ObjectiveTo observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis （NASH） and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin （IL）-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group， with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules， while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0， 12， and 24， the traditional Chinese medicine （TCM） syndrome score， body mass index （BMI）， liver fat content assessed by Fibroscan （CAP value）， the level of alanine transaminase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transferase （GGT）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acid （FFA）， and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% （23/37） in the control group and 85.71% （30/35） in the treatment group， with a statistically significant difference （χ² = 5.14， P<0.05）. At weeks 12 and 24 after treatment， the TCM syndrome score， BMI， CAP value， TC， TG， LDL-C， and FFA were all significantly lower in both groups compared to pre-treatment levels， while the HDL-C level significantly increased （P<0.05）. The effect was better at week 24 （P<0.05） than at week 12 （P<0.05）， and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment （P<0.05）. After 24 weeks of treatment， both groups exhibited significant reductions in IL-18 and IL-1β levels （P<0.05）. The treatment group demonstrated superior efficacy compared to the control group after treatment （P<0.05）. Both groups experienced decreases in ALT， AST， and GGT levels after treatment （P<0.05）. However， there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group， nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia， exhibiting hepatoprotective， anti-inflammatory， lipid-regulating， and weight-reducing effects.

Nonalcoholic fatty liver disease（NAFLD） is the most common chronic liver disease in the world. Because of its complex pathogenesis， high clinical prevalence and large population， it poses a great threat and challenge to public health in the world. Therefore， active intervention measures are needed. Currently， western medicine is effective in reducing weight， reducing liver fat content， improving glucose-lipid metabolism and insulin resistance. However， for patients with NAFLD-related fibrosis and cirrhosis， there is still a lack of sufficient histological evidence to support its benefits， and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD， but there are many problems such as poor implementation and low compliance of patients， and the clinical efficacy is not ideal. Traditional Chinese medicine（TCM） has the significant advantages of multiple pathways and multiple targets. Berberine， the active ingredient of TCM， can interfere with the production of NAFLD from multiple pathways， including increasing energy consumption， weight loss， improving glucose-lipid metabolism， improving insulin resistance， anti-inflammatory， anti-oxidation， regulating intestinal flora， restoring bile acid homeostasis， anti-fibrosis and so on， which can play a positive role in the treatment of NAFLD. At the same time， it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption， improving oral bioavailability， increasing the highest biological distribution in the liver， enhancing the overall therapeutic effect of NAFLD， and reducing adverse drug reactions， which could provide reference for clinical medication.

ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.

With the change in environmental pollution and lifestyle， the incidence and mortality of cancer are increasing year by year， which is a serious threat to human life and health. Autophagy is a process in which eukaryotic cells use lysosomes to degrade cytoplasmic proteins and damaged organelles under the regulation of autophagy-related genes. It plays a dynamic inhibiting or promoting role in the occurrence and development of cancer and is involved in the regulation of tumor formation， proliferation， metastasis， and response to anticancer therapy. With the deepening of the research on the mechanism of cancer， a variety of cancer treatment methods have been established， such as chemotherapy， radiotherapy， surgery， immunotherapy， and gene therapy. Pharmacological or genetic inhibition of autophagy has been shown to enhance the lethal effect of various anticancer treatments on tumor cells， suggesting that inhibition of autophagy is an effective sensitization strategy in cancer therapy. Meanwhile， over-stimulation of autophagy may also provide a new method for the treatment of drug-resistant cancer cells with high apoptotic thresholds. As a treasure of Chinese culture， traditional Chinese medicine plays an important role in the adjuvant treatment of cancer with its advantages of multi-target， multi-pathway， and small side effects. In recent years， many positive results have been achieved in the study of natural autophagy regulatory factors of traditional Chinese medicine in cancer， and they have been widely verified in different autophagy regulatory models. This article outlines the mechanism of autophagy， summarizes the dual regulatory role of autophagy in tumor biology， and collects relevant studies published in the databases of China National Knowledge Infrastructure (CNKI） and Wanfang Data for nearly 10 years that affect the role of tumorigenesis and development by regulating autophagy. The article also collates autophagy rules of tumor cells induced by traditional Chinese medicine and its active ingredients， so as to provide a certain reference for the research on the development and application of anti-tumor drugs.

The banana Fusarium wilt (BFW) caused by Fusarium oxysporum f. sp. cubense tropical race4 (FocTR4) is difficult to control worldwide, which causes a huge economic losse to banana industry. The purpose of this study was to screen Trichoderma strains with antagonistic activity against FocTR4, to isolate and purify the active compound from the fermentation broth, so as to provide important biocontrol strains and active compound resources. In this work, Trichoderma strains were isolated and screened from the rhizosphere soil of crops, and the strains capable of efficiently inhibiting FocTR4 were screened by plate confrontation, and further confirmed by testing inhibition for the conidial germination and mycelial growth of FocTR4. The phylogenetic tree clarified the taxonomic status of the biocontrol strains. Moreover, the active components in the fermentation broth of the strains were separated and purified by column chromatography, the structure of the most active component was analyzed by nuclear magnetic resonance spectroscopy (NMR), the BFW control effect was tested by pot experiments. We obtained a strain JSHA-CD-1003 with antagonistic activity against FocTR4, and the inhibition rate from plate confrontation was 60.6%. The fermentation broth of JSHA-CD-1003 completely inhibited the germination of FocTR4 conidia within 24 hours. The inhibition rate of FocTR4 hyphae growth was 52.6% within 7 d. A phylogenetic tree was constructed based on the ITS and tef1-α gene tandem sequences, and JSHA-CD-1003 was identified as Trichoderma brevicompactum. Purification and NMR identification showed that the single active compound was trichodermin, and the minimum inhibitory concentration (MIC) was 25 μg/mL. Pot experiments showed that the fermentation broth of strain JSHA-CD-1003 was effective against BFW. The control rate of leaf yellowing was 47.4%, and the rate of bulb browning was 52.0%. Therefore, JSHA-CD-1003 effectively inhibited FocTR4 conidial germination and mycelium growth through producing trichodermin, and showed biocontrol effect on banana wilt caused by FocTR4, thus is a potential biocontrol strain.
Fusarium ; Musa ; Phylogeny ; Trichodermin ; Hypocreales

AIM:To investigate the expression of centromere protein-H(CENP-H)in adrenocortical carcino-ma(ACC)and its relationship with disease progression and prognosis,and to explore the impact of CENP-H gene knock-down on the viability and migration of ACC cells.METHODS:The mRNA expression level of CENP-H in 76 ACC pa-tients and 128 healthy controls,and its correlations with tumor stages and prognosis were analyzed by GEPIA2 database.The mRNA expression of CENP-H in different stages of ACC and its correlation with disease prognosis were further ana-lyzed by ULCAN database.The protein expression of CENP-H was examined by immunohistochemical staining of paraffin-embedded ACC and normal adrenal gland specimens.Knockdown of CENP-H by siRNA(siCENP-H)was performed in human ACC cell line H295R.The viabilty of H295R cells transfected with siCENP-H or siNC was measured by CCK-8 as-say,the cell migration was detected by wound-healing assay,and the protein levels of CENP-H,p-ERK1/2,t-ERK1/2,p-P38,t-P38,p-JNK1/2 and t-JNK1/2 were detected by Western blot.RESULTS:The mRNA level of CENP-H was signifi-cantly higher in ACC than that in normal controls,and was correlated with tumor stages and prognosis.The protein level of CENP-H was significantly higher in ACC specimens than that in normal adrenal gland.Knockdown of CENP-H in H295R cells resulted in decreased cell viability and migration.The protein levels of p-P38 and p-JNK1/2 were decreased in si-CENP-H group.CONCLUSION:CENP-H is highly expressed in ACC,and is correlated with tumor stages and poor prognosis.Knockdown of CENP-H can inhibit the viability and migration of ACC cells,and its mechanism may related to inactivation of P38 and JNK signaling pathways.

OBJECTIVE To investigate the inhibitory effect and mechanism of 5,6-dimethylxanthe-none-4-acetic acid(DMXAA)on metastasis of Lewis lung cancer(LLC)in mice.METHODS The inhibi-tory effect of DMXAA on tumor metastasis was analyzed via an LLC xenograft tumor model and LLC metastatic tumor model.The mice of LLC xenograft tumor model were randomly divided into three groups:model group(physiological saline containing 1%DMSO,ip,once every two days),model+suni-tinib group(30 mg·kg-1,ip,once every two days),and model+DMXAA group(25 mg·kg-1,ip,once).Tumor volume and body mass were measured once every two days after administration.Two and five days after administration,tumor mass was measured by sacrificing the mice,followed by immunofluores-cence staining of tumor tissues.Platelet/endothelial cell adhesion molecule-1(CD31)and α-smooth muscle actin(α-SMA)were used to analyze the vascular structure of tumor tissues.The tumor hypoxia level was detected using the hypoxia probe pimonidazole staining.The mice of LLC metastatic tumor model were randomly divided into three groups:model group(physiological saline containing 1%DMSO,ip,twice a week),model+sunitinib group(60 mg·kg-1,ip,twice a week),and model+DMXAA group(25 mg·kg-1,ip,once).At the Two and five weeks after administration,the in vivo tumor growth and metastasis were observed and quantified using a small animal live imaging system.RESULTS Compared with the model group,the tumor volume and mass of the model+sunitinib group and model+ DMXAA group were significantly reduced(P<0.05,P<0.01),and DMXAA took effect faster and more significantly than sunitinib.At the same time,compared with the model group,the body mass in the model+sunitinib group decreased significantly(P<0.05),but there was no significant difference in body mass the model+DMXAA group.Compared with the model group,model+sunitinib had no effect on tumor metastasis,but model+DMXAA significantly reduced tumor metastasis two weeks after administration(P<0.01).Compared with the model group,the coverage rate of α-SMA/CD31 in the model+sunitinib group and model+DMXAA group increased significantly(P<0.05).Compared with the model group,there was no significant change in the tumor hypoxia area in the model+sunitinib group,but this in the model+DMXAA group decreased significantly(P<0.01).CONCLUSION DMXAA significantly inhibits the growth and metastasis of LLC in mice,and its mechanism may be related to its improvement of tumor vascular normalization and hyposic microenvironments.

Objective To explore the diagnostic value of MRI radiomics model for clinically significant prostate cancer(csPCa)in the transition zone with prostate imaging reporting and data system(PI-RADS)3-4.Methods According to the ratio of prostate cancer(PCa)∶benign prostatic hyperplasia(BPH)=1∶1,the relevant data of patients with transition zone lesions confirmed by pathology were retrospectively collected.Patients were divided into csPCa group and non-csPCa group according to pathological results.Region of interest(ROI)were drawn along the edge of the lesion in T2WI,diffusion weighted imaging(DWI),and apparent diffusion coeffi-cient(ADC)sequences,the radiomics features were extracted,and a single sequence logistic regression model was constructed and validated after feature cleaning and screening.The diagnostic performances of the radiomics model for transition zone csPCa were evaluated and compared.Results A total of 204 patients were included,and there were 94 cases in the csPCa group and 110 cases in the non-csPCa group.There were statistically significant differences in PI-RADS,prostate volume(PV),prostate specific antigen(PSA)and its derivative indicators between csPCa and non-csPCa groups.In the validation set,the area under the cunve(AUC)of the ADC model was 0.766,and the DeLong test showed that the diagnostic performance of the ADC model was significantly higher than that of the DWI and T2WI models.Conclusion When the PI-RADS classification of transition zone lesion is 3-4,the ADC radiomics model has good diag-nostic performance for csPCa,which can reduce unnecessary biopsy in some patients.Radiomics is expected to become a more objec-tive and accurate medical diagnostic tool.

Objective To investigate the impact of O-linked β-N-acetylglucosamine(O-GlcNAc)modification levels in the amygdala on stress resilience.Methods A restraint stress model was established in male C57BL/6J mice by confining them for 24 hours,followed by by 7days of rest.Behavioral assays,including the tail suspension test,forced swimming test and fear conditioning test,were conducted.Subsequently,the mice were euthanized,and the hippocampus,cortex,and amygdala were isolated.O-GlcNAc modification levels in these brain regions were assessed using enzyme-linked immunosorbent assay(ELISA).Using stereotaxic brain injection techniques,the O-GlcNAcase(OGA)inhibitor,O-GlcNAc transferase(OGT)inhibitor,and OGA and OGT adeno-associated viruses were administered to regulate O-GlcNAc levels in the amygdala before their effects on stress-related behavior were observed.Results The restraint stress group showed significantly increased anxiety,depressive-like behavior,and impaired memory.Concomitantly,O-GlcNAc levels in the amygdala were significantly decreased post-stress and were negatively correlated with behavioral performance.Mice with higher stress resilience exhibited significantly higher levels of O-GlcNAc in the amygdala than more sensitive ones.Upregulation of O-GlcNAc levels in the amygdala via Thiamet-G or adeno-associated virus-O-GlcNAc transferaseinjections increased O-GlcNAc levels,alleviated depressive-like behavior and enhanced stress resilience.In contrast,downregulation of O-GlcNAc levels through OSMI-1 or adeno-associated virus-O-GlcNAcase injections reduced the O-GlcNAc levels,exacerbated depressive-like behavior and reduced resilience to stress.Conclusion O-GlcNAc modification levels in the amygdala play a critical role in regulating stress resilience following restraint stress in mice.

OBJECTIVE To investigate the damage effect and potential toxic mechanism of SARS-CoV-2 spike protein(S protein)on human neuroblastomacells(SH-SY5Y).METHODS SH-SY5Y were treated with S protein at concentrations of 25,50,75,and 100 mg·L-1 for 24 h.Cell viability of SH-SY5Y was detected using the CCK-8 assay.The cytotoxic lactate dehydrogenase(LDH)detection kit was used to measure the release rate of LDH,and the 5-ethynyl-2′-deoxyuridine(EdU)-488 cell prolifera-tion kit was used to assess cell proliferation.The ATP detection kit was used to measure intracellular ATP content.The JC-1 fluorescent probe method was employed to detect the mitochondrial membrane potential(MMP)of cells.Seahorse XF was used to measure mitochondrial respiratory and glycolytic capacity.RESULTS Compared with the cell control group,cell viability was significantly reduced in S protein 25,50,75 and 100 mg·L-1 groups(P<0.01),and the half-inhibition concentration(IC50)was 65.05 mg·L-1.The LDH release rate wassignificantly increased(P<0.01)and the proportion of EdU positive cellswas significantly reduced(P<0.01)in S protein 25,50,75 and 100 mg·L-1 groups.S protein signifi-cantly reduced intracellular ATP content(P<0.01)at the concentrations of 75 and 100 mg·L-1,while significantly reduced intracellular MMP(P<0.05,P<0.01)at the concentrations of 50 and 75 mg·L-1.S protein 50 mg·L-1 increased the maximum value of basal glycolysis levels and glycolytic capacity(P<0.05,P<0.01),and S protein 25 and 50 mg·L-1 increased the maximum value of respiration capacity(P<0.05,P<0.01).SH-SY5Y cell viability was positively correlated with the intracellular ATP content and the MMP level(r2=0.9209,P=0.001;r2=0.6170,P=0.0025),and negatively correlated with the maximum level of basal glycolysis and glycolytic capacity(r2=0.5194,P=0.0285;r2=0.6664,P=0.0073),and nega-tively correlated with ATP production capacity(r2=0.8204,P=0.0008).CONCLUSIONS protein decreases the viability of SH-SY5Y cells and inhibited cell proliferation.The mechanism may be closely related to the disorder of energy metabolism.