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Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.
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Objective:To investigate the effect of aucubin on behaviors and excessive activation of astrocytic in attention deficit/hyperactivity disorder (ADHD) model mice.Methods:Twelve wild-type C57BL/6 pregnant mice (female, clean grade) were intraperitoneally administered with esketamine (15 mg/kg) to establish an ADHD model in offspring mice. The offspring mice were divided into control+ saline group, control+ aucubin group, Ketamine+ saline group and Ketamine+ aucubin group according to the nest matching principle with 15 in each group.At 14 days after birth, mice in the control+ aucubin group and Ketamine+ aucubin group were administered with aucubin (5 mg/kg, once a day) by gavage for 5 days. Mice in control+ saline group and Ketamine+ saline group were administered with equal volume of 0.9% sodium chloride solution. The offspring mice were housed with their mothers in the same cage until 21 days after birth. Twenty-one days after birth, the offspring mice were evaluated by open field test and elevated plus maze tests. Immunofluorescence assay was used to detect the expression of glutamate decarboxylase 2 (GAD2), γ- aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) in the amygdala. The morphological changes of astrocytes were quantitatively analyzed by Sholl analysis. GraphPad Prim 9.0.1 software was used for statistical analysis. The comparison of multiple groups was conducted by one-way ANOVA or Kruskal-Wallis test.Results:(1)The results of behavioral experiments showed that the total distance traveled in the open field test and the residence time in open arm of the elevated plus maze were statistically significant ( F=236.90, H=39.92, both P<0.001). The total distance ((7 044±249)mm, (22 891±2 175)mm, P<0.05) and the residence time in open arm(12.69(9.86, 17.24)s, 2.72(0.57, 3.87)s, P<0.05) of mice in Ketamine+ saline group were both higher than those in control+ saline group.The total distance((22 891±2 175)mm, (8 252±839)mm, P<0.05) and the the residence time in open arm(5.45(1.13, 10.99)s, 12.69(9.86, 17.24)s, P<0.05) of Ketamine+ aucubin group were both lower than those of Ketamine+ saline group.(2)The immunofluorescence results showed that the levels of GAD2, GABA and GFAP intensity in amygdala of mice in the four groups were statistically significant ( F=145.50, 50.08, 53.83, all P<0.05). Compared with control+ saline group, the fluorescence intensities of GAD2 ((100.00±9.60)%, (24.86±4.14)%, P<0.05) and GABA ((100.00±16.84))%, (25.48±5.70)%, P<0.05) of Ketamine+ saline group were down-regulated, and the GFAP((100.00±18.02)%, (223.80±25.85)%, P<0.05) was up-regulated. Compared with Ketamine+ saline group, the fluorescence intensities of GAD2 ((24.86±4.14)%, (56.08±6.55)%, P<0.05) and GABA((25.48±5.70)%, (52.59±15.74)%, P<0.05) in Ketamine+ aucubin group were up-regulated, but the fluorescence intensity of GFAP ((223.80±25.85)%, (157.10±22.10)%, P<0.05) was down-regulated.(3)Sholl analysis indicated that the number of the intersections between the astrocyte processes or the branches of astrocyte processes was statistically significant in the 4 groups ( F=12.47, P<0.05). Compared with control+ saline group, the number of the intersections in Ketamine+ saline group((2.07±0.48), (1.67±0.72), P<0.05) increased. While the number of the intersections in Ketamine+ aucubin group was lower than that of Ketamine+ saline group ((1.20±0.78), (2.07±0.48), P<0.05). Conclusion:Aucubin administration can alleviate ADHD-like behaviors in offspring mice, and the mechanism may be associated with the inhibition of excessive astrocytic activation.
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Objective:To investigate the icariin on cognitive function and astrocytic pyroptosis in hemorrhagic shock resuscitation model mice.Methods:Forty-eight SPF grade C57BL/6 mice (male) were randomly divided into four groups ( n=12 in each group): Sham operation control group (Group C), hemorrhagic shock and resuscitation group (Group H), hemorrhagic shock and resuscitation plus icariin group (Group HI) and hemorrhagic shock resuscitation plus icariin and SSK1 group (Group HIS, SSK1 was a phosphorylation agonist of mitogen-activated protein kinase p38(p38MAPK). The mice in Group H, HI and HIS were subjected to hemorrhagic shock and resuscitation model by bleeding and retransfusion via left femoral vein; the mice in Group HI and HIS were administered with icariin (10 mg/kg) intragastrically for 7 days; the mice in Group C and H were administered with the same amount of normal saline containing dimethyl sulfoxide(DMSO). The mice in Group HIS were administered with SSK1 (0.5 mg/kg) intraperitoneally, but the mice in Group C, H and HI were only administered with the same amount of normal saline containing DMSO.At 15 days after resuscitation, novel objective recognition test and fear conditioning test were used to assess cognitive dysfunction of mice.Microtubule-associated protein 2(MAP2), a specific marker protein of neurons reflecting astrocytic pyroptosis in the hippocampus of mice, were detected by immunofluorescence assay so as to assess neuronal injury and astrocytic pyroptosis.The levels of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the hippocampus were evaluated by Western blot.SPSS 21.0 software was used for data analysis, multiple samples among groups were compared by one-way ANOVA, and SNK- q test was used for further pairwise comparison. Results:The results of new object recognition test showed that the difference of new object recognition index among the four groups was statistically significant ( F=50.75, P<0.05). The new object recognition indexes in H group(22.7±6.9), HI group(40.1±7.0) and HIS group (22.5±7.5) were significantly lower than that in C group (58.5±11.2). The index in HI group was higher than that in H group, while the index in HIS group was lower than that in HI group (all P<0.05). The results of the fear conditioning test showed that there was a statistically significant difference in the percentage of freezing time among the four groups of mice ( F=60.54, P<0.05). And the percentage of freezing time in H group((21.8±5.0)%), HI group ((38.4±7.4) %)and HIS group((21.3±4.2)%)were lower than that in C group((49.1±7.0)%), which in HI group was higher than that in H group ( P<0.05)and which in HIS group was lower than that in HI group(all P<0.05). The results of immunofluorescence showed that there were significant decreases of MAP2 intensity ((35.3±9.3)%, (63.3±6.1)%, (28.7±10.3)%) but increases of pyroptotic astrocytes ((24.5±4.2)%, (9.3±1.5)%, (22.1±3.3)%) in the H, HI and HIS groups compared with those of C group ((106.7±19.7) %, (3.4±2.0)%). There was an increase of MAP2 intensity but a decrease of pyroptotic astrocytes in the HI group compared with those in H group, and there was a decrease of MAP2 intensity but an increase of pyroptotic astrocytes in the HIS group compared with those of HI group (all P<0.05). The Western blot results showed that there were significant increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the H, HI and HIS groups compared with C group, there were decreases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HI group compared with H group, and there were increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HIS group compared with those in HI group (all P<0.05). Conclusion:Icariin alleviates hemorrhage shock and resuscitation-induced cognitive dysfunction and astrocytic pyroptosis in mice, and the mechanism may be associated with inhibition of phosphorylated p38MAPK.
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Background and aims: Cardiac enzymes are recognized as a valuable tool for predicting the prognosis of various cardiovascular diseases. The prognostic value of alpha-hydroxybutyrate dehydrogenase (α-HBDH) in patients with intracerebral hemorrhage (ICH) was ambiguous and not evaluated. Methods: Two hundred and thirteen Chinese patients with ICH participated in the study from December 2018 to December 2019. Laboratory routine tests and cardiac enzymes, including α-HBDH level, were examined and analyzed. All the patients were classified into two groups by the median value of α-HBDH: B1 <175.90 and B2 ≥175.90 U/L. The clinical outcomes included functional outcome (according to modified Rankin Scale (mRS) score ≥3), all-cause death, and recurrent cerebro-cardiovascular events 1 year after discharge. Associations between the α-HBDH and the outcomes were evaluated using logistic regression analysis. Univariate survival analysis was performed by the Kaplan-Meier method and log-rank test. Results: Of the 213 patients, 117 had α-HBDH ≥175.90 U/L. Eighty-two patients had poor functional outcomes (mRS≥3). During the 1-year follow-up, a total of 20 patients died, and 15 of them had α-HBDH ≥175.90 U/L during the follow-up time. Moreover, 24 recurrent events were recorded. After adjusting confounding factors, α-HBDH (≥175.90) remained an indicator of poor outcome (mRS 3-6), all-cause death, and recurrent cerebro-cardiovascular events. The ORs for B2 vs. B1 were 4.78 (95% CI: 2.60 to 8.78, P = 0.001), 2.63 (95% CI: 0.80 to 8.59, P = 0.11), and 2.40 (95% CI: 0.82 to 7.02, P = 0.11) for poor functional outcomes with mRS ≥ 3, all-cause death, and recurrent cerebro-cardiovascular events, respectively. Conclusion: Increased α-HBDH at admission was independently related to poor functional outcome and all-cause mortality in patients with ICH at 1-year follow-up.
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BACKGROUND AND AIMS: The apolipoprotein B (apoB)/apolipoprotein A1 (apoA1) ratio is a key indicator in predicting future cardiovascular outcomes. However, it is still unclear whether the ratio of apoB/apoA1 is a better predictor of the outcomes after intracerebral hemorrhage (ICH). Therefore, we aimed to assess the relationships between the ratio of apoB/apoA1 and functional outcomes, all-cause mortality, and stroke recurrence in ICH patients. METHODS: Two hundred and sixteen Chinese ICH patients participated in this study from December 2018 to December 2019. Laboratory routine tests including hematology analysis, coagulation tests, and lipid levels were examined. The clinical outcomes included functional outcomes evaluated by the modified Rankin Scale score (mRS), all-cause death, and stroke recurrence 1 year after discharge. Associations between the apoB/apoA1 ratio and the outcomes were evaluated using logistic regression analysis. Based on multivariate analysis, we constructed a nomogram. Univariate survival analysis was performed by the Kaplan-Meier method and log-rank test. All the patients were classified into two groups by the median value of the apoB/apoA1 ratio: B1 < 0.8 and B2 ≥ 0.8. RESULTS: Of the 216 patients, 107 had an apoB/apoA1 ratio ≥ 0.8. Eighty-five patients had poor functional outcomes (mRS ≥ 3), and 32 patients had severe functional outcomes (mRS ≥ 4). During the 1-year follow-up, a total of 18 patients died, and 13 patients had apoB/apoA1 ratio levels ≥0.8 during the 1-year follow-up period. Moreover, 16 recurrent strokes were recorded. Adjustments for age, sex, smoking, alcohol, body mass index, lipid levels, and hematoma site and volume showed that a high apoB/apoA1 ratio was significantly related to adverse functional outcomes and all-cause mortality. The ORs for B2 versus B1 were 3.76 (95% CI: 1.37 to 10.40, p = 0.010), 22.74 (95% CI: 1.08 to 474.65, p = 0.044), and 7.23 (95% CI: 1.28 to 40.88, p = 0.025) for poor functional outcomes with mRS ≥ 3, mRS ≥ 4, and all-cause mortality, respectively. CONCLUSION: An increased apoB/apoA1 ratio at admission was independently related to poor functional outcome and all-cause mortality in ICH patients at the 1-year follow-up.
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Apolipoproteins B , Stroke , Apolipoprotein A-I , Asian People , Cerebral Hemorrhage , HumansABSTRACT
Objective@#To explore dynamics of parenting styles of adolescents from 1999 to 2019 from the perspective of intergenerational conflict, to provide support for family education and adolescent healthy development.@*Methods@#Using a multistage stratified cluster random sampling method, the unified questionnaire was administered to 2 590 students in the same sampling junior and senior high schools in 1999, 2009, and 2019 using the Egna Minnen av Barndoms Uppfostran own memories of parental rearing practices in childhood(EMBU).@*Results@#Overall there were differences in the nine factors of parenting styles across generations ( F = 12.07-72.52, P <0.01), with decreasing ratings of warmth and understanding of father and mother (F1, M1), over interference of father (F3) over generations(F1:46.72±9.41, 45.87±11.33, 43.61±11.27; M1:51.56±9.38, 51.03±11.59, 46.23± 12.27 ; F3:19.03±4.00, 18.29±4.32, 17.95±4.51), and all other parenting styles rated higher in 2019 than in 2009 and 1999(except for the over protection and over interference of mother, and punishment, firm control of mother). Parenting styles across generations (except for the rejection and denial of father among girls) showed gender difference.The overall gender trend coincided with the total population trend. Parenting styles across generations varied significantly among middle and high school students( F =3.92-47.27, P <0.05 ), changes in F1 and F3 factors coincided with the overall decreasing trend. Factor analysis showed that parenting styles could be classified into two dimensions, with varied factor loading across generation.@*Conclusion@#Intergenerational decreases in parental emotional warmth and paternal interfering are observed in a sex and grade specific manner. Based on the diversity of needs and population differentiation, optimal intervention for comprehensive health development of adolescents are in great need to keep pace with the times and promoting the high quality development of adolescents.
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Objective:To explore the safety and feasibility of optimized pathological evaluation system of donor's kidney and modified surgery during adult dual kidney transplantation(DKT)and evaluate its effectiveness to provide more alternative protocols for kidney transplantation from extended criteria donors.Methods:DKT was performed in 10 recipients using the same protocol from June 2019 to May 2021.And retrospective reviewing was performed for clinical data, including characteristics of donors and recipients, optimized pathological evaluation system, modified surgery, treatment regimens, complications and follow-ups.Results:There were 8 male and 2 female donors with an age of(57.9±12.8)years and BMI(24.1±4.1)kg/m 2.The percentage of DCD was 70% and DBD 30%.The serum creatinine before procurement was 107.6(93.3-163.5)μmol/l.Zero-point puncture biopsy was performed for both kidneys and optimized pathological evaluation system was implemented(Banff criteria & Remuzzi score). The pathological results indicated that glomerular sclerosis for left and right kidneys were 2.0(1.5-2.0)and 1.5(1.0-2.0). And Remuzzi score for left and right kidneys were(4.4±1.2)and(3.6±1.5)points respectively.All recipients were male with an age of(43.1±9.0)years and BMI(22.2±1.9)kg/m 2.All PRAs were negative pre-operation.Modified surgery was performed in all recipients(two kidneys were implanted outside iliac vessels without patch and artery of superior kidney was anastomosed to internal iliac artery). Operative duration was(195±54.3)min and serum creatinine before discharge 125.0(102.0-199.0)μmol/L.Renal dynamic scintigraphy indicated that glomerular filtration rate was(30.0±8.2)ml/min for left kidney and(29.2±13.9)ml/min for right kidney.MRA results indicated that morphologies of renal arteries and veins were regular.The time between operation and discharge was(22.4±4.7)days.Compared with SKT, serum creatinine before discharge of DKT was lower and DGF incidence of DKT was higher without statistical significance.The time between operation and discharge was longer for DKT than that for SKT( P<0.05). The complications consisted of 20% donor derived infection(DDI)and 50% DGF.And there was no surgical complication associated with vessels and ureter.Renal function remained stable during 6-month follow-ups. Conclusions:Optimized pathological evaluation system of donor's kidney and modified surgery during adult dual kidney transplantation are both safe and feasible.The postoperative function of transplanted dual kidney is successfully restored.However, long-term follow-ups are required for evaluating its effectiveness.
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Objective:To analyze the clinical characteristics and risk factors of ischemic stroke in young adults.Methods:A retrospective analysis was conducted on 80 ischemic stroke patients (age ≤45 years) admitted to Beijing Tiantan Hospital from March 2019 to October 2019 as the young stroke group, and 117 ischemic stroke patients (age >45 years) hospitalized during the same period as the middle-aged and elderly stroke group. The blood test indexes of the two groups were compared, and the risk factors related to stroke, including smoking history, drinking history, hypertension, hyperlipidemia and diabetes history, were compared and analyzed. Two sets of independent sample t-test, Mann-Whitney U-test or χ2 test were used to compare the above indicators of patients in the two groups. Results:The activated partial prothrombin time, protein S, uric acid, homocysteine and D-dimer levels in middle-aged and elderly stroke group were (29.73±3.40) s, (105.58±27.23) %, (297.29±85.99) μmol/L, (17.58±14.45) μmol/L and (2.75±3.08) mg/L, respectively. Compared with the middle-aged and elderly stroke group, the young stroke group had higher activated partial thrombin time (31.51±6.75) s, protein S (115.20±26.97) %, uric acid (326.82±93.51) μmol/L, homocysteine (22.63±16.98) μmol/L and lower D dimer level of (1.19±2.88) mg/L compared with the elder group, the difference between the two groups was statistically significant ( t values were 2.17, 2.01, 2.20, 2.14 and 2.13, respectively, P values were 0.032, 0.046, 0.029, 0.039 and 0.034, respectively). The positive rate of lupus anticoagulant in young stroke group was 12.5% (4/32), which was higher than 1.8% (1/57) in middle-aged and elderly stroke group, and there was significant difference between the two groups (χ 2=4.46, P=0.035). The proportions of smoking and drinking in young stroke group were 63.8% (51/80) and 62.5% (50/80), respectively, which were higher than 49.6% (58/117) and 47.9% (56/117) in middle-aged and elderly stroke group, and there was significant difference between the two groups (χ 2 values were 3.86 and 4.09; P values were 0.04 and 0.04). The proportion of hypertension and diabetes in young stroke group was 48.8% (39/80) and 17.5%(14/80), respectively, which were lower than 63.2%(74/117) and 30.8%(36/117) in middle-aged and elderly stroke group, and there was significant difference between the two groups (χ 2 values were 4.08 and 4.56; P values were 0.043 and 0.033). According to the levels of uric acid and homocysteine, young stroke was divided into different subgroups and compared.The creatinine level of high uric acid group (≥416 μmol/L) was (90.08±28.46) mmol/L, which was higher than that of normal uric acid group (<416 μmol/L) of (63.37±22.2) mmol/L. There was significant difference between the two groups ( t value was 2.23, P value was 0.046). The levels of fibrinogen and creatinine in high homocysteine group (≥15 μmol/L) were (3.27±1.09) g/L and (72.13±28.69) mmol/L, respectively which were significantly higher than those in normal homocysteine group (<15 μmol/L) of (2.78±0.67) g/L and (58.92±12.08) mmol/L, There was significant difference between the two groups (the t values were 2.32 and 2.51; P values were 0.023 and 0.014). Conclusions:Compared with middle-aged and elderly stroke, young ischemic stroke has higher levels of prothrombin time, protein S, uric acid and homocysteine, lower levels of D dimer and higher positive rate of lupus anticoagulant. At the same time, the proportion of smoking and drinking was higher in young stroke group, but the proportion of hypertension and diabetes was relatively lower.
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Objective:To investigate the effect of activation of microglia in prefrontal cortex on long-term spatial memory in post-stroke depression mice.Methods:Forty-eight male C57BL/6 mice were divided into sham operation group, stroke group, post-stroke depression group and depression group according to the random number table method with 12 in each group, and 36 mice were divided into solvent group, enrofloxacin group and minocycline group according to the random number table method with 12 in each group.Middle cerebral artery occlusion (MCAO) was use to establish the stroke model, and forced swimming was used to establish the depression model.The post-stroke depression model mice were received MCAO first and then received forced swimming on the 4th day after stroke to establish the model.Mice in enrofloxacin group and minocycline group were treated with enrofloxacin and minocycline injection once a clay for 14 days from the 5th day after stroke, respectively.Forced swimming test and sugar water preference test were used to evaluate the depression of mice in each group, Morris water maze test was used to detect the spatial memory function of mice in each group, and Nissl staining and immunofluorescence staining were used to detect the neuronal function and the number and type of microglia activation.The expression of inflammatory cytokines IL-6 and IL-1β were detected by Western blot.GraphPad Prism 8.0.1 statistical software was used for statistical analysis.The single factor variance analysis was used to compare the difference among multiple groups, and pairwise comparison was performed with SNK- q test. Results:(1) There were statistically significant differences in depression, learning and memory, neuron damage, activation of microglia, inflammatory factors and other indicators in sham operation group, stroke group, post-stroke depression group and depression group ( F=43.58-255.70, all P<0.05). Compared with stroke group, post-stroke depression group had longer floating immobility time ((222.70±29.12) s, (79.25±46.78) s, P<0.05), the preference rate of sugar water was significantly lower ( (49.44±6.19) %, (84.49±4.73) %, P<0.05), and the average value of platform approach after correction was higher((125.00±9.95) mm, (96.79±12.57) mm, P<0.05), Nissl bodies expression was lower ((53.50±15.78) cells /mm 2, (85.67±17.52) cells /mm 2, P<0.05), NeuN positive expression rate was lower ((29.78±3.70) %, (45.73±4.51) %, P<0.05), the percent of M1 microglia expression was significantly higher ((75.55±8.84) %, (58.19±5.69) %, P<0.05), the percent of M2 microglia expression was lower ((43.46±5.11)%, (57.14±5.40)%, P<0.05), and the expression levels of IL-6 ((1.14±0.03), (0.94±0.05), P<0.05) and IL-1β((1.17±0.03), (0.56±0.04), P<0.05) were significantly higher.(2) Depression, learning and memory, neuron injury, activation of microglia, inflammatory factors and other indicators of mice in solvent group, enrofloxacin group and minocycline group were significantly different ( F=7.13-94.35, all P<0.05). Compared with enrofloxacin group, mice in minocycline group had shorter floating immobility time ((169.30±13.04) s, (224.30±22.60) s, P<0.05) and higher sugar water preference rate ((62.81±7.75) %, (47.71±8.11) %, P<0.05), the mean value of platform approach estimation after water maze correction was lower ((97.66±14.56) mm, (120.20±12.08) mm, P<0.05), and the expression level of Nissl bodies was higher ((80.17±10.55) cells /mm 2, (52.00±8.94) cells /mm 2, P<0.05), NeuN expression rate was high ((45.04±3.62) %, (28.88±4.50) %, P<0.05), Iba-1 expression was lower ((97.33±10.67) cells/mm 2, (112.50±6.54)cells/mm 2, P<0.05), the percent of M1 microglia expression was lower ((54.43±5.22) %, (73.82±6.88) %, P<0.05), and the percent of M2 microglia expression was significantly higher ((51.86±6.22) %, (36.30±5.72) %, P<0.05). The expression levels of IL-6 ((0.75±0.06), (1.21±0.07), P<0.05) and IL-1β ((0.61±0.06) (1.09±0.09), P<0.05) were lower. Conclusion:The long-term spatial memory impairment of post-stroke depression mice is aggravated, which is related to the neuron damage caused by increased activation of M1 microglia in PFC area.Inhibition of M1 microglia by minocycline can effectively improve the spatial memory ability of mice.
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Objective:To analyze the laboratory tests and clinical characteristics of patients with lupus anticoagulant-positive cerebral infarction.Methods:A retrospective analysis of 216 patients with cerebral infarction hospitalized in Beijing Tiantan Hospital from January 2016 to October 2021 was performed, and the patients were divided into LA-positive cerebral infarction group (168 cases) and LA-negative cerebral infarction group (48 cases) according to the detection of lupus anticoagulant (LA) in cerebral infarction patients, and the laboratory test data between the two groups were compared, and the risk factors related to cerebral infarction, including body mass index (BMI), smoking history, drinking history, hypertension, hyperlipidemia, diabetes history, were included for comparative analysis. LA was performed using the silica clotting time (SCT) method and the modified diluted russell viper venom time (dRVVT) method, respectively. The dRVVT method was used to detect LA. The LA-positive cerebral infarction group was divided into three subgroups according to the positive detection, namely, the dRVVT single-positive group (110 cases), the SCT single-positive group (40 cases) and the double-positive group (18 cases), and the comparison of laboratory indices between different subgroups was performed.The measurement data of normal distribution between the two groups were compared by independent sample t-test, and the mean between multiple groups was compared by ANOVA; The rank sum test was used to compare the median between the measurement data groups that did not conform to the normal distribution, and the χ 2 test was used to compare the counting data groups. Results:The levels of antithrombin Ⅲ and protein C of the LA-positive group ((102.85±14.39)% and (108.52±22.62)%) were all lower than those of the LA-negative group ((110.16±11.10)% and (116.34±18.14)%), the difference was statistically significant ( t values were 3.25, 2.20, P values were 0.001, 0.029, respectively). The levels of fibrinogen, homocysteine, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate, white blood cells and neutrophil were (3.43(3.07,4.03) g/L), (17.92(14.07,23.71) μmol/L), (6.97(2.33,11.46) mg/L), (15.00(6.75,29.00) mm/h), (8.61(6.72,10.86)×10 9/L) and (5.81(4.39,7.91)×10 9/L), all were higher than those in the LA-negative group with values of (3.14(2.68, 3.62) g/L), (14.62(12.49, 18.41) μmol/L), (3.18(2.09,4.32) mg/L), (9.50(3.75,19.00) mm/h), (7.20(6.22,8.33)×10 9/L) and (4.47(4.02,5.57)×10 9/L), and the differences were statistically significant ( Z values were 2.77, 2.89, 3.32, 2.45, 3.15 and 3.76, P values were 0.006、0.004、0.001, 0.014, 0.002 and <0.001, respectively). There were no significant differences in age, gender, BMI, personal history, past medical history and other laboratory indicators between the two groups (all P>0.05). Comparison among different subgroups in LA positive group showed that D dimer and hs-CRP levels in double-positive group were 0.58(0.50,0.84) mg/L and 7.77(5.94,21.61) mg/L, higher than those in SCT single-positive group with values of 0.45(0.32,0.56) mg/L and 2.98(1.09,6.07) mg/L, and protein S level of double-positive group (97.36±25.45)% was lower than that in SCT single-positive group (114.85±22.74)%, the differences were statistically significant (all P<0.05). D dimer, prothrombin time, hs-CRP and neutrophil levels in dRVVT single-positive group were (0.58(0.50,0.84) mg/L), (11.40(11.10,12.10) s), (6.97(4.07,11.97) mg/L) and (5.83(4.51,8.27)×10 9/L), which were higher than those in SCT single-positive group with values of (0.45(0.32,0.56) mg/L), (11.15(10.70,11.43) s), (2.98(1.09,6.07) mg/L) and (5.08(3.92,6.07)×10 9/L), the difference was statistically significant (all P<0.05). Protein C and triglyceride levels were ((105.65±20.62)%) and (1.38(1.05, 1.75) mmol/L) in dRVVT single-positive group, which were lower than those in SCT single-positive group with values of ((117.05±20.86)% and 1.60(1.29,2.36) mmol/L), the differences were statistically significant (all P<0.05). Conclusion:There were significant differences between LA positive and LA negative cerebral infarction patients in laboratory examination. In LA positive cerebral infarction patients, the levels of fibrinogen, homocysteine, hs-CRP, white blood cells, neutrophil and erythrocyte sedimentation rate were higher, while the levels of anticoagulant protein antithrombin Ⅲ and protein C were lower. It is of great significance to pay close attention to the level and change of laboratory related risk factors in patients with LA positive cerebral infarction and give early intervention and treatment for the prevention of the occurrence and recurrence of cerebral infarction.
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In order to adapt to the development of higher medical education, it is imperative to carry out a student-centered teaching reform of pathophysiology guided by the cultivation of "clinical competence". The main contents of this teaching reform of pathophysiology include: the teaching content layout has been reconstructed to promote classroom teaching with clinical manifestation, new media means such as blackboard online teaching system, WeChat public platform and Chaoxing virtual classroom have been applied to assist students in their learning, and students are encouraged to conduct literature retrieval and reading, and then make presentation PPT for a literature of interest and report to all students to cultivate students' independent learning and sustainable development ability via flipped classroom. The practice shows that the student-centered teaching reform of pathophysiology guided by the cultivation of "clinical competence" has gained successful results.
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Objective:To evaluate the role of stimulator of interferon genes (STING) signaling pathway in carbon monoxide (CO)-releasing molecule-3 (CORM-3)-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 320-380 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), ischemia-reperfusion group (IR group), CORM-3 group (C group) and STING agonist ADU-S100 group (A group).Hepatic ischemia-reperfusion injury models were developed by reversible ligation of left middle hepatic artery, portal vein and bile duct branches for 45 min, followed by reperfusion in anesthetized animals in IR, C and A groups.In group C, CORM-3 4 mg/kg was injected into the femoral vein immediately after reperfusion.The equal volume of normal saline containing dimethyl sulfoxide was injected into the femoral vein in S, IR and A groups.At 1.5 h after injection into the femoral vein, ADU-S100 10 mg/kg was intraperitoneally injected in A group, and the equal volume of normal saline was given instead in S, IR and C groups.The serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were determined at 3 h of reperfusion.The rats were sacrificed at 12 h of reperfusion, and liver tissues were collected for determination of the content of CO (by colorimetry), expression of interleukin-1beta (IL-1β), IL-18, Bcl-2, Bax, interferon regulatory factor 3 (IRF3), phosphorylated IRF3 (p-IRF3), STING, NOD-like receptor protein 3 (NLRP3), aspirin D (GSDMD) and activated caspase-1 (by Western blot), and pyroptosis and apoptosis rates of hepatocytes (by immunofluorescence staining).The liver injury was scored. Results:Compared with group S, the serum ALT and AST concentrations, liver injury score, CO content, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, and the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group IR ( P<0.05).Compared with group IR, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly decreased, the CO content was increased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was down-regulated, and the Bcl-2/Bax ratio was increased in group C ( P<0.05).Compared with group C, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, the CO content was decreased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group A ( P<0.05). Conclusions:The mechanism by which CORM-3 attenuates hepatocyte pyroptosis and apoptosis may be related to the inhibition of activation of STING signaling pathway in a rat model of hepatic ischemia-reperfusion.
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Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.
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The development of an effective scaffold for bone defect repair is an urgent clinical need. However, it is challenging to design a scaffold with efficient osteoinduction and antimicrobial activity for regeneration of bone defect. In this study, we successfully prepared a hydroxyapatite (HA) porous scaffold with a surface-specific binding of peptides during osteoinduction and antimicrobial activity using a three-dimensional (3D) printing technology. The HA binding domain (HABD) was introduced to the C-terminal of bone morphogenetic protein 2 mimetic peptide (BMP2-MP) and antimicrobial peptide of PSI10. The binding capability results showed that BMP2-MP and PSI10-containing HABD were firmly bound to the surface of HA scaffolds. After BMP2-MP and PSI10 were bound to the scaffold surface, no negative effect was observed on cell proliferation and adhesion. The gene expression and protein translation levels of type I collagen (COL-I), osteocalcin (OCN) and Runx2 have been significantly improved in the BMP2-MP/HABP group. The level of alkaline phosphatase significantly increased in the BMP2-MP/HABP group. The inhibition zone test against Staphylococcus aureus and Escherichia coli BL21 prove that the PSI10/HABP@HA scaffold has strong antibacterial ability than another group. These findings suggest that 3D-printed HA scaffolds with efficient osteoinduction and antimicrobial activity represent a promising biomaterial for bone defect reconstruction.
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Objective:To explore the early warning value of carbapenem-resistant Klebsiella pneumoniae (CRKP) positivity in liver transplantation recipients with rectal swabs, examine the risk factors of CRKP bloodstream infection and provide the relevant treatments.Methods:From June 2018 to December 2019 in Organ Transplantation Research Institute Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science & Technology, 148 cases of liver transplantation recipients with positive CRKP rectal swabbing were recruited. Clinical data were retrospectively analyzed. And the risk factors of CRKP bloodstream infections were examined for intervention and non-intervention groups to observe the effect of interventions of CRKP bloodstream infections.Results:Among them, 23 cases (15.5%) were positive for CRKP and 5 cases (21.7%) were infected with CRKP bloodstream. Rectal swab culture was negative in 125 cases and no bloodstream infection occurred. Long-term use of broad-spectrum antimicrobial agents, severe basic diseases (severe hepatitis), postoperative delayed graft liver function recovery, acute renal failure requiring renal replacement therapy (RRT) and postoperative anti-thymocyte globulin (ATG) induction were risk factors. In intervention group, there were 2 cases (11.1%) of 18 patients with positive CRKP in rectal swab culture in late stage. Among 5 CRKP-positive recipients without intervention, 3 cases (60%) developed later CRKP bloodstream infection. The incidence of bloodstream infection was significantly lower in intervention group than that in non-intervention group ( P<0.05). Conclusions:Rectal swab culture for liver transplantation recipients provides early warning for CRKP bloodstream infection. Interventions for CRKP positive high-risk recipients with rectal swab culture may reduce the occurrence of CRKP bloodstream infection and lower the risk of CRKP bloodstream infection in liver transplantation recipients.
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Objective:To investigate the value of two-dimensional ultrasound combined with shear wave elastography (SWE) in assessing perineal body characteristics in patients with stress urinary incontinence(SUI).Methods:Sixty-four patients with stress urinary incontinence from December 2019 to August 2020 in the Affiliated Hospital of Qingdao University were selected as the SUI group, in addition, seventy healthy females at the same time were selected as the control group. The clinical information data were collected, two-dimensional ultrasound and SWE examination were performed to obtain the perineal body length, height, perimeter, area and the maximum(Emax) and the mean(Emean) modulus of elasticity both at the resting and maximum Valsalva conditions, ROC curve was plotted to evaluate the effectiveness of elastic modulus in evaluating perineal body in SUI.Results:In the resting state, the length, height, perimeter and area of perineal body in the SUI group were not significantly different from those of the control group ( P=0.590, 0.291, 0.082, 0.063). At the maximum Valsalva, the perineal body length, height, perimeter and area in the SUI group were significantly different from those of the control group ( P=0.005, 0.010, 0.001, 0.008). In the resting, the Emax and Emean values of perineal body elastic modulus in the SUI group were higher than those in the control group, but the difference was not statistically significant [(36.61±9.81)kPa vs (34.66±10.38)kPa, (27.43±9.78)kPa vs (26.97±8.85)kPa, all P>0.05]. At the maximum Valsalva, the Emax and Emean of the SUI group were significantly smaller than those of the control group, with statistically significant difference[(47.73±8.03)kPa vs (58.06±10.02)kPa, (35.78±7.89)kPa vs (44.33±9.62)kPa, all P<0.001]. The area under ROC curve of Emax and Emean at the maximum Valsalva was 0.738 and 0.647 respectively, the Emax was better than the Emean in assessment of the characteristics of perineal body in SUI patients. Conclusions:Two-dimensional ultrasound combined with SWE technique can quantitatively evaluate the characteristics of perineal body and provide an important imaging method for the diagnosis of SUI.
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Objective:To analyze the clinical characteristics and risk factors of clopidogrel resistance after intracranial arterial stent implantation in patients with ischemic cerebrovascular disease.Methods:Retrospective case-control study was used.A total of 360 patients with ischemic cerebrovascular disease hospitalized in Beijing Tiantan Hospital from January 2017 to December 2018 were selected.All patients received intracranial arterial stenting and received double anti-platelet drugs after operation.Patients were divided into clopidogrel resistance group and non-resistance group according to the inhibition rate of platelet aggregation measured by thromboelastography.Clinical data and laboratory indicators of patients in the two groups were compared using two independent sample T tests and Mann-Whitney U tests, and possible risk factors of clopidogrel resistance were analyzed by Logistic regression.Results:White blood cell (WBC) count, neutrophils count, lymphocyte count, cholesterol, LDL cholesterol, and serum homocysteine levels in the clopidogrel non-resistant group were (6.58±1.45)×10 9/L, (4.01±1.05)×10 9/L, 1.83(1.49, 2.23)×10 9/L, (3.63±0.85) mmol/L, 1.93(1.53, 2.31) mmol/L, and 14.3(11.80, 17.00) μmol/L, respectively.Compared with the clopidogrel non-resistant group, the WBC count, neutrophils count, lymphocyte count, cholesterol, LDL cholesterol and serum homocysteine levels in the clopidogrel resistant group were all higher (7.19±1.53) ×10 9/L, (4.40±1.05) ×10 9/L, 2.03(1.63, 2.58)×10 9/L, (4.02±0.99) mmol/L, 2.04(1.68, 2.78) mmol/L and 15.90(12.25, 22.20) μmol/L, respectively.The difference was statistically significant ( t=3.277, t=2.867, Z=2.457, t=3.409, Z=2.705 and Z=2.220, respectively; P value were 0.001, 0.004, 0.014, 0.001, 0.007 and 0.026, respectively). Logistic regression analysis showed that high serum homocysteine ( OR=1.031, 95% CI 1.006-1.057, P=0.015) was an independent risk factor for clopidogrel resistance. Conclusion:Patients with clopidogrel resistance have high leucocyte, blood lipid, homocysteine and other clinical characteristics.High serum homocysteine is an independent risk factor for clopidogrel resistance.
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The procurement, preservation and transportation of the donor organs directly affect the clinical prognosis of the recipients. The establishment of process optimization and quality control standards of organ procurement, preservation and transportation contributes to improving the quality and utilization rate of donor organs and reducing the medical risk. According to Guide to the Quality and Safety of Organs for Transplantation (6th edition) proposed by European Union, the 11th chapter of organ procurement, preservation and transportation was interpreted and summarized in this article.
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Objective:To investigate the risk factors of Crohn′s disease (CD)-related gastrointestinal stenosis, and to summarize and analyze the corresponding treatments.Methods:From January 2010 to December 2018, 122 patients diagnosed with CD and hospitalized in the Seventh Medical Center, PLA General Hospital were selected including 72 patients in gastrointestinal stenosis group and 50 patients in non-gastrointestinal stenosis group. The gender, age of onset, course of disease, location of lesions involved (Montreal classification), disease activity, extraintestinal manifestations, application of therapeutic drugs, and complications were compared between the two groups. The treatment of CD patients with gastrointestinal stenosis was analyzed. Multivariate logistic regression was used to analyze the risk factors of CD patients with gastrointestinal stenosis. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The age of onset of patients in gastrointestinal stenosis group was older than that in non-gastrointestinal stenosis group ((37.6±15.1) years old vs. (30.8±14.7) years old), and course of disease was longer than that of non-gastrointestinal stenosis group (72 months, 11 to 492 months vs. 45 months, 3 to 240 months); and the differences were statistically significant ( t=-2.044, Z=-2.770; P=0.018, 0.006). The proportion of patients with ileum involvement of the gastrointestinal stenosis group was lower than that of the non-gastrointestinal stenosis group (69.4%, 50/72 vs. 86.0%, 43/50), and the proportion of severe patients was higher than that of the non-gastrointestinal stenosis group (15.3%, 11/72 vs. 4.0%, 2/50); and the differences were statistically significant ( χ2=4.463 and 3.942, P=0.035 and 0.047). There were no significant differences in gender, use of therapeutic drugs, extraintestinal manifestations, application of therapeutic drugs or the incidence of complications between the patients of two groups (all P>0.05). The results of multivariate logistic regression showed that the age of onset and course of disease were risk factors of CD-related gastrointestinal stenosis ( β=0.028, odds ratio ( OR)=1.028, 95% confidence interval ( CI) 1.000 to 1.056, P=0.046; β=0.008, OR=1.008, 95% CI 1.002 to 1.015, P=0.013). Further stratified analysis revealed that the incidence rates of CD-related gastrointestinal stenosis in patients with age of onset over 40 years old and course of disease more than five years were higher than those of patients with age of onset less than 40 years old and course of disease less than five years (76.3%, 29/38 vs. 51.2%, 43/84; 68.4%, 39/57 vs. 50.8%, 33/65), and the differences were statistically significant ( OR=3.072, 95% CI 1.298 to 7.272, P=0.009; OR=2.101, 95% CI 1.002 to 4.406, P=0.048). Among the 72 CD patients with gastrointestinal stenosis, 15 cases (20.8%) were treated with medicine and nutrition, without endoscopic or surgical treatment. Fifty-two patients (72.2%) underwent surgical treatment, among them six patients (11.5%) received twice surgery, the interval between the two operations was 46 months (1 to 204 months), and eight patients (15.4%) had postoperative complications. Twenty-one patients (29.2%) were treated with endoscopic dilatation, and no complications occurred after surgery. Five patients (23.8%) underwent surgical treatment during the follow-up period. Conclusions:The age of onset over 40 years old and the course of disease more than five years are the risk factors of CD-related gastrointestinal stenosis. Individualized medical treatment is the basis for the treatment of CD-related gastrointestinal stenosis. Surgery is still the main treatment. The endoscopic treatment is safety and can delay or avoid surgery to a certain extent.
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Objective:To evaluate the effect of carbon monoxide-releasing molecule-3 (CORM-3) on blood transfusion-related acute lung injury in rats with traumatic brain injury (TBI).Methods:Seventy-two clean-grade healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 4 groups ( n=18 each) using the random number table method: sham operation group (group S), TBI group (T group), TBI plus 10 ml/kg plasma transfusion group (TP group), and TBI plus 10 ml/kg plasma transfusion plus CORM-3 group (TPC group). TBI was induced by dropping a 20-g weight from 20 cm height falling freely in anesthetized rats.Plasma 10 ml/kg was infused via the femoral vein after TBI in TP and TPC groups.The rats were sacrificed at 24 h after plasma transfusion, and lung tissues were obtained for determination of wet/dry weight (W/D) ratio, cell apoptosis, and expression of caspase-3, Bid, Bim and Puma (by Western blot). The lung injury score was calculated using the results of HE staining.Lung ultrasonography was performed for assessment of sonographic score, and the apoptosis rate was calculated by the TUNEL staining method. Results:Compared with S group, the W/D ratio, lung injury score, sonographic score and apoptosis rate were significantly increased, and the expression of activated caspase-3, Bid, Bim and Puma was up-regulated in the other three groups ( P<0.05). Compared with T group, the W/D ratio, lung injury score, sonographic score and apoptosis rate were significantly increased, and the expression of activated caspase-3, Bid, Bim and Puma was up-regulated in TP group ( P<0.05). Compared with TP group, the W/D ratio, lung injury score, sonographic score and apoptosis rate were significantly decreased, and the expression of activated caspase-3, Bid, Bim and Puma was down-regulated in TPC group ( P<0.05). Conclusion:CORM-3 can reduce acute lung injury related to blood transfusion in rats with TBI, and the mechanism may be related to inhibiting cell apoptosis in lung tissues.
