AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease.METHODS:Male SD rats were randomly divided into normal control ( NC) group, high fat ( HF) group and HF+liraglutide ( Lira) group.The rats in HF group and HF+Lira group were given high-fat diet for 16 weeks.After 12 weeks of high-fat diet feeding in HF+Lira group, Lira (600μg? kg-1? d-1 ) was intraperitoneally injected for 4 weeks.At the end of the 16th week, the rats were killed.The pathologi-cal changes of the liver were observed under optical microscope.The serum levels of alanine aminotransferase ( ALT) , as-partate aminotransferase ( AST) , triglyceride ( TG) and total cholesterol ( TC) were detected by automatic biochemical an-alyzer.TG contents of liver were measured by GPO-PAP method.The fasting insulin ( FINS) was determined by ELISA, and insulin resistance index was assessed by homeostasis mode assessment ( HOMA-IR) .The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR.RESULTS:Compared with NC group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF group were obviously increased (P<0.01).Compared with HF group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF+Lira group were all obviously decreased (P<0.05 or P<0.01).The mRNA expression of SOCS-3 and SREBP-1c in HF group was signifi-cantly higher than that in NC group (P<0.01).The mRNA expression of SOCSV3 and SREBP-1c in HF+Lira group was significantly decreased as compared with HF group (P<0.05).CONCLUSION:Liraglutide may improve the IR and re-
duce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c, so as to play a therapeutic role in nonalcoholic fatty liver disease.

Objective: Throughing the investigation and analysis of seven cases of acute lung injury caused by a welding operation, the hazards and production pathways of harmful gases such as phosgene and nitrogen oxides are understood, which will serve as a reference for preventing similar events in the future. Methods: Throughing the accident scene environment investigation and clinical case analysis, combined with the laboratory test results, carried on the comprehensive analysis. Results: The accident caused a total of 7 people to suffer from acute lung injury to varying degrees. Three of them were sent to the ICU ward for treatment due to acute respiratory failure. After active treatment, 7 people were discharged from the hospital with obvious relief. Conclusion Welding is also a kind of profession that causes the high incidence of acute lung injury accidents. It is necessary to strengthen the knowledge training and protection awareness education of welding workers to avoid the occurrence of acute harmful gas poisoning accidents.

Objective To investigate the effects of curcumin on myosin light chain kinase(MLCK)in the intestinal mucosa of rats with nonalcoholic fatty liver disease(NAFLD). Methods 35 SD rats were randomly di-vided into the normal control group ,the high fat group and the curcumin group. The high fat group ,curcumin group were given high fat diet for 16 weeks. After 8 weeks of high fat feeding in the curcumin group ,the rats were gavaged with 200 mg/(kg·d)curcumin for 8 weeks. The levels of ALT,AST,LPS and DAO in blood and expres-sion of MLCK in the intestinal mucosa were detected. The changes of liver pathology and tight junction(TJ)of the intestinal mucosa were observed. Results Compared with the control group,the blood levels of ALT,AST,LPS and DAO in the high fat group were obviously increased(P<0.05);Compared with the high fat group,the blood levels of ALT、AST、LPS and DAO in the curcumin group were obviously decreased (P < 0.05). In the high fat group ,hepatocellular steatosis was obvious ,while in the curcumin group hepatocellular steatosis was decreased. TJ was disrupted in the high fat group ,and the intercellular space was larger in the TJ group than the control group (P<0.05). The intercellular space was narrower in the curcumin group than the high fat group(P<0.05). The expression of MLCK in the high fat group was significant higher than that in the control group(P<0.05). The pos-itive staining in the curcumin group was significant lower than that in the high fat group (P < 0.05). Conclusion Curcumin can ameliorate hepatic steatosis by downregulating expression of MLCK in the intestinal mucosa of rats with NAFLD,improving TJ structure of the intestinal mucosa.

Arsenic is a widely occurring metalloid element in the natural environment and is one of the primary carcinogens identified by the World Health Organization (WHO), but the specific carcinogenic mechanism is currently unclear. In recent years, through toxicological studies on arsenic, it has been found that exposure to arsenic can affect cellular metabolism in the body, which may be closely related to the carcinogenic mechanism of arsenic. Therefore, the authors review the research progress on arsenic exposure-induced effects on glucose metabolism, lipid metabolism, and amino acid metabolism, with a view to providing a theoretical basis for the study of the mechanism of arsenic carcinogenesis.

As an emerging drug delivery technology,microneedles can puncture the skin's stratum corneum to create micron-sized conduits,painlessly,minimally invasive,and efficiently deliver drugs into viable epidermis or dermis for local or systemic therapeutic effects.This paper reviews the current clinical trials of microneedles used in the treatment of various diseases,elaborates on the characteristics of various types of microneedles,and summarizes the latest research progress of microneedles used to treat skin tumors,including chemotherapy,photothermal and photodynamic therapy,immunotherapy,gene therapy,and combination therapy.This review provides ideas and directions for further research on microneedles in treating skin tumors.

Objective:To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing.Methods:Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results:Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] ( t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] ( t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] ( t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests ( t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) ( t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) ( t=3.88, P=0.005; t=3.02, P=0.017). Conclusions:The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

Mice ; Animals ; Rett Syndrome ; Longevity ; Methyl-CpG-Binding Protein 2 ; Disease Models, Animal ; Phenotype

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Humans ; Hematopoietic Stem Cell Transplantation ; Multiple Myeloma/therapy* ; Transplantation, Autologous ; Retrospective Studies ; Combined Modality Therapy ; Stem Cell Transplantation/adverse effects*