OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

Objective To explore the effect of A.muciniphila gavage on intestinal microbiota and gut-brain interaction disorders(DGBIs)in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder(HAND).Methods Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-,9-,and 12-month-old wild-type(WT)mice and gp120tg transgenic mice.The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage(2×108 CFU/mouse)for 6 weeks.After the treatment,immunohistochemistry,ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins,MBP and IL-1β,eosinophil infiltration,serum lipopolysaccharide(LPS)levels,and colonic expressions of occludin,ZO-1,IL-10,TNF-α and INF-γ mRNA.Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice.Results Compared with WT mice,the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus,increased serum LPS levels and decreased colonic expression of glycosylated mucin.A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight.The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β,INF-γ and IL-1β levels and obviously lowered IL-10 level;all these changes were significantly mitigated by A.muciniphila gavage,which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice.Conclusion The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice.The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes,and A.muciniphila gavage can reduce intestinal barrier injury,colonic inflammation and eosinophil activation,cognitive impairment and brain neuron injury in these mice.

Objective:To explore the correlations between the cerebral infarction area and cytokines and immune status in patients with acute ischemic stroke,and to provide the theoretical basis for immunotherapy of the patients with different degrees of cerebral infarction.Methods:Sixty-seven patients with acute ischemic stroke within 72 h of the onset were randomly selected according to the inclusion and exclusion criteria,and were divided into large-area cerebral infarction group(n=34)and non-large-area cerebral infarction group(n=33)on the basis of the biggest infarction area in the sequences of magnetic resonance diffusion-weighted imaging(CDWI).Clinical baseline characteristics such as gender,age,and medical history were collected from the patients in two groups,the serum levels of interleukin(IL)-2,IL-6,IL-10,and IL-17A,tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ)were measured using flow cytometry;the absolute values of lymphocytes(LYM#),lymphocyte percentages(LYM％),and neutrophil/lymphocy ratios(NLR)in peripheral blood of the patients caiculated,and the ratios of IFN-γ/IL-4,TNF-α/IL-4,and TNF-α/IL-10 rations were also calculated.The values of National Institutes of Health Stroke Scale(NIHSS)scores of the patients were evaluatd on the basis of the assessment of clinical neurological signs.The correlations of the cerebral infarction area and NIHSS score,cytokines and immune status groups of the patients in two were tested by rank correlation analysis.Results:Compared with non-large-area cerebral infarction group,the serum levels of IL-2,IL-6,IL-10,IL-17A,TNF-α,and IFN-γ as well as the NLR in the peripheral blood of the patients in large-area cerebral infarction group were significantly increased(P＜0.01),while the LYM#,LYM％and TNF-α/IL-4 were significantly decreased(P＜0.01).There was a positive correlation between cerebral infarction area and NIHSS score in the patients in large-area cerebral infarction group(rs=0.521,P＜0.05),and there was a significantly positive correlation between cerebral infarct area and NIHSS score in the patients in non-large-area cerebral infarction group(rs=0.721,P＜0.001).The NIHSS scores were positively correlated with serum IL-6(rs=0.306,P=0.005),IL-4(rs=0.252,P＜0.001),IL-2(rs=0.109,P=0.025),IL-17A(rs=0.405,P＜0.001),and IFN-γ(rs=0.146,P＜0.001)levels in two groups;no correlations were found between NIHSS scores and TNF-α(rs=0.039,P=0.726)and IL-10(rs=0.121,P=0.192)levels.NIHSS scores of the patients in two groups had negative correlatious with the serum level of LYM#(rs=-0.026,P=0.036)and LYM％(rs=-0.008,P=0.002),and had positive correlated with NLR(rs=0.315,P=0.009).Conclusion:The infarction area of the patients with actue cerebral infarction is correlated with the NIHSS score,the inflammatory response,the degree of adaptive immune injury,and the immune status.The have positive correlation with cytokines and immune markers and the overall size of the infarction area.Compared with the patients with non-large-acea cerebral infarction,the immunosuppression of the patients with large-area infarcted areas is more likely to occure.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective To analyze the changes of serum humoral immunity related indicators, including immunoglobulins (Ig), complement and C-reactive protein (CRP) in patients with occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) at different stages. Methods A total of 131 OMDT patients were selected as the study subjects using a retrospective analysis method, and liver function and humoral immunity related indicators were collected for analysis in the early stage and the recovery stage of the disease. Results The abnormality of liver function among study subjects was 89.3% (117/131) in the early stage of the disease, with mild, moderate, and severe liver damage accounting for 61.8%, 5.3%, and 22.1%, respectively. The levels of serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, total bilirubin, alkaline phosphatase, total bile acid, IgG and CRP in the early stage increased ( all P<0.01), while the level of serum cholinesterase and C3 decreased (both P<0.01) compared with the recovery stage. However, there was no significant difference in the level of serum albumin, globulin, IgA, IgM and C4 or albumin/globulin ratio between the early stage and the recovery stage (all P>0.05). The level of patients′ serum IgA in the group with severe liver function injury was lower than that in the group with mild to moderate liver function injury in the recovery stage (P<0.05). The level of serum C3 in the patients with severe liver function injury was lower than that in the group with mild to moderate liver function injury in the early stage (P<0.05). Conclusion Serum IgG and CRP levels increased and C3 level decreased in OMDT patients at the early stage of the disease, which was correlated with the degree of liver function injury. It is suggested that humoral immune response is involved in the autoimmune liver injury in OMDT patients.

ObjectiveTo investigate the relationship between plasma surfactant protein⁃A （SP⁃A） expression level and silicosis progression， and to provide early evidence for exploring whether SP⁃A can be used as a biomarker for clinical monitoring of silicosis disease progression. MethodsWe recruited 187 silicosis patients in Guangdong Province hospital for occupational disease prevention and treatment between November， 2019 and November，2020. Their peripheral venous blood samples were collected for the plasma isolation. The level of pulmonary SP⁃A was detected by enzyme-linked immunosorbent assay. ResultsThere was a statistically significant difference in the level of SP⁃A among the silicosis groups （P<0.05）， and the plasma SP-A level of the silicosis patients in stage Ⅲ was higher than that in stage Ⅰ and stage Ⅱ （P<0.05）. Smoking had effect on plasma SP⁃A levels， Age， working years and drinking had no effect on plasma SP⁃A levels. ConclusionThe expression level of SP⁃A in the plasma of silicosis patients is increased， which has a certain correlation with the disease stage， and plays a certain early warning role in the occurrence and development of silicosis， and may be a potential biomarker for the diagnosis and prognosis of silicosis.

Objective: To investigate the role of surfactant associated protein-A (SP-A) in the development and progression of silicosis, and its mechanism. Methods: Homozygous and heterozygous mice of SP-A knockout of specific pathogen free (SPF) grade were selected for mating, and mice with SP-A^-/- genotype were selected for subsequent experiments. SP-A wild-type (SP-A^+/+) and SP-A^-/- mice were divided into SP-A^+/+ control group, SP-A^-/- control group, SP-A^+/+ silicosis group and SP-A^-/- silicosis group with six mice in each group by random number table method. Mice in both silicosis groups were given 20.0 μL 250 g/L silica suspension by tracheal exposure, and mice in both control groups were injected with 0.9% sodium chloride solution at the same volume. On the 28th day after modeling, mice were sacrificed. Lung tissues were used for lung histopathology examination. The apoptosis of alveolar type Ⅱ epithelial cells of mice was detected by TUNEL method. The mRNA expression of B-lymphoblastoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 in lung tissues of mice was detected by quantitative real-time polymerase chain reaction. Results: The histopathological result of mice showed that thickened alveolar septum, scattered silicon nodule and collagen fiber formation were observed in the mice lungs of SP-A^+/+ silicosis group, and a large number of inflammatory cells were observed in silicosis nodule, after exposure to silica dust. SP-A^-/- silicosis group resulted in a more severe pulmonary inflammation and interstitial fibrosis compared to SP-A^+/+ silicosis group. The apoptosis of alveolar type Ⅱ epithelial cells and the mRNA relative expression levels of Bax, Caspase-3 and Caspase-9 in lung tissues of mice in each silicosis groups were increased compared with their control groups (all P<0.05). The above four indexes of mice in SP-A^-/- silicosis group were higher than those in SP-A^+/+ silicosis group (all P<0.05). There was no significant difference in the expression of Bcl-2 mRNA in lung tissues of these four groups (P>0.05). Conclusion: Knockout of SP-A can aggravate inflammation and pulmonary fibrosis in silicosis model mice, and promote apoptosis of alveolar type Ⅱ epithelial cells. The mechanism may be related to the Bcl-2/Bax/Caspase-3 signaling pathway which affects the apoptosis of mitochondrial pathway.

Objective:To compare the effects of staged percutaneous coronary intervention(PCI)after emergency PCI and emergency culprit-only PCI on clinical outcomes of elderly patients with ST-segment elevation myocardial infarction(STEMI)and multivessel disease.Methods:A retrospective analysis was performed on 389 elderly patients with STEMI and multivessel lesions, aged ≥70 years and within 12 h of onset, admitted to the Clinical College of Thoracic Medicine, Tianjin Medical University, between January 2014 and September 2019.According to different revascularization strategies, enrolled patients were divided into the culprit-only PCI group(79.18%, 308)and the staged PCI group(20.82%, 81). Kaplan-Meier analysis and the Cox proportional hazards regression model were used to compare the incidences of major adverse cardiac and cerebrovascular events(MACCE), all-cause death, cardiac death, recurrent myocardial infarction, stroke and ischemia-driven revascularization between the two groups and to evaluate the effects of different revascularization strategies on MACCE and all-cause death.Then subgroup analysis was performed.Results:During a 56-month follow-up, 131 patients developed MACCE and 96 patients died.Compared with the culprit-only PCI group, the staged PCI group had a lower risk of MACCE( HR: 0.404, 95% CI: 0.227-0.716, P=0.002), all-cause death( HR: 0.354, 95% CI: 0.171-0.730, P=0.005), cardiac death( HR: 0.363, 95% CI: 0.157-0.838, P=0.018), and recurrent myocardial infarction( HR: 0.229, 95% CI: 0.055-0.953, P=0.043). There was no significant difference in the incidence of stroke or ischemia-driven revascularization between the two groups( P>0.05). The reduced risk with staged PCI for MACCE and for all-cause mortality persisted in all subgroups.Multivariate Cox proportional hazards regression revealed that, after adjusting for confounding factors, staged PCI was an independent protective factor for MACCE( HR: 0.44, 95% CI: 0.239-0.815, P=0.009)and for all-cause death( HR: 0.390, 95% CI: 0.90, P=0.020). Conclusion:Compared with culprit-only PCI, staged PCI can significantly improve the long-term prognosis of elderly patients ≥70 years with STEMI and multivessel disease within 12 h of onset.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.