ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Objective:To explore the mechanism by which miRNA-4469 (miR-4469) regulates the proliferation and invasion of renal cancer cells in vitro.Methods:The survival differences of patients with different expression levels of miR-4469 were analyzed based on the OncomiR database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the expression of miR-4469 in renal cancer cell lines ACHN, OS-RC-2, SK-RC-20, 769-P, A498 and normal renal tubular epithelial cell line HK-2, and the renal cancer cells with the lowest expression level of miR-4469 were divided into miR-4469 group and control group, and were transfected with miR-4469 mimic and negative control sequence, respectively. The CCK-8 assay was used to detect the cell proliferation ability (expressed as absorbance value) in the two groups, and Transwell assay was used to analyze the number of invasive cells in the two groups. TargetScan Release 8.0 software was used to predict the binding site between miR-4469 and protein disulfide isomerase A4 (PDIA4) mRNA, and dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-4469 and PDIA4 mRNA. qRT-PCR method was used to detect the expression of PDIA4 mRNA in cells of each group, and Western blotting method was used to detect the expression levels of PDIA4 protein and PI3K-AKT-m-TOR pathway proteins in cells of each group.Results:Analysis of relevant data from the OncomiR database showed that compared with patients with low miR-4469 expression, the overall survival of renal cancer patients with high miR-4469 expression was better ( P < 0.001). The relative expression of miR-4469 in each renal cancer cell line was lower than that in HK-2 cells (all P < 0.05), and the expression of miR-4469 in 769-P cells was the lowest, which were selected to perform the subsequent experiments. The proliferation ability of 769-P cells in the miR-4469 group was lower than that in the control group ( P < 0.01). The number of 769-P cell invasions in the miR-4469 group were less than that in the control group [(19±3) cells vs. (64±7) cells, t = 5.44, P = 0.002]. Compared with the co-transfection of wild-type PDIA4 and miR-4469 negative sequence group, the relative luciferase activity of cells in the co-transfection of wild-type PDIA4 and miR-4469 mimic sequence group was lower (0.42±0.07 vs. 1.01±0.08, t = 5.74, P = 0.001); there was no statistical difference in cell luciferase activity between the co-transfected mutant PDIA4 and miR-4469 negative sequence group and the co-transfected mutant PDIA4 and miR-4469 mimic sequence group (0.99±0.11 vs. 1.02±0.11, t = 0.19, P = 0.001). The relative expression levels of PDIA4 mRNA in 769-P cells in the miR-4469 group were lower than that in the control group (0.98±0.23 vs. 7.19±2.23, t = 2.77, P = 0.032). Compared with the control group, the expression of PDIA4 protein and PI3K-AKT-m-TOR pathway-related p-PI3K, p-AKT, p-mTOR, and p-SGK1 proteins in 769-P cells in the miR-4469 group were all lower (all P < 0.05). Conclusions:miR-4469 may be related to the survival of renal cancer patients, and its expression is down-regulated in various renal cancer cell lines. miR-4469 may inhibit the proliferation and invasion of renal cancer 769-P cells by regulating the PI3K-AKT-m-TOR pathway through PDIA4.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

Objective To compare the cost and utility of aflibercept and conbercept for the treatment of wet age-related macular degeneration(wetAMD),in order to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods The incremental cost-utility ratio(ICUR)was obtained by using Markov model to simulate the survival of the two treatment regimens over the 5-year period,calculating costs and health outputs separately.Univariate sensitivity analysis was used to determine the impact of the parameter on ICUR,and probability sensitivity analysis was used to determine the influence of the uncertainty of each model parameter on the research results.One times the 2022 gross domestic product(GDP)per capita of China was used as the willingness-to-pay threshold(WTP)to judge its economy.Results Over the simulation period,the compazine regimen was significantly economical against the aflibercept regimen,with an ICUR of-1 528 840 per quality-adjusted life year(QALY),which was lower than the WTP.Univariate sensitivity analysis showed that the transition probability between mild and moderate visual status between the two regimens and the number of aflibercept injections per year were significant influencing factors of ICUR.Probabilistic sensitivity analysis pointed to a significant cost-utility advantage for conbercept at a WTP of one times GDP(probability of 65.9％),which was a more robust result.Conclusion For the treatment of wetAMD,conbercept has a cost-utility advantage compared with aflibercept.

Objective:To better evaluate the prevalence and epidemiological characteristics of metabolic-associated fatty liver disease (MAFLD) based on liver transient elastography.Methods:It was a cross-sectional study. A total of 6 961 patients without hepatitis, who underwent liver transient elastography examination at the Department of Hepatology, Zhongnan Hospital of Wuhan University from November, 2021 to April, 2022 were included. The patients were categorized into normal and mild, moderate, severe MAFLD groups according to FibroTouch controlled attenuation parameters (CAP). The CAP values among different body mass index (BMI) groups were compared using analysis of variance. The distribution characteristics and the incidence of MAFLD in different age, gender, body mass index(BMI), blood glucose and lipids groups using the chi-square test.Results:The total detection rate of MAFLD and severe MAFLD in the population with a BMI≥28.0 kg/m 2 was 99.6% and 71.8%, respectively. The detection rate of MAFLD in people with normal BMI was 28.4%. The detection rate of MAFLD in women of childbearing age or in the perimenopausal period were both significantly lower than that in men of the same age (40.3% vs 54.9%, χ 2=20.78, P<0.001; 43.1% vs 58.4%, χ 2=27.43, P<0.001), but there was no statistically significant difference in MAFLD detection rate between postmenopausal women and men of the same age. The detection rates of MAFLD in the group with abnormal blood glucose and lipids were both significantly higher than those in the group with normal blood glucose and lipids [69.7%(196/281) vs 35.2%(2 354/6 680), χ 2=138.36, P<0.001; 54.3%(1 696/3 124) vs 37.1%(1 420/3 837), χ 2=207.99, P<0.001]. Conclusion:Non-hepatitis patients had a higher prevalence of MAFLD. The BMI, gender, age, blood glucose, and lipids levels are all strongly associated with MAFLD.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

In this study,nine hybridoma cells secreting monoclonal antibodies against deltamethrin were prepared,and the monoclonal antibody 4D4E11 with best sensitivity was selected to develop indirect enzyme-linked immunosorbent assay (ic-ELISA) and gold nanoparticle-based lateral flow immunoassay (LFIA) for detection of deltamethrin. The optimal working buffer for ic-ELISA was 0.01 mol/L phosphate buffer (pH 7.4) containing 0.2 mol/L NaCl and 20％ methanol,while 0.01 mol/L phosphate buffer (pH 7.4) containing 1 mol/L NaCl,5‰Tween-20 and 10％methanol for LFIA. Under the optimal conditions,the half inhibition concentration (IC50) and limit of detection (IC10) of ic-ELISA were 10.60 ng/mL and 1.43 ng/mL respectively,and the limit of detection of the developed LFIA was 0.5μg/mL. The developed ic-ELISA and LFIA showed no cross-reactivities (CRs) with eight kinds of analogues of deltamethrin,which indicated the excellent specificity of proposed immunoassays. The average recoveries of the ic-ELISA in spiked tomato,cabbage and lettuce samples were 79.8％-92.6％with relative standard deviations of 0.8％-5.5％. The detection results of LFIA were consistent with the spiked concentrations in the range of 1-5 mg/kg. Meanwhile,the results of ic-ELISA and LFIA showed close correlation with high performance liquid chromatography (HPLC) in the test of blind lettuce samples. The experimental results demonstrated that the two immunoassays proposed here were suitable for rapid detection of deltamethrin with high sensitivity and high accuracy.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.