ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

Objective: To investigate the spatial clustering characteristics of varicella public health emergency events in Nanjing City from 2017 to 2022, so as to provide the evidence for the development of varicella prevention and control strategies. Methods: Data of varicella public health emergency events in Nanjing City from 2017 to 2022 were collected through Emergency Public Health Management Information System of Chinese Disease Prevention and Control Information System. The software ArcGIS 10.2 was employed for trend-surface analysis, spatial autocorrelation analysis and hotspot analysis to understand the spatial clustering characteristics of varicella public health emergency events. Results: A total of 84 varicella public health emergency events were reported in Nanjing City from 2017 to 2022, with an average attack rate of 2.53% (2 558 cases). Ⅳ-level events were predominant, accounting for 90.48% (76 events). The trend-surface analysis showed lower incidence of varicella public health emergency events in the west of Nanjing City and higher in the east, and lower in the north and higher in the south. The global spatial autocorrelation analysis showed that there was a positive spatial correlation in varicella public health emergency events in 2017 and 2019, indicating spatial clustering (P<0.05). The hot spots were Jiangning District, Gaochun District, Yuhuatai District and Jianye District. Conclusion The incidence of varicella public health emergency events in Nanjing City from 2017 to 2022 has spatial aggregation, with a concentration in suburban areas such as Jiangning District and Gaochun District.

Neurodevelopmental disorders(NDDs)are chronic developmental brain disorders that can affect cognition,motor,social adaptation,behavior and so on due to multiple genetic or acquired causes.Natural polysaccharides are synthesized by living organisms,located in the cell wall,inside and between cells,and outside the cells,and are essential components of life activities.Previous studies have found that natural polysaccharides play an important role in neurological diseases,which mainly ameliorate the behavioral abnormalities and clinical symptoms caused by anti-oxidative stress,anti-neuronal apoptosis,anti-neuroinflammation,anti-excitatory amino acid toxicity,and regulation of the brain-gut axis.This review summarizes the intervention role of 17 bioactive polysaccharides from plants and fungi in neurological diseases,aiming to provide new ideas for the research and treatment of NDDs.

Objective:To investigate the effects of mixed probiotics on food allergy and the underlying mechanism.Methods:BALB/c mice on the 15 th day of pregnancy were randomly (random number table method) classified into the control group, food allergy model group and mixed probiotics group.Mice in the food allergy model and mixed pro-biotics group were subjected to ovalbumin (OVA) sensitization after birth, and those in the mixed probiotics group were then given probiotic solution by gavage from day 21 to day 35.Mice in control group were similarly given 9 g/L saline.Twenty-four hours after the last OVA sensitization, intestinal histopathological sections were prepared to observe intestinal pathological changes.Blood smears were prepared to detect eosinophil count.In addition, serum samples were collected to measure cytokine levels and OVA specific antibodies.The number of dendritic cells (DCs) and regulatory T cells (Tregs) in mouse mesenteric lymph nodes was calculated.Differences among 3 groups were compared by the One- Way ANOVA or Kruskal- Wallis H test. Results:Compared with those of food allergy model group, diarrhea score, the ratio of eosinophils and serum levels of interleukin(IL)-4, IL-5, IL-13, mast cell protease 1 (MCPT-1), and OVA specific antibodies IgE and IgG were significantly lower in mixed probiotics group[(2.00±0.71) points vs.(3.22±0.97) points, (2.28±1.61)% vs.(10.99±2.26)%, (413.68±22.81) ng/L vs.(708.78±27.66) ng/L, (36.64±3.74) ng/L vs.(46.05±4.95) ng/L, (201.37±65.61) ng/L vs.(495.22±96.66) ng/L, (31 924.15±1 177.77) ng/L vs.(36 175.77±618.29) ng/L, (9.10±8.08) ng/L vs.(19.69±0.84) ng/L, (30.50±8.81) ng/L vs.(190.32±6.40) ng/L], while IL-10 level was significantly higher[(164.12±3.88) ng/L vs.(123.90±7.31) ng/L] ( t=3.37, 8.72, 16.07, 3.90, 7.40, 7.95, 3.91, 44.00 and 7.76, respectively, all P<0.01). Compared with those of food allergy model group, programmed cell death ligand 1 (PD-L1) level on the surface of CD 103+ DCs and CD 103+ CD 80-CD 40-DCs, the proportion of Tregs in CD4 + T cells, and the level of programmed cell death 1 (PD-1) on the surface of Tregs were significantly higher in mixed probiotics group[(75.59±0.45)% vs.(45.60±4.73)%, (67.56±1.87)% vs.(37.12±6.07)%, (8.24±0.69)% vs.(6.20±0.66)%, (11.25±3.12)% vs.(4.08±2.33)%]( t=7.88, 4.48, 3.63 and 3.71, all P<0.01). Conclusions:Mixed probiotics can alleviate the symptoms of food allergy and inflammatory response of young rats through mediating Tregs via the PD-1/PD-L1 pathway.

Objective:To retrieve, evaluate, and summarize the best evidence for the assessment of gastrointestinal function in critically ill patients by bedside ultrasound.Methods:Guidelines, evidence summaries, group standards, expert consensus, systematic reviews, and randomized controlled trials on the assessment of gastrointestinal function in critically ill patients by bedside ultrasound were retrieved by computer on domestic and foreign guideline websites, society websites and databases based on evidence-based nursing. The search period was from January 1, 2010 to April 30, 2021. The quality of the article was independently assessed by two researchers using the Appraisal of Guidelines for Research and Evaluation Ⅱ and the critical appraisal tool of the Joanna Briggs Institute (JBI) in Australia (2016) . Combined with the judgment of the research team, the data from the article that met the criteria were extracted and the evidence was graded and recommended according to the JBI quality level of evidence system (2014 Edition) .Results:A total of 22 articles were included, involving 5 guidelines, 1 evidence summary, 1 group standard, 6 expert consensuses, 4 systematic reviews, and 5 randomized controlled trials. A total of 33 pieces of evidence were summarized from 6 aspects, namely, the feasibility of nurses applying bedside ultrasound, fundamentals of ultrasound assessment of gastrointestinal tract, ultrasound assessment of gastric contents, ultrasound assessment of gastric motility, ultrasound assessment of bowel, ultrasound guided enteral nutrition program.Conclusions:Nurses who have been systematically trained can use ultrasound to assess gastrointestinal function in critically ill patients in real time. Ultrasound-guided enteral nutrition for critically ill patients needs to be standardized and improved, and many studies need to be carried out.

Objective To compare the effects of sevoflurane and propofol anesthesia on endothelial glycocalyx degradation in the patients undergoing abdominal surgery.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 25-75 yr,weigbing 45-80 kg,scheduled for elective open colon or rectal surgery,were divided into 2 groups (n =30 each) using a random number table method:sevoflurane anesthesia group (group S) and propofol anesthesia group (group P).In group S,1.5％-2.5％ sevoflurane was inhaled for maintenance of anesthesia.In group P,propofol was intravenously infused at 50-150 μg · kg-1 · m-1 to maintain the bispectral index value at 40-60.The concentrations of heparan sulfate (HS),syndecan-1 and vascular cell adhesion molecule-1 (VCAM-1) in serum were determined after tracheal intubation (T0),at 1 h after skin incision (T1),at 2 h after skin incision (T2),at the end of operation (T3) and at 24 h after operation (T4).Blood gas analysis and blood biochemical test were performed at T0 and T4,and strong ion gap (SIG) was calculated.Results Compared with the baseline at T0,the concentrations of serum HS at T2-4 and syndecan-1 at T3-4 and SIG at T4 were significantly increased,and the concentrations of serum ALB at T4 were decreased in S and P groups (P＜0.05).Compared with group P,the concentrations of serum HS at T3,4 and syndecan-1 at T4 and SIG at T4 were significantly decreased,the concentrations of serum ALB at T4 were increased (P＜0.05),and no significant change was found in the serum concentrations of VACM-1 and lactate in group S (P＞0.05).Conclusion Compared with propofol anesthesia,sevoflurane anesthesia is more helpful in decreasing endothelial glycocalyx degradation and in reducing vascular endothelial damage in the patients undergoing abdominal surgery.

Objective:To explore the diagnostic value of ultrasound-guided fine needle aspiration biopsy(US-FNAB)for thyroid nod-ules.Methods:The clinical characteristics and cytopathological diagnosis of patients with thyroid nodules in Tianjin Medical University General Hospital were analyzed retrospectively;the results of the cytopathological and pathological diagnoses were compared and an-alyzed.Results:Of the 1,241 US-FNAB samples,the ratio of men to women with thyroid nodules was 1:3.83(257/984).The incidence of thyroid nodules gradually increased from the age of 20 years and declined after the age of 60 years.The nodules,which were less than or equal to 1.0 cm in size,accounted for 51.57%(640 cases),and Thyroid Imaging Reporting And Data System(TIRADS)classifica-tion 4 accounted for 86.38%(1 072 cases).Of cyto-pathological diagnoses,22.00%(273 cases)were non-diagnostic,9.75%(121 cases) were benign,30.62%(380 cases)were atypia with undetermined significance,32.15%(399 cases)were suspicious for malignancy,and 5.48%(68 cases)were malignant.In the 302 patients who underwent surgery,the number of cases of clear diagnoses,unavailable di-agnoses,and atypia of undetermined significance were 203,21,and 78,respectively.In the 203 cases of clear diagnoses,the sensitivi-ty,specificity,positive predictive value,negative predictive value,precision,and misdiagnoses following US-FNAB of thyroid nodules were 100.00%(201/201),50.00%(1/2),99.50%(201/202),100.00%(1/1),99.51%(202/203),and 0.49%(1/203),respectively.In the 78 cases that were atypia of undetermined significance,the malignancy rate was 70.51%.Whether the atypia of undetermined signifi-cance was malignant or not was related to the TIRADS classification(P<0.05),and not related to the age,sex,tumor size,or location of the nodules(P>0.05).Conclusions:US-FNAB has high diagnostic value for thyroid nodules and is worthy of being popularized widely.If it replaced some intra-operative frozen sectioning procedures,it may reduce intra-operative waiting time and financial burden of pa-tients.

Objective Curculiginis extract has good scavenging effects on oxygen free radicals, and there is no curculiginis extract for AD research at home.The aim of this study was to explore the influence of Curculigoside on the cognitive learning and memory functions of senile dementia model rats induced by D-galactose combined with β-protein amyloid β25-35 (Aa25 35) and the expression level of hippocampus B-cell lymphoma-2 (Bcl-2), Bax, estrogen receptor (ER) protein and mRNA.Methods Forty SD rats weredivided into the control group (equal saline was intraperitoneal injected for six weeks consecutively, and equal saline was injected to the bilateral hippocampus in the seventh week), the model group (galactose was intraperitoneal injected for six weeks consecutively, and 4 mmol/L Aβ25-35 was injected to the bilateral hippocampus in the seventh week), the low dosage group and the high dosage group randomly (the stomach irrigation of low dosage 24mg/kg or the high dosage 72mg/kg curculigoside was applied every day, for 8 weeks), 10 rats in each group.After the treatment , the Morris water maze was conducted to test the space learning and memory functions of rats;the flow cytometry method was conducted to analyze the neuronal apoptosis conditions;the western blot was conducted to detect Bcl-2, Bax and ER protein level;the Realtime PCR was conducted to detect Bcl-2, Bax and ER mRNA level.Results Morris water maze test results: Compared with the model group, the escape latency (EL) of the rats of the model group, the low dosage group and the high dosage group on the 2nd, the 3rd, the 4th and the 5th day significantly extends (P<0.01), and the high dosage group significantly shortens (P<0.05) than the low dosage group.Space exploration test results: Compared with the proportion of the distance swum within the quadrant by the rats in the model group in the total distance [(30.14±5.10)%], that of the low dosage group, the high dosage group and the control group [(41.98±4.78)%, (46.17± 9.31)% and (50.13±6.81)%] significantly increases (P<0.01);in addition, the high dosage group is higher than the low dosage group (P<0.05).Compared with the apoptosis rate of rates in the model group[(7.11±1.78)%], that of the high dosage group, the low dosage group and the control group[(5.53±1.45)%], (4.11±1.03)% and (3.08±1.33)% significantly decreases (P<0.05).Compared with the control group, the Bcl-2 and Bax protein expression of the model group significantly increases, and the cell Bcl-1 and Bax of cells significantly decreases (P<0.05).Compared with the model group, the Bcl-2 and ER protein expression as well as the Bcl-2/Bax of the high dosage group and the low dosage group significantly increase, and the Bax protein expression significantly decreases (P<0.05).Compared with the mRNA expression (1.00 and 1.00) of Bcl-2 and ER in the control group, the mRNA expression (1.31 and 1.98) of the Bcl-2 and Bax in the model group significantly increases (P<0.05);compared with the mRNA expression (1.13 and 1.08) of Bcl-2 and ER in the model group, the Bcl-2 (1.95 and 2.01) and mRNA expression (1.81 and 1.96) of ER of the high dosage group and the low dosage group significantly increase (P<0.01).Conclusion Curculigoside plays an improving role in space learning and memory functions of senile dementia model rats, with the mechanism may be related to the protection to the hippocampus neurons by restraining Bax expression and neuronal apoptosis through the up-regulation of hippocampus ER and Bcl-2 expressions.

Avian influenza virus H6N1 subtype has been circulating in aquatic bird and terrestrial bird,and is the most frequently detected subtype of influenza A virus in those hosts.Genetic analysis results suggested that this virus might be the progenitor of the highly pathogenic avian influenza H5N1 virus,as seven of eight gene segments of those viruses had a common source.As continuing evolution of H6N1,it could spread across species barriers to mammals and had strong infection ability in mice,swine and ferrets.Serological epidemiological survey showed that a few people were positive for H6 avian influenza virus antibody and then the world's first human infection with influenza virus H6N1 subtype was reported in May 2013.Therefore,with the expansion of the host range of the virus,gene mutation and gene reassortment of H6N1 virus can occur in these hosts,and then it may evolve into novel variant strain with infected human potential.