OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

Breast cancer is one of the most common cancers in women， which seriously threatens women's health. Early diagnosis and precise treatment of breast cancer are helpful to improve the prognosis of patients. This article summarizes the research status of bacteria and their metabolites in the development and treatment of breast cancer， and discusses in detail the role and mechanism of bacteria and their metabolites in the development and intervention of breast cancer. These mechanisms include regulation of inflammation and immune response， DNA damage， and regulation of cell biological characteristics. Engineering bacteria have become one of the hotspots in the field of breast cancer treatment in recent years due to their natural advantages in targeting tumors and activating immunity. This article further summarizes the research progress of engineered bacteria in the treatment of breast cancer， aiming to provide an important reference for formulating targeted treatment strategies and improving the prognosis of patients. Although bacteria and their metabolites affect the development and treatment of breast cancer through a variety of mechanisms， and can enhance the therapeutic effect of cancer and reduce the adverse effects of treatment， the clinical application of bacteria in anti-breast cancer therapy still faces numerous challenges. The highly individualized composition of bacteria leads to the lack of universality of treatment， and the complex interaction between bacteria and host further increases the difficulty of research. In the future， it is urgent to further explore the mechanism of bacteria and their metabolites affecting the development and treatment of breast cancer， and promote the clinical application of bacteria in anti-breast cancer treatment.

To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

Emerging evidence suggests that ferroptosis,an iron-dependent form of regulated cell death,plays a criti-cal role in the genesis of liver fibrosis through inducing hepatic stellate cell(HSC)ferroptosis to inhibit liver fibrosis or inducing hepatic ferroptosis to potentiates liver fibrosis.Pharmacologically targeting at ferroptosis with its inducers can slow down the progression of liver fibrosis in vitro and in vivo model.This review suggests that pharmacological in-duction of HSC ferroptosis might be used as a potential novel targeted therapy for the treatment of liver fibrosis.

Objective To assess the tear film stability and morphological characteristics of the tarsal gland in myopic children.Methods In this prospective descriptive study,myopic children who performed refractive examinations in the Pediatric Ophthalmology & Refraction Clinic,Jinan Mingshui Eye Hospital from November 2021 to November 2022 were in-cluded.An Ocular Surface Disease Index(OSDI)questionnaire survey was carried out;tear meniscus height(TMH),non-invasive first breakup time(NIf-BUT)and images of the tarsal glands were obtained by OCULUS Keratograph 5M compre-hensive ocular surface analyzer.In addition,the atrophy and tortuosity of tarsal glands were scored to analyze the tear film stability and clinical characteristics of tarsal glands in myopic children.Results A total of 48 myopic children(91 eyes)aged from 7 to 16(10.25±2.23)years were recruited,including 27 males(56.25％)and 21 females(43.75％).The aver-age TMH was(0.19±0.04)mm(95％CI:0.18-0.19)and the average NIf-BUT was(5.40±2.62)s(95％CI:4.90-5.94);the TMH was positively correlated with NIf-BUT(r=0.223,P=0.034).The tarsal gland atrophy score was 1(0,1).The tortuosity score of the upper and lower tarsal gland was 0(0,1)and 0(0,0),respectively,with a statistically significant difference(Z=3.692,P＜0.001).In all subjects,49 eyes(53.85％)had tarsal gland atrophy,and 37 eyes(40.66％)had tarsal gland tortuosity.There were significant differences in TMH and NIf-BUT between children aged＜12 years and children aged ≥12 years(both P＜0.05).There was a significant difference in TMH between children with an OSDI score＜13 and children with an OSDI score ≥ 13(t=2.305,P=0.026).There was a significant difference in NIf-BUT between mild and moderate myopia children(t=2.300,P=0.024);the spherical equivalent was positively correlated with NIf-BUT(r=0.283,P=0.023).Conclusion Children with mild to moderate myopia show low tear film stability and a certain proportion of abnormal morphology in tarsal glands.In addition to the refractive status of children,attention should also be paid to ocular surface health in the refraction clinic.

Objective:To explore the application effect of the modified sandwich teaching method based on constructivism theory in clinical teaching of neurology nursing interns.Methods:A total of 29 nursing interns who practiced in the Department of Neurology of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from June 2020 to May 2021 were selected as the control group, using the conventional clinical nursing teaching method, and 28 nursing interns who practiced from June 2021 to May 2022 were selected as the observation group, using the modified sandwich teaching method based on constructivism theory. Before graduating from the Department of Neurology, nursing interns in the two groups were compared in terms of the teaching effects, such as the score of learning initiative, theoretical examination, operation examination, and nursing round report. SPSS 25.0 was used for t test and chi-square test. Results:The score for each dimension (learning driving force, learning objectives, in-depth learning, controlled learning, and solid learning) and total score in the observation group were significantly higher than those in the control group ( P<0.05). There was no significant difference between the two groups in the scores of theoretical examination and operation examination (89.11±3.58 vs. 88.97±2.74, 93.79±2.48 vs. 93.86±2.20; P>0.05); the scores of nursing rounds in the observation group were significantly higher than those in the control group (88.61±2.60 vs. 83.38±3.97, P<0.05). Conclusions:The modified sandwich teaching method based on constructivism theory can enhance the learning initiative and comprehensive analysis ability of nursing interns in the Department of Neurology. It is suitable for clinical nursing teaching in the Department of Neurology and is worth popularizing.

Objective:To explore the value of radiomics and deep learning in predicting the efficacy of initial transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods:This was a cohort study. The imaging and clinical information of HCC patients treated with TACE in the Second Affiliated Hospital of Harbin Medical University from January 2015 to January 2021 were collected retrospectively. A total of 265 patients were divided into response group (175 cases) and non-response group (90 cases) according to the modified solid tumor efficacy evaluation criteria (mRECIST) 1 to 2 months after initial TACE. According to the proportion of 8∶2, the patients were randomly divided into training group (212 cases, 140 responders and 72 non-responders) and test set (53 cases, 35 responders and 18 non-responders). Univariate and multivariate logistic regression was used to screen clinical variables and construct a clinical model. The radiomics features were extracted from the preoperative CT images, and radiomics model was constructed after feature dimensionality reduction. Using the deep learning method, three residual network (ResNet) models (ResNet18, ResNet50 and ResNet101) were established, and their effectiveness was compared and integrated to build a deep learning model with best performance. Univariate and multivariate logistic regression was used to combine pairwise three models to establish the combined model. The receiver operating characteristic curve was used to evaluate the performance of the model to distinguish between TACE response and non-response groups.Results:In the test set, the area under the curve (AUC) of the clinical model and the radiomics model in the differentiation between response and non-response after TACE were 0.730 (95% CI 0.569-0.891) and 0.775 (95% CI 0.642-0.907). The AUC of ResNet18, ResNet50 and ResNet101 were 0.719, 0.748 and 0.533, respectively. The AUC for deep learning model obtained by integrating ResNet18 and ResNet50 was 0.806 (95% CI 0.665-0.946). After pairwise fusion, the combined deep learning-radiomics model showed the highest performance, with an AUC of 0.843 (95% CI 0.730-0.956), which was better than those of the deep learning-clinical model (AUC of 0.838, 95% CI 0.719-0.957) and the radiomics-clinical model (AUC of 0.786, 95% CI 0.648-0.898). Conclusions:The combined model of radiomics and deep learning has high performance in predicting the curative effect of TACE in patients with HCC before operation.

ObjectiveTo study the bioactive secondary metabolites of Talaromyces sp. TP21 and their bioactivities. MethodThe secondary metabolites of Talaromyces sp. TP21 were isolated by high performance liquid chromatography （HPLC）， normal phase and reversed phase column chromatography combined with molecular networking and bioassay-guided fractionation， and their structures were determined by nuclear magnetic resonance （NMR） and high resolution mass spectrometry （HR MS）. The inhibitory effects of the compounds on the growth of the lung cancer cell line A549 and the liver cancer cell line Hep G2 were measured by themethyl thiazolyl tetrazolium （MTT） method. The antimicrobial activities of the compounds were measured with Staphylococcus aureus and human oral cavity-derived Saccharomyces cerevisiae as the indicator microorganisms. ResultSeventeen compounds were isolated from the secondary metabolites of Talaromyces sp. TP21 and identified as ergochrome C （1）， daldiniaeschsone A （2）， seco-blennolide B （3）， penitholabene （4）， penicichrysogene A （5）， orsellinic acid （6）， griseofulvin （7）， isorhodoptilometrin （8）， （+）-5-chloromitorubrinic acid （9）， penicillixanthone A （10）， pentacecilide B （11）， pentacecilide C （12）， chrodrimanin C （13）， chrodrimanin E （14）， chrodrimanin H （15）， chrodrimanin F （16）， and 3-hydroxypentacecilide A （17）. ConclusionCompounds 1-5， 11-12， and 17 were isolated from Talaromyces for the first time. Among them， compounds 4， 7， and 10-12 exhibited inhibitory activities against the growth of A549 and Hep G2 cells， with the median inhibitory concentration below 50 μmol·L^-1. Furthermore， compounds 9 and 10 showed inhibitory activities against S. aureus and human oral cavity-derived S. cerevisiae， with the minimum inhibitory concentration of 8-128 mg·L^-1.

[Objective] To establish a real-time fluorescence quantitative PCR nucleic acid detection method of human parvovirus B19 and validate the method systematically. [Methods] Specific primers and probes for the highly conserved regions of the three genotypes of B19 virus were designed, and B19 quantitative amplification standard curves were established. The accuracy, precision (repeatability and intermediate precision), linear range, quantification limit, detection limit, specificity, anti cross contamination, genotyping and anti-interference ability of this method were verified. [Results] When the quantitative reference range for B19 virus was 2.0×10¹ to 1.0×10⁸ IU/mL, a double logarithmic regression analysis was performed between the measured values and the theoretical values, and the regression equation R²≥0.98 showed good linear correlation. The quantification limit was 20 IU/mL, with a detection rate of 100%. The detection limit was 10 IU/mL, and the detection rate is 95.23%. Three genotypes of B19 virus samples can be effectively detected. The plasma of seven non B19 pathogens, including hepatitis A virus, hepatitis B virus, hepatitis C virus, human immuno-deficiency virus, human cytomegalovirus, hepatitis E virus and Treponema pallidum, was non reactive and has good species specificity. Simultaneously, in the presence of seven other concurrent pathogens, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. When the hemoglobin concentration was 431 mg/dL, triglycerides (1 269 turbidity) and unconjugated bilirubin concentration was 20 mg/dL, this method was non reactive for all three common plasma interfering substances. In the presence of three common plasma interfering substances, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. The deviation between the detection values of standard substances at two concentration levels of S1 (E5 IU/mL) and S2 (E4 IU/mL) and the target values were≤±0.5 log value. The CV values of positive sample 1 (concentration level E5 IU/mL) and positive sample 2 (concentration level E4 IU/mL) for daily precision confirmation and continuous 5-day intra-day precision confirmation were both≤5%. [Conclusion] This method has strong specificity, high sensitivity, wide linear range, stability, reliability and high accuracy, and can be used for the detection of human parvovirus B19 nucleic acid in plasma.