Myeloid Deletion of Cdc42 Protects Liver From Hepatic Ischemia-Reperfusion Injury via Inhibiting Macrophage-Mediated Inflammation in Mice.

BACKGROUND & AIMS: Hepatic ischemia-reperfusion injury (HIRI) often occurs in liver surgery, such as partial hepatectomy and liver transplantation, in which myeloid macrophage-mediated inflammation plays a critical role. Cell division cycle 42 (Cdc42) regulates cell migration, cytoskeleton rearrangement, and cell polarity. In this study, we explore the role of myeloid Cdc42 in HIRI. METHODS: Mouse HIRI models were established with 1-hour ischemia followed by 12-hour reperfusion in myeloid Cdc42 knockout (Cdc42mye) and Cdc42flox mice. Myeloid-derived macrophages were traced with RosamTmG fluorescent reporter under LyzCre-mediated excision. The experiments for serum or hepatic enzymic activities, histologic and immunologic analysis, gene expressions, flow cytometry analysis, and cytokine antibody array were performed. RESULTS: Myeloid deletion of Cdc42 significantly alleviated hepatic damages with the reduction of hepatic necrosis and inflammation, and reserved hepatic functions following HIRI in mice. Myeloid Cdc42 deficiency suppressed the infiltration of myeloid macrophages, reduced the secretion of proinflammatory cytokines, restrained M1 polarization, and promoted M2 polarization of myeloid macrophages in livers. In addition, inactivation of Cdc42 promoted M2 polarization via suppressing the phosphorylation of STAT1 and promoting phosphorylation of STAT3 and STAT6 in myeloid macrophages. Furthermore, pretreatment with Cdc42 inhibitor, ML141, also protected mice from hepatic ischemia-reperfusion injury. CONCLUSIONS: Inhibition or deletion of myeloid Cdc42 protects liver from HIRI via restraining the infiltration of myeloid macrophages, suppressing proinflammatory response, and promoting M2 polarization in macrophages.

Selective Oxidation of Cyclohexane to Cyclohexanol/Cyclohexanone by Surface Peroxo Species on Cu-Mesoporous TiO2.

Selective oxidation of cyclohexane to cyclohexanol/cyclohexanone (KA-oil) is an important chemical process, which is still constrained by low conversion and selectivity and high energy consumption. In this study, Cu-doped mesoporous TiO2 (Cu-MT) has been successfully synthesized via calcinating MIL-125(Ti) doped with copper acetylacetonate, which shows high reactivity in selective oxidation of cyclohexane to KA-oil by persulfate (PS) with the desirable cyclohexane conversion of 16.8% and a selectivity of 98.0% under mild conditions and the low ratio of PS/cyclohexane of 1:1. A series of characterizations and density functional theory calculations reveal that the doped Cu(I,II) on Cu-MT is the reactive site for non-radical activation of PS with the moderate elongation of the O-O bond in PS, which then abstracts 1H (1H+ + 1e-) from cyclohexane to form Cy• and eventually KA-oil. This study gives new insight on the importance of moderately activated PS in selective oxidation of C-H.

Executive function characteristics of preschool children with high functioning autism and children with global developmental delay / 中华行为医学与脑科学杂志

Objective:To investigate the characteristics of executive function of preschool children with high functioning autism spectrum disorder (HFA) and with global developmental delay (GDD), and the differences among HFA, GDD and typically developmental (TD) children.Methods:From January 2020 to January 2021, 20 male HFA, 20 male GDD and 20 male TD children aged 4-6 years who visited the Psychological Behavior Clinic of the Child Health Department of Guiyang Maternal and Child Health Hospital and the Developmental Behavior Clinic of the Children Health Department of the Ninth People's Hospital in Chongqing were selected for comparative study.The executive function of HFA, GDD and TD children was assessed with the behavior rating scale of executive function-preschool version(BRIEF-P) and the executive function task program (EF-TOUCH). SPSS 26.0 software was used for statistical analysis, including variance test, independent sample t-test, χ2 test, Kruskal Wallis test and Mann-Whitney U test. Results:In the EF-TOUCH program task, the accuracy of the three groups of children's performance in the pig task (Pig), the silly sounds game (SSG), the working memory task (pick the picture, PTP) and the task of cognitive flexibility (something's the same, STS) were statistically different(Pig: HFA group: 0.87(0.76, 0.99), GDD group: 0.97(0.85, 0.99), TD group: 1.00(0.98, 1.00), χ2=15.646, P<0.001; SSG: HFA group: 0.76(0.53, 0.91), GDD group: 0.76(0.65, 0.99), TD group: 0.94(0.76, 1.00), χ2=6.448, P=0.040; PTP: HFA group: 0.66±0.18, GDD group: 0.66±0.19, TD group: 0.78±0.11; F=3.221, P=0.048; STS: HFA group: 0.67(0.63, 0.70), GDD group: 0.72(0.46, 0.78), TD group: 0.87(0.83, 0.90), χ2=26.898, P<0.001). The accuracies of Pig, SSG, PTP and STS in HFA group were significantly lower than those in TD group(all P<0.05), and the accuracies of Pig and STS in GDD group were significantly lower than those in TD group(both P<0.05). In inhibition control, there were statistically differences in response time of Pig and SSG among the three groups (Pig: HFA group: (1 694.36±222.83)ms, GDD group: (1 513.46±244.91)ms, TD group: (1 444.84±197.95)ms, F=5.810, P=0.005; SSG: HFA group: (2 202.42±195.58)ms, GDD group: (2 116.52±323.27)ms, TD group: (1 937.17±252.74)ms, Z=4.610, P=0.014). There were no significant differences in the reaction time of Arrows task ( P>0.05). There were significant differences in BRIEF-P inhibition control, organizational planning, inhibition self-regulation, cognitive flexibility and total scores among the three groups ( P<0.05), while there were no significant differences in the scores of other factors and dimensions ( P>0.05). Conclusion:The executive function of pre-school children with high functioning autism spectrum disorder and children with global developmental delay is impaired.The executive function of children with high functioning autism spectrum disorder and children with global developmental delay is significantly different from that of typically developmental children of the same age.Moreover, the executive function of children with HFA is more severely damaged from all components than that of children with GDD.

Comparison of executive function between preschool-aged male children with high functioning autism and typically developing children / 中华行为医学与脑科学杂志

Objective:To discuss the executive function (EF) characteristics of preschool aged male children diagnosed as high-functioning autism (HFA), and to compare the EF differences between HFA and typically developing (TD) children.Methods:Twenty-six preschool male HFA children aged 4-5 years old and chronological age and gender matched TD children were recruited respectively. Parent questionnaire behavior rating scale of executive function-preschool version (BRIEF-P) and executive function battery EF-TOUCH were adopted to explore the EF characteristics and the differences between the two groups. SPSS 22.0 software was used for statistical analysis, including descriptive statistics, χ2 test, t-test and Mann-Whitney U test. Results:EF-TOUCH results demonstrated significant differences with correct proportions of inhibition tasks (Arrow, Pig, silly sounds game (SSG)), working memory task (pick the picture (PTP)) and cognitive flexibility task (something′s the same (STS)) between groups (Arrow: Z=-2.278, P=0.023; Pig: Z=-2.599, P=0.009; SSG: Z=-1.985, P=0.047; PTP: t=2.635, P=0.011; STS: Z=-3.556, P=0.000). The accuracy rate in HFA group were significantly lower than TD group (HFA group: Arrow: 0.76 (0.57, 0.92), Pig: 0.95 (0.90, 1.00), SSG: 0.85 (0.57, 0.94), PTP: 0.74±0.11, STS: 0.77 (0.62, 0.90); TD group: Arrow: 0.92 (0.78, 0.95), Pig: 1.00 (0.98, 1.00), SSG: 0.94 (0.82, 1.00), PTP: 0.81±0.09, STS: 0.93 (0.82, 0.97)). Reaction time(RT) of Pig task was longer in HFA group than TD group (HFA: (1 624.29±234.33)ms; TD: (1 481.39±220.78)ms, t=-2.263, P=0.028). RTs of Arrow and SSG for both groups were not significantly different ( P>0.05). Children of HFA group exhibited worse inhibition and working memory(WM) than TD children in BRIEF-P(inhibition: HFA group (60.73±10.47), TD group (54.73±6.87); WM: HFA group (68.04±11.51), TD group (61.69±8.44))( t=-2.443, P=0.018; t=-2.267, P=0.028 respectively). No significant differences were found in the rest factors and domains for both groups (all P>0.05). Conclusions:Apparent inhibition control, working memory and cognitive flexibility deficiencies were found in preschool aged male HFA children. There are significant EF differences between preschool aged male HFA and typically developing children.

Effects of Transcranial Direct Current Stimulation over Vagus Nerve on Dysphagia after Stroke / 中国康复理论与实践

Objective:To study the effect of transcranial direct current stimulation (tDCS) regulating excitability of the vagus nerve on dysphagia after stroke. Methods:From September, 2020 to February, 2021, 28 patients with dysphagia after stroke were randomly divided into control group (n = 14) and tDCS group (n = 14). Both groups accepted swallowing function training, and tDCS group received anodal tDCS over vagus nerve, while the control group received sham tDCS. They were assessed with modified Mann Assessment of Swallowing Ability (MMASA) and Australian Therapy Outcome Measures (AusTOMs)-swallowing scale before and after treatment. Results:The scores of MMASA (|t| > 5.593, P < 0.001) and AusTOMs swallowing scale (|Z| > 2.121, P < 0.05) increased in both groups after treatment, and were higher in tDCS group than in the control group (|t| = 2.439, |Z| = 2.079, P < 0.05). Conclusion:Anodal tDCS over vagus nerve may further release dysphagia after stroke.

Efficacy of family rehabilitation treatment performed by parents under the guidance of professionals in children with autism spectrum disorder: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy of family rehabilitation treatment performed by parents under the guidance of professionals in children with autism spectrum disorder (ASD).@*METHODS@#In the prospective study, 60 children with ASD, aged 24-60 months, were randomly divided into an observation group and a conventional group. The parents of the children in the conventional group received an online training on basic knowledge and rehabilitation training of ASD alone, and those in the observation group received the online training and performed family rehabilitation treatment under the guidance of a professional team. Psycho-Education Profile Third Edition (PEP-3) and Childhood Autism Rating Scale (CARS) were used to evaluate the changes in related abilities after intervention.@*RESULTS@#After 6 months of intervention, the scores of all dimensions of the PEP-3 scale in the observation group and most dimensions of the conventional group significantly increased (@*CONCLUSIONS@#An online training on basic knowledge and rehabilitation training of ASD for parents can improve the abilities and core clinical symptoms of children with ASD. The family rehabilitation treatment model with a team of professionals as the resource platform and parents as the performer has a more significant efficacy on improving the language, sports, and other abilities and alleviating the severity of the symptoms in children with ASD.

Rosiglitazone Inhibits Activation of Hepatic Stellate Cells via Up-Regulating Micro-RNA-124-3p to Alleviate Hepatic Fibrosis.

BACKGROUND: The activation of hepatic stellate cells (HSCs) is involved in hepatic fibrogenesis and is regulated by the decreased expression of peroxisome proliferator-activated receptor γ (PPARγ). Rosiglitazone (RGZ) is a highly potent agonist of PPARγ. AIMS: To clarify molecular regulatory mechanism of RGZ in the activation of HSCs in hepatic fibrosis. METHODS: A mouse model of hepatic fibrosis was established by carbon tetrachloride with or without RGZ intervention. A vector carrying pcDNA-HOTAIR was constructed and injected into a mouse model. HSCs were isolated from liver tissue and activated by transforming growth factor-ß. The expression of miR-124-3p, HOTAIR, Col1A1, α-SMA, and PPARγ mRNAs was measured by quantitative real-time PCR. The level of PPARγ was measured by Western blotting. The interaction between HOTAIR and PPARγ was assessed by RNA immunoprecipitation (RIP) and RNA pull-down. The target gene of miR-124-3p was determined by luciferase reporter assay and RNA interference approaches. RESULTS: The expression of Col1A1 and α-SMA was reduced after RGZ intervention. Different expressions of HOTAIR and miR-124-3p were observed in liver tissue and HSCs. The luciferase reporter assay and RNA interference approaches indicated that miR-124-3p negatively regulated HOTAIR expression. RIP and RNA pull-down results revealed that PPARγ was interacted by HOTAIR. The therapeutic effect of RGZ on hepatic fibrosis was reversed by overexpression of HOTAIR. CONCLUSIONS: RGZ inhibits the activation of HSCs by up-regulating miR-124-3p. The silencing of HOTAIR by miR-124-3p in HSC activation provided the foundation to understand interactions of ncRNAs and potential treatment target in hepatic fibrosis.

Linking 1D Transition-Metal Coordination Polymers and Different Inorganic Boron Oxides To Construct a Series of 3D Inorganic-Organic Hybrid Borates.

Three inorganic-organic hybrid borates, M(1,4-dab)[B5O7(OH)3] [M = Zn (1), Cd (2), 1,4-dab = 1,4-diaminobutane)] and Co(1,3-dap)[B4O7] (3, 1,3-dap = 1,3-diaminopropane), which integrated characteristics of 1D coordination polymers and 1D/3D inorganic boron oxides have been obtained under solvothermal conditions. Compounds 1 and 2 are isostructural and crystallize in a centrosymmetric space group P21/c; the 3D achiral structures of 1 and 2 consist of the nonhelical Zn/Cd-1,4-dap coordination polymers and 1D B-O chains. Compound 3 crystallizes in a chiral space group P43212; the helical Co-1,3-dap coordination polymer chains are entrained within a 3D B-O network and finally form the chiral framework. Compounds 1-3 represent good examples of using coordination polymers to construct mixed-motif inorganic-organic hybrid borates. Compounds 1 and 2 display blue luminescence when excited with UV light.

Ethyl pyruvate reverses development of Pseudomonas aeruginosa pneumonia during sepsis-induced immunosuppression.

Sepsis is characterized by an innate immune response and the following immune dysfunction which can increase the emergence of secondary infections. Ethyl pyruvate (EP) has multiple immunoregulation functions in several serious illnesses, such as burn injury, severe sepsis and acute respiratory syndrome. However, little data was shown the effect of EP administration on immunosuppression post-CLP and the following secondary infection. The cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa (PA) was used as a clinically relevant two-hit model of sepsis. We assessed the survival rate, lung damage and lung bacterial clearance in vehicle or EP treatment group to demonstrate the lung response to Pseudomonas aeruginosa of septic mice. Then cytokines including lung IL-6, IL-1ß, IL-10 and plasma HMGB1, apoptosis of splenic immune cells and Foxp3 level on regulatory T cells (Tregs) were studied to demonstrate the mechanisms of EP administration on two-hit mice. We found that the susceptibility of septic mice to Secondary Pseudomonas aeruginosa pneumonia could be down-regulated by ethyl pyruvate treatment and the protective effects of EP may via decreasing lung IL-10 and plasma HMGB1 expression, inhibiting the function of Tregs and relieving the apoptosis of splenic immune cells. The "immune paralysis" post-sepsis still remains a rigorous challenge for curing sepsis, our study may aid in the development of new therapeutic strategies to this problem.

Study on the relationship between serum oxytocin levels and social competence in children with autism / 重庆医学

Objective To explore the difference of serum oxytocin levels between autistic children and healthy children at the age of 3-5,and the relationship between serum oxytocin levels and social competence in children with autism.Methods Twenty-five autistic children and twenty healthy children were tested by an enzyme-linked immunosorbent assay to evaluate the oxytocin levels;the SRS was used to evaluate social competence of children with autism.Results Mann-Whitney test showed there were significantly differences in oxytocin level between autistic children and healthy children(P<0.05).The social competence of autistic children was negatively correlated to oxytocin levels(r=-0.735,P<0.01).Multiple liner regression analyses showed that oxytocin level was an impact factor of the social competence of autistic children(F=11.931,P<0.01).Conclusion This study indicates that the serum oxytocin level maybe a factor which influence the social competence of autistic children.

Precision medicine in breast cancer research / 复旦学报（医学版）

Breast cancer is the most common malignant tumor in women,and its incidence has increased in recent years in China.Evidence-based medicine has made great achievements in systemetic treatment of breast cancer,which laid the foundation for standardized treatment of breast cancer.Additionally,precision medicine provides more refined,individualized treatment for breast cancer patients.Breast cancer research in multiomic analysis,ctDNA,intratumour heterogeneity and interaction between tumor and microenvironment has broad prospects.

[Treatment of calcaneal fractures by fixation of Kirschner needle and thread cancellous bone screw through sinus tarsi interstice].

OBJECTIVE: To explore the effect of fixation of Kirschner needle and thread cancellous bone screw through the sinus tarsi interstice for the treatment of calcaneal fractures. METHODS: From January 2009 to December 2012,20 patients with calcaneal fracture were treated by minimally invasive Kirschner wire and threaded cancellous bone screw fixation and bone graft,including 12 males and 8 females with an average age of 39 years old ranging from 21 to 65. Among them, 8 cases were left foot, 12 were right foot. According to Sanders's classification, 8 cases were type II, 10 cases were type III, 2 cases were type IV. RESULTS: All patients were followed up from 6 to 16 months with an average of 12 months. The incision were healed. Böhler angle were increased from preoperative (17.75 +/- 4.22) degrees to postoperative (26.85 +/- 7.37) degrees (t = 4.308, P = 0.000). Gissane angle were reduced from preoperative (137.05 +/- 24.91) degrees to postoperative (113.75 +/- 13.17) degrees (t = 7.083, P = 0.000). At 3 months after operation, the scores of AOFAS were 85.50 +/- 7.99; the results were excellent in 5 feet and good in 11 feet, fair in 3 feet, and poor in 1 foot. CONCLUSION: Minimally invasive fixation of Kirschner needle and thread cancellous bone screw fixation is a simple operation, it can get reliable fixation, easy to remove, low cost, less postoperative complications, and it is a good treatment of calcaneal fracture.

[Inflammatory pseudotumor-like follicular dendritic cell tumor of spleen].

OBJECTIVE: To study the clinicopathologic features of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen. METHODS: One case of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen was examined macroscopically and microscopically. Immunohistochemical study for CD21, CD23, CD35, clusterin, S-100 protein, vimentin, smooth muscle actin, CD1a, CD68, ALK protein, CD30, CD31, CD34, CD3 and CD20 was performed on formalin-fixed, paraffin-embedded sections by standard EnVision method. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was also carried out. RESULTS: Macroscopically, inflammatory pseudotumor-like follicular dendritic cell tumor was large in size, tan-colored, soft to rubbery in consistance and associated with central hemorrhage and necrosis. Histological examination showed scattered follicular dendritic cells admixed with abundant lymphocytes and plasma cells in the background, simulating inflammatory pseudotumor. On high-power magnification, the follicular dendritic cells possessed a moderate amount of pale to lightly eosinophilic cytoplasm, with indistinct cell borders. The nuclei were ovoid or spindly, with vesicular or stippled chromatin and small distinct, often centrally located, nucleoli. Some of the tumor cells showed nuclear pleomorphism and contained irregular foldings of nuclear membrane, coarse chromatin and prominent eosinophilic nucleoli. Mitotic figures were rarely identified. Immunohistochemical study showed that the tumor cells were positive for vimentin, clusterin, smooth muscle actin and CD68. They were weakly and focally positive for CD35 and S-100 protein, but negative for CD21, CD23, CD1a, ALK protein, CD30, CD31 and CD34. Most of the background lymphocytes were of T-lineage (CD3-positive) ,some were CD20 (B-cell marker)-positive. EBV RNA was demonstrated in the tumor cells by in-situ hybridization analysis. CONCLUSIONS: Inflammatory pseudotumor-like follicular dendritic cell tumor is a rarely encountered low-grade malignancy with distinctive morphologic pattern. It is associated with EBV infection.

Inflammatory pseudotumor-like follicular dendritic cell tumor of spleen / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen.</p><p><b>METHODS</b>One case of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen was examined macroscopically and microscopically. Immunohistochemical study for CD21, CD23, CD35, clusterin, S-100 protein, vimentin, smooth muscle actin, CD1a, CD68, ALK protein, CD30, CD31, CD34, CD3 and CD20 was performed on formalin-fixed, paraffin-embedded sections by standard EnVision method. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was also carried out.</p><p><b>RESULTS</b>Macroscopically, inflammatory pseudotumor-like follicular dendritic cell tumor was large in size, tan-colored, soft to rubbery in consistance and associated with central hemorrhage and necrosis. Histological examination showed scattered follicular dendritic cells admixed with abundant lymphocytes and plasma cells in the background, simulating inflammatory pseudotumor. On high-power magnification, the follicular dendritic cells possessed a moderate amount of pale to lightly eosinophilic cytoplasm, with indistinct cell borders. The nuclei were ovoid or spindly, with vesicular or stippled chromatin and small distinct, often centrally located, nucleoli. Some of the tumor cells showed nuclear pleomorphism and contained irregular foldings of nuclear membrane, coarse chromatin and prominent eosinophilic nucleoli. Mitotic figures were rarely identified. Immunohistochemical study showed that the tumor cells were positive for vimentin, clusterin, smooth muscle actin and CD68. They were weakly and focally positive for CD35 and S-100 protein, but negative for CD21, CD23, CD1a, ALK protein, CD30, CD31 and CD34. Most of the background lymphocytes were of T-lineage (CD3-positive) ,some were CD20 (B-cell marker)-positive. EBV RNA was demonstrated in the tumor cells by in-situ hybridization analysis.</p><p><b>CONCLUSIONS</b>Inflammatory pseudotumor-like follicular dendritic cell tumor is a rarely encountered low-grade malignancy with distinctive morphologic pattern. It is associated with EBV infection.</p>

[Clinical analysis of early stage thrombolytic therapy with venous urokinase for acute myocardial infarction in 24 cases].

OBJECTIVE: To observe the therapeutic effect of early stage thrombolytic therapy with venous urokinase for acute myocardial infarction (AMI). METHOD: The clinic data of 24 patients treated with early stage thrombolytic therapy with venous urokinase and 18 conventional therapy were reviewed, and the repatency of the coronary artery and T-wave inversion within 24 h after the treatment were evaluated. RESULT: The repatency rate of urokinase group and conventional therapy group was 62.5% and 15.0%, respectively, showing significant difference (P<0.05). Shorter delay of administration of thrombolytic therapy after infarction onset resulted in higher rate of repatency. CONCLUSION: Early stage thrombolytic therapy with venous urokinase can improve the therapeutic effect and reduce the mortality rate of AMI, and is therefore recommended for clinical application.

Synergetic transactivating effect of HCV core and HBV X proteins on SV40 early promoter/enhancer / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate the synergetic transactivating effects of HCV core and HBV X proteins.</p><p><b>METHODS</b>HCV core and HBV X protein-expressing plasmids were constructed with the vector pcDNA3.1(-). The plasmids were transfected into HepG2 cells and cotransfected Hep2 cells with reporter plasmid Psv-lacZ by lipofectamine plus reagents. The virus proteins produced in transient expression system were detected at the transcription and translation levels. The activity of b-galactosidase was detected, which reflected the transactivating function of the proteins.</p><p><b>RESULTS</b>The expression of plasmids were detected in soluble protein cell extracts of transiently transfected HepG2 cells. HCV core protein activated the b-galactosidase expression at a value 4.9 times higher than the control, while HBV X protein activated at a value 3.5 times. It arrived at 9 times transfected with the plasmids simultaneously. The activating effect increased in relation to the amount of plasmids.</p><p><b>CONCLUSIONS</b>The results suggested that the two kinds of virus proteins have transactivating effect on SV40 early promoter/enhancer, and they acted synergistically. These contribute to explain the mechanisms of liver injury or tumorigenesis induced by HCV or/and HBV infection.</p>