OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

Objective:To evaluate the clinical characteristics of Crohn's disease (CD) patients with secondary upper gastrointestinal fistulas and analyze risk factors for recurrence.Methods:A restrospective observational research method was performed. Clinical data of CD patients with secondary upper gastrointestinal fistulas treated at Eastern Theater General Hospital of PLA from January 2010 to August 2024 were analyzed. Based on postoperative recurrence of upper gastrointestinal fistulas, the patients were divided into recurrence group and non-recurrence group. Differences in clinical data between the two groups were compared, and further multivariate Logistic regression analysis was used to identify the risk factors for fistula recurrence.Results:A total of 72 CD patients with secondary upper gastrointestinal fistulas were included, consisting of 48 males and 24 females, with a mean age of 39±12 years and a disease duration of 97±56 months, accounting for 2.8% of all CD patients undergoing surgeries during the same period. Among these patients, 75 upper gastrointestinal fistulas from 72 patients were identified, including 67 patients of simple duodenal fistula, 2 of simple gastric fistula, and 3 of double fistulas (2 of double duodenal fistulas and 1 of duodenal fistula combined with gastric fistula) .The preoperative diagnostic positivity rates were 55.6% (40/72) for gastroscopy, 54.2% (39/72) for upper gastrointestinal contrast imaging, 22.2% (16/72) for abdominal CT, and 22.2% (16/72) for colonoscopy. A history of biologic therapy was present in 33.3% (24/72) of patients, but none achieved fistula healing. All 72 patients underwent surgical treatment, with primary lesion surgical approaches including resection with anastomosis (37 patients, 51.4%) and resection with stoma (35 patients, 48.6%). Except for one gastric fistula treated by resection, all other fistulas underwent primary repair. During a median follow-up of 69 (40, 113) months, 8 patients (11.1%) required reoperation due to recurrent upper gastrointestinal fistulas (classified as the recurrence group), while the remaining 64 patients were assigned to the non-recurrence group. Univariate analysis revealed that the recurrence group had a higher proportion of patients aged 30-40 years ( P = 0.003), malnutrition ( P = 0.040), and anastomosis near the duodenum ( P = 0.047), but a lower proportion of postoperative biologic use ( P = 0.007) .Multivariate Logistic regression analysis showed that malnutrition and anastomosis near the duodenum were not the risk factors for duodenal fistula recurrence (both P > 0.05) . Conclusions:Upper gastrointestinal fistulas secondary to CD are rare, predominantly presenting as simple duodenal fistulas. Diagnosis primarily relies on gastroscopy and gastrointestinal contrast imaging. Biologic therapy shows poor efficacy, and most patients do not recur after the primary repair surgery of duodenal fistulas.

Objective:To evaluate the clinical characteristics of Crohn's disease (CD) patients with secondary upper gastrointestinal fistulas and analyze risk factors for recurrence.Methods:A restrospective observational research method was performed. Clinical data of CD patients with secondary upper gastrointestinal fistulas treated at Eastern Theater General Hospital of PLA from January 2010 to August 2024 were analyzed. Based on postoperative recurrence of upper gastrointestinal fistulas, the patients were divided into recurrence group and non-recurrence group. Differences in clinical data between the two groups were compared, and further multivariate Logistic regression analysis was used to identify the risk factors for fistula recurrence.Results:A total of 72 CD patients with secondary upper gastrointestinal fistulas were included, consisting of 48 males and 24 females, with a mean age of 39±12 years and a disease duration of 97±56 months, accounting for 2.8% of all CD patients undergoing surgeries during the same period. Among these patients, 75 upper gastrointestinal fistulas from 72 patients were identified, including 67 patients of simple duodenal fistula, 2 of simple gastric fistula, and 3 of double fistulas (2 of double duodenal fistulas and 1 of duodenal fistula combined with gastric fistula) .The preoperative diagnostic positivity rates were 55.6% (40/72) for gastroscopy, 54.2% (39/72) for upper gastrointestinal contrast imaging, 22.2% (16/72) for abdominal CT, and 22.2% (16/72) for colonoscopy. A history of biologic therapy was present in 33.3% (24/72) of patients, but none achieved fistula healing. All 72 patients underwent surgical treatment, with primary lesion surgical approaches including resection with anastomosis (37 patients, 51.4%) and resection with stoma (35 patients, 48.6%). Except for one gastric fistula treated by resection, all other fistulas underwent primary repair. During a median follow-up of 69 (40, 113) months, 8 patients (11.1%) required reoperation due to recurrent upper gastrointestinal fistulas (classified as the recurrence group), while the remaining 64 patients were assigned to the non-recurrence group. Univariate analysis revealed that the recurrence group had a higher proportion of patients aged 30-40 years ( P = 0.003), malnutrition ( P = 0.040), and anastomosis near the duodenum ( P = 0.047), but a lower proportion of postoperative biologic use ( P = 0.007) .Multivariate Logistic regression analysis showed that malnutrition and anastomosis near the duodenum were not the risk factors for duodenal fistula recurrence (both P > 0.05) . Conclusions:Upper gastrointestinal fistulas secondary to CD are rare, predominantly presenting as simple duodenal fistulas. Diagnosis primarily relies on gastroscopy and gastrointestinal contrast imaging. Biologic therapy shows poor efficacy, and most patients do not recur after the primary repair surgery of duodenal fistulas.

BACKGROUND:Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis,but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis. OBJECTIVE:To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach. METHODS:The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies.The outcome event of osteonecrosis was derived from the FinnGen Biobank database.Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis.Causal inference was conducted using inverse variance weighting,MR-Egger,and weighted median methods.F-statistic was calculated to ensure the robustness of instrumental variables.Cochran's Q test and leave-one-out method were used for heterogeneity testing.MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing.PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results. RESULTS AND CONCLUSION:Causal relationships were found between serum selenium,phosphate,vitamin C,vitamin E,and osteonecrosis through Mendelian randomization analysis.Serum selenium,vitamin C,and vitamin E were found to have a protective effect on osteonecrosis,while excessive intake of phosphate increased the risk of osteonecrosis.No heterogeneity or horizontal pleiotropy was observed during the study,and Mendelian randomization statistical power(Power value>80%)indicated the reliability of the aforementioned four results.These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis.

Objective:To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support.Methods:It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results:Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO 2/FiO 2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH 2O (1 cmH 2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis ( P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO ( P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO ( P<0.05) and gradually increased from 24 h after ECMO. Conclusions:The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Objective:To investigate the efficacy of modified anti-mesenteric functional end-to-end anastomosis (Kono-S) on Crohn's disease (CD) .Methods:A retrospective cohort study was conducted. Clinical data of CD patients who underwent modified Kono-S surgery at Jinling Hospital of Medical School of Nanjing University from January 2020 to April 2023 were collected. Primary endpoint was postoperative endoscopic recurrence rate. Secondary endpoints were postoperative complication rate within 30 days, postoperative clinical recurrence rate, and factors influencing endoscopic recurrence. Endoscopic recurrence was defined as Rutgeerts score of i2b or higher at the anastomotic stomas. Clinical recurrence was defined as Crohn's disease activity index (CDAI) >150 points based on the endoscopic recurrence. Patients were divided into recurrence and non-recurrence groups according to the endoscopic recurrence, and univariate analysis and multivariate Logistic regression analysis were used to identify factors of endoscopic recurrence.Results:A total of 75 CD patients [46 men, 29 women; mean age, (38.5 ± 14.1) years; mean CDAI score, (71.8 ± 22.6) points] were included. Sixty patients underwent partial small bowel resection, 6 underwent ileocecal resection, 6 underwent right hemicolectomy, and 3 underwent subtotal colectomy. The operation time was (116 ± 27) minutes, and the time of the modified Kono-S anastomosis construction was (24 ± 4) minutes. Incidence rate of Clavien-Dindo grade Ⅱ or higher complications was 12% (9/75) within 30 days postoperatively, with no intra-abdominal infectious complication and death. During the follow-up period of 15 (6, 23) months, 39 patients underwent endoscopic examination, and the endoscopic recurrence rate was 20.5% (8/39) and clinical recurrence rate was 2.6% (1/39) . Male was identified as the independent risk factor for endoscopic recurrence ( OR = 18.7, 95% CI: 1.7-200.8, P = 0.02) . Conclusion:Modified Kono-S is a safe and convenient treatment for CD with a low risk of anastomotic endoscopic recurrence, however, male patients are more prone to the recurrence.

Objective:To investigate the impact of preoperative anti-tumor necrosis factor (anti-TNF) -α monoclonal antibody therapy on postoperative infectious complications in patients with Crohn′s disease (CD) after intestinal resection with primary anastomosis.Methods:The clinical data of CD patients who underwent intestinal resection with primary anastomosis at Jinling Hospital from January 2017 to December 2021 were retrospectively analyzed. Propensity score matching was used to match patients who did not receive or received anti-TNF treatment within 12 weeks before surgery at a ratio of 1∶2. The relationship between preoperative anti-TNF treatment and postoperative infectious complications was analyzed, and the related risk factors of postoperative infectious complications were analyzed by logistic regression analysis.Results:A total of 501 patients with CD who underwent resection and primary anastomosis were collected. After propensity score matching, 135 patients with CD were included in the analysis, 45 in the treatment group and 90 in the control group. There were no significant differences in the incidence of overall postoperative complications (24.4% vs. 25.6%, P = 0.889) and infectious complications (13.3% vs. 14.4%, P = 0.861) between the two groups. Previous history of intestinal resection due to CD and surgical site of colon were independent risk factors for infectious complications within 30 days after surgery. Conclusion:Previous history of intestinal resection of CD and colon surgery are associated with infectious complications after intestinal resection with primary anastomosis.

Objective:To investigate the efficacy of modified anti-mesenteric functional end-to-end anastomosis (Kono-S) on Crohn's disease (CD) .Methods:A retrospective cohort study was conducted. Clinical data of CD patients who underwent modified Kono-S surgery at Jinling Hospital of Medical School of Nanjing University from January 2020 to April 2023 were collected. Primary endpoint was postoperative endoscopic recurrence rate. Secondary endpoints were postoperative complication rate within 30 days, postoperative clinical recurrence rate, and factors influencing endoscopic recurrence. Endoscopic recurrence was defined as Rutgeerts score of i2b or higher at the anastomotic stomas. Clinical recurrence was defined as Crohn's disease activity index (CDAI) >150 points based on the endoscopic recurrence. Patients were divided into recurrence and non-recurrence groups according to the endoscopic recurrence, and univariate analysis and multivariate Logistic regression analysis were used to identify factors of endoscopic recurrence.Results:A total of 75 CD patients [46 men, 29 women; mean age, (38.5 ± 14.1) years; mean CDAI score, (71.8 ± 22.6) points] were included. Sixty patients underwent partial small bowel resection, 6 underwent ileocecal resection, 6 underwent right hemicolectomy, and 3 underwent subtotal colectomy. The operation time was (116 ± 27) minutes, and the time of the modified Kono-S anastomosis construction was (24 ± 4) minutes. Incidence rate of Clavien-Dindo grade Ⅱ or higher complications was 12% (9/75) within 30 days postoperatively, with no intra-abdominal infectious complication and death. During the follow-up period of 15 (6, 23) months, 39 patients underwent endoscopic examination, and the endoscopic recurrence rate was 20.5% (8/39) and clinical recurrence rate was 2.6% (1/39) . Male was identified as the independent risk factor for endoscopic recurrence ( OR = 18.7, 95% CI: 1.7-200.8, P = 0.02) . Conclusion:Modified Kono-S is a safe and convenient treatment for CD with a low risk of anastomotic endoscopic recurrence, however, male patients are more prone to the recurrence.

Objective:To investigate the impact of preoperative anti-tumor necrosis factor (anti-TNF) -α monoclonal antibody therapy on postoperative infectious complications in patients with Crohn′s disease (CD) after intestinal resection with primary anastomosis.Methods:The clinical data of CD patients who underwent intestinal resection with primary anastomosis at Jinling Hospital from January 2017 to December 2021 were retrospectively analyzed. Propensity score matching was used to match patients who did not receive or received anti-TNF treatment within 12 weeks before surgery at a ratio of 1∶2. The relationship between preoperative anti-TNF treatment and postoperative infectious complications was analyzed, and the related risk factors of postoperative infectious complications were analyzed by logistic regression analysis.Results:A total of 501 patients with CD who underwent resection and primary anastomosis were collected. After propensity score matching, 135 patients with CD were included in the analysis, 45 in the treatment group and 90 in the control group. There were no significant differences in the incidence of overall postoperative complications (24.4% vs. 25.6%, P = 0.889) and infectious complications (13.3% vs. 14.4%, P = 0.861) between the two groups. Previous history of intestinal resection due to CD and surgical site of colon were independent risk factors for infectious complications within 30 days after surgery. Conclusion:Previous history of intestinal resection of CD and colon surgery are associated with infectious complications after intestinal resection with primary anastomosis.

Strictureplasty (SP) is a surgical technique that applies to patients with obstructive Crohn′s disease (CD) caused by intestinal stricture. It can relieve the intestinal obstruction without removing the intestinal canal, preserve the bowel length as much as possible, and avoid the occurrence of short bowel syndrome. With the continuous improvement of surgical techniques and the requirement for the treatment of complicated intestinal strictures, SP has gradually evolved from the original Heineke-Mikulicz (H-M) and Finney procedures to various improved and innovative versions.And the research on the efficacy and safety of different procedures is increasing gradually. This paper will review and discuss the research progress of SP in CD.