Objective:To explore the antitumor effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma (DLBCL) and its mechanism.Methods:The 6-week-old female BALB/c mice were selected, and the bilateral murine subcutaneous B-cell lymphoma model was established with murine B-cell lymphoma A20 cells. The subcutaneous tumor-bearing mice were randomly divided into untreated group (without treatment), ADU-S100 in situ vaccine treatment group (intratumoral injection of interferon gene stimulating factor agonist ADU-S100), doxorubicin in situ vaccine treatment group (intratumoral injection of doxorubicin), and ADU-S100/doxorubicin in situ vaccine treatment group (intratumoral injection of ADU-S100 and doxorubicin) by using random number table method, with 5 mice in each group. The right tumors of the bilateral subcutaneous tumor-bearing mice were defined as proximal tumors, and the left tumors of the bilateral subcutaneous tumor-bearing mice were defined as distal tumors. Only the proximal tumors were treated via the intratumoral route, and the distal tumors were not treated. On day 23 after tumor inoculation, the percentages of CD11c + dendritic cells (DC), CD8 + CD11c + DC and CD80 + CD11c + DC in the spleen of mice in each group were detected by flow cytometry. The splenocytes of mice in each group were stimulated with A20 tumor cell lysate in vitro, the percentages of 5'-ethynyl-2'-deoxyuridine-positive (EdU +) cells and tumor necrosis factor-α-positive (TNF-α +) cells in CD8 + T cells in each in situ vaccine treatment group were detected by flow cytometry, and the killing effect of cytotoxic T lymphocyte (CTL) in each group was measured by using the lactate dehydrogenase (LDH) cytotoxicity assay kit. The mice treated with ADU-S100/doxorubicin in situ vaccine were intraperitoneally injected with anti-mouse CD8α (clone 53-6.7) mAb or isotype control on days 7, 12 and 17 after tumor inoculation to eliminate CD8 + cells. On day 23 after tumor inoculation, the proximal and distal tumor volumes of mice in the ADU-S100/doxorubicin in situ vaccine combined with anti-mouse CD8α (clone 53-6.7) mAb or isotype control treatment group were measured, the percentages of CD8 + T cells and CD8 + CD11c + DC in the spleen of tumor-bearing mice in these two groups were detected by flow cytometry, and the infiltration of CD8 + T cells in the tumor tissues from these two groups was detected by immunohistochemistry (IHC) staining. Results:On days 11, 14, 17, 20 and 23 after tumor inoculation, the proximal and distal tumor volumes of mice in each treated group were lower than those in the untreated group (all P < 0.05). The proportions of CD11c + DC in the spleen of the untreated group, ADU-S100 in situ vaccine treatment group, doxorubicin in situ vaccine treatment group and ADU-S100/doxorubicin in situ vaccine treatment group were (4.92±0.63)%, (7.54±0.84)%, (7.45±0.86)% and (11.63±0.85)%, respectively, and the difference was statistically significant ( F = 72.30, P < 0.001); the proportions of CD8 + CD11c + DC were (1.36±0.34)%, (4.02±0.43)%, (4.22±0.61)% and (6.11±0.73)%, respectively, and the difference was statistically significant ( F = 76.09, P < 0.001); the proportions of CD80 + CD11c + DC were (0.51±0.24)%, (1.69±0.23)%, (1.82±0.25)% and (4.09±0.39)%, respectively, and the difference was statistically significant ( F = 167.40, P < 0.001). The CTL responses and the proportion of EdU + cells and TNF-α + cells in CD8 + T cells in each in situ vaccine treatment group were higher than those in the untreated group (all P < 0.05). Furthermore, the enhanced CTL responses and the increased proportion of EdU + cells and TNF-α + cells in CD8 + T cells were observed in the ADU-S100/doxorubicin in situ vaccine treatment group as compared to the ADU-S100 in situ vaccine treatment group and doxorubicin in situ vaccine treatment group (all P < 0.05). The proportions of CD8 + T cells and CD8 + CD11c + DC in the spleen of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were lower than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05) and both proximal and distal tumor volumes of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were larger than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05). Conclusions:ADU-S100/doxorubicin in situ vaccine can induce profound regression of proximal tumors in bilateral murine subcutaneous B-cell lymphoma model and generate systemic immune responses capable of partially inhibiting distant tumor growth, and the antitumor efficacy of ADU-S100/doxorubicin in situ vaccine may require CD8 + CD11c + DC-mediated CD8 + T cell immune responses.

Objective To investigate the expression of zinc finger protein 382(ZNF382)in diffuse large B-cell lymphoma(DLBCL)tissue and its relationship with clinical pathological characteristics and prognosis of DLBCL patients.Methods A total of 57 DLBCL patients admitted to the Department of Hematology,Luoyang Central Hospital from January 2014 to December 2018 were selected as the research subjects.The biopsy pathological specimens and clinical data of DLBCL patients were collected;another 20 patients of reactive proliferative lymph node tissue preserved in the Department of Pathology,Luoyang Central Hospital were taken as the control group.The expression of ZNF382 in DLBCL tissue and reactive proliferative lymph node tissue was detected by En vision two-step method.The difference of ZNF382 expression was compared between DLBCL tissue and reactive proliferative lymph node tissue.The correlations of ZNF382 expression with the clinical features such as age,gender,primary tumor site,Ann Arbor stage,international prognostic index(IPI)score,Hans typing,B-symptoms,bone marrow infiltration,giant masses,Eastern Cooperative Oncology Group(ECOG)score,β2-microglobulin(β2-MG),serum lactate dehydrogenase(LDH),Ki67,and chemotherapy regimen of DLBCL patients were analyzed by univariate analysis;the survival curve was drawed by Kaplan Meier method,and the univariate and multivariate survival analysis were performed by log-rank tests and Cox proportional risk regression models.Results The expression level of ZNF382 in DLBCL tissue was significantly lower than that in reactive proliferative lymph node tissue(Z=-5.056,P＜0.01).The expression level of ZNF382 was correlated with IPI score,Ann Arbor stage,Hans typing,B-symptoms,bone marrow infiltration and giant masses of DLBCL patients(P＜0.05);the expression level of ZNF382 was not associated to gender,age,primary site,ECOG score,β2-MG,serum LDH,Ki67,and whether the chemotherapy regimen combined with rituximab or not of DLBCL patients(P＞0.05).Among the 57 DLBCL patients,the treatment was effective in 36 patients(63.20％)and ineffective in 21 patients(36.80％);the expression level of ZNF382 in tumor tissue of DLBCL patients with effective treatment was significantly higher than that of DLBCL patients with ineffective treatment(Z=-2.895,P＜0.05).The 2-year event free survival rate of DLBCL patients in the ZNF382 high expression group was significantly higher than that in the ZNF382 low expression group(x2=17.955,P＜0.001).The results of univariate survival analysis showed that female,primary lymph nodes,B-symptoms,bone marrow infiltration,giant masses,IPI score≥3,elevated β2-MG,Ki67＞70％,non-germinal center B-cell-like lymphoma,Ann Arbor stageⅢ-Ⅳ and low expression of ZNF382 were risk factors for poor prognosis in DLBCL patients(P＜0.05).The results of multivariate analysis showed that primary lymph nodes,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were independent influencing factors for poor prognosis in DLBCL patients(P＜0.05).Conclusion ZNF382 protein is low expressed in the tumor tissues of DLBCL patients,which is closely related to the occurrence,development and prognosis of DLBCL;and it can be used as an indicator for evaluating the prognosis of DLBCL.

Objectives:To analyze the safety and clinical effect of airway diagnosis in multifactor suspicious difficult airway patients with complex mouth restriction after entering the operating room.Methods:From March 2018 to May 2023, a total of 21 patients with suspicious difficult airway with complex mouth restriction were collected from the Northwest Women′s and Children′s Hospital and the Third Affiliated Hospital of Air Force Military Medical University, who were evaluated according to LEMON airway evaluation rule. Ventilation capacity score, airway airway score with soft vision mirror and comprehensive airway score of difficult airway were performed after admission to the operating room. Patients diagnosed with non-difficult airway were divided into group N and patients diagnosed with difficult airway were divided into group D. The number and proportion of patients in the two groups were counted, and the process of airway diagnosis, the way of airway establishment, the results, the frequency of hypoventilation during airway establishment, the number of intubation, and the time of airway establishment were analyzed.Results:A total of 15 patients in group N, accounting for 71.4%, underwent rapid intravenous induction nasal intubation after diagnosis of non-difficult airway, and the intubation was successful all the time. No hypoventilation occurred in all patients during intubation. A total of 6 patients in the group D, accounting for 28.6%, were assisted by pure oxygen mask ventilation after diagnosis of difficult airway, and underwent awake nasotracheal intubation after recovery. 4 patients were successfully intubated once, 2 patients were successfully intubated twice, and 1 patient experienced one hypopnea during the evaluation of ventilation capacity. The airway establishment time of the group N was (9.3±0.8)min, and that of the group D was (20.0±2.0)min, the difference was statistically significant ( P<0.05). The airway establishment time of all patients was (12.0±5.0)min, and the awake intubation time was (12.0±0.7.0)min. The proportion of patients satisfied with anesthesia in the group N was higher than that in the group D, and the difference was statistically significant ( P<0.05). No agitation during sevoflurane induction or recovery was observed in both groups. Conclusions:The diagnosis procedure of difficult airway can be safely applied to patients with multi-factor suspicious difficult airway with complex mouth restriction. Most of these patients do not have truly difficult airways; The application of difficult airway diagnosis procedures in these patients can significantly reduce unnecessary awake endotracheal intubation; Compared with the direct choice of awake intubation, following the difficult airway diagnosis procedure does not increase airway establishment time in such patients.

Objective:To understand the real experience of occlusion therapy in caregivers for children with congenital cataract, and provide reference for visual rehabilitation of children with congenital cataract after surgery.Methods:This article adopts a qualitative research method, using the purposive sampling method, a total of 14 caregivers of children with congenital cataracts who visited Guangzhou Women and Children's Medical Center of Guangzhou Medical University from October 2022 to April 2023 were selected, and a semi-structured interview was conducted using phenomenological research methods. Transcription, coding, analysis and theme extraction of interview data was conduceted using Colaizzi 7-step analysis method.Results:A total of three themes and seven sub themes were extracted, namely emotional experience (obvious sense of shame and positive development), difficulties in responding (difficulties in initial occlusion therapy, lack of effective coping methods and impaired confidence in treatment) and lack of support from others (lack of professional support and lack of family support) .Conclusions:Caregivers of children with congenital cataract have obvious stigma, difficulties in occlusion therapy and lack effective coping styles and support from others. Medical staff should pay attention to the psychology of the caregivers, build a standard postoperative visual function rehabilitation program, make reasonable use of health education means, help them establish positive treatment beliefs, improve medical professional support and promote family support.

Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

Objective To explore whether stimulator of interferon genes(STING)agonist ADU-S100 could enhance the antitumor immune response of a chitosan(CS)nanoparticle-mediated DNA vaccine containing a tumor-specific antigen Dickkopf-related protein 1(DKK1)in multiple myeloma(MM).Methods CS-DNA nanoparticles were prepared by using the compound coprecipitation method.The particle sizes and Zeta potential of the CS-DNA nanoparticles were measured by using the Zetasizer Nano-ZS laser particle size analyzer.The DNA protection effect and in vivo DNA expression efficiency of the CS-DNA nanoparticles were assessed by using gel retardation assay and Western blot,respectively.The lentiviruses expressing human DKK1(hDKK1)genes were used to establish MPC-11 cells(MPC-11-hDKK1)which stably expressed hDKK1,and the MPC-11-hDKK1 cells were subcutaneously given to mice to construct tumor models.The tumor-bearing mice were randomly divided into a control group(intramuscular injection of CS-pcDNA3.1),an ADU-S100 immunization group(subcutaneous injection of ADU-S100),a CS-pDKK1 immunization group(intramuscular injection of CS-pDKK1)and an ADU-S1OO/CS-pDKK1 co-immunization group(intramuscular injection of CS-pDKK1+subcutaneous injection of ADU-S100),with 5 mice in each group.The tumor-bearing mice in each group were immunized 3 times at 10-day intervals according to the corresponding immunization schedule.The size of tumor was measured every week.On day 42 after MPC-11-hDKK1 cell inoculation,the tumor weight of mice in each immunization group was measured;the percentages of CD11c+dendritic cell(DC),CD8+CD11c+DC and major histocompatibility complex class Ⅱ(MHCII)+CD11c+DC subsets in the spleen of mice in each immunization group were detected by using flow cytometry.The splenocytes of mice in each group were stimulated with recombinant hDKK-1 protein in vitro,the percentage of EdU+cells in CD8+T lymphocytes in each immunization group was detected by using flow cytometry,and the killing effect of cytotoxic T lymphocyte(CTL)in each group was assessed by using the lactate dehydrogenase(LDH)cytotoxicity assay kit.Results The particle size and Zeta potential of the CS-DNA nanoparticles were(204.3±2.31)nm and(15.47±1.01)mV,respectively.Gel retardation assay showed that DNA enveloped in CS nanoparticles could be completely retarded.Western blot analysis indicated that CS-DNA nanoparticles could be effectively expressed in vivo.The relative expression of DKK1 protein was significantly higher in MPC-11-hDKK1 cells than in MPC-11-Ctrl cells(P＜0.05).On days 7 and 14 after MPC-11-hDKK1 cell inoculation,there was no significant difference in tumor volume of mice between the ADU-S100 immunization group,CS-pDKK1 immunization group,ADU-S100/CS-pDKK1 co-immunization group and the control group(P＞0.05);on days 21,28,35 and 42 after MPC-11-hDKK1 cell inoculation,the tumor volumes of mice in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S100/CS-pDKK1 co-immunization group were significantly lower than those in the control group(P＜0.05);the tumor volume of mice in the ADU-S100/CS-pDKK1 co-immunization group was significantly lower than that in the ADU-S100 immunization group and CS-pDKK1 immunization group(P＜0.05).On day 42 after MPC-11-hDKK1 cell inoculation,the tumor weight of mice in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S1 OO/CS-pDKK1 co-immunization group was significantly lower than that in the control group(P＜0.05);the tumor weight of mice in the ADU-S100/CS-pDKK1 co-immunization group was significantly lower than that in the ADU-S100 immunization group and CS-pDKK1 immunization group(P＜0.05).The proportions of CD11c+DC,CD8+CD11c+DC and MHCII+CD11c+DC subsets in the spleen of mice in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S100/CS-pDKK1 co-immunization group were significantly higher than those in the control group(P＜0.05).The proportions of CD11c+DC,CD8+CD11c+DC and MHCII+CD11c+DC subsets in the spleen of mice in the ADU-S100/CS-pDKK1 co-immunization group were significantly higher than those in the ADU-S100 immunization group and CS-pDKK1 immunization group(P＜0.05).The CTL killing effect and the proportion of EdU+cells in CD8+T lymphocytes in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S1OO/CS-pDKK1 co-immunization group were significantly higher than those in the control group(P＜0.05);the CTL killing effect and the proportion of EdU+cells in CD8+T lymphocytes in the ADU-S100/CS-pDKK1 co-immunization group were significantly higher than those in the ADU-S100 immunization group and CS-pDKK1 immunization group(P＜0.05).Conclusion STING agonist ADU-S100 can significantly improve the antitumor immunity of the CS-pDKK1 nanoparticle vaccine in MM,and this vaccine strategy provides a potential treatment approach for MM.

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans ; Fibroblast Growth Factors ; Phosphatidylinositol 3-Kinases/metabolism* ; Central Nervous System/metabolism* ; Signal Transduction/physiology* ; Alzheimer Disease

Objective:To investigate the risk factors for concomitant cardiac autonomic neuropathy in diabetic patients and to develop a Nomogram prediction model.Methods:One hundred and fifty-eight diabetic patients admitted to in Southern Hospital Zengcheng Branch from March 2019 to March 2021 were selected. Patients with normal heart rate variability were the diabetic group, and patients with abnormal heart rate variability were the group with diabetes mellitus complicated by cardiac autonomic neuropathy. Logistic regression analysis was used to analyze the risk factors of cardiac autonomic neuropathy. Nomogram models were developed and model performance was evaluated. Decision curve analysis (DCA) was used to assess the net clinical benefit of the Nomogram model.Results:Comparison of general data showed that fasting blood glucose, tumour necrosis factor-α (TNF-α), glomerular filtration rate (eGER), uric acid, C-reactive protein (CRP), interleukin-6 (IL-6), free fatty acids (FFA), standard deviation of sinus heart beat RR interval (SDNN), and duration of diabetes compared to the diabetic group had statistically significant ( P<0.05); the results of the subject work characteristics (ROC) curve analysis showed that the best cut-off values for fasting glucose, TNF-α, eGFR, uric acid, CRP, IL-6, FFA, SDNN and duration of diabetes were >7.53 mmol/L, >98.45 ng/L, ≤94.79 ml/(min·1.73 m 2), > 87.3 μmol/L, >6.22 μmol/L, >37.84 ng/L, >839.19 μmol/L, ≤ 95.88 ms, >9 years; multi-factorial Logistic regression analysis showed that fasting glucose (>7.53 mmol/L), TNF-α (>98.45 ng/L), CRP (>6.22 μmol/L), IL-6 (>37.84 ng/L), FFA (>839.19 μmol/L), SDNN (≤95.88 ms), and duration of diabetes (>9 years) were risk factors for the development of cardiac autonomic neuropathy in diabetic patients; internal validation showed that the Nomogram model predicted a C-index of 0.706 (95% CI 0.668 - 0.751) for the risk of cardiac autonomic neuropathy. The DCA results showed that the Nomogram model predicted a risk threshold of >0.25 for the development of cardiac autonomic neuropathy and that the Nomogram model provided a net clinical benefit. Conclusions:There are many risk factors for cardiac autonomic neuropathy, and the nomogram model based on risk factors in this study has good predictive power and may provide a reference for clinical screening of high-risk patients and further improvement of treatment planning.

ABSTRACT OBJECTIVE To explore the pharmacological mechanism of trace elements in preterm low birth weight infants through network pharmacology. METHODS Targets associated with trace elements were obtained from Drugbank database and TTD database. Genes related to preterm low birth weight infants were collected from GeneCards database and DisGeNET database. Two groups of data were intersected to get mapping targets. Protein-protein interaction network of mapping targets were constructed by STRING database. Candidate targets were screened by Cytoscape 3.6.1 and ranked to obtain key targets. The major trace elements were defined by establishing network of “trace elements-candidate targets”. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) term enrichment analysis was performed via g:Profiler software to predict the molecular mechanisms and related pathways of trace elements on preterm low birth weight infants. RESULTS A sum of 211 targets of trace elements in preterm low birth weight infants were screened, including 26 candidate targets and three key targets: albumin(ALB), glyceraldehyde-3-phosphate dehydrogenase(GAPDH) and fibronectin 1(FN1). The major trace elements were copper(Cu) and zinc(Zn), regulating 22 and 19 targets respectively. KEGG pathway enrichment analysis predicted that three major pathways were complement and coagulation cascades, cholesterol metabolism as well as lipid and atherosclerosis. CONCLUSION The major trace elements Cu and Zn may cause neuronal damage and reduce the risk of oxidative stress-related diseases in premature infants through the regulation of GAPDH, ceruloplasmin(CP), superoxide dismutase 1(SOD1), etc. The appropriate levels of Cu and Zn for preterm infants may regulate cholesterol metabolism and other signaling pathways and therefore reduce the risk of cardiovascular diseases in premature infants and adult. Further investigation of the pharmacological mechanism of trace elements in preterm infants is necessary to provide a more sufficient theoretical basis for the good growth and development of preterm infants.

Objective:To evaluate the therapeutic efficacy of interposition urethroplasty on glandular hypospadias and severe penile curvature.Methods:A total of 9 cases of congenital glandular hypospadias and 2 cases of congenital severe penile curvature (>30°) treated with the interposition urethroplasty technique in the Shenzhen Children′s Hospital from November 2008 to December 2019 were retrospectively analyzed.The mean age of initial surgery was 40 (25-109) months.Two cases were surgically treated with one-staged interposition urethroplasty and the remaining were treated with two-staged interposition urethroplasty.They were followed up for 8 months to 12 years, including the penile morphology, urination, urethrocutaneous fistula, urethral stricture and uroflowmetry.Continuous variables were presented as ± s deviation, Student′s t-test was used for comparison between groups. Results:The median length of interposition urethra was 3.2 (2.2-4.2) cm.The cosmetic appearance of penis was good without residual chordee, urethral stricture or urethral diverticulum in all patients.Two cases had urethrocutaneous fistula(one-staged repair and two-staged repair were performed in one case respectively), which were successfully repaired by re-operation.The maximum of uroflowmetry in patients at 3 months [(8.3±1.0) mL/s] and 6 months [(6.7±1.9) mL/s] after surgery was significantly lower than that of children in healthy control group [(10.5±3.7) mL/s] ( t=3.221, 3.864, all P<0.05). However, there was no significant difference in 1-year maximum of uroflowmetry postoperatively between surgically treated patients [(10.5±3.7) mL/s] and healthy control group ( P>0.05). Conclusions:Interposition urethroplasty is an effective and safe treatment for glandular hypospadias and/or severe penile curvature in children.