ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

Objective To construct the triple pre-rehabilitation program for the patients undergoing pancreaticoduodenectomy to provide a theoretical basis for the preoperative management of this operation mode.Methods The raft plan was formed by the literature research and group discussion,then the experts were invited to conduct the two rounds of expert consultation,and the final draft of the plan was finally formed.Results The draft plan included the 3 first-level items,9 second-level items and 28 third-level items.The questionnaire recovery rate of the two rounds of expert correspondence was 100%,and the authority coef-ficients were 0.88 and 0.93,respectively.The mean importance and feasibility scores of each item in the two rounds of expert consultation were ≥3.5,and the coefficient of variation was<0.25.The first draft of the final formation plan included the 3 first-level items,9 second-level items and 31 third-level items.Conclusion This program has ne-cessity,scientificity and feasibility.Clarifying the specific contents and scope of preoperative management of this operation mode could provide a theoretical basis for medical staff to carry out pre-rehabilitation.

Objective:To investigate the molecular mechanism by which neuroplastin 65 (Np65) regulates lipopolysaccharide (LPS)-induced macrophage polarization, and elucidate the effect of Np65 on macrophage polarization during inflammation.Methods:Bone marrow-derived macrophages from C57BL/6 wild-type mice and Np65 knockout mice with the same background were prepared. Quantitative real-time PCR was used to detect the expression of related genes including Nptn, CD80, CD86, TNF-α, IL-1β, IL-6, CD206, CD163, Ym1, Arg1, IL-10, CD14 and TLR4 in macrophages. The expression of CD86 and CD206 molecules on the surface of macrophages was measured by flow cytometry. Western blot was used to detect the expression of related proteins and their phosphorylation levels in macrophages including p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), p65, signal transducers and activators of transcription 3 (STAT3), Janus kinase 1 (JAK1), JAK2 and protein kinase B (AKT). Co-immunoprecipitation was used to detect the binding of Np65 to CD14 or TLR4. Immunofluorescence confocal analysis was used to identify the colocalization of Np65 with CD14 or TLR4 in the cells. One-way analysis of variance and paired Student′s t test were used for statistical analysis. Results:LPS or IL-4 could activate macrophages and upregulate the Np65 gene expression ( P<0.05). Np65 deficiency resulted in a significant downregulation of the expression of macrophage M1 polarization-related markers CD80, and CD86 as well as the cytokines TNF-α, IL-1β and IL-6 at mRNA level ( P<0.01). However, the expression of M2 polarization markers CD206, CD163, Ym1, Arg1 and IL-10 at mRNA level were increased significantly ( P<0.05). Co-immunoprecipitation and immunofluorescence confocal analysis revealed the significant co-localization of Np65 with CD14. Furthermore, Np65 deficiency resulted in significantly down-regulated phosphorylation of p38, ERK, and p65 in M1 macrophages, and significantly increased STAT3 phosphorylation in M2 macrophages. Conclusions:Np65 participates in the polarization of macrophages towards the M1 type and inhibits M2 type polarization through affecting the phosphorylation of multiple key proteins in macrophage polarization-related signaling pathways, thereby regulating the activation of macrophages during inflammation.

Objective: To identify the functional connectivity characteristics of insula, sensory and social related brain regions in boys with autism spectrum disorder(ASD), to explore the central nervous basis of sensory abnormality affecting core symptoms in boys with ASD. Methods: Resting state functional magnetic resonance imaging (rs fMRI) data were collected from 34 boys with ASD and 29 typical development boys (TD group). Based on functional connectivity analysis, the sensory related brain regions, insula, and social related brain regions were taken as regions of interest to calculate the functional connectivity (FC) level between the regions of interest, the differences between the two groups were compared and the results were corrected by FDR. The Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS) and Autism Spectrum Quotient-Children s Version (AQ-Child) were used to assess the core phenotypes of boys with ASD. Results: Compared with the TD group, the levels of FC between tactile brain regions and insula, olfactory brain regions and insula, auditory brain regions and insula in boys with ASD group were significantly increased. The level of FC between the insula and bilateral amygdala，insula and the medial prefrontal cortex(mPFC) were significantly increased( P <0.05).Pearson correlation analysis showed that the level of FC between auditory brain region(BA42)and left insula in ASD group was negatively correlated with the scores of communication subscale of ADOS( r =-0.44)，social interaction subscale of ADOS( r =-0.43), communication & social interaction subscale of ADOS( r =-0.49),attention to details subscale of AQ-Child( r =-0.41). The level of FC between the right insula and right amygdala was positively correlated with the attention switch subscale of AQ-Child( r =0.38), the level of FC between right insula and mPFC was positively correlated with the scores of repetitive behavior subscale of ADOS( r =0.48), the attention switch subscale of AQ-Child( r =0.49), total scale subscale of AQ-Child( r =0.41), total scale of CARS( r =0.41)( P < 0.05 ). Conclusion The levels of FC between insula and sensory related, social related brain regions are abnormal in children with ASD, which have significant correlations with clinical symptoms. In depth studies can be conducted to explore underlying neutral mechanisms.

Objective: To explore the differences of sensory manifestations between ASD children and typical development children, and to clarify the characteristics of sensory abnormalities in ASD and their relationship with various clinical symptoms, so as to provide scientific basis for early identification and specific intervention. Methods: A total of 265 ASD children who received rehabilitation training in autism rehabilitation institutions in Heilongjiang Province were collected as the case group, and 223 typical development children in ordinary kindergartens and schools in Harbin were taken as the control group. Short Sensory Profile (SSP) was used to evaluate the difference of children s sensory perception level between the two groups, and Social Response Scale (SRS) and Autism Behavior Checklist (ABC) were used to evaluate the severity of symptoms including social disorder of autistic children. The correlation between SSP scores in ASD group and clinical scales was analyzed. Results: The comparison of SSP scores between the two groups found that the median scores of all sensory dimensions in ASD group (tactile=33, taste/smell=18, motion sensitivity=13, Low response/sensation seeking=28, auditory filtering=19, low strength=22, visual/auditory=20) were lower than those of the healthy control group( Z =-2.73,-4.36,-3.17,-5.09,-11.00,-10.45,-3.43, P <0.05). The abnormal rate of multisensory score in children in ASD group was 55.1%, and that in control group was 21.2%, with significant difference( χ 2=57.15, P <0.05). Correlation analysis showed that SSP score in ASD group was negatively correlated with all dimensions of SRS, nonverbal communication, and social function of ADI-R scale, ADOS communication and social interaction, and total scores of ABC and CARS( P < 0.05 ). Conclusion Children with ASD have atypical sensory experiences, especially in auditory filtering dimension, and the level of atypical sensation is related to the severity of clinical symptoms of autism. In the future clinical diagnosis, treatment and research, it is necessary to strengthen the ability to recognize the sensory symptoms of children with ASD, so as to realize the early diagnosis and intervention.

Objective To investigate the clinical effects of two methods of compressive coverage with aseptic gauze dressing and alginate dressing on haemostasis in placement of peripherally inserted central catheter(PICC)so as to provide a new dressing method for clinical application.Methods A total of 416 breast cancer patients undergoing PICC were randomly divided into two groups,with 208 per group.In the control group,the puncture sites for PICC were dressed with aseptic gauze immediately after the placement of PICC,with a daily aseptic gauze dressing change once per 24 hours.In the trial group,the puncture sites were dressed with alginate dressing immediately after the placement of PICC,with a weekly dressing change at the 7th day after PICC placement,while no local bleeding on the puncture site.The incidence,within 24 hours,of bleeding,degree of comfort,frequency and cost of dressing change as well as the infection rate within 7 days after the PICC placement were monitored and compared between the groups.Results A total of 205 patients in the control group and 208 in the observation group had completed the study.In the trial group,the incidence of bleeding at puncture sites within 24 hours after placement of PICC was significantly lower than that of the control group(27.88%vs.38.05%,χ2=4.829,P=0.028).The frequency of dressing change within 24 hours in the observation group was significantly less than that of the control group(Z=205.235,P<0.001).The cost of dressing change in the observed groups was also significantly less than that of the control group(56.94 vs.10.20 yuan in average,Z=-8.990,P<0.001).The incidence rates of local pain and itche reported by the patients in the observation group were significantly lower than those in the control group(Z=-12.079,P<0.001;Z=-12.194,P<0.001).No infection at the puncture site was observed in both groups.Conclusions Application of alginate dressing immediately after PICC placement in breast cancer patients can extend the time for initial dressing change up to 7 days in the patient without bleeding at the puncture site within 24 hours after the placement of PICC.An alginate dressing can reduce the incidence of bleeding at the puncture site,increase the comfort of patients,lower the frequency and cost of dressing change hence the nursing workload.

Objective: To investigate the effect of chrysotile exposure on ribosomal DNA (rDNA) copy number and DNA damage response, so as to provide insights into the mechanism of asbestos-induced carcinogenesis. Methods: Human pleural mesothelial MeT-5A cells were treated with chrysotile suspensions at doses of 1.25, 2.5 and 5 μg/cm2 (low-, medium-, high-dose group), while PBS served as controls. MeT-5A cells were harvested 6, 24, 48 and 72 h post-treatment, and the rDNA copy numbers and the BIRC5, HRAS, GINS4 and RRM2 mRNA expression were determined using a quantitative real-time PCR (qPCR) assay. The apoptosis of MeT-5A cells and DNA damage were detected using Muse cell analyzer. The rDNA copy numbers, DNA damage responses and BIRC5, HRAS, GINS4 and RRM2 mRNA expression were compared in MeT-5A cells treated with different doses of chrysotile suspensions. Results: There were significant differences in 45S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 6, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 45S rDNA copy numbers were measured in low-, medium- and high-dose groups than in the control group 6 h post-treatment, while significantly higher 45S rDNA copy numbers were found in the high-dose group than in low- and medium-dose groups 48 and 72 h post-treatment (all P<0.05). There were significant differences in 5S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 24, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 5S rDNA copy numbers were measured in medium- and high-dose groups than in the control group 24 and 48 h post-treatment, while significantly lower 5S rDNA copy numbers were found in medium- and high-dose groups than in the low-dose group 24, 72 h post-treatment (all P<0.05). There were significant differences in the overall apoptotic rate of MeT-5A cells among groups at different time points, and the overall apoptotic rate of MeT-5A cells were significantly higher in medium- and high-dose groups than in the control group (all P<0.05), with late-stage apoptosis predominantly detected. There were significant differences in the rates of ATM activation and DNA double-strand break in MeT-5A cells among groups 72 h post-treatment, and higher rates of ATM activation and DNA double-strand break were measured in medium- and high-dose groups than in the control group (all P<0.05). In addition, there were significant differences in the relative mRNA expression of BIRC5, HRAS, GINS4 and RRM2 genes among groups 24 and 48 h post-treatment, and significantly lower BIRC5, HRAS, GINS4 and RRM2 mRNA expression was quantified in medium- and high-dose groups than in the control group (all P<0.05). Conclusion Exposure to chrysotile may induce rDNA copy number variations and altered expression of nucleolar proteins in human pleural mesothelial cells, which may be involved in the regulation of DNA damage responses.

Objective: To explore the functional connectivity between the visual brain regions and whole brain in children with autism spectrum disorder (ASD) at resting state, and to further analyze the correlation with their clinical manifestations. Methods: The functional magnetic resonance imaging (fMRI) data of 34 boys with ASD enrolled from ASD designated rehabilitation institutions and 29 healthy boys enrolled from several kindergartens in Heilongjiang were collected. Based on the resting-state functional connectivity magnetic resonance imaging (rs-fc MRI) analysis, the BA17 of the primary visual brain region and the BA18/19 of the higher visual brain region were taken as the regions of interest (ROI) to calculate the functional connectivity level between the visual brain regions and whole brain, and the differences between the two groups were compared. Multiple developmental scales were used to evaluate the behavior of ASD children, and Pearson correlation analysis was used to explore the relationship between functional connection strength and autistic behavior. Results: The ASD group had decreased positive connectivity between BA17 and the right fusiform gyrus (FFG), and was negatively correlated with social interaction of ADI-R and the total scores of CARS (r=-0.41, -0.48, P<0.05); ASD group had decreased positive connectivity between BA17 and the left FFG, there was a negative correlation with social motivation of SRS (r=-0.43, P<0.05); ASD group had decreased positive connectivity between BA17 and the left posterior cingulate gyrus (PCG). Children with ASD had decreased positive connectivity between BA18/19 and left calcarine fissure and surrounding cortex (CAL), which was positively correlated with attention conversion of AQ, total scores of CARS (r=0.43, 0.40, P<0.05), and the children with ASD had deceased positive connectivity between BA18/19 and right precuneus (PCUN). Conclusion In resting state, the functional connectivity of primary and higher visual brain regions and whole brain of ASD children is different from that in healthy children, and there is a significant correlation between abnormal level and autistic behaviors.

Objective To evaluate the effect of high flow nasal catheter oxygen (HFNCO) therapy on extubation failure rate,reintubation rate,and incidence of related complications within 48 h after extubation in mechanically ventilation patients.Methods A prospective,single-center,randomized controlled trial was conducted in the ICU of a teaching hospital affiliated to a medical university.A total of 77 patients with mechanical ventilation duration of ≥ 48 h and met the condition of spontaneous breathing test (SBT) were selected.The patients whose LUS ≥ 14 at 30 min of SBT were enrolled,and were randomly (random number) divided into 3 groups according to different oxygen therapies:the traditional oxygen therapy group,the noninvasive ventilation (NIV) group,and the HFNCO group.The effect of oxygen therapy and outcomes after extubation were compared among the three groups.The measurement data were presented as the mean±standard deviation (SD),and the numeration data were expressed as ratio or constituent ratio.The independent sample t test and LSD-t test were used for the comparisons between the two groups and the one-way ANOVA for differences between multiple groups.The differences between enumeration data were assessed by chi-square test.A P＜0.05 was considered statistically significant.Results There was no significant difference in gender,age and other general conditions between the two groups (P＞0.05).The NIV group and HFNCO group had lower extubation failure rate (14.29％,15.38％ vs 34.87％) and reintubation rate (10.7％,11.54％ vs 21.74％) than the convertional oxygen therapy group (P＜0.05).In addition,the traditional oxygen therapy group had longer mechanical ventilation duration [(24.33±4.42) d vs (8.58±1.09) d,(8.37±2.43) d],antibiotic use time [(19.21±4.37) d vs (8.34±2.54) d,(7.41±1.06) d],and ICU hospitalization time [(27.27±4.24) d vs (10.38±2.07) d,(9.44±0.79) d],all P＜0.05.Conclusions Treatment with HFNCO or NIV after extubation can effectively reduce the rates of extubation failure and reintubation,and improve the outcome of the mechanical ventilation.There is no difference in clinical efficiency between the NIV group and HFNCO group.However,compared with NIV,HFNCO can effectively reduce respiratory rate and avoid the retention of CO2,which has a wider application prospect in clinical practice.