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.

AIM: To systematically evaluate the efficacy and safety of low-concentrations atropine eye drops in controlling adolescent myopia.METHODS:A computer search was conducted on Wanfang Data, CNKI, VIP, PubMed, Cochrane Library, and Embase databases from January 2010 to March 2024 on clinical studies on low-concentration atropine eye drops for controlling adolescent myopia. Two researchers independently screened trials, extracted data, evaluated risk of bias and quality, and used Review Manager5.4 software to perform Meta-analysis.RESULTS:A total of 17 articles, involving 3 764 cases and 3 952 eyes, were included. The Meta-analysis showed that compared with the control group, low concentrations of atropine could effectively slow down the growth of axial length [MD=-0.15, 95% CI(-0.20, -0.10), P<0.00001], significantly controlled the changes in spherical equivalent [MD=0.39, 95% CI(0.29, 0.48), P<0.00001], and had a significant effect on pupil diameter [MD=0.80, 95% CI(0.33,1.28), P=0.0010] and amplitude of accommodation [MD=-2.54, 95%CI(-4.49, -0.60), P=0.01].CONCLUSION:Low-concentrations atropine are effective in controlling spherical equivalent and axial length of myopia in adolescents, significantly affecting pupil diameter and amplitude of accommodation, and effectively delaying the progression of myopia.

BACKGROUND/AIMS: Microvascular invasion (MVI) is an established risk factor for hepatocellular carcinoma (HCC). However, prediction models that specifically focus on the individual prognoses of HCC patients with MVI is lacking. METHODS: A total of 385 HCC patients with MVI were randomly assigned to training and validation cohorts in a 2:1 ratio. The outcomes were disease-free survival (DFS) and overall survival (OS). Prognostic nomograms were established based on the results of multivariate analyses. The concordance index (C-index), calibration plots and Kaplan-Meier curves were employed to evaluate the accuracy, calibration and discriminatory ability of the models. RESULTS: The independent risk factors for both DFS and OS included age, tumor size, tumor number, the presence of gross vascular invasion, and the presence of Glisson's capsule invasion. The platelet-to-lymphocyte ratio was another risk factor for OS. On the basis of these predictors, two nomograms for DFS and OS were constructed. The C-index values of the nomograms for DFS and OS were 0.712 (95% confidence interval [CI], 0.679 to 0.745; p<0.001) and 0.698 (95% CI, 0.657 to 0.739; p<0.001), respectively, in the training cohort and 0.704 (95% CI, 0.650 to 0.708; p<0.001) and 0.673 (95% CI, 0.607 to 0.739; p<0.001), respectively, in the validation cohort. The calibration curves showed optimal agreement between the predicted and observed survival rates. The Kaplan-Meier curves suggested that these two nomograms had satisfactory discriminatory abilities. CONCLUSIONS: These novel predictive models have satisfactory accuracy and discriminatory abilities in predicting the prognosis of HCC patients with MVI after hepatectomy.
Calibration ; Carcinoma, Hepatocellular ; Cohort Studies ; Disease-Free Survival ; Hepatectomy ; Humans ; Multivariate Analysis ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate

Objective To evaluate the efficacy of unilateral atlanto-axial transpedicle screw fixation plus iliac bone graft for treatment of unstable atlas fractures combined with unilateral pedicle dysplasia or comminuted fractures.Methods A retrospective case control study was made on 44 patients with unstable atlas fractures surgically treated between January 2012 to June 2016.Unilateral atlanto-axial transpedicle screw fixation combined with iliac bone graft was performed for 22 patients combined with unilateral pedicle dysplasia or comminuted fractures in Group A[15 males,seven females;(37.5 ± 13.4)years],and bilateral atlanto-axial transpedicle screw fixation combined with iliac bone graft was performed for 22 patients without unilateral pedicle dysplasia or comminuted fractures in Group B [14 males,eight females;(38.1 ± 13.3)years].Between-group differences were compared concerning operation time,intraoperative blood loss,length of hospital stay,success rate of screw placement,postoperative atlantoaxial stability,surgery-related complications,visual analog scale (VAS),Japanese orthopedic association score (JOA) and bone fusion.Results Mean duration of follow-up was 28.4 months (range,14-48 months).In Group A,operation time was (123.4 ± 18.2) min,blood loss was (218.5 ± 80.2) ml,hospital stay was (7.1 ± 1.0)d,success rate of screw placement was 100％,postoperative atlanto-axial stability of all patients was obtained,and no complications occurred.In Group B,operation time was (173.4 ± 12.4) min,blood loss was (318.2 ± 61.7) ml,hospital stay was (7.2 ± 0.8) d,success rate of screw placement was 100％,postoperative atlanto-axial stability of all patients was obtained,and no complications occurred.There were significant differences in operation time and blood loss between the two groups (P ＜0.01),while not in hospital stay,success rate,postoperative atlant-oaxial stability,complication incidence,VAS and JOA (P ＞ 0.05).Conclusion Both treatments are effective,but unilateral atlanto-axial transpedicle screw fixation combined with iliac bone graft is associated with relatively shorter operation time and less blood loss and hence is considered as a better choice for treatment of unstable atlas fractures.

This paper reported 13 cases of delayed traumatic chest wall abscess from January 2012 to January 2015.All the patients were associated with type 2 diabetes.After local puncture for confirmative diagnosis, a chest wall abscess dissection was carried out as soon as possible.At each site of upper and lower pole, an indwelling drainage tube was placed for irrigation and negative pressure suction.Sensitive antibiotics were selected based on susceptibility test results.The drainage tubes were removed 7-14 days after surgery.There were 8 cases of primary healing of incision and 5 cases of secondary healing of incision.All the patients were cured.Follow-ups for 6-36 months (average, 17 months) showed no recurrence.