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Objective@#To understand the prevalence, diagnosis and treatment of chronic critical illness (CCI) in China.@*Methods@#The clinical data of 472 adult patients admitted to ICU in 53 hospitals, including basic information, disease-related data, nutrition program, etc., were collected on May 10, 2019, by means of multi-center cross-sectional study. If surgical intervention was needed or the occurrence of the disease was directly related to the surgery, ICU patients were regarded as surgical ICU cases (n=211). In this study, the diagnostic criteria for CCI were: (1) admission to ICU >14 days;(2) combined with persistent organ dysfunction. The prevalence,distribution and treatment of CCI and surgery-related CCI were recorded and analyzed. The Mann-Whitney U test, chi-square test or Fisher exact test were used for comparative analysis.@*Results@#Among the 472 ICU patients from 53 hospitals, 326 were male (69.1%) and 146 were female (30.9%). The prevalence of CCI was 30.7% (145/472). Among 211 surgery-related ICU patients, 57 developed CCI with a prevalence of 27.0%. As compared to non-CCI patients, higher APACHE II score [median (IQR) 13.5 (10.0, 18.3) vs. 11.0 (7.0, 16.0), U=2970.000, P=0.007], higher Charlson comorbidity index [median (IQR) 4.0 (2.0, 7.0) vs. 3.0 (1.0, 5.0), U= 3570.000, P=0.036] and higher ratio of breath dysfunction [68.4% (39/57) vs. 48.1% (74/154), χ2=6.939, P=0.008] and renal dysfunction [42.1% (24/57) vs. 18.2% (28/154), χ2=12.821, P<0.001] were found in surgery-related CCI patients. While SOFA score, Glasgow coma score and other visceral function were not significantly different between surgery-related CCI and non-CCI patients (all P>0.05). NUTRIC score showed that surgery-related CCI patients had higher nutritional risk [43.9% (25/57) vs. 26.6%(41/154), U=5.750, P=0.016] and higher ratio of mechanical ventilation [66.7% (38/57) vs. 52.3% (79/154), χ2=3.977, P=0.046] than non-CCI patients. On the survey day, the daily caloric requirements of 50.2% (106/211) of surgery-related ICU patients were calculated according to the standard adult caloric intake index (104.6 to 125.5 kJ·kg-1·d-1, 1 kJ=0.239 kcal), and the daily caloric requirements of 46.4% (98/211) of patients were calculated by physicians according to the severity of the patient′s condition. 60.2% (127/211) of nutritional support therapy was enteral nutrition (including a combination of enteral and parenteral nutrition), while the remaining patients received parenteral nutrition (24.6%, 52/211), simple glucose infusion (9.0%, 19/211), or oral diet (6.2%, 13/211). The target calorie of CCI group was 104.6 (87.9, 125.5) kJ·kg-1·d-1, and the actual calorie intake accounted for 0.98 (0.80, 1.00) of the target calory. In the non-CCI group, the target calorie was 104.6 (87.9, 125.5) kJ·kg-1·d-1, and the actual calorie consumed accounted for 0.91 (0.66, 1.00) of the target calorie. There was no statistically significant difference between two groups (P=0.248, P=0.150).@*Conclusion@#The prevalence of CCI and surgery-related CCI in ICU is high, along with severe complications, respiratory and renal dysfunction and mechanical ventilation. Surgical patients admitted to ICU are at high nutritional risk, and active and correct nutritional support is essential for such patients.
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Objective To study the effect of inhibiting the expression of FOXD1 gene on the radiosensitivity of colorectal cancer cells. Methods The expressions of FOXD1 mRNA and protein in human colorectal cancer tissues and cells were detected by Real-time PCR ( qRT-PCR) and Western blot. The colorectal cancer cell line HCT116 was irradiated with 0, 2, 4 and 6 Gy of X-rays. The expression of FOXD1 in each groups were detected by qRT-PCR and Western blot. HCT116 cells were transfected with FOXD1 siRNA and its negative control and termed as si-FOXD1 group and si-NC group. When these cells were irradiated with 4 Gy X-rays, they were termed as si-FOXD1+4 Gy group and si-NC+4 Gy group. Cell proliferation was detected with MTT method, cell survival fraction was measured with colony formation assay, and DNA-PK activity was detected by TECT DNA-PK kit. The siRNA-transfected colorectal cancer cells were inoculated into BALB/c nude mice to establish the xenograft model. After irradiation, the volume and quality of the subcutaneous transplanted tumors were measured every 5 days. Results The expression of FOXD1 mRNA and protein in colorectal cancer tissues was higher than that in adjacent normal tissues (t=5. 579, 4. 816, P<0. 05). The mRNA(t=5. 85-17. 62, P<0. 05)and protein(t=9. 04-11. 42, P<0. 05) expression of FOXD1 in different colorectal cancer cell lines was higher than that in colonic mucosa epithelial cell line NCM460. The expression of FOXD1 in colorectal cancer cells HCT116 was increased after radiation in a dose dependent manner(t=9. 13-44. 15, P<0. 05). Transfection of si-FOXD1 effectively inhibited the expression of FOXD1 (t=10. 51, P<0. 05), decreased proliferation (t=10. 41, P <0. 05), increased radiosensitivity with a radiosensitization ratio of 1. 797, and reduced the radiation-induced DNA-PK activity ( t = 6. 20, P < 0. 05 ) in colorectal cancer cells. After localized irradiation, the tumor volume and weight in nude mice transplanted with si-FOXD1 HCT116 cells were significantly smaller than those in HCT116 (t=11. 29, 3. 69, P<0. 05). Conclusions Knock-down of FOXD1 gene increases the radiosensitivity of colorectal cancer cells and inhibits the growth of colorectal cancer xenograft in nude mice, which provides a potential target gene in improving the effect of radiotherapy on colorectal cancer.
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Objective To investigate the effect of FAM83A on the stem cell-like phenotype, chemosensitivity and radiosensitivity of PANC-1 cells, aiming to provide new ideas for clinical combination therapy of pancreatic cancer. Methods The PANC-1 cells with stable silencing FAM83A were constructed by using lentivirus and validated by qPCR and Western blot. Flow cytometry was used to detect the number of CD133 positive cells and cellular apoptosis; the sphere formation assay was used to test the ability of sphere formation of PANC-1 cells;the effect of gecitabine on the cell viability was detected by MTT assay;the effect of radiation on the proliferation of PANC-1 cells was detected by colony formation assay; the effect of FAM83A on Wnt/β-catenin pathway was examined by Western blot. Results The expressions of FAM83A protein ( 0.83 ± 0.08 ) and mRNA ( 0.29 ± 0.03 ) in PANC-1 cells with stable silencing FAM83A were significantly lower than those in the scrambled control group, respectively (1.95 ± 0.19, 0.98 ± 0.09;t=9.410, 12.600, P<0.05). After silencing FAM83A, the expression of stem cell marker CD133 (8.97 ± 0.62) and the sphere formation ability (8 ± 1) also decreased significantly compared with the scrambled group, respectively (21.60 ± 2.60, 25 ± 3; t=8.184, 9.311, P<0.05), and the stem cell-like phenotype of PANC-1 cells was also significantly inhibited. When PANC-1 cells were silenced by FAM83A and further treated with 50 μmol/L gecitabine at 72 h, the activity of FAM83A-silenced PANC-1 cells (32.33 ± 3.05)％ was significantly lower than that of the gecitabine alone treated group (63.06 ± 5.98)％ (t=6.378, P<0.05), and the apoptosis rate of FAM83A-silenced PANC-1 cells (76.52 ± 8.34) ％ was significantly higher than that of gemcitabine alone group (40.88 ± 4.91)％(t=7.929, P<0.05). After silencing FAM83A combined with IR irradiation, the activity of PANC-1 cells (43.25 ±4.21)％ was significantly lower than that of IR alone (78.13 ± 7.98)％ (t=6.694, P<0.05), and the apoptosis rate (44.56 ± 5.32)％ was significantly increased compared with IR alone (15.15 ±1.95)％ (t = 8.990, P < 0.05). After silencing FAM83A, the expression of Active-β-catenin was significantly decreased while the expression of p-β-catenin was significantly increased, the expression of β-catenin in the nucleus was significantly reduced, although total β-catenin had no significant change, and the activity of Wnt/β-catenin signaling pathway was significantly inhibited. Conclusions Silencing FAM83A could significantly reduce the stem cell-like traits and enhance the chemosensitivity and radiosensitivity of pancreatic cancer cells to gemcitabine and radiation via Wnt/β-catenin signaling pathway, which may provide a new target for targeted and combination therapy of pancreatic cancer.
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BACKGROUND: Pioglitazone is a common hypoglycemic drug capable of improving proliferation and activation, and inhibiting apoptosis of endothelial progenitor cells (EPCs). We speculated that the combined use of pioglitazone and EPCs transplantation could have significant improving effects on hyperglycemia and kidney function after diabetes mellitus.OBJECTIVE: To investigate the improving effect of EPCs transplantation combined with pioglitazone treatment on the kidney function of diabetic rat models.METHODS: The 15 of 75 Wistar rats were randomly selected and served as normal control group (no treatment). Animal models of type 1 diabetes mellitus were made in the rest 60 rats through the intraperitoneal injection of 40 mg/kg streptozotocin for continuous 5 days. The human EPCs (labeled by CM-Dil) were recovered, cultured and preserved until transplantation. After 4 weeks of modeling, the 60 rat models were randomly divided into model group (PBS injection), pioglitazone group, EPCs transplantation group and combined treatment group, followed by tail vein injection of EPCs suspension and/or intragastric administration of 20 mg/kg pioglitazone for continuous 4 days. After 8 weeks of treatment, the levels of glucose, insulin and creatinine in serum, urea nitrogen and urine protein during 24 hours were determined. The number and distribution of EPCs labeled by CM-Dil were detected by fluorescence microscope, the apoptosis in kidney cells was tested by TUNEL method, and the kidney weight/body weight ratio in rats was calculated.RESULTS AND CONCLUSION: Compared with the model group, the blood glucose and serum creatinine levels and the urea nitrogen and urine protein concentrations during 24 hours were significantly decreased (P pioglitazone group > EPCs transplantation group > combined treatment group (P < 0.05). To conclude, the EPCs transplantation combined with pioglitazone treatment can decrease the blood glucose and serum creatinine levels and urea nitrogen and urine protein concentrations, improve the serum insulin level, reduce cell apoptosis in the kidney, and remit the kidney dysfunction of diabetic rats to a certain extent.
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Objective To discuss clinical significance on early diagnosis of brain injury in premature infants with multiple sequence joint inspection of magnetic resonance imaging (MRI).Methods The brain MRI findings of 160 premature infants treated by Neonatal Intensive Care Unit were analyzed retrospectively.Results In 160 premature infants,brain injury occurred in 76 cases,the incidence of brain injury was 47.5％.Ischemic lesions were seen more in brain injury in premature infants,cerebral white matter injury was the most common,especially periventricular leukomalacia.Ischemic brain injury performed patchy or large sheet increased signal intensity on T1-weighted images(T1 WI),decreased signal intensity on T2-weighted images (T2WI) and obviously increased signal intensity on diffusion weighted imaging (DWI) in half egg circle center and around the lateral ventricle.Periventricular leukomalacia performed patchy decreased signal intensity on T1WI,increased signal intensity on T2WI and decreased signal intensity on DWI.Periventricular-intraventricular hemorrhage was seen more in hemorrhagic lesions.Hemorrhage stove was performed different signal because of different bleeding time.MRI performance in acute phase was iso-signal or slightly decreased signal intensity on T1WI,increased signal intensity on T2WI,increased signal intensity on T1WI,slightly decreased signal intensity on T2WI in early subacute,increased signal intensity on T1 WI and T2WI in late subacute and obviously decreased signal intensity on magnetic sensitive weighted imaging.The detection rate of ischemic lesions by DWI was higher than the conventional MRI,and DWI could show cerebral white matter damage of premature infants much earlier than the conventional MRI.The detection rate of hemorrhage stove by susceptibility weighted imagingc (SWI) was higher than the conventional MRI (x2 =23.78,P ＜ 0.05),and SWI could show hemorrhagic lesions much earlier than conventional MRI (x2 =27.02,P ＜ 0.05).Conclusions MRI,especially combined multiple sequence checking,could provide accurate imaging evidence for the early diagnosis of brain injury in premature infants.
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Objective To explore the effects of atorvastatin on inflammatory factors(hs-CRP,TNF-αand IL-6 levels )of coronary heart disease. Methods 160 patients with coronary artery disease were selected which were treated in Nanyang Municipal Central Hospital from January 2010 to July 2014.The 160 CHD patients were divided into two groups using the random number table method.On the basis of conventional treatment,patients of the experimental group were given atorvastatin,but the patients of control group were given only the other conventional treatment.Patients of two groups were tested about inflammatory factors before treatment and after two months treatment,and then analyzed and compared.Results It had no statistically significant difference on hs-CRP,TNF-αand IL-6 levels in patients of the two groups before treatment;it had statistically significant difference on hs-CRP,TNF-αand IL-6 levels in patients of the two groups of two months after treatment(P<0.05 );differences on hs-CRP,TNF-αand IL-6 levels of patients between pre-treatment and after treatment of two months in the experimental group were statistically significant (P<0.05 );however,it was opposite in the control group.Conclusion Atorvastatin could significantly reduce the levels of inflammatory factors(hs-CRP、TNF-αand IL-6)of patients with coronary artery disease.It has important clinical value.