OBJECTIVE To investigate the effect and mechanism of morin on alveolar bone resorption in periodontitis mice based on the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS The mice were randomly divided into control group， model group， morin group （40 mg/kg）， SRT1720 （SIRT1 activator） group （5 mg/kg）， and morin+EX527 （SIRT1 inhibitor） group （40 mg/kg morin+7.5 mg/kg EX527）， with 18 mice in each group. Except for control group， mice in other groups were subjected to silk ligation to establish periodontitis model. After successful modeling， mice in each group were treated with corresponding medicinal solutions or normal saline intragastrically or intraperitoneally， once a day， for two consecutive weeks. After the last medication， serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6 and IL-10 were measured. The distance between the cementoenamel junction and alveolar bone crest was determined， and bone volume fraction and bone mineral density were calculated. Pathological changes of periodontal tissue were observed， and the number of osteoclasts was measured. mRNA expressions of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） in periodontal tissue， the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） as well as protein expressions of SIRT1， PGC-1α， and Nrf2 were determined. RESULTS Compared with model group， the alveolar bone resorption and inflammatory cell infiltration in the periodontal tissues of mice were improved in morin group and SRT1720 group. The serum levels of TNF-α， IL-1β and IL-6， the distance between cementoenamel junction and alveolar bone crest， the number of osteoclasts in periodontal tissue， RANKL mRNA expression and the MDA level were decreased， shortened and reduced significantly （ P ＜0.05）； however， serum level of IL-10， bone volume fraction and bone mineral density， OPG mRNA expression in periodontal tissue， SOD level and protein expressions of SIRT1， PGC-1α and Nrf2 were increased significantly （ P ＜0.05）. Compared with morin group， the above pathological changes were significantly aggravated in the morin+EX527 group； and the levels of quantitative indicators were markedly reversed （ P ＜0.05）. CONCLUSIONS Morin may inhibit alveolar bone resorption in periodontitis mice by activating the SIRT1/PGC-1α/Nrf2 pathway to reduce inflammatory reaction and oxidative stress.

OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

This study aimed to investigate the effects of the peptide secreted protein isthmin-1 (ISM1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. ISM1 expression in NSCLC was detected by immunohistochemistry (IHC). ISM1 was overexpressed in lung cancer cell lines by transient transfection of ISM1 plasmids, or establishing ISM1 overexpression stable cell lines, or by treating cells with recombined ISM1 (rISM1). CCK-8 was used to examine cell growth. The intracellular signal transduction pathways regulated by rISM1 were analyzed by transcriptome sequencing, and verified by qRT-PCR and Western blot. The levels of intracellular ROS and apoptosis were further detected using the kit. The results showed that the expression of ISM1 was decreased in human NSCLC tissue samples compared to normal lung tissue samples. Overexpression of ISM1 or rISM1 treatment significantly suppressed the growth of lung cancer cells. RNA sequencing revealed that rISM1 mainly regulated the FoxO signaling pathway. rISM1 treatment decreased the expression of FoxO3 and FoxO1, increased reactive oxygen species (ROS) production, and induced cell apoptosis. These results suggest that ISM1 can inhibit the growth of NSCLC by regulating the FoxO signaling pathway. These findings provide new strategies for cancer therapy.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To explore the application effectiveness of Artificial Intelligence Generated Content(AIGC)in immuno-logy education and optimize teaching models to enhance students'clinical thinking and self-directed learning abilities.Methods:A questionnaire survey was conducted to analyze the current application status of AIGC among 105 university teachers.Taking"TypeⅠHypersensitivity"as an example,integrating AI tools to generate dynamic case scenarios and multimodal resources.Teaching effective-ness was evaluated through classroom practices and student questionnaires.Results:88.32%of teachers recognized AIGC's role in im-proving preparation efficiency,and 61.54%of students reported significantly improved learning outcomes.However,71.43%of teach-ers expressed concerns about increased student dependency,and 55.84%of teachers emphasized challenges in content quality control.Conclusion:AIGC effectively enhances teaching interactivity and personalized learning.Future efforts should focus on optimizing con-tent authority,establishing ethical guidelines,and promoting the development of human-AI collaborative educational models.

Objective:To investigate the role of rheum tanguticum polysaccharide(RTP)in treating ulcerative colitis(UC)by improving intestinal flora.Methods:UC model was established,rats were divided into normal control group,model group and RTP treatment group.The integrity of colonic mucosa,submucosa and muscularis were observed by HE staining.Expressions of TNF-α,IL-6,IL-8 and IL-1β in serum were assessed by ELISA.16S rRNA sequencing was performed to analyze the composition and differences of intestinal flora in rats.Results:UC rats had symptoms such as loose stools,blood in the stool,anal filth,chills and mental malaise.RTP treatment could significantly improve the symptoms and reduce DAI scores(P<0.05).HE staining showed that the colonic struc-ture of UC rats was necrotic and inflammatory cells infiltrated submucosa.RTP treatment could significantly promote the repair and regeneration of mucosal epithelium.RTP could significantly inhibit inflammatory response and downregulate the expression of inflam-matory factors in UC rats(P<0.05).Composition and abundance of intestinal flora in UC rats were significantly different from that of normal control group.Staphylococcus was significantly increased,while Collinsella,Allobaculum,Chlamydia and Holdemanella were significantly decreased.RTP treatment could improve intestinal flora,reduce the abundance of Staphylococcus,and increase the abundance of Collinsella,Allobaculum,Chlamydia and Holdemanella.Conclusion:RTP can be used to treat UC in rats by inhibiting inflammation and improving intestinal flora.

Objective To investigate the diagnostic and therapeutic value of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis therapy in the treatment of acute uncomplicated appendicitis.Methods A retrospective analysis was conducted on the clinical data of 39 patients with acute uncomplicated appendicitis who underwent single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis treatment at the Endoscopy center of the hospital from September 2022 to September 2024.Observe the endoscopic manifestations,the rate of maternal and child basket stone removal,the rate of appendiceal stent implantation,the technical success rate,the clinical success rate,the operation time,the hospital stay,the incidence of complications,the visual analogue scale(VAS)score 6 hours after the operation,and the inflammatory indicators 24 hours after the operation.Results In 28 cases(71.8%),congestion and edema could be seen at the opening of the appendix under colonoscopy.In 10 cases(25.6%),pus could be seen flowing out of the opening of the appendix under colonoscopy.In 32 cases(82.1%),a large amount of pus could be seen in the lumen of the appendix under subscopy.In 20 cases(51.3%),appendiceal fecalith could be seen in the lumen of the appendix under subscopy.The technical success rate of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis treatment was 100.0%(39/39).The operation time was(21.08±7.49)min;Hospital stay:(3.97±2.08)days;Eight cases(20.5%)of patients underwent endoscopic maternal basket stone removal.Appendiceal stent implantation was performed in 14 cases(35.9%)of patients.The clinical success rate is 97.4%(38/39).One patient's clinical symptoms and inflammatory indicators did not improve after the operation,and was transferred to the surgery department for appendectomy.The VAS score of 38 patients was less than 3 points 6 hours after the operation,and the abdominal pain symptoms were significantly relieved.The white blood cell count and the percentage of neutrophils 24 hours after the operation decreased significantly compared with those before the operation,and the differences were statistically significant(P<0.05).None of the 39 patients had complications.The postoperative follow-up was(5.94±4.03)months,and recurrence occurred in 3 cases(7.7%).Conclusion single-use mother-baby choledocoscope-assisted endoscopic retrograde appendicitis therapy is safe and effective in the diagnosis and treatment of acute uncomplicated appendicitis,which is worthy of further promotion and popularization in clinical practice.

Objective To develop an expert consensus on the subcutaneous injection of targeted drugs for breast cancer,to guide clinical nursing practice.Methods A consensus building group was established to create the initial draft of the consensus based on a review of literature.From December 2023 to February 2024,a total of 84 experts from various fields including breast cancer clinical nursing or medical practice,pharmacology,cancer hospital nursing or medical management were invited to participate in 2 rounds of expert letter consultations.Additionally,an on-site expert discussion meeting and an online expert finalization meeting were conducted to finalize the draft"consensus".Results The finalized consensus includes sections covering basic drug introduction,drug injection nursing(injection personnel,injection preparation,injection points,observation and recording after injection),nursing care for adverse reactions,patient education and follow-up.Conclusion This consensus is scientific and practical.It can serve as a valuable reference for clinical practice related to subcutaneous therapy using targeted drugs for breast cancer.

Objective:To evaluate the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) combined with peroral cholangioscopy in the treatment of gallbladder stones with common bile duct stones.Methods:Clinical data of 19 patients with gallbladder stones and common bile duct stones admitted to the Digestive Endoscopy Center, Jilin People’s Hospital from July 2019 to November 2024 were retrospectively analyzed, including 13 males and 6 females, aged (68.2±14.2) years. All patients underwent ERCP combined with peroral cholangioscopy. Perioperative data, including the long diameter of the common bile duct stone, the long diameter of the gallbladder stone, the number of stones, ERCP operative time, gallbladder stone extraction time, stone clearance status, hospitalization duration, and complications, were recorded. Postoperative follow-up was conducted through outpatient visits or telephone consultations to monitor recurrence.Results:The long diameter of the common bile duct stones was (9.55±2.86) mm, and the long diameter of the gallbladder stones was 4.0(3.0, 5.5) mm. Among the 19 patients, 5 had single gallbladder stones, and 14 had multiple stones. The ERCP operative time was (49.0±18.4) min, and the gallbladder stone extraction time was (25.0±11.7) min. The methods used for handling the gallbladder neck were as follows: two cases involved stone removal after 6 mm balloon dilation; six cases involved stone removal after metal stent placement; three cases involved the placement of a plastic stent in the gallbladder for three months, followed by stone extraction using ERCP combined with peroral cholangioscopy; eight cases were treated directly for stone removal without specific procedures. Among the 19 patients, 11 completed stone removal within one treatment, while eight required a second treatment. All patients had complete clearance of both common bile duct and gallbladder stones under direct peroral cholangioscopy. No severe complications occurred postoperatively, although two cases developed post-ERCP pancreatitis. The postoperative hospitalization time was 8.0 (6.0, 10.0) d. The follow-up duration for the 19 patients was 14.0 (8.5, 20.0) months. One patient had a recurrence of gallbladder stones 12 months postoperatively, while no other patients had recurrence at the final follow-up.Conclusion:ERCP combined with peroral cholangioscopy is a safe and feasible approach for treating gallbladder stones with common bile duct stones.

Objective:To analyze the efficacy of endovascular treatment for venous outflow tract obstruction after liver transplantation.Methods:A retrospective analysis was conducted on the data of 7 patients with venous outflow tract obstruction after liver transplantation admitted to Beijing Friendship Hospital, Capital Medical University from November 2020 to December 2024. Among them, there were 5 males and 2 females, with the age of (22.3±8.1) years. The primary diseases included 2 cases of Budd-Chiari syndrome, 1 case of hepatic veno-occlusive disease, 1 case of portal veno-hepatic sinus vascular disease, 1 case of ornithine carbamoyltransferase deficiency, 1 case of primary biliary cirrhosis, and 1 case of autoimmune cirrhosis. Analyze the patient's clinical manifestations, obstruction of venous outflow tract, hemoglobin levels within one week before and one week after the operation, endovascular treatment conditions, and intraoperative complications such as abdominal hemorrhage and vascular injury. Ultrasound was used to measure the depth of ascites and pleural effusion. All patients were followed up immediately after the operation through phone calls or follow-up visits. The clinical symptoms, abdominal vascular ultrasound, enhanced CT and survival status of the patients were followed up.Results:All 7 patients were diagnosed with venous outflow tract obstruction by intraoperative angiography, including 1 cases of inferior vena cava obstruction, 2 cases of hepatic vein obstruction, and 4 cases of vena cava combined with hepatic vein obstruction. A total of 12 endovascular treatments were performed on 7 patients. Among them, 4 patients received balloon dilation and angioplasty once, 1 patient received balloon dilation and angioplasty twice, 1 patient underwent hepatic vein stent implantation after 2 hepatic vein balloon dilation and angioplasty, and 1 patient underwent intrahepatic portosystemic shunt via jugular vein after 2 hepatic vein balloon dilation and angioplasty. The abdominal distensionof the patients were all relieved after the operation, the ascites and pleural effusion decreased, and the edema symptoms of the lower extremities disappeared. There were no intraoperative complications. The preoperative hemoglobin of 7 patients was (113.4±34.0) g/L, and the postoperative hemoglobin was (126.6±34.8) g/L, which increased significantly compared with that before the operation, and the difference was statistically significant ( t=-0.71, P=0.038). Seven patients were followed up for 6 to 24 months, with a median of 12 months. None of them had obvious symptoms including abdominal distension. Abdominal ultrasound and CT indicated that the blood flow of the transplanted liver was unobstructed, and no patient died. Conclusion:Venous outflow tract obstruction after liver transplantation can cause severe symptoms. Endovascular treatment is an effective treatment for venous outflow tract obstruction after liver transplantation.