly,both of which were paralleled for 3 months. The on-line storage stability of quality control materials in the pipeline was evaluated by comparing the coefficients of variation ( CV) of the quality control results between the two patterns. Effect of automated quality control application was evaluated using 6 indicators, including the results′ variation of automatically performed and manually performed quality controls, the out-of-controlled rate, the consumption of quality control materials, the change of staff workload, the impact on the testing time of the first sample, and the failure rate of automated quality control. Results:(1) Storage stability of quality control materials in the pipeline: under the pattern of weekly refresh of the biochemical quality control materials, except for total carbon dioxide (TCO 2) (the CVs of low and high level quality control were respectively 20.24% and 21.82%) and sodium (the CV of low level quality control was 1.51%) that were greater than the allowable variation set by the laboratory, the CVs of the rest tests meet the lab requirements on the allowable variations. (2) The results′ variation of quality control in automatically performed and manually performed control patterns: in the patterns of daily refresh of biochemical quality control materials and weekly refresh of immunoturbidimetric and chemiluminescent quality control materials, the CVs of both low and high levels of quality control were lower in the automatically performed control pattern than that in manually performed pattern for 8 chemiluminescent items of dehydroepiandrosterone sulfate, estradiol, follicle stimulating hormone, luteinizing hormone, serum ferritin, serum folic acid, vitamin B12 and testosterone, 3 immunologic items of complement 3, C reactive protein and immunoglobulin G, and 10 biochemical items of alkaline phosphatase, glucose, calcium, chloride, potassium, lactate dehydrogenase, sodium, urea, low density lipoprotein cholesterol, and adenosine deaminase. The out-of-control rates of biochemistry, immunoturbidimetric and chemiluminescence tests in both quality control patterns conformed with the clinical routine work requirements. (3) Comparison of quality control materials′ consumption: compared with manually performed quality control, weekly consumption of automatically performed chemiluminescent quality control materials decreased 37.5% (from 8 ml to 5 ml); weekly consumption of automatically performed immunoturbidimetric quality control materials decreased 33.3% (from 3 ml to 2 ml). (4)Comparison of staff workload and first sample testing time: compared with manually performed quality control, automatical quality control reduced manual work by about 156 steps per week, and the daily initial testing time was earlier by 15 min on average. The failure rate was 54.5% (37/64) during the early-stage application of the automated quality control which dropped to 10.2% (13/128) in the late-stage. Conclusion:The results of automated quality control detected in the pipeline system meet the quality indicators′ requirements of the laboratory, and the application of automated quality control can improve the quality control, save costs, reduce workload, and improve work efficiency.

Handling health emergency in public hospitals / 现代医院

Public hospitals play a dominant role in providing medical services.Meanwhile,they are also critical for un-dertaking missions to handle health emergencies.This paper analyzes the necessity,current situation,and existing weaknesses of the health emergency capacity of public hospitals.It also conducts a comparative study of the emergency response mechanisms of foreign medical institutions.This paper aims to explore a well-developed design for health emergency in public hospitals that is suitable for China's medical conditions and to provide a feasible model for promoting high-quality health emergency management.

Prevalence of condylar morphological changes in individuals with class II malocclusion

Abstract This observational, cross-sectional study with retrospective collection was aimed to evaluate the prevalence of morphological changes in mandibular condyles in individuals with class II malocclusion, classified according to different vertical growth patterns (brachyfacial, mesofacial, and dolichofacial), through cone beam computed tomography (CBCT). Seventy CBCT images (140 mandibular condyles) were selected from individuals without orthodontic treatment, of both sexes, aged between 25 and 50 years. No statistically significant differences were found between facial patterns; however, there was a higher relative prevalence of bone changes in dolichofacial individuals with flattening (62%), sclerosis (44%), and subchondral bone cyst (20%). Erosion and osteophytes prevailed in mesofacial (39%), and brachyfacial individuals (32%), respectively. Thus, there was no statistically significant difference in the prevalence of degenerative changes between the vertical skeletal patterns. Flattening was the most prevalent change, whereas subchondral bone cyst was the least prevalent among the three groups studied. The observational design of this study makes it possible to analyze image banks to verify the correlation of morphological changes in the temporomandibular joint in different facial patterns in patients with class II malocclusion. A limitation of the study is that clinical characteristics were not evaluated.

Comparison of prediction ability of two extended Cox models in nonlinear survival data analysis / 南方医科大学学报

OBJECTIVE@#To compare the predictive ability of two extended Cox models in nonlinear survival data analysis.@*METHODS@#Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability).@*RESULTS@#For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance.@*CONCLUSION@#In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.

Comparison of 7 methods for sample size determination based on confidence interval estimation for a single proportion / 南方医科大学学报

OBJECTIVE@#To compare different methods for calculating sample size based on confidence interval estimation for a single proportion with different event incidences and precisions.@*METHODS@#We compared 7 methods, namely Wald, AgrestiCoull add z2, Agresti-Coull add 4, Wilson Score, Clopper-Pearson, Mid-p, and Jefferys, for confidence interval estimation for a single proportion. The sample size was calculated using the search method with different parameter settings (proportion of specified events and half width of the confidence interval [ω=0.05, 0.1]). With Monte Carlo simulation, the estimated sample size was used to simulate and compare the width of the confidence interval, the coverage of the confidence interval and the ratio of the noncoverage probability.@*RESULTS@#For a high accuracy requirement (ω =0.05), the Mid-p method and Clopper Pearson method performed better when the incidence of events was low (P < 0.15). In other settings, the performance of the 7 methods did not differ significantly except for a poor symmetry of the Wald method. In the setting of ω=0.1 with a very low p (0.01-0.05), failure of iteration occurred with nearly all the methods except for the Clopper-Pearson method.@*CONCLUSION@#Different sample size determination methods based on confidence interval estimation should be selected for single proportions with different parameter settings.

Evaluation methods of clinical efficacy of traditional Chinese medicine / 中国中药杂志

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

Problems and thoughts in clinical safety evaluation of traditional Chinese medicine / 中国中药杂志

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Mutational Spectrum and Prognosis Analysis of Young Patients with Diffuse Large B-Cell Lymphoma Based on Next-Generation Sequencing / 中国实验血液学杂志

OBJECTIVE@#To investigate the mutational spectrum in young patients with diffuse large B-cell lymphoma (DLBCL) based on next generation sequencing (NGS), and to provide a basis for in-depth understanding of the molecular biological characteristics and accurate prognosis of young DLBCL.@*METHODS@#From March 2009 to March 2021, 68 young DLBCL patients with complete initial diagnosis data from the Department of Hematology, The People's Hospital Xinjiang Uygur Autonomous Region were retrospectively analyzed, and their paraffin-embedded tissues were subjected to targeted sequencing analysis by NGS technology (including 475 Target genes), and the differences in gene mutation profiles and signaling pathways between high-risk patients with aaIPI ≥2 and low-intermediate risk patients with aaIPI <2 were compared.@*RESULTS@#A total of 44 high-frequency mutation genes were detected in 68 young DLBCL patients. By comparing the high-frequency mutation genes in aaIPI high-risk group and low-intermediate risk group, it was found that CARD11 mutation in aaIPI high-risk group was significantly higher than that in low-intermediate risk group (P =0.002), while MGA mutation (P =0.037) only appeared in the aaIPI high-risk group, and SPEN mutation (P =0.004) only appeared in the aaIPI low-intermediate risk group. The high-frequency mutation genes and clinical indicators of the aaIPI high-risk group were included in the survival analysis, and the results showed that TP53 (P =0.009, P =0.027), POU2AF1 (P =0.003, P =0.006) and CCND3 (P =0.040, P =0.014) genes mutations were associated with worse PFS and OS, while B2M was associated with better PFS (P =0.014) and OS (P =0.013). Multivariate COX regression analysis showed that the TP53, POU2AF1 and CCND3 were independent risk factors for PFS（P ＝0.021，P =0.005，P =0.020） and OS（P ＝0.042，P =0.010，P =0.013）.@*CONCLUSION@#The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.

Effects of chronic fluoride exposure on spatial learning and memory and hippocampal PI3K/Akt/mTOR signaling pathway in second offspring rats / 中华地方病学杂志

Objective:To study the effects of chronic fluoride exposure on spatial learning and memory and the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in hippocampus of second offspring (F2 generation) rats.Methods:Sixteen clean-grade healthy SD pregnant rats were randomly divided into four groups according to their body mass [(200 ± 50) g] using a random number table method: the control group [0 mg/L sodium fluoride (NaF)], and the low, medium, and high fluoride groups (60, 120, 240 mg/L NaF), with four rats in each group. Fluoride exposure was carried out from the 0th day of pregnancy to the 21st day of birth (PND21) of first offspring (F1 generation) rats through free drinking water. The F1 generation rats continued to be exposed to fluoride at the same dose and method as the female rats in the same group until the 90th day of birth (PND90). Six rats (male to female ratio 2∶1) were selected from each group and housed together. Female F1 were continuously exposed with the same method until PND21 of the F2 generation rats. Eight F2 generation rats (4 males and 4 females, with a male to female ratio of 1∶1 in the same litter) were randomly selected from each group and exposed to NaF with corresponding concentrations from PND22 to PND90. Before the execution of F2 generation rats, Morris water maze experiment was used to examine spatial learning and memory ability. After execution, real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of PI3K, Akt, and mTOR in the hippocampus, respectively.Results:Compared with the control group days 2 - 4 [(46.72 ± 4.24), (24.87 ± 3.15), (14.10 ± 2.52) s], the escape latency of F2 generation rats was prolonged in the medium and high fluoride groups on the second day [(53.96 ± 3.45), (54.48 ± 6.20) s] and on the fourth day [(19.47 ± 2.51), (25.02 ± 3.86) s], and in the low, medium and high fluoride groups on the third day [(32.37 ± 4.56), (37.32 ± 4.65), (41.79 ± 7.08) s, P < 0.05]. Compared with the control group, the first arrival time of F2 generation rats in the high fluoride group was prolonged, while the number of crossing platforms in both the medium and high fluoride groups decreased ( P < 0.05). Except for mTOR mRNA in the low fluoride group, the mRNA and protein expression levels of PI3K, Akt, mTOR in the hippocampus of rats in all other exposure groups were lower than those in the control group ( P < 0.05). The results of correlation analysis showed that NaF concentration was positively correlated with the escape latency and the first arrival time of F2 generation rats on days 1 - 4 ( r = 0.44, 0.57, 0.79, 0.80, 0.58, P < 0.05), and negatively correlated with the mRNA and protein expression levels of PI3K, Akt, mTOR in the hippocampus of F2 generation rats, as well as the number of crossing platforms ( r = - 0.71, - 0.67, - 0.73, - 0.61, - 0.58, - 0.71, - 0.82, P < 0.05). Conclusion:Chronic fluoride exposure can lead to spatial learning and memory impairment in F2 generation rats, and its mechanism of action may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway in the hippocampus.

Characteristics analysis of families of retinal vascular disease with leukoencephalopathy and systemic damage / 中国神经精神疾病杂志

Objective To investigate the clinical data,brain pathology and molecular genetic characteristics of retinal vascular disease families with leukoencephalopathy and systemic damage.Methods The clinical data of two families of RVCL-S(retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations,RVCL-S)were collected and family maps were drawn to analyze the clinical manifestations,imaging,brain pathology and molecular genetic characteristics.Results Family 1:there were 3 male cases and the age of onset was 10 years,29 years and 40 years,respectively.Family 2:there was one male case and the age of onset was 32 years.Both families presented with retinal vascular disease,leukoencephalopathy and multi-system damage,the latter including liver,kidney and digestive tract involvement.There were 4 asymptomatic carriers in two families.The cranial CT of family 1-Ⅱ2 showed lamellar low density near the posterior corner of the left ventricle with multiple intracranial high density calcification.Brain MRI plain scan showed lateral ventricle lesions.The brain MRI plain and enhancement scans of family 1-I5 showed frontotemporal cortex lesions with peripheral edema and space occupying effect,and the ring enhancement was remarkable.The brain MRI plain scan and enhancement scan of family 2-Ⅱ1 showed the right and left frontal lobe lesions,accompanied by peripheral edema and enhancement,and the occupying effect was obvious.The operative pathology of brain tissue from family 1-I5 showed endothelial cell hyperplasia.The pathological manifestations of family 2-Ⅱ1 encephalopathy were consistent with"cerebral infarction"after two operations.The small blood vessels in the small intestinal wall showed endothelial cell proliferation.Molecular genetics:TREX1 D272Rfs heterozygous mutation was present in family 1-Ⅱ2,and his offspring including two daughters and one son were asymptomatic mutation carriers.TREX1 S246Ifs heterozygous mutation was detected in the 2-Ⅱ1 gene of the family which was not found in either the father or the mother found the mutation,and the son was asymptomatic carrier of the mutation.Conclusion The main clinical manifestations of RVCL-S are retinal vascular disease,nervous system involvement and multi-system damage.Imaging findings showed that intracranial lesions were space-occupying,accompanied by peripheral edema and enhancement.The pathological features were small vessel endothelial cell proliferation and lumen stenosis.Genetic results confirmed the presence of TREX1 gene mutation.

Effects of exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation on ventricular electrical conduction during hypothermic cardiac ischemia-reperfusion in rats / 中华麻醉学杂志

Objective:To evaluate the effects of exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation on ventricular electrical conduction during hypothermic cardiac ischemia-reperfusion (I/R) in rats.Methods:SPF neonatal Sprague-Dawley rats of either sex, aged 1-2 days, were used, and primary cardiac fibroblasts were extracted by differential adhesion method. The cells were passaged for 2-4 generations. When the cell density reached 60%-70%, the cells were transferred and exposed to 95% N 2 + 5% CO 2 for 1 h at 4 ℃, and then exposed to 95% air + 5% CO 2 for 24-48 h at 37 ℃, and then exosomes were extracted. Twenty-four SPF healthy adult male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were divided into 3 groups ( n=8 each) according to the random number table method: control group (group C), hypothermic cardiac IR group (I/R group) and exosome + hypothermic cardiac IR group (Exo-IR group). At 48 h before equilibrium perfusion, 1.5 ml (200 μg) of exosomes secreted by cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation was injected into the tail vein in Exo-IR group, and PBS 1.5 ml was injected into the tail vein in C group and IR group each. Group C received 110 min equilibration perfusion. After 20 min of equilibration, the perfusion was suspended for 60 min (global ischemia) followed by 30 min of reperfusion in IR and Exo-IR groups. Microelectrode arrays were applied at 20 min of equilibrium perfusion and 15 and 30 min of reperfusion to obtain myocardial conduction velocity (CV), absolute conduction inhomogeneity (P 5-95) and inhomogeneity index (P 5-95/P 50) on the left ventricular surface of isolated rat hearts. Results:Compared with group C, the CV was significantly decreased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were increased in IR and Exo-IR groups ( P<0.05). Compared with IR group, CV was significantly increased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were decreased in Exo-IR group ( P<0.05). Conclusions:Exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation can improve ventricular electrical conduction during hypothermic cardiac I/R in rats.

Galectin-3 and ischemic stroke / 国际脑血管病杂志

Ischemic stroke is a disease with high incidence, high disability and high mortality rates. As a key regulator of microglia activation and proliferation, galectin-3 may have dual effects on ischemic stroke. This article reviews the structure and function of galectin-3, as well as its roles in ischemic stroke.

Effects of different early sedation levels on clinical outcomes of ICU patients with mechanical ventilation / 中国实用护理杂志

Objective:To investigate the current sedation level of patients with mechanical ventilation in ICU, and to explore the influence of early different sedation levels on clinical outcomes, so as to provide theoretical basis for better guidance of clinical sedation evaluation and implementation of sedation strategy management.Methods:This study was a retrospective longitudinal study. The 201 patients with invasive mechanical ventilation who underwent sedation in the Department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January to December 2021 were selected by convenience sampling method. According to the results of Richmond Agitation-Sedation Scale(RASS), the patients were divided into deep sedation group (98 cases) and shallow sedation group (103 cases). The influencing factors of endotracheal intubation retention time and outcome were investigated by Cox multifactor analysis.Results:In the early sedation ≤48 h after the start of mechanical ventilation, 63.2%(2 143/3 389) of patients with invasive mechanical ventilation had a RASS score of shallow sedation, 35.2%(1 194/3 389) of patients with deep sedation, and 1.5%(52/3 389) of patients with insufficient sedation. Cox multivariate regression analysis showed that age, sedation level, duration of invasive mechanical ventilation and continuous renal replacement therapy were the factors influencing the indentation time of tracheal insertion ( χ2 values were 4.73 to 74.31, all P<0.05); early deep sedation was a risk factor for delayed extubation ( HR=0.499, 95% CI 0.276-0.903, P<0.05); gender, sedation level, invasive mechanical ventilation duration, acute physiology and chronic health evaluation Ⅱ scores, admission mode, continuous renal replacement therapywere the influencing factors of patient outcomes ( χ2 values were 4.41 to 26.20, all P<0.05). The deeper the sedation, the worse the patient outcomes ( HR=0.568, 95% CI 0.335-0.963 all P<0.05) . Conclusions:The early sedation level is related to the retention time and outcome of tracheal intubation in ICU patients with mechanical ventilation, and different sedation levels affect the clinical outcome of patients. The retention time of tracheal intubation in patients with shallow sedation was shortened, which was beneficial to the outcome of patients.Therefore, sedation evaluation should be strengthened in clinical work, and sedation methods should be selected according to the needs of patients. In the absence of contraindications, the shallow sedation strategy should be implemented as soon as possible. This study provides some reference and theoretical basis for the formulation and management of clinical sedation strategies.

Relationship between Sestrin2 and mtDNA-NLRP3 inflammasome pathway during endotoxin-induced myocardial injury in mice / 中华麻醉学杂志

Objective:To evaluate the relationship between Sestrin2 and mitochondrial DNA (mtDNA)-NOD-like receptor associated protein 3 (NLRP3) inflammasome pathway during endotoxin-induced myocardial injury in mice.Methods:One hundred and eighty-four clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were used in this study. One hundred and sixty-eight mice were divided into 7 groups ( n=24 each) using the random number table method: normal control group (N group), lipopolysaccaride(LPS) group (L group), mtDNA group, LPS+ mtDNA group (M group), normal control+ negative control adeno-associated virus (AAV-NC)group (NC group), LPS+ mtDNA+ AAV-NC group (MC group), and LPS+ mtDNA+ Sestrin2 overexpression adeno-associated virus (AAV-Sestrin2) group (MSgroup). Another 10 mice were used to detect the transfection effect of AAV-Sestrin2, and the left 6 mice were used for mtDNA extraction. The model of endotoxemia was developed by intraperitoneal injection of LPS 10 mg/kg. mtDNA 5 mg/kg was intraperitoneally injected in mtDNA group, and mtDNA 5 mg/kg was intraperitoneally injected at 30 min after LPS injection in M group.AAV-Sestrin2 150 μl was injected via the tail vein in MS group, and the equal volume of AAV-NC was injected via the tail vein in MC and NC groups. Four weeks after virus injection, LPS 10 mg/kg was intraperitoneally injected and 30 min later mtDNA 5 mg/kg was intraperitoneally injected in MS and MC groups. Blood samples were collected at 24 h after LPS injection for determination of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities (by biochemical assay), concentrations of serum cardiac troponin I (cTnI), interleukin-18 (IL-18) and interleukin-1beta (IL-1β)(by enzyme-linked immunesorbent assay), and expression of mtDNA (by quantitative real-time polymerase chain reaction). The animals were sacrificed after the end of blood sampling and myocardial tissues were obtained for determination of the contents of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and adenosine triphosphate (ATP) and expression of NOD-like receptor associated protein 3 (NLRP3), active subunit p20 of caspase-1 (caspase-1p20) and apoptosis-associated microprotein (ASC) in myocardial tissues (by Western blot) and for microscopic examination of the pathological changes after HE staining (with a light microscope). Results:Compared with N group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in L group and mtDNA group.Compared with L group and mtDNA group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in M group. Compared with M group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly decreased, the expression of mtDNA was down-regulated, the ROS content in myocardial tissues was decreased, the T-AOC and ATP contents in myocardial tissues were increased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was down-regulated( P<0.05), and the pathological changes of myocardial tissues were significantly attenuated in MS group. Conclusions:Sestrin2 can reduce endotoxin-induced myocardial injury in mice by alleviating mitochondrial damage, inhibiting oxidative stress, protecting mtDNA from oxidative damage, and then inhibiting mtDNA-NLRP3 inflammasome pathway.

Prognostic Predictive Value of ITPKB Mutation's Variant Allele Frequency in Diffuse Large B-cell Lymphoma / 肿瘤防治研究

Objective To investigate the correlation between ITPKB mutation's variant allele frequency (VAF) and prognosis of diffuse large B-cell lymphoma (DLBCL). Methods This study included 155 patients with DLBCL initially diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. Paraffin-embedded tumor tissue specimens were obtained, and tumor tissue DNA was extracted. A total of 475 hotspot genes including ITPKB were detected by the next generation sequencing to analyze the relationship of the VAF of high-frequency mutant gene with progression-free survival (PFS) and overall survival (OS). Results The mutation frequency of ITPKB was 18.71%. The PFS was significantly shorter in the patients with ITPKB mutations than in those without mutations (37 months vs. 108 months; HR=1.643, 95%CI: 0.920-2.934, P=0.093). The R-language based web tool was used to find the best VAF cutoff to differentiate prognosis. The patients were divided into two groups (VAF High vs. VAF Low+Wt) according to their VAF values. The optimal VAF threshold for ITPKB was 27.48% (HR=3.480, 95%CI: 1.70-7.13, P=0.00027). Multivariate Cox analysis was conducted using clinical indicators such as age, gender, COO classification, IPI, and LDH, and the results showed that PFS was associated with high ITPKB VAF (≥28%) (HR=3.592, 95%CI: 1.738-7.425, P < 0.001) which was an independent adverse predictor of PFS. Conclusion The high load of ITPKB mutation is an independent risk factor for the PFS of patients with DLBCL, and the VAF of ITPKB mutation has a prognostic predictive value for patients with DLBCL.

Role of SIRT1 and associated microRNAs in dexmedetomidine-induced alleviation of renal injury in diabetic mice / 中华麻醉学杂志

Objective:To evaluate the role of silencing regulatory protein (SIRT1) and its associated microRNAs (miRNAs) in dexmedetomidine-induced attenuation of renal damage in diabetic mice.Methods:SPF grade C57 male mice, aged 8 weeks, in which diabetes mellitus model was developed by intraperitoneal injection of 1% streptozotocin, were used.Thirty mice in which the model was successfully developed were divided into 5 groups ( n=6 each) using the random number table method: diabetes mellitus group (D group), diabetes mellitus + dexmedetomidine group (DD group), diabetes mellitus + dexmedetomidine + EX527 group (DDE group), diabetes mellitus + dexmedetomidine + miR-34a-3p-agomir group (DDH group), and diabetes mellitus + dexmedetomidine + miR-34a-3p-agomirNC group (DDC group). Six normal mice were selected as control group (C group). Dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h, 3 times in total in DD, DDE, DDH and DDC groups.miR-34a-3p-agomir and miR-34a-3p-agomirNC 2.5 mmol were intraperitoneally injected via the tail vein at 72 h before dexmedetomidine administration once every 3 days, 2 times in total in DDH and DDC groups, respectively.SIRT1 inhibitor EX527 10 mg/kg was intraperitoneally injected at 1 h before dexmedetomidine administration in group DDE.At 24 h after the end of administration, serum concentrations of IL-6, IL-18, Cr and BUN, contents of nitric oxide (NO) and total antioxidant capacity (T-AOC), ROS activity, and expression of SIRT1, FoxO3a and P53 protein and mRNA, and expression of miR-217, miR-138 and miR-34a in renal tissues were determined. Results:Compared with group C, the serum IL-6, IL-18, Cr and BUN concentrations, contents of T-AOC and NO, and ROS activity were significantly increased, the expression of P53 protein and mRNA, miR-34a, miR-217 and miR-138 was up-regulated, and the expression of SIRT1 and FoxO3a protein and mRNA was down-regulated in group D ( P<0.05). Compared with group D, serum IL-6, IL-18, Cr and BUN concentrations, ROS activity and NO content were significantly decreased, T-AOC content was increased, the expression of SIRT1 and FoxO3a protein and mRNA was up-regulated, and the expression of miR-34a was down-regulated in group DD ( P<0.05). Compared with group DD, the serum IL-6, IL-18, Cr and BUN concentrations, NO content and ROS activity were significantly increased, T-AOC content was decreased, and the expression of SIRT1 and FoxO3a protein and mRNA was down-regulated in group DDE and group DDH ( P<0.05), no significant change was found in the expression of P53 protein and mRNA, miR-217, miR-34a and miR-138 in group DDE ( P>0.05), and the expression of P53 protein and mRNA and miR-34a was significantly up-regulated in group DDH ( P<0.05). Conclusions:The mechanism by which dexmedetomidine attenuates renal injury may be related to down-regulation of miR-34a expression, which further up-regulates SIRT1/FoxO3 expression and decreases oxidative stress in diabetic mice.

Case report of pseudoelevated serum testosterone in women and literature review / 中华检验医学杂志

Objective:The characteristics of women with false elevated testosterone were analyze and the literature was reviewed to provide reference for clinical laboratory identification of false elevated testosterone.Methods:The characteristics of three patients with false elevated testosterone in Peking Union Medical College Hospital were analyzed retrospectively, and the results of different detection platforms and methods for the determination of testosterone levels were compared. International and domestic literatures related to false elevation of testosterone and detection methods of testosterone were searched for a comprehensive analysis from PUBMED and CNKI.Results:The levels of testosterone in 3 female patients were elevated by immunoassay and normal by mass spectrometry. They were excluded from the diagnosis of hyperandrogenemia. A total of 38 literatures related to testosterone detection were retrieved, of which 9 case reports of pseudohyperandrogenemia, among which 12 cases of pseudohyperandrogenemia were reported in 2 domestic literatures in 2021. All cases were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Previous studies have clearly indicated that the result of routine immunoassay in clinical laboratory for the determination of female testosterone have poor correlation with the results of LC-MS/MS, with varying degrees of deviation.Conclusions:Immunoassay tests for female testosterone is susceptible to interference and lead to elevated false results. It is suggested that clinical laboratories evaluate the detection methods used and establish a identification program, and confirm samples with suspected pseudoelevated testosterone elevation using other immune platforms or LC-MS/MS.

Efficacy of prostatic arterial interventional embolization in the treatment of benign prostatic hyperplasia patients with prostatic volume greater than 80 milliliter / 中国医师进修杂志

Objective:To investigate the effect of interventional embolization of prostate artery in patients with benign prostatic hyperplasia with prostatic volume>80 ml.Methods:A total of 56 patients with BPH combined with hypertension, diabetesand heart disease with prostate volume>80 ml in Meizhou People′s Hospital from April 2018 to November 2020 were selected. They were divided into the study group and the control group according to a simple random number table, 28 cases in each group. The patients in the study group were performed prostatic arterial embolization, and the patients in the control group were performed transurethral resection of the prostate. The efficacy, perioperative conditions, preoperative and 1 month after operation serum total prostate specific antigen (TPSA) level, free prostate specific antigen (FPSA) level, prostate volume, and international prostate symptom score (IPSS) were compared between the two groups. The sexual life quality after operation for 6 months was compared between the two groups.Results:The efficacy of the two groups had no significant difference ( P>0.05). The intraoperative blood loss, postoperative catheterization, postoperative hospital stay in the study group were less than those in the control group: (10.65 ± 1.89) ml vs. (119.64 ± 23.60) ml, (2.16 ± 0.39) d vs. (3.05 ± 0.61) d, (3.03 ± 1.82) d vs. (7.10 ± 2.39) d, the differences were statistically significant( P<0.05). The levels of serum TPSA, FPSA and prostate volume, IPSS at the first month after surgery in the two groups had no significant differences ( P>0.05). After operation for 6 months, the scores of Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) and International Index of Erectile Function (IIEF-5) in the study group were higher than those in the control group: (18.63 ± 2.51) scores vs. (15.71 ± 2.29) scores, (16.38 ± 4.14) scores vs. (13.98 ± 3.82) scores, the differences were statistically significant ( P<0.05). Conclusions:Prostate arterial embolization is effective in BPH patients with prostate volume>80 ml and underlying diseases. Compared with transurethral prostatectomy, it has the advantage of faster recovery after surgery, and it has an ideal effect in controlling diseases, improving urination function, and quality of sexual life.