OBJECTIVE: To review the progress on materials with lysosomal escape function. METHODS: Based on the original researches in recent years, the structure properties and escape mechanism of materials with lysosomal escape function were introduced in the present paper. RESULTS: The materials which can help the drug/gene to get out of the lysosomes were summarized and classified into two groups in the accordance with their escape mechanism: breaking the lysosomes by raising the osmotic pressure or destabilizing the membrane structure of lysosomes. CONCLUSION: The materials with lysosomal escape function, as a novel drug delivery tool, has promising application for the delivery of drug/gene and need to be studied deeply before the materials get widely applied.

Animals ; Extremities ; blood supply ; Heparin ; pharmacology ; Male ; Mesentery ; blood supply ; Microcirculation ; drug effects ; Rats ; Rats, Wistar ; Reperfusion Injury ; Splanchnic Circulation ; drug effects

OBJECTIVETo investigate the methylation of p16(INK4a) and RB gene, and the expression of p16(INK4a) in meningiomas.

METHODSMethylation-specific polymerase chain reaction (MSP) was used to detect the methylation of p16(INK4a) and RB in 50 cases of meningiomas, and immunostaining was performed to analyze the protein expression of p16(INK4a) in 25 of those cases.

RESULTSNo methylation was found in the benign meningiomas, whereas methylation of p16(INK4a)or RB occurred in 6(37.5%) cases of grade II tumors and 4(28.6%) cases of grade III tumors, and among these cases, an atypical meningioma showed methylation of both genes. Thirteen cases showed p16(INK4a) positive expression, but none of them was methylated.

CONCLUSIONThe methylation of p16(INK4a) or RB is related with the tumorigenesis and progression of atypical and anaplastic meningiomas, and a probable mechanism is that methylation causes the loss of expression and leads to dysfuncation of the p16(INK4a)/cyclin D1/CDK4/RB pathway.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cyclin D1 ; genetics ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinases ; genetics ; DNA Methylation ; Female ; Genes, Retinoblastoma ; Genes, p16 ; Humans ; Male ; Meningeal Neoplasms ; genetics ; Meningioma ; genetics ; Middle Aged ; Proto-Oncogene Proteins

PURPOSE: To provide the insight into the role of LXR alpha on the progression of diabetic nephropathy, we measured the production of extracellular matrix in the cultured mesangial cells treated with the LXR agonist. METHODS: With the mesangial cells extracted from C57BL6 mice, we cultured them in the presence of 25 mM glucose with or without TO901317, an agonist of LXRalpha We transfected siRNAs of SREBP1 and LXR alpha into the mesangial cell to suppress the activity of the two genes. RESULTS: TO901317 increased expressions of LXR alpha, SREBP-1, TGF beta-1, and collagen IV and triglyceride amount in mesangial cells cultured in 25mM glucose. These effects of TO901317 were attenuated by inhibiting transcription of LXR alpha or SREBP-1 with transfection of siRNAs. In mesangial cells transfected with siRNA of SREBP-1, changes by TO901317 were attenuated regardless of increased expression of LXR alpha. That suggested the activation of SREBP-1, an downstream gene of LXR alpha, would be more important to induce changes in mesangial cells by TO901317. CONCLUSION: The TO901317, an agonist of LXR alpha, increases extracellular matrix, collagen IV, and TGF beta-1 production in cultured mesangial cells. The SREBP-1 as well as dyslipidemia in mesangial cells enhanced by LXR agonist would be the important mechanism to induce those changes.
Animals ; Collagen ; Diabetic Nephropathies ; Dyslipidemias ; Extracellular Matrix ; Glucose ; Hypertriglyceridemia ; Liver ; Mesangial Cells ; Mice ; Orphan Nuclear Receptors ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 1 ; Transfection

Objective To explore the effect of exercise training on irritable bowel syndrome patients with constipation.Methods Totals of 50 cases were randomly divided into control group and experimental group,25 cases in each group.The patients in control group received routine nursing care,experimental group were based on the use of exercise training for nursing intervention.Curative effect in the two groups were compared,and the quality of life before and after intervention was assessed by IBS-QOL.Results After intervention in experimental group,total effective rate of experimental group was significantly higher than that of control group (92.0％ vs 76.0％,U =-2.900,P ＜ 0.01).Improvement of anxiety (92.5 ± 17.5),picky eating(89.9 ± 17.2),worried about health (89.1 ± 15.7) and social reaction (86.5 ± 16.4) in experimental group were superior to pre-intervention (t =3.405,5.610,5.149,2.370,respectively; P ＜ 0.05),also to control group (t =2.734,2.028,2.541,2.023,respectively; P ＜ 0.05).Conclusions Exercise training helps to improve the patient's quality of life,which can enhance the curative effects.

Objective To discuss the effect of aloe ointment application and point massage in nursing aged constipation patients in beds.Methods 54 cases of aged patients in beds were randomly divided into the control group and the experimental group,each with 27 cases.The control group received point massage and conventional nursing,while the experimental group received aloe ointment application for intervention in addition.Two groups' defecating time,stool shape change,therapeutic effect and recurrent constipation were compared.Results The total effective rate after intervention was 92.59％ in the experimental group and 66.66％ in the control group,and the difference was statistically significant (x2 =5.59,P ＜ 0.05).The rate of recurrent constipation was 4％ in the experimental group and 50％ in the control group,with statistically significant difference (x2 =10.85,P ＜ 0.01).Both defecating time and stool shape change were better in the experimental group than in the control group,and the differences were statistically significant (U =-2.329,-2.728; respectively; P ＜ 0.05).Conclusions Aloe ointment has good curative effects and maintenance,which can help improve patients' quality of life.

Aim To investigate the potential mechanism of Jiawei Duhuo Jisheng Mixture regulating intestinal flora in the treatment of knee osteoarthritis(KOA)by 16S rRNA sequencing.Methods Eight-week-old male C57 mice were randomly divided into three groups:sham group,DMM group,and model+Jiawei Duhuo Jisheng Mixture group(Mixture group),6 mice per group.KOA model was induced by destabilization of medial meniscus surgery.16.25 mL·kg-1 dose mixture was given daily to the mixture group,and normal saline was given to the sham and DMM group.After eight weeks,the knee joints and colons of mice were collected,and the knee joints were prepared into paraffin sections,and the cartilage changes were observed with Safranin O-Fast Green and immunohistochemistry staining.16S rRNA sequencing of intestinal contents was performed to observe the changes of intestinal flora.Results Compared with model group,Jiawei Duhuo Jisheng Mixture could significantly reduce cartilage wear and OARSI score(P=0.033 5,P=0.029 5).16S rRNA sequencing showed that Jiawei Duhuo Jisheng Mixtrue could change the intestinal flora richness of KOA model mice,and improve the Alpha diversity(Chao1,Simpson)and Beta diversity(PCoA,NMDS).LefSe analysis showed that there were species with significant difference in abundance among the three groups(P=0.001),mainly including Lactobacillus,Firmicutes,Proteobacteria and other species.MetaCyc analysis indicated that Jiawei Duhuo Jisheng Mixture had effects on various metabolic pathways such as fatty acid,sugar and amino acid of intestinal flora(P<0.05).Conclusions Jiawei Duhuo Jisheng Mixtrue can effectively protect the articular cartilage and delay the progression of KOA.The mechanism may be through regulating the intestinal flora structure,protecting the intestinal barrier and reducing the inflammatory response.

Objective: To probe the potential utility of Wilms tumor 1 (WT1) as a marker of minimal residual disease (MRD) in acute myeloid leukemia (AML) to estimate the relapse-predicting cut-off value. Methods: Quantitative assessment of bone marrow WT1 mRNA level was preformed using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) assay. The expression levels of WT1 dynamically measured with RQ-RT-PCR were retrospectively analyzed in 121 AML cases (not including acute promyelocytic leukemia) achieving complete remission (CR) after induction therapy followed by consolidation therapy. By comparing WT1 levels of patients with different post-therapy outcomes, the investigators used the receiver operating characteristic (ROC) curve to determine WT1 threshold so as to predict their clinical relapses. Then prognoses and the significance of intervention were analyzed between WT1 positive and negative patients according to the cut-off value of WT1. Results: According to ROC curve, WT1 level higher than 2.98% predicted the possibility of relapse. For simplicity and clinical application, 3.00% was used as the cut-off value of WT1 level for relapse. WT1 levels in 41 patients at diagnosis were detected, meanwhile 3 patients whose WT1 levels at diagnosis below 3.00% were excluded, then the median WT1 level of the rest 38 patients at diagnosis was 44.09% (range 7.19%-188.06%) . The median WT1 level in remission was 0.48% (352 samples, range 0-8.41%) . The median WT1 level at diagnosis was higher than that in remission. Excluding the 3 patients with WT1 level at diagnosis under 3.00%, the relapse rate of WT1 positive group (>3.00% during consolidation phase and follow-up) and WT1 negative group (≤3.00%) was 70.0% (14/20) and 12.2% (12/98) respectively (P<0.001) . The median time from WT1 positivity to clinical relapse was 58 days. Conclusions WT1 expression level above 3.00% was associated with markedly high risk of relapse, which could be as a useful marker for monitoring MRD following consolidation therapy.

Objective: To investigate the effect of taraxerol on autophagy of breast cancer MCF-7 cells in vitro, and explore the related mechanisms. Method: The effect of various doses of taraxerol (12.5, 25, 50, 100, 200 μmol·L^-1) on proliferation of MCF-7 cells was detected by methye thiazolye telrazlium (MTT) assay. The autophagy-inducing effect of taraxerol was observed by acridine orange staining, transmission electron microscope (TEM) and immunofluorescence. The expressions of autophagy-related proteins and the changes of mammalian target of rapamycin (mTOR) signaling pathway were determined by Western blot analysis. Result: The viability of MCF-7 cells was significantly inhibited by taraxerol. Acridine orange staining indicated that the acidic lysosomes increased significantly after treatment with taraxerol in MCF-7 cells. The autophagic structure in the treated group was observed by TEM. Immunofluorescence showed that the expression of microtubule-associated protein 1 light chain 3 (LC3) in the cells of the drug group was increased. Western blot demonstrated that the protein expressions of LC3-Ⅱ and Beclin-1 were increased in taraxerol-treated MCF-7 cells (P<0.05,P<0.01), respectively. Compared with 100 μmol·L^-1 taraxerol group, combination group (taraxerol + 3-methyladenine, 3-MA) showed the down-regulation of LC3-Ⅱ in the MCF-7 cells (P<0.05).And expressions of phosphorylated mammal target of rapamycin (p-mTOR) and phosphorylated eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) were decreased in MCF-7 cells after treatment with taraxerol (P<0.05, P<0.01). Conclusion: Taraxerol can induce autophagy in MCF-7 cells, which may be related to the inhibition of mTOR signaling pathway.

Non-alcoholic fatty liver disease (NAFLD) incidence is rapidly increasing and become the most common chronic liver disease globally. NAFLD also possesses a risk of developing cardiovascular, kidney, and other diseases. To date, NAFLD still faces difficulties in early diagnosis and treatment options. Thus, early detection, prevention, optimally individualized treatment selections, and prediction of prognosis all are the keys in clinical NAFLD control. Although there are assessment tools available for NAFLD severity appraisal using different clinical parameters, it becomes a hot topic of research in the field for how to optimize non-invasive assessment methodologies. Artificial intelligence (AI) and machine learning are increasingly being used in healthcare, especially in assessment and analysis of chronic liver disease, including NAFLD. This review summarized and discussed the most recent progress of AI and machine learning in differential diagnosis of NAFLD and evaluation of NAFLD severity, in order to provide treatment selections, i.e., the novel AI diagnosis models based on the electronic health records and laboratory tests, ultrasound and radiographic imaging, and liver histopathology data. The therapeutic models discussed the personalized lifestyle changes and NAFLD drug development. The NAFLD prognosis model reviewed and predicted how NAFLD-changed liver metabolisms affect prognosis of patients. This review also speculated future prospective research hot spots and development in the filed for how to utilize the existing AI models to distinguish NAFLD and non-alcoholic steatohepatitis (NASH) and assess NAFLD fibrosis status.