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 investigate the effects of short-peptide-based enteral nutrition on nutritional status, immune function, and chemotherapy-related adverse reactions in children with acute lymphoblastic leukemia (ALL).Methods:A total of 106 children with ALL receiving chemotherapy at the Affiliated Hospital of Jining Medical University between January 2021 and April 2022 were enrolled. According to the principle of between-group baseline data matching, the patients were divided into observation group and control group by random number table method, with 53 cases in each group. All patients received chemotherapy according to the CCCG-ALL-2020 protocol established by the Multi-center Cooperative Group of the Chinese Society of Pediatric Oncology (2020). The control group received a regular diet, while the observation group received a regular diet supplemented with short-peptide-based enteral nutrition. The incidence rates of malnutrition, hypoproteinemia, hypoalbuminemia, abnormal immunoglobulin levels (IgG, IgM, IgA), and adverse reactions (liver injury, infection) were compared between both groups before chemotherapy and at the end of each of the following seven chemotherapy phases: Induction remission therapy (PVDL), Induction remission therapy (CAT), Early intensification therapy (CAT+), Consolidation therapy (HDMTX), Interim maintenance therapy, Reinduction therapy, and prior to the end of Maintenance therapy. Normally or approximately normally distributed measurement data were expressed as xˉ± s and compared by independent samples t-test. Counting data were expressed as n (%) and compared by χ2 test. Results:During the CAT phase, the incidence of malnutrition was significantly lower in the observation group than in the control group [20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034]. The incidence of hypoproteinemia was significantly lower in the observation group during HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [47.2% (25/53) vs. 69.8% (37/53), χ2=5.60, P=0.018; 45.3% (24/53) vs. 67.9% (36/53), χ2=5.53, P=0.019; 41.5% (24/53) vs. 64.2% (34/53), χ2=5.45, P=0.020; 28.3% (15/53) vs. 54.7% (29/53), χ2=7.62, P=0.006, respectively]. The incidence of hypoalbuminemia was significantly lower in the observation group during CAT+, HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [5.7% (3/53) vs. 22.6% (12/53), χ2=6.29, P=0.012; 9.4% (5/53) vs. 26.4% (14/53), χ2=5.19, P=0.023; 9.4% (5/53) vs. 28.3% (15/53), χ2=6.16, P=0.013; 7.6% (4/53) vs. 24.5% (13/53), χ2=5.68, P=0.017; 3.8% (2/53) vs. 18.9% (10/53), χ2=6.01, P=0.014, respectively]. For IgG, incidence was significantly lower in the observation group during Interim maintenance, Reinduction, and prior to the end of Maintenance therapy [7.6% (4/53) vs. 22.6% (12/53), χ2=4.71, P=0.030; 20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034; 11.3% (6/53) vs. 26.4% (14/53), χ2=3.94, P=0.047, respectively]. For IgM, incidence was significantly lower in the observation group during the CAT and CAT+ phases [45.3% (24/53) vs. 66.0% (35/53), χ2=4.63, P=0.032; 58.5% (31/53) vs. 77.4% (41/53), χ2=4.33, P=0.037, respectively]. For IgA, incidence was significantly lower in the observation group during Reinduction therapy and Interim maintenance [22.6% (12/53) vs. 45.3% (24/53), χ2=6.06, P=0.014; 9.4% (5/53) vs. 24.5% (13/53), χ2=4.28, P=0.038, respectively]. For liver injury, incidence was significantly lower in the observation group during the CAT, CAT+, and prior to the end of Maintenance phases [22.6% (12/53) vs. 43.4% (23/53), χ2=5.16, P=0.023; 26.4% (14/53) vs. 50.9% (27/53), χ2=6.72, P=0.010, 11.3% (6/53) vs. 26.4%(14/53), χ2=3.94、 P=0.047,respectively]. For infection, incidence was significantly lower in the observation group during the CAT+ and HDMTX phases [35.9% (19/53) vs. 56.6% (30/53), χ2=4.59, P=0.032; 24.5% (13/53) vs. 43.4% (23/53), χ2=4.21, P=0.040, respectively]. Conclusions:Short-peptide-based enteral nutrition demonstrates significant advantages in the treatment of pediatric ALL. It provides substantial support for patient treatment and recovery by improving nutritional status, modulating immune function, and reducing chemotherapy-related adverse reactions.

Objective To investigate the effects of miR-338-3p on interleukin(IL)-13-induced human bronchial epithelial cell line(BEAS-2B)injury and airway inflammation in mice with ovalbumin(OVA)-induced asthma.Methods OVA was used to replicate an asthma model of mice,which were divided into control group,model group,miR-NC agomir and miR-338-3p agomir intervention groups.HE staining microscopy was employed to ob-serve the pathological morphology of lung tissue,while TUNEL staining was used to assess cell apoptosis in lung tis-sue.ELISA was conducted to measure the levels of interleukin-1β(IL-1β)and tumor necrosis factor(TNF)-α in lung tissue.The BEAS-2B cells were subjected to IL-13-induced injury and divided into control group,IL-13 group,IL-13+miR-NC group,and IL-13+miR-338-3p mimic group.Cell viability was assessed with MTT assay.Flow cytometry was employed to evaluate cell apoptosis.The level of IL-1β and TNF-α in cells was measured by ELISA.The targeting relationship between miR-338-3p and Ras homologous(Rho)was investigated using bioinfor-matics analysis,luciferase assay,Western blot,and functional repair assay.Results Compared to the model group,the miR-338-3p agamid intervention group exhibited a significant reduction in inflammatory cell infiltration and airway wall thickening in lung tissue,as well as decreased cell apoptosis and the level of IL-1β and TNF-α in lung tissue(P＜0.05).Compared to the control group,cell viability of BEAS-2B cells in the IL-13+miR-338-3p mimic group exhibited a significant increase(P＜0.05),while apoptosis and level of IL-1β and TNF-α within the cells demonstrated a notable decrease(P＜0.05).Rho was a target gene of miR-338-3p,and over-expression of Rho attenuated the effect of miR-338-3p mimic on IL-13-induced injury and inflammation in BEAS-2B cells.Conclusions Up-regulation of miR-338-3p can inhibit asthma-related airway inflammation and injury of lung epi-thelial cells with a potential mechanism targeting at Rho gene.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Objective:To investigate the effects of short-peptide-based enteral nutrition on nutritional status, immune function, and chemotherapy-related adverse reactions in children with acute lymphoblastic leukemia (ALL).Methods:A total of 106 children with ALL receiving chemotherapy at the Affiliated Hospital of Jining Medical University between January 2021 and April 2022 were enrolled. According to the principle of between-group baseline data matching, the patients were divided into observation group and control group by random number table method, with 53 cases in each group. All patients received chemotherapy according to the CCCG-ALL-2020 protocol established by the Multi-center Cooperative Group of the Chinese Society of Pediatric Oncology (2020). The control group received a regular diet, while the observation group received a regular diet supplemented with short-peptide-based enteral nutrition. The incidence rates of malnutrition, hypoproteinemia, hypoalbuminemia, abnormal immunoglobulin levels (IgG, IgM, IgA), and adverse reactions (liver injury, infection) were compared between both groups before chemotherapy and at the end of each of the following seven chemotherapy phases: Induction remission therapy (PVDL), Induction remission therapy (CAT), Early intensification therapy (CAT+), Consolidation therapy (HDMTX), Interim maintenance therapy, Reinduction therapy, and prior to the end of Maintenance therapy. Normally or approximately normally distributed measurement data were expressed as xˉ± s and compared by independent samples t-test. Counting data were expressed as n (%) and compared by χ2 test. Results:During the CAT phase, the incidence of malnutrition was significantly lower in the observation group than in the control group [20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034]. The incidence of hypoproteinemia was significantly lower in the observation group during HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [47.2% (25/53) vs. 69.8% (37/53), χ2=5.60, P=0.018; 45.3% (24/53) vs. 67.9% (36/53), χ2=5.53, P=0.019; 41.5% (24/53) vs. 64.2% (34/53), χ2=5.45, P=0.020; 28.3% (15/53) vs. 54.7% (29/53), χ2=7.62, P=0.006, respectively]. The incidence of hypoalbuminemia was significantly lower in the observation group during CAT+, HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [5.7% (3/53) vs. 22.6% (12/53), χ2=6.29, P=0.012; 9.4% (5/53) vs. 26.4% (14/53), χ2=5.19, P=0.023; 9.4% (5/53) vs. 28.3% (15/53), χ2=6.16, P=0.013; 7.6% (4/53) vs. 24.5% (13/53), χ2=5.68, P=0.017; 3.8% (2/53) vs. 18.9% (10/53), χ2=6.01, P=0.014, respectively]. For IgG, incidence was significantly lower in the observation group during Interim maintenance, Reinduction, and prior to the end of Maintenance therapy [7.6% (4/53) vs. 22.6% (12/53), χ2=4.71, P=0.030; 20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034; 11.3% (6/53) vs. 26.4% (14/53), χ2=3.94, P=0.047, respectively]. For IgM, incidence was significantly lower in the observation group during the CAT and CAT+ phases [45.3% (24/53) vs. 66.0% (35/53), χ2=4.63, P=0.032; 58.5% (31/53) vs. 77.4% (41/53), χ2=4.33, P=0.037, respectively]. For IgA, incidence was significantly lower in the observation group during Reinduction therapy and Interim maintenance [22.6% (12/53) vs. 45.3% (24/53), χ2=6.06, P=0.014; 9.4% (5/53) vs. 24.5% (13/53), χ2=4.28, P=0.038, respectively]. For liver injury, incidence was significantly lower in the observation group during the CAT, CAT+, and prior to the end of Maintenance phases [22.6% (12/53) vs. 43.4% (23/53), χ2=5.16, P=0.023; 26.4% (14/53) vs. 50.9% (27/53), χ2=6.72, P=0.010, 11.3% (6/53) vs. 26.4%(14/53), χ2=3.94、 P=0.047,respectively]. For infection, incidence was significantly lower in the observation group during the CAT+ and HDMTX phases [35.9% (19/53) vs. 56.6% (30/53), χ2=4.59, P=0.032; 24.5% (13/53) vs. 43.4% (23/53), χ2=4.21, P=0.040, respectively]. Conclusions:Short-peptide-based enteral nutrition demonstrates significant advantages in the treatment of pediatric ALL. It provides substantial support for patient treatment and recovery by improving nutritional status, modulating immune function, and reducing chemotherapy-related adverse reactions.

Objective:To analyze the epidemiological characteristics and risk factors of rotavirus infected in children aged 3-5 years seeking treatment for diarrhea in Jining area.Methods:The epidemiological data of 698 children aged 3-5 years seeking treatment for diarrhea in Jining area hospitals from September 2022 to September 2023 were collected, and fecal samples were collected for laboratory examination. The epidemiological characteristics of the rotavirus infection were analyzed, and logistic regression analysis was applied to analyze the risk factors of rotavirus infection in children aged 3-5 years seeking treatment for diarrhea in Jining area. A predictive model of rotavirus infection in children aged 3-5 years seeking treatment for diarrhea in Jining area was established based on decision tree, and the predictive performance of the model was verified by receiver operating characteristic (ROC) curve.Results:The detection of rotavirus antigen showed 302 positive cases, with a positive rate of 43.27% (302/698). Gender distribution: There was no statistically significant difference in the positive rate of rotavirus infection in these diseased children etween different genders ( χ2=1.862, P=0.172). Age distribution: The positive rate of rotavirus infection in these diseased children showed a decreasing trend with age ( χ2=28.893, P<0.001). Time distribution: There was a statistically significant difference in the positive rate of rotavirus infection in these diseased children among different months ( χ2=241.607, P<0.001), showing obvious seasonal characteristics, the high incidence months were from October to the following March, the highest positive rate was in December, and the lowest was in July. Rotavirus genotype: The G genotype result showed that G9 was the most common, P genotype result showed that P[8] was the most common, and the G/P combination genotype result showed that G9P[8] was the most common. Multivariate Logistic regression analysis showed that having finger sucking habits ( OR=4.193, P=0.018), lack of vaccination against rotavirus ( OR=1.947, P=0.002), whether to clean hands before feeding ( OR=4.719, P=0.007), and a history of contact with rotavirus infected children ( OR=4.976, P=0.001) were independent risk factors for rotavirus infection in children aged 3-5 years old who seek treatment for diarrhea in Jining area. The sensitivity of the decision tree model was 58.94%, the specificity was 87.12%, and the AUC was 0.814, indicating that the four selected risk factors could predict rotavirus infection well. Conclusions:Children aged 3-5 years old who seek treatment for diarrhea in Jining area have a relatively high positive rate of rotavirus infection, showing obvious age and time characteristics. The genotype distribution was mainly G9, P[8], and G9P[8]. Rotavirus infection is related to finger sucking habits, lack of vaccination against rotavirus, whether to clean hands before feeding, and a history of contact with rotavirus infected children.

Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5％.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)× 109/L,which was significantly higher than 41.0(22.0,82.5)×109/L of wild-type patients(P＜0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P＞0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2 and M4,less frequently in M3 and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P＞0.05).A total of 118 AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6 than wild-type ones(P＜0.01).97.1％of 34 patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2％),NRAS(32.4％),FLT3-ITD(32.4％),DNMT3A(32.4％)and KRAS(23.5％),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon 3.ALL of them are exclusively missense mutations,and most often present in conjunction with NPM1 mutations.FAB typing of PTPN11 mutation is mostly manifested as M5 subtype,which is associated with higher platelet counts.

Objective:To establish a model to predict the overall survival(OS)rate of patients with diffuse large B-cell lymphoma(DLBCL)based on systemic inflammatory indicators,and study whether the new model combined with inflammatory related parameters is more effective than the conventional model using only clinical factors to predict the OS of patients with DLBCL.Methods:The clinical data of 213 patients with DLBCL were analyzed retrospectively.Backward stepwise Cox regression analysis was used to screen independent prognostic factors related to OS,and a nomogram for predicting OS was constructed based on these factors.Akaike information criterion(AIC)and Bayesian information criterion(BIC)were used to evaluate the fitting of the model,the consistency index(C-index),area under receiver operating characteristic(ROC)curve(AUC)and calibration curve were used to evaluate the prediction accuracy of nomogram,and decision curve analysis(DCA)and Kaplan Meier curve were used to evaluate the clinical practicability of nomogram.Results:Multivariate analysis confirmed that age,ECOG PS score,serum lactate dehydrogenase(LDH)level,systemic immune inflammatory index(SII),and prognostic nutritional index(PNI)were used to construct the nomogram.The AIC and BIC of the nomogram were lower than the International Prognostic Index(IPI)and the National Comprehensive Cancer Network(NCCN)-IPI,indicating that the nomogram had better goodness of fit.The C-index and AUC of the nomogram were higher than IPI and NCCN-IPI,indicating that the prediction accuracy of the nomogram had been significantly improved,and the calibration curve showed that the prediction results were in good agreement with the actual survival results.DCA showed that the nomogram had better clinical net income.Kaplan Meier curve showed that patients could be well divided into low-risk,medium-risk and high-risk groups according to the nomogram score(P＜0.001).Conclusion:The nomogram combined with inflammatory indicators can accurately predict the individual survival probability of DLBCL patients.

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.
Animals ; Medicine, Chinese Traditional ; Heart Failure ; Heart Diseases ; Chronic Disease ; Models, Animal