ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang （DCQD） on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins ［claudin-1， tumor necrosis factor （TNF）-α， interleukin （IL）-6， endogenous antimicrobial peptide mCRAMP， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88）］ in sepsis. Fifty C57BL/6 mice were randomized into sham， model， low- and high-dose （4 g∙kg^-1 and 8 g∙kg^-1） DCQD， and ulinastatin groups （n=10）. Before， during， and after the day of modeling surgery， each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay （ELISA） was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue， which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP， TLR4， and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction， on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force， hydrogen bonding， and other conjugated systems. The results of animal experiments showed that compared with the model group， low- or high-dose DCQD lowered the D-lactic acid level in the serum （P<0.01）， alleviated damage to the ileal tissue and mucosal edema， protected the small intestine villus integrity， reduced inflammatory cell infiltration， promoted the expression of claudin-1 （P<0.01）， lowered the IL-6 level （P<0.01）， up-regulated the mRNA and protein levels of mCRAMP （P<0.01）， and down-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.01） in the ileal tissue. In addition， high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue （P<0.01）， and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue （P<0.05）. ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation， repair intestinal mucosal damage， improve the tight junction protein level， and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

Acute Stanford type A aortic dissection has the characteristics of acute onset, severe condition and high mortality. Once making a definite diagnosis, surgical treatment is needed as soon as possible. It is difficult for cardiac surgeons to treat the acute aortic dissection involving the aortic sinus, which is an important risk factor for death. Improving the surgical treatment for the aortic sinus can be a key to improving the prognosis. In this review, we will introduce the modified sandwich technique for acute Stanford type A aortic dissection and the prognosis, and summarize the experiences of different modified sandwich techniques. However, there is still no unified standardized technique in aortic root repair, and there is a lack of large studies with long-term follow-up, so it is necessary to further improve the aortic root repair techniques.

Objective:To search, evaluate and integrate the best evidence of the best evidence for emergency service surge capacity.Methods:According to the "6S" model of evidence resources, the related evidence on emergency service surge capacity in Guidelines International Network, National Guideline Clearinghouse, Canadian Medical Association CPG Infobase, Scottish Intercollegiate Guidelines Network, European Society for Emergency Medicine, the American College of Emergency Physicians, Emergency Nurses Association, Cochrane Library, PubMed, Embase, CINAHL, Web of Science, BMJ Best Practice, UpToDate,CKNI, Wanfang, and VIP database were searched by computer. The retrieval time limit was from the establishment of the database to Dec 31, 2023. Literature quality assessment and data extraction were performed by 2 researchers.Results:A total of 11 articles were included in this study, including 1 guideline, 7 expert consensuses and 3 systematic reviews, which summarized 43 pieces of evidence involving 7 categories, namely core elements, organizational management, space management, personnel allocation, material allocation, education and training, and support services.Conclusions:The best evidence summarized in this study can provide a reference for emergency service to improve surge capacity. In clinical application, emergency departments should focus on organizational, space, personnel and materials management, combined with the type of emergency events, to maximize their routine, emergency and crisis response capabilities, so as to respond to medical surges effectively.

Social anxiety disorder has a significant negative impact on individuals'social interaction and normal life,and childhood trauma plays an important role in the occurrence and development of SAD.Childhood trauma affects the development of self-awareness,impairs the ability of information processing,hinders the normal development of prefrontal cortex-limbic system loop and default mode network,and causes abnormal secretion of glucocorticoid and oxytocin,which leads to individuals'inability to correctly understand social clues and reasonably regulate emotions,and thus unable to produce adaptive emotional and behavioral responses in social situations,which may lead to SAD.In conclusion,childhood trauma has a lasting adverse effect on social function from both psychological and physiological aspects.

Objective:To evaluate the effect of closed-loop therapy system in adult non-mechanical ventilation patients in order to provide evidence-based basis for promoting the safety of oxygen therapy.Methods:Randomized controlled trials of closed-oxygen therapy system on the percentage within SpO 2 target, the incidence of hypoxaemia or hyperoxia, oxygen consumption, the mean oxygen therapy days, as well as the length of hospital stay in adult non-mechanical ventilation patients were searched in PubMed, Web of Science, Embase, Cochrane, CNKI, Wanfang, VIP from inception to June 30, 2022. Data extraction, and literature quality evaluation were performed by two researchers independently, RevMan 5.3 was used for meta-analysis. Results:A total of 5 articles including 502 patients were included. The results showed that the closed oxygen therapy system could significantly improve the percentage of time within SpO 2 target of patients ( SMD=1.56, 95% CI 1.22-1.90, Z=9.04, P<0.001) and reduce the percentage of time with hypoxaemia ( SMD=-0.35, 95% CI-0.50--0.19, Z=4.37, P<0.001) or hyperoxia ( SMD=-0.91, 95% CI-1.07--0.75, Z=11.04, P<0.001) of patients. Moreover, the mean oxygen flow rate of closed oxygen therapy ( SMD=-0.64, 95% CI-1.25--0.03, Z=2.07, P<0.05), the mean oxygen therapy days ( SMD=-0.55, 95%, CI-1.06--0.03, Z=2.08, P<0.05), as well as the length of hospital stay ( SMD=-1.68, 95% CI-2.22--1.14, Z=6.11, P<0.001) were lower than those of patients with manual adjustment systems. Conclusion:The closed oxygen therapy system can promote the safety of oxygen use, but it needs clinical application to further explore.

Objective To investigate the effect of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) on the proliferation, migration and tumor immune microenvironment of colorectal cancer cells and its possible molecular mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of IGF2BP2 and MYC in colorectal cancer and adjacent tissues. The expression of IGF2BP2 in HCT-116 and SW480 human colorectal cancer cells was silenced by RNA interference (RNAi), and the silencing effect was detected by quantitative real-time PCR. After knocking down IGF2BP2, colony formation assay, CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were employed to detect cell colony formation and proliferation ability. Transwell^TM assay was used to detect cell migration ability. Quantitative real-time PCR was used to detect the mRNA expression of IGF2BP2, MYC, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). The protein expression of IGF2BP2 and MYC was detected by western blot. The binding ability of IGF2BP2 and MYC in HCT-116 cells was detected by quantitative real-time PCR after RNA immunoprecipitation. Results The results of TCGA database showed that the expression of IGF2BP2 and MYC in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the survival time of colorectal cancer patients with high expression of IGF2BP2 was shorter. After silencing IGF2BP2, the viability, proliferation and migration of HCT-116 and SW480 cells were decreased. The mRNA expression of MYC, TGF-β and IL-10 in IGF2BP2 knockdown group was significantly decreased, while the expression of TNF-α mRNA was increased. The expression of MYC protein and the stability of MYC mRNA were significantly decreased. RIP-qPCR results showed that IGF2BP2 could bind to MYC mRNA. Conclusion Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression.
Humans ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Colorectal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Interleukin-10/metabolism* ; RNA, Messenger ; RNA-Binding Proteins/metabolism* ; Transforming Growth Factor beta/genetics* ; Tumor Microenvironment/immunology* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-myc/metabolism*

Objective:To investigate the synchronized feature patterns of local field potentials in the hippocampus (HPC) and prefrontal cortex (PFC) during working memory based on time-varying spectral coherence so as to support the study of information processing mechanisms in working memory.Methods:The local field potentials (LFPs) signals of the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) were collected from six SD rats during the performance of a spatial working memory task in the Y-maze, and the time-frequency distributions of vHPC and mPFC LFPs were calculated by applying the short-time Fourier transform (STFT) to determine the characteristic frequency bands of the working memory and then to investigate the synchronized patterns of vHPC and mPFC LFPs based on the coherent of the time-varying frequency spectrum. Finally, support vector machines were applied to explore the feasibility of applying spectral coherence values to predict working memory.Results:When rats performed working memory tasks correctly, the energy of the theta band (4 - 12 Hz) of the HPC and PFC increased (all P < 0.01), and the spectral coherence value of the theta band of the HPC-PFC increased ( P < 0.05). Support vector machine training and prediction using the average peak spectral coherence and the difference between the peak and the onset when correctly and incorrectly executing the working memory as features resulted in 89% accuracy, 90% precision, 88% recall, and 88% F1 scores, all of which were statistically significant differences compared to the results of the randomly disrupted labeled data rearranging (all P < 0.05). Conclusions:Synchronized synergy in the HPC-PFC theta band is one of the potential mechanisms for correctly performing information processing in working memory.

Objective To investigate the possible mechanism of circ RNA in the pathogenesis of epilepsy.Methods In this study,circRNA expression profiles in peripheral venous blood of epileptic patients and healthy controls were studied by using circRNA gene chip technology,and differentially expressed circrnas were screened.Bioinfor-matics databases such as circPrimer,circMir and TargetScan were used to analyze its possible role in epilepsy and adenovirus vector was constructed.Thirty male adult C57BL/6 mice were randomly divided into control group,empty vector group and circ_0017178 overexpressed group(10 mice/group).Normal saline,empty plasmid ade-novirus vector and circ_0017178 overexpressed adenovirus vector were injected into the hippocampus of the three groups respectively.The change of animal behavior of mice in each group was observed after the establishment of pentetrazole epilepsy model,and the apoptosis of hippocampal tissue cells of mice in each group was analyzed by Tunel staining.Results The results of gene microarray showed that circ_0069272,circ_0033065,circ_0017178,circ_0073442,circ_0033063 and circ_0049415 in epilepsy group were up-regulated significantly compared with the control group.And circ_0083773,circ_0088262,circ_0016396 decreased significantly.Circ_0017178 might be the most associated with epilepsy.Through bioanalysis,circ_0017178 might regulate 39 epilepsy genes by combi-ning 20 miRNA and possess potential m6A,IRES and ORF1 binding sites.In the experiment of pentatetrazole epi-leptic mice,compared with the empty carrier group and the control group,the latency period of epilepsy in the circ_0017178 overexpression group was shortened(P＜0.05),the seizure time was prolonged(P＜0.05),and the seizure frequency increased(P＜0.05).There was no statistical significance between the empty carrier group and the control group(P＞0.05).In animal experiments,compared with the empty vector group and the control group,the apoptosis degree of hippocampal tissue of epileptic mice in the circ_0017178 overexpression group sig-nificantly increased(P＜0.05),but there was no statistical significance between the empty vector group and the control group(P＞0.05).Conclusion Circ_0017178 significantly increases in the expression profile of peripher-al blood mononuclear cells in patients with epilepsy,which may act as a"molecular sponge"of miRNA in epilepsy and has the potential of m6A methylation and protein translation.Circ_0017178 may increase the susceptibility and severity of epilepsy by promoting apoptosis in penetetrazole epileptic mice.

Objective:To compare the clinical characteristics and analyze the prognostic factors between human immunodeficiency virus (HIV)-infected patients and non-HIV-infected immunocompromised patients with pneumocystis pneumonia (PCP) complicated with acute respiratory failure (ARF) in intensive care unit (ICU).Methods:The clinical data of patients with PCP complicated with ARF admitted in ICU of The First Affiliated Hospital of Zhengzhou University and The Sixth People′s Hospital of Zhengzhou City between May 2018 and October 2020 were retrospectively reviewed. All subjects were divided into HIV-infected group and non-HIV-infected immunocompromised group. General characteristics and underlying diseases of patients in the two groups were analyzed. Laboratory parameters, treatment and outcomes between two groups were compared. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis, and univariate and multivariate logistic regression models were used to identify the risk factors for the clinical outcome. Results:A total of 129 PCP complicated with ARF patients were enrolled, including 75 HIV-infected patients and 54 non-HIV-infected immunocompromised patients. Only 10.7%(8/75) patients of HIV-infected group received anti-retroviral therapy (ART), but none of the patients in either groups had previously received trimethoprim-sulfamethoxazole (TMP-SMX) for PCP prophylaxis. Acute physiology and chronic health evaluation (APACHE) Ⅱ score of HIV-infected group was 18.7±6.0, which was higher than that in non-HIV-infected immunocompromised group (13.1±4.4) when admitted in ICU ( t=-5.45, P<0.001). Hypoproteinemia was common in both groups. Ninety-six percent (72/75) of HIV-infected patients had CD4 + T lymphocyte counts lower than 200/μL and 84.0%(63/75) of patients had CD4 + T lymphocyte counts even lower than 50/μL, while 5.74%(31/54) of patients in non-HIV-infected immunocompromised group had CD4 + T lymphocyte counts lower than 200/μL. The CD4 + /CD8 + T lymphocyte counts ratio was 0.05(0.02, 0.12) in HIV-infected group, which was lower than that in non-HIV-infected immunocompromised group (0.96(0.64, 1.44)), and the difference was statistically significant ( Z=-9.16, P<0.001). The length of ICU stay and hospital stay of non-HIV-infected immunocompromised patients were 10.0(7.0, 14.0) days and 18.0(11.8, 32.5) days, respectively, which were both longer than those in HIV-infected patients (7.0(4.0, 9.0) days and 13.0(7.0, 23.0) days, respectively), and the differences were both statistically significant ( Z=-3.58 and -2.73, respectively, both P<0.050). The hospital mortality of HIV-infected patients was 57.3%(43/75), which was significantly higher than that in non-HIV-infected immunocompromised patients (38.9%, 21/54) ( χ2=4.27, P=0.039). Multivariable logistic regression identified that lactic dehydrogenase (LDH), C-reactive protein (CRP) and APACHE Ⅱ score were the risk factors for the clinical outcome of HIV-infected patients (odds ratio ( OR)= 1.006, 1.015 and 1.736, respectively, all P<0.050). The partial pressure of oxygen in arterial blood/fractional concentration of inspiratory oxygen (PaO 2/FiO 2), LDH and CD4 + T lymphocyte counts were the risk factors for the clinical outcome of non-HIV infected immunocompromised patients ( OR=0.970, 1.008 and 0.989, respectively, all P<0.050). Conclusions:PCP patients with ARF are critically ill with high mortality rate. LDH, CRP and APACHEⅡscore are predictors for prognosis of HIV-infected patients with PCP, while PaO 2/FiO 2, LDH and CD4 + T lymphocyte counts are predictors for prognosis of non-HIV infected immunocompromised patients with PCP.

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α₂ adrenoceptor (α₂AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α₂AR-mediated sympathetic-sensory coupling.
Animals ; Ganglia, Spinal ; Hyperalgesia/etiology* ; Myocardial Ischemia/complications* ; Pain, Referred/complications* ; Rats ; Sympathetic Nervous System