ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.024.].

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective:To carry out a scoping review on the development process, main forms, main contents and outcome indicators of decision aids for thyroid cancer patients, providing a theoretical basis for future research in China.Methods:The Arksey and O'Malley's methodological framework was used to analyze the literature. Electronic retrieval was conducted in PubMed, Cochrane Library, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Database, and the search period was from database establishment to August 21, 2023.Results:A total of 11 articles were included. The forms of decision aids included paper decision support manuals, web-based decision support tools, conversation support tools and so on. The main content was to provide disease knowledge and the advantages and disadvantages of various treatment plans, help patients clarify their values, understand patient preferences, and assist doctors and patients make decisions. Outcome indicators involved treatment choice, medical knowledge, decision conflict, decision regret, decision satisfaction, anxiety and so on.Conclusions:The application of decision aids has a positive effect in thyroid cancer patients. Future research should encourage many people to participate in decision-making in order to improve the quality of decision-making for thyroid cancer patients.

Familial glucocorticoid deficiency type 4(FGD4) is a rare autosomal recessive disorder caused by mutations in the nicotinamide nucleotide transhydrogenase(NNT) gene. The article presented clinical data, laboratory results, and genetic mutation findings of a child with FGD4. Additionally, a retrospective analysis of the clinical data of FGD4 patients reported domestically and internationally was conducted, summarizing the types of gene mutations and clinical characteristics. This case identifies novel mutation sites in the NNT gene, providing a basis for the early diagnosis and treatment of FGD4 patients.

Objective:To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). Methods:Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. Results:Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c. 677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group ( P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. Conclusion:The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

Objective:To discuss the protective effect of sodium butyrate(NaB)on acute liver injury in the mice induced by lipopolysaccharide(LPS)combined with D-galactosamine(D-Gal),and to clarify its mechanism.Methods:Thirty male Kunming mice were randomly divided into control group,model group,and NaB group,and there were 10 mice in each group.The mice in NaB group were given 200 mg·kg-1·d-1 NaB,while the mice in control group and model group were given an equal volume of sterile water.The mice in model group and NaB group were intraperitoneally injected with 20 μg·kg-1 LPS and 600 mg·kg-1 D-Gal to induce the acute liver injury models.The body weights and liver weights of the mice in various groups were detcted,and the liver index was calculated.HE staining was used to observe the pathomorphology of liver tissue of the mice in various groups;kits were used to detect the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,and the activities of total superoxide dismutase(T-SOD)and catalase(CAT),and the levels of malondialdehyde(MDA)in liver tissue of the mice in various groups;Western blotting method was used to detect the expression levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in liver tissue of the mice in various groups.Results:There were no significant differences in body weights of the mice among various groups(P>0.05).Compared with control group,the liver index of the mice in model group was significantly increased(P<0.01).Compared with model group,the liver index of the mice in NaB group was significantly decreased(P<0.01).The HE staining results showed that the liver tissue of the mice in control group exhibited normal structure,with clear boundaries of hepatocytes,consistent size,radially arranged around the central vein,and the nucleus located in the center of the cells;in model group,the arrangement of hepatocytes was disordered,the cells were swollen,there were multiple foci of hepatocellular necrosis,inflammatory cell infiltration,and hemorrhage;compared with model group,the cells in NaB group showed improved hepatocellular structure and reduced inflammatory infiltration.Compared with control group,the activities of ALT and AST in serum of the mice in model group were significantly increased(P<0.01);compared with model group,the activities of ALT and AST in serum of the mice in NaB group were significantly decreased(P<0.05 or P<0.01).Compared with control group,the activities of T-SOD and CAT in liver tissue of the mice in model group were significantly decreased(P<0.01),and the level of MDA was significantly increased(P<0.01);compared with model group,the activities of T-SOD and CAT in liver tissue of the mice in NaB group were significantly increased(P<0.05 or P<0.01),and the level of MDA was significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in model group were significantly decreased(P<0.05);compared with model group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in NaB group were significantly increased(P<0.01).Conclusion:NaB has a protective effect on LPS/D-Gal induced acute liver injury in the mice,and its mechanism may be related to the upregulation of the expressions of Nrf2 and HO-1 proteins and the increas of the activity of oxidant enzyme in liver tissue by NaB,thereby reduces the liver oxidative stress level of liver.