Stroma surrounding the tumor cells plays crucial roles for tumor progression. However, little is known about the factors that maintain the symbiosis between stroma and tumor cells. In this study, we found that the transcriptional regulator-signal transducer and activator of transcription 3 (Stat3) was frequently activated in cancer-associated fibroblasts (CAFs), which was a potent facilitator of tumor malignancy, and formed forward feedback loop with platelet-activating factor receptor (PAFR) both in CAFs and tumor cells. Importantly, PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells. Two central Stat3-related cytokine signaling molecules-interleukin 6 (IL-6) and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs. Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model. Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.

BACKGROUND: Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis. METHODS: CCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells. RESULTS: RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein. CONCLUSION CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.
Humans ; HeLa Cells ; RNA, Long Noncoding/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Vimentin/metabolism* ; MicroRNAs/metabolism* ; Colonic Neoplasms/genetics* ; RNA-Binding Proteins/metabolism* ; Gene Expression Regulation, Neoplastic/genetics* ; Cell Movement/genetics*

Among current novel druggable targets, protein–protein interactions (PPIs) are of considerable and growing interest. Diacylglycerol kinase α (DGKα) interacts with focal adhesion kinase (FAK) band 4.1-ezrin-radixin-moesin (FERM) domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma (ESCC) cells. Chrysin is a multi-functional bioactive flavonoid, and possesses potential anticancer activity, whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment. In this study, we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo, whereas produced no toxicity to the normal cells. Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKα contributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex. This study has illustrated DGKα/FAK complex as a target of chrysin for the first time, and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.

Objective:To know the critical care resources of the different class-hospitals in Guizhou Province, China, and to provide the direction and evidence for quality improvement and discipline construction of critical care medicine in Guizhou Province.Methods:The resource status of the departments of intensive care unit (ICU) in Guizhou Province was obtained through form filling and/or field investigation. The forms were filled and submitted from May 2017 to February 2018, and the field investigation (some of the hospitals) was carried out in March 2018. The data of hospitals in Guizhou Province in 2018, was obtained from the official website of Health Committee of Guizhou Province, which was released online on November 28th, 2019. The obtained data were summarized and analyzed according to different aspects such asthe status of ICU construction, main equipment configuration and technology implementation.Results:There were 39 third-class hospitals and 77 second-class hospitals included in this study, which accounted for 76.5% (39/51) of third-class public hospitals and 50.0% (77/154) of second-class public hospitals respectively. Among them, there were 86.8% (33/38) of third-class general hospitals and 50.4% (69/137) of second-class general hospitals respectively. In terms of ICU construction, compared with the ICUs of second-class hospitals, the ICUs of third-class hospitals were established earlier [years: 2011 (2008, 2012) vs. 2013 (2011, 2015), P < 0.01], had more ICU beds, doctors and nurses [15 (11, 20) vs. 8 (6, 10), 9 (8, 11) vs. 6 (5, 7), 25 (20, 41) vs. 15 (12, 19), respectively, all P < 0.01]. However, there were no significant differences regarding the doctor-bed ratio and the nurse-bed ratio in ICUs between second-class hospitals and third-class hospitals. In terms of main equipment configuration, compared with the ICUs of second-class hospitals, the ICUs of third-class hospitals had more ventilators, higher ratio of ventilators to beds, more infusion pumps, higher ratio of infusion pumps to beds, more monitor, gastrointestinal nutrition pumps and single rooms, and higher proportion of ICUs equipped with negative pressure rooms [ventilators: 14 (10, 18) vs. 6 (4, 8), ratio of ventilators to beds: 1.0 (0.7, 1.1) vs. 0.8 (0.6, 1.0), infusion pumps: 10 (6, 20) vs. 5 (3, 8), ratio of infusion pumps to beds: 0.8 (0.0, 1.0) vs. 0.0 (0.0, 0.4), monitor: 18 (13, 24) vs. 9 (6, 12), gastrointestinal nutrition pumps: 2 (1, 5) vs. 1 (0, 3), single rooms: 2 (1, 3) vs. 1 (0, 3), proportion of ICUs equipped with negative pressure rooms: 53.8% (21/39) vs. 31.5% (23/73), respectively, all P < 0.05]. Furthermore, there were higher proportions of ICUs equipped with portable ventilator, pulse indicator continuous cardiac output monitoring (PiCCO), intra-aortic balloon pump (IABP), extra-corporeal membrane oxygenation (ECMO), B ultrasound machine, bronchoscope, pressure of end-tidal carbondioxide (P ETCO 2) monitoring, bispectral index (BIS) monitoring, bedside gastroscopy, the apparatus used for the prevention of deep vein thrombosis of lower extremity in third-class hospitals than in second-class hospitals [portable ventilator: 86.7% (26/30) vs. 59.6% (28/47), 43.3% (13/30) vs. 1.5% (1/66), 14.3% (4/28) vs. 0% (0/65), 10.7% (3/28) vs. 0% (0/65), 62.5% (20/32) vs. 37.3% (25/67), 97.1% (33/34) vs. 63.6% (42/66), 60.6% (20/33) vs. 28.4% (19/67), 17.2% (5/29) vs. 0% (0/65), 27.6% (8/29) vs. 1.5% (1/65), 77.4% (24/31) vs. 52.3% (34/65), respectively, all P < 0.05]. In terms of skills development, there were more ICUs carried out intracranial pressure monitoring, abdominal pressure monitoring, ultrasound diagnosis, bronchoscope examination and treatment and blood purification in third-class hospitals than in second-class hospitals [31.6% (12/38) vs. 14.7% (11/75), 75.7% (28/37) vs. 38.6% (27/70), 61.5% (24/39) vs. 24.3% (18/74), 89.7% (35/39) vs. 45.9% (34/74), 92.3% (36/39) vs. 48.6% (36/74), respectively, all P < 0.05]. Conclusions:The data were mainly derived from public general hospitals in Guizhou Province. Compared with the ICUs of second-class hospitals, the ICUs of third-class hospitals were founded earlier and larger, had better hardware configuration and could carry out more skills. However, the human resource situations were similar between second-class hospitals and third-class hospitals. Both second-class hospitals and third-class hospitals have a need to improve the allocation of manpower and equipment and expand various skills in ICUs, while it is more urgent for second-class hospitals.

Objective:To discuss the feasibility of offering specialized courses of critical care medicine in undergraduate clinical medicine education, so as to alleviate the shortage of critical care medicine staffs and lay a foundation for improving the success rate for the treatment of critical cases.Methods:The undergraduates majoring in clinical medicine from 2008 to 2011 in Guizhou Medical University (the former Guiyang Medical College) were enrolled. After they had been enrolled in the undergraduate education for 3 years and were ready for Grade four, which meant basic medicine teaching had been completed and clinical medicine teaching was about to start, they were introduced and preached to each discipline, including critical care medicine. The undergraduates were free to choose professional direction of clinical training in Grade four. Students majoring in clinical medicine from 2012 to 2014 were free to choose their major direction when they entered the school.Results:From September 2011 to July 2019, the university had cultivated 246 undergraduates majoring in clinical critical care medicine from 2008 to 2014, and the critical care medicine professional team of affiliated hospital had undertaken 540 teaching hours. By July 2019, all students had graduated on time, with an employment rate of 100%. Forty students took postgraduate programs in our school and other schools, accounting for 16.3%.Conclusions:Professional education of critical care medicine in the undergraduate course of clinical medicine can mobilize students' interest in learning and subjective initiative, which is conducive to career selection. During the clinical training, the students can identify and timely cure critical care cases in the early stage, and partly alleviate the current shortage of critical care medical staffs.

肺癌的发病机制非常复杂，目前仍未明确。研究发现miRNA是肿瘤中的一组重要的调节因子，与肺癌的发生发展密 切相关，异常表达后可作为致癌miRNA或抑癌miRNA参与调控信号通路基因的表达，影响肺癌细胞的增殖、迁移、侵袭、转移等 过程。本文就miRNA作为抑癌或致癌基因在肺癌发生发展中机制的最新研究进展进行综述。

Objective To investigate the clinical value of single-incision laparoscopic inguinal high ligation in children with recurrent inguinal hernia . Methods Clinical data of 30 pediatric recurrent inguinal hernia cases treated with single-incision laparoscopy in our hospital between January 2011 and February 2016 were analyzed retrospectively .The patients were aged 1-11 years old (mean, 6.1 ±3.3 years old).For indirect inguinal hernia, a non-absorbable suture was placed around the extra-peritoneal space of the inguinal inner ring by means of a needle with a thread hole and a hooked needle under laparoscope , and the hernial sac was highly ligated by knotting the purse string suture .If a direct inguinal hernia was identified , a similar method was used to ligate the hernial sac , and the umbilical artery fold was sutured to the Hesselbach ' s triangle in order to enhance the weak tissue . Results After surgeries, we found 28 cases were recurrent indirect inguinal hernia (4 cases with contralateral concealed hernia ), and the other 2 cases were direct inguinal hernia .The operation time ranged from 12 to 45 min (mean, 21.4 ±8.2 min).All th cases recovered with inconspicuous scars , and no recurrence or complications were found during a follow-up for 2-53 months ( mean, 23.9 ±12.5 months). Conclusions Single-incision laparoscopic inguinal high ligation is a safe and effective procedure for children with recurrent inguinal hernia .This procedure does not cause obvious scars for patients , and can diagnose and treat the occult hernia and direct hernia at the same time .

OBJECTIVETo study the effects of RhoA down-regulation by RNA interference on the invasion of tongue carcinoma Tca8113 and SCC-4.

METHODSDetermination of the human RhoA sequence as well as the design and constructionof a short specific small interfering RNAs (siRNA) were performed. The siRNA of RhoA gene was transfected into humantongue squamous cell carcinoma Tca8113 and SCC-4 cells line by Lipofectamine 2000. Quantitative real-time polymerasechain reaction was used to examine the mRNA expressionlevels of RhoA. Protein expressions of mRNA, galectin-3,and matrix metalloproteinase (MMP)-9 were evaluated byWestern blot. Transwell invasion assay was performed toassess the invasion ability of tongue carcinoma.

RESULTSRhoA expressions in Tca8113 and SCC-4 cells were reducedsignificantly after transfection of RhoA-siRNA. Protein levels f galectin-3 and MVP-9 were also down-regulated significantly. Invasion ability was inhibited as well.

CONCLUSIONRhoA-siRNA can effectively inhibit RhoA expression in Tca8113 and SCC-4 cells. The invasion ability of tongue carcinoma cells decreased with down-regulation of the protein expressions of galectin-3 and MMP-9, indicating that RhoA-siRNA can inhibit invasion of tongue carcinoma. Results show that RhoA may play an important role in the processes of invasion and metastasis of tongue carcinoma.

Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Down-Regulation ; Galectin 3 ; metabolism ; Gene Silencing ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Tongue Neoplasms ; genetics ; metabolism ; pathology ; Transfection

Objective To investigate the effect of fluorouracil for injection on methylene tetrahydrofolate reductase ( MTHFR ) , glutathione S-transferase ( GST) and tumor markers in patients with advanced gastric cancer.Methods Forty-eight cases with advanced gastric cancer were selected from August 2013 to August 2014 in the hospital and divided into two groups.The control group (n=24) were treated with capecitabine plan, and the experiment group ( n=24 ) were treated with fluorouracil for injection plan.MTHFR concentration, GST activity and tumor markers [ carbohydrate antigen-199(CA199), carcinoembryonic antigen (CEA), alpha fetoprotein(AFP)] levels were compared before and after treatment.ResuIts Compared with control group, MTHFR concentration of experiment group was higher (P<0.05), GST activity was lower (P<0.05), the tumor markers levels were lower (P<0.05), total effective rate of clinical symptoms was higher [16(66.67) vs.22(91.67), χ2 =4.55, P<0.05], and incidence of adverse reactions was lower [14(58.33) vs.6(25.00), χ2 =5.49, P<0.05].ConcIusion Fluorouracil for injection chemotherapy could increase the serum MTHFR concentration, reduce GST activity, and its clinical curative effect is obvious with less adverse reactions, which has important significance in treatment of patients with advanced gastric cancer.

Objective Mitotic spindle and midbody are both microtubule-based temporary structures during cell growth and play essential roles in mitosis.The purpose of this study was to establish a mature and efficient method to extract mitotic spindle and midbody.Methods Through the cell cycle synchronization method,mitotic spindle or midbody was made appear inside cells.Low permeability swelling and glycerol gradient centrifugation principles were then used to extract spindle and midbody.Results By Western Blot and immunofluorescence staining,the extracts were identified as mitotic spindle and midbody.Conclusions The successful extraction of mitotic spindle and midbody from synchronized Hela cells will provide foundation for identifying the proteins located in cell during mitosis,and be of great significance to the study of molecular regulation mechanisms of mitosis and tumorigenesis.