ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

ObjectiveTo investigate the expression of C1q tumor necrosis factor-related protein 3 （C1QTNF3） in liver cancer tissue， its association with the clinicopathological features of patients， and its potential value in predicting the prognosis of liver cancer. MethodsRelated data were collected from TIMER， UALCAN， TNMplot， and GEO databases， and the bioinformatics methods were used to measure the expression level of C1QTNF3 in pan-cancer， normal tissue/liver cancer tissue， and cancerous tissue/paracancerous tissue. Cancerous and paracancerous tissue samples were collected from 90 patients with liver cancer， and related clinical data were collected， including age， sex， tumor diameter， and tumor number. The independent-samples t test or the paired t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used to investigate the association between the expression level of C1QTNF3 and the survival of patients with liver cancer. The Cox regression model was used to identify the risk factors for the prognosis of patients with liver cancer， and the receiver operating characteristic （ROC） curve was used to analyze the ability of C1QTNF3 expression at different time points for predicting the prognosis of patients with liver cancer. ResultsThe bioinformatics analysis showed that the expression of C1QTNF3 was upregulated in various malignant tumors， especially in liver cancer tissue （P<0.001）， and the expression level of C1QTNF3 in liver cancer tissue was significantly higher than that in normal tissue and paracancerous tissues （all P<0.01）. The immunohistochemical staining results of 90 patients with liver cancer showed that C1QTNF3 was mainly expressed in cytoplasm， with a small amount in nucleus， and it had negative expression in paracancerous tissue and positive expression in liver cancer tissue. The positive expression rate and strong positive expression rate of C1QTNF3 protein in liver cancer tissue were significantly higher than those in paracancerous tissue （positive expression rate： 76.67% vs 33.33%， χ²=34.141， P<0.01； strong positive expression rate： 54.44% vs 5.56%， χ²=51.217， P<0.01）. The liver cancer patients with a tumor diameter of ≥5 cm， an advanced stage， the presence of liver cirrhosis， negative HBsAg， and gamma-glutamyl transpeptidase （GGT）≥50 U/L had a significantly higher strong positive expression rate of C1QTNF3 protein than those with a tumor diameter of <5 cm， an early stage， the absence of liver cirrhosis， positive HBsAg， and GGT<50 U/L （all P<0.05）. The univariate Cox regression analysis showed that tumor diameter， recurrence， and C1QTNF3 expression were influencing factors for the prognosis of patients with liver cancer （all P<0.05）， and the multivariate Cox regression analysis showed that the expression level of C1QTNF3 and recurrence were independent risk factors for the survival of patients with liver cancer （both P<0.05）. The survival curve analysis showed that for all patients with liver cancer， the patients with high （strong positive） expression of C1QTNF3 had significantly lower overall survival rate and disease-free survival rate than those with low expression （χ²=17.010 and 13.647， both P<0.001）； for liver cancer patients with a tumor diameter of ≥5 cm， an early/advanced stage， recurrence， the presence of liver cirrhosis， positive HBsAg， alanine aminotransferase （ALT） <40 U/L， ALT≥40 U/L， and GGT≥50 U/L， the patients with high expression of C1QTNF3 had a significant reduction in overall survival rate （χ²=11.086， 5.578， 5.295， 19.159， 16.391， 13.774， 10.119， 8.152， and 12.035， all P<0.05）. The ROC curve analysis showed that C1QTNF3 expression had the strongest predictive potential at 5 years， with an area under the ROC curve of 0.77. ConclusionC1QTNF3 is highly expressed in liver cancer tissue， and the expression level of C1QTNF3 and recurrence are closely associated with the survival of patients with liver cancer. Patients with high expression of C1QTNF3 protein tend to have a lower survival rate.

Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

As a glucocorticoid drug with wide clinical application， triamcinolone acetonide can be administered by multiple routes， such as eye， nose， joint cavity， and skin， for the treatment of various local diseases such as arthritis， macular edema， rhinitis， and urticaria. As a drug with extremely low solubility in water， the dose form of triamcinolone acetonide is closely correlated with administration route and site. The dosage form of triamcinolone acetonide administered via injection（including joint cavity injection， vitreous injection， suprachoroidal injection， intramuscular injection） is mainly suspension， and the representative drugs include Kenalog-40®， Zilretta®， Triesence®， Xipere®， etc.； the dosage forms of nasal mucosal administration are mostly sprays， and the representative drug is Nasacort®； the dosage forms of oral mucosal administration are mostly patches， ointments and creams， and the representative drug is Oracort®； the dosage forms for transdermal administration are mostly ointments， creams and lotions， and the representative drugs include Trianex®， Teva-Triacomb®， etc. At present， the research on dosage forms of triamcinolone acetonide by various administration routes mainly focuses on the construction of delivery carriers， the addition of cosolvents or the use of new delivery tools.

[摘 要] 目的：探讨贝母素乙对结肠癌HCT116细胞增殖的抑制作用及其分子机制。方法：利用不同浓度的贝母素乙处理人结肠癌细胞HCT116和正常结肠上皮细胞CCD841 CON，通过CCK-8法和结晶紫染色法检测贝母素乙对HCT116和CCD841 CON细胞增殖活力的影响，流式细胞术和WB法检测贝母素乙对HCT116细胞周期及其细胞周期相关蛋白表达的影响。构建HCT116移植瘤裸鼠模型和AOM/DSS结肠癌小鼠模型，观察贝母素乙对小鼠模型肿瘤生长和OS的影响，免疫组化法和WB法检测对移植瘤或肿瘤组织中细胞周期相关蛋白CDK4、CDK6和cyclin D1表达的影响。结果：贝母素乙可显著抑制结肠癌HCT116细胞的增殖能力（P<0.01），诱导HCT116细胞周期G0/G1期阻滞（P<0.01），降低CDK4、CDK6和cyclin D1的蛋白表达水平（均P<0.01）。荷瘤小鼠实验结果显示，贝母素乙（0.75 mg/kg）显著抑制HCT116细胞移植瘤的生长并延长荷瘤裸鼠的OS（P<0.05或P<0.01），降低AOM/DSS模型小鼠的体质量、延长OS、减少癌变肠组织的肿瘤个数和肿瘤体积，下调肿瘤组织中CDK4、CDK6和cyclin D1的蛋白表达（P<0.01或P<0.05）。结论：贝母素乙通过下调CDK4、CDK6和cyclin D1的表达水平，引起细胞周期G0/G1期阻滞，从而抑制结肠癌HCT116细胞的增殖。

ObjectiveTo investigate the effect of iridoid glycosides from Boschniakia rossica （IGBR） on epithelial-mesenchymal transition （EMT） of HepG2 hepatoma cells induced by transforming growth factor-beta 1 （TGF-β1）. MethodsHepG2 hepatoma cells were induced by 10 μg/L TGF-β1 to construct an EMT model of hepatoma cells. The cells were divided into control group （treated with serum-free DMEM）， model group （treated with 10 μg/L TGF-β1）， and IGBR group （treated with 10 μg/L TGF-β1 and 500 mg/L IGBR）， and all cells were cultured for 48 hours. Cell adhesion assay， wound healing assay， and Transwell chamber assay were used to observe the migration and invasion abilities of cells. RT-PCR and Western blot were used to measure the mRNA and protein expression levels of E-cadherin， N-cadherin， and vimentin in cells， and Western blot was used to measure the protein expression levels of Slug， Twist1， ZEB1， p-STAT3， and STAT3. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the independent-samples t test was used for comparison between two groups. ResultsAfter TGF-β1 induction， HepG2 cells in the model group showed long spindle-shape changes， while those in the control group showed polygonal epithelia-like changes. Compared with the model group， the IGBR group had a significant reduction in cell adhesion rate and significant inhibition of cell migration and invasion abilities （all P<0.05）， as well as significant increases in the mRNA and protein expression levels of E-cadherin （P<0.05）， significant reductions in the mRNA and protein expression levels of N-cadherin and vimentin （all P<0.05）， and significant reductions in the protein expression levels of Slug， Twist1， ZEB1， and p-STAT3 （all P<0.05）. ConclusionIGBR can inhibit TGF-β1-induced EMT process in HepG2 cells， thereby attenuating cell adhesion， migration， and invasion abilities， and it can also upregulate E-cadherin， downregulate N-cadherin and vimentin， and upregulate the protein expression of Slug， Twist1， ZEB1， and STAT3， possibly by inhibiting the STAT3 pathway to downregulate the EMT transcription factors such as Slug， Twist1， and ZEB1.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.