The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective To investigate the morphological and proteomic differences in exosomes(EXOs)during the stor-age of leukocyte-free apheresis platelets(LFA-Plt),evaluate the quality of platelets in storage and predict the function of EXOs at different storage periods.Methods EXOs were isolated by ultracentrifugation,then the morphological observation was performed by electron microscope.Particle size analysis and WB protein index detection were performed.4D Label-free quantitative proteomics technology was used to perform quantitative and bioinformatics analysis on identified proteins.Protein differential analysis on the LFA-Plt EXO between group day 3 and day 5 was performed,and GO function and KEGG path-way enrichment analysis on differential proteins was conducted.Results Cup shaped,CD9/TSG101 enriched and Calnexin(-)EXO was successfully obtained.The particle size(nm)of LFA-Plt EXO for day 3 and day 5 were(82.2±19.6)and(83.4±19.4)respectively,and the protein concentration(μ g/uL)were(0.55±0.13)and(0.51±0.08)respectively,with no statistically significant difference between two groups(P＞0.05).1 504 proteins were identified in all samples.GO func-tional enrichment analysis showed that the LFA-Plt EXO proteins were mainly concentrated in the cell membrane,extracel-lular domain and proteasome core complex,and were related to the binding ability of proteins,ATP,calcium ions and GTP,and mainly participated in processes such as redox,protein hydrolysis and signal transduction.KEGG functional annotation showed that the EXO proteins mainly participated in material transportation and catabolism,genetic information processing,and were closely related to human tumors and viral bacterial infections,affecting the metabolism of human immune system.Compared with day 3,day 5 EXO showed significant up-regulation in 16 proteins.The GO enrichment analysis showed that 16 upregulated proteins were mainly associated with adenosine homocysteine activity and 6-phosphofructose kinase activity,and were mainly involved in the metabolism of organic nitrogen compound.KEGG enrichment pathway analysis showed that the most important function of upregulated proteins was participating in signaling pathway for oocyte maturation mediated by progesterone.Conclusion Under the preparation and storage conditions of LFA-Plt in our center,platelet quality can be relatively stable.The functions of EXO proteins varies with different storage periods,which may affect the effectiveness of platelet transfusion.

AIM:To investigate the effects and mechanism of long noncoding RNA PCED1B antisense strand 1(lncRNA PCED1B-AS1)on the proliferation,migration,invasion and apoptosis of papillary thyroid carcinoma(PTC)cells.METHODS:Human PTC cells were cultured in vitro.The expression of PCED1B-AS1 and fused in sarcoma(FUS)was measured by RT-qPCR.The effects of knockdown/overexpression of PCED1B-AS1/FUS on the migration and invasion of PTC cells were detected via Transwell assay.The effects of knockdown/overexpression of PCED1B-AS1/FUS on PTC cell proliferation were analysed via CCK-8 and plate colony assay.The effect of knockdown PCED1B-AS1 on PTC cell apoptosis was determined by flow cytometry.The target binding of PCED1B-AS1 and FUS was determined with bioin-formatics and RNA immunoprecipitation(RIP)experiments.Fluorescence in situ hybridization experiment was performed to verify whether PCED1B-AS1 colocalises with FUS.The mitogen-activated protein kinase(MAPK)signaling pathway-re-lated proteins were detected via Western blot.RESULTS:(1)PCED1B-AS1 expression was significantly higher and FUS expression was significantly lower in PTC cells compared with normal thyroid Nthy-ori3-1 cell(P<0.05).(2)Knockdown of PCED1B-AS1 and overexpression of FUS inhibited PTC cell migration,invasion and proliferation,and promoted apopto-sis(P<0.05).(3)Bioinformatics analysis and RIP assay verified the existence of targeted binding of PCED1B-AS1 to FUS(P<0.05).(4)PCED1B-AS1 and FUS colocalised in the cytoplasm.(5)Inhibition of PCED1B-AS1 decreased the expression of MAPK signaling pathway-related proteins p-ERK 1/2,p-JNK and p-P38(P<0.05).CONCLUSION:ln-cRNA PCED1B-AS1 inhibits the proliferation,migration and invasion,and promotes the apoptosis of PTC cells,and its mechanism may be related to the expression of FUS and the MAPK signaling pathway.

Objective:To share the results of laparoscopic assisted proximal gastrectomy λ- shaped modified double tract reconstruction.Method:This study retrospectively included 3 patients during January 2024 from the Department of Gastric Surgery at the First Affiliated Hospital of Nanjing Medical University using the λ-shaped modified double tract reconstruction. The procedure of the λ-shaped modified double tract reconstruction is as follows. After completing proximal gastrectomy, the jejunum is transected 15 cm from the Treitz ligament. A suture is made 18-20 cm from the distal jejunum to mark the esophagojejunal anastomosis site. A circular stapler anvil is inserted through the distal jejunum, and the remaining end of the jejunum is turned to the right. The circular stapler is pierced through the marked site for an esophagojejunal end-to-end anastomosis, which is reinforced with a barbed suture continuously. A 60mm linear stapler is used to close the remaining end of the jejunum. We then mark the gastric side of the gastrojejunal anastomosis with suture in the middle of the anterior wall of the residual stomach, and mark the jejunal side of the gastrojejunal anastomosis at a distance of about 2 cm and 8 cm from the residual end of the distal jejunum. We make an opening of about 0.5 cm and use a 60 mm linear stapler to perform anastomosis on the jejunal side of the anterior wall of the residual stomach according to the markings, so that the distance between the esophagojejunal anastomosis and the gastrojejunal anastomosis is 10-12 cm. The common opening is closed with barbed wire. About 50 cm below the esophagojejunal anastomosis, the small intestine opening is anastomosed side to side using a circular stapler and the common opening is closed. Return the jejunum into the abdominal cavity to complete the reconstruction of the λ-shaped double tract reconstruction. We analyzed the surgery and postoperative conditions, including surgery time, anastomosis time, intraoperative bleeding, tumor size and pathology, postoperative mobilization, passage of gas and water intake time, discharge time, postoperative complications, and postoperative gastrointestinal imaging to observe the passage of food through the gastric and intestinal loops.Results:Three patients successfully received laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction. The surgical time was 155 minutes, 240 minutes, and 160 minutes, respectively; The postoperative time for first ambulation was 20 hours, 18 hours, and 26 hours, respectively. The time for passage of gas was 59 hours, 83 hours, and 75 hours, respectively. The drinking time was 66 hours, 87 hours, and 90 hours, respectively. The postoperative discharge days were all 7 days. No surgical related complications occurred. On the 6th day and 3 months after surgery, gastrointestinal angiography was performed. The contrast agent passed smoothly through the jejunal loop and residual stomach jejunal loop, and both sides were unobstructed. No contrast agent was found to retrograde to the esophagojejunal anastomosis.Conclusion:Laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction is safe and feasible, as it improves the diversion of food through the residual stomach while ensuring anti-reflux effects.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To compare the clinical efficacy of arthroscopic partial and complete repair for massive rotator cuff tears.Methods:A total of 32 patients who underwent arthroscopic partial repair of massive rotator cuff tears in the Department of Sports Medicine, Peking University Third Hospital from March 2016 to December 2019 were retrospectively analyzed, including 15 males and 17 females, aged 62±6.8 years (range, 51-77 years), with 5 cases on the left side and 27 cases on the right side. Cause of injury: 4 cases were injured by car accident, 8 were injured by fall, and 20 had no obvious cause. 32 patients who underwent arthroscopic complete repair of massive rotator cuff tears during the same period were included according to a sample size of 1∶1 matched based on age, sex, tear size and fat infiltration index. Clinical outcomes were evaluated using the visual analogue scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) shoulder score, Simple Shoulder Test (SST) score, and range of motion. Fatty infiltration and cuff healing were assessed using the Goutallier and Sugaya classifications on MRI, respectively.Results:All patients successfully completed the surgery and were followed up for 46.1±11.3 months (range, 36-72 months). Preoperative and final follow-up VAS scores were 6.6±1.8 and 1.6±1.1 in the complete repair group, and 6.4±1.9 and 1.4±1.3 in the partial repair group. Both groups showed significant postoperative improvement ( P<0.05), with no significant difference between groups at the final follow-up ( t=-0.729, P=0.468). The ASES score, UCLA shoulder score, and SST at the final follow-up were 81.7±6.5, 28.6±2.9, and 9.8±2.5, respectively, in the complete repair group, and 82.4±7.3, 28.1±2.6, and 9.1±1.9 in the partial repair group, and the difference between the groups was not statistically significant ( P>0.05). In the complete repair group, one case underwent reverse shoulder replacement for rotator cuff re-tear two years after surgery, and one case developed pseudoparalysis for rotator cuff re-tear 8 months after surgery but had no significant pain and did not receive further treatment; in the partial repair group, two cases underwent tendon transposition surgery for shoulder pain. Conclusion:Arthroscopic partial repair improves shoulder function and reduces pain in patients with massive rotator cuff tears, with similar efficacy to complete repair and has high surgical safety.

Objective:To share the results of laparoscopic assisted proximal gastrectomy λ- shaped modified double tract reconstruction.Method:This study retrospectively included 3 patients during January 2024 from the Department of Gastric Surgery at the First Affiliated Hospital of Nanjing Medical University using the λ-shaped modified double tract reconstruction. The procedure of the λ-shaped modified double tract reconstruction is as follows. After completing proximal gastrectomy, the jejunum is transected 15 cm from the Treitz ligament. A suture is made 18-20 cm from the distal jejunum to mark the esophagojejunal anastomosis site. A circular stapler anvil is inserted through the distal jejunum, and the remaining end of the jejunum is turned to the right. The circular stapler is pierced through the marked site for an esophagojejunal end-to-end anastomosis, which is reinforced with a barbed suture continuously. A 60mm linear stapler is used to close the remaining end of the jejunum. We then mark the gastric side of the gastrojejunal anastomosis with suture in the middle of the anterior wall of the residual stomach, and mark the jejunal side of the gastrojejunal anastomosis at a distance of about 2 cm and 8 cm from the residual end of the distal jejunum. We make an opening of about 0.5 cm and use a 60 mm linear stapler to perform anastomosis on the jejunal side of the anterior wall of the residual stomach according to the markings, so that the distance between the esophagojejunal anastomosis and the gastrojejunal anastomosis is 10-12 cm. The common opening is closed with barbed wire. About 50 cm below the esophagojejunal anastomosis, the small intestine opening is anastomosed side to side using a circular stapler and the common opening is closed. Return the jejunum into the abdominal cavity to complete the reconstruction of the λ-shaped double tract reconstruction. We analyzed the surgery and postoperative conditions, including surgery time, anastomosis time, intraoperative bleeding, tumor size and pathology, postoperative mobilization, passage of gas and water intake time, discharge time, postoperative complications, and postoperative gastrointestinal imaging to observe the passage of food through the gastric and intestinal loops.Results:Three patients successfully received laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction. The surgical time was 155 minutes, 240 minutes, and 160 minutes, respectively; The postoperative time for first ambulation was 20 hours, 18 hours, and 26 hours, respectively. The time for passage of gas was 59 hours, 83 hours, and 75 hours, respectively. The drinking time was 66 hours, 87 hours, and 90 hours, respectively. The postoperative discharge days were all 7 days. No surgical related complications occurred. On the 6th day and 3 months after surgery, gastrointestinal angiography was performed. The contrast agent passed smoothly through the jejunal loop and residual stomach jejunal loop, and both sides were unobstructed. No contrast agent was found to retrograde to the esophagojejunal anastomosis.Conclusion:Laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction is safe and feasible, as it improves the diversion of food through the residual stomach while ensuring anti-reflux effects.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To systematically evaluate the qualitative study on the sexual health needs of patients with ostomy based on theoretical domains framework (TDF), providing reference for clinical care and practice.Methods:A comprehensive search was conducted for qualitative studies on the sexual experience of ostomy patients in the China National Knowledge Infrastructure, Wanfang Data, VIP database, China Biology Medicine, PubMed, Embase, Web of Science, Cochrane Library, Elton B. Stephens Company (EBSCO), Elsevier Scopus (SCOPUS), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, with a timeframe of from the creation of the databases to April 15, 2024. The Joanna Briggs Institute Evidence Based Healthcare Center Critical Appraisal Tool was used to evaluate the quality of eligible literature, and the theoretical domain framework was used to integrate the extracted results.Results:A total of 11 articles were included and 51 results were extracted. Based on the theoretical framework, map the sexual health needs of ostomy patients to six core areas: knowledge, skills, optimism, outcome beliefs, environment and resources, and emotions.Conclusions:Medical staff should pay attention to the sexual health needs of patients with intestinal stomas. Based on the six core areas of knowledge, skills, optimism, outcome beliefs, environment and resources, and emotions, they should deeply explore the factors that affect their sexual health, provide professional guidance and comprehensive care, and improve their sexual health level and quality of life.

Objective To investigate the effect of Trichomonas vaginalis macrophage migration inhibitory factor (TvMIF) on THP-1 macrophages.. Methods Recombinant TvMIF protein was prokaryotic expressed and purified, and endotoxin was removed after identification. Following exposure to TvMIF at concentrations of 0, 1, 5, 10, 50 and 100 ng/mL, the cytotoxicity of the recombinant TvMIF protein to THP-1 macrophages was tested using cell counting kit (CCK)-8 assay, and the apoptosis of THP-1 macrophages and reactive oxygen species (ROS) were detected using flow cytometry. The relative expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β) and IL-18 genes was quantified using real-time fluorescent quantitative PCR (qPCR) assay, and the expression of caspase-1, NLRP3, gasdermin D (GSDMD), gasdermin D N-terminal (GSDMD-NT) and pro-IL-1β proteins were determined using Western blotting assay. Results Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) displayed successful expression and purification of the recombinant TvMIF protein with a molecular weight of 15.5 kDa, and the endotoxin activity assay showed the successful removal of endotoxin in the recombinant TvMIF protein (endotoxin concentration < 0.1 EU/mL), which was feasible for the subsequent studies on protein functions. Flow cytometry revealed that the recombinant TvMIF protein at a concentration of 10 ng/mL and less promoted the apoptosis of THP-1 macrophages, and the highest apoptotic rate of THP-1 macrophages was seen following exposure to the recombinant TvMIF protein at a concentration of 5 ng/mL, while the recombinant TvMIF protein at concentrations of 50 and100 ng/mL inhibited the apoptosis of THP-1 macrophages. Exposure to the recombinant TvMIF protein at a concentration 1 ng/mL resulted in increased ROS levels in THP-1 macrophages. qPCR assay quantified significantly elevated caspase-1, NLRP3, IL-18 and IL-1β expression in THP-1 macrophages 8 hours post-treatment with the recombinant TvMIF protein at a concentration 1 ng/mL, and Western blotting determined increased caspase-1, NLRP3, pro-IL-1β, GSDMD and GSDMD-NT protein expression in THP-1 macrophages following exposure to the recombinant TvMIF protein at a concentration 1 ng/mL. Pretreatment with MCC950 significantly reduced GSDMD and GSDMD-NT protein expression. Conclusions High-concentration recombinant TvMIF protein inhibits macrophage apoptosis, while low-concentration recombinant TvMIF protein activates NLRP3 inflammasome and promotes macrophage pyroptosis.