Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib / 中华肿瘤杂志

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease / 中华心血管病杂志

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center / 中华心血管病杂志

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft / 中华心血管病杂志

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

A pilot study of late-onset neuromyelitis optica spectrum disorder disease based on brain three-dimensional structural MRI / 中华放射学杂志

Objective:To explore the different patterns of brain structural abnormalities in patients with delayed neuromyelitis optica pedigree disease (LO-NMOSD) and its relationship with clinical neuropsychological scale score based on the quantitative analysis of three-dimensional (3D) brain structure MRI.Methods:Patients with neuromyelitis optica pedigree disease in remission (NMOSD group) who received treatment at Jilin University First Hospital from January 2016 to December 2018 were prospectively included and divided into LO-NMOSD subgroup and early-onset NMOSD (EO-NMOSD) subgroup according to whether the age of first onset was>50 years. Another age-and sex-matched healthy volunteers with NMOSD patients were recruited as the control group. 3D brain T 1WI and T 2 fluid-attenuated inversion recovery sequence imaging were acquired, and clinical data, neuropsychological scores of all subjects were analyzed. Total gray matter volume (GMV), cerebral gray matter fraction (GMF), cerebral white matter fraction (WMF), and cerebral white matter high signal fraction (WMHF) were obtained by quantitative analysis of MRI data using voxel-based morphology and lesion segmentation tool techniques. Analysis of covariance was used to compare the differences in brain structure between LO-NMOSD subgroup and EO-NMOSD subgroup, NMOSD group and control group. Partial correlation analysis was used to analyze the correlation between GMF, WMHF and patient clinical data, neuropsychological scale scores, and the correlation between WMHF and GMF, WMF. Results:There were 47 cases in the NMOSD group, including 7 males and 40 females aged 18-66 years. Among them, there were 20 cases in the LO-NMOSD subgroup and 27 cases in the EO-NMODS subgroup. The control group consisted of 50 individuals (13 males and 37 females, aged 18 to 77 years). Compared with the control group, the GMV of the right caudate nucleus in the LO-NMOSD group was reduced ( t=3.33, P<0.05), and the GMV of multiple brain regions in the bilateral frontal and temporal lobes in the EO-NMOSD group was reduced considerably (FDR corrected, P<0.05), which was consistent with the NMOSD group. After adjusting for age, there was no statistically significant difference in WMHF between the LO-NMOSD and EO-NMOSD groups ( F=0.22, P=0.644). The LO-NMOSD subgroup showed a negative correlation between global GMF and the extended disability status scale (EDSS) score ( r=-0.53, P=0.025). WMHF in the NMOSD group was positively correlated with annual recurrence rate and EDSS ( r=0.35 and 0.35, respectively, and P=0.017 and 0.018, respectively), while other indicators were not correlated ( P>0.05). The EO-NMOSD subgroup WMHF showed a negative correlation with GMF and WMF ( r=-0.76, -0.70, respectively, P<0.001). The NMOSD group showed a negative correlation between WMHF and GMF, WMF ( r=-0.38, -0.55, respectively, P<0.05). There was no correlation between WMHF and GMF, WMF in the LO-NMOSD subgroup ( P>0.05). Conclusions:The extent and location of gray matter atrophy in patients with LO-NMOSD are different from those of EO-NMOSD. The correlation between WMHF and brain structural changes and clinical data is different between the two groups of patients. These suggest that LO-NMOSD patients may have different patterns of brain structural damage.

Tetrahydroxy stilbene glycoside ameliorates neuroin-flammation for Alzheimer's disease via cGAS-STING / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Cornel iridoid glycoside alleviates microglia-mediated inflammatory response via NLRP3/calpain pathway / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.

A multivariate generalizability analysis of the short version of depression-anxiety-stress scale / 中华行为医学与脑科学杂志

Objective:To test the reliability of the short version of the depression-anxiety-stress scale (DASS-21) in adolescents through generalizability theory.Methods:Total of 458 adolescents from three middle schools in Guizhou and Sichuan province were surveyed with the DASS-21 from November to December 2021.Based on multivariate generalization theory(MGT), the generalization coefficients, reliability indexes and variance contribution ratios were calculated.mGENOVA 2.1 was used for data analysis.Results:The generalizability coefficient and reliability index for the total scale of DASS-21 were 0.927 and 0.922, respectively.The generalizability coefficients of depression, anxiety and stress subscales were 0.808-0.840, and the dependability indexes were 0.789-0.832.The contribution ratios of depression, anxiety and stress subscales to the general score were 33.20%, 33.94% and 32.86%, respectively.The stress subscale (34.95%) contributed the most to the relative error variance, and the anxiety subscale (36.98%) contributed the most to the absolute error variance.Conclusion:The DASS-21 has excellent test reliability in adolescents, and it can be used both as the norm-referenced test and the criterion-referenced test in the actual assessment of negative emotions in adolescents.

Research progress of sepsis-associated acute kidney injury based on Gut-Kidney axis / 中华危重病急救医学

Sepsis-associated acute kidney injury (SA-AKI), as a common renal dysfunction in sepsis, has become one of the major diseases threatening human health with increasing morbidity and mortality. Based on the theory of "gut-kidney axis", the intestine and kidney have a two-way synergistic relationship in sepsis. Intestinal flora imbalance, endogenous metabolite imbalance, and impaired endothelial barrier integrity are involved in renal injury, and the increase of renal inflammatory mediators interferes with the composition of intestinal microorganisms. Therefore, understanding the intestinal-renal crosstalk mechanism of SA-AKI will help to provide a potential basis for new treatment strategies for SA-AKI.

Efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure and its effect on N-terminal pro-brain natriuretic peptide level / 中国基层医药

Objective:To investigate the clinical efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure and its effect on N-terminal pro-brain natriuretic peptide (NT-pro BNP) level.Methods:The clinical data of 89 patients with chronic heart failure who received treatment in Jinan 2 nd People's Hospital from January 2020 to April 2022 were retrospectively analyzed. These patients were divided into Group A ( n = 48) and Group B ( n = 41) according to different treatment methods. Group A was treated with sacubitril and valsartan combined with bisoprolol. Group B was treated with sacubitril and valsartan combined with metoprolol. All patients were treated for 3 months. Clinical efficacy as well as heart function and NT-pro BNP level pre- and post-treatment were compared between the two groups. The incidence of adverse reactions was calculated in each group. Results:Total response rate in group A was significantly higher than that in group B [95.83% (46/48) vs. 82.93% (34/41), χ2 = 4.05, P < 0.05]. After treatment, the left ventricular ejection fraction in both groups increased significantly and the left ventricular ejection fraction in group A was significantly higher than that in group B ( t = 2.19, P < 0.05). After treatment, NT-pro BNP level in group A was (416.51 ± 30.56) ng/L, which was significantly lower than (450.20 ± 35.79) ng/L in group B ( t = 4.79, P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:The efficacy of sacubitril and valsartan combined with bisoprolol in the treatment of chronic heart failure is superior to that of sacubitril and valsartan combined with metoprolol. The former can greatly decrease NT-pro BNP level. Corresponding drugs can be selected for the treatment of chronic heart failure according to the actual needs of patients.

Comparison of iodine nutritional status and disease monitoring results among children in water source high iodine areas of Henan Province in 2017 and 2019 / 中华地方病学杂志

Objective:To compare the coverage rate of non-iodized salts, children's iodine nutrition and the change trend of goiter rate between the original water source high iodine areas in Henan Province in 2017 and the newly designated water source high iodine areas in 2019.Methods:Using a cross-sectional survey method, household edible salt monitoring was conducted in all 20 counties (cities, districts) with high iodine content in Henan Province in 2017. Ten counties (cities, districts) were selected to monitor water iodine, urinary iodine and thyroid volume of children aged 8 to 10 years. A total of 4 430 salt samples and 1 012 urine samples were collected, and thyroid volume of 1 012 children were measured. In 2019, monitoring of household edible salt, water iodine, urinary iodine, and thyroid volume was carried out in all 55 newly designated counties (cities, districts) with high iodine village. A total of 9 835 salt samples and 9 830 urine samples were collected, and the thyroid volume of 8 896 children was measured. The monitoring results of two years were compared, and the relationship between children's urinary iodine and goiter rate was analyzed by univariate logistic regression.Results:In 2019, the water iodine content in newly designated high iodine areas decreased compared to the original high iodine areas in 2017 (119.8 to 191.0 μg/L), and the difference was statistically significant ( Z = - 2.48, P = 0.013). The rate of non-iodized salts in 2019 was only 35.5% (3 494/9 835), significantly lower than that in 2017 (96.2%, 4 263/4 430, χ 2 = 4 536.74, P < 0.001). The median urinary iodine of children in 2017 and 2019 were 338.2 and 317.8 μg/L, respectively, the difference between the two years was statistically significant ( Z = - 2.46, P = 0.014). In 2017 and 2019, the goiter rate of children aged 8 to 10 years was 1.5% (15/1 012) and 2.1% (187/8 896), respectively, and there was no significant difference between the two years (χ 2 = 1.76, P = 0.185). The results of univariate logistic regression analysis showed that, compared with the control group with urinary iodine < 100 μg/L, the risk of goiter rate (but the enlargement rate did not exceed 5%) increased with the increase of urinary iodine level (100 - 199, 200 - 299 and ≥300 μg/L groups), and the differences were statistically significant [odds ratio ( OR) = 8.64, 7.68, 10.69, P < 0.05]. Conclusion:After the implementation of the new demarcation standard for areas with excessive iodine in water sources, the supply of non-iodized salts in Henan Province is relatively lagging behind, and the iodine nutrition level of children is still high, but the goiter rate is relatively stable.

Analysis of iodine nutritional level of residents in iodine adequate areas of Henan Province in 2020 / 中华地方病学杂志

Objective:To investigate the iodine nutritional level of residents in iodine adequate areas in Henan Province, and provide basis for making policy of targeted guidance and rational iodine supplementation.Methods:In the 156 counties of Henan Province in 2020, one township was selected from each location (east, west, south, north and middle) in each county; one school was selected from each township; 40 children aged 8-10 years in the school and 20 pregnant women in the township were selected to collect their urine and salt samples to test urine and salt iodine levels. One third of the counties were selected to examine the thyroid gland of children. Individuals lived in villages with water iodine between 40 and 100 μg/L were included in the study.Results:In iodine adequate areas, a total of 2 097 salt samples were collected from children and tested, the consumption rate of qualified iodized salt was 93.6% (1 962/2 097). A total of 2 096 urine samples were collected from children and tested, and the median urinary iodine was 288.0 μg/L. The goiter rate of children was 0.7% (5/723). A total of 1 068 salt samples from pregnant women were tested, and the consumption rate of qualified iodized salt was 93.0% (993/1 068). A total of 1 068 urine samples from pregnant women were tested, with a median urinary iodine 232.7 μg/L. Stratified by water iodine (40-59, 60-79, 80-100 μg/L), the median urinary iodine of children was 273.8, 288.6, and 305.9 μg/L, respectively, statistically significantly different between groups ( H = 15.79, P < 0.001); the goiter rate of children was ≤2%, and the difference between groups was statistically significant (χ 2 = 7.31, P = 0.026); but the median urinary iodine of pregnant women was not significantly different ( H = 1.82, P = 0.402). Under different water iodine conditions, there was no significant difference in urinary iodine levels in children and pregnant women between the high salt iodine concentration group (≥21 mg/kg) and the low salt iodine concentration group (< 21 mg/kg, P > 0.05). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is relatively high, and the iodine nutrition of pregnant women is appropriate. The goiter rate of children is at a relatively low level. Continuous surveillance should be conducted to comprehensively evaluate the iodine nutrition level. Various measures will be taken by regions and populations.

Genetic diversity of mitochondrial cytochrome b gene of Taenia asiatica in Dali Bai Autonomous Prefecture, Yunnan Province / 中华地方病学杂志

Objective:In order to investigate the genetic diversity of mitochondrial cytochrome b (Cytb) gene of Taenia asiatica ( T. asiatica) in Dali Bai Autonomous Prefecture (Dali Prefecture), Yunnan Province. Methods:From May 2019 to August 2021, a total of 131 samples of Taenia were collected from patients admitted to the Dali Prefecture Institute of Schistosomiasis Control, involving five locations (i.e., five groups), including Dali City (58 samples), Weishan Yi and Hui Autonomous County (Weishan County, 14 samples), Midu County (18 samples), Yangbi Yi Autonomous County (Yangbi County, 24 samples) and Eryuan County (17 samples). Primers were designed based on mitochondrial Cytb gene sequence, and part of the Cytb gene sequence was amplified by PCR, then sequenced and homology comparisons were performed. MEGA 7.0 and DNASP 5.10.01 were used to analyze the measured sequence, and data such as base composition, genetic distance, genetic diversity parameters, genetic differentiation index and gene flow were obtained. Results:The amplified fragments of Cytb gene in 131 samples of Taenia were 235 bp. After homology comparisons, they were all T. asiatica. The average contents of A, T, G and C bases were 23.8%, 42.3%, 24.0% and 9.9%, respectively. Of the 131 samples of T. asiatica, 12 haplotypes were defined. The haplotype diversity and nucleic acid diversity were 0.295 9 and 0.006 0, respectively. The ranges of genetic differentiation index and gene flow among the five groups were-0.053 00 to 0.050 40 and 4.710 31 to 162.087 66, respectively. The genetic distance between the five groups ranged from 0.003 5 to 0.009 0, of which the genetic distance between Midu County and Weishan County was the largest, and the genetic distance between Dali City and Yangbi County was the smallest. Conclusions:The mitochondrial Cytb gene of T. asiatica in Dali Prefecture has rich genetic diversity. There is frequent gene exchange among the five groups, and no significant genetic differentiation has been formed.

Construction of cell factories for production of valencene in Saccharomyces cerevisiae / 药学学报

Valencene, a kind of sesquiterpenoid with a citrus flavor, is mainly found in Valencia orange and is commonly used in cosmetics and food additives, as well as industrial synthetic nootkatone. In this study, synthetic biology was used to create a Saccharomyces cerevisiae cell factory to produce valencene. Fistly, valencene synthase gene (CnVS) from Callitropsis nootkatensis was inserted into the chromosome of the chassis strain YTT-T5. The resulting strain VAL-01 could produce 1.1 mg·L-1 valencene. Protein fusion technique was used, different valencene synthases were compared and the copy number of key genes was adjusted, yielding valencene to 436.4 mg·L-1. Then, knocking-out the transcription factor ROX1 resulted in valencene improvement by 17.4%. Moreover, the induction system of galactose was regulated, transcription factor PDR3 and INO2 were overexpressed. The engineered strain VAL-10 could produce 2 798.6 mg·L-1 valencene by high cell density fermentation method (nearly 2 500 times higher than VAL-01). This study provides a basis for green production of valencene.

Analysis of results of national personal dose monitoring ability assessment in 2016—2021 / 中国辐射卫生

Objective To analyze the results of national personal dose monitoring intercomparison and assessment of Hubei Provincial Hospital for Occupational Disease in 2016—2021, to investigate the influencing factors for monitoring results, and to improve the ability of personal dose monitoring. Methods The assessment was completed according to the requirements of The National Comparison Scheme for Individual Dose Monitoring Ability and Testing Criteria of Personnel Dosimetry Performance for External Exposure (GBZ 207—2016). Results The assessment results were qualified in 2016—2017 and 2020 and excellent in 2018—2019 and 2021. Conclusion The ability of personal dose monitoring in our laboratory has been continuously improved. The monitoring results are accurate and the data processing is standardized, which meet the requirements of relevant standards for personal external exposure dose monitoring.

LOXL1-AS1 Aggravates Myocardial Ischemia/Reperfusion Injury Through the miR-761/PTEN Axis

Background and Objectives@#Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. @*Methods@#Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines.Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. @*Results@#After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to upregulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. @*Conclusions@#LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.

Reliability and validity assessment of Daily Stressors Evaluation Scale for Urban Secondary School Students / 中国学校卫生

Objective@#To formulate an evaluation scale on daily stressors with good reliability and validity for urban secondary school students, and to provide a tool for psychological stress assessment.@*Methods@#Based on steps of instrument development, a pool of items regarding the daily stressors of junior/senior high school students was constructed by combining existing scales of adolescent life events or stressors, and a preliminary survey was conducted for items analysis and dimension evaluation among 393 middle and high school students in 2 districts of Shanghai. Then confirmatory factor analysis of the scale was conducted among 2 949 students collected by stratified cluster sampling from 11 districts in Shanghai.@*Results@#The final 28 item daily stressors evaluation scale for urban secondary school students, with an overall Cronbach s alpha coefficient of 0.94, consists of 8, 7, 7, and 6 items for the four dimensions of academic stress, physical and psychological stress, interpersonal stress and family stress, respectively. The Guttman s split half reliability was 0.88, and the test retest reliability was 0.68. Total scores of the 28 items reflect general psychological stress level of participants, with higher scores representing higher stress intensity. The confirmatory factor analysis showed that the root mean squared error of approximation ( RMSEA ) and the standardized root mean square residual ( SRMR ) were both less than 0.08, while all fit indexes were above 0.8.@*Conclusion@#The Daily Stressors Evaluation Scale for Urban Secondary School Students, with good reliability, validity and model goodness of fit, can be applicable for urban secondary school students.