OBJECTIVE: To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification. METHODS: Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg·d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β -protein 1-42 (A β_1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). RESULTS: A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and A β_1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01). CONCLUSIONS DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Male ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Brain/drug effects* ; Metabolomics ; Mice, Inbred C57BL ; Neuronal Plasticity/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cyclic AMP/metabolism* ; Reactive Oxygen Species/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Mice ; Amyloid beta-Peptides/metabolism* ; Signal Transduction/drug effects* ; Alzheimer Disease/drug therapy* ; Superoxide Dismutase/metabolism*

Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.

The cycling of iodine in the atmosphere and ocean plays a critical role in climate and environmental change.Ice cores and tree rings,as ideal climate archives,can provide essential data for paleoclimate reconstruction through accurate iodine analysis.However,iodine concentrations in ice core samples are as low as 0.01 μg/L,and as low as 0.01 μg/g in tree rings.Most currently reported analytical methods face challenges in accurately quantifying such low levels.In this study,a highly sensitive analytical method for trace iodine in environmental samples was developed based on inductively coupled plasma mass spectrometry(ICP-MS),incorporating a collision/reaction cell under the optimized collision/reaction gas conditions.Collision/reaction cell mode was employed to evaluate potential interferences in determination of trace iodine by ICP-MS.The results indicated that peak tailing from adjacent mass-to-charge ratios and polyatomic ion interferences could be considered negligible.However,residual iodine in ultrapure water constituted the major source of background,highlighting the need for strict control of sample pretreatment and procedural blanks in trace-level iodine analysis.By utilizing collision focusing effect of helium,the measurement sensitivity of iodine was enhanced to 3.5×105 cps(counts per second)/(μg/L),and the detection limit was reduced to 0.002 μg/L.The developed method exhibited a deviation of less than 2.3%in measurement of low-concentration standard solutions,indicating good accuracy.For actual samples and blanks,the precision of repeated measurements within 2 h was better than 1.6%,demonstrating excellent repeatability.No significant memory effect was observed during the measurements.The established method was successfully applied to determination of trace iodine in ice cores,tree rings,and other environmental samples,providing a robust technical foundation for investigating the role of iodine in climate and environmental change.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To compare the differences in exploratory behaviors between infants with high-risk autism spectrum disorder (HR-ASD) and normal development (TD) infants, and to explore the relationship between exploratory behaviors and the severity of ASD symptoms.Methods:A total of 31 infants aged 6-23 months with HR-ASD in the Pediatric Clinic, the Affiliated Brain Hospital of Nanjing Medical University from January 2019 to August 2020 were retrospectively recruited in the HR-ASD group, and 37 TD infants aged from 6 to 23 months in Nanjing were selected as the TD group.The development level of the 2 groups was evaluated by Gesell development scale, and the depth and breadth of exploratory behaviors were measured in free play.Autism Diagnostic Observation Schedule (ADOS) was used to evaluate the severity of ASD symptoms in HR-ASD group.Differences in exploratory behaviors between the 2 groups were analyzed by the independent sample t-test and Chi- square test. Pearson′ s correlation analysis was performed to explore the correlation between exploratory behaviors and symptom severity in HR-ASD group.Binary Logistic regression analysis was used to explore the discrimination efficiency of sexual behavior in the 2 groups. Results:Compared with TD group, the depth and breadth of exploratory behaviors in HR-ASD group were significantly lower (55.06±25.73 vs.132.78±44.69, 4.42±2.20 vs.8.78±3.28)( t=-8.95, -6.53, all P<0.01), and atypical exploratory behavior and avoidance withdrawal behavior were significantly worse [18 cases(58.06%) vs.6 cases(16.22%), 10 cases(32.26%) vs.3 cases(8.11%)]( χ2=15.30, 6.36, all P<0.05). Significant differences in the frequency and duration of object exploration, environmental exploration and social exploration were detected between HR-ASD group and TD group (3 vs. 0 vs. 0, 45 vs. 0 vs. 0)(all P<0.01). Pearson correlation analysis showed that, the frequency of object exploratory behavior was positively correlated with the dimension of ADOS in HR-AD group ( r=0.40, P<0.05); while the duration of object exploratory behavior, the complexity of object explo-ratory behavior and the depth of exploratory behavior were negatively correlated with CARS score ( r=-0.45, -0.47, -0.42, all P<0.05). The depth of exploratory behavior was negatively correlated with the stereotyped dimension of ADOS ( r=-0.40, P<0.05). Binary Logistic regression analysis showed that the depth of exploratory behavior had a discrimination effect ( P<0.01). Conclusions:The characteristics of exploratory behaviors in HR-ASD infants are abnormal, especially the distinguishing effect on the depth of exploratory behaviors, which can be used as a candidate behavioral index for early screening of ASD.

Objective: To investigate risk factors and epidemiological characteristics of bacillary dysentery outbreaks in three schools, and to provide scientific basis for the prevention and control of the epidemic in the future. Methods: Case definition was established. All suspected, possible and confirmed cases of all students and faculty members from 3 schools (A, B, C) were selected for epidemiological investigation. Control group was used for case-control analysis, and relevant samples were collected for laboratory testing. Results: A total of 132 cases were found in 3 schools, all of which were from students, with the incidence rate of 17.74%. The morbidity in kindergarten A was 20.00%, in center primary school B it was 21.74%, and in junior middle school C it was 11.61%. Cohort studies and casecontrol studies suggested that schools are exposed places and that washing hands with raw water in schools was possible risk factor [OR(95%CI) =4.50(1.01-20.11)]. Nine stool samples were tested in laboratory, among which 8 were positive for Shigella(88.99%), and Shigella was detected in the end nodes of school s pipeline network, the water samples from canteen bucket, and the floor drains of sewer pipe. Conclusion The bacillary dysentery outbreaks in 3 schools was caused by Shigella, which may be due to fecal contamination of domestic water in 3 schools before the start of the school year. It is suggested to strengthen the management of centralized water supply and construction in rural areas, intensify the supervision at all levels, and sanitation and disinfection before school opens at all levels.

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Objective:To investigate the prognostic value of 18F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ( 18F-FDG-PET-CT) in Hodgkin′s lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV max) of lesion and liver SUV (rLL), SUV max reduction between baseline PET (PET-0) and PET-end (ΔSUV max), and Deauville 5-point scale (5-PS). Methods:Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV max were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results:There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference ( P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference ( P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS ( r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95% CI: 0.825-1.000) and 0.91 (95% CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods ( P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients ( P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL ( P<0.05). Conclusions:The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.

Objective:To investigate the prognostic value of 18F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ( 18F-FDG-PET-CT) in Hodgkin′s lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV max) of lesion and liver SUV (rLL), SUV max reduction between baseline PET (PET-0) and PET-end (ΔSUV max), and Deauville 5-point scale (5-PS). Methods:Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV max were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results:There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference ( P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference ( P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS ( r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95% CI: 0.825-1.000) and 0.91 (95% CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods ( P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients ( P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL ( P<0.05). Conclusions:The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.