Association between cognitive impairment and main metals among oldest old aged 80 years and over in China / 中华预防医学杂志

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

Association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China / 中华预防医学杂志

Objective: To investigate the association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B12 and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B12, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B12 level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B12 level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B12 level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q1, Q3) level of plasma vitamin B12 was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B12 level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B12 (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B12 with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.

Association of greenness exposure with waist circumference and central obesity in Chinese adults aged 65 years and over / 中华预防医学杂志

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [β (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (Pinteraction=0.022). Compared with the Q1 group in NDVI, WC of Q2 and Q3 groups in rural decreased, and the β (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (Pinteraction=0.284). Compared with the Q1 group in NDVI, the risk of central obesity in the Q2 and Q3 groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (Pnonlinear=0.006) and central obesity (Pnonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

Prediction for recurrence following antithyroid drug therapy for Graves' hyperthyroidism

ABSTRACT Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusions: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Status quo of current clinical drug regimens for small cell lung cancer and new progress in the potential target drug therapeutic regimens / 中国药房

Small cell lung cancer （SCLC） accounts for about 15% in lung cancer and is highly malignant， heterogeneous and invasive. Etoposide combined with platinum-based chemotherapy is the basis of standard first-line treatment for extensive-stage SCLC， but suffers from the problem of susceptibility to drug resistance and relapse. In recent years， the emergence of new immunological drugs and novel cytotoxic drugs has improved the survival of SCLC patients to a certain extent， especially bringing therapeutic hope to patients with relapsed/refractory SCLC. In this paper， we review the current clinical drug regimens and the new progress of potential target drug therapeutic regimens for the treatment of SCLC. At present， the first-， second- and third-line schemes of SCLC include etoposide+carboplatin， atezolizumab+etoposide+platinum， adebrelimab， topotecan， docetaxel， etc.； the current drug targets for the treatment of SCLC mainly focus on topoisomerase Ⅱ/Ⅰ， DNA， the immune checkpoint molecules programmed death-1/programmed death-ligand 1， tubulin， etc. The potential target drug therapeutic options include alisertib+ paclitaxel， rovalpituzumab， APG-1252， etc.， and mainly focus on DNA damage response pathways and immune pathways， which can achieve the prolongation of patient survival by exerting anti-tumor effects through aurora kinase A and other potential targets.

Protein phosphatase 4 catalytic subunit (PP4C) increases hepatitis B virus X protein levels and promotes its biological functions / 中华微生物学和免疫学杂志

Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.

Relationship between preoperative serum albumin concentrations and postoperative delirium in patients undergoing total knee/hip arthroplasty / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.

Relationship between preoperative estimated glomerular filtration rate and postoperative delirium / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative estimated glomerular filtration rate (eGFR) and postoperative delirium (POD) in the patients.Methods:Six hundred and twenty-five patients, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia, were included. Peripheral blood samples were collected before surgery, and serum creatinine levels were measured by the sarcosine oxidase method, and eGFR was calculated using the MDRD equation. After successful spinal-epidural puncture, cerebrospinal fluid 2 ml was collected for determination of β-amyloid 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group (NPOD group) according to the occurrence of POD. The logistic regression analysis was used to identify the risk factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic (ROC) curve was drawn to evaluate the accuracy of eGFR and biomarkers in predicting POD.Results:A total of 514 patients were finally enrolled in this study, and the incidence of POD was 16.7%. The logistic regression analysis showed that decreased eGFR and increased levels of P-tau and T-tau in CSF were risk factors for POD, while increased CSF Aβ42 level, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD after adjusting for multiple confounding variables ( P<0.05). Analysis of mediating effet: The direct effect of eGFR on POD was -0.0 005 267, the total effect was 0.0 046 446, T-tau had a partly mediating role and the mediating effect accounted for 11.3% of the total effect. The area under the ROC curve of eGFR and CSF biomarker in predicting POD was 0.812( P<0.001). Conclusions:Preoperative decrease in eGFR is a risk factor for POD, and T-tau in CSF serves as a key mediator in the relationship between eGFR and POD.

Relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fracture / 中华麻醉学杂志

Objective:To evaluate the relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fractures.Methods:Forty-five clean-grade healthy male C57/BL6 mice, aged 5-7 months, were divided into 3 groups ( n=15 each) using the random number table method: control group (group C), anesthesia group (group A) and anesthesia surgery group (group AS). Group C received no treatment. Group A was anesthetized with isoflurane inhaled for 15 min. In AS group, intramedullary nail fixation of tibial fracture was performed under anesthesia through inhalation of 2% isoflurane. Morris water maze test and open field test were performed before anesthesia/on 1 day before surgery and after anesthesia/on 1, 3 and 7 days after operation. Five mice were randomly selected after the behavioral experiments were completed at each time point, and hippocampal tissues were taken after the animals were sacrificed for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, chemokine (c-c motif) ligand 12 (CCL2), CCL5, CCL8, iNOS and Arg-1 mRNA (by quantitative real-time polymerase chain reaction), expression of iNOS and Arg-1 proteins (by Western blot), and percentage of CD11b, CD45, CD86 and CD206 cells in hippcampal area (by immunofluorescence staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the platform was reduced after operation, the expression of TNF-ɑ, IL-6, CCL5 and CCL8 mRNA and iNOS protein and mRNA was up-regulated, the expression of Arg-1 protein and mRNA was down-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells in the hippocampus were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05), and no significant change was found in the parameters mentioned above in group A ( P>0.05). Compared with group A, the escape latency was significantly prolonged after surgery, the frequency of crossing the platform was reduced after surgery, the expression of iNOS mRNA was up-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05). Conclusions:The occurrence of PND may be related to increased polarization to M1 macrophages in the hippocampus and decreased polarization to M2 macrophages in mice with tibial fracture, which further leads to central inflammatory responses.

Relationship between preoperative SARS-CoV-2 vaccination and postoperative delirium / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative SARS-CoV-2 vaccination and postoperative delirium(POD) in the patients.Methods:A total of 938 participants of either sex, aged 50-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists Physical Status classificationⅠorⅡ, with preoperative Mini-Mental State Examination score ≥24, without communication barriers, undergoing elective knee or hip joint replacement under combined spinal-epidural anesthesia from June 2020 to June 2022 in Qingdao Municipal Hospital, were enrolled. The vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was recorded. The cerebrospinal fluid 2 ml was extracted after the puncture needle was successfully inserted into the subarachnoid space for determination of the concentrations of Aβ42, total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay (by enzyme-linked immunosorbent assay). The Aβ42/t-tau and Aβ42/p-tau ratios were calculated. POD was assessed using the Confusion Assessment Method twice a day within 7 days after surgery or before discharge.The patients were divided into POD group and non-POD group according to whether they developed POD. The risk factors of which P values were less than 0.20 in the univariate logistic regression would enter the multivariate logistic regression analysis to investigate the relationship between SARS-CoV-2 vaccine and level of cerebral spinal fluid (CSF) biomarkers and POD. Results:Eight hundred and seventy-four patients were finally enrolled in the analysis, of which 169 patients developed POD, with an incidence of 19.3%.The results of logistic regression showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation, preoperative concentrations of Aβ42 in CSF, and increase in Aβ42/t-tau and Aβ42/p-tau ratios were protective factors for POD, and preoperative elevated concentrations of t-tau and p-tau in CSF were risk factors for POD ( P<0.05). After gender, age, preoperative Mini-Mental State Examination score, years of education, history of drinking, hypertension, diabetes mellitus and coronary heart disease were added to eliminate the influence of confounding factors, the results still showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was a protective factor for POD. Conclusions:Vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation is a protective factor for POD in patients.

Expression and role of the TRPC family in TGF-β1-induced calcium influx in podocytes / 生理学报

The TRPC family consists of multiple important cationic channels in mammals that participate in a variety of physiological and pathological processes. Our previous studies have shown that transforming growth factor-β1 (TGF-β1) increases the expression of TRPC6 in podocytes, but the roles of other members of the TRPC family in podocytes require further investigation. In this study, we investigated the effect of TGF-β1 on the expression of the TRPC family and the role of the TRPC family in the changes of the intracellular Ca2+ concentration ([Ca2+]i) in podocytes induced by TGF-β1. The model of podocyte injury was established by treatment with TGF-β1 in immortalized glomerular podocytes (MPC5) in vitro. qRT-PCR and Western blot were used to detect the effect of TGF-β1 on the mRNA and protein expression of each TRPC family member. After the expression of each TRPC family member was knocked down by a siRNA-based approach and blocked by SKF96365, respectively, free cytosolic Ca2+ was measured using the fluorescent Ca2+ indicator Fluo-3/AM, and the dynamic change of [Ca2+]i in podocytes was detected by a dynamic high-speed calcium imaging system. The results showed that TGF-β1 increased the protein expression of TRPC1/3/6 in podocytes, but had no effects on the protein expression of TRPC4. The protein expression levels of TRPC5/7 were only affected by 4 ng/mL and 8 ng/mL TGF-β1, respectively. TGF-β1 increased TRPC1/3/6 mRNA levels in podocytes, however had no effects on TRPC4/5/7 mRNA. TGF-β1 significantly increased [Ca2+]i in podocytes. Knockdown of TRPC1/4/5/7 in podocytes had no significant effect on the [Ca2+]i induced by TGF-β1, but TRPC3/6 knockdown significantly decreased the [Ca2+]i. There was no significant difference in the [Ca2+]i between the TRPC6 siRNA-treated group and SKF96365-treated group, but the [Ca2+]i of the TRPC3 siRNA-treated group was significantly higher than that of SKF96365-treated group. These results demonstrate that TGF-β1 increases the expression of the TRPC1/3/6 in podocytes. TGF-β1 increases [Ca2+]i in podocytes, which is dependent on the TRPC3/6 expression. Our results also suggest that the effect of TRPC6 on [Ca2+]i in podocytes may be greater than that of TRPC3.

Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years / 中华流行病学杂志

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Identification and analysis of 2 Corynebacterium diphtheria strains in Guangdong Province / 中华预防医学杂志

Objective: To identify and analyze two strains of C. diphtheriae in Guangdong Province by combining whole genome sequencing with traditional detection methods. Methods: The C. diphtheriae was isolated from Guangzhou in 2010 and Zhuhai in 2020 respectively. Isolates were identified by API Coryne strips and MALDI-TOF-MS. Genomic DNA was sequenced by using Illumina. The assembly was performed for each strain using CLC software. J Species WS online tool was used for average nucleoside homology identification, then narKGHIJ and tox gene were detected by NCBI online analysis tool BLSATN. MEGA-X was used to build a wgSNP phylogenetic tree. Results: GD-Guangzhou-2010 was Belfanti and GD-Zuhai-2020 was Gravis. ANIb between GD-Guangzhou-2010 and C. belfantii was 99.61%. ANI between GD-Zhuhai-2020 and C. diphtheriae was 97.64%. BLASTN results showed that the nitrate reduction gene narKGHIJ and tox gene of GD-Guangzhou-2010 was negative, while GD-Zhuhai-2020 nitrate reduction gene narKGHIJ was positive. There were two obvious clades in wgSNP phylogenetic tree. The first clades included all Mitis and Gravis types strains as well as GD-Zhuhai-2020. The second clades contained all isolates of C.belfantii, C.diphtheriae subsp. lausannense and GD-guangzhou-2010. Conclusion: Two non-toxic C. diphtheriae strains are successfully isolated and identified. The phylogenetic tree suggests that GD-Guangzhou-2010 and GD-Zhuhai-2020 are located in two different evolutionary branches.

A follow up study depressive and anxiety symptoms of children in Wuhan City, Hubei Province / 中国学校卫生

Objective@#To investigate the progression of depressive and anxiety symptoms of children, especially whose parents were frontline workers in the combat of the coronavirus disease 2019 (COVID-19), and to provide evidence for children s mental health promotion.@*Methods@#In June and December 2020, two surveys were conducted among the children in a primary school in Qiaokou District, Wuhan. The questionnaire included demographic information, student learning conditions, and depressive/anxiety symptoms.@*Results@#A total of 963 children completed both surveys. The detection rate of depressive and anxiety symptoms at follow up was significantly higher than that at the baseline survey (depressive symptoms: OR=1.45, 95%CI =1.16-1.83; anxiety symptoms: OR=1.79, 95%CI =1.41-2.28, P <0.01). There was no statistically significant change in depressive/anxiety symptoms among children whose parents were frontline workers compared with those whose parents were not( P >0.05). Girls, lower learning efficiency, and less interaction with teachers in class were risk factors for depressive or anxiety symptoms of children( P < 0.05 ).@*Conclusion@#Mental health status of children requires continuous attention. Moreover, timely psychological protection should be given to prevent the occurrence of psychological problems and the further deterioration of psychological problems.

Accuracy and influencing factors of type B2 vessels for predicting the invasion depth of superficial esophageal squamous cell carcinoma under narrow band imaging-magnifying endoscopy / 中华消化内镜杂志

Objective:To evaluate type B2 vessels for predicting the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) under narrow band imaging-magnifying endoscopy (NBI-ME), and to analyse the influencing factors of over-prediction and under-prediction.Methods:A total of 86 SESCC patients with 86 lesions confirmed by postoperative pathology, who underwent NBI-ME to evaluate the invasion depth of esophageal tumor and were observed for type B2 vessels in Department of Digestive Endoscopy of Fujian Provincial Hospital from January 2015 to April 2020, were included in the case-control study. According to the postoperative pathological results, the patients were divided into the correct prediction group ( n=25) and the wrong prediction group ( n=61), and the accuracy of prediction was calculated. The wrong prediction group was further divided into the over-prediction group ( n=49) and the under-prediction group ( n=12) to find the influencing factors of over-prediction and under-prediction, respectively. Further, multivariate Logistic analysis was performed to explore the independent influential factors for the prediction. Results:The accuracy of type B2 vessels under NBI-ME for predicting the invasion depth of SESCC was only 29.07% (25/86), and the over-prediction rate and under-prediction rates were 56.98% (49/86) and 13.95% (12/86), respectively. Univariate analysis showed that the classification of type B2 area ( χ2=36.25, P<0.001), the distinct endoscopic features (nodules, thickening and obvious depression, χ2=22.90, P<0.001), and inflammation around type B2 vessels ( χ2=9.54, P=0.004) were related to the over-prediction of the invasion depth of SESCC, and the distinct endoscopic features were related to the under-prediction of the invasion depth ( P=0.016). Multivariate Logistic regression analysis showed that B2-narrow (type B2 area ≤5 mm) ( P<0.001, OR=241.988,95% CI:15.229-3 845.252) and inflammation around type B2 vessels ( P=0.033, OR=12.801, 95% CI: 1.226-133.713) were independent risk factors for over-predicting the invasion depth of SESCC, while the distinct endoscopic features were independent protective factors for over-prediction ( P<0.001, OR=0.012, 95% CI: 0.001-0.150). The distinct endoscopic feature was an independent risk factor for under-predicting invasion depth of SESCC with type B2 vessels ( P=0.027, OR=7.899, 95% CI: 1.259-49.565). Conclusion:The accuracy of predicting the invasion depth of SESCC is low only based on type B2 vessels in NBI-ME, and over-prediction is prone to occur. B2-narrow, inflammation around type B2 vessels and without nodules, thickening and obvious depression are closely related to the over-prediction of invasion depth of SESCC by type B2 in NBI-ME, and nodules, thickening and obvious depression are closely associated with the under-prediction. However, whether the combined assessment of type B2 vessels under NBI-ME and endoscopic manifestation can improve the accuracy of prediction needs to be confirmed by further studies.

Relationship between preoperative mild cognitive impairment and postoperative delirium in patients undergoing total knee/hip arthroplasty / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative mild cognitive impairment (MCI) and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:A total of 625 patients, aged 50-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing total knee and hip arthroplasty under combined spinal-epidural anesthesia from September 2021 to February 2022, were included.One day before surgery, the cognitive function was assessed using the Mini-Mental State Examination and the Montreal Cognitive Assessment scale.The patients were divided into non-MCI group (NMCI group) and MCI group according to the diagnostic criteria of MCI.The concentrations of amyloid beta 40 (Aβ40), amyloid beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) in cerebrospinal fluid (CSF) were detected by enzyme-linked immunosorbent assay.The development of POD was assessed on 1-7 days after operation.The relationship between MCI and POD and relationship of concentrations of β40, Aβ42, T-tau and P-tau in CSFA, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio with POD and MCI were analyzed using binary logistic regression.Results:Compared with NMCI group, the incidence of POD was significantly increased, the concentrations of Aβ42 and Aβ40 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio were decreased, and T-tau and P-tau concentrations in CSF were increased in MCI group ( P<0.05).The results of logistic regression analysis showed that before and after adjusting for confounding factors, increased MCI and concentrations of P-tau and T-tau in CSF were the risk factors for POD, and increased concentrations of Aβ42 and Aβ40 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD ( P<0.05); elevated concentrations of P-tau and T-tau in CSF were risk factors for MCI before and after adjusting for confounding factors, and increased concentrations of Aβ4 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio, and Aβ42/T-tau ratio were protective factors for MCI after adjusting for confounding factors ( P<0.05). Conclusions:Preoperative MCI are risk factors for POD in the patients undergoing total knee/hip arthroplasty.

Ubiquitin-specific peptidase 22 (USP22) regulates the level and function of hepatitis B virus X protein / 中华微生物学和免疫学杂志

Objective:To investigate the effects of the interaction between ubiquitin-specific peptidase 22 (USP22) and hepatitis B virus X protein (HBx) on the protein level and the biological function of HBx.Methods:The interactions between HBx and USP22 were analyzed by GST pull-down, co-immunoprecipitation assay and confocal laser scanning assay. USP22 recombinant plasmids or specific siRNA were transiently co-transfected with HBx plasmids. Western blot were used to detect the protein level of HBx. The half-life and degradation pathway of HBx in the transfected cells treated with cycloheximide (CHX) or proteasome inhibitor MG132 were detected. In vivo ubiquitination assay was used to detect the ubiquitination of HBx with USP22 overexpression. Moreover, dual-luciferase reporter assay and colony formation assay were used to analyze the effects of USP22 on the biological function of HBx. Results:USP22 could interact with HBx in vivo and in vitro. USP22 significantly increased the stability of HBx and inhibited the proteasome-mediated degradation of HBx protein by reducing the ubiquitination of HBx, thereby enhancing the biological function of HBx. Conclusions:USP22 inhibited HBx protein degradation through ubiquitin-dependent proteasome pathway, thus enhancing the stability and biological function of HBx.

Relationship between preoperative levels of serum uric acid and postoperative delirium / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative levels of serum uric acid (SUA) and postoperative delirium (POD).Methods:Seven hundred and fifty patients of either sex, aged 50-90 yr, with American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective knee replacement under spinal-epidural anesthesia, were selected.Venous blood samples were collected before anesthesia and levels of SUA were determined by enzyme-coupled assay.L 3-4 was selected as the puncture space, and the cerebrospinal fluid (CSF) specimens were obtained from the subarachnoid space for determination of concentrations of β-amyloid 42, total tau (t-tau) and phosphorylated tau (p-tau) by enzyme-linked immunosorbent assay.The patients were divided into hyperuric acid group (group HS) and non-hyperuric acid group (group NS) according to clinical diagnostic criteria of hyperuricemia, and into POD group (group POD) and non-POD group (group NPOD) according to the occurrence of POD.Logistic regression was used to identify the risk factors for POD.The mediating effect of CSF biomarkers was analyzed.The efficacy of SUA and CSF biomarker concentrations in predicting POD was evaluated using the receiver operating characteristic curve. Results:A total of 699 patients were finally enrolled in the study, and the incidence of POD was 21.5%.The results of logistic regression analysis after adjusting for multiple confounding factors, such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history, showed that increased concentrations of SUA and p-tau and t-tau in CSF were risk factors for POD ( P<0.05). The results of mediation analysis showed that the concentrations of p-tau and t-tau in CSF were the mediating factors of the relationship between SUA and POD, with mediating effects of 0.000 301 (95% confidence interval 0-0.000 152) and 0.000 236 (95% confidence interval 0-0.000 092), respectively, and the intermediary proportion were 14.9% and 11.7%, respectively.The area under the receiver operating characteristic curve of SUA in predicting POD was 0.774 ( P<0.05). Conclusions:Increased preoperative SUA is a risk factor for POD, and the accuracy of predicting POD is high, and concentrations of p-tau and t-tau in CSF are mediators of SUA affecting POD.

Research progress on mental health of school age children under major public health emergencies / 中国学校卫生

Abstract@#Children were vulnerable groups in major public health emergencies. In 2020, the coronavirus disease 2019 (COVID-19) pandemic was widespread in the world. The mental health of school age children has become a worldwide concern. Herein, we conducted this review to evaluate the impact of COVID-19 on the mental health of general children and special children with a high risk of psychological problems, focusing on the prevalence of anxiety, depression, and post traumatic stress disorder among school age children in different countries and regions during the COVID-19 epidemic. Considering the susceptibility between individuals and the accessibility of social resources, we further explored the child, family, and social related factors affecting the mental health of school age children. Finally, some suggestions on the construction of children s mental health service system in major public health emergencies were put forward at the national, school family community, and individual levels. Building a safe and reliable child mental health protection network required the joint efforts of all sectors of society.

Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico / Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.