Background and purpose:Senescent cancer-associated ifbroblasts (CAFs) in tumor microenvi-ronment are known to mediate the invasion and radio- or chemo-resistance of epithelial cancers. The inflammatory cytokine IL-6 derived from CAFs may promote the invasion and radio-resistance of epithelial cervical cancer. However, the detailed mechanism is not clear. This study aimed to investigate the effects of IL-6 on CAFs senescence, cervical cancer cell invasiveness and radio-resistance.Methods:CAFs from cervical cancer, normal ifbroblasts (NFs) from nor-mal cervical tissues, and cervical cancer cell lines including HeLa, Siha and ME180 were used in this study. Different treatments of cells with IL-6 and inhibitors of STAT3 and Notch were conducted to investigate the alterations of cellular senescence, STAT3/Notch signaling, cell invasiveness, and radiotherapy-induced apoptosis by using cell staining, immunolfuorescence, Western blot, and lfow cytometery.Results:This study found that the conditioned medium (CM) of CAFs or IL-6 could activate the STAT3 and Notch signaling to promote cellular senescence and cervical cancer cell invasiveness. Co-culture of cervical cancer cells HeLa or Siha along with CAFs also increased the invasiveness of can-cer cells, but further treatments of cells by addition of an IL-6 antibody or the inhibitors of STAT3 (S31-201) or Notch (DAPT) blocked the cancer cell invasion. Meanwhile, this study also found that STAT3 functions at the upstream of the Notch signaling to up-regulate Jagged-1, one of the key ligands of Notch in ifbroblasts or epithelial cancer cells through IL-6-mediated autocrine or paracrine pathways, which eventually confers the radio-resistance of cervical cancer cells/tissues.Conclusion:CAFs in tumor microenvironment could induce cervical cancer cell invasiveness and radio-re-sistance through IL-6/STAT3-mediated Notch activation, and that targeting of the STAT3/Notch signaling-associated molecules may improve the effcacy of radiotherapy for cervical cancer.

Objective To study the clinical effect of short covering method in preventing the recurrence of amblyopia in older children and adolescents. Methods According to the digital table, 146 older children and adolescents ( 200 eyes ) with amblyopia were randomly divided into two groups, each group had 73 patients (100 eyes). The comprehensive therapy group was given 1 month of comprehensive treatment after the corrected visual acuity was more than or equal to 0. 9,and the visual acuity was reviewed within 2-6 months after the termina-tion of treatment. The short covering group was continuously given comprehensive therapy 1 month of treatment after the corrected visual acuity of the amblyopic eye was greater than or equal to 0. 9,then changed to short covering for 2-3 hours every day,in the visual focus time like class or homework time to cover,covering the first half of the year, every month for one time of review on vision. The changes of visual acuity in the two groups were compared before and after treatment,and the qualities of life of patients before and after treatment was compared. Results In the short covering group,all of them had improved visual acuity after treatment. Among them, the improvement of 1 line had 18 eyes,the improvement of 2 lines and above had a total of 82 eyes. In the combined therapy group,the visual acuity decreased after treatment in 70 eyes. Among them,there were 30 eyes with a drop of 1 line,40 eyes with a decrease of 2 lines and more than 2 lines,and the other 30 eyes remained unchanged. Before treatment,100 eyes of all the patients in the short covering group were followed by the center of the eye,after treatment,the treatment of the eyes of 71 cases (90 eyes) turned to the center or the relative center of the eye,there were 2 cases(4 eyes) remained in the center of the eyes. After treatment,in the comprehensive therapy group,73 cases(100 eyes) were still at the center of the eye. Before treatment,there was no statistically significant difference in quality of life between the two groups[(59. 37 ± 6. 72)points vs. (59. 35 ± 6. 76)points,t=0. 145,P>0. 05]. After treatment,the quality of life in the short covering group was significantly better than that in the comprehensive therapy group[(95. 18 ± 4. 21) points vs. (50. 01 ± 2. 59)points,t=7. 655,P<0. 05]. Conclusion The clinical effect of preventing recurrence of amblyopia in older children and adolescents with short covering method is exact, which can effectively improve the visual acuity of patients and watching nature,improve the patients' quality of life,it is worthy of popularization and application.

Background: Dysregulation of intestinal flora is a key risk factor for colorectal cancer (CRC). In recent years, traditional Chinese medicine preparations and probiotics have been increasingly applied in the prevention of CRC. Aims: To investigate the preventive effect of Panax notoginseng saponins (PNS) combined with Bacillus subtilis on CRC. Methods: Thirty female BALB/c mice were randomly divided into normal control group (NC group), model group, PNS group, Bacillus subtilis group and PNS combined with Bacillus subtilis group (PaB group). CRC mice model was constructed by azoxymethane (AOM)/dextran sulfate sodium (DSS) method. During the experiment, the mice were weighed, and disease activity index (DAI) score was evaluated. The length of colorectum and tumor number were measured. Serum interleukin (IL) - 6 and IL - 10 contents were determined by ELISA. 16S rRNA sequencing was used to analyze the composition of intestinal flora. Results: Compared with model group, DAI score was significantly decreased (P<0.001), colorectal length was significantly increased (P<0.001), number of tumor was significantly decreased (P<0.001), tumor volume was significantly decreased (P<0.01), serum IL-6 content was significantly decreased (P<0.000 1), and serum IL-10 content was significantly increased in PaB group (P<0.000 1). The results of intestinal flora sequencing showed that Simpson index was significantly decreased in PaB group than in model group (P<0.05), Shannon index and Chao index were significantly increased (P<0.05), abundance of Bacteroidota was significantly increased (P<0.01), abundances of Firmicutes, Helicobacter and Oscillibacter were significantly decreased (P all <0.05), abundance of Lactococcus was significantly increased (P<0.05). Conclusions: The combination of PNS and Bacillus subtilis can effectively alleviate the occurrence of CRC caused by AOM/DSS, and its mechanism may be related to the improvement of composition of intestinal microbial community.

INTRODUCTION: The burden of frequent attenders (FAs) of emergency departments (EDs) on healthcare resources is underestimated when single-centre analyses do not account for utilisation of multiple EDs by FAs. We aimed to quantify the extent of multiple ED use by FAs and to characterise FAs. METHODS: We reviewed nationwide ED attendance in Singapore data from 1 January 2006 to 31 December 2018 (13 years). FAs were defined as patients with ≥4 ED visits in any calendar year. Single ED FAs and multiple ED FAs were patients who attended a single ED exclusively and ≥2 distinct EDs within the year, respectively. Mixed ED FAs were patients who attended a mix of a single ED and multiple EDs in different calendar years. We compared the characteristics of FAs using multivariable logistic regression. RESULTS: We identified 200,130 (6.3%) FAs who contributed to1,865,704 visits (19.6%) and 2,959,935 (93.7%) non-FAs who contributed to 7,671,097 visits (80.4%). After missing data were excluded, the study population consisted of 199,283 unique FAs. Nationwide-linked data identified an additional 15.5% FAs and 29.7% FA visits, in addition to data from single centres. Multiple ED FAs and mixed ED FAs were associated with male sex, younger age, Malay or Indian ethnicity, multiple comorbidities, median triage class of higher severity, and a higher frequency of ED use. CONCLUSION A nationwide approach is needed to quantify the national FA burden. The multiple comorbidities and higher frequency of ED use associated with FAs who visited multiple EDs and mixed EDs, compared to those who visited a single ED, suggested a higher level of ED burden in these subgroups of patients. The distinct characteristics and needs of each FA subgroup should be considered in future healthcare interventions to reduce FA burden.
Comorbidity ; Emergency Service, Hospital ; Ethnicity ; Humans ; Logistic Models ; Male ; Retrospective Studies ; Triage

Objective: To report the clinical and pathological features of primary proximal epithelioid sarcoma (PES) in skull base. Methods: The clinical and pathological features of four cases of PES in skull base from Sanbo Brain Institute of Capital Medical University and Kunming Sanbo Brain Institute were analysed retrospectively. Results: Three cases was female, and one male, the age ranged from 46 to 52 years.All cases occurred in skull base, and sellar region was the main site of involvement.Under the microscope, the tumor cells characterized by epithelioid cell changes, with or without rhabdoid tumor cells.Mitotic figure was active.Immunohistochemical staining showed that AE1/AE3, EMA and CD34 were variously expression in tumor cells.INI-1 protein was lost in all cases.Three cases were detected by FISH, and INI1 (22q11.2) gene locus was absent in them.Three patients died less than 3 months after surgery, and case 4 was under treatment after five months of surgery. Conclusions Primary PES in skull base mostly occurs in sellar region and its clinical prognosis is poor.It features with epithelioid/rhabdoid tumor cells with lack granuloma structure as distal ES.It has epithelial and mesenchymal differentiation characteristics.CD34 is always positive.INI1 gene deletion and protein loss expression are characteristic molecular alteration of PES.