Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

Objective:To analyze the risk factors leading to the failure of enhanced recovery after surgery (ERAS) in inflammatory bowel disease (IBD) patients with colorectal resection.Methods:A retrospective case-control study was conducted. Clinical data of consecutive IBD patients who received colorectal resection under ERAS protocol in Jingling Hospital from January 2019 to February 2021 were analyzed. ERAS failure was defined as prolonged postoperative length of hospital stay, or unplanned reoperation, accidental readmission or death within 30 days after operation. The patients were divided into failed ERAS group and successful ERAS group according to whether the ERAS failed. Univariate and Logistic multivariate analyses were performed to identify the risk factors of ERAS failure in IBD patients with colorectal resection.Results:A total of 216 patients were enrolled. There were 65 patients in failed ERAS group and 151 in successful ERAS group. Univariate analysis showed that compared with successful ERAS group, the ratio of body mass index (BMI) <18.5 kg/m 2 (61.5% vs.46.4%, P = 0.041) , the ratio of preoperative nutritional risk screening tools 2002 (NRS-2002) score ≥3 points (69.2% vs. 48.3%, P = 0.005) , the ratio of preoperative modified Glasgow prognostic score (mGPS) = 2 points (30.8% vs. 10.6%, P<0.001) , the ratio of preoperative steroids use within 4 weeks before operation (44.6% vs. 23.8%, P<0.001) , the ratio of neostomy (63.1% vs. 46.4%, P = 0.024) , the ratio of intraoperative infusion volume>3 L (44.6% vs. 21.9%, P = 0.038) were higher in failed ERAS group, while the the ratio of preoperative enteral nutrition was lower (53.8% vs. 68.2%, P = 0.044) . Multivariate analysis showed that preoperative NRS-2002 score ≥3 points ( OR = 2.212, 95% CI: 1.133-4.321, P = 0.020) , mGPS = 2 points ( OR = 3.510, 95% CI: 1.555-7.926, P = 0.003) and preoperative steroids use within 4 weeks before operation ( OR = 2.600, 95% CI: 1.313-5.146, P = 0.006) were the independent risk factors of ERAS failure in IBD patients with colorectal resection. Conclusions:ERAS failure is more likely to occur in IBD patients after colorectal resection with charactertics including preoperative NRS-2002 score ≥3 points, mGPS=2 points, and preoperative steroids use within 4 weeks before operation. Preoperative nutritional preconditioning, perioperative hormone discontinuation, and control of preoperative inflammatory response may promote the successful implementation of ERAS in IBD patients with surgery.

Objective:To analyze the risk factors leading to the failure of enhanced recovery after surgery (ERAS) in inflammatory bowel disease (IBD) patients with colorectal resection.Methods:A retrospective case-control study was conducted. Clinical data of consecutive IBD patients who received colorectal resection under ERAS protocol in Jingling Hospital from January 2019 to February 2021 were analyzed. ERAS failure was defined as prolonged postoperative length of hospital stay, or unplanned reoperation, accidental readmission or death within 30 days after operation. The patients were divided into failed ERAS group and successful ERAS group according to whether the ERAS failed. Univariate and Logistic multivariate analyses were performed to identify the risk factors of ERAS failure in IBD patients with colorectal resection.Results:A total of 216 patients were enrolled. There were 65 patients in failed ERAS group and 151 in successful ERAS group. Univariate analysis showed that compared with successful ERAS group, the ratio of body mass index (BMI) <18.5 kg/m 2 (61.5% vs.46.4%, P = 0.041) , the ratio of preoperative nutritional risk screening tools 2002 (NRS-2002) score ≥3 points (69.2% vs. 48.3%, P = 0.005) , the ratio of preoperative modified Glasgow prognostic score (mGPS) = 2 points (30.8% vs. 10.6%, P<0.001) , the ratio of preoperative steroids use within 4 weeks before operation (44.6% vs. 23.8%, P<0.001) , the ratio of neostomy (63.1% vs. 46.4%, P = 0.024) , the ratio of intraoperative infusion volume>3 L (44.6% vs. 21.9%, P = 0.038) were higher in failed ERAS group, while the the ratio of preoperative enteral nutrition was lower (53.8% vs. 68.2%, P = 0.044) . Multivariate analysis showed that preoperative NRS-2002 score ≥3 points ( OR = 2.212, 95% CI: 1.133-4.321, P = 0.020) , mGPS = 2 points ( OR = 3.510, 95% CI: 1.555-7.926, P = 0.003) and preoperative steroids use within 4 weeks before operation ( OR = 2.600, 95% CI: 1.313-5.146, P = 0.006) were the independent risk factors of ERAS failure in IBD patients with colorectal resection. Conclusions:ERAS failure is more likely to occur in IBD patients after colorectal resection with charactertics including preoperative NRS-2002 score ≥3 points, mGPS=2 points, and preoperative steroids use within 4 weeks before operation. Preoperative nutritional preconditioning, perioperative hormone discontinuation, and control of preoperative inflammatory response may promote the successful implementation of ERAS in IBD patients with surgery.

Objective:To investigate pouch function, quality of life, and their influencing factors after ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) .Methods:Clinical data of 111 patients undergoing IPAA in the UC database at Department of General Surgery, Jinling Hospital from 2014 to 2020 were retrospectively analyzed. Through the questionnaire, pouch functional score (PFS) and Cleveland global quality of life (CGQL) were obtained. These patients were diveided into two groups according to the PFS score. Univariate and multivariate analysis were used to compare the clinical features and reveal the risk factors of PFS.Results:A total of 111 patients were enrolled in this study, including 65 males and 38 females. 63 patients were in the good pouch function group, and 48 in the poor pouch function group. The median score of PFS was 7 (3.0-10.0) . Univariate analysis showed that compared with the good pouch function group, the poor pouch function group had a longer duration of disease before operation[44.5 (21.0-86.0) months vs. 14.0 (5.0-70.0) months, P = 0.005], a shorter follow-up time[16.0 (7.0-28.8) months vs. 26.0 (15.0-39.0) months, P = 0.020], and a higher proportion of pouchitis (29.1% vs. 12.9%, P = 0. 031) . The multivariate logistic regression analysis showed duration of disease before operation ( OR = 0.974, 95% CI: 0.951-0.997, P = 0.030) and pouchitis ( OR = 3.251, 95% CI: 1.168-9.045, P = 0.024) were the independent risk factor of PFS in UC patients.The median CGQL was 0.77 (0.67-0.87) . The median surgical satisfaction score was 9.0 (8.0-10.0) . There was a correlation between CGQL and PFS ( rs = -0.376, P<0.001) . Conclusions:Most patients recover well after IPAA, and are highly satisfied with the operation. A good pouch function has a positive influence on the quality of life.

Objective:To investigate pouch function, quality of life, and their influencing factors after ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) .Methods:Clinical data of 111 patients undergoing IPAA in the UC database at Department of General Surgery, Jinling Hospital from 2014 to 2020 were retrospectively analyzed. Through the questionnaire, pouch functional score (PFS) and Cleveland global quality of life (CGQL) were obtained. These patients were diveided into two groups according to the PFS score. Univariate and multivariate analysis were used to compare the clinical features and reveal the risk factors of PFS.Results:A total of 111 patients were enrolled in this study, including 65 males and 38 females. 63 patients were in the good pouch function group, and 48 in the poor pouch function group. The median score of PFS was 7 (3.0-10.0) . Univariate analysis showed that compared with the good pouch function group, the poor pouch function group had a longer duration of disease before operation[44.5 (21.0-86.0) months vs. 14.0 (5.0-70.0) months, P = 0.005], a shorter follow-up time[16.0 (7.0-28.8) months vs. 26.0 (15.0-39.0) months, P = 0.020], and a higher proportion of pouchitis (29.1% vs. 12.9%, P = 0. 031) . The multivariate logistic regression analysis showed duration of disease before operation ( OR = 0.974, 95% CI: 0.951-0.997, P = 0.030) and pouchitis ( OR = 3.251, 95% CI: 1.168-9.045, P = 0.024) were the independent risk factor of PFS in UC patients.The median CGQL was 0.77 (0.67-0.87) . The median surgical satisfaction score was 9.0 (8.0-10.0) . There was a correlation between CGQL and PFS ( rs = -0.376, P<0.001) . Conclusions:Most patients recover well after IPAA, and are highly satisfied with the operation. A good pouch function has a positive influence on the quality of life.

Background:Acute severe gastrointestinal bleeding is one of the severe complications of Crohn's disease (CD),and clinical data conceming its mechanism,characteristics and treatment are rare.Aims:To analyze the clinical characteristics and prognosis of acute severe gastrointestinal bleeding in CD.Methods:Clinical data of CD patients with acute severe gastrointestinal bleeding from January 2009 to April 2017 at Jinling Hospital were retrospectively analyzed,and the effect of various factors on rebleeding rate was analyzed.Results:Altogether 44 cases had acute severe gastrointestinal bleeding.Small intestine,ileocecum and anastomosis were the main bleeding sites,and 17 cases occurred with obscure bleeding site.History of enterectomy was found in 20 cases.Surgery was performed in 22 cases.Rebleeding occurred in 13 cases,including 11 cases within 1-year.No significant differences in rebleeding rate and 1-year rebleeding rate were found between patients received surgery and non-surgery treatment,patients with emergency surgery and selective surgery (P ＞0.05).Rebleeding rate was significantly lower in patients with bleeding site resected than in paitents with obscure bleeding stie (P ＜ 0.05),however,no significant difference in 1-year rebleeding rate was found betwwen the two groups (P =0.083).Conclusions:The incidence of acute severe gastrointestinal bleeding in CD is rather low,and the major bleeding sites are small intestine (among patients without enterectomy history) and anastomosis (among patients with enterectomy history).Surgery with bleeding site resected can decrease the recurrence of bleeding,which might be a protective factor for preventing rebleeding in CD patients.

OBJECTIVETo compare short-term outcomes of laparoscopic vs. open intestinal resection in patients with Crohn's disease (CD) under enhanced recovery after surgery(ERAS) program.

METHODSClinical data of 51 CD patients receiving laparoscopic surgery under ERAS program at our IBD center between January 2013 and March 2014 were retrospectively analyzed. Laparoscopic cases were matched to those undergoing open surgery from June 2011 to December 2012 with age, gender, location and behavior of disease. Intraoperative and postoperative data were collected.

RESULTSFifty-one laparoscopic cases were matched with 51 open cases. Laparoscopic group had a shorter median length of postoperative hospital stay (7 d vs. 9 d, P=0.034), shorter median time to first passage of gas(45 h vs. 59 h, P=0.024), shorter time to bowel movement(58 h vs. 76 h, P=0.018), less intraoperative estimated blood loss (35 ml vs. 75 ml, P=0.034) and longer median operative time (145 min vs. 105 min, P=0.003). Postoperative complications, reoperation and 30-day re-admission rates were similar and there was no mortality in the two groups.

CONCLUSIONLaparoscopic surgery is a safe and acceptable option for CD patients, and it promotes recovery of gastrointestinal movement and shortens postoperative hospital stay.

Case-Control Studies ; Crohn Disease ; Humans ; Laparoscopy ; Length of Stay ; Operative Time ; Postoperative Complications ; Reoperation ; Retrospective Studies ; Treatment Outcome

Objective To compare short-term outcomes of laparoscopic vs. open intestinal resection in patients with Crohn′s disease (CD) under enhanced recovery after surgery(ERAS) program. Methods Clinical data of 51 CD patients receiving laparoscopic surgery under ERAS program at our IBD center between January 2013 and March 2014 were retrospectively analyzed. Laparoscopic cases were matched to those undergoing open surgery from June 2011 to December 2012 with age , gender, location and behavior of disease. Intraoperative and postoperative data were collected. Results Fifty-one laparoscopic cases were matched with 51 open cases. Laparoscopic group had a shorter median length of postoperative hospital stay (7 d vs. 9 d, P=0.034), shorter median time to first passage of gas(45 h vs. 59 h, P=0.024), shorter time to bowel movement (58 h vs. 76 h, P=0.018), less intraoperative estimated blood loss (35 ml vs. 75 ml, P=0.034) and longer median operative time (145 min vs. 105 min, P=0.003). Postoperative complications, reoperation and 30-day re-admission rates were similar and there was no mortality in the two groups. Conclusion Laparoscopic surgery is a safe and acceptable option for CD patients, and it promotes recovery of gastrointestinal movement and shortens postoperative hospital stay.