Long-term CXCR3 antagonist AMG487 mitigated acute graft-versus-host disease by inhibiting T cell activation in a murine model.

BACKGROUND: Lymphocyte migration plays a key role in the development of acute graft-versus-host disease (aGVHD). Blocking lymphocyte migration by targeting chemokine receptors, such as CXCR3, may be a promising strategy for preventing and treating aGVHD. Our previous studies have shown that short-term CXCR3 antagonist treatment combined with cyclosporine A alleviated aGVHD. However, the effect of long-term AMG487 treatment on aGVHD survival has not been thoroughly investigated. METHODS: A murine aGVHD model was used to examine the expression of CXCR3 in donor T cells. The effects of short- and long-term AMG487 treatment on aGVHD survival were assessed. The infiltration of donor T cells into the liver and spleen tissues and the activation of donor T cells in splenic tissues were also examined. RESULTS: CXCR3 was consistently highly expressed in donor T cells in a murine aGVHD model. Long-term AMG487 treatment, but not short-term, improved survival and aGVHD outcomes (p < 0.05). Furthermore, long-term AMG487 administration reduced the number of donor T cells in the liver but increased the number of donor T cells in the spleen (p < 0.05). Long-term AMG487 treatment also inhibited donor T cell activation in the spleen (p < 0.05). CONCLUSION: This study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy.

Association between BMI and age at menarche or spermarche among both sexes: Findings from six successive national surveys in China.

Background: To explore trends of the association between body mass index (BMI) and age at menarche or spermarche and its urban-rural disparities from 1995 to 2019. Methods: A total of 912 753 children and adolescents - including 519 940 9-18 years old girls and 392 813 11-18 years old boys - were involved in six successive cross-sectional surveys conducted across 30 provinces in China from 1995 to 2019. Data on menarche and spermarche was collected using the status quo method, where same-gender physicians conducted face-to-face interviews to determine if children and adolescents had experienced their first menstrual cycle or ejaculation (yes/no). The median age at menarche or spermarche was estimated by probit analysis. Anthropometric measurements measured the height and weight of the study subjects. Children and adolescents were classified into thinness, normal range of weight, overweight, and obesity. t test was used to compare the differences in BMI between premenarchal and postmenarchal girls or prespermarcheal and postspermarcheal boys. Logistic regression was used to explore the associations between BMI/nutritional status and menarche or spermarche stratified by urban or rural residency status. Results: From 1995 to 2019, BMI in all age groups growth over time, and the values of BMI among children and adolescents under 15 who had menarche or spermarche were more significant than those without menarche or spermarche. In 2019, for girls, thinness was associated with delayed menarche (odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.24-0.28), while overweight (OR = 1.99; 95% CI = 1.85-2.14) and obesity (OR = 2.20; 95% CI = 1.92-2.53) was associated with advanced menarche. For boys, thinness was associated with delayed spermarche (OR = 0.71; 95% CI = 0.65-0.78), overweight was associated with advanced spermarche (OR = 1.08; 95% CI = 1.01-1.15) while obesity had no association with spermarche. The OR between BMI and menarche in 1995 was 1.35 (95% CI = 1.33-1.37), which decreased to 1.19 (95% CI = 1.18-1.20) by 2019. The OR between BMI and spermarche in 1995 was 1.10 (95% CI = 1.09-1.11), which decreased to 1.02 (95% CI = 1.02-1.03) by 2019. The trends by urban-rural stratification were consistent with the total sample. Conclusions: We have established a dose-response relationship between BMI and menarche in girls, whereas the association appears to be nonlinear in boys, and the associations were diminishing. Similar findings were observed in both urban and rural areas. Considering the dual adverse effects of obesity and early puberty on health, the results of this study suggest that sexual health education should be strengthened, especially among obese girls. Further research on the influencing factors and biological mechanisms of early puberty will be beneficial.

The Effect of Unintended Facet Arthrodesis on the Treatment Outcome of Dynamic Neutralization System for Lumbar Degenerative Diseases.

Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.

Learning Curve for Using Endoscopic Saphenous Vein Harvesting in Coronary Artery Bypass Grafting / 中山大学学报(医学科学版)

ObjectiveTo investigate the application of endoscopy in obtaining the great saphenous vein （GSV） during coronary artery bypass grafting （CABG） and explore the learning curve， with a particular focus on common challenges encountered during the learning process and their impact on early clinical outcomes. MethodsA retrospective analysis was conducted on clinical data from 83 patients who underwent off-pump CABG with endoscopic GSV harvesting at the First Affiliated Hospital of Zhengzhou University from July 2013 to April 2014. Patients were categorized into four groups based on the chronological order of their hospitalization： Group A （novice group， n=20）， Group B （proficient group， n=20）， Group C （progressive group， n=20）， and Group D （mature group， n=23）. Differences in perioperative and midterm follow-up outcomes among the groups were analyzed to determine the learning curve period. ResultsThe study population had a mean age of （60.22±8.06） years and a mean body weight of （69.77±11.66） kg. Comorbidities included hypertension （24 cases）， diabetes （26 cases）， and subacute cerebral infarction （14 cases）. The novice group exhibited significantly shorter GSV length-to-harvest time ratio relative to the other three groups （P<0.001） and a significantly higher incidence of main vein damage （P=0.006）. However， there was no statistically significant difference in graft patency at the 1-year follow-up. ConclusionThorough and reliable technical training in endoscopic GSV harvesting is essential to minimize vascular injury caused by novice operators. Approximately 20 cases of hands-on experience and a careful self-analysis of procedural challenges are likely required to achieve proficiency in GSV harvesting.

Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Effects of cortisol-awakening response on multi-target tracking in children with attention deficit hyperactivity disorder: the mediating role of working memory / 中华行为医学与脑科学杂志

Objective:To explore the mediating role of working memory (WM) in the cortisol-awakening response (CAR) and multiple object tracking (MOT) in children with attention deficit hyperactivity disorder (ADHD).Methods:92 children with ADHD (ADHD group) and 94 typically developing children (control group) were selected from January 2022 to October 2022. Salivary cortisol levels were detected and analyzed in all children at four time points after awakening. Children's WM and MOT performance were assessed by the 1-back and MOT paradigms, respectively. SPSS 26.0 software was used for t-test and Pearson correlation analysis of the data, and plug-in PROCESS model 4 of SPSS 26.0 was used for mediated effects analysis. Results:(1) ADHD group showed significantly lower CAR, 1-back accuracy and MOT performance((30.97±5.63), (81.33±10.64) %, (2.36±0.37)) than the control group((32.41±3.48), (91.19±7.12) %, (2.62±0.28))( t=-2.09, -7.22, -5.31, all P<0.05). (2) Pearson analysis showed that CAR was positively correlated with 1-back accuracy ( r=0.293, P<0.01) and MOT performance ( r=0.740, P<0.01). 1-back accuracy was positively correlated with MOT performance ( r=0.368, P<0.01). (3) WM partially mediated the effect of CAR on MOT in children with ADHD, accounting for 6.13% (0.003/0.049) of the total effect. Conclusion:Children with ADHD have deficits in MOT.WM plays a mediating role between CAR and MOT performance in children with ADHD.

Clinical observation of goserelin combined with estradiol valerate in the treatment of endometriosis in patients of childbearing age after laparoscopic surgery / 中国药房

OBJECTIVE To observe the efficacy and safety of goserelin combined with estradiol valerate in the treatment of endometriosis （EMs） in patients of childbearing age after laparoscopic surgery. METHODS The clinical data of 144 patients with EMs of childbearing age who underwent laparoscopic surgery in our hospital from January 2020 to December 2022 were collected retrospectively， and those patients were divided into control group （70 cases） and combination group （74 cases） based on different postoperative medication regimens. Control group was given Acetate goserelin sustained-release implant on the 1st to 5th day of their first menstrual cycle after laparoscopic surgery， while combination group was additionally given Estradiol valerate tablets on the basis of control group. The short-term and long-term efficacy of 2 groups were observed； preoperative and postoperative pain scores， ovarian reserve function， and the incidence of adverse reactions were all recorded in 2 groups. RESULTS There was no statistically significant difference in short-term total effective rate， 1-year postoperative recurrence rate and the incidence of decreased libido， vaginal dryness， gastrointestinal reactions， rash， or arrhythmia between two groups （P＞0.05）. The natural pregnancy rate of combination group was significantly higher than control group at 1 year after surgery， while the incidence E-mail：wanghuiling0518@126.com of early miscarriage， hot flashes and sweating， emotional fluctuations， insomnia and fatigue， joint muscle pain， dizziness and headache were significantly lower than control group （P＜0.05）. However， at 6 months after surgery， pain scores and the levels of anti-Müllerian hormone， follicle stimulating hormone， luteinizing hormone， estradiol of both groups were significantly lower than before surgery in the same group， while the number of antral follicle count was significantly higher than before surgery in the same group； the levels of anti-Müllerian hormone， luteinizing hormone， estradiol， and the number of antral follicles in the combination group were significantly higher than control group， while pain score and follicle stimulating hormone level were significantly lower than control group （P＜0.05）. CONCLUSIONS The combination of goserelin and estradiol valerate after laparoscopic surgery has a significant therapeutic effect and good safety in the treatment of EMs of childbearing age.

Clinical features of autoimmune encephalitis secondary to epidemic encephalitis B in 5 children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with autoimmune encephalitis (AE) secondary to epidemic encephalitis B (EEB).@*METHODS@#A retrospective analysis was performed on the medical data of five children with EEB with "bipolar course" who were treated in Children's Hospital Affiliated to Zhengzhou University from January 2020 to June 2022.@*RESULTS@#Among the five children, there were three boys and two girls, with a median age of onset of 7 years (range 3 years 9 months to 12 years) and a median time of 32 (range 25-37) days from the onset of EEB to the appearance of AE symptoms. The main symptoms in the AE stage included dyskinesia (5/5), low-grade fever (4/5), mental and behavioral disorders (4/5), convulsion (2/5), severe disturbance of consciousness (2/5), and limb weakness (1/5). Compared with the results of cranial MRI in the acute phase of EEB, the lesions were enlarged in 3 children and unchanged in 2 children showed on cranial MRI in the AE stage. In the AE stage, four children were positive for anti-N-methyl-D-aspartate receptor antibody (one was also positive for anti-γ-aminobutyric acid type B receptor antibody), and one was negative for all AE antibodies. All five children in the AE stage responded to immunotherapy and were followed up for 3 months, among whom one almost recovered and four still had neurological dysfunction.@*CONCLUSIONS@#EEB can induce AE, with anti-N-methyl-D-aspartate receptor encephalitis as the most common disease. The symptoms in the AE stage are similar to those of classical anti-N-methyl-D-aspartate receptor encephalitis. Immunotherapy is effective for children with AE secondary to EEB, and the prognosis might be related to neurological dysfunction in the acute phase of EEB.

Trend of age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were -0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and -0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were -0.071 years and 0.006 years, respectively, while those in rural areas were -0.082 years and -0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were -0.064, -0.099, -0.091, -0.080, -0.096 and -0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and -0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Predictive value of the maximum aggregation rate of platelet for septic shock and septic shock with disseminated intravascular coagulation / 中华危重病急救医学

Objective:To investigate the predictive value of the maximum aggregation rate (MAR) of platelet for septic shock and septic shock with disseminated intravascular coagulation (DIC).Methods:A retrospective case-control study enrolled patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022. The basic data, dynamic platelet aggregation rate, blood routine, inflammation indicators, sequential organ failure assessment (SOFA) and other clinical indicators within 24 hours after admission were collected. Septic patients were divided into the shock group and the non-shock group according to the presence of septic shock; then refer to the International Society on Thrombosis and Hemostasis (ISTH) standard, patients with septic shock were divided into the shock DIC group and the shock non-DIC group according to the presence of dominant DIC. Compared the differences in platelet aggregation function between these groups, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the MAR for septic shock and septic shock with DIC. Spearman correlation analysis was used to analyze the correlation of MAR with inflammation indicators and the severity of illness in patients with sepsis.Results:A total of 153 sepsis patients were included and 61 with septic shock (including 17 with dominant DIC and 44 without dominant DIC). Compared with the non-shock group, the level of procalcitonin (PCT), C-reactive protein (CRP), and SOFA score were significantly higher in the shock group [PCT (mg/L): 6.90 (2.50, 23.50) vs. 0.87 (0.26, 5.75), CRP (mg/L): 156.48 (67.11, 230.84) vs. 90.39 (46.43, 182.76), SOFA score: 11.00 (8.00, 14.00) vs. 5.00 (3.00, 8.00), all P < 0.05]. The platelet count (PLT) and the MAR induced by adenosine diphosphate (ADP), adrenaline (A), collagen (COL), and arachidonic acid (AA; ADP-MAR, A-MAR, COL-MAR, AA-MAR) in the shock group were significantly decreased [PLT (×10 9/L): 101.00 (49.00, 163.50) vs. 175.50 (108.25, 254.50), ADP-MAR: 28.50% (22.00%, 38.05%) vs. 45.90% (33.98%, 60.28%), A-MAR: 38.90% (30.00%, 55.40%) vs. 65.15% (54.38%, 72.53%), COL-MAR: 27.90% (20.85%, 36.55%) vs. 42.95% (33.73%, 54.08%), AA-MAR: 24.70% (16.40%, 34.20%) vs. 46.55% (28.33%, 59.20%), all P < 0.05]. Subgroup analysis revealed that, compared with the shock non-DIC group, the SOFA scores were significantly higher in patients in the shock DIC group (13.29±5.23 vs. 10.39±3.58, P < 0.05), the PLT and COL-MAR in the shock DIC group were significantly reduced [PLT (×10 9/L): 36.00 (22.00, 67.50) vs. 115.50 (84.25, 203.75), COL-MAR: 21.50% (17.85%, 32.60%) vs. 30.95% (22.98%, 38.53%), all P < 0.05]. ROC curve analysis showed that A-MAR had a higher predictive value for septic shock, and the area under the ROC curve (AUC) was 0.814 [95% confidence interval (95% CI) was 0.742-0.886, P = 0.000]. When the optimal cut-off value was 51.35%, the sensitivity was 68.9%, the specificity was 82.6%, the positive predictive value was 0.724 and the negative predictive value was 0.800. COL-MAR had some predictive value for septic shock with DIC, and the AUC was 0.668 (95% CI was 0.513-0.823, P = 0.044). When the optimal cut-off value was 21.90%, the sensitivity was 52.9%, the specificity was 79.5%, the positive predictive value was 0.500, and the negative predictive value was 0.813. Spearman correlation analysis showed that the MAR induced by each inducer was negatively correlated with inflammatory indicators and SOFA scores in sepsis patients, with A-MAR showing the strongest correlation with SOFA score ( r = -0.327, P = 0.000). Conclusions:MAR, an indicator of platelet aggregation function, shows predictive value for septic shock and septic shock with DIC, and it could be used to for evaluating the severity of patients with sepsis. In addition, tt alsocan be used as a monitoring index to predict the changes of sepsis patients and to guide the treatment.

Effects of simulated gas of warm pressure charge explosion on neurobehavior and hippocampal neurogenesis in rats / 中华行为医学与脑科学杂志

Objective:To investigate the effects of thermobaric charge explosion simulated gas on long-term neurobehavior and hippocampal neurogenesis in rats.Methods:A total of 48 male SPF grade SD rats aged 8-10 weeks were randomly divided into control group, 5 min exposure group, 10 min exposure group and 15 min exposure group, with 12 rats in each group. Twenty-eight days after inhalation of infection, the anxiety-like behavior of rats was evaluated by an elevated cross maze, and the learning and memory function of rats was evaluated by two-way active avoidance experiment. The number of positive cells of rat hippocampal dentate gyrus neural stem cells marker molecule neural epithelial cell protein (SOX2) and mature neuron marker molecular neuronal nuclei (NeuN) was detected by immunofluorescence staining. Western blot was used to detect SOX2 and NeuN protein expression in the hippocampal tissues of rats. GraphPad prism 8.0 software was used for data analysis.The comparison of repeated measurement design data was carried out by repeated measurement ANOVA.One-way ANOVA was used for inter group comparisons, and Tukey test was used for pairwise comparison. Hippocampal nerve cells were counted using the Image J software.Results:(1) The experimental results of the elevated cross maze showed that the percentage of arm opening and the percentage of open arm residence time in each group had significant group effects ( F=22.31, 5.43, all P<0.05). The percentage of open arm entry times of rats in the 5 min, 10 min and 15 min exposure group ((28.85±1.47)%, (15.04±4.69)%, (12.66±2.89)%) and the percentage of residence time in open arm ((12.12±2.64)%, (12.16±1.11)%, (8.73±3.52)%) were all lower than those of the control group ((65.40±1.86)%, (42.92±3.12)%) (all P<0.05). There were no statistically significant differences in pairwise comparison among the three exposure groups (all P>0.05). (2)During the memory acquisition period, the results of repeated-ANOVA showed that the time main effect ( F=56.46), the group main effect ( F=16.64) and the interaction effect had significant differences( F=4.21)(all P<0. 05). The difference values of active avoidance number between the 4th day and 1st day among the four groups were significant different ( F=68.63, P<0.05). During the memory reproduction period, there were significant differences in active avoidance number and active avoidance time among the four groups ( F=8.17, 8.28, both P<0.05). The active avoidance numbers in 10 min and 15 min exposure groups((2.50±0.26) times, (2.33±0.06) times)were significantly lower than those in the control group ((8.33±3.72) times) (both P<0.05), and the active avoidance time ((6.25±0.40)s, (6.61±1.63)s) were significantly higher than those in the control group((3.69±1.41)s) (both P<0.05). The active avoidance numbers in 10 min and 15 min exposure groups were significantly lower than that in 5 min exposure group (both P<0.05). (3) The results of immunofluorescence staining showed that the numbers of SOX2-positive cells in the four groups were statistically significant ( F=5.33, P<0.05). The SOX2-positive cells in 15 min exposure group (4.33±1.12) was significantly lower than that in control group (7.67±1.52) ( P<0.05). The numbers of NeuN-positive cells in the four groups were significantly different ( F=11.06, P<0.05), and the NeuN-positive cells in the 10 min and 15 min exposure groups((105.67±8.50), (88.33±9.50)) were significantly lower than that in the control group (127.00±6.56) ( P<0.05). The NeuN-positive cells in 15 min exposure group were significantly lower than that in 5 min exposure group (110.67±8.32) ( P<0.05). (4) Western blot results showed that the relative expression of SOX2 and NeuN proteins in the four groups was statistically significant ( F=11.560, 7.035, both P<0.05). The relative expression of SOX2 and NeuN proteins in the 15 min exposure group were significantly lower than those in control group (both P<0.05). The relative expression of SOX2 protein in 15 min exposure group was significantly lower than that in 5 min exposure group ( P<0.05). Conclusion:Acute exposure to warm pressure charge explosion simulated gas can lead to anxiety-like behavior, learning and memory deficits in rats, and significantly reduce the protein expression levels of hippocampal dentate gyrus neural stem cells and mature neuronal marker molecules SOX2 and NeuN.

Effects of poly(A) tails with different lengths on mRNA expression in vitro and stability of transcription template in Escherichia coli / 中华微生物学和免疫学杂志

Objective:To investigate the effects of poly(A) tails with different lengths on mRNA expression in vitro and the passage stability of transcription template with poly (A) tail in Escherichia coli ( E. coli). Methods:Plasmids with poly(A) tails of 38, 60, 103, 125 and 126 (60 nt+ 6 nt spacer+ 60 nt) nt were designed and constructed. Then the plasmids were linearized by single enzyme digestion and used as transcription template for preparing enhanced green fluorescent protein (EGFP)-mRNA. EGFP-mRNA containing poly(A) tails of different lengths were transfected into 293T cells and the expression of EGFP was detected by flow cytometry. As to stability test, the template plasmids with poly (A) tail of 125 and 126 nt were transformed into E. coli TransStbl3 and Top10 competent cells. Seven clones were selected for culture and plasmid extraction, and then the plasmids were digested by restriction enzyme and detected by capillary electrophoresis. For passage stability, three correctly sequenced clones of each group were selected for continuous passage at 37℃, and the plasmids were extracted and digested every two generations for capillary electrophoresis. At the same time, the correctly sequenced clones of 125 nt group were also passaged at 30℃, and the plasmids were also extracted and digested every two generations for capillary electrophoresis. Results:The transcription templates with poly(A) tail of different lengths were successfully constructed. Flow cytometry showed that the fluorescence expression of the template plasmids with poly (A) tail of 103 and 125 nt were significantly higher than that of 38 and 60 nt. The fluorescence expression of the plasmid with poly (A) tail of 126 nt was significantly higher than that of all other groups. The percentages of stable sequences of the template plasmid with poly(A) tail of 125 nt in TransStbl3 and Top10 competent cells were 76% and 91%, respectively. The results of continuous passage showed that poly(A) tail of 125 nt could be stable to the 4th generation at 37℃ in both TransStbl3 and Top10 competent cells, and stable to the 16th and 10th generations at 30℃. The percentages of stable sequences of the template plasmid with poly(A) tail of 126 nt in TransStbl3 and Top10 competent cells were 95% and 48%, respectively. The results of continuous passage showed that poly(A) tail of 126 nt could be stable to the 12th generation at 37℃ in both TransStbl3 and Top10 competent cells.Conclusions:The length and composition of poly(A) tail in mRNA affected the expression of target protein. Adding a spacer with a length of 6 nt to poly(A) tail and low temperature culture were both helpful to improve the stability of the template plasmid, which provided a reference for the design and preparation of in vitro transcription template of mRNA vaccine.

Preparation and immunogenicity evaluation of recombinant influenza hemagglutinin trimer vaccine / 中华微生物学和免疫学杂志

Objective:To prepare a recombinant hemagglutinin trimer (HA-Tri) vaccine against influenza viruses and to study its immunogenicity in a mouse model.Methods:A stable CHO cell line that could express HA-Tri was constructed. Western blot, single radial immunodiffusion, protein particle size detection and N-glycosylation site analysis were performed for qualitative and quantitative analysis of the recombinant protein. According to the different treatment conditions such as dosage and adjuvant, BALB/c mice were divided into 11 groups and subjected to consistent immunization procedures. Serum neutralizing antibody titers were measured on 56 d after the first immunization to evaluate the immunogenicity of HA-Tri.Results:The constructed CHO cells could secret and express HA-Tri proteins. The HA-Tri proteins were biologically active and capable of forming precipitation rings in the single radial immunodiffusion. The particle size of HA-Tri was approximately 18.79 nm and 10 N-glycosylation sites were detected, including high mannose, complex glycoforms and heterozygous glycoforms. After prime-boost immunization, there was no statistically significant difference in the titers of neutralizing antibodies induced in mice by 3.75 μg of HA-Tri in combination with RFH01 adjuvant and 15 μg of monovalent vaccine stock solution ( P=0.431 2, U=36). Serum antibody titers in the HA-Tri+ RFH01 groups were higher than those in the corresponding HA-Tri groups without RFH01 adjuvant, and the highest titer was induced in the 15 μg HA-Tri+ RFH01 group, which was 1 280. Conclusions:The recombinant HA-Tri protein was successfully prepared. HA-Tri in combination with RFH01 adjuvant could induce humoral immune responses against influenza viruses in BALB/c mice, which would provide reference for the development of influenza virus recombinant subunit vaccines.

Immunogenicity of quadrivalent influenza virus subunit vaccine combined with RFH01 adjuvant in mice / 中华微生物学和免疫学杂志

Objective:To evaluate the immunogenicity of a quadrivalent subunit vaccine combined with RFH01 adjuvant in a mouse model.Methods:Identification tests were performed on four monovalent influenza virus subunit vaccine stock solutions according to the methods described in Part 3 of the Chinese Pharmacopoeia 2020 Edition. In the study of the quadrivalent subunit vaccine combined with RFH01 adjuvant, 460 female BALB/c mice (6-8 weeks old) were randomly divided into 46 groups including experimental groups, vaccine control group, negative control group and blank group with 10 mice in each group. In the study of the quadrivalent subunit vaccine in old and young mice, 80 female 10-month-old and 80 female 10-week-old BALB/c mice were randomly divided into 16 groups ( n=10) including monovalent influenza virus vaccine group, quadrivalent subunit vaccine group, quadrivalent subunit vaccine+ RFH01 adjuvant group, chicken embryo quadrivalent split vaccine control group and PBS group. All mice were immunized by intramuscular injection. At 21 d after the primary immunization, a booster immunization was conducted using the same strategy. Blood samples were collected at 21 d and 42 d after the primary immunization for serum separation. Haemagglutination inhibition (HI) test was performed to detect the antibody levels in mouse serum samples. Results:After the booster immunization, the positive conversion rates in all vaccine+ RFH01 adjuvant groups reached 100%, and the geometric mean titers (GMTs) of serum antibodies were significantly higher than those of the vaccine groups without RFH01 adjuvant. There were significant differences in serum antibody titers between the monovalent/quadrivalent subunit vaccine groups with and without RFH01 adjuvant. After the booster immunization, the titers of serum antibodies against H1N1, H3N2, B/Victoria and B/Yamagata in the 10-week-old mice were significantly higher than those in the 10-month-old mice.Conclusions:The monovalent and quadrivalent influenza virus vaccines in combination with RFH01 adjuvant could elicit higher antibody titers in young (6-10 weeks old) and old (10 months old) mice, showing good immunogenicity.

Advances in the diagnosis of bladder cancer based on Raman spectroscopy / 中华泌尿外科杂志

Bladder cancer is one of the common tumors of urinary system. Early detection and treatment can reduce the recurrence rate and mortality. Currently, it is difficult to balance the diagnostic specificity and sensitivity of traditional diagnostic methods. However, Raman spectroscopy, as a molecular diagnostic technology, can reveal the difference between normal urinary tract epithelial tissue and urinary tract epithelial cell carcinoma of the bladder at the molecular level, which has the characteristics of faster and more accurate diagnosis compared with traditional diagnostic techniques. This paper reviews the research progress of Raman spectroscopy in the diagnosis of bladder cancer.

A calibration curve model based on sine function / 中华检验医学杂志

Objective:This paper is to propose a calibration model based on sine function which enables more choices to determine the functional relationship between the absorbance and the concentration of the tested substance.Methods:This paper uses Taylor series expansion and Levenberg-Marquardt to obtain the optimal parameters for the Sine model and then summarizes the characters of the Sine model. On the basis of these characters, this paper compares and evaluates the experimental data processed by the Sine model from four aspects: correctness, precision, linearity and correlation.Results:The generated sine function calibration model achieved deviations within ±3% of the national standard substance, precision ( CV%) less than 2%, and a linear correlation coefficient greater than 0.990 within the measurement range of 32-710 mg/L. The correlation coefficients between the sine model and other well-performing linear calibration models for 104 clinical samples were all greater than 0.990. Conclusions:The performance evaluation of the prealbumin assay kit using the sine function calibration model meets industry standards and shows good correlation with the results of clinical sample measurements. This indicates that the sine function calibration model can serve as a new calibration model for in vitro diagnostic research and clinical applications.

Comparison of qualitative diagnostic value of 3 methods based on 18F-FDG PET-CT for solitary pulmonary nodules / 肿瘤研究与临床

Objective:To compare the value of 3 methods (threshold method, visual method and CT method) based on 18F-FDG PET-CT for qualitative diagnosis of solitary pulmonary nodules (SPN). Methods:The clinical characteristics, pathological results, CT signs and maximum standardized uptake value (SUV max) of 226 SPN patients who underwent 18F-FDG PET-CT and met lung imaging reporting and data system (Lung-RADS1.1) grading criteria grade 2-4 in Shanxi Province Cancer Hospital from January 2015 to January 2019 were retrospectively analyzed, and the diagnostic efficacy of threshold method (according to SUV max), visual method [according to the degree of fluorodeoxyglucose (FDG) uptake in the mediastinum or liver blood pool] and CT method (according to Lung-RADS1.1 grading criteria) for SPN were compared by using receiver operating characteristic (ROC) curve. The highest diagnostic accuracy of CT method and the highest diagnostic accuracy of threshold method and visual method were combined as PET-CT comprehensive diagnosis method, and the diagnostic efficiency of which was compared with the other methods. Results:Among the 226 patients with SPN, 174 cases were malignant and 52 cases were benign in pathology. ROC curve analysis showed that the area under the curve (AUC) of CT method 2 (defined Lung-RADS1.1 grade 4A and below as benign, grade 4B and above as malignant) in CT methods for qualitative diagnosis of SPN was 0.622, the sensitivity was 87.93%, and the accuracy was 76.11%, the diagnostic efficiency was higher than method 2. The AUC of the threshold method 1 (defined solid nodules that SUV max≥2.5 and ground-glass nodules that SUV max≥1.14 as malignant, the others as benign) in threshold methods for qualitative diagnosis of SPN was 0.675, the sensitivity was 85.06%, and the accuracy was 76.99%, the diagnostic efficiency was higher than other methods in the threshold methods and visual methods. The AUC of PET-CT comprehensive diagnosis method (combination of CT method 2 and threshold method 1) for qualitative diagnosis of SPN was 0.652, the sensitivity was 97.70%, and the accuracy was 82.74%, the diagnostic efficiency was higher than other methods. Conclusions:There is no significant difference among threshold method, visual method and CT method based on 18F-FDG PET-CT in qualitative diagnosis of SPN. The diagnostic efficiency of combining CT method with threshold method is significantly improved.

Lipid peroxidation changes induced by dibutyl phthalate in allergic asthma mice / 环境与职业医学

Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.