Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To study the antifungal activity of a new series of triazole compounds with n-propyl side chain and disubstituted benzyl structure. Methods Eleven target compounds were designed and synthesized. The structures were confirmed by ¹H NMR, and some compounds were confirmed by ¹³C NMR or HRMS. Three fungal strains were selected as experimental strains, and the antifungal activity was tested in vitro according to the standardized antifungal sensitivity test method recommended by National Committee for Clinical Laboratory Standards (NCCLS). Results Compound B11 showed better activity against candida albicans SC5314 than fluconazole and was comparable to posaconazole; Compounds B10, B11 and B4 showed better activity against cryptococcus neoformanis H99 than fluconazole, while compounds B2, B3, B5, B6 and B7 showed similar activity to fluconazole against cryptococcus neoformanis H99; while all compounds showed poor activity against aspergillus fumigatus. Conclusion Some of the target compounds with n-propyl side chain and disubstituted benzyl group structure had certain antifungal activity and could be identified as potential lead antifungal drugs.

Objective To investigate the pathogenesis of superficial mycosis among naval trainees, and observe the efficacy of a novel antifungal drug. Methods A questionnaire survey was conducted on the onset, medication and recurrence of superficial fungal infection among the trainees from January, 2020 to July, 2020. At the same time, the new antifungal drug sulconazole nitrate spray was provided for treatment and the drug efficacy was observed. Results The participants generally lacked understanding and attention to superficial fungal infections. The incidence rate of superficial fungal infection was 52%, of which 76.2% of patients had recurrence of superficial fungal infection. The sulconazole nitrate spray showed great effect against these infections. Conclusion The trainees should understand the causes of superficial fungal infection through health education and seek medical treatment and medication in time. The cure rate of superficial fungal infections could only be improved through the collaborative management of the school, hospital, and trainees to reduce the impact of these infections on naval trainees’ work and life.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective To explore the early prognosis and the risk factors of delayed graft function (DGF) of the recipients undergoing liver transplantation from donor liver with moderate-to-severe steatosis. Methods Clinical data of 475 donors and 475 recipients undergoing liver transplantation from donor liver of organ donation after citizen's death were retrospectively analyzed. According to the classification criteria of steatosis proposed by Australia National Liver Transplantation Unit (ANLTU), all recipients were divided into the S0 group (no steatosis, n=308), S1 group (mild steatosis, n=97), S2 group (moderate steatosis, n=52) and S3 group (severe steatosis, n=18), respectively. The early postoperative death and incidence of postoperative complications were statistically compared among each group. The risk factors from donors, recipients and operation leading to DGF were analyzed by univariate and multivariate logistic regression models. Results The incidence of postoperative DGF in the S2 and S3 groups was significantly higher than that in the S1 and S0 groups (all P < 0.05). The incidence of postoperative DGF in the S3 group was remarkably higher than that in the S2 group (P < 0.05). The early postoperative fatality, the incidence of primary nonfunction (PNF) of the transplant liver, postoperative bleeding, infection, biliary complications and vascular complications did not significantly differ among each group (all P > 0.05). Univariate regression analysis showed that severe steatosis of donor liver, long cold ischemia time, high model for end-stage liver disease (MELD) score and tumors of the recipients before operation were the risk factors of DGF (all P < 0.05). Multivariate logistic regression analysis demonstrated that moderate-to-severe steatosis of donor liver, cold ischemia time > 8 h and MELD score > 30 of the recipients were the independent risk factors for early postoperative DGF. Conclusions The early-stage incidence of DGF after adult liver transplantation from donor liver with moderate-to-severe steatosis is high, whereas it does not affect the early survival rate of the recipients. The selection of donor liver with moderate-to-severe steatosis should be considered in combination with cold ischemia time of the donors and MELD score of the recipients before operation, etc.

Objective To investigate the effect of high-fat diet(HFD)on liver damage caused by autoimmune hepatitis(AIH)in mice.Methods Fifty C57BL/6 male mice were divided randomly into four groups:standard chow(SC)group,HFD group,AIH + SC group and AIH+ HFD group.AIH model was built after feeding for one week and all mice were sacrificed after four weeks.Liver and spleen tissues and serum were collected. Liver histopathology was detected by HE staining. Serum alanine aminotransperase(ALT)and aspartate aminotransferase(AST)levels were measured.Western blot analysis and real-time polymerase chain reaction(PCR)analysis were used to test the expressions of NLR pyrin domain containing 3(NLRP3)and cysteinyl aspartate specific proteinase 1(Caspase-1).The concentrations of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α were analyzed using enzyme linked immunosorbent assay technology.The amount of Th17 cells in spleen was analyzed by FACS.Means among groups were analyzed with one-way ANOVA.SNK-q analysis was used for groups with homogeneity of variance, while nonparametric test was used for groups with variance nonhomogeneity.Results Histologically,the H&E staining of liver tissue from HFD group showed adipose degeneration,and there was inflammation around vessel in AIH+SC group.Moreover,in AIH+HFD group,the inflammation was more serious with mildly adipose degeneration.Compared with SC group,serum levels of ALT and AST increased in HFD group and AIH +SC group,and greatest increase was observed in AIH+ HFD group.The differences were statistically significant(F=57.12 and 37.58, both P<0.05).The proportions of Th17 cells in SC group,HFD group,AIH+ SC group and AIH+HFD group were(2.98 ± 0.90)%,(6.89 ± 0.99)%,(6.47 ± 1.08)% and(9.96 ± 0.83)%, respectively.The differences among all groups were statistically significant(F=54.05,P<0.05).The concentrations of IL-1β,IL-6 and TNF-α in each group were as follows:SC:IL-1β[(7.62 ± 2.81)ng/L],IL-6 [(106.54 ± 53.08)ng/L],T NF-α[(107.26 ± 36.20)ng/L];HFD:IL-1β[(25.06 ± 7.09)ng/L],IL-6 [(220.11 ± 47.41)ng/L],TNF-α[(273.77 ± 33.62)ng/L];AIH+SC:IL-1β[(17.49 ± 5.68)ng/L],IL-6 [(260.73 ± 50.29)ng/L],TNF-α[(250.49 ± 81.63)ng/L];AIH+ HFD:IL-1β[(52.04 ± 10.22)ng/L], IL-6[(785.93 ± 70.91)ng/L],TNF-α[(913.97 ± 64.57)ng/L].The differences were statistically significant(F=44.66,242.15 and 233.49,respectively,all P<0.05).The expressions of NLRP3 and Caspase-1 were significantly increased in AIH+ HFD group than the other three groups(all P<0.05). Conclusions High-fat diet potentiates liver damage induced by autoimmune hepatitis,which might relate to the secretion of pro-inflammatory cytokines,the activation of Th17 cells and the NLRP3 inflammasome as well as pyroptosis.