Cellular dysfunction caused by vesicle transport is associated with a variety of diseases.The trans-Golgi network(TGN)to endosome transport is an important pathway of vesicle transport,and its defects leading to protein balance disorders has been linked to many diseases such as cancer,neurodegenerative diseases and diabetes mellitus.Gol-gi-associated gamma-adaptin ear-containing ADP-ribosylation factor-binding protein 2(GGA2)is a crucial protein in-volved in TGN-endosomal transport.It plays a significant role in the regulation of several diseases,including cancer,Al-zheimer disease,type 2 diabetes mellitus and cerebral ischemia,by mediating protein transport with important biological significance.This article provides an overview of the molecular structure of GGA2,its role in regulating clathrin-mediated protein transport between TGN and endosomes,and its potential implications for a variety of diseases.

Objective To study the clinical characteristics and related factors affecting the severity of acute tinnitus in patients.Methods A retrospective analysis was conducted on the data of 319 patients with acute tinni-tus.All patients had detailed case history,including basic patient information,tinnitus location,course of disease,acoustic characteristics of tinnitus,hearing loss,combined headache,dizziness,aural fallness,earache and other symptoms,as well as accompanying clinical diseases.All patients completed the tinnitus handicap inventory(THI),generalized anxiety disorder(GAD-7),patient health questionnaire(PHQ-9),pittsburgh sleep quality index(PSQI),hyperacusis questionnaire(HQ),type D personality scale-14(DS-14),etc.The mild tinnitus group was determined based on a THI score of ≤36.The moderate tinnitus group was determined based on a THI score of 38～56.The severe to extremely severe tinnitus group was determinded based on THI 56～100.THI grouping was used as the dependent variable and the above factors as independent variables.The correlation between each factor and the severity of acute tinnitus was analyzed using ordered multinomial logistic regression.Results Among 319 patients with acute tinnitus,158(49.5％)were in the mild tinnitus group,and 72(22.6％)were in the moderate tinnitus group,and 89(27.9％)were in severe to extremely severe tinnitus group.Ordered multinomial logistic re-gression analysis found that hyperacusis(OR=3.921),anxiety(OR=2.495),depression(OR=2.921),and D-type personality(OR=0.349)were associated with the severity of acute tinnitus(P＜0.05),with more serere tin-nitus in these patients.Conclusion Hyperacusis,anxiety,depression,and D-type personality may be factors that affect the severity of acute tinnitus,so high attention should be paid when treating patients with acute tinnitus.

Objective To search and evaluate the relevant evidence of blood purification and anticoagulant management of perioperative liver transplantation patients,and to summarize the best evidence,so as to provide evidence-based evidence for clinical blood purification and anticoagulant management practice.Methods Evidence-based questions were determined.Systematic search was conducted on relevant domestic and foreign databases and websites for clinical decisions,guidelines,evidence summaries,system evaluations,and expert consensuses related to blood purification anticoagulation management.The retrieval period is from the establishment to May 2,2023.Literature screening,quality evaluation and evidence summary were conducted by 2 researchers.Results A total of 17 articles were included,including 2 clinical decisions,3 guidelines,2 evidence summaries,4 systematic evaluations and 6 expert consensuses.24 pieces of best evidence were summarized from 6 dimensions,including coagulation function evaluation,anticoagulant strategy,mode selection,vascular access,standardized operation implementation points and personnel organization management.Conclusion The best evidence was summarized in the study on perioperative blood purification and anticoagulant management of liver transplantation,which can provide evidence-based basis for clinical medical staff to implement anticoagulant management.However,it is necessary to further carry out evidence-based practice of perioperative blood purification and anticoagulant management of liver transplantation to verify its anticoagulation effect and nursing safety in clinical practice.

Objective·To investigate the composition of immune cells in tumor microenvironment of colorectal cancer(CRC),and examine the proportion,phenotype and effector function of natural killer(NK)cells in CRC.Methods·Fresh tumor tissues,paired normal tissues adjacent to tumor,and peripheral blood samples in the same cohort were collected from CRC patients.Tissues were digested and prepared into single cell suspension.The major immune cell lineages were detected by flow cytometry.t-Distributed stochastic neighbor embedding(t-SNE)and statistical analysis were used to analyze the composition of immune cells in tumor microenvironment of CRC.To analyze the phenotype of NK cells,the expression levels of activation markers,including CD16,CD27,CD69,human leukocyte antigen-DR(HLA-DR),and T cell immunoglobulin domain and mucin domain-3(TIM-3),were detected by flow cytometry.NK cell subsets:CD38lowNK cells and CD38highNK cells were also examined by flow cytometry.To assess the effector function of NK cells,they were stimulated with cell stimulation cocktail and the expression levels of interferon-γ(IFN-y),tumor necrosis factor-α(TNF-α),and granulocyte-macrophage colony-stimulating factor(GM-CSF)were measured by flow cytometry.Results·Twenty-five pairs of fresh tumor tissues and normal tissues adjacent to tumor,and 15 peripheral blood samples in the same cohort were collected from CRC patients.The tumor microenvironment of CRC included diverse immune cell types,including T cells,B cells,NK cells and myeloid cells.The proportions of T cells(P=0.000)and myeloid cells(P=0.026)in tumor tissues were significantly higher than those in normal tissues.By contrast,the proportion of NK cells(P=0.007)in tumor was significantly reduced.The proportion of B cells was comparable between tumor and normal tissues.Compared to normal tissues,NK cells in tumor tissues expressed significantly lower CD27(P=0.000)and CD69(P=0.001),while the expression levels of CD16(P=0.008),HLA-DR(P=0.000)and TIM-3(P=0.024)were significantly elevated.The results indicated that NK cells in CRC tumor exhibited a phenotype of late activation and exhaustion.According to the expression level of CD38,NK cells could be divided into two subsets,CD38highNK cells and CD38lowNK cells.The proportion of CD38highNK cells(P=0.003)in tumor tissues was significantly lower than that in normal tissues,while the proportion of CD38lowNK cells was unaffected.Compared to CD38lowNK cells,CD38highNK cells expressed higher CD27,meanwhile significantly less CD16,NKp46,CD57,CD94,HLA-DR and CD158a(P=0.000).These results suggested that CD38highNK cells were at early differentiation state.The secretion of cytokines IFN-y(P=0.032),TNF-α(P=0.042),and GM-CSF(P=0.019)by tumor-infiltrated NK cells was significantly decreased compared to that in normal tissues.The results showed that the function of tumor-infiltrated NK cells was impaired.Conclusion·Together,these data suggest that NK cell compartment is disrupted in tumor tissues of CRC,leading to the impaired anti-tumor immunity mediated by NK cells.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Objective:To explore the risk factors of oral-mucosal pressure injury (OMPI) in patients with tracheal intubation in ICU and to establish a nomogram model.Methods:Using the convenient sampling method, a total of 640 patients with oral tracheal intubation admitted to ICU of the First Affiliated Hospital of Xinjiang Medical University from January to May 2023 were selected as the research objects. They were divided into the occurrence group ( n=286) and the non-occurrence group ( n=354) according to whether OMPI occurred or not. Binomial Logistic regression analysis was used to explore the risk factors for OMPI in patients with tracheal intubation in ICU. A risk nomogram model was created based on independent risk factors, and internal verification was conducted by Bootstrap repeated sampling method. Results:OMPI occurred in 286 of 640 ICU patients with tracheal intubation. Binomial Logistic regression analysis showed that high APACHEⅡ score, modified Beck oral score greater than or equal to 11 points, use of sedative drugs, prone ventilation, long retention time of tracheal catheter, low oxygenation index less than 200 mmHg (1 mmHg=0.133 kPa) and tracheal catheter fixation frequency of 1 time /24 h were the risk factors for OMPI in patients with tracheal intubation in ICU ( P<0.05). A risk nomogram model for OMPI in patients with tracheal intubation in ICU was established based on independent risk factors. The results showed that the predictive performance (area under the receiver operating characteristic curve of subjects was 0.918, 95% confidence interval was 0.897 to 0.938) and calibration (χ 2 value of 4.647, P=0.795) of the risk nomogram model for OMPI in patients with tracheal intubation in ICU were good. When the threshold probability was 0 to 1, the decision curve showed that the model had good clinical effectiveness. Conclusions:The OMPI risk nomogram model of tracheal intubation patients in ICU established in this study has good calibration and differentiation, which can be used as an effective tool for screening high-risk patients.

Objective:To explore the application effect of home rehabilitation exercise prescription in non-surgical treatment of patients with lumbar disc herniation.Methods:Using the convenient sampling method, a total of 66 patients with non-surgical treatment of lumbar disc herniation who visited Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January to August 2023 were selected as the research objects. The patients were divided into the control group and the observation group using the random number table method, with 33 cases in each group. The control group implemented routine home rehabilitation nursing measures, while the observation group formed an outpatient home rehabilitation nursing team based on this, constructed a home rehabilitation exercise prescription and implemented targeted home rehabilitation training. Pain Numberic Rating Scale (NRS), Oswestry Disability Index (ODI), Modified Japanese Orthopaedic Association (JOA) Scores and exercise compliance were compared between the two groups after 6 weeks of home rehabilitation.Results:After 6 weeks of home rehabilitation exercise, NRS score and ODI score of observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05). The JOA score and compliance score of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Home rehabilitation exercise prescription can promote the rehabilitation of patients with non-surgical treatment of lumbar disc herniation, effectively relieve pain, improve the symptoms of limb dysfunction and improve the compliance of rehabilitation exercise.

Objective:To investigate the efficacy and safety of sivelestat sodium in patients with sepsis.Methods:The clinical data of 141 adult patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to January 1, 2022 were retrospectively analyzed. The patients were divided into the sivelestat sodium group ( n = 70) and the control group ( n = 71) according to whether they received sivelestat sodium or not. The efficacy indexes included oxygenation index, procalcitonin (PCT), C-reactive protein (CRP), white blood count (WBC), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) before and after 7 days of treatment, as well as ventilator supporting time, the length of ICU stay, the length of hospital stay and ICU mortality. The safety indicators included platelet count (PLT) and liver and kidney function. Results:There were no significant differences in age, gender, underlying diseases, infection site, basic drugs, etiology, oxygenation index, biochemical indexes, SOFA and APACHE Ⅱ scores between the two groups. Compared with the control group, the oxygenation index in 7 days was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 233.5 (181.0, 278.0) vs. 202.0 (153.0, 243.0), P < 0.01], the levels of PCT, CRP, alanine aminotransferase (ALT) and APACHE Ⅱ score were significantly decreased in the sivelestat sodium group [PCT (μg/L): 0.87 (0.41, 1.61) vs. 1.53 (0.56, 5.33), CRP (mg/L): 64.12 (19.61, 150.86) vs. 107.20 (50.30, 173.00), ALT (U/L): 25.0 (15.0, 43.0) vs. 31.0 (20.0, 65.0), APACHE Ⅱ: 14 (11, 18) vs. 16 (13, 21), all P < 0.05]. However, there were no significant differences in SOFA, WBC, serum creatinine (SCr), PLT, total bilirubin (TBil), aspartate aminotransferase (AST) in 7 days between the sivelestat sodium group and the control group [SOFA: 6.5 (5.0, 10.0) vs. 7.0 (5.0, 10.0), WBC (×10 9/L): 10.5 (8.2, 14.7) vs. 10.5 (7.2, 15.2), SCr (μmol/L): 76.0 (50.0, 124.1) vs. 84.0 (59.0, 129.0), PLT (×10 9/L): 127.5 (59.8, 212.3) vs. 121.0 (55.0, 211.0), TBil (μmol/L): 16.8 (10.0, 32.1) vs. 16.6 (8.4, 26.9), AST (U/L): 31.5 (22.0, 62.3) vs. 37.0 (24.0, 63.0), all P > 0.05]. The ventilator supporting time and the length of ICU stay in the sivelestat sodium group were significantly shorter than those in control group [ventilator supporting time (hours): 147.50 (86.83, 220.00) vs. 182.00 (100.00, 360.00), the length of ICU stay (days): 12.5 (9.0, 18.3) vs. 16.0 (11.0, 23.0), both P < 0.05]. However, there were no significant differences in the length of hospital stay and ICU mortality between the sivelestat sodium group and the control group [the length of hospital stay (days): 20.0 (11.0, 27.3) vs. 13.0 (11.0, 21.0), ICU mortality: 17.1% (12/70) vs. 14.1% (10/71), both P > 0.05]. Conclusions:Sivelestat sodium is safe and effective in patients with sepsis. It can improve the oxygenation index and APACHE Ⅱ score, reduce the levels of PCT and CRP, shorten ventilator supporting time and the length of ICU stay. No adverse reactions such as liver and kidney function injury and platelet abnormality are observed.

OBJECTIVE: To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites. METHODS: A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities. CONCLUSIONS Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Sepsis/metabolism* ; Inflammation

Objective: To explore the social functioning characteristics of children with co ocurrence of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) for intervention reference. Methods: The Chinese Version of Swanson Nolan and Pelham, Version IV Scale-Parent Form(SNAP-IV), the Chinese Version of Weiss Functional Impairment Scale-Parent(WFIRS-P), and the Questionnaire-Children with Difficulties (QCD) were applied to 192 children with ADHD, 243 children with co occurrence of ADHD and ODD, who firstly visited the Department of Children Psychological Health of Zhuhai Maternal and Child Health Care Hospital, and 118 healthy control children from a school in Zhuhai. Results: The scores of attention deficit factor in SNAP-Ⅳ scale of children in three groups were[1.9(1.7, 2.1), 1.8(1.6, 1.9), 1.0(0.6, 1.2)], the scores of hyperactive impulsivity were[1.8(1.4, 2.1), 1.6(1.1, 1.8), 0.7(0.2, 1.0)] the scores of oppositional defiant were[1.6(1.5, 1.9), 1.0(0.8,1.1), 0.8(0.5, 1.0)], the differences were statistically significant( H=268.44, 237.97, 418.66, P <0.01). The dimensions and total scores of the three groups of children s WFIRS-P scale were family[0.8(0.6, 1.1), 0.6(0.3, 0.8), 0.3(0.1, 0.6)]; learning and school[0.8(0.5, 1.1), 0.8(0.5, 1.0), 0.3(0.1, 0.5)]; life skills[1.0(0.7, 1.2), 0.8(0.6, 1.0), 0.6(0.4, 0.8)]; self management [1.0(0.3, 1.0), 0.7(0.3, 1.0), 0.3(0.0, 0.7)]; social activities [0.7(0.4, 1.0), 0.6(0.3, 0.9), 0.3(0.0, 0.4 )]; adventure activities[0.3(0.2, 0.5), 0.2(0.1, 0.4), 0.1(0.0, 0.2)]; the total score[0.8(0.6, 1.0), 0.6(0.5, 0.8), 0.4( 0.2 , 0.6)], the difference between the groups was statistically significant( H=108.82, 122.45, 60.17, 40.58, 96.17, 76.57, 138.30, P <0.01). The difference between the QCD scale scores of children in the three groups was statistically significant[30.0( 24.0 , 37.0), 32.0(27.0, 40.0), 47.0(37.0, 52.3), H=124.65, P <0.01). Multiple regression analysis showed that attention deficit, and oppositional defiant symptoms were associated with both the total WFIRS-P score and the QCD score of children( R 2= 0.40 , 0.25, P <0.05). Conclusion Children with co occurrence of ADHD and ODD have more severe deficits in all dimensions of social functioning than children with ADHD, which might be associated with attention deficit and oppositional defiant symptoms.