Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.

Objective To investigate the expression of circular RNA ubiquitin-associated protein 2(circ-UBAP2)and RAS-related C3 botulinum toxin substrate 1(Rac1)in cervical cancer tissues and their relation-ship with radiotherapy efficacy and prognosis.Methods A total of 96 patients with cervical cancer admitted to the hospital from January 2019 to May 2021 were selected as the research subjects.Detect the expression of circ-UBAP2 and Rac1 in the cancer tissues and adjacent tissues of the patients.The clinical data of the patients were recorded.According to the radiotherapy efficacy,they were divided into patients with effective radiother-apy(n=62)and patients with ineffective radiotherapy(n=34),and the relationship between the expressions of circ-UBAP2 and Rac1 and the radiotherapy efficacy was analyzed.The survival conditions of the patients were followed up for 3 years and they were divided into the survival group(n=81)and the death group(n=15),and the clinical data of the two groups were compared.The relationship between the expressions of circ-UBAP2 and Rac1 and the survival prognosis of patients was analyzed by Kaplan-Meier.The risk factors influ-encing the prognosis of patients were analyzed by Cox regression.Results The circ-UBAP2 expression and the positive rates of Rac1 expression in cancer tissues were both higher than those in adjacent tissues,and the difference was statistically significant(P＜0.05).The effective rate of radiotherapy in patients with high ex-pression of circ-UBAP2 and Rac1 in cancer tissues was lower than that in patients with low expression of circ-UBAP2 and Rac1,and the difference was statistically significant(P＜0.05).The 3-year overall survival rate and average survival duration of patients with high expression of circ-UBAP2 and Rac1 in cancer tissues were lower than those of patients with low expression of circ-UBAP2 and Rac1,and the difference was statistically significant(P＜0.05).There were statistically significant differences in clinical stage,tumor differentiation degree,expressions of circ-UBAP2 and Rac1,and the proportion of lymph node metastasis between the two groups(P＜0.05).The results of Cox regression analysis showed that clinical stage Ⅱ B-Ⅲ,poorly differen-tiated tumor degree,high expression of circ-UBAP2 and Rac1,and lymph node metastasis were risk factors af-fecting the prognosis of patients(P＜0.05).Conclusion circ-UBAP2 and Rac1 are abnormally highly ex-pressed in cervical cancer tissues and are related to the radiotherapy efficacy and prognosis.

Lung cancer is the malignant tumor with the highest incidence and mortality among the Chinese.Tumor node metastasis(TNM)staging established by the American Joint Committee on Cancer(AJCC)and International Union Against Cancer(UICC)is a commonly used criterion,but it still has limitations in judging the prognosis of non-small cell lung cancer(NSCLC)patients.With the advantages of real-time and convenient sampling,the immune score based on peripheral blood biomarkers have the ability to predict prognosis and efficacy of NSCLC patients,which have been developed and validated in clinical studies.However,clinical impleruentation of peripheral immune scores is still not widely in NSCLC patients.Therefore,this study introduces and evaluates the 6 peripheral immune scores and reviews the reseach progress of them in the treatment of NSCLC.

Objective Based on the epidemic situation of hepatitis B and liver cancer patients in Nantong from 2019 to 2022, to analyze the trend of hepatitis B virus DNA (HBV-DNA) changes and provide theoretical basis for the prevention and treatment of hepatitis B and liver cancer. Methods The data of patients with hepatitis B and liver cancer in Nantong Cancer Hospital were collected, and the general data, the time of infection with hepatitis B and the results of quantitative HBV-DNA test were statistically analyzed. Results A total of 487 patients with hepatitis B and liver cancer were collected, including 395 males and 92 females. Among them, patients aged 51-60 were the most common, accounting for 28.34%, followed by those aged 41-50 and 61-70, accounting for 23.00% and 21.56% respectively. In addition to 84 patients with unknown infection time, most of the patients with hepatitis B infection time distributed in 11 to 20 years, followed by 21 to 30 years and 1 to 10 years. Except for 126 patients with unknown levels of HBV DNA, the positive rate of HBV DNA in 361 patients was 64.82%. Between 2019 and 2022, except for patients with unknown levels of HBV-DNA, the proportion of patients with HBV-DNA<500 copies/mL showed an upward trend, while the proportion of patients with HBV-DNA (103-106) copies/mL showed a downward trend. Conclusion Sex and the time of infection with hepatitis B are high risk factors for hepatitis B liver cancer. Most patients with liver cancer are positive for HBV-DNA, which needs to be tested regularly to guide antiviral treatment.

Objective To detect the relative expression level of long non-coding RNA nuclear enriched a-bundant transcript(NEAT)1 in peripheral serum of patients with gastric cancer,and to explore the possibili-ty of its application in the auxiliary diagnosis of gastric cancer.Methods A total of 101 patients with newly diagnosed gastric cancer in Nantong Tumor Hospital from November 2017 to December 2019 were selected as the gastric cancer group,60 patients with benign gastric lesions were selected as the gastric benign lesions group,and 76 healthy people were selected as the control group.The relative expression levels of lncRNA NEAT1,carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)in serum samples of each group were detected,and the correlation between lncRNA NEAT1 and clinicopathological parameters was ana-lyzed.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of lncRNA NEAT1,CEA and CA19-9 alone or in combination.Results The relative expression levels of lncRNA NEAT1 in serum of gastric cancer group,gastric benign disease group and control group were 2.163(1.357,2.843),1.176(0.677,1.381)and 1.063(0.570,1.308),respectively,and the difference was statistically significant(H=52.467,P＜0.001).The relative expression level of serum lncRNA NEAT1 in gastric cancer patients was not related to gender(P=0.353)and age(P=0.382),but was related to tumor size(P=0.031),TNM stage(P=0.037)and lymph node metastasis(P=0.046).The relative expression level of lncRNA NEAT1 in serum of gastric cancer patients was not correlated with CEA and CA19-9(P＞0.05).The ROC curve showed that the area under the curve and sensitivity of lncRNA NEAT1 in the diagnosis of gastric cancer were higher than those of CEA and CA19-9.The combined diagnosis of the three had the highest diagnostic efficiency.Conclusion The relative expression of lncRNA NEAT1 in peripheral blood of patients with gastric cancer is increased,and it is correlated with some clinicopathological parameters.lncRNA NEAT1 may be a new marker for auxiliary diagnosis of gastric cancer.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K _D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl₄-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

Biochromatography is a new chromatographic technology with great development potential. It has been widely used in drug screening and biomolecular interaction analysis. The core of this technology is the chromatographic stationary phase of biomolecules. Nowadays, it mainly develops cell membrane chromatography, artificial biomimetic membrane chromatography and the various immobilization strategies to directly immobilizes proteins on the stationary phase carrier. This paper reviews the research progress of new biochromatographic stationary phase and the application of biochromatographic analysis based on new stationary phase. And, the applications of biochromatographic stationary phase and micro biochromatographic analysis system based on monolithic column are prospected.

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed