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 explore the factors affecting changes of disc angle (ΔDA) during oblique lateral interbody fusion (OLIF) and establish a predictive model of ΔDA.Methods:This retrospective study included 119 patients with 174 segments undergoing OLIF procedures between July 2017 and August 2019 in Beijing Jishuitan Hospital. 45 males and 74 females with an average age of 62.1±9.8 years (33-86 years) were included. The lordotic cages were all 6 degrees. Radiographic parameters included preoperative and postoperative disc angle (DA), disc height (DH), ΔDA on flexion-extension views (ΔDA-FE), cage location and cage inclination. Pearson correlation coefficient and machine-learning techniques were utilized to identify factors related to ΔDA. Based on machine leaning techniques, ten-fold cross-validation for model training and validation were used to develop a predictive linear model for ΔDA.Results:The average ΔDA was 3.9°±4.8° with preoperative disc angle (preoperative DA) of 5.3°±5.0°. The average change of posterior DH (ΔPDH) was 3.1±2.1 mm with preoperative posterior DH of 6.6±1.9 mm. The average change of anterior DH was 6.1±3.2 mm. Pearson correlation analysis showed a significant negative correlation between ΔDA and preoperative DA ( r=-0.713, P<0.001), cage location ( r=-0.183, P=0.016), and ΔDA-FE ( r=-0.153, P=0.044). PDH changes were significantly negatively correlated with preoperative PDH ( r=-0.444, P<0.001) and positively correlated with cage location ( r=0.218, P=0.004). ΔDA was 10.8°±3.2° for negative preoperative DA (indicating kyphotic), 5.0°±3.7° for preoperative DA between 0° and 6°, and 1.0°±4.1° for preoperative DA>6°. A predictive model was developed using ten-fold cross-validation, resulting in the formula ΔDA=7.9°-0.8×preoperative DA ( R=0.707, MAE=2.837). Conclusion:Disc angle changes in OLIF primarily depend on the preoperative disc angle, secondly on cage location. The predicting model based on machine-learning techniques using preoperative disc angle facilitates preoperative planning for OLIF procedures.

Objective To compare the clinical outcomes between oblique lumbar interbody fusion(OLIF)and transforaminal lumbar interbody fusion(TLIF)for patients with degenerative spondylolisthesis during 2-year follow-ups.Methods Patients with symptomatic degenerative spondylolisthesis who underwent OLIF(46 cases)and TLIF(45 cases)between July 2017 and September 2020 with 2-year follow-ups were retrospectively reviewed.One level or two-level lumbar fusion were included.The primary outcomes were Visual Analogue Scale(VAS)and Oswestry Disability Index(ODI)at 2 years after surgery.The secondary outcomes included radiographic parameters,fusion rate,cage subsidence rate,and permanent nerve injury rate.Results No significantly different changes were noted in VAS-back[2(2,3)vs.2(2,2),P=0.943],VAS-leg[2(2,2)vs.2(2,2),P=0.988],and ODI[17％(10％,22％)vs.14％(10％,22％),P=0.417]between the OLIF group and the TLIF group,respectively.Greater restoration of disc height and segmental lordosis were obtained in the OLIF group[mean,(11.9±1.5)mm and 15.7°±7.2°]than in the TLIF group[mean,(9.2±2.0)mm and 12.5°±5.9°]at postoperative 2-year(P＜0.001 and P=0.029).The subsidence rate was lower in the OLIF group than in the TLIF group[19.6％(9/46)vs.40.0％(16/40),P=0.037].The fusion rates at postoperative 2-year were 93.5％(43/46)in the OLIF group and 87.5％(35/40)in the TLIF group,having no significant difference(P=0.562).The rates of permanent nerve injury were similar between the two groups[4.3％(2/46)vs.6.7％(3/45),P=0.980]at postoperative 2-year.Conclusion Short segment OLIF doesn't show better clinical outcomes and fusion rate than TLIF for degenerative spondylolisthesis,except for greater disc height restoration,greater segmental lordosis,and lower subsidence rate at postoperative 2-year.

Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Objective:To evaluate the effect of oblique lateral interbody fusion (OLIF) combined with posterior fixation on segmental alignment in the treatment of degenerative spondylolisthesis (DS).Methods:The clinical data of 40 patients with DS who underwent OLIF combined with posterior fixation from July 2017 to December 2019 were retrospectively analyzed. There were 7 males and 33 females, aged 45-81 years, with an average age of 65.7±9.06 years. The total number of slip segments was 43, including 37 levels at L 4, 5, 5 levels at L 3, 4, and 1 level at L 2, 3. According to the decompression methods, the patients were divided into two groups. 22 patients with 23 levels were treated with direct decompression combined with laminectomy, and 18 patients with 20 levels were treated with indirect decompression without laminectomy. All patients underwent preoperative and intraoperative imaging examination. The disc height (DH), slip ratio (SR) and segmental lordosis (SL) were measured by preoperative CT and intraoperative fluoroscopy images. One-way repeated measures ANOVA was used to compare the radiographic parameters of the segmental alignment prior to cage implantation, following cage insertion and posterior fixation. Bonferroni test was used to compare the radiographic parameters between groups. Results:In the OLIF combined with the posterior fixation, there were statistically significant differences in the radiographic parameters of segmental alignment at different stages of operation [DH ( F=147.786, P<0.001) , SR ( F=83.754, P<0.001) , SL ( F=38.296, P<0.001) ]. DH increased from 7.99±1.39 mm to 11.69±1.72 mm ( P<0.001), SR decreased from 10.67%±4.67% to 8.66%±4.50% ( P=0.001) and SL increased from 7.26°±2.73° to 7.85°±2.30° ( P=0.425). After combined posterior fixation, SR further decreased from 8.66%±4.50% to 2.07%±4.00% ( P<0.001), SL further increased from 7.85°±2.30° to 10.72°±3.08° ( P<0.001), and DH had no significant change ( P=1.000). There was no significant difference in radiographic parameters between the direct decompression group and the indirect decompression group when prior to cage implantation, following cage insertion and following posterior fixation, respectively. Conclusion:OLIF combined with posterior fixation in the treatment of DS can further reduce the slip rate of patients with lumbar degenerative spondylolisthesis and increase the lordosis angle of the surgical segment. At the same time, the direct decompression combined with laminectomy has no significant effect on the segmental alignment.

Objective:To explore the long-term clinical efficacy and complications of modified spinous process splitting laminoplasty using coralline hydroxyapatite (SLAC).Methods:The patients who underwent SLAC surgery in this hospital from 2005.5 to 2011.7 were included retrospectively. The perioperative data were collected and followed up. A total of 165 cases were included. Among them, there were 115 males and 50 females; the average age was 56.5±11.4 years (range: 26-84 years), and the average follow-up period was 136.5±23.2 months (range: 108-182 months). The modified Japanese Orthopedic Association (mJOA) score, the neck disability index (NDI) score were used to evaluate the clinical symptoms of patients, and follow-up imaging to observe the changes in cervical spine curvature and mobility.Results:In terms of functional score: mJOA score increased from 11.4±2.9 before surgery to 15.0±1.8 in the early postoperative period but dropped to 14.0±2.5 at the last follow-up ( F=77.096, P<0.001), and NDI score decreased from 19.2%±14.4% before surgery to 13.0%±15.0% in the early postoperative period, but it rose to 14.0%±14.9% at the last follow-up ( F=6.915, P<0.001). The improvement rate of mJOA was 63.5% (early postoperatively) and 50.8% (last follow-up). Regarding the curvature of the cervical spine, the C 2-C 7 Cobb angle decreased from 14.8°±9.1° before surgery to 11.1°±10.5°, and it was maintained at the last follow-up (11.0°±10.1°) ( F=1.083, P=0.342). The cervical spine range of motion decreased significantly, mainly because the Cobb angle in the flexion position decreased from -19.8°±13.6° before the operation to -3.7°±10.6° at the last follow-up ( P<0.001). Seventy-two patients (44.0%) had complications after operation. Six patients (3.6%) developed neurological symptoms aggravated during follow-up, and their mJOA decreased by more than 3 points. 62 patients (37.6%) developed axial symptoms, of which 7 cases were relieved early (within 6 months post-op), 55 patients had persisted symptom and 17 cases (10.3%) remained painful. C 5 nerve root palsy occurred in 10 cases (6.1%) after the operation, 9 cases resolved within two years and the last patient did not resolve. Conclusion:SLAC surgery can effectively alleviate the patient's neurological symptoms and maintain long-term efficacy and cervical lordosis. The occurrence of persistent axial symptoms and the loss of cervical flexion range are long-term complications after SLAC surgery.

Objective:To preliminarily evaluate the feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy (CRP).Methods:A descriptive cohort study was carried out. The clinical and follow-up data of 19 patients who received laparoscopic Parks procedure due to CRP in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2013 to March 2019 were retrospectively analyzed. Inclusion criteria: (1) serious late complications occurred after pelvic radiotherapy, e.g.serious intractable hematochezia (hemoglobin <70 g/L), intractable anal pain (numerical rating scale >7), rectostenosis, perforation, and fistula. (2) imaging examinations including colonoscopy, pelvic MRI and/or chest, abdomen and pelvic CT were performed before surgery to confirm the lesions. Exclusion criteria: (1) preoperative or intraoperative diagnosis of tumor recurrence; (2) only ostomy was performed after laparoscopic exploration; (3) after neoadjuvant radiotherapy for rectal cancer; (4) incomplete medical records. Surgical procedures: (1) Laparoscopic exploration: tumor recurrence was excluded, and the range of radioactive damage in the intestine was determined. Marks were made on the proximal sigmoid colon without grossly obvious edema, thickening or radioactive injuries. (2) Abdominal operation: the right mesentery of sigmoid colon and rectum was opened, inferior mesenteric vein and inferior mesenteric artery were divided and the Toldt gap was expanded inwards and cephalad. The outside of left hemicolon was freed, the gastrocolic ligament was opened, the splenic flexure was fully mobilized, and the rectum was separated from the rear, side and front to the lowest point. Then perineal operation was performed. (3) Perineal operation: the whole layer of rectum wall was cut thoroughly at 1cm below the lesion's lower margin, the space around the rectum was fully separated, the rectum and sigmoid colon was pulled out through the anus and cut off at the site of the grossly normal intestine, the diseased bowel was removed and a coloanal anastomosis was made. (4) A protective stoma was performed. Conditions of operation, complication and symptom relief were summarized. A descriptive statistic method was used to analyze the results.Results:All the 19 patients were female with a median age of 53 (interquartiles, 50, 56) years old, of whom 18 patients had primary cervical cancer. Surgical indications: 9 cases were rectovaginal fistula; 9 cases were intractable anal pain, among whom 7 were complicated with deep rectal ulcer; and 1 case was intractable hematochezia with deep rectal ulcer. Eighteen cases completed laparoscopic Parks procedure, while 1 case was converted to laparotomy. The median operative time was 215 (131, 270) minutes, the median bleeding volume was 50 (50, 100) ml, and the median hospital stay was 12 (11, 20) days. There was no perioperative death. Ten cases had postoperative complications, including 3 cases of serious complications (CD grade IIIb and above) within 30 days after operation, of whom one case developed pelvic infection caused by rectovaginal, rectovesical and rectourethral fistula and acute renal failure (IVa); 2 cases developed orifice prolapse and parastomal hernia (IIIb). Seven cases had anastomosis-related complications, including 4 cases of grade A anastomotic leakage and 3 cases of anastomotic stenosis. Symptoms of CRP in the whole group were significantly relieved or disappeared after one year of the operation. Five cases achieved stoma closure.Conclusions:Laparoscopic Parks procedure for chronic radiation proctopathy is safe and feasible, and can effectively improve symptoms. However, the incidence of anastomotic complications is high, so the surgical indications should be strictly controlled.

Objective:To preliminarily evaluate the feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy (CRP).Methods:A descriptive cohort study was carried out. The clinical and follow-up data of 19 patients who received laparoscopic Parks procedure due to CRP in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2013 to March 2019 were retrospectively analyzed. Inclusion criteria: (1) serious late complications occurred after pelvic radiotherapy, e.g.serious intractable hematochezia (hemoglobin <70 g/L), intractable anal pain (numerical rating scale >7), rectostenosis, perforation, and fistula. (2) imaging examinations including colonoscopy, pelvic MRI and/or chest, abdomen and pelvic CT were performed before surgery to confirm the lesions. Exclusion criteria: (1) preoperative or intraoperative diagnosis of tumor recurrence; (2) only ostomy was performed after laparoscopic exploration; (3) after neoadjuvant radiotherapy for rectal cancer; (4) incomplete medical records. Surgical procedures: (1) Laparoscopic exploration: tumor recurrence was excluded, and the range of radioactive damage in the intestine was determined. Marks were made on the proximal sigmoid colon without grossly obvious edema, thickening or radioactive injuries. (2) Abdominal operation: the right mesentery of sigmoid colon and rectum was opened, inferior mesenteric vein and inferior mesenteric artery were divided and the Toldt gap was expanded inwards and cephalad. The outside of left hemicolon was freed, the gastrocolic ligament was opened, the splenic flexure was fully mobilized, and the rectum was separated from the rear, side and front to the lowest point. Then perineal operation was performed. (3) Perineal operation: the whole layer of rectum wall was cut thoroughly at 1cm below the lesion's lower margin, the space around the rectum was fully separated, the rectum and sigmoid colon was pulled out through the anus and cut off at the site of the grossly normal intestine, the diseased bowel was removed and a coloanal anastomosis was made. (4) A protective stoma was performed. Conditions of operation, complication and symptom relief were summarized. A descriptive statistic method was used to analyze the results.Results:All the 19 patients were female with a median age of 53 (interquartiles, 50, 56) years old, of whom 18 patients had primary cervical cancer. Surgical indications: 9 cases were rectovaginal fistula; 9 cases were intractable anal pain, among whom 7 were complicated with deep rectal ulcer; and 1 case was intractable hematochezia with deep rectal ulcer. Eighteen cases completed laparoscopic Parks procedure, while 1 case was converted to laparotomy. The median operative time was 215 (131, 270) minutes, the median bleeding volume was 50 (50, 100) ml, and the median hospital stay was 12 (11, 20) days. There was no perioperative death. Ten cases had postoperative complications, including 3 cases of serious complications (CD grade IIIb and above) within 30 days after operation, of whom one case developed pelvic infection caused by rectovaginal, rectovesical and rectourethral fistula and acute renal failure (IVa); 2 cases developed orifice prolapse and parastomal hernia (IIIb). Seven cases had anastomosis-related complications, including 4 cases of grade A anastomotic leakage and 3 cases of anastomotic stenosis. Symptoms of CRP in the whole group were significantly relieved or disappeared after one year of the operation. Five cases achieved stoma closure.Conclusions:Laparoscopic Parks procedure for chronic radiation proctopathy is safe and feasible, and can effectively improve symptoms. However, the incidence of anastomotic complications is high, so the surgical indications should be strictly controlled.

Objective: To investigate the clinical features of childhood epilepsy with occipital paroxysms. Methods: The clinical data of 33 children admitted to our hospital from 2015 to 2019 were retrospectively analyzed. Results: The children were divided into three groups: idiopathic group (n=20), structural group (n=10) and genetic group (n=3). Among the structural etiology group, there were 1 case of megagyrus malformation, 1 case of focal cortical dysplasia type Ⅱ (FCDⅡ), 1 case of gestational age infant with enlarged ventricle, and 7 cases of perinatal ischemic-hypoxic encephalopathy (HIE). In the genetic group, there were 1 case of PCDH19 gene mutation, 1 case of cyclin-dependent kinase like 5 (CDKL5) deficiency disorder and 1 case of Wolf-Hirschhorn syndrome. All three groups had ocular motor symptoms and secondary motor symptoms. Compared with the structural group, patients of the idiopathic group had more autonomic symptoms, less visual symptoms, longer ictal duration, less episodes, less abnormal background rhythm, and more epileptic discharges in the frontal lobe or Rolandic area. The genetic group had frequent seizures and the CDKL5 deficiency disorder patient had slowed background and spasms. Compared with the other two groups, patients of the idiopathic group had fewer MRI abnormalities, better seizure control effect, and better prognosis. Conclusions There are many causes of childhood epilepsy with occipital paroxysms. The idiopathic group accounts for a large proportion. The visual symptoms and autonomic symptoms are different between groups. Background abnormalities are detected more often in the structural group and the genetic group, which is also helpful for differential diagnosis. The treatment options and prognosis of different groups vary greatly. The overall therapeutic effect and prognosis of the idiopathic group are better than those of the structural group and the genetic group.