BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Objective To observe the effect of Bushen Huoxue formula on interleukin-17(IL-17)in rats with recurrent spontaneous abortion(RSA).Methods RS A model rats were constructed by intraperitoneal injection of estradiol benzoate.Forty RSA model rats were randomly divided into model group,control group and experimental-L,-H groups,with 10 rats per group.Another 10 healthy pregnant rats were set as blank group.The experimental-L,-H groups were given 7.77 and 15.54 g·kg-1 of Bushen Huoxue formula solution by gavage.The control group was given 2.10 mg·kg-1of dydrogesterone solution by gavage.The blank group and the model group were given equal amount of 0.9％NaCl by gavage.The dose of administration for the five groups was 10 mL·kg-1,once a day,for 9 days.The number of live fetuses,embryo loss,and embryo loss rate in each group were observed.The proportion of Th 17 cells in the peripheral blood was detected by flow cytometry.The expression levels of interleukin-6(IL-6),IL-17 and IL-23 proteins in the decidual tissues were detected by Western blotting.Results The number of live fetuses in the experimental-H,control,model and blank groups were 11.50±2.84,11.50±3.10,6.30±1.25 and 12.50±3.24;the number of embryos lost were 1.80±0.42,1.90±0.57,4.90±1.37 and 0;the rates of embryo loss were(14.01±4.52)％,(14.79±6.06)％,(43.50±9.49)％and 0;the proportions of Th17 cells in the peripheral blood were(3.12±0.47)％,(3.10±0.59)％,(5.31±1.16)％and(2.54±0.71)％;the relative expression levels of IL-6 protein were 0.19±0.04,0.18±0.05,0.85±0.16 and 0.11±0.03;the relative expression levels of IL-17 protein were 0.28±0.04,0.29±0.05,0.84±0.12 and 0.09±0.01;the relative expression levels of IL-23 protein were 0.35±0.04,0.34±0.06,0.90±0.11 and 0.08±0.01,respectively.Comparing experimental-H group and model group,comparing control group and blank group,the above indexes were statistically significant(all P＜0.05).Conclusion Bushen Huoxue formula can reduce embryo loss,improve placental tissue pathology,reduce Th 17 cell proportion and its related cytokines IL-6,IL-17,IL-23 expression in rats with RSA.

Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg^-1）， and oseltamivir group （40 mg·kg^-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1^-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

Tumor is one of the serious problems threatening human health. There are some limitations in the delivery of commonly used tumor therapy technologies, and the therapeutic effect is not satisfactory, so new anti-tumor strategies need to be developed. The process of tumor cells using glycolysis to produce energy under aerobic conditions is called aerobic glycolysis, which is closely related to tumor growth, proliferation and metastasis, and can provide a new target spot for tumor treatment. Nano drug delivery system has been widely used in targeted tumor therapy because of its advantages of targeted drug delivery, improved anti-tumor efficacy and reduced toxic side effects. Numerous studies have shown that more and more nano drug delivery systems regulates aerobic glycolytic metabolism by targeting to potential targets such as signaling factors or reaction products of aerobic glycolytic process in tumors, and therefore enhance the anti-tumor effect. This paper reviews the application of nano drug delivery system in regulating tumor aerobic glycolysis, and provides theoretical references for realizing efficient targeted tumor therapy.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.

Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P＜0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.