BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective To observe the effect of early enteral nutrition (EEN) on nutritional indicators and clinical outcomes in patients with severe heart failure undergoing mechanical ventilation. Methods Thirty-four patients with severe heart failure (grade Ⅲ-Ⅳ of cardiac function) and pulmonary infections undergoing mechanical ventilation admitted to intensive care unit (ICU) of Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from May 2017 to April 2018 were enrolled. They were randomly divided into EEN group and delayed enteral nutrition (DEN) group. Both groups were given routine treatment, including mechanical ventilation, improvement of cardiac function, anti-infection, protection of vital organ function, regulation of blood sugar and adjustment of electrolyte and acid-base balance. The patients in EEN group received enteral nutrition (EN) within 48 hours after ICU admission, and in DEN group, EN was started after the patients had spent the early stage of stress and had stable vital signs (48 hours after ICU admission). The changes in serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), nutritional indicators and liver function indicators at ICU admission and 7 days after treatment were compared between the two groups. The time needed for patients to reach EN target, duration of mechanical ventilation, length of ICU stay, and the 28-day mortality were recorded, and complications were observed. Results There was no significant difference in serum BNP, CRP, nutritional indicators or liver function indicators at ICU admission between the two groups. After treatment for 7 days, BNP and CRP in both groups were decreased significantly as compared with those at ICU admission [BNP (ng/L): 592.1±370.9 vs. 2 517.7±1 163.4 in EEN group, 621.9±418.8 vs. 2 251.5±1 006.8 in DEN group; CRP (mg/L): 46.0±19.6 vs. 59.8±22.5 in EEN group, 40.5±18.8 vs. 61.2±24.6 in DEN group, all P < 0.05], pre-albumin (PA) and transferrin (TF) were significantly increased [PA (g/L): 0.18±0.05 vs. 0.15±0.06 in EEN group, 0.17±0.04 vs. 0.12±0.06 in DEN group; TF (g/L): 1.6±0.4 vs. 1.5±0.4 in EEN group, 1.7±0.5 vs. 1.4±0.5 in DEN group, all P < 0.05]. However, there was no significant difference in the above indicators after treatment between the two groups (all P > 0.05). There was no significant change in liver function after treatment in both groups. The EN treatment was successfully completed in both groups. Some patients developed abdominal distension and diarrhea in varying degrees, which were alleviated by slowing down the infusion rate, supplemented by gastrointestinal motility drugs and intestinal flora adjustment drugs. The time needed to reach EN target in EEN group was significantly earlier than that in DEN group (hours: 42.4±10.2 vs. 53.8±17.1, P < 0.05), the duration of mechanical ventilation (days: 14.2±8.7 vs. 13.4±7.9), the length of ICU stay (days: 17.8±6.7 vs. 18.3±5.6) and 28-day mortality [5.9% (1/17) vs. 11.8% (2/17)] showed no significant difference as compared with those in DEN group (all P > 0.05), and it did not increase the incidence of aspiration pneumonia [23.5% (4/17) vs. 17.7% (3/17), P > 0.05]. Conclusion EEN could help to achieve nutritional goals as soon as possible, improve the nutritional status of the body, and provide conditions and basis for further treatment of severe heart failure patients.

Objective: To explore the value of plasma cell-free DNA (cfDNA) in the assessment of inflammatory bowel disease (IBD) activity. Methods: From July 2014 to June 2017, 145 IBD patients from the First Affiliated Hospital of Fujian Medical University were selected. The plasma content of cfDNA was detected by picogreen-based fluorescent quantitative method. At the same period, 37 healthy individuals were enrolled as control group. The correlation between cfDNA content and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IBD activity was analyzed. The diagnostic capability of cfDNA in IBD activity was assessed by the receiver operating characteristic (ROC) curve. T-test was performed for comparison between two independent samples, and Pearson correlation coefficient test was used for correlation analysis between two variants. Results: The content of plasma cfDNA of patients with Crohn′s disease (CD) and patients with ulcerative colitis (UC) were (29.17±2.07) μg/L and (26.86±1.97) μg/L, respectively; which were both higher than those of healthy control group (21.10±1.02) μg/L, and the differences were statistically significant (t=2.609 and 2.082, both P<0.05). Moreover, the content of cfDNA of patients with active CD or UC were (35.72±3.26) μg/L and (32.37±3.42) μg/L, respectively, which were both higher than those of patients with CD or UC in remission ((21.12±1.43) μg/L and (20.82±1.02) μg/L), and the differences were statistically significant (t=3.806 and 3.116, both P<0.01). The cfDNA content of CD patients was positively correlated with CRP, ESR and disease activity (r=0.555, 0.393 and 0.400, all P<0.01). The cfDNA content of UC patients was also positively correlated with CRP, ESR and disease activity (r=0.640, 0.421 and 0.360, all P<0.01). The diagnostic capability of the combination of CRP and ESR was the highest in CD diagnosis, with the area under curve (AUC) value being 0.841, and the sensitivity and specificity being 81.4% and 74.3%, respectively. The diagnostic capability of the combination of cfDNA, CRP and ESR was the highest in UC diagnosis, with the AUC value being 0.851, and the sensitivity and specificity being 74.3% and 96.9%, respectively. Conclusions Increased cfDNA levels in IBD patients are correlated with IBD activity. Detection of cfDNA is helpful in the identification of active IBD, and the combination of ESR and CRP can improve the diagnostic efficiency of UC.

Objective To explore the application value of single-door laminoplasty via Y type nano-bone plate in treating multilevel cervical spondylotic myelopathy (MCSM) and analyze the short-term efficacy.Methods From January 2013 to December 2016,79 cases of MCSM were treated with single-door laminoplasty via Y type nano-bone plate to evaluate the improvement of post-operative neurological function by the Japanese Orthopaedic Association (JOA) evaluation system.We also measured cervical curvature of cervical X-ray and C5 sagittal diameter of the spinal canal before operation and 6 months after operation to understand the maintenance and enlargement of the spinal canal.The improvement degree of spinal cord compression was evaluated by preoperative and postoperative cervical MRI.Osseous healing on the open door side and the door shaft side was observed with the aid of three-dimensional spiral CT.Results Follow-up ranged from 6 to 36 months,with an average of (20.4±7.9)months.Preoperative JOA score was (8.6 ± 1.3) points and JOA score 6 months after operation was (14.3 ± 1.5)points (P ＜ 0.05).JOA improvement rate was (68.6 ± 15.8)％;postoperative follow-up X-ray and threedimensional spiral CT showed that the spinal canal had satisfying enlargement,the door shaft side all had osseous healing,the open door side osseous healing was not obvious,and there was no lamina collapse or reclosing.Sagittal diameter of theC spinal canal was (8.9±l.1)mm before operation and (15.1±l.1)mm 6 months after operation (P＜0.05).The spinal canal enlargement rate was (70.8±22.3)％,cervical curvature was (14.8± 7.0)°preoperatively and (15.1±6.7)°postoperatively with no significant difference (P＞0.05).Conclusion EOLP via Y type nano-bone plate is safe and efficacious in treating MCSM.It not only provides a good immediate fixation,but also provides the possibility for the open door side lateral osseous fusion.

Objective To investigate the efficacy and safety of transthoracic minimally invasive occlusion operation guided by transesophageal echocardiography for the treatment of congenital atrial or/and ventricular septal defects (ASD/VSD).Methods The clinical data of a total of 44 patients who underwent surgical occlusion operation from September 2013 to June 2015 were summarized.The whole course of occlusion procedure were dynamically monitored and guided by transesophageal echocardiography.All the patients were followed up regularly by electrocardiogram and echocardiograph.Results Among the 44 patients,43 patients(28 VSDs and 16 ASDs,including one patient suffered with VSD and ASD simultaneously)were occluded successfully,and the other patient with VSD who failed in the surgery was converted to open heart repair.The occlusion operations were finished within 22 to 48 min.The length of incision spaned from 2 to 4.5 cm.The ventilator was used for 1 to 5 hours.The total drainge volumes were recorded each patient from 0 to 50 mL.The postoperative hospitalization stay was 2 to 6 days,and all patients survived and were discharged.During the follow-up of 1 to 12 months, there was no cases with A-V conduction block,valve incompetent,cardiac arrhythmia and residual shunt of heart septel defect.Conclusion Transthoraic mini-invasive surgical occlusion of atrial and ventricular septal defects is a therapeutic method with less trauma,higher safety and feasiblity,faster recovery,and the short-term therapeutic effect is satisfying.

Objective To study the effects of mirabilite stuck on umbilical region combined with early enteral nutrition (EEN) on gastrointestinal function and serum inflammatory mediators in patients with mechanical ventilation. Methods Sixty-four patients with mechanical ventilation admitted to the Department of Intensive Care Unit of the Second Affiliated Hospital of Zhejiang Traditional Chinese Medical University from January to December 2016 were enrolled, and they were divided into an observation group and a control group by random number table, 32 cases in each group. The control group was treated with routine western medicine+ EEN, and the observation group was treated additionally with mirabilite stuck onto umbilical region on the basis of the treatment of the control group. The clinical effect was observed after 7 days of treatment. The differences in gastrointestinal function scores and the levels of serum inflammatory mediators were compared between the two groups before and after treatment.Results After treatment, gastrointestinal function scores of the diarrhea, bowel sound, abdominal distension and the levels of white blood cell count (WBC), serum procalcitonin (PCT), serum C-reactive protein (CRP) were decreased significantly in both groups compared with those before treatment, and the degrees of decreasing in above index levels after treatment in the observation group were more obvious than those in the control group [diarrhea: 0.72±0.03 vs. 1.59±0.21, bowel sounds: 0.87±0.05 vs. 1.54±0.18, abdominal distension: 0.77±0.04 vs. 1.63±0.09, WBC (×109/L): 9.87±1.25 vs. 12.46±2.04, PCT (μg/L): 5.43±1.02 vs. 9.65±1.63, CRP (mg/L): 56.87±4.52 vs. 89.43±8.24, allP < 0.05].Conclusion Applying mirabilite stuck on umbilical region combined with EEN can effectively promote the recovery of gastrointestinal function and significantly decrease the levels of serum inflammatory mediators in patients with mechanical ventilation.

Objective To explore the effect of adriamycin on the characteristics of colony derived from human adrenal cortical carcinoma cells (ACC) SW-13.Methods Treatment with Adriamycin (ADM) was used in BALB/c-nude mouse tumor xenograft model established using the ACC cell line SW-13.The characteristic of colony was assessed for the formation rates,the percentagc of three colony types and growth curve of single cell.Hoechst33342 dyeing test was used to test drug resistance.Results The Single-cell colony formation rate of experimental group were significantly higher than control group (P ＜ 0.05),and the holoclone percentage of experimental group were significantly higher than control group (P ＜ 0.05).In the Hoechst33342 dyeing tcst,the fluorescence intensity of control was higher than experimental group.Conclusion The treatment of ADM in vivo is beneficial for the colony formations of ACC cell and the formations rate of holoclone,and can improve the ability of drug resistance of ACC cell SW-13.

Objective High expression of multi-resistant transporter ATP-binding cassette super family G member 2 (ABCG2) is a major cause of drug resistance and chemotherapeutic failure of cancer .This study was to investigate the significance of ABCG2 expression in adrenocortical cancer cells after cyclophosphamide ( CTX) intervention in vivo . Methods Ten male and fe-male BALB/C-nu mice were randomly divided into a cyclophosphamide ( CTX) group and a control of equal number .SW-13 cells were subcutaneously injected into the nude mice to establish a model of subcutaneous transplantation tumor , followed by intraperitoneal injec-tion of CTX and isotonic saline solution into the two groups of mice , respectively .Then the expression of ABCG 2 in tumor tissue and primarily cultured cells was detected by immunohistochemistry and flow cytometry . Results The expression of ABCG 2 in the tumor tissue was significantly higher in the CTX than in the control group ([69.1 ±1.83]%vs [53.4 ±1.65]%, P<0.05), and so was that in the primarily cultured cells ([97.89 ±1.36]% vs [81.88 ±8.31]%, P<0.05). Conclusion The ABCG2 gene is in-volved in the drug resistance of adrenocortical carcinoma and may be a therapeutic target of the malignancy .

Objective To study the inhibition activity of volatile oil from Mappianthus iodoies on SPC-A-1 and BEL-7402 cancer cells.Methods The volatile oil in Mappianthus iodoie was extracted by SFE-CO2.MTT assay was employed to test the antitumor effect of volatile oil from Mappianthus iodoies in two kinds of malignant tumor cell lines,with IC50 applied to evaluate the degree of inhibition activity.Results When the dose of volatile oil from Mappianthus iodoies was 200 μg/ml,the inhibition ratios of the tumor cell was in excess of 50％,the IC50 was 169.54,695.21 μg/ml respectively.Conclusion Volatile oil from Mappianthus iodoies extracted by SFE-CO2 has obvious inhibition activity on SPC-A-1 and BEL-7402 cancer cells.

Objective To explore the characteristics and ecological risk assessment of heavy metals pollution in the fluvial sediment in Hengyang section of Xiang river.Methods The fluvial sediments in 18 sites in 10 sections of Hengyang section of Xiang river were collected for determination of heavy metals(Cu,Zn,As,Hg,Cd,Cr,Pb) in 2007.The accumulation levels of heavy metals in the fluvial sediment and their potential ecological risks were assessed by the Hankanson potential ecological risk(PER) factors method.Results The average potential ecological risk index of Cd in sediment of Xiang river was 352.1 with the highest ecological risk,the index of Hg was 272.1 with higher ecological risk,the index of Pb and As was 150.1 and 104.7 with high ecological risk,the index of Cr,Zn and Cu were all lower than 40 with low ecological risk.On the whole,the integrated pollution index of seven kinds of heavy metal was 913.4.Conclusion The fluvial sediment of Hengyang section of Xiang rive has been polluted by heavy metals in a certain degree and is characterized as a complex pollution situation with a higher ecological risk.