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 predictive value of inflammatory markers for stroke-associated pneumonia(SAP)in patients with acute ischemic stroke(AIS)based on the nomogram model.Methods According to whether pneumonia occurred,259 AIS patients were divided into SAP group(81 cases)and non-SAP group(178 cases).The clinical data of the two groups were compared.The systemic inflammatory response index(SIRI),systemic immunoinflammatory index(SII)and neutrophil to lymphocyte ratio(NLR)were calculated according to the formula.The variables with statistically significant differences were included in the multivariate binary Logistic regression model to screen out the independent risk factors for SAP in AIS patients.The independent risk factors were used to construct a predictive model,and the predictive ability of the two models,which only included traditional factors and included inflammatory indicators at the same time,was further compared from the aspects of discrimination,calibration,clinical practicability and so on.Reclassification analysis was used to evaluate the extent to which the nomogram model improved the predictive value of SAP risk in AIS patients.Results Compared with those in the non-SAP group,the rates of smoking,diabetes,dysphagia,leukocytes,neutrophils,lymphocytes,triglyceride level,NIHSS score on admission,SIRI,SII and NLR were significantly increased in the SAP group,and the rate of hypertension was decreased(all P＜0.05).Diabetes mellitus(OR =2.505,95%CI:1.070-5.850,P =0.034),dysphagia(OR =3.492,95%CI:1.501-8.119,P =0.004),NIHSS score on admission(OR = 1.310,95%CI:1.188-1.446,P＜0.001),SIRI(OR =2.417,95%CI:1.327-4.401,P =0.008),NLR(OR =1.434,95%CI:1.101-1.860,P =0.007)were independent risk factors for SAP in AIS patients.The area under the curve was 0.788(95%CI:0.725-0.852,P＜0.001)for the prediction model without inflammatory factors and 0.884(95%CI:0.838-0.930,P＜0.001)for the prediction model with independent risk factors.The calibration curve showed a good consistency between the predicted risk and the observed results.The decision curve showed that the model had a significant net benefit for predicting SAP.In addition,by calculating the net reclassification index(NRI)and the comprehensive discriminant improvement index(IDI),it was found that the nomogram model had a significant improvement in predicting the risk of SAP in AIS patients.Internal verification also proves the reliability of the nomogram model.Conclusions SIRI and NLR are independent predictors of SAP in AIS patients on admission.Adding SIRI and NLR to the traditional model can significantly improve the ability to identify the risk of SAP occurrence in AIS patients.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.

dengue fever, in Nanchang City, providing a scientific basis for effective prevention and control of dengue fever. Methods　The Breteau Index (BI) method and double-layer trapping method were used to monitor the density of Ae. albopictus larvae and adults, respectively. The monitoring results were summarized and analyzed. SPSS 26.0 software was used for statistical analysis. Differences in BI at different time points were analyzed by the Chi-square test, and differences in net trap index or BI across different times and habitats by analysis of variance or the Kruskal-Wallis test, and the risk of dengue fever transmission was assessed. Results　The average BI in Nanchang City between 2018 and 2023 was 4.08, which showed a downward trend year by year (χ2=189.809, P<0.001), with the highest in 2019 and the lowest in 2022. The average Attraction-Collection Index was 1.17 mosquitoes/(trap·hour). Both the BI and trapping index of the whole city showed significant seasonal fluctuations, each displaying a single peak, with the peak values occurring in July at 5.63 and 1.83 mosquitoes/(trap·hour), respectively, and the lowest in October at 2.28 and 0.51 mosquitoes/(trap·hour), respectively. The BI and trapping index of urban areas were both higher than those of parks, construction sites, and hospitals. In different habitats, the trend of changes in BI in different months showed an unimodal curve, with the peak appearing from June to August, while the BI trends varied across different years. From 2018 to 2023, there was a dengue transmission risk in 30.56% (11/36) of monitored months, and the BI value in June 2018 reached the threshold for dengue fever outbreak risk. Conclusion　 The annual fluctuation trend of the density of Aedes mosquitoes as vectors in Nanchang City shows a decreasing trend, but there is still a risk of local transmission of dengue fever. To prevent dengue outbreaks caused by imported pathogens, it is necessary to strengthen comprehensive management of breeding grounds in the external environment, enhance monitoring of vector Ae. Albopictus, and take effective control measures in time.

The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.

Objective: To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) . Methods: The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups. Results: There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34⁺ cells infused were 10.74 (4.80-22.86) ×10⁸/kg and 12.19 (5.14-17.25) ×10⁸/kg (P=0.866) , 3.57 (0.68-7.80) ×10⁶/kg and 4.00 (3.02-8.42) ×10⁶/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups. Conclusion The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.

Objective: To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome. Methods: The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen. Results: There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×10⁸/kg in the PNH group and 10.81 (3.96-33.40) ×10⁸/kg in the PNH-AA group (P=0.668) . The median doses of CD34⁺ cells infused were 5.00 (3.14-8.42) ×10⁶/kg and 3.57 (1.97-6.17) ×10⁶/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) . Conclusions allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.

OBJECTIVE:To study the chemical constituents of Euonymus amygdalifolius.METHODS:Silica gel column chromatogram,gel column chromatogram,TLC and semi-preparative HPLC were adopted to isolate and purify ethanol extract from E.amygdalifolius.The structure of compounds was analyzed and identified according to physical and chemical properties,spectral data (mass spectrurn,hydrogen spectrum and carbon spectrum).RESULTS:Ten compounds were isolated from ethanol extract of aerial part of E.amygdalifolius,i.e.taraxerol (1),sophoradiol (2),taraxerone (3),sorghumol (4),heptaecanoic acid (5),octadecenoic acid (6),β-Sitosterol (7),daucosterol (8),epifriedelinol (9) and friedelin (10).CONCLUSIONS:Above compounds are all isolated from E.amygdalifolius for the first time;compounds 1,2,4,5,6 are isolated and obtained from Euonymus A.for the first time.The study lay a foundation for quality evaluation of E.amygdalifolius.

Objective To investigate the differences in susceptibility to Lewis lung carcinoma and T lymphocyte subsets in the immune microenvironment between young and elderly mice.Methods Six C57/B6 mice at two months(young)and six mice at twelve months(aged)were injected with Lewis lung carcinoma cells at the dose of 1 × 106 in the left armpit to establish a murine model of lung carcinoma.The weight and tumor growth were monitored.Blood samples for routine blood tests were collected after 24 days.The proportions of CD4+ and CD8+T cells in the spleen were detected by flow cytometry,and the infiltration of CD4+,CD8+ T cells and related effector T cells in the tumor microenvironment were determined in the same way.Results The body weight of tumor bearing mice in the aged group was significantly higher than that in the young group(P ＜0.001);The tumor weight in the aged group(5.084±0.528)g was significantly higher than that in the young group(2.963 ±0.378)g(t =3,349,P =0.012);Routine blood tests showed that the numbers of leukocytes and subsets(except mononuclear)in the aged group were significantly lower than in the young group(P ＜0.05);Flow cytometry found that the effector and memory/effector CD4+T cell ratios in the spleen were significantly higher in the aged group than in the young group(P ＜0.001)and the expression of effector and memory/effector CD8+T cells in the tumor microenvironment was also significantly higher than in the young group(P ＜0.05);Quantitative expression values of IL-6 and IL-10 in the tumor microenvironment were 25090±3820 and 10670± 1793 in the aged group and 6252±864 and 3061±451 in the young group,respectively.Moreover,the expression levels of IL-6 and IL-10(t =3.925,P =0.01;t =3.552,P =0.02)in the tumor microenvironment in the aged group were significantly lower than those in the young group.Conclusions Young mice are more susceptible to Lewis lung carcinoma,probably as a result of differences in inflammation and immunity.