Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC₅₀） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg^-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC₅₀ of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L^-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.

Pregnant women with bipolar disorder(BD)are a high-risk pregnancy state.Necessary psychotropic drug treatment,special stress reactions,bad living habits,and fluctuations in pregnancy hormones all increase the risk of pregnancy to a certain extent.Risks of complications such as hypertension,gestational diabetes,premature birth and spontaneous abortion.Drugs can penetrate the placental blood-brain barrier and enter the maternal-fetal microcirculation.Combined with the effects of genetic genes and the environment,they can induce neurodevelopmental abnormalities in the fetus,leading to congenital malformations,attention deficit hyperactivity disorder,autism spectrum disorder and other diseases after birth.The mode of delivery may also be affected.Women with BD often give birth by caesarean section.It is particularly important to weigh the choice of drug types and dosages,which will help improve the accuracy of clinical risk management and disease control of pregnancy-related mental disorders.

Objective:Using retrogradely trans-monosynaptic tracing method mediated by rabies virus(RV)to ob-serve presynaptic neuronal distributions of vesicular glutamate transporter 2(VGLUT2)-positive neurons of the med-iodorsal thalamic nucleus(MD)in whole brain.Methods:The helper viruses of RV were injected into the right MD of VGLUT2-ires-Cre mice,and two weeks later RV was injected into the same area.After another one week,perfusion was taken and whole brain scanning was performed to observe the distributions of RV-labeled presynaptic neurons throughout the brain.Results:After RV virus was injected into the MD of VGLUT2-ires-Cre mice,dense presynaptic neurons were observed in the cortex and brainstem.RV labeled neurons were mostly distributed in primary motor cortex(M1),sec-ondary motor cortex(M2),medial prefrontal cortex,orbitofrontal cortex and insular cortex at the cortical level.Tha-lamic retrogradely labeled neurons were mostly found in reticular thalamic nucleus and lateral hypothalamic area,and retrogradely labeled neurons in the brainstem were mainly distributed in lateral parabrachial nucleus,periaqueductal grey matter and dorsal raphe nucleus.Conclusion:The results in the present experiment suggest that VGLUT2-positive neurons within the MD can receive ascending information transmission from the brainstem,or regulation from the reticu-lar nucleus of thalamus.As a higher-order thalamus,MD can also receive descending projections from the cortex,and is involved in a variety of functions.Our results provide morphological basis for the study of the function and the related neural circuit of the MD.

Objective:To observe the projections from tyrosine hydroxylase(TH)positive neurons in locus coerule-us(LC)to tachykinin-1(TAC1)neurons in paraventricular nucleus of the thalamus(PVT),and morphologically determine whether they are involved in transmission and modulation of nociceptive information.Methods:TAC1-ires-Cre mice were hybridized with Rosa26:CAG-LSL-tdTomato(Ai9)mice.And spared nerve injury(SNI)induced neu-ropathic pain model was established with TAC1-ires-Cre::Ai9 mice to observe the colocalization of TAC1 and Fos and the close appositions between TAC1/FOS double-labeled neurons and TH positive axonal terminals.The distribution of the TH positive neurons and FG retrogradely labeled neurons were observed in the LC after Fluorogold(FG)was injec-ted into the PVT.Finally,the coexistences of TH positive neurons and RV labeled neurons in the LC were observed after injection of RV-mediated retrograde tracing system.Results:TAC1 positive neurons were shown with red fluores-cence in TAC1-ires-Cre::Ai9 mice.TAC1/FOS double-labeled neurons were found in the PVT of the SNI model.Some TAC1/FOS double labeled neurons made close appositions with TH positive axonal terminals.FG retrogradely labeled neurons were observed in the LC after FG injected into the PVT,and some of the FG labeled neurons coexisted with TH positive neurons.Using RV retrograde transsynaptic tracing virus,the results showed that presynaptic neurons of TAC1 positive neurons in the PVT were found in the LC,and most of the presynaptic neurons were TH positive neu-rons.Conclusion:TH positive neurons in the LC project to TAC1 positive neurons of the PVT,forming LCTH+-PVTTAC1+neural circuit,which were activated by nociceptive information.It demonstrates that this pathway plays a role in pain transmission or regulation.

Objective Clarify the basis of the commonly used Tibetan medicinal material"YeGexing",the chemical structure and pharmacological activity were investigated,then provide a basis for standardizing clinical medication,quality control,and rational use of resources.Methods Using literature research;plant taxonomy identification summary of chemical composition investigation and pharmacological activity identification,combined with resource distribution,clinical use status investigation and analysis.Results Tibetan medicine"Yegexing"involved 7 species in 2 families,4 genera,that is Sambucus Linn.from Caprifoliaceae,Senecio L.,Synotis(C.B.Clarke)C.Jeffrey et Y.L.Chen,Saussurea DC.from Compositae.The earliest used"Yegexinggabao"or"white"should be Senecio dianthus.and Senecio solidagineus.in the literature;"Yegexingnabao"or"black"should be Saussurea epilobioides.and Sambucus adnate.;S.raphanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.).S.chinensis.are the main substitutes used in Yunnan,Gansu,and western Sichuan,and are commonly used in the market.YeGexing mainly contains terpenes,flavonoids,alkaloids,phenolic acids and other chemical components;YeGexing black is mainly used for"healing",white is mainly used for"anti-inflammatory",which corresponds to modern pharmacological research on anti-inflammatory,antioxidant,antibacterial and other activities.Conclution In view of the fact that the origin of"Yegexing"involves a variety of plants from different families and genera,"Yegexing"has become a collective name for these plant medicinal materials.According to the lextual results and the research progress on chemical structure and pharmacological activity,from the perspective of conducive to standardizing clinical medication,ensuring efficacy and quality of medicinal materials,its name and variety should be standardized as:"??????(???????????????????/)Yegexinggabao"(that is,the white one),the source is S.dianthus.(S.erythropappa.),S.solidagineus.(S.solidaginea.),S.raphalanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.);"(???????????????????????/)Yegexingnabao"(that is,the black one),the source is S.epilobioides.and S.adnata.and S.chinensis are independent medicines.We should strengthen the investigation of the resources and use status of substitutes in various places,the comparative research on the medicinal material basis and biological activity of different resource species,and standardize their varieties-names-bases to make rational use of their resources.

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and post-pancreatectomy.The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion feedback.Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement therapy.Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota.Pancreatic exocrine secretions and changes in duodenal pH as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota.In turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk.Going forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

Objective To investigate the feasibility of using contrast-enhanced T1WI radiomics in predicting the pathological grade in rectal adenocarcinoma.Methods The MRI and pathological data of 127 patients with rectal adenocarcinoma were analyzed retrospectively.ITK-SNAP software was used to manually draw region of interest(ROI)in rectal cancer on axial T,WI enhanced images.The radiomics features were extracted by the Pyradiomics software from ROI.The task was divided into two parts:task 1("high & non-high"group)predicted the high-differentiation and moderate/low-differentiation of the tumor;task 2("moderate & low"group)predicted the tumor's moderate-differentiation and low-differentiation in"non-high"group.Maximum relevance and minimum redundancy(mRMR)method was used to screen features.The five methods including least absolute shrinkage and selection operator(LASSO),logistic regression(LR),naive Bayes(NB),random forest(RF),and support vector machine(SVM)were used to build the models,and the efficiency of each model was evaluated and compared.Results In task 1,the area under the curve(AUC)of five methods were 0.86,0.90,0.59,1.00,0.99 in the training cohort and 0.71,0.62,0.53,0.67,0.64 in the testing cohort.In task 2,the AUC of five methods in the training cohort were 0.93,0.85,0.67,0.92,0.89,and in the testing cohort were 0.86,0.80,0.50,0.78,0.71.The models constructed by LASSO in both tasks were the dominant models,the AUC of the fusion model in the testing cohort which combined with age,gender and the dominant Radiomics score(Radscore)was 0.80[95％confidence interval(CI)0.63-0.96]in task 1,and the accuracy,sensitivity and specificity were 78.94％,77.78％,and 79.31％respectively.They were 0.89(95％CI 0.74-1.00),90.00％,95.65％,and 71.43％,respectively in task 2.The calibration curves showed that the fusion models had a good goodness of fit.Conclusion Based on the establishment of two dichotomous models,the radiomics based on the contrast-enhanced T1 WI is feasible in predicting the high,moderate and low differentiation degree of rectal adenocarcinoma.

Objective To explore the mechanism of Zishen Jianpi Huayu Tablets(Corni Fructus,Notoginseng Radix et Rhizoma,Astragali Radix,Puerariae Lobatae Radix,Spatholobi Caulis,Rehmanniae Radix)in the treatment of diabetic retinopathy(DR)by means of network pharmacology and molecular docking technique,and verified by in vitro experiments.Methods The active components of Zishen Jianpi Huayu Tablets and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the BATMAN-TCM database.Drug target proteins were converted to their corresponding gene names through the UniProt database.DR-related targets were searched using"diabetic retinopathy"as a keyword in GeneCards,DrugBank,OMIM,and TTD databases.Common targets between the disease and the drug were identified using the Venny tool.These common targets were analyzed using the String database,a protein-protein interaction(PPI)network was constructed.Topological heterogeneity analysis was performed using Cytoscape 3.9.1 to select core targets and create a PPI network diagram.These common targets were entered into the Metascape database for Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to identify potential action pathways.Molecular docking of the main active components and core targets was performed using Auto Dock tools software,followed by further experimental validation.The CCK-8 assay was used to assess the effect of Zishen Jianpi Huayu Tablet medicated serum on the cell viability of Human Retinal Microvascular Endothelial Cells(HRmECs)under high glucose conditions,and RT-qPCR was used to measure the expression of IL-1β,AKT1,VEGFA,and TP53 mRNA in HRmECs.Results(1)The effective components and corresponding target proteins of Zishen Jianpi Huayu Tablets were screened by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database.The disease-related targets of DR were searched by GeneCards,OMIM and TTD databases.The use of VENNY platform for drug active components target and DR disease-related target to take intersection(common target),that is,Zishen Jianpi Huayu Tablets in the treatment of DR potential target.The network of"drugs-active components-common targets"was constructed to screen out the key active components of Zishen Jianpi Huayu Tablets in the treatment of DR.Import the common target into STRING database,obtain the PPI network relationship,and screen out the core target.Metascape platform was used to analyze the GO function and KEGG pathway enrichment of the common targets.The key active components and core targets were verified by Autodock 4 software for molecular docking.(2)The drug-containing serum and blank serum of Zishen Jianpi Huayu Tablets was prepared.Human retinal microvascular endothelial cells(HRmECs)were randomly divided into 5 groups:the control group(low-sugar DMEM medium+10%blank serum),high-glucose group(high-sugar DMEM medium+10%blank serum)and Zishen Jianpi Huayu Tablets containing low-,medium-and high-dose serum(high-sugar DMEM medium+10%low-,medium-and high-dose drug containing serum)were detected after 48 hours of culture.The proliferative activity of HRmECs cells was detected by CCK-8 method,and the mRNA expressions of IL-1β,AKT1,VEGFA and TP53 in HRmECs cells were detected by RT-qPCR method.Conclusion Zishen Jianpi Huayu Tablets may act on core targets such as IL-1β,IL-6 and VEGFA,as well as key pathways such as NF-κB signaling pathway,AGE-RAGE signaling pathway and PI3K-AKT pathway through various active components such as quercetin,kaempferol and rehmannia flavonoids,so as to play a therapeutic role in DR.

OBJECTIVE To prepare anemoside B4 （AB4） and programmed cell death ligand 1 （PDL1） siRNA （siP） co- delivered cRGD-modified targeting liposomes （AB4/siP-c-L）， and to study the cellular uptake in vitro. METHODS The cRGD- modified AB4-loaded targeted liposomes （AB4-c-L） were prepared by ethanol injection. AB4-c-L was mixed with 20 nmol/L siP in the same volume and AB4/siP-c-L was obtained through electrostatic adsorption. The particle size， Zeta potential， morphology， encapsulation efficiency and drug content， in vitro release behavior and serum stability of AB4/siP-c-L were investigated by laser scattering particle size tester， transmission electron microscopy， ultrafiltration centrifugation， dialysis and agar-gel electrophoresis block test. Cellular uptake of AB4/siP-c-L by Lewis lung cancer cells LLC and its intracellular localization were evaluated by flow cytometry and confocal laser scan technique. RESULTS The average particle size of AB4/siP-c-L was （187.4±3.1） nm， and the Zeta potential was （33.5±1.4） mV. AB4/siP-c-L was spheroidal in shape. The encapsulation efficiency and content of AB4 were （95.2±0.4） % and （1.0±0.2） mg/mL， respectively. AB4/siP-c-L could better package siP， and exhibited good serum stability， obvious pH sensitivity and sustained release property. The uptake rate of AB4/siP-c-L by LLC cells was significantly higher than that of free drug， and was able to accumulate in cytoplasm. CONCLUSIONS AB4/siP-c-L can effectively realize the co-loading of AB4 and gene drug siP， which has certain in vitro targeting to LLC cells.