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 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.

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.

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.

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.

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.

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.

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

To evaluate the value of endoscopic retrograde cholangiopancreatography(ERCP)and SpyGlass in the diagnosis of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). Data of patients who underwent ERCP and SpyGlass in Hangzhou First People′s Hospital from January 2016 to December 2019 were analyzed. ERCP and SpyGlass features, complications, clinicopathologic characteristics and prognosis were retrospectively analyzed.A total of 9 patients (5 benign lesions and 4 malignant lesions) were included.ERCP was successfully performed in 9 cases, while SpyGlass was technically successful in 8 cases. Endoscopy showed mucus outflow from the papilla in 5 cases, and the mucus was removed by the balloon of ERCP in 8 cases.ERCP showed bile duct diffuse dilatation and filling defects in all patients. SpyGlass found the mucus in the bile duct in all patients. SpyGlass showed lesion mucosa were fish-egg like without vascular images (Ⅱtype, 3 cases), fish-egg like with vascular images (Ⅲ type, 1 case), villous (Ⅳtype, 4 cases). SpyGlass defined extent of the lesion in 8 cases. SpyGlass found that the lesion involved the intra and extrahepatic bile ducts in one case. Therefore, liver transplantation was recommended to avoid surgical exploration. One type Ⅲ lesion underwent a direct biopsy. The pathology showed moderate dysplasia, which was consistent with the postoperative pathology. No complication occurred. ERCP combined with SpyGlass could clarify the scope of IPMN-B and provide basis for surgical options, which is safe and effective in IPMN-B diagnosis.

Objective: This study aimed to analyze and summarize the implementation of the primary prevention program for stroke in Shanghai rural community and evaluate its preventive effect. Methods: A cluster sampling method was used to select approximately 50 000 community natural population from a town in Fengxian District of Shanghai. A primary stroke prevention program was established and implemented in the community from 2008 to 2010 and from 2012 to 2015. The prevention program inclueded stroke health education for the whole population, screening of high risk population of stroke, and therapeutic intervention and management plan for individuals aged≥50 years. The intervention measures were followed up every 2 months. From 2008 to 2015, new stroke cases were monitored dynamically and reviewed annually with classification of stroke diagnosis. The effect of community primary prevention of stroke program was evaluated by the dynamic changes in stroke incidence. Results: From 2008 to 2015, a total of 422 600 individuals were monitored, including 20 500 men and 217 600 women. In 2008, 7 828 individuals were screened and 2 129 individuals were at high risk of stroke were screened, with a high risk rate of 27.2%. In 2012, 2 877 individuals were screened, and 725 individuals were at high risk of stroke were screened, with a high risk rate of 25.2%. The standardized incidence of stroke in this community was 158.1, 105.4, 86.6, 77.6, 89.3, 77.4, 50.7, and 42.3 per 100 000 respectively. The overall incidence image roughly showed a downward trend except 2012(trend test P<0.01). There was no significant difference in the incidence of stroke between men and women in each year. The incidence of stroke increased significantly with age (trend test P<0.01). The age composition of stroke patients is slightly different between different sexes. The proportion of male patients with stroke aged <70 years was significantly higher than that of female patients with stroke, while the proportion of female patients with stroke age>70 years was significantly higher than that of male patients with stroke (P<0.01). Cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage accounted for 20.76%, 75.14%, and 4.10%, respectively. Conclusion Based on lifestyle intervention and treatment and control of risk factors, screening high-risk individuals for therapeutic intervention in community population can significantly reduce the incidence of stroke.