Abstract:Objective:　To detect the dynamic changes of mitochondria in hippocampal neurons of APP/PS1 double transgenic Alzheimer’s disease (AD) mice at different months and explore its significance. Methods:　Twenty male APP/PS1 double transgenic AD mice were selected and divided into 3-month-old group, 6-month-old group, 9-month-old group and 12-month-old group, with C57 mice as the control group. The morphological changes of mitochondria in hippocampal neurons were observed by electron microscope. Western blot was used to detect the expression levels of autophagy-related proteins LC3 and P62, the expression levels of mitochondrial autophagy-related proteins PINK1, Parkin and Miro1, and the expression levels of mitochondrial outer membrane protein Tom20. Results:　Electron microscopy study showed that the pathological changes of mitochondria damage in hippocampus neurons of APP/PS1 double transgenic AD mice were gradually aggravated with the increase of months, namely that, mitochondria showed obviously edema, transparent and irregularly arranged, broken or even disappeared cristae. Western blot results showed that compared with the wild mouse group, the expression levels of LC3, P62, PINK1 and Parkin protein were significantly increased in 6-month-old, 9-month-old and 12-month-old mice (P<0.05), while Miro1 protein was significantly decreased (P<0.05), and the expression level of Tom20 had no statistical significance (P>0.05). Conclusion: With the increase of age, the pathological changes of mitochondria in hippocampal neurons are dynamic in APP/PS1 double transgenic AD mice. Mitophagy is dynamically enhanced but accompanied by mitochondrial clearance obstacles.

Abstract:Objective:　This study aims to explore the potential effects and mechanisms of heat shock pretreatment (HSP) on bone marrow mesenchymal stem cells (BMSCs) in chemotherapy microenvironment. Methods:　The optimal condition of HSP was identified. Cisplatin was added to the heat shock pretreated bone marrow mesenchymal stem cells (HS-MSCs) medium to simulate the chemotherapy microenvironment. The effect of HSP on the biological characteristics of HS-MSCs was explored. The proliferation of BMSCs was detected by CCK-8 assay, the viability was measured by Hoechst33342/PI, and the apoptosis was detected by flow cytometry. The potential mechanisms of HSP were further explored from the perspective of heat shock proteins and autophagy. The expression of heat shock protein 70 (Hsp70), Hsp90, Beclin1 and LC3B after HSP were detected by Western blot. The number of autophagosomes was observed by transmission electron microscopy. Results:　In simulated chemotherapy microenvironment, the apoptosis rate of heat shock model group was lower than that of model group. In addition, the proliferation rate of the heat shock model group was higher than that of the model group, while the ratio of bright blue/dark red fluorescence cells was lower than that of the model group. The expressions of Hsp70 and Hsp90 were significantly up-regulated with time and reached the peak at 48 hours after HSP. Meanwhile, the number of autophagosomes, the expression of Beclin1 and the ratio of LC3BⅡ/LC3BⅠwere all decreased after HSP.Conclusion: HSP can improve the viability and anti-apoptosis ability of BMSCs under the chemotherapy microenvironment, and its effect may be related to the enhancement of Hsp70 and Hsp90 expressions and the weakening of autophagy level.

Abstract:Objective:　To investigate the effect and mechanism of anesthesia drug propofol on cerebral ischemia-reperfusion (IR) injury in rats. Methods:　Seventy-two healthy male SD rats were randomly divided into sham operation group, model group, propofol (Pro) group, Pro+DPCPX group, Pro+LY294002 group, Pro+DPCPX+LY294002 group, with 12 rats in each group. The middle cerebral artery was blocked by the intravascular endothelial method, and a focal cerebral IR injury model was established. Rats were scored for neurological function 24 hours after reperfusion. Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by Enzyme-linked immunosorbent assay (ELISA). The brain was detected by Triphenyl tetrazolium chloride (TTC) staining infarct volume, the expression of Bcl-2 positive cells was detected by immunohistochemistry, and the expression of Akt and p-Akt was detected by Western blot. Results:　Compared with the model group, propofol effectively reduced the neurological score of IR rats and the volume of cerebral infarction, increased the expression rate of Bcl-2 positive cells in brain tissue, and effectively reduced the expression levels of plasma inflammatory factor TNF-α and IL-1β in IR rats (P<0.05). At the same time, propofol significantly increased the level of p-Akt expression in the cerebral cortex (P<0.05), and the PI3K/Akt signaling pathway in IR rats interfered with by propofol was highly activated. When the experimental rats were treated with the PI3K in-hibitor LY294002, the neuroprotective effect of propofol was significantly inhibited and the therapy was ineffective. Its in-hibitory effect was comparable to that of A1R receptor antagonist DPCPX. Conclusion: Propofol can activate A1R in IR rat models by inhibiting the excitatory amino acid toxicity, promote the expression of p-Akt, further activate the PI3K/Akt signaling pathway, up-regulate the expression level of Bcl-2 in brain tissue, and exert anti-apoptotic effects. At the same time, it can down-regulate the expression of inflammatory factors TNF-α and IL-1β, reduce the body’s inflammatory response, and thus exerts a good therapeutic effect.

Abstract:Objective:　To explore the inhibitory effect of curcumin inhibits tubulointerstitial fibrosis after renal ischemia-reperfusion through TGF-β/Smads signaling pathway. Methods:　Forty healthy SD rats were randomly divided into sham operation group, model group, low dose group and high dose group. Clamped and loosened renal pedicle to make renal ischemia-reperfusion rat model. Serum creatinine (Scr) and urea nitrogen (BUN) levels, collagen content in kidney tissue, pathological changes of kidney tissue and expression of TGF-β1, Smad3 and Smad7 protein in kidney were measured. Results:　The shape of renal tubules was normal in sham-operation group, and there were significant pathological changes of renal tubular fibers in model group. The pathological changes of tubulointerstitial fibers in low dose group and high dose group were significantly improved, and the improvement degree in high dose group was higher than that in low dose group. The renal tubulointerstitial fibrosis score, Scr, BUN, collagen content, TGF-β1 and Smad3 in the model group were significantly higher than those in the sham operation group, and Smad7 was significantly lower than that in the sham operation group (P<0.05). The tubulointerstitial fibrosis score, Scr, BUN, collagen content, TGF-β1 and Smad3 in low dose group and high dose group were significantly lower than those in model group, and Smad7 was significantly higher than that in model group (P<0.05). The scores of renal tubulointerstitial fibrosis, Scr, BUN, collagen content, TGF-β1 and Smad3 in high dose group were significantly lower than those in low dose group, and Smad7 was significantly higher than that in low dose group (P<0.05). Conclusion: Curcumin can inhibit tubulointerstitial fibrosis after renal ischemia-reperfusion, and the mechanism may be inhibition of TGF-β/Smad signal transduction pathway.

Abstract:Objective:　To explore the stability of circadian rhythm and its correlation with depression and the longitudinal effects in college students. Methods:　From September to November, 2018 to 2020, an online questionnaire was issued to assess the circadian rhythm, depression, sleep quality, physical symptoms and life event stress of the freshmen, and they were followed and repeatedly evaluated for two years. Logistic regression model was established to analyze the independent correlation factors of depression in baseline assessment. Mixed effect model was established to analyze the stability of circadian rhythm, longitudinal change of depression and the influencing factors of depression. Results:　The detection rate of depression was 24.2%, 52.1% (4 301/8 244) of college students were eveningness, 45.0% (3 708/8 244) were intermedia circadian rhythm, and 2.9% (235/8 244) were morningness. Binary Logistic regression analysis suggested that eveningness (OR=1.526), worse sleep quality (OR=1.540), more serious physical symptoms (OR=1.115), and more stressful life events (OR=1.046) were more likely to have depression mood. The results of mixed effect model suggest that circadian rhythm was still a stable individual characteristic, although the score of morningness-eveningness questionnaire decreases by 1.948 points per year on average. While the standard score for depression increased by an average of 0.104 points per year, analysis of the fixed effects of the model suggested that baseline eveningness (β₀₁=0.028), sleep quality (β₀₂=0.052), physical symptoms (β₀₃=0.017), and life event stress (β₀₄=0.007) positively predicted the increase of standard depression scores. Moreover, students with poorer sleep quality (β₁₂=-0.012) and more stressful life events (β₁₄=-0.002) had a faster increase rate of standard depression score. Conclusion: Although the circadian rhythm is a stable individual characteristic, it will change over time in the college students, and eveningness is one of the important predictors of depression, prompting that circadian rhythm is a crisis intervention for college students’mental health.

Abstract:Objective:　To evaluate the efficacy and safety of early tranexamic acid (TXA) intervention in reducing hidden blood loss (HBL) after osteoporotic distal femoral fracture. Methods:　Retrospective analysis was performed. Elderly patients with osteoporotic distal femoral fracture (≥65 years old) admitted to our hospital from October 2018 to October 2020 were collected as the research subjects, and they were divided into TXA group (October 2018 to October 2019) and NS group (October 2019 to October 2020) according to the time of admission. TXA group was given 2 g of TXA intravenous infusion immediately after admission, and NS group was given the same amount of NS intravenous infusion immediately after admission. The general data, changes of hemoglobin (HGB), hematocrit (HCT) and HBL 1-3 days after trauma, the rate of blood transfusion and the incidence of deep vein thrombosis/pulmonary embolism were analyzed and compared between the two groups. Results:　A total of 87 patients were included, including 45 cases in TXA group and 42 cases in NS group. There were no statistically significant differences in general data between the two groups (P>0.05). The levels of HGB and HCT in TXA group and NS group 1-3 days after trauma decreased with the time extension after admission (P<0.05). The level of HGB in TXA group was higher than that in NS group 2 and 3 days after injury (P<0.05), and the level of HCT in TXA group was lower than that in NS group 1-3 days after injury (P<0.05). HBL in TXA group and NS group increased with time prolongation 1-3 days after injury (P<0.05). HBL in TXA group was lower than that in NS group 1-3 days after injury (P<0.05). There were statistically significant differences in the rate of blood transfusion after injury between the two groups (P<0.05), and there was no statistically significant difference in the incidence of venous thrombosis in lower extremity between the two groups (P>0.05). Conclusion: In elderly patients with osteoporotic distal femoral fracture, hidden blood loss can’t be ignored after injury. Early post-injury (≤6 h) TXA intervention can effectively reduce the amount of hidden blood loss and blood transfusion rate, and does not increase the incidence of deep vein thrombosis, which is safe and feasible.

Abstract:Objective:　To investigate the applicative value of enzyme-linked immunosorbent assay (ELISA) reaction model which took pneumococcal choline binding protein A (rCbpA) as antigen in detecting patients with community acquired pneumonia (CAP). Methods:　The specific primers of cbpA gene sequence were designed and synthetized, and proliferated according to PCR, finally, the cloning plasmids PGM-T/cbpA and expressing plasmids were constructed. Recombinant rCbpA was expressed after the inducing of isopropyl phosphorothioate (IPTG); ELISA model (rCbpA as antigen) was constructed and was used to detect IgM and IgG in the control group and CPA group. And results were compared with sputum culture and blood culture and were analyzed by Chi-square text. Results:　The recombinant protein CbpA was obtained and rCbpA-ELISA was established. The sensitivity detected by the rCbpA-IgM in pneumococcal CAP patients was 22.5%, which had no statistically significant difference by blood and sputum culture method (χ²=3.529, P=0.060; χ²=0.075, P=0.785). But its specificity was 100%, which was significantly higher than that by sputum culture (χ²=12.754, P=0.000). The sensitivity detected by rCbpA-IgG mode to detect pneumococcal CAP patients was 50%, which was statistically different from the sensitivity by blood culture and sputum culture (χ²=17.635, P=0.000; χ²=7.912, P=0.005). Conclusion: The serum recombinant protein rCbpA has high specificity to IgM and high sensitivity to IgG. Moreover, advantages including fast detection and objective judgment result, can improve the diagnostic value of pneumococcal infections.

Abstract:Objective:　To investigate the effect of delayed cord clamping (DCC, clamping the cord after 60 s of delivery) on the clinical outcome in extremely preterm infants (gestational week<32 weeks). Methods:　The clinical data of 100 cases of extremely premature infants from 2017 to 2019 were retrospectively analyzed and were divided into the experiment group (50 extremely premature infants with DCC) and the control group[50 extremely premature infants with immediate cord clamping (ICC, clamping within 15s after delivery)]. The level of hemoglobin (HB) and hematocrit (HCT) were compared after 24 hours and 2 weeks of birth between two groups, and the incidence of anemia and the amount of blood transfusion during hospitalization were also compared between two groups. The incidence of neonatal necrotizing enterocolitis, neonatal hyperbilirubinemia, periventricular intraventricular hemorrhage (PVH-IVH) and neonatal polycythemia was compared between the two groups. Results:　After 24 hours and 2 weeks of birth, the hemoglobin in the experimental group was higher than that in the control group, with statistically significant difference (P<0.05). The hematocrit between two groups after 24 hours of birth had no statistical difference, but it in the experimental group was higher than that in the control group at 2 weeks after birth (P<0.05). There were significant differences in the incidence of anemia, transfusion and periventricular-intraventricular hemorrhage between two groups (P<0.05), but there was no significant difference in the incidence of hyperbilirubinemia, neonatal necrotizing enterocolitis and neonatal polycythemia between two groups. Conclusion: DCC can reduce the incidence of anemia, transfusion and PVH-IVH in extermely premature infants during hospitalization.

Abstract:Objective:　To study the clinical significance of red blood cell distributioin width to platelet ratio (RPR) in the diagnosis, treatment and staging of multiple myeloma (MM), and to comprehensively analyze the applicative value of RPR combined with other relevant indicators. Methods:　A total of 51 eligible MM patients who were diagnosed in the North China University of Science and Technology Affiliated Hospital from October 2013 to October 2018 were collected as the case group, while 51 healthy subjects who underwent examination in the same period of time in the same hospital were selected as the control group for retrospective analysis. RPR was calculated based on blood routine results, and the differences in RPR, inflammatory indexes including, red blood cell distribution width (RDW), C-reactive protein (CRP), albumin/globumin (A/G), platelet (PLT), mean platelet volume (MPV), D-dimmer (D-D), classic staging index beta 2-macroglobulin (β₂-MG) and prognostic evaluation indicator lactate dehydrogenase (LDH) between two groups were compared. According to ISS staging criteria, MM patients were divided into three groups: phaseⅠ, Ⅱ, andⅢ. The differences between RPR and related indexes in different stages were analyzed. The correlation of RPR and inflammatory indicators A/G, coagulation indicators MPV and D-D, and classical staging indicator β₂-MG were respectively studied in the case group. Results: There were statistically significant differences in RPR, inflammatory indexes, coagulation indexes, the classic staging index and prognosis evaluation indicator between the case group and the control group (P=0.000, 0.000, 0.000, 0.000, 0.004, 0.006, 0.000, 0.000, 0.000). For the comparison of indicators among three groups, RPR and other indicators had statistical significance (P=0.000). By pairwise comparison, levels of RPR, RDW, CRP, LDH, D-D and β₂-MG were increased with the development of the disease, while levels of PLT, A/G and MPV were decreased with the development of the disease. For the correlation analysis between RPR and some indicators in the case group, RPR was positively correlated with D-D and β₂-MG (r=0.590, 0.803; P=0.000, 0.000), and was negatively correlated with A/G and MPV (r=-0.583, -0.500; P=0.000, 0.000). Conclusion: RPR can reflect the inflammation and bleeding state, and has certain clinical auxiliary significance for the diagnosis, treatment and staging of MM.

Abstract:Objective:　To evaluate the postoperative complication of early cervical cancer and analyze its risk factors by using the Clavien-Dindo/CTCAE complications classification system. Methods:　The clinical data of 412 patients with early cervical cancer from the our hospital from January 2008 to December 2015 were retrospectively analyzed, among which 54 were excluded without surgery, 23 did not meet the FIGO staging criteria, 60 clinical data were missed, and 27 withdrew from follow-up. Finally, a total of 248 patients with early cervical cancer were included. The patients were 44.5 (25, 85) years old and had a body mass index (BMI) of 22.9 (14.6, 45) kg/m². The system was used to grade patients during and after surgery. Univariate analysis of patient baseline data was performed. Variables with P<0.2 were included in the multivariate logistic regression model to determine risk factors for intraoperative and postoperative complications. Kaplan-Meier survival curve was used to analyze the overall survival rate and log-rank test was used. Results:　There were 31 cases (14.1%) of severe complications (Clavien-Dindo/CTCAETC≥3), 120 cases (48.4%) of non-serious complications, and 97 (39.1%) of no complications. Multivariate logistic regression model showed that BMI>30 kg/m²was an independent risk factor for intraoperative complications (OR=4.90, 95%CI=1.72-20.44, P=0.020). The parauterine invasion (OR=7.39, 95%CI=1.37-39.72, P=0.020), and preoperative radiotherapy (OR=3.98, 95%CI=1.29-12.34, P=0.016) were independent risk factors for serious postoperative complications. Conclusion: BMI>30 kg/m², parauterine invasion and preoperative radiotherapy are independent risk factors for intraoperative and postoperative complications.

Abstract:Objective:　To improve the ileum bladder abdominal wall fistula and evaluate its clinical effect. Methods:　From January 2010 to January 2020, the general data, perioperative condition and postoperative complications of the patients who underwent the modified ileum bladder abdominal wall fistula (the study group) and Bricker operations (the control group) were analyzed retrospectively. Results:　There were 35 cases in the study group and 48 cases in the control group. There was no significant difference in the general clinical data between two groups (P>0.05). The average operation time in the study group was (76.3±5.5) min, which was significantly shorter than that in the control group of (111.0±5.4) min (P<0.05). However, there was no statistical difference in bleeding, hospitalization time, drainage time, ureteral stent removal time and postoperative TNM staging between two groups (P>0.05). The incidence of total renal function abnormality, dermatitis around the stoma and scar in the study group were significantly lower than that in the control group (P<0.05), but leakage of urine, replacement of bladder stones, necrosis or stenosis of ileostomy between two groups had significant differences (P>0.05). The incidence of adhesive ileus and hydronephrosis in the study group was 0%, which was significantly lower than that in the traditional ileostomy group (12.7%, 15.9%) (P<0.05). Conclusion: The improved ileum bladder abdominal wall fistula has more reliable clinical effect and shorter operation time, and can avoid the complications of Bricker’s operation and traditional ileum bladder abdominal wall fistula, which is expected to become a more ideal urinary diversion operation.

Abstract:Objective:　To explore the guiding significance of model for end-stage liver disease (MELD) score in patients with hepatitis B virus (HBV) -related liver failure choosing different ways of artificial liver: plasma exchange (PE), double plasma molecular adsorption system (DPMAS) and PE+DPMAS. Methods:　The clinical data of 210 patients with HBV-related liver failure were analyzed retrospectively. All patients were divided into three intervals according to the MELD value at admission: MELD<30, 30≤MELD<40 and MELD≥40.Patients in each interval were divided into three groups according to different ways of artificial liver: the PE group, the DPMAS group and the PE+DPMAS group. Changes of laboratory indexes, MELD score, 4-week effective rate and 12-week mortality rate before and after treatment in three MELD groups were compared. Results:　①In all MELD intervals, the ALT, AST, TBIL and MELD scores in three groups before and after treatment were significantly decreased (P<0.05). Only in the 30≤MELD<40 interval, the decrease rate of TBIL and MELD decrease in the PE+DPMAS group were was the highest, with statistical difference (P<0.01), while there was no significant difference between intergroups in the other two MELD intervals.②In all MELD intervals, the PTA in the PE+DPMAS group and the PE group was increased and the difference between two groups was not statistically significant. PTA in the DPMAS group was decreased, with statistical significance (P<0.01). ③In all MELD intervals, there was no significant change in creatinine (Cr) before and after treatment, with no significant difference among three groups (P>0.05). ④In the MELD<30 interval, the efficiency of 4-week among three groups was not statistically significant (P>0.05), and PE group had the highest mortality at 12 week (P<0.05). In the 30≤MELD<40 interval, the PE+DPMAS group had the highest efficiency (P<0.05) and the lowest case fatality (P<0.01), and the difference was statistically significant; in the MELD≥40 interval, there was no significant difference among three groups in the efficiency and mortality (P>0.05). Conclusion: MELD score can be used for choosing artificial liver in patients with HBV-related liver failure. Patients in MELD<30 interval, prefer to DPMAS, while patients with liver failure in 30≤MELD<40 interval prefer to PE+DPMAS. But for patients in MELD≥40 interval, all artificial liver treatment are poor, therefore, liver transplantation should be performed as soon as possible.

Abstract:Objective:　To analyze the current situation of birth defects in Sichuan Province in recent years and put forward feasible preventive reference measures, so as to further reduce the level of birth defects in Sichuan Province and improve the quality of the born population. Methods:　The hospital monitoring data of birth defects in the whole province from 2010 to 2018 were analyzed and related database was established. Epidata 3.1 was used to input the data and SPSS 22.0 software was used to conduct statistics and analysis. Results:　From 2010 to 2018, the overall incidence of birth defects in the province was 150.51 per 10 000, a decrease of 20.70 percent in 2018 when compared with 2010.Some serious birth defects, such as neural tube defects, had a significant downward trend. Congenital heart disease had been becoming the first order deformity for six years in a row. Conclusion: The prevention and treatment of birth defects in ethnic minority areas and rural areas should be well carried out, the construction of the network system of birth defects should be strengthened, the prenatal diagnosis level of the whole province should be improved, and the implementation of birth defects policy and investment should be the focus of the prevention and treatment of birth defects in the whole province.

Abstract:Objective:　To investigate the short-term prognostic risk factors of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) treated with artificial liver and to establish a prognostic evaluation model. Methods:　The model for end stage liver disease (MELD) combined with total bilirubin rebound rate (TBRR) was used to establish a 90-day prognostic model for HBV-ACLF patients. The relevant laboratory indexes of 114 patients with HBV-ACLF before and after artificial liver treatment in our hospital were retrospectively analyzed. According to the outcome of 90 days after admission, they were divided into the survival group and the death group. The risk factors of patients’short-term death were tested by univariate analysis, binary logistic regression analysis and other methods, the predictive model was establish, and the ROC curve was drawn to compare the predictive value. Results:　Total bilirubin (TBil), creatinine (Crea), prothrombin time (PT), international normalized ratio (INR), TBRR, total bilirubin actual resident rate (TBARR), MELD, MELD and Child-Turcotte-Pugh (CTP) in the death group were higher than those in the survival group, while prothrombin activity (PTA) was lower than those in the survival group (P<0.05). There was no significant difference in total bilirubin clearance rate (TBCR) between groups (P=0.852). Binary logistic regression analysis revealed that TBRR, MELD and CTP were independent risk factors for 90-day mortality in patients with HBV-ACLF. Three prognostic prediction models of MELD, MELD-TBRR and MELD-TBRR-CTP were established, with the area under the receiver operating characteristic curve (AUC) of 0.786, 0.875 and 0.897, sensitivity of 58.33%, 88.46%, and 86.11%, and specificity of 70.51%, 86.11%and 79.49%, respectively. There was no significant difference in AUC between MELD-TBRR and MELD-TBRR-CTP (P=0.200). Conclusion: TBRR, MELD and CTP are independent risk factors for short-term mortality of patients with HBV-ACLF treated with artificial liver, and MELD combined with TBRR has a good predictive value for short-term prognosis of HBV-ACLF after artificial liver treatment.

Abstract:Objective:　To analyze the differential expression of IEC-6 small intestinal epithelial-derived exosomal miRNAs stimulated by TNF-α. Methods:　IEC-6 cells were stimulated with TNF-α (final concentration of 50 ng/mL) for 4h (the TNF-α-exosome group), and the supernatant was collected. The exosomes in the supernatant were extracted by the total exosome isolation kit combined with ultracentrifugation. Transmission electron microscopy, nanoparticle tracking analysis (NTA) and Western blot were performed to identify exosomes. High throughput sequencing was used to compare the differential expression of exosome miRNAs between the control-exosome group (IEC-6 normally incubated with TNF-α-free medium) and the TNF-α-exosome group. Target Scan, miRDB and miRWalk were used to predict target genes of differential miRNAs, cytoscape was applied for the construction of miRNAs-target genes network and DAVID annotation tools were applied on target genes to analyze the biological functions of genes. Results:　The transmission microscopy showed that there were a large number of exosomes, which were round or elliptical lipid bilayer vesicles, heterogeneously distributed, with a diameter about 50 nm to 200 nm. NTA showed that the main peak of the particle size was 141.9 nm, the concentration was 3.41×10⁹particle/mL. Western blot results showed that the exosome marker protein CD63 was positive. High-throughput sequencing screened six differentially expressed exosomal miRNAs (|log₂ (fold change) |>2, P<0.05). Compared with the control-exosome group, rno-miR-125a-5p (|log₂ (fold change) |=3.689 0) and rno-miR-351-5p (|log₂ (fold change) |=3.803 1) in the TNF-α-exosome group were significantly down-regulated, and rno-miR-125b-5p (|log₂ (fold change) |=2.933 0), rno-miR-542-3p (|log₂ (fold change) |=2.995 6), rno-miR-30c-5p (|log₂ (fold change) |=3.065 0) and rno-miR-20a-5p (|log₂ (fold change) |=2.890 8) in the TNF-α-exosome group were obvious down-regulated. Six differentially expressed miRNAs target genes were predicted by using the miRNA target gene prediction website and 158 genes were obtained and the network of six miRNAs were constructed. DAVID annotation showed that the target genes of down-regulated miRNAs were mainly involved in 1 Kyoto encyclopedia of genes and genomes (KEGG) pathway and 12 gene ontology_biological process (GO_BP), 15 gene ontology_cell component (GO_CC), 3 gene ontology_molecular function (GO_MF). Conclusion: Exosomes derived from TNF-α-induced small intestinal epithelial cells contain rich miRNAs, and their expression profiles are significantly different. With the help of high throughput sequencing and related database, more information about the exosomal miRNAs derived from small intestinal epithelial cells and its function are revealed, and a new perspective for the pathogenesis of small intestinal mucosal injury-related diseases are provided.

Abstract:Objective:　To investigate the clinical factors affecting the prognosis of elderly patients with advanced gastric cancer. Methods:　SEER*Stat software was used to extract patients with advanced gastric cancer aged 65-85 years with pathological diagnosis from 2010 to 2016.The univariate and multivariate Cox regression analysis were used to investigate the clinical factors affecting the prognosis of elderly patients with advanced gastric cancer. Results:　Cox multivariate regression showed that the HR for 75-85 years was 1.33 (95%CI=1.20-1.49, P=0.000); the HR for middle and high differentiation was 0.82 (95%CI=0.71-0.93, P=0.003), and 0.61 (95%CI=0.43-0.86, P=0.005); HR of tumor size in 31-60 mm, 61-90 mm, ≥91 mm were 1.16 (95%CI=1.01-1.33, P=0.035), 1.2 (95%CI=1.01-1.42, P=0.035), and 1.53 (95%CI=1.26-1.85, P=0.000). With the increase of LNR, the HR also increased (P≤0.001); the HR of bone metastases was 1.4 (95%CI=1.08-1.81, P=0.01), and the HR of multiple metastatic sites was 1.54 (95%CI=1.30-1.83, P=0.000); and the HR for multiple primary cancer was 0.66 (95%CI=0.48-0.92, P=0.013). Conclusion: Independent prognostic factors affecting advanced gastric cancer in the elderly include age, degree of differentiation, tumor size, LNR, number of tumors, and metastatic sites. However, because LNR information and access are dependent on the implementation of surgery, but the proportion of advanced gastric cancer surgery is low, so it’s practical application value in the prognosis prediction of advanced gastric cancer is debatable.

Abstract:Objective:　To explore the potential target genes, signal transduction pathways and molecular mechanisms of MicroRNAs regulating matrix metalloproteinases (MMPs) in breast cancer using bioinformatics analysis. Methods:　Gene chips samples of normal mammary gland tissues and breast cancer tissues were downloaded from GEO database and TCGA database. The differentially expressed genes between normal tissue samples and breast cancer tissues were analyzed by R software package Limma. KEGG pathway analysiswas performed for the screened differentially expressed genes. Results:　Through trend analysis of differentially expressed genes, 544 significantly up-regulated genes and 1 030 significantly down-regulated genes were screened, among which MMP1/3/9/11/13/28 could be related genes that mediate invasive progression of breast cancer. Survival analysis showed that the high expression of MMP1/3/9/11/13 was associated with poor prognosis, and the high expression of MMP1 was an independent risk factor for breast cancer (P<0.01). Conclusion: The integrative bioinformatics analysis performed in the present study suggests that the expression of MMPs is increased in breast cancer and other cancer tissues, and the expression of MMPs can significantly affect the prognosis of breast cancer patients. Compared with other MMPs, MMP1 may be an appropriate target for targeted therapy in patients with breast cancer.

Abstract:Objective:　To perform a bioinformatics analysis of the gene chip associated with spinal cord injury (SCI) in rats, so as to provide new ideas for clarifying the molecular mechanism of secondary SCI. Methods:　Firstly, data sets GSE464 and GSE45006 of rat SCI mRNA expression profile were downloaded from the GEO database. The R language limma package was used to screen differential expression genes (DEGs) of injured and normal spinal cord and obtain the intersection. Then GO, KEGG and GSEA analyses were performed. Subsequently, the STRING online tool and Cytoscape software were used to construct and visualize a protein-protein interaction (PPI) network, and the cytoHubba plug-in was used to select the hub gene. Finally, the GOSemSim package was used to predict interactions between proteins encoded by the hub gene. Results:　A total of 226 DEGs were screened. Functional annotation and pathway enrichment analysis showed that DEGs were mainly involved in biological processes (BP), which contained response of cells to inflammation, regulation of ions, regeneration and repair; mainly participated in the main cellular components (CC) including presynaptic membrane, axonal ends and neuron projection endpoints; mediated the molecular function (MF): ATP phosphorylation, structural composition of the cytoskeleton, and binding to calcium-dependent proteins. Enriched pathways were mainly TNF, AGE-RAGE, NF-κB and Toll-like receptors. A total of 10 hub genes were obtained, namely Tubb5, Prkcd, Anxa2, Gns, Fabp5, Ctsc, Lyz2, Gusb, Vat1, and Grn, and were closely related with SCI. Among them, Prkcd, Ctsc, Vat1, Gns and Lyz2 genes in SCI lacked studies, and were worthy of further study. Conclusion: This study identifies hub genes and signaling pathways that may be involved in secondary SCI, and provides a new theoretical basis for the molecular mechanism of secondary SCI.

Abstract:Objective:　To analyze the differential miRNAs and target genes of normal striated muscle and rhabdomyosarcoma (RMS) tissues by using bioinformatics methods, so as to provide new ideas for RMS study. Methods:　GEO2R was used to analyze the differential miRNAs of RMS. Sangerbox was used to draw volcanic maps. TargetScan, miRDB and miRwalk were used to predict the intersection of target genes. Enrichr was used to analyze GO enrichment analysis and KEGG signaling pathway of target genes. Cytoscape combined survival analysis was used to screen the hub gene and its molecular regulatory network with miRNAs. Results:　According to GEO2R analysis, 2 549 differential miRNAs were obtained, of which 1 318 and 1 231 miRNAs were up-regulated and down-regulated, respectively. According to|log₂FC|>1.5 and P<0.05, six differential miRNAs (up-regualted: miR-410-3p, miR-381-3p, miR-483-3p and miR-376a-3p; down-regulated: miR-29c-3p and miR-145-5p) were screened. TargetScan, miRDB and miR-walk predicted the target genes of the six differential miRNAs, and a total of 1 262 target genes were obtained from the Veen plot. GO enrichment and KEGG signal pathway analysis of differential miRNAs-target genes revealed that enrichment was in the regulation of RNA polymeraseⅡand regulated the signal pathway of stem cell pluripotency and the Hippo signaling pathway. After cytoscape analysis screening top10 hub genes, it combined with survival curve analysis showed that high expression of FBXL3 and low expression of SPSB4, VHL, SMAD4, NRAS and KRAS had a better prognosis. Conclusion: Utilizing bioinformatics to analyze differential miRNAs-target genes of normal striated muscle and RMS, miR-145-5p (SPSB4, FBXL3, SMAD4, NRAS), miR-29c-3p (VHL) and miR-381-3p (KRAS) are screened, which can provide potential molecular targets for the study of RMS.

Abstract:Objective:　To predict the target genes of rno-miR-181b-5p selected from Small RNA sequence and to perform bioinformatics analysis and identification for laying a foundation for the biological function of miR-181b-5p in the treatment of cerebral ischemia-reperfusion injury with biliverdin. Methods:　The target genes of rno-miR-181b-5p were screened through TargetScan, miRDB and miRwalk databases respectively. Then, bioinformatic analysis of these intersection target genes of the three databases were performed by gene ontology analysis and KEGG pathway analysis. Subsequently, dual luciferase reporter gene assays were performed to identify the targets, and the expression changes of endothelial cell specific molecule-1 (Ems1) after overexpression of miR-181b-5p in rat vascular endothelial cells were detected by RT-QPCR and Western blot. Results:　There were 28 target genes intersected by the three databases, which were mainly located in such GO items of biological process as regulating stimulus response (P=0.013), regulating cell growth (P=0.014) and positive regulation (P=0.048). The cellular component of these genes principally were involved in such GO items as intracellular membrane-bounded organelles (P=0.045) and adherens junction (P=0.049). At the molecular function level, these target genes were significantly involved in such GO items as mRNA 5’-UTR binding (P=0.017), receptor binding (P=0.032), and protein binding (P=0.046). The KEGG pathway analysis demonstrated that these genes were mainly enriched in synaptic vesicle circulation (P=0.024), basal transcription factors pathway (P=0.040) and RIG-I-like receptor signaling pathway (P=0.047), etc. The results of dual luciferase reporter gene assays suggested rno-miR-181b-5p could target and regulate Esm1 genes. Moreover, RT-QPCR and Western blot results also showed that overexpression of miR-181b-5p can negatively regulate Esm1 in rat vascular endothelial cells.Conclusion: rno-miR-181b-5p may play an important biologically role in the treatment of cerebral ischemia-reperfusion injury in rats with biliverdin by targeting regulation of Esm1 gene.

Abstract:Acute lung injury (ALI) is a life-threatening clinical syndrome during the clinical course in critically ill patients. The identification of novel biomarkers for early diagnosis and finding more effective treatments of ALI are topics on current research. High mobility group box-1 protein (HMGB1) is a late inflammatory mediator associated with sepsis, malignancy, and immune disease. Expression of HMGB1 may reflect the severity of inflammation and tissue damage, which indicates a potential role for HMGB1 as a prognostic biomarker and a potential target for blocking inflammatory pathways in ALI. Several studies have shown that HMGB1 regulates autophagy. Autophagy, also called typeⅡprogrammed cell death, is an important biological process which maintains cellular homeostasis. Studies have shown that HMGB1 and autophagy are involved in the pathogenesis of many lung diseases including ALI, while the underlying specific mechanisms remain to be determined. This review provides an update on the role of HMGB1 and autophagy in ALI.

Abstract:Rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) is a special type of rhegmatogenous retinal detachment (RRD), with characteristics of acute onset, rapid development and poor prognosis. At present, there is no definite conclusion about its pathogenesis and mechanism. Recent studies have shown that retinol-binding protein 4 (RBP4) is a novel adipocytokine and can participate in the occurrence and development of RRDCD. This paper systematically concluded papers at home and abroad, and reviewed the correlation between RBP4 and RRDCD.

Abstract:Protein palmitoylation is the only fully reversible post-translational lipidation modification for proteins and appears as a ubiquitous mechanism controlling properties and functions of many proteins which exists in physiological processes. Palmitoylation can be achieved by adding long chain lipids into intracellular cysteine residues of soluble transmembrane proteins through unstable thioester bonds. The addition of lipids can increase protein hydrophobicity, which can influence protein structure, assembling, maturation, transportation and function. This review introduces the process of palmitoylation, such as the prediction of palmitoylation sites, the acquisition of palmitoylated proteins, the inhibition of palmitoylation and the use of activators, which brings out the method for combining palmitoylated proteins with mass spectrometry, highlighting the regulatory role of protein function and further discussing its impact on protein transport.

Abstract:Radiation-induced bystander effects (RIBE) means that radiated cells transmit the damage effect to the irradiated cells through a certain mechanism and irradiated cells show similar biological damage effects to radiated cells. In recent years, many kinds of regulatory proteins and signaling pathways have been found to be involved in apoptosis, proliferation, cell cycle arrest and other biological effects in the process of heavy ion RIBE. This article reviewed the mechanism of these regulatory proteins and signaling pathways in heavy ion RIBE.

Abstract:A large number of studies have shown that vaccines immunized by nasal mucosa can induce the production of immunoglobulin A (IgA), which is expected to be one of the effective ways of vaccine. However, immunization with the vaccine nasal mucosa alone does not induce strong IgA production in the nasal cavity. It is necessary to add an adjuvant to activate the innate immune response and enhance antigen-specific IgA production and cellular response. At present, there are many kinds of nasal mucosal immune adjuvants, but its specific action mechanism of promoting immune responses remains unclear. This article discusses the pathway of nasal mucosal immune adjuvant in promoting immune response in nasal-associated lymphoid tissue (NALT), and provides a reference for further research on nasal mucosal immune adjuvant.

Abstract:β-thalassemia and sickle cell anemia (SCA) are hemoglobin diseases caused by abnormal β-globin, occurring in South-east Asia, South Asia, North Africa and the Mediterranean region with different degrees. Elevated fetal hemoglobin (HbF) levels can significantly improve their clinical symptoms. B-cell lymphoma/leukemia 11A (BCL11A), a zinc finger structure transcription factor, plays an important negative regulatory role in fetal-to-adult hemoglobin expression. Down-regulated BCL11A activates γ-globin, so as to increase fetal hemoglobin expression, alleviating clinical symptoms of β-thalassemia and SCA. This article focuses on the mechanism of BCL11A on γ-globin, and the treatment of β-thalassemia and SCA based on BCL11A, thereby providing a theoretical basis for the study of β-globin disease.