Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

Objective:To explore the prognostic value of serum free light chain in chronic lymphocytic leukemia patients.Methods:Retrospective cohort study was conducted. One hundred and fifty-six newly diagnosed chronic lymphocytic leukemia(CLL) patients in the first affiliated hospital of Nanjing Medical University from January 2016 to December 2020 were included in the retrospective analysis. Among them, there were 106 males and 50 females, with a median age of 60.7 (53.4, 66.0) years old.Serum sample was collected, serum free light chains were detected, and patients were divided into a treatment group (106 cases) and a follow-up group (50 cases) based on the presence of treatment indications.The threshold of serum free light chain(sFLC) was defined by the reference range of the instruction manual and ROC curve. Three indicators were used, including sFLCR, sFLC(κ+λ) and sFLC(κ-λ). Patients were divided into normal sFLCR group ( n=61)and abnormal group( n=95), as well as sFLC (κ+λ) low value group ( n=88) and high value group ( n=68), and sFLC (κ-λ) low value group ( n=64) and high value group ( n=92).The abnormal group and high value group were enrolled as the experimental group, while the normal group and low value group were enrolled as control group. Chi-square test and Fisher′s exact test were used to compare the clinical data, cytogenetics, and molecular biology characteristics of patients in two groups, Kaplan-Meier method was used to analyze the median treatment-free survival (TFS) of the patients, and Cox regression was used to screen the prognostic factors of the patients. Results:The proportion of Rai stage Ⅰ-Ⅳ ( χ2=8.16, P<0.05 and χ2=7.63, P<0.05 and χ2=5.45, P<0.05), Binet stage B-C( χ2=4.11, P<0.05 and χ2=9.43, P<0.05 and χ2=7.34, P<0.05), β 2-microglobulin>3.5 mg/L( χ2=5.13, P<0.05 and χ2=18.3, P<0.05 and χ2=12, P<0.05), ATM gene mutation rate( χ2=6.21, P<0.05 and χ2=4.88, P<0.05 and χ2=5.19, P<0.05), and immunoglobulin heavy chain variable region (IGHV) mutation free rate ( χ2=18.9, P<0.05 and χ2=24.6, P<0.05 and χ2=10.4, P<0.05)in the experimental group were significantly higher than that in control group 1 ( P<0.05). Multivariate analysis indicated that sFLC(κ+λ) ( HR=1.615,95% CI 1.012-2.576, P=0.044), β 2-microglobulin>3.5 mg/L( HR=2.103,95% CI 1.356-3.262, P=0.001) and TP53 deletion and/or mutation( HR=1.892,95% CI 1.082-3.308, P=0.025) were independent prognostic factors affecting the patients time to first treatment(TFT). Conclusions:Serum free light chains can predict the risk of early treatment and have good prognostic significance in newly diagnosed CLL patients.

OBJECTIVE: To explore the clinical effect of personalized puncture planning before surgery using Picture Archiving and Communication System (PACS) in the treatment of osteoporotic vertebral compression fractures in the elderly. METHODS: A total of 69 elderly patients with osteoporotic vertebral compression fractures treated by percutaneous vertebroplasty from January 2020 20 to December 2021 with more than 1 year of follow-up were analyzed retrospectively. Thirty-four patients were individualized for preoperative planning with PACS software (observation group), including 8 males and 26 females, with a mean age of (73.30±7.96) years old;and 35 patients were treated with conventional treatment (control group), including 7 males and 28 females, with a mean age of (77.30±7.84) years old. The operation time, the amount of cement injection, cement leakage rate, bone watertight diffusion and refracture within 1 year between two groups were observed and compared. The Cobb's angle, low back pain visual analogue scale(VAS) and the modified Oswsetry disability indexes(ODI) before surgery and 1 day, 1 year after surgery were compared between two groups. RESULTS: Both groups successfully completed the operation without serious surgical complications, 2 refractures occurred in the control group. The operation time in the observation group was(41.9±11.9) min, which was less than that in the control group (52.7±13.6) min (P<0.05). There was no significant difference in the cement injection volume between two groups (P>0.05). Two cases of cement leakage in the observation group was less than 8 in the control group (P<0.05). The bone cement distribution index of two groups had significant difference(P<0.05). There were no significant differences between two groups in Cobb's angle of the injured vertebras and ODI before and 1 day after surgery(P>0.05), however, the comparative differences were statistically significant at 1 year after surgery(P<0.05). There was no significant difference in the VAS between two groups at each time period(P>0.05). CONCLUSION Using the PACS software to plan personalized puncture scheme can reduce the operation time, reduce the cement leakage rate, improve the diffusion of bone cement and longer maintain the postoperative form of vertebral body and the functional state of patients' lumbar back.
Humans ; Male ; Female ; Aged ; Vertebroplasty/methods* ; Fractures, Compression/diagnostic imaging* ; Spinal Fractures/diagnostic imaging* ; Osteoporotic Fractures/diagnostic imaging* ; Aged, 80 and over ; Retrospective Studies ; Radiology Information Systems

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective:To assess the presence of chemotherapy-induced abnormal myocardial perfusion using SPECT myocardial perfusion imaging (MPI) in patients with malignant hematologic diseases before hematopoietic stem cell transplantation (HSCT), and to explore its predictive value for mid-to-long-term mortality risk after transplantation.Methods:From March 2016 to August 2022, 139 patients with malignant hematologic diseases (80 males, 59 females; age (45.7±13.0) years) who underwent resting MPI to assess the presence of chemotherapy-induced abnormal myocardial perfusion before HSCT at the First People′s Hospital of Changzhou were prospectively included. Baseline-data were collected and patients were followed up for mid-to-long-term (≥100d) adverse outcomes after transplantation. Overall survival (OS) of each patient was recorded. The χ2 test and independent-sample t test were used for data analysis. Cox regression analysis was utilized to identify independent risk factors affecting OS. Kaplan-Meier method and log-rank test were used for survival analysis. Results:The median follow-up time of 139 patients was 41.6(19.5, 65.6) months, with all-cause mortality of 28.8%(40/139), and the cardiovascular mortality was 42.5%(17/40). The prior cardiotoxic therapies rate (anthracycline dose ≥250mg/m 2) was higher in the death group compared to that in the survival group (15.0% (6/40) vs 5.1% (5/99); χ2=3.87, P=0.049). Pre-transplant abnormal myocardial perfusion rate was also higher in the death group compared to that in the survival group (55.0%(22/40) vs 22.2%(22/99); χ2=15.19, P<0.001). But pre-transplant left ventricular ejection fraction (LVEF) was lower in the death group compared to that in the survival group ((60.4±5.2)% vs (62.9±3.9)%; t=-3.07, P=0.003). Cox multivariate regression analysis showed that the abnormal myocardial perfusion indicated by MPI before transplantation was an independent risk factor affecting OS after HSCT in patients with malignant hematologic diseases (hazard rate ( HR)=2.70, 95% CI: 1.33-5.46, P=0.006). Kaplan-Meier analysis showed the 1-, 2-, 5-year OS rates of patients with the abnormal myocardial perfusion and the normal myocardial perfusion were 73.5%, 69.1%, 49.2% and 94.6%, 89.9%, 81.6%, respectively, with significant difference ( χ2=17.01, P<0.001). Conclusions:Patients with abnormal myocardial perfusion detected by MPI before HSCT for malignant hematologic diseases have a poorer prognosis, characterized by lower post-transplantation OS rates. The utilization of MPI for assessing abnormal myocardial perfusion before transplantation in patients with malignant hematologic diseases can aid in predicting the mid-to-long-term mortality risk after transplantation.

Objective:To observe the application value of Yifei Fumai Tang in the treatment of difficulty offline and intensive care unit-acquired weakness(ICU-AW).Methods:Used random number table method,60 patients with difficulty offline and ICU-AW who were admitted to our hospital from June 2022 to June 2024 were divided into control group(received conventional Western medicine comprehensive treatment,n=30)and study group(received Yifei Fumai Tang treatment in addition to the control group,n=30).Medical Research Council(MRC),Barthel Index(BI)scores,clinical indicators(total mechanical ventilation time,weaning success rate,secondary intubation rate,ICU stay,and mobilization time),diaphragm thickness,diaphragm mobility,and incidence of adverse reactions between two groups were compared.Results:Compared with the control group at 7 d after treatment and 14 d after treatment,the MRC and BI scores in the study group were higher(P＜0.05).Compared with the control group,the study group had lower rate of secondary intubation rate,shorter total mechanical ventilation time,ICU stay time,and mobilization time,higher weaning success rate,and greater diaphragm thickness,diaphragm mobility(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Yifei Fumai Tang combined with Western Medicine in the treatment of Difficulty Offline and ICU-AW,can effectively improve the prognosis of patients,shorten total mechanical ventilation time,ICU stay,mobilization time,increase weaning success rate,and improve respiratory function.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".