The aim of this study was to prepare a high drug-carrying capacity micellar drug delivery system(CTD@Sol)of the polymer zebra tetracycline and to preliminarily investigate the feasibility of this drug delivery system for the treatment of breast cancer.Firstly,CTD@Sol was prepared using sol as the carrier material and CTD as the model drug,and its pharmacological properties such as appearance and morphology,particle size,potential and in vitro release were evaluated.The growth inhibitory and apoptotic effects of CTD@Sol on breast cancer(4T1)cells were investigated by MTT assay and Annexin V-FITC/PI double staining assay;the uptake efficiency of 4T1 to this delivery system was investigated by flow cytometry;and the in vivo tissue distribution of the delivery system and the targeting of tumour tissues were investigated by small animal in vivo imaging technique.The results showed that CTD@Sol appeared as a light pale blue creamy white colour,with an average particle size of(159.73±1.96)nm,a PDI of 0.198±0.006,Zeta potential of-(47.60±1.77)mV,an encapsulation rate of(90.29±1.69)%and a drug loading capacity of(45.00±0.84)%;the in vitro release and haemolysis experiments showed that the drug release rate of CTD@Sol in acidic environment(pH 5.5)was significantly faster than that in neutral environment(pH 7.4),suggesting that the system is acid-sensitive and has good biosafety under endocytosed pH conditions.Cellular uptake,cytotoxicity and apoptosis experiments showed that CTD@Sol was more lethal to 4T1 cells,and the sol-gel polymer micelles as a drug delivery vehicle could significantly improve the cellular uptake efficiency of the drug;in vivo experiments showed that the delivery system had a significant targeting effect on tumour tissues.In conclusion,this study has successfully produced a CTD@Sol drug delivery system with high drug loading capacity(>45%),good pharmacological performance,strong targeting and biosafety,which has the potential to be used in the treatment of breast cancer.

Quarantine insects are economically important pests that frequently invade new habitats.A rapid and accurate monitoring method to trace the geographical sources of invaders is required for their prevention,detection,and eradication.Current methods based on genetics are typically time-consuming.Here,we developed a novel tracing method based on insect gut microbiota.The source location of the insect gut microbiota can be used to rapidly determine the geographical origin of the insect.We analyzed 179 gut microbiota samples from 591 individuals of 22 quarantine insect species collected from 36 regions in China.The gut microbiota of these insects primarily included Actinobacteria,Bacteroidetes,Cyanobacteria,Firmicutes,Proteobacteria,and Tenericutes.The diversity of the insect gut microbiota was closely associated with geographical and environmental factors.Different insect species could be distinguished based on the composition of gut microbiota at the phylum level.Populations of individual insect species from different regions could be distin-guished based on the composition of gut microbiota at the phylum,class,and order levels.A method for determining the geographical origins of invasive insect species has been established;however,its practical application requires further investigations before implementation.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.

Objective:To explore the evaluate of neutrophil gelatinase-associated lipocalin (NGAL) , combined with neutrophil/lymphocyte ratio (NLR) in the early prognosis of patients with acute paraquat poisoning (APP) .Methods:In March 2019, 108 APP patients admitted to Emergency Medicine Department of Hebei Medical University from January 2017 to December 2018 were selected as the observation group, 60 healthy people in the same period were see as the control group according to the results of diagnosis and 28-day survival, the observation group was divided into 51 death group and 57 survival group. The correlation between NGAL, NLR and the death of APP patients was analyzed, to explore the value of NGAL and NLR in predicting the death of APP patients.Results:Compared with the Control group, the NGAL and NLR in the observation group were significantly higher ( P<0.01) , and the NGAL and NLR in the death group were significantly higher ( P<0.05) . The results showed that NGAL and NLR were positively correlated with the death of APP patients on 28th day, and the Correlation Coefficient was 0.456 and 0.638 at 2nd Day ( P<0.01) The area under the ROC curve of NGAL, NLR and their combination were 0.764, 0.869 and 0.905, respectively. Conclusion:The combined detection of NGAL and NLR has important clinical significance in the early prediction of 28-day mortality in APP patients.

Objective:To investigate the effect of transcranial direct current stimulation (tDCS) on cognitive function of delayed encephalopathy after carbon monoxide poisoning (DEACMP) .Methods:A total of 58 patients with DEACMP admitted to the Emergency Medicine Department of Hudson International Peace Hospital from January 2018 to January 2020 were included. According to the random number table, the patients were randomly divided into study group and control group, with 29 patients in each group. Patients in both groups were given nutritional nerve therapy, improved microcirculation, adrenal cortical hormone and other drugs, as well as hyperbaric oxygen and rehabilitation training, once per day. The study group was treated with tDCS (electrode pads were placed and current stimulation was given 30 min/time) 1/d on the basis of conventional treatment, while the control group was treated with tDCS pseudo stimulation (electrode pads were placed and current stimulation was given for 10 s) 1/d for 30 days consecutively. The auditory event-related potential P300 (ERP-P300) was tested before and 30 days after treatment, and the Mini-Mental State Examination (MMSE) scale, Barthel index (BI) and the National Institutes of Health Neurological Impairment score (NIHSS) were used to evaluate and analyze the patients.Results:There was no significant difference in scores between the two groups before treatment (all P>0.05) . After 30 days of treatment, the MMSE score, orientation, memory, attention and computing power, and language ability of the study group were all higher than those of the control group, and the differences were statistically significant ( P<0.05) . 90 days after treatment, the BI of the study group was higher than that of the control group ( P<0.05) . After 30 days of treatment, the NIHSS score of the study group was significantly lower than that of the control group ( P<0.05) . The latency of ERP-P300 in the study group was shorter than that in the control group, and the amplitude was higher than that in the control group at 30 days after treatment, and the difference was statistically significant ( P<0.05) . The latency of ERP-P300 was negatively correlated with the total MMSE score before and after DEACMP treatment ( r=-0.837, -0.819, P<0.05) . The latency of ERP-P300 was negatively correlated with orientation, attention and computing power, and language ability before treatment ( r=-0.698, -0.675, -0.742, P<0.05) . Conclusion:TDCS treatment can help improve the cognitive function of DEACMP patients, and ERP-P300 test can help determine the cognitive function severity of patients.

Objective:To explore the evaluate of neutrophil gelatinase-associated lipocalin (NGAL) , combined with neutrophil/lymphocyte ratio (NLR) in the early prognosis of patients with acute paraquat poisoning (APP) .Methods:In March 2019, 108 APP patients admitted to Emergency Medicine Department of Hebei Medical University from January 2017 to December 2018 were selected as the observation group, 60 healthy people in the same period were see as the control group according to the results of diagnosis and 28-day survival, the observation group was divided into 51 death group and 57 survival group. The correlation between NGAL, NLR and the death of APP patients was analyzed, to explore the value of NGAL and NLR in predicting the death of APP patients.Results:Compared with the Control group, the NGAL and NLR in the observation group were significantly higher ( P<0.01) , and the NGAL and NLR in the death group were significantly higher ( P<0.05) . The results showed that NGAL and NLR were positively correlated with the death of APP patients on 28th day, and the Correlation Coefficient was 0.456 and 0.638 at 2nd Day ( P<0.01) The area under the ROC curve of NGAL, NLR and their combination were 0.764, 0.869 and 0.905, respectively. Conclusion:The combined detection of NGAL and NLR has important clinical significance in the early prediction of 28-day mortality in APP patients.

Objective:To investigate the effect of transcranial direct current stimulation (tDCS) on cognitive function of delayed encephalopathy after carbon monoxide poisoning (DEACMP) .Methods:A total of 58 patients with DEACMP admitted to the Emergency Medicine Department of Hudson International Peace Hospital from January 2018 to January 2020 were included. According to the random number table, the patients were randomly divided into study group and control group, with 29 patients in each group. Patients in both groups were given nutritional nerve therapy, improved microcirculation, adrenal cortical hormone and other drugs, as well as hyperbaric oxygen and rehabilitation training, once per day. The study group was treated with tDCS (electrode pads were placed and current stimulation was given 30 min/time) 1/d on the basis of conventional treatment, while the control group was treated with tDCS pseudo stimulation (electrode pads were placed and current stimulation was given for 10 s) 1/d for 30 days consecutively. The auditory event-related potential P300 (ERP-P300) was tested before and 30 days after treatment, and the Mini-Mental State Examination (MMSE) scale, Barthel index (BI) and the National Institutes of Health Neurological Impairment score (NIHSS) were used to evaluate and analyze the patients.Results:There was no significant difference in scores between the two groups before treatment (all P>0.05) . After 30 days of treatment, the MMSE score, orientation, memory, attention and computing power, and language ability of the study group were all higher than those of the control group, and the differences were statistically significant ( P<0.05) . 90 days after treatment, the BI of the study group was higher than that of the control group ( P<0.05) . After 30 days of treatment, the NIHSS score of the study group was significantly lower than that of the control group ( P<0.05) . The latency of ERP-P300 in the study group was shorter than that in the control group, and the amplitude was higher than that in the control group at 30 days after treatment, and the difference was statistically significant ( P<0.05) . The latency of ERP-P300 was negatively correlated with the total MMSE score before and after DEACMP treatment ( r=-0.837, -0.819, P<0.05) . The latency of ERP-P300 was negatively correlated with orientation, attention and computing power, and language ability before treatment ( r=-0.698, -0.675, -0.742, P<0.05) . Conclusion:TDCS treatment can help improve the cognitive function of DEACMP patients, and ERP-P300 test can help determine the cognitive function severity of patients.

Objective: To investigate the strong expression (S+) of P53 and BCL2 proteins in MYC/BCL2 double-expression DLBCL (DEL) and whether they can be used for the prognostic evaluation and stratified diagnosis of DELs. Methods: Tissue microarray were made by filed FFPE blocks of 174 DLBCL cases. The translocation of MYC, BCL2 and BCL6 genes were detected by FISH, and the proteins were detected by IHC. Data of clinicopathologic features and follow up of patients were collected and OS (overall survival) and PFS (progression free survival) were analyzed by statistics. Results: Eight double-hit lymphomas (DHLs) were identified in all cases, and 45 DELs were selected from 166 remaining cases, which have no significant difference in OS and PFS compared with non-DEL cases (P=0.668 and P=0.790) . Of 42 DEL-cases with follow up data, 24 cases with P53+ or/and BCL2 (S+) are significantly shorter OS and PFS than others (P=0.003 and P=0.000) , in which the cases with P53+/BCL2 (S+) co-expression were the worst prognosis, and P53/BCL2 co-weaker positive DEL cases even have superior OS and PFS than those non-DELs. Although statistics showed that the cases of P53+ or/and BCL2 (S+) have a lower OS and PFS in total cases (P=0.063 and P=0.024) , it is not the case when the DEL-cases take out from total cases, that is the cases with P53+ or/and BCL2 (S+) are as similar OS and PFS as others in non-DEL group (P=0.590 and P=0.550) . Conclusion The strong expression of P53 and BCL2 proteins can be used as indicators of stratified diagnosis and poor prognosis of DEL.

Objective To investigate the expression of c-kit and analyze its relationship with proliferating cell nuclear antigen (PCNA) in RCC subtypes and its clinical progression. Methods Expression of c-kit protein was retrospectively studied with immunohistochemistry in paraffin sections from 137 cases of clear renal cell carcinoma (CCRCC), 82 papillary renal cell carcinoma (PRCC), 51 chromophobe renal cell carcinoma (ChRCC). Results The positive rate of c-kit in ChRCC was 94.1%(48/51), it was statistically higher than that in CCRCC (16. 1%, 22/137) and PRCC (28.1 %, 23/82)(P=0. 001 ). In ChRCC, the positive expression of c-kit was related with TNM stages. The positive expression of PCNA was related with the grade in CCRCC and PRCC. But there was no relationship between PCNA expression and grade of ChRCC. It also had the relationship with the metastasis in CCRCC. Conclusions The expression of c-kit in ChRCC is higher than in other subtype of RCC, and associated with tumor local progression. That makes c-kit as a helpful marker to discriminate different subtypes of kidney cancer.

Objective To study the effect of macrophage, its stimulating factor, granulocyte macrophage colony-stimulating factor (GM-CSF), the combination of GM-CSF and macrophage on the survival of rat deep epigastric perforator flap (DEP). Methods The stable animal model of DEP flap in Sprague-Dawley rat mimicing human deep inferior epigastric perforator flap in breast reconstruction was established. The rats were treated with subcutaneous injection of recombined rat GM-CSF or rat peritoneal macrophages, respectively, or combination of GM-CSF/ Macrophages. Normal saline was used as parallel negative control. The rats were sacrificed and flap specimens were harvested on day 7 after operation, the flaps survival area were measured by the method of rubbings and the survival proportion of flaps were calculated, Von Will brand factor were detected by immunohistochemistry and microvessel density (MVD), and were calculated with microscopic study, and collagen were stained and quantified by Masson staining. Results Survival proportion of flaps in group GM-CSF (53.08% ± 8. 76% ) was not different with that in macrophages group (47. 95% ± 4. 92% ), and both of these two groups were significantly higher than parallel negative control group (43.28% ± 5.27% ) but significantly lower than combination GM-CSF/ macrophages group ( 61.68% ± 6. 60% ). For MVD, flap in GM-CSF group ( 24. 82 ± 4. 18 ) was not significantly different with macrophages group (24.30 ± 3.02 ), and both of these two groups were significantly higher than group parallel negative control (21.37 ± 2.65 ) but significantly lower than combination GM-CSF/macrophages group ( 29. 82 ± 4. 74). Collagen deposition in the flaps in GM-CSF group (17. 25% ± 2. 85% ) were significantly higher than parallel negative control group (14.41% ± 2. 89% ), macrophages group ( 12. 69% ± 3.55% ) were lower than parallel negative control group but there was no significant difference. That in combination GM-CSF/macrophages group (20.31% ± 3.01% )was significantly higher than GM-CSF group ( P < 0. 05 ). Conclusion Treatment with rat GM-CSF or macrophage can significantly promote the survival of the flaps. Combined application of GM-CSF and macrophage could synergetically promote the survival of the flaps, the vasculogenesis and the collagen deposition.