OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To explore the status of working ability of patients with ankylosing spondylitis(AS)in China from multi-center,multi-level and multi-dimensional perspectives,and analyze the influencing factors of working ability in AS patients,so as to improve the outcome of working ability disorder in AS patients.Methods The demographic data,working ability and disease-related information of 253 AS patients admitted to 10 hospitals in 9 centers in China from Mar.2022 to Sep.2023 were collected.Work productivity and activity impairment questionnaire was used to investigate the working status.The influencing factors of working ability disorder were analyzed,and the correlations of the work ability with the severity of disease,self-assessment,and mental health status were discussed.Results A total of 253 patients with AS were enrolled,of which 197(77.87％)were employed,76(30.04％)were in normal working status,and 177(69.96％)had disorder in working ability.Multivariate logistic regression analysis showed that the course of AS,Bath ankylosing spondylitis functional index,Bath ankylosing spondylitis measurement index,functional assessment of chronic illness therapy-fatigue,ankylosing spondylitis disease activity score-erythrocyte sedimentation rate,Assessment of Spondyloarthritis International Society health index,depression,anxiety,and patient global assessment were important factors affecting the working ability of patients.Conclusion There is a high proportion of work ability disorder in Chinese AS patients,and the severity of the disease,psychological state and self-reported outcome are closely related to the status of work ability.

Heterotopic ossification is an important pathological link leading to disability in ankylosing spondylitis （AS）. Imbalance of bone immune microenvironment is the initiating factor for heterotopic ossification in AS， while abnormal osteogenic potential of bone marrow mesenchymal stem cells （BMSCs） is the core link. From the perspective of "bone sweat pore-kidney visceral manifestation" in traditional Chinese medicine， it is believed that dysfunction of "kidney visceral manifestation" is the basis for the induction of heterotopic ossification by bone immune microenvironment and BMSCs， and "bone sweat pore" is their important setting. Accordingly， it is proposed that the kidney and sweat pore should be nourished and regulated to reshape the bone immune microenvironment and BMSCs function， and that obstruction should be removed and the marrow should be unblocked to eliminate the pathological factors that lead to AS heterotopic ossification. This provides a new perspective and basis for the treatment of AS with traditional Chinese medicine.

Ankylosing spondylitis(AS)is a worldwide refractory autoimmune disease whose exact etiology is not fully under-stood,and disorders of body's immune system are currently thought to play an important driving role in development of AS.Previous studies generally attach great importance to role of T cells in pathogenesis of AS.With in-depth research on AS,more and more evidence indicates that both innate immune cells and adaptive immune cells can trigger AS and are closely related to three core patho-logical links of AS,namely inflammation,bone destruction and new bone formation.In this article,we discuss mechanisms involved in development of AS by both innate and adaptive immune cells,with aim of providing new ideas for treatment of AS.

AIM:To explore the mechanism of berberine on breast cancer cells based on network pharmacology and in vitro cell experiments.METH-ODS:Firstly,berberine and breast cancer were tak-en as the research objects,the intersection targets of the two were screened by VEEN diagram,GO function and KEGG enrichment analysis were per-formed by R language,and molecular docking and visualization were carried out by Autodock Vina and Pymol software.Then,berberine treated breast cancer MCF-7 cells for 24 h,and then in vi-tro cell experiments were performed.CCK-8 was used to detect cell viability,Edu and plate cloning were used to detect cell proliferation and cloning,and apoptosis was detected by An-nexin V-FITC/PI double staining and Western blot.Laser confocal and CETSA were used to verify the binding effect of berberine and AKT1 protein.RESULTS:The results of network pharmacology showed that berberine had a good binding to the core targets AKT1,AKT2 and MAPK3.Berberine(20,40,80 μmol/L)signifi-cantly inhibited the proliferation and cloning ability of MCF-7 cells in a concentration-dependent man-ner(P＜0.05,P＜0.01).The results of laser confocal and CETSA experiments showed that berberine and AKT1 had a binding effect,and the stability of the two was enhanced after the combination.CONCLU-SION:Berberine inhibits MCF-7 cell proliferation and induces apoptosis in human breast cancer cells by targeting binding to AKT1 protein.

AIM:To explore the mechanism of berberine on breast cancer cells based on network pharmacology and in vitro cell experiments.METH-ODS:Firstly,berberine and breast cancer were tak-en as the research objects,the intersection targets of the two were screened by VEEN diagram,GO function and KEGG enrichment analysis were per-formed by R language,and molecular docking and visualization were carried out by Autodock Vina and Pymol software.Then,berberine treated breast cancer MCF-7 cells for 24 h,and then in vi-tro cell experiments were performed.CCK-8 was used to detect cell viability,Edu and plate cloning were used to detect cell proliferation and cloning,and apoptosis was detected by An-nexin V-FITC/PI double staining and Western blot.Laser confocal and CETSA were used to verify the binding effect of berberine and AKT1 protein.RESULTS:The results of network pharmacology showed that berberine had a good binding to the core targets AKT1,AKT2 and MAPK3.Berberine(20,40,80 μmol/L)signifi-cantly inhibited the proliferation and cloning ability of MCF-7 cells in a concentration-dependent man-ner(P＜0.05,P＜0.01).The results of laser confocal and CETSA experiments showed that berberine and AKT1 had a binding effect,and the stability of the two was enhanced after the combination.CONCLU-SION:Berberine inhibits MCF-7 cell proliferation and induces apoptosis in human breast cancer cells by targeting binding to AKT1 protein.

Ankylosing spondylitis(AS)is a worldwide refractory autoimmune disease whose exact etiology is not fully under-stood,and disorders of body's immune system are currently thought to play an important driving role in development of AS.Previous studies generally attach great importance to role of T cells in pathogenesis of AS.With in-depth research on AS,more and more evidence indicates that both innate immune cells and adaptive immune cells can trigger AS and are closely related to three core patho-logical links of AS,namely inflammation,bone destruction and new bone formation.In this article,we discuss mechanisms involved in development of AS by both innate and adaptive immune cells,with aim of providing new ideas for treatment of AS.

Objective:To investigate the dynamic changes of diaphragm and limb skeletal muscle in patients with sepsis by bedside ultrasound and their correlation with the ratio of blood urea/creatinine ratio (UCR) in 7 days after intensive care unit (ICU) admission.Methods:A prospective observational study was conducted. A total of 55 patients with sepsis admitted to ICU of General Hospital of Ningxia Medical University from June 2022 to February 2023 were selected as the research objects. General information, laboratory indicators [urea, serum creatinine (SCr), and UCR] on days 1, 4, and 7 of ICU admission, and prognostic indicators were observed. Bedside ultrasound was used to assess the dynamic changes of diaphragm morphology [including diaphragmatic excursion (DE), end-inspiratory diaphragm thickness (DTei), and end-expiratory diaphragm thickness (DTee)] on days 1, 4, and 7 of ICU admission, as well as limb skeletal muscle (quadriceps femoris) morphology [including rectus femoris-muscle layer thickness (RF-MLT), vastus intermedius-muscle layer thickness (VI-MLT), and rectus femoris-cross sectional area (RF-CSA)]. Diaphragm thickening fraction (DTF) and RF-CSA atrophy rate were calculated, and the incidence of diaphragm and limb skeletal muscle dysfunction was recorded. The correlation between ultrasound morphological parameters of diaphragm and quadriceps and UCR at each time points in 7 days after ICU admission was analyzed by Pearson correlation.Results:A total of 55 patients with sepsis were included, of which 29 were in septic shock. As the duration of ICU admission increased, the incidence of diaphragm dysfunction in patients with sepsis increased first and then decreased (63.6%, 69.6%, and 58.6% on days 1, 4, and 7 of ICU admission, respectively), while the incidence of limb skeletal muscle dysfunction showed an increasing trend (54.3% and 62.1% on days 4 and 7 of ICU admission, respectively), with a probability of simultaneous occurrence on days 4 and 7 of ICU admission were 32.6% and 34.5%, respectively. The UCR on day 7 of ICU admission was significantly higher than that on day 1 [121.77 (95.46, 164.55) vs. 97.00 (70.26, 130.50)], and RF-CSA atrophy rate on day 7 was significantly higher than that on day 4 [%: -39.7 (-52.4, -22.1) vs. -26.5 (-40.2, -16.4)]. RF-CSA was significantly lower on day 7 compared to day 1 [cm 2: 1.3 (1.0, 2.5) vs. 2.1 (1.7, 2.9)], with all differences being statistically significant (all P < 0.05). Pearson correlation analysis showed that RF-CSA on day 7 of ICU admission was negatively associated with the UCR on the same day ( r = -0.407, P = 0.029). Conclusions:Diaphragmatic dysfunction in patients with sepsis occurred early and can be improved. Limb skeletal muscle dysfunction occurred relatively later and progresses progressively. The RF-CSA on day 7 of ICU admission may be a reliable measure of limb skeletal muscle dysfunction in patients with sepsis, can be an indicator of early identification and diagnosis of ICU-acquired weakness (ICU-AW). Continuous loss of muscle mass occurring in septic patients is mainly associated with persistent organismal catabolism, and undergoes significant changes around a week in ICU.

Ankylosing spondylitis is a refractory autoimmune disease,and heterotopic ossification is one of the most important pathological features.The mechanism of heterotopic ossification in ankylosing spondylitis involves many aspects,including ossification-related genes,ossification-related factors,ossification-related cells,ossification signaling pathways,and mechanical stress.This article elaborates the pathogenesis of heterotopic ossification in ankylosing spondylitis from different aspects of multiple channels,pathways,targets,and factors,hoping to provide reference for expanding clinical and basic research and in-depth understanding of ankylosing spondylitis.

Objective To explore the mechanism of Prunella vulgaris and Scutellaria barbata herb pair against breast cancer based on network pharmacology and in vitro cell experiments.Methods The effective components and targets of Prunella vulgaris and Scutellaria barbata herb pair were screened.GeneCards and OMIM databases were used to find breast cancer targets,and then drug-active ingredient-key target network and protein-protein inter-action(PPI)were constructed.R language was used to perform GO function and KEGG pathway enrichment analy-sis and survival analysis.Then the screened active components and core targets were verified by molecular docking.Cell viability was detected by CCK-8 assay.EdU and flow cytometry were used to detect cell proliferation and apop-tosis.The protein expression levels of p-AKT1,AKT1,β-catenin and c-MYC were detected by Western blot.Results Through databases analysis,a total of 36 active components and 105 intersection targets were screened out,the core components were quercetin,luteolin,kaempferol,wogonin and baicalein.Through PPI and survival analysis,the key targets were AKT1,ESR1,CASP3 and MYC.GO analysis contained 4 303 enrichment results,KEGG analysis contained 232 pathways.Molecular docking showed that the core components had strong binding ability with the key targets.Cell experiments showed that the core active ingredient quercetin could inhibit the proliferation of breast cancer cells and promote their apoptosis(P＜0.05),and down-regulate the expression levels of p-AKT1,β-catenin and c-MYC proteins(P＜0.05).Conclusion The active components quercetin in Prunella vulgaris and Scutel-laria barbata herb pair may play a role through AKT1/β-catenin signaling pathway,which provides a scientific refer-ence for the study of its mechanism of action in the treatment of breast cancer.