Objective:To investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (hUCMSC-ex) in wounds with escharectomy and skin grafting in scalded rats.Methods:The study was an experimental study. Twelve male Sprague-Dawley (SD) rats aged 6-8 weeks were divided into combined treatment group, fixed+allogeneic skin group, autologous skin+allogeneic skin group, and allogeneic skin group by random number table method (the same grouping method hereinafter), with 3 rats in each group. The four groups of rats were inflicted with scalded wounds on the back and performed with escharectomy, and then the wounds of rats in combined treatment group were fixed with a metal ring (the same fixing method hereinafter) and transplanted with autologous skin grafts and allogeneic skin grafts, and the other three groups of rats were fixed and/or transplanted with skin grafts corresponding to the group name. At 14, 21, and 28 d after surgery, the wound healing area in the four groups of rats was measured. Another 15 male SD rats aged 6-8 weeks were divided into normal group with no treatment, high exosome group, low exosome group, supernatant group, and phosphate buffer solution (PBS) group, with 3 rats in each group. The last 4 groups of rats were treated as that in the above-mentioned combined treatment group, and then were injected around the wounds with 200 μL of PBS containing 100 μg of hUCMSC-ex, 200 μL of PBS containing 50 μg of hUCMSC-ex, 200 μL of supernatant with no hUCMSC-ex, and 200 μL of PBS at 0 (immediately), 7, 14, and 21 d after surgery, respectively. At 14, 21, and 28 d after surgery, the wound healing area in the four groups of rats was measured. The wound neo-epithelial tissue of rats in high exosome group and PBS group at 28 d after surgery and the normal skin tissue of rats in normal group at the same time point were taken, and the differentially expressed proteins were screened by label-free quantitative proteomics method; the two up-regulated and differentially expressed proteins, the immunoglobulin G1 heavy chain constant region (IGHG1) and cystatin A (CSTA) with the largest and second largest fold changes in comparison between high exosome group and PBS group were selected, and their protein expressions were detected by Western blotting. The number of samples in all experiments was 3.Results:At 14, 21, and 28 d after surgery, the wound healing area in combined treatment group, autologous skin+allogeneic skin group, and allogeneic skin group of rats was significantly larger than that in fixed+allogeneic skin group ( P<0.05), the wound healing area in autologous skin+allogeneic skin group of rats at 21 d after surgery and that in allogeneic skin group of rats at 14 and 21 d after surgery was significantly larger than that in combined treatment group ( P<0.05), and the wound healing area in allogeneic skin group of rats at 14 d after surgery was significantly larger than that in autologous skin+allogeneic skin group ( P<0.05). The wound healing area of rats in high exosome group and low exosome group at 14, 21, and 28 d after surgery and in supernatant group at 14 and 28 d after surgery was significantly larger than that in PBS group ( P<0.05); the wound healing area in high exosome group of rats at 14 and 21 d after surgery was significantly larger than that in supernatant group ( P<0.05), and the wound healing area at 14 d after surgery was significantly larger than that in low exosome group ( P<0.05); the wound healing area in low exosome group of rats at 14 d after surgery was significantly larger than that in supernatant group ( P<0.05). Compared with that in PBS group, 332 proteins were differentially expressed in the neo-epithelial tissue of the wounds in high exosome group of rats at 28 d after surgery ( P<0.05), among which the protein expressions of IGHG1 and CSTA were significantly up-regulated (with fold change of 12.60 and 2.27, respectively, P<0.05). Compared with those of normal skin tissue in normal group, 1 400 and 1 057 proteins were differentially expressed in the neo-epithelial tissue of the wounds in high exosome group and PBS group of rats at 28 d after surgery, respectively. The protein expressions of IGHG1 and CSTA in the wound neo-epithelial tissue in high exosome group of rats at 28 d after surgery were significantly larger than those in normal skin tissue of rats in normal group ( P<0.05) and those in PBS group ( P<0.05). Conclusions:hUCMSC-ex may accelerate the repair process of wounds with escharectomy and skin grafting and improve the quality of wound healing in scalded rats by regulating the protein expressions of IGHG1 and CSTA.

Objective:The DNA aptamers of lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vasculitis, were screened and a visual detection method using unlabeled nucleic acid aptamer-gold nanoparticle (AuNP) probe was established.Method:Lp-PLA2 aptamers were screened through 8 cycles of incubation binding, ssDNA isolation, PCR amplification and single strand recovery by the magnetic bead fixation SELEX technique. The affinity and specificity of the aptamers were validated using surface plasmon resonance technology and flow cytometry, and the secondary structure of the aptamer and its three-dimensional molecular docking with the target protein were simulated by computer software. Subsequently, aptamer-AuNP complex was prepared, and the color change was caused by salt-induced condensation of the AuNP solution by target competitive binding. Then, the target concentration was detected by measuring the absorbance of the solution with a spectrophotometer. The linear relationship between the sample absorbance and concentration of Lp-PLA2 were established under the optimal determine conditions.Results:Three Lp-PLA2 aptamers B76-2, B76-4 and B76-5 with high affinity and strong specificity were obtained, and the dissociation constants were 1.07, 1.26 and 1.75 nmol/L, respectively. Then AuNP colorimetric sensing method based on B76-2 aptamer was successfully constructed. The linear range and detection limit of Lp-PLA2 were 20-500 ng/ml and 78 ng/ml, respectively, and the reaction time was 30 min, which could specifically distinguish the target from other thrombotic markers such as thrombin and myeloperoxidase.Conclusion:A simple, rapid and specific visual detection method for visually detecting Lp-PLA2 was established by using aptamer-AuNP colorimetric assay.

Objective : To explore the association of time in range(TIR) and glucose management indicator ( GMI) with the risk of type 2 diabetic nephropathy (DN) ． Methods : The clinical data of 215 patients with type 2 diabetes mellitus (T2DM) were collected and analyzed．According to the results of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio( UACR) ，they were divided into 117 patients with T2DM and 98 patients with DN．The clinical data，biochemical indicators and continuous glucose monitoring ( CGM) indicators of the two groups were compared．Logistic regression was used to analyze the influencing factors of DN risk．The predictive value of TIR and GMI on the risk of DN was evaluated by receiver operating characteristic (ROC) curve. Results: There were significant differences in age，duration of diabetes，systolic blood pressure，glycosylated hemoglobin ( HbA1c) ，fasting plasma glucose (FPG) ，2 hour postprandial plasma glucose (2hPG) ，creatinine( Cr) ，UACR, eGFR between the two groups(P＜0. 05) ．There were statistically significant differences between the two groups in the CGM indexes of GMI，mean absolute difference of mean of daily differences ( MODD) ，glucose above target range time(TAR) and TIR(P＜0. 05) ．The results of logistic regression analysis showed that TIR was a protective factor of DN．In the ROC curve analysis of TIR prediction DN，the area under the ROC curve was 0. 718 (95% CI = 0. 648 ～0. 789，P＜0. 001) ，and the Yoden index was 0. 38．At this time，the sensitivity was 66. 7% ，and the specificity was 71. 3%．In the ROC curve analysis of GMI prediction DN，the area under the ROC curve was 0. 701 (95% CI = 0. 629 ～0. 774，P＜0. 001) ，and the Yoden index was 0. 368．At this time，the sensitivity was 63. 3% ， and the specificity was 73. 5%． Conclusion Specifically，lower TIR and higher GMI increase the risk of DN.

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Objective To investigate the effect of gaseous effluent from the six generator sets on the radiation level of the surrounding terrestrial environment in Daya Bay Nuclear Power Base after the operation of Ling’ao Nuclear Power plant. Methods The radiation level in the peripheral environment of the Base was monitored using the thermoluminescence dosimeter （TLD）. Twenty-five monitoring sites were set around the Base to investigate the variation of radiation level over a long period of time by collecting the TLDs every three months. Results From 2011 to 2020, the annual γ dose rate of the 25 sites ranged from 76.7 to 207.1 nGy/h, with an average value of (123.3 ± 5.7) nGy/h and a relative deviation of 2%-12%. The TLD monitoring and instantaneous measuring results of γ dose rate were consistent with the survey of the State Environmental Protection Administration in the 20th century and the baseline level prior to the operation of the nuclear power plant. Conclusion There are great differences in natural environmental radiation level across the TLD monitoring sites. The overall environmental γ radiation level within 50 km of the nuclear power base remains unchanged. The emission of gaseous effluent from the operation of the nuclear power plant does not have a cumulative impact on the radiation level of surrounding environment.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Objective:To study the correlation between liver imaging reporting and data system (LI-RADS) category with tumor differentiation, Ki67 index, microvascular infiltration, and predictive prognosis in hepatocellular carcinoma (HCC).Methods:We retrospectively analyzed the clinical and radiological data of 178 patients with HCC who were confirmed by histopathological studies after liver resection between January 2015 and September 2020 at Lishui Central Hospital and Lishui People’s Hospital. There were 156 males and 22 females, with age of (57±10) years old. These patients were assessed for LI-RADS categories according to the 2018 version of LI-RADS, and they were divided into 4 groups according to the assessment results: 12 patients with LI-RADS-3 (the LI-RADS-3 group); 26 patients with LI-RADS-4 (the LI-RADS-4 group); 102 patients with LI-RADS-5 (the LI-RADS-5 group); and 38 patients with LI-RADS-M (the LI-RADS-M group). The patients' general information, tumor markers, pathology and other clinical data were recorded. Correlation analysis between the LI-RADS category with pathology was performed by the Kendall's tau-b test. Survival analysis between groups was performed by the Kaplan-Meier analysis. The Cox regression risk model was used to analyze the relationship between these variables with the risk of death.Results:The Kendall's tau-b test showed that LI-RADS category was positively correlated with the degree of tumor differentiation ( t=0.204, P=0.002), but not with microvascular infiltration and Ki 67 index ( P>0.05). All patients were followed up for 4.2 to 84.2 months (median follow-up 36.3 months). By the end of follow-up, 31 patients had died and 147 patients were alive. The cumulative 1-year and 3-year survival rates of the LI-RADS-5 group were 97% and 90% respectively, which were significantly higher than those in the LI-RADS-M group (81% and 63%), and the LI-RADS-4 group (96% and 81%), ( P<0.05). The cumulative 1-year and 3-year survival rates of patients in the LI-RADS-3 group were 100% and 67% respectively, and there was no statistically significant difference with the LI-RADS-5 group ( P>0.05). The Cox multivariate regression analysis showed that tumor glycoantigen 199 (>50 μl/ml) to be an independent influencing factor in survival of HCC patients ( HR=0.43, 95% CI: 0.24-0.76, P=0.004). Conclusion:The LI-RADS category of HCC was positively correlated with the degree of tumor differentiation, and patients with HCC meeting the LI-RADS-5 criteria had relatively better prognosis.

Objective:To develop and evaluate the reliability and validity of risk behavior scale for in-home unintentional injury in urban children aged 0-6 years in China.Methods:Through literature review, expert consultation and pre-survey, the final scale was determined with 10 dimensions and 54 items. A total of 1 104 children aged 0-6 years were randomly selected by using multi-stage stratified cluster sampling in the urban area of Changsha and their guardians were invited to participate in this questionnaire survey. The information about the basic characteristics, incidence of unintentional injury and risk behaviors of the children were collected. Cronbach's α coefficient and split-half reliability were used to evaluate the reliability of the scale. Pearson correlation coefficient, Spearman correlation coefficient and factor analysis were used to evaluate the content validity and structural validity of the scale respectively. The children were divided into two groups according to the incidence of unintentional injury, and t-test was used to analyze the discriminant validity of the scale. Results:The children risk behavior scale had 54 items in 10 dimensions. A total of 1 094 valid questionnaires were returned and the effective response rate was 99.09%. The incidence of unintentional injury in the children was 18.65% (204/1 104). The Cronbach's α coefficient of the scale was 0.94, and the split-half reliability was 0.87. The Pearson correlation coefficients between each dimension and the total scale were 0.50-0.84 (all P<0.001). A total of 11 common factors were extracted from the total scale, and the cumulative variance contribution rate was 56.52%. The average factor load of 54 items was more than 0.30. The fitting indexes of the scale were 0.06 for root mean square error of approximation, 0.78 for comparative fit index, 0.79 for goodness-of-fit index, and 0.77 for adjusted goodness-of-fit index. The children with injuries had higher scores than those without injuries, the difference was significant ( P<0.001). Conclusion:The scale developed has good reliability and validity on assessing the risk behaviors of unintentional injury in urban children in China.

Objective:To investigate the effect of Salvia miltiorrhiza injection combined with human adipose derived stem cells (hADSC) on the survival rate of autologous fat granules implanted in nude mice.Methods:A total of 24 healthy 8 weeks old female nude mice weighing (23±3) g were randomly divided into four groups ( n=6): Group A was given fat granules 0.5 ml; Group B: fat granules 0.5 ml+ hADSC; Group C: Salvia miltiorrhiza 0.5 g/(kg·d) + fat granules 0.5 ml, and Group D: Salvia miltiorrhiza injection 0.5 g/(kg·d) + fat granules + enrichment. 3 nude mice were randomly selected from each group for 15 days after transplantation and stained with conventional HE. Immunohistochemical staining was performed to count the number of microvessels. On the 30th day after surgery, the remaining 3 nude mice in each group were sacrificed. The specimens were stained with HE and the volume of each specimen was measured. Results:Graft appearance was observed by naked eye: 15 days after the operation, all the specimens were formed completely. The new capillaries were shaped on the surface of the capsule. The boundaries of the capsule and the surrounding tissue were obvious. The activity was good, the hardness of the texture was medium, and the loose connective tissue was connected to the surrounding tissue. On the 30 day after operation, the volume of the graft was smaller than that at the beginning of transplantation, and fat liquefaction and necrosis were seen in some tissues. Blood vessel density values of immunohistochemical sections of fat transplantation in each group 15 days after surgery were compared pairwisely. The differences between the groups were statistically significant ( P<0.05). Lsd-t method was used for pairwise comparison of fat graft volume values of each group 30 days after surgery, and the difference between each group was statistically significant ( P<0.05). Conclusions:The combined use of Salvia miltiorrhiza injection and hADSCs can effectively promote the reconstruction of the early vascular system of the fat granule transplantation and improve the survival rate of fat particles more effectively than the individual use.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.