Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

The seco-prezizaane-type sesquiterpenes (SPS), as a special class of sesquiterpenes with a highly oxidative five-ring cage structure and seven consecutive chiral centers, are isolated from the genus Illicium, which have a variety of biological activities, including neurotoxicity and neurotrophic effects, etc. This review summarizes the chemical constituents and pharmacological effects of SPS, and discusses the potential trend and scope of future research.

Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.

Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.

ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract （COE） affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer （PLGC） by regulating the leucine-rich repeat containing G protein-coupled receptor 5 （Lgr5）/Wingless （Wnt）/β-catenin signaling pathway based on a gastric organoid injury model. MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG， 0.02 mg·L^-1）. Gastric organoid injury models were randomly divided into normal group， model group （0.02 mg·L^-1 MNNG）， low， medium， and high dose （5， 10， 20 mg·L^-1） groups of COE， and Wnt inhibitor Dickkopf-related protein 1 （DKK1） （0.5 mg·L^-1） group， and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium （MTT） assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin （HE） staining. The expression levels of Lgr5， Mucin2 （MUC2）， Mucin5AC （MUC5AC）， Mucin6 （MUC6）， Wnt， and β-catenin in gastric organoids under different drug concentrations were detected by Western blot （WB）. ResultCompared with the normal group， the number， volume， and activity of gastric organoids in the model group were decreased （P<0.01）， while the expressions of Lgr5， MUC2， Wnt， and β-catenin were significantly increased （P<0.01）. The expressions of MUC5AC and MUC6 were significantly decreased （P<0.01）. Compared with the model group， the number and volume of gastric organoids in the low， medium， and high dose groups of COE were all improved （P<0.01）， and the vitality of gastric organoids was significantly enhanced （P<0.01）. The effect was the most significant at a COE concentration of 20 mg·L^-1 （P<0.01）. The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced （P<0.01）， while the expression of MUC5AC and MUC6 were significantly increased in the low， medium， and high dose groups of COE （P<0.05， P<0.01）. Compared with the model group， Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids （P<0.05， P<0.01） and reduce the expression of MUC2， Wnt， and β-catenin. In addition， the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend （P<0.01）. ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5， MUC2， Wnt， and β-catenin and promoting the expression of MUC5AC and MUC6， thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the serum levels of homocysteine(HCY)and cystatin C(Cys-C)in patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)associated renal injury,and to explore the diagnostic value of combined detection of HCY and Cys-C in ANCA-associated renal injury.Methods We selected 70 ANCA-positive patients with renal injury admitted to the Department of Nephrology in our hospital from January 2016 to January 2019.Another 48 patients with ANCA-positive but not complicated with renal injury were in simple ANCA positive group while 50 patients with physical examination who came to the hospital during the same period were in control group.Healthy patients served as the control group.By comparing the differences in the test results of different groups,the area under the curve(AUC)of each test index for ANCA-positive renal injury was determined,and the correlation and diagnostic value of combined detection of HCY and Cys-C for ANCA-related renal injury were calculated.Results The levels of HCY and Cys-C in the ANCA positive combined with renal injury group,the pure ANCA positive group,and the control group differed significantly(P＜0.05).The positive rates of HCY and Cys-C in the two groups were significantly different(P＜0.05).The sensitivity and specificity of HCY and Cys-C in combination for the diagnosis of ANCA-positive related renal injury were significantly higher than those of the above indicators alone(P＜0.05).ROC curve results showed that HCY combined with Cys-C had a better diagnosis for patients with positive ANCA and associated renal injury and a higher correlation.Conclusion HCY combined with Cys-C is closely correlated to ANCA-related renal injury,and the combined detection has a positive effect on the diagnosis of patients with ANCA-positive related renal injury,and has guiding value for the treatment of patients.

AIM: To analyze the causes of blindness and low vision in patients with visual disability in Yangpu District of Shanghai from 2019 to 2022.METHODS:Cross-sectional study. A total of 1 604 patients who participated in the evaluation of visual disability in Shanghai Yangpu District Kongjiang Hospital, from April 2019 to December 2022 were selected for the study. The grade of visual disability and the main causes of blindness and low vision were determined by trained doctors.RESULTS:A total of 804 patients with visual disabilities were identified, with 87.31% aged 60 and above. The causes of visual disability were high myopic retinopathy(30.47%), age-related macular degeneration(23.26%), glaucoma(17.04%), and diabetic retinopathy(11.07%). Glaucoma(36.96%)is the leading cause of blindness.CONCLUSION: The majority of patients with visual disability are aged 60 years and above. More attention should be paid to the elderly population. Comprehensive prevention, treatment and rehabilitation measures should be applied in different diseases based on classification, so as to early reduce the occurrence of visual disability.