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 analyze the correlation between serum interleukin-37(IL-37)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)with disease severity in chronic obstructive pulmonary disease(COPD)patients with systemic inflammatory response syndrome(SIRS),and evaluate their combined predictive value for prognosis.Methods A total of 150 patients with COPD and SIRS in Zigong First People's Hospital from January 2023 to March 2024 were selected as the study group,and 150 patients with COPD were selected as the control group.The groups were compared for general data and serum IL-37 and NLRP3 levels upon admission.The serum IL-37 and NLRP3 levels of patients with different disease severities in the study group were compared to analyze their correlation with disease severity.28-day prognosis of both groups was compared,and the serum IL-37 and NLRP3 levels of patients with poor and good prognosis in the study group were analyzed.Univariate and multivariate Logistic regression was used to assess factors influencing poor prognosis in COPD patients with SIRS.The predictive value of serum IL-37 and NLRP3 for poor prognosis was evaluated,and their interactive effects on patient outcomes were analyzed.Results The study group's serum IL-37 and NLRP3 levels were higher upon admission compared to the control group(P<0.05);serum IL-37 and NLRP3 levels in extremely severe patients were higher than those in severe,moderate,and mild patients,with severe patients higher than moderate and mild patients,and moderate patients higher than mild patients(P<0.05);serum IL-37 and NLRP3 levels at admission were positively correlated with the disease severity of COPD patients with SIRS(P<0.05);patients with poor prognosis had higher serum IL-37 and NLRP3 levels upon admission compared to those with good prognosis(P<0.05);serum IL-37 and NLRP3 levels at admission were independent risk factors for poor prognosis in COPD patients with SIRS(P<0.05);the AUC for predicting poor prognosis using serum IL-37 and NLRP3 alone were 0.805 and 0.834,respectively,while the combined AUC was 0.920,which was higher than the individual AUCs(P<0.05);interaction analysis showed that high serum IL-37 and NLRP3 levels exhibited a positive super-multiplicative interaction in the prognosis of COPD patients with SIRS(P<0.05).Conclusion Serum IL-37 and NLRP3 levels in COPD patients with SIRS were positively correlated with disease severity,and the combined serum IL-37 and NLRP3 showed high predictive efficacy for patient prognosis.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

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 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.

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.