Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

Objective To develop an evidence-based practice program for ICU eye care and evaluate its application effect using Stetler model of research utilization.Methods The systematic search was carried out in domestic and foreign guid elines,systematic reviews,evidence summaries,expert consensuses on eye care for ICU patients.The quality of the included literature was evaluated and the evidence was summarized.The evidence based on expert advice,clinical context and stakeholder opinions was screened.According to Stetler model of research utilization,the evidence translation/application was formulated from 3 aspects,including method,level and type of evidence application,and the evidence translation was implemented using a stepwise trial design.Five ICUs in a tertiary hospital in Zhejiang Province were selected,and the order of enrollment of each ICU was determined by computer-generated random numbers from April to september,2022.In the first month,all ICUs were in pre-evidence-based practice period,and in the second month,an ICU was trained and entered the evidence-based practice period.Until the 6th month,all ICUs entered the evidence-based practice period.Then the rate of ocular symptoms and implementation rate of eye care measures were compared before and after EBP.Results A total of 1 540 patients were included.With regard to the implementation rate of eye care measures,the rate of lubricant use and suspected ocular infection management in patients at high risk for ocular complications in evidence-based practice period was significantly higher compared with pre-evidence-based practice period(P＜0.001),and no statistically significant difference was found in the rate of eyelid closure.The incidence of conjunctival exposure,subconjunctival hemorrhage,conjunctival congestion,and ocular discharge in non-neurology critical care patients decreased compared with pre-evidence-based practice period(P＜0.05),and the incidence of conjunctival edema and conjunctival congestion in NICU patients decreased compared with pre-evidence-based practice period as the intervention continued(P＜0.001).Conclusion Evidence-based practice in eye care for ICU patients using Stetler model of research utilization can standardize the practice of eye care for ICU patients and improve the quality of care.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Objective:To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China.Methods:A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors.Results:The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ2=7.91 and 8.06, both P=0.005) and vitamin D ( χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR=0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ2=93.22 and 202.54, both P<0.001). Conclusions:Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

The expression of vascular endothelial growth factor(VEGF)in ovarian cancer tissues is closely related to the degree of malignancy of ovarian cancer,and can be an effective target for ovarian cancer treatment.Bevacizumab,as a monoclonal antibody targeting VEGF,can inhibit tumor neovascularization and tumor growth,and is used for the treatment of ovarian cancer,cervical cancer,metastatic colorectal cancer and other malignant tumors.Bevacizumab administered by intraperitoneal perfusion has good efficacy for malignant ascites in tumor patients,and can alleviate patients'clinical symptoms.In recent years,more studies have explored the clinical application method,therapeutic efficacy and related adverse effects of bevacizumab intraperitoneal instillation in the treatment of ovarian cancer,and this article is a review in this field,aiming to provide reference for the clinical treatment of ovarian cancer.

Objective: To understand the incidence of delayed vaccination with the national immunization program vaccines among children aged 0-6 years in Xuhui District, Shanghai, and to evaluate the safety of delayed vaccination. Methods: A stratified random sampling was used to obtain six vaccination clinics in Xuhui District, Shanghai. The vaccination records of children 0-6 years from these six vaccination clinics were collected from the Shanghai Immunization Program Information Management System. Adverse events following immunization (AEFI) data were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiology was used to analyze the data. Children were divided into the timely vaccination group and delayed vaccination group according whether they were delayed in vaccination (received one month or more after the recommended age among children aged ≤1 year; received three months or more after the recommended age among children aged >1 year). The safety of four vaccination methods-individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination-were further compared. Differences between groups were compared using chi-square test. Results: From 2019 to 2021, six vaccination clinics in Xuhui District administered 124 031 doses of the national immunization program vaccines among children aged 0-6 years, and delayed vaccinations accounted for 25.99% (32 234/124 031) of these doses. In 2020, the delayed vaccination rate during the first-level COVID-19 public health emergency response period in Shanghai was significantly higher than that in the same period in 2019 (34.70% vs. 24.19%, χ²=136.23, P<0.05). The delayed vaccination rate during the COVID-19 vaccination campaign in 2021 was significantly higher than that in the same period in 2019 (25.27% vs. 22.55%, χ²=82.80, P<0.05). From 2019 to 2021, a total of 475 cases of AEFI were reported in six vaccination clinics, with a reported incidence of 382.97 per 100 000 doses, including 421 cases of common adverse reaction (88.63%, 339.43 per 100 000 doses), 51 cases of rare adverse reaction (10.74%, 41.12 per 100 000 doses) and 3 cases of coincidences (0.63%, 2.42 per 100 000 doses). The reported incidence of AEFI among delayed vaccinations was significantly lower than that among timely vaccinations (291.62 per 100 000 doses vs. 415.05 per 100 000 doses). The incidence of AEFI for the four delayed vaccination methods (individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination) was lower than that for timely vaccination. There were significant differences between the groups except for the routine vaccination group (χ²=9.82, P<0.05; χ²=5.46, P<0.05; χ²=2.97, P>0.05; χ²=11.89, P<0.05). Conclusions: In Xuhui District of Shanghai, 25.99% of doses of the national immunization program vaccines administered to children 0-6 years were delayed. Delayed vaccination does not increase the risk of AEFI compared with timely vaccination.

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens