Objective:To explore the value of the amyloid-tau-neurodegeneration (ATN) framework in neuroimaging based on PET for diagnosing mild cognitive impairment (MCI) and Alzheimer′s disease (AD), and analyze its relationship with clinical cognition.Methods:From May 2022 to March 2024, a total of 98 cases (23 males and 75 females, age (67.8±8.6) years) with a diagnosis of AD, MCI, or non-AD (control patients, CP) who underwent 18F-FDG, 18F-AV45, and 18F-AV1451 PET/CT imaging in the Second Affiliated Hospital of Guangzhou Medical University were included retrospectively. The clinical data, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) scores were recorded. Cases were divided into MCI group, mild AD group, moderate AD group, moderate-severe AD group, and CP group. PET images were visually and semi-quantitatively evaluated. SUV mean and SUV ratio (SUVR) were obtained from independent brain regions of 18F-FDG ( n=8), 18F-AV45 ( n=14) and 18F-AV1451 ( n=14). ROC curve analysis was performed with clinical diagnosis as a criterion. The consistency between visual assessment and the clinical diagnosis was analyzed by Cohen′s Kappa coefficient. Semi-quantitative comparisons between groups were performed using the independent-sample t test, one-way analysis of variance, Mann-Whitney U test, or Kruskal-Wallis rank sum test. Age was used as a covariate to calculate the partial correlation coefficient between SUVR and cognitive scores. Results:The sensitivity and specificity of comprehensive visual assessment in diagnosing AD+ MCI were 87.65%(71/81) and 14/17 respectively, showing a moderate consistency with clinical diagnosis ( Kappa=0.60, P<0.001). Semi-quantitative analysis showed that 18F-FDG uptakes in all independent brain regions of MCI patients were higher than those of AD patients, whereas the uptakes of 18F-AV45 and 18F-AV1451 were lower ( t values: 2.66-3.95, z values: 4.98-15.04, all P<0.05). The difference in 18F-AV45 uptake among the three subgroups of AD was relatively small ( H values: 0.46-4.06, F values: 0.03-0.08, all P>0.05). Except for the medial temporal and occipital lobes, the 18F-AV1451 uptake in the moderate-severe AD group tended to be higher than that in the moderate and mild AD groups, though not statistically significant ( H values: 0.20-5.17, all P>0.05). 18F-FDG PET semi-quantitatively distinguished MCI from CP with a high sensitivity (13/14), 18F-AV45 demonstrated a high sensitivity for diagnosing AD+ MCI (92.59%, 75/81), and 18F-AV1451 had a high specificity for distinguishing AD from MCI (14/14) (AUCs: 0.87, 0.90 and 0.92). The uptakes of 18F-FDG in gray matter of AD and MCI patients were positively correlated with MMSE and MoCA scores ( r values: 0.30-0.43, 0.29-0.45, all P<0.05), while the uptakes of 18F-AV45 and 18F-AV1451 were negatively correlated with MMSE and MoCA scores ( 18F-AV45, r values: from -0.39 to -0.30, from -0.38 to -0.30, all P<0.05; 18F-AV1451, r values: from -0.50 to -0.28, from -0.53 to -0.28, except for medial temporal lobe P>0.05, all others P<0.05). Conclusion:The PET-based neuroimaging ATN framework is helpful for early diagnosis of MCI and AD, as well as for AD staging, and may reflect the disease progression and clinical cognitive status of AD to a certain extent.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). Materials and Methods: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. Results: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87–13.40]), IVHG (3.64 [2.15–6.24]), and RHE (7.90 [4.93–12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52–0.66]), IVHG (0.72 [0.64–0.81]), and RHE (0.61 [0.54– 0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36–15.30] and 10.10 [7.10–14.60], respectively, for the blend sign and 2.75 [1.64–4.67] and 2.62 [1.60–4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. Conclusion Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

Objective:To investigate the effect of biological maternal sounds on blood gas analysis index, mechanical ventilation time, oxygen therapy time and hospital stay in mechanically ventilated children with severe pneumonia.Methods:This study was a randomized controlled trial. From June 2020 to November 2020, 128 mechanically ventilated children with severe pneumonia in Hunan Children′s Hospital were selected by convenient sampling method and divided into four groups with 32 cases in each group by random number table method. Group A was given routine nursing care, group B was given mother sounds, group C was given mother cardiotone, group D was given biological maternal sounds. Data of blood gas analysis index, mechanical ventilation duration, oxygen therapy duration, hospital stays were collected for comparative analysis.Results:Finally, group A, B, C, and D included 28, 30, 28 and 28 cases, respectively. There was no statistically significant difference in PaO 2 among the four groups on the 1st to 2nd day after intervention ( P>0.05), but PaO 2 on the 3rd to 7th day after intervention were (75.57 ± 12.88), (77.71 ± 15.81), (78.21 ± 14.51), (78.64 ± 17.71), (79.04 ± 11.57) mmHg (1 mmHg=0.133 kPa), (81.71 ± 17.89), (82.93 ± 18.36), (82.68 ± 15.47), (83.25 ± 14.24), (83.77 ± 13.90) mmHg, (80.89 ± 18.78) (82.11 ± 13.34), (82.96 ± 14.20), (83.43 ± 14.37), (83.68 ± 12.64) mmHg, (84.54 ± 18.77), (86.29 ± 10.94), (86.96 ± 10.53), (87.46 ± 12.64), (89.08 ± 12.21) mmHg, with statistically significant differences ( F values were 41.17 - 332.68, all P<0.01). Further pairwise comparison revealed that PaO 2 in group B and group C were higher than those in group A on the 3rd to 7th day after intervention, while those in group D were higher on the 3rd to 7th day after intervention than those in group A, B, and C, with statistically significant differences( t values were 3.35- 4.75, all P<0.01). There was no statistically significant difference in PaCO 2 among the four groups on the 1st to 4th day after intervention ( P>0.05), but PaCO 2 on the 5th to 7th day after intervention was (47.31 ± 2.89), (46.18 ± 2.06), (41.94 ± 2.09) mmHg, (44.73 ± 1.76), (41.38 ± 1.30), (38.33 ± 1.16) mmHg, (44.81 ± 1.24), (41.23 ± 1.89), (38.73 ± 2.55) mmHg, (40.83 ± 1.78), (37.87 ± 1.43), (34.78 ± 2.05) mmHg, with statistically significant differences ( F=29.48, 36.12, 34.52, all P<0.05). Further pairwise comparison revealed that PaCO 2 in group B and group C were lower than those in group A on the 5th to 7th day after intervention, while PaCO 2 in group D were lower than those in groups A, B, and C, with statistically significant differences ( t values were 3.37-4.85, all P<0.01). During the analysis of PaO 2 and PaCO 2 in the four groups at different time points, the interaction effects were not statistically significant ( P>0.05). There was no significant difference in invasive mechanical ventilation duration, non-invasive mechanical ventilation duration and hospital stay among the four groups after intervention ( P>0.05). The oxygen therapy time of the four groups were (8.61 ± 6.40), (6.17 ± 4.80), (6.23 ± 2.75), and (3.75 ± 2.10) days, with statistically significant differences ( F=17.27, P<0.01). Further pairwise comparison revealed that the oxygen therapy time in group B and group C was shorter than that in group A, while group D was significantly shorter than that in groups A, B, and C, with statistically significant differences ( t values were 4.02-4.74, all P<0.01). Conclusions:Biological maternal sounds is superior to maternal sound and mother cardiotone in improve the blood gas analysis index, shorten the oxygen treatment time, which is worthy of clinical promotion in neonatal unaccompanied ward.

Objective:To explore the neural mechanism of language dysfunction in patients with subacute stroke using functional near-infrared spectroscopy (fNIRS).Methods:Sixteen patients with non-fluent aphasia after subacute stroke (aphasia group), 16 patients with non-aphasia after stroke (non-aphasia group), and 16 healthy middle-aged and elderly subjects (control group) were enrolled into our study. The 6-min resting-state data of fNIRS were collected. Four language-related regions, Broca area, Wernicke area, dorso lateral prefrontal cortex (DLPFC), and supplementary motor area (SMA), were selected as regions of interest (ROIs), and the whole brain functional connection strength and functional connection strength in ROIs and between each two ROIs were analyzed by NirSpark software.Results:Compared with the control group (0.53±0.15) and non-aphasia group (0.47±0.12), the aphasia group had significantly decreased whole brain functional connection strength (0.29±0.14, P<0.05). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the left Wernicke area, right Wernicke area, left Broca area, left SMA area, right SMA area and left DLPFC area ( P<0.05, FDR). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the right Wernicke-left Wernicke area, right Wernicke-right Broca area, right Wernicke-left Broca area, right Wernicke-right DLPFC area, right Wernicke-left DLPFC area, right Wernicke-right SMA area, right Wernicke-left SMA area, left Wernicke-right Broca area, left Wernicke-left Broca area, left Wernicke-right DLPFC area, left Wernicke-left DLPFC, left Wernicke-right SMA area, left Wernicke-left SMA area, right Broca-left Broca area, right Broca-left DLPFC area, right Broca-right SMA area, right Broca-left SMA area, left Broca-right DLPFC area, left Broca-left DLPFC area, left Broca-right SMA area, left Broca-left SMA area, right DLPFC-left DLPFC area, right DLPFC-right SMA area, right DLPFC-left SMA area, left DLPFC-right SMA area, left DLPFC-left SMA area, and right SMA-left SMA area ( P<0.05, FDR). Conclusion:Abnormal functional connectivity strength of the whole brain and language-related key brain areas might be the neural mechanism of language dysfunction in patients with non-fluent aphasia after subacute stroke.

ObjectiveTo analyze the epidemiological characteristics of senile dementia death in Jing’an District from 2016 to 2020， as well as the trends of mortality， standardized mortality， years of life lost （YLL） due to early death， years lived with disability （YLD）， and disability-adjusted life year （DALY）， and to provide scientific basis for the prevention and control of senile dementia. MethodsThe distribution of senile dementia in terms of gender， age， marital status and education level was investigated in the senile dementia death cases from 2016 to 2020 in Jing’an District. The YLL， YLD， DALY and their rates of the residents of Jing’an District from 2016 to 2020 were calculated by using Global Burden of Disease （GBD 2019） research method and results in combination with the corresponding population data. ResultsCompared to those without dementia， deaths with dementia were more likely to be female， more likely to be over 80 years old， less likely to be married， and more likely to have education level under middle school. Among the deaths with dementia， only 27.70% of the primary cause of death was dementia， and the other main causes were cerebrovascular disease， coronary heart disease and diabetes mellitus， which accounted for 25.54%， 17.81% and 7.28%， respectively. There was a significant gender difference in the burden of disease on senile dementia in Jing’an District. Mortality， standardized mortality， YLL， YLD and DALY rates of females were higher than those of males. The burden of disease on senile dementia increased with age. The change trend of mortality and YLL rate from 2016 to 2020 was not statistically significant， while the YLD rate and DALY rate showed an upward trend， which was statistically significant. ConclusionAs the life span of residents in Jing’an District increases and the population aging deepens， the burden of disease on senile dementia is still heavy. This requires extensive attention of the whole society， and active exploration of prevention and control strategies and measures for senile dementia， so as to improve the life quality of patients and reduce the burden of disease.

OBJECTIVES: Low dose computed tomography (LDCT) is the best method for early diagnosis of lung cancer. Even though it has been widely used in clinic, the selection of screening objects and the management scheme of pulmonary nodules are still not unified among research institutions. This study aims to evaluate the effect of LDCT in detection effect and follow-up process for pulmonary nodules in asymptomatic participants. METHODS: A total of 1 600 asymptomatic participants (37 to 82 years old), who came from Yantian District People's Hospital, Southern University of Science and Technology, received LDCT. The lung nodules were categorized into positive nodules and semi-positive nodules, and according to the density of positive nodules they were categorized into 4 types: solid nodules (SN), partial solid nodules (pSN), pure ground glass nodules (pGGN), and pleural nodules (PN). The number, detection rate, imaging findings, follow-up change of lung nodules, and the postoperative pathological results of positive nodules were recorded and analyzed. RESULTS: Lung nodules were found in 221 cases by LDCT. The total detection rate of lung nodule was 13.8% (221/1 600), and the detection rate in positive nodules was 4.9% (79/1 600). The detected nodules were mainly single (173 cases), solid (133 cases) and semi-positive nodules (142 cases). Most of nodules (177 cases) had no change in the follow-up process. The enlargement and/or increased density of nodules (5 cases) were lung cancer. Pathological results were obtained in 10 cases, 8 cases were malignant (1 small cell lung cancer and 7 adenocarcinomas), 2 cases were benign (cryptococcal infection and alveolar epithelial dysplasia). The detection rate of lung cancer was 0.5% (8/1 600), and the proportion of early lung cancer was 75% (6/8). CONCLUSIONS LDCT screening can identify and increase the detection rate in the early lung cancer, which is an effective screening method. It is safe and feasible to take regular follow-up and re-examination for nodules with diameter less than 5 mm. When the size and or density of nodule increases, it indicates the malignant prognosis of the nodule and timely clinical intervention is needed.
Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Early Detection of Cancer/methods* ; Humans ; Lung Neoplasms/pathology* ; Mass Screening/methods* ; Middle Aged ; Tomography, X-Ray Computed/methods*

OBJECTIVE: To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection. METHODS: DOX-loaded PELA staple fibers (F_DOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of F_DOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (G_CA4P/F_DOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of G_CA4P/F_DOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments. RESULTS: The average length of F_DOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with G_CA4P/F_DOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm³ in G_CA4P/F_DOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G_4A4P/F_DOX. CONCLUSION As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.
Animals ; Breast Neoplasms/drug therapy* ; Cell Line, Tumor ; Delayed-Action Preparations/therapeutic use* ; Doxorubicin/therapeutic use* ; Female ; Heterografts ; Humans ; Hydrogels/therapeutic use* ; Mice ; Mice, Inbred BALB C ; Phosphates

Background Diabetes mellitus is a major public health issue at present. Previous studies have shown that ambient air pollution is a risk factor for diabetes. Objective This study aims to explore the acute effects of ambient air pollution on diabetes related death in Shanghai Jing’an District. Methods Daily air pollution data, meteorological data, and diabetes related mortality data in 2013−2019 in Shanghai Jing’an District were collected. A generalized additive model (GAM) was established to conduct time-series analysis on the short-term effect of ambient air pollution on diabetes related mortality, and gender- and age-stratified analysis on susceptibility of various groups to ambient air pollution exposures. Results For every 10 μg·m⁻³ increase of the concentrations of PM_2.5, PM₁₀, SO₂, and NO₂, the diabetes related mortality increased by 2.47% (95%CI: 1.56%−3.38%), 2.02% (95%CI: 1.29%−2.75%), 5.75% (95%CI: 2.99%−8.58%), and 3.93% (95%CI: 2.49%−5.39%) at lag05 respectively (P<0.05). In the stratified analysis, exposures to increased concentrations of PM_2.5, PM₁₀, SO₂, and NO₂ raised the mortality risks from diabetes in male, female, and ≥65 years oldgroups (P<0.05). However, the differences in mortality risks from diabetes due to air pollution within gender and age groups were statistically insignificant. Conclusion In Shanghai Jing'an District, the elevated levels of ambient air pollutants, including PM_2.5, PM₁₀, SO₂, and NO₂, are significantly associated with the increase of diabetes related mortality, and there are lag effects and cumulative effects. The ≥65 years olds are more susceptible to the impact of air pollution on diabetes related deaths.

OBJECTIVE：To study the effects of limonin on immune function and apo ptosis-related factors expression in MFC gastric cancer bearing model mice. METHODS ：MFC gastric cancer bearing model was established by inoculating MFC gastric cancer cells into the right armpit of mice. After modeling ，model mice were divided into model group ，cyclophosphamide group （positive control ，25 mg/kg）and limonin high-dose ，medium-dose and low-dose groups （100，50 and 25 mg/kg），with 10 mice in each group. Other groups were given relevant medicine intragastrically ，once a day ，for consecutive 14 days，except that model group was given 0.5％ sodium carboxymethyl cellulose intragastrically. Before administration and after last administration ，the body weight of mice was measured ；spleen，thymus and tumor tissue were taken after the last administration to calculate the spleen index，thymus index and tumor inhibition rate. The percentage of CD 4+ and CD 8+ T lymphocytes ，CD4+/CD8+ ratio were detected by flow cytometry. The expression of immune function related indexes （IL-2，IL-10，IFN-γ）in serum were detected by ELISA. RT-PCR and Western blot assay were adopted to detect relative mRNA and protein expression of apoptosis-related factors [cytochrome C （Cyt-C），Bcl-2，Bax] in tumor tissue of mice. RESULTS ：There was no significant difference in body weight among the other groups except that of cyclophosphamide group was decreased significantly ，compared with model group （P＜0.05）. Inhibitory rate of tumor were （58.16 ± 7.07）％ ，（37.09 ± 4.26）％ ，（27.30 ± 3.64）％ ，（15.13 ± 2.95）％ in cyclophosphamide group ，limonin high-dose ，medium-dose and low-dose groups. Compared with model group ，spleen index ， thymus index ，the percentages of CD 4+ and CD 8+T lymphocyte cells ，CD4+/CD8+ ratio，serum levels of IL- 2 and IL- 10，relative mRNA and protein expression of Bcl- 2 in tumor of mice in cyclophosphamide group as well as the expression of IL- 10，relative mRNA and protein expression of Bcl- 2 in limonin groups were decreased significantly （P＜0.05）. The expression of IFN-γ，relative mRNA and protein expression of Cyt-C and Bax of cyclophosphamide group as well as spleen index （except for low-dose group ）， thymus index ， the percentage of CD 4 + and CD 8 + T lymphocytes，CD4+/CD8+ ratio，the expression of IL- 2 and IFN-γ，and relative mRNA and protein expression of Cyt-C and Bax in limonin groups were increased significantly （P＜0.05）. CONCLUSIONS ：Limonin can inhibit tumor growth in MFC gastric cancer bearing model mice ，and the side effects are relatively weak. Its mechanism is related to the improvement of immune function and the induction of apoptosis.