Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Objective To screen for differentially expressed apoptosis-related circular RNAs(circRNAs)in osteoblasts from steroid-induced osteonecrosis of the femoral head(SONFH)and to investigate their roles and mechanisms in osteoblast apoptosis.Methods MC3T3-E1 cells were cultured and divided into two groups:Control and DEX-treated.Western blot analysis was employed to evaluate the expression levels of BCL2-Associated X protein(Bax)and B-cell lymphoma 2(Bcl-2).Cell apoptosis was assessed using TUNEL staining and flow cytometry.RNA was extracted from both normal and DEX-treated MC3T3-E1 cells,followed by RNA-seq to identify differen-tially expressed circular RNAs(circRNAs).The functions and pathways of these circRNAs were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).The differentially expressed mmu_circ_0000818 was selected for further verification at the cellular level.Its chromosomal location and conservation were examined using the UCSC Genome Browser Gateway and circBase.Overexpression plasmids and small interfering RNAs(siRNAs)targeting mmu_circ_0000818 were constructed and transfected into the cells.Subsequently,apop-tosis in MC3T3-E1 cells from each group was evaluated by flow cytometry.Results Compared with the control group,the apoptosis rate of MC3T3-E1 cells was significantly increased in the DEX group(P<0.01).Differen-tially expressed circRNAs were identified based on log2foldchange(≥2)and P value(P<0.05).Relative to the control group,there were 234 differentially expressed circRNAs in the DEX group,including 138 up-regulated and 96 down-regulated circRNAs.GO and KEGG enrichment analyses of the target genes of these differentially expressed circRNAs revealed significant associations with apoptosis and the PI3K-Akt signaling pathway.qRT-PCR results demonstrated that the expression level of mmu_circ_0000818 was markedly higher in the DEX group com-pared to the control group(P<0.01).Analysis using the UCSC Genome Browser and CircBase indicated that mmu_circ_0000818,located at chromosome 17:78712463-78715086,is formed by the cyclization of exons 6-7 of the Crim1 gene and exhibits high conservation across species.Flow cytometry results indicated that knockdown of mmu_circ_0000818 attenuated DEX-induced apoptosis in MC3T3-E1 cells,while overexpression of mmu_circ_0000818 exacerbated apoptosis.Conclusions CircRNA mmu_circ_0000818 was significantly upregulated in DEX-treated MC3T3-E1 cells,and its downregulation mitigated DEX-induced apoptosis.Consequently,mmu_circ_0000818 may represent a promising therapeutic target for the prevention and treatment of SONFH.

Objective To screen for differentially expressed apoptosis-related circular RNAs(circRNAs)in osteoblasts from steroid-induced osteonecrosis of the femoral head(SONFH)and to investigate their roles and mechanisms in osteoblast apoptosis.Methods MC3T3-E1 cells were cultured and divided into two groups:Control and DEX-treated.Western blot analysis was employed to evaluate the expression levels of BCL2-Associated X protein(Bax)and B-cell lymphoma 2(Bcl-2).Cell apoptosis was assessed using TUNEL staining and flow cytometry.RNA was extracted from both normal and DEX-treated MC3T3-E1 cells,followed by RNA-seq to identify differen-tially expressed circular RNAs(circRNAs).The functions and pathways of these circRNAs were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).The differentially expressed mmu_circ_0000818 was selected for further verification at the cellular level.Its chromosomal location and conservation were examined using the UCSC Genome Browser Gateway and circBase.Overexpression plasmids and small interfering RNAs(siRNAs)targeting mmu_circ_0000818 were constructed and transfected into the cells.Subsequently,apop-tosis in MC3T3-E1 cells from each group was evaluated by flow cytometry.Results Compared with the control group,the apoptosis rate of MC3T3-E1 cells was significantly increased in the DEX group(P<0.01).Differen-tially expressed circRNAs were identified based on log2foldchange(≥2)and P value(P<0.05).Relative to the control group,there were 234 differentially expressed circRNAs in the DEX group,including 138 up-regulated and 96 down-regulated circRNAs.GO and KEGG enrichment analyses of the target genes of these differentially expressed circRNAs revealed significant associations with apoptosis and the PI3K-Akt signaling pathway.qRT-PCR results demonstrated that the expression level of mmu_circ_0000818 was markedly higher in the DEX group com-pared to the control group(P<0.01).Analysis using the UCSC Genome Browser and CircBase indicated that mmu_circ_0000818,located at chromosome 17:78712463-78715086,is formed by the cyclization of exons 6-7 of the Crim1 gene and exhibits high conservation across species.Flow cytometry results indicated that knockdown of mmu_circ_0000818 attenuated DEX-induced apoptosis in MC3T3-E1 cells,while overexpression of mmu_circ_0000818 exacerbated apoptosis.Conclusions CircRNA mmu_circ_0000818 was significantly upregulated in DEX-treated MC3T3-E1 cells,and its downregulation mitigated DEX-induced apoptosis.Consequently,mmu_circ_0000818 may represent a promising therapeutic target for the prevention and treatment of SONFH.

Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Objective:To investigate the targeted surveillance combined with cluster management on isolation protector use rate and hand hygiene qualification rate in caregivers of patients with respiratory tract multidrug-resistant bacterial infections.Methods:Second Hospital of Shanxi Medical University began to perform targeted surveillance combined with cluster management among caregivers of patients with multidrug-resistant bacterial infections in July 2019. The caregivers of 50 patients with respiratory tract multidrug-resistant bacterial infections who were admitted before targeted surveillance combined with cluster management were included in the pre-implementation group. The caregivers of 50 patients with respiratory tract multidrug-resistant bacterial infections who were admitted after targeted surveillance combined with cluster management were included in the post-implementation group. Multidrug-resistant bacterial infections in caregivers, isolation protector use rate, environmental disinfection and hand hygiene qualification rate were compared between before and after 6 months of targeted surveillance combined with cluster management. The application value of targeted surveillance combined with cluster management in the prevention of respiratory tract multidrug-resistant bacterial infections was analyzed.Results:The number of caregivers with respiratory tract multidrug-resistant bacterial infections in the post-implementation group was lower than that in the pre-implementation group (5 vs. 13, P < 0.05). The proportion of caregivers who wear a mask (94.11%), isolation clothes (80.39%) and gloves (98.03%) in the post-implementation group was significantly higher than that in the pre-implementation group (70.00%, 62.00%, 78.00%, χ2 = 10.027, 4.911, 9.683, all P < 0.05). The proportion of caregivers who were qualified in terms of hand hygiene (82.35%), object surface (76.47%), and keeping the air fresh in the post-implementation group was significantly higher than that in the pre-implementation group (64.00%, 58.00%, 64.00%, χ2 = 4.341, 3.915, 5.450, all P < 0.05). Conclusion:Targeted surveillance combined with cluster management can effectively help prevent respiratory tract multidrug-resistant bacterial infections in caregivers and increase isolation protector use rate and hand hygiene qualification rate.

OBJECTIVE：To optimize the extractio n technology of Fritillaria pallidiflora polysaccharides（FPSP），and to study its structure. METHODS ：Using the yield of FPSP as response value ，Box-Behnken design-response surface methodology was adopted to optimize solid-liquid ratio ，extraction temperature and extraction time of FPSP extraction technology. Structural properties of FPSP was characterized by UV spectrum ，FTIR，GC-MS，Congo red staining ，SEM，XRD and thermogravimetric analysis. RESULTS：The optimal technology parameters of FPSP were solid-liquid ratio of 1∶28（g/mL），extraction temperature of 94 ℃， extraction time of 2.5 h；the yield of FPSP was 16.25％（n＝3），the error of which to theoretical yield （16.58％）was 0.33％. FPSP contained xylose ，glucose and galactose with a molar ratio of 1∶58.02∶0.73，and trace amount of mannose ；there was a weak absorption peak near the wavelength of 280 nm；belonged to α-configuration pyranopolysaccharide. FPSP was in triple-helical structure. The surface of FPSP was a network structure formed by irregular particles. FPSP had both crystalline and amorphous structures. FPSP had good thermostability. CONCLUSIONS ：The optimized extraction technology of FPSP is reasonable ，and has high extraction yield. The research might provide reference for the further development and utilization of F. pallidiflora .

Objective To investigate the effect of flavopiridol on the proliferation,invasiveness and apoptosis of human prostate cancer cell line LNCaP,and to explore the possibility of its application in clinical treatment.Methods MTT assay was used to detect cell proliferation,cell invasion in vitro was detected by Transwell assay,and flow cytometer was used to observe apoptosis.Results Flavopiridol inhibited the growth of LNCaP cells in a concentration-dependent and time-dependent way (P ＜ 0.05),and reduced the ability of invasion capacity.After treated by 10 nmol/L flavopiridol for 24 h,the apoptosis rate was increased significantly to (7.5±0.9) ％ compared with the control group [(5.3±0.5) ％] (P ＜ 0.05).Conclusion Flavopiridol can inhibit proliferation of LNCaP cells and induce apoptosis,which may be applicable for the treatment of prostate cancer.

Objective To investigate the expression of hepatocyte growth factor ( HGF ) and its relationship with microsatellite instability ( MSI) and their influence on survival in patients with colorectal cancer. Methods Immunohistochemistry ( IHC) was used to detect the expression of HGF and MSI in 98 specimens of colorectal cancer. Tumors lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as MSI, and the rest were considered as microsatellite stable ( MSS) . The associations between expression and clinicopathological factors were assessed using Chi?square tests. Kaplan?Meier curves, log?rank test, and Cox regression were used to analyze the association between biomarker expressions and overall survival. Results The incidence rate of MSI in 98 colorectal specimens was 32. 7%, and was statistically significantly correlated with the location of tumor and differentiation degree ( P<0.05) . The HGF?expression rate was 71.4%. The patients with an MSI tumor had a significantly higher HGF expression, compared with the patients with an MSS tumor (P=0.048). The 5?year survival rate of MSI group and MSS group were 39.8% and 58.7%, respectively (P=0.009). The 5?year survival rate of HGF?positive group and HGF?negative group were 46.2% and 67.9% ( P=0.035) . The multivariate analysis showed that lymphocytic infiltration, TMN stage, MSI and HGF are independent prognostic factors in colorectal cancer ( P<0. 05 for all ) . Conclusions HGF is highly expressed in colorectal cancer patients with microsatellite instability. Both microsatellite instability and HGF are independent factors affecting the prognosis in patient with colorectal cancer.

Objective To investigate the expression of hepatocyte growth factor ( HGF ) and its relationship with microsatellite instability ( MSI) and their influence on survival in patients with colorectal cancer. Methods Immunohistochemistry ( IHC) was used to detect the expression of HGF and MSI in 98 specimens of colorectal cancer. Tumors lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as MSI, and the rest were considered as microsatellite stable ( MSS) . The associations between expression and clinicopathological factors were assessed using Chi?square tests. Kaplan?Meier curves, log?rank test, and Cox regression were used to analyze the association between biomarker expressions and overall survival. Results The incidence rate of MSI in 98 colorectal specimens was 32. 7%, and was statistically significantly correlated with the location of tumor and differentiation degree ( P<0.05) . The HGF?expression rate was 71.4%. The patients with an MSI tumor had a significantly higher HGF expression, compared with the patients with an MSS tumor (P=0.048). The 5?year survival rate of MSI group and MSS group were 39.8% and 58.7%, respectively (P=0.009). The 5?year survival rate of HGF?positive group and HGF?negative group were 46.2% and 67.9% ( P=0.035) . The multivariate analysis showed that lymphocytic infiltration, TMN stage, MSI and HGF are independent prognostic factors in colorectal cancer ( P<0. 05 for all ) . Conclusions HGF is highly expressed in colorectal cancer patients with microsatellite instability. Both microsatellite instability and HGF are independent factors affecting the prognosis in patient with colorectal cancer.

Objective To investigate the expression of the enhancer of zeste homolog 2 (EZH2) gene and its significance in colorectal adenocarcinoma.Methods Immunohistochemistry and Western blot was used to assess the expression of EZH2 in human colorectal adenocarcinoma tissues,colorectal adenoma tissues and non-cancerous adjacent colorectal tissues.The relationships between EZH2 and each clinical pathology parameter were analyzed.Results The results of immunohistochemical trail showed that the expression rates of EZH2 in colorectal adenocarcinoma,colorectal adenoma and non-cancerous adjacent colorectal tissues were 80.56 ％ (87/108),62.5 ％ (25/40) and 5.00 ％ (2/40),respectively (P ＜ 0.05).Western blot revealed that the expression level of EZH2 in colorectal adenocarcinoma tissues,colorectal adenoma tissues and non-cancerous adjacent colorectal tissues level 0.549±0.145,0.283±0.023 and 0.107±0.022,respectively.The level in colorectal adenocarcinoma tissues (0.549±0.145) and colorectal adenoma (0.283±0.023) was significantly higher than that in non-cancerous adjacent colorectal tissues (0.107±0.022).Compared with colorectal adenoma tissues,level in colorectal adenocarcinoma tissues was significantly higher.There were significant differences among the three groups (F =20.113,P ＜ 0.05).The ratio of high expression level of EZH2 in colorectal adenocarcinoma tissues was closed related with tumorgenesis,differentiation,TNM staging and lymphatic metastsis (all P ＜ 0.05).However,no correlation was revealed between EZH2 expression and the age,gender (both P ＞ 0.05).Conclusion The expression of EZH2 may be associated with the tumorgenesis invasion,metastasis and progression of colorectal adenocarcinoma.