Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

In recent years, remarkable advances have been made in lung transplantation regarding donor evaluation, perioperative support, and immune regulation, laying a foundation for improving the long-term survival of recipients. The rational application of extended criteria donor lungs and the popularization of ex vivo lung perfusion technology have enhanced the utilization efficiency and safety of marginal donor lungs. Refined assessment of risk factors such as donors’ smoking history and infectious status has reduced the incidence of primary graft dysfunction and postoperative infection. In terms of recipient management, individualized assessment systems have been gradually optimized. The standardized application of intraoperative extracorporeal membrane oxygenation and the development of minimally invasive surgical techniques have effectively alleviated perioperative injuries. The optimization of postoperative immunosuppressive regimens and advances in rejection monitoring technologies have further improved the long-term survival of grafts. Nevertheless, chronic graft dysfunction and recurrent or refractory infections remain the major bottlenecks restricting long-term prognosis. Future research should focus on expanding donor sources, improving the repair quality of marginal donor lungs, promoting precise immunosuppression and anti-infection strategies, and comprehensively enhancing the long-term survival rate and quality of life of lung transplant recipients.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Objective:To explore the effectiveness of immersive virtual reality (VR)-guided core stability-assisted training in improving the balance of ischemic stroke survivors.Methods:Sixty-six hemiplegic ischemic stroke survivors were randomly divided into a conventional rehabilitation training group (CON) of 32 and an immersive VR-guided core stability-assisted training group (VR-TOT) of 34. In addition to basic internal medical treatment, the CON group underwent conventional rehabilitation therapy, while the VR-TOT group received VR-guided core stability-assisted training. Before and after 4 weeks of the treatments, the subjects′ balance was evaluated using the Fugl-Meyer balance scale. A three-dimensional force platform was used to collect the sway amplitude, sway speed, peripheral area and total trajectory length of the center of pressure COP of the bilateral plantar in the left-right and anterior-posterior directions while the subjects stood with the eyes open and closed.Results:After the treatments, the average Fugl-Meyer balance scores of both groups had improved significantly. In the eyes-open condition, after the treatment, there was a significant decrease in the average COP sway amplitude in the anteroposterior direction on the hemiplegic side among the CON group, as well as in both the mediolateral and anteroposterior directions on both sides in the VR-TOT group. The sway velocity in the anteroposterior direction on the hemiplegic side had decreased significantly in both groups, and the sway velocity in both the mediolateral and anteroposterior directions on the non-hemiplegic side had also decreased significantly. In the CON group the peripheral area on the non-hemiplegic side had decreased and the total trajectory length had shortened significantly. In the VR-TOT group there were significant decreases in the peripheral area on both sides and in the total trajectory length on both sides. Comparing the two groups after treatment, the peripheral area on the hemiplegic side in the VR-TOT group was significantly smaller. In the eyes-closed condition, the sway amplitude of the COP on the hemiplegic side in the anteroposterior direction and on the non-hemiplegic side in both the mediolateral and anteroposterior directions had decreased significantly in the VR-TOT group after the treatment. The average sway velocity had decreased significantly in the anteroposterior direction on the non-hemiplegic side in the CON group. In the VR-TOT group this was observed in the anteroposterior direction on the hemiplegic side and in both the mediolateral and anteroposterior directions on the healthy side. In the CON group the average peripheral area of the COP on the hemiplegic side had decreased, and the total trajectory length had shortened, both significantly. In the VR-TOT group, the peripheral area on the non-hemiplegic side had decreased significantly as well.Conclusions:Core stability-assisted training based on immersive virtual reality can effectively improve the balance of ischemic stroke survivors. It shows promise for clinical application.

Objective:To investigate the expression of RNA binding protein ELAVL1 in prostate cancer(PCa),especially hor-mone-sensitive prostate cancer(HSPC),and its relationship with tumor proliferation.This study further aims to reveal the molecular mechanism by which ELAVL1 promotes HSPC proliferation by stabilizing SOX4 mRNA in an m6A-dependent manner.Methods:The expression of ELAVL1 in PCa tissues and its relationship with prognosis were analyzed in the Cancer Genome Atlas(TCGA)data-base,and the differences in HSPC and hormone-resistant prostate cancer(HRPC)were compared.And its relationship with prognosis were analyzed in the Cancer Genome Atlas(TCGA)database,and the differences in HSPC and hormone-resistant prostate cancer(HRPC)were compared.Western blot was used to detect ELAVL1 protein expression in PCa cell lines.After ELAVL1 knockdown by siRNA,cell proliferation was evaluated using CCK-8 assays,and changes in downstream target genes were detected by RT-qPCR.Tumor xenograft experiments in nude mice were performed to further assess the impact of ELAVL1 on tumor growth.The interaction be-tween ELAVL1 and SOX4 mRNA was verified by RIP-seq.And the mRNA and protein levels of SOX4 after knockdown of ELAVL1 were detected by RT-qPCR and Western blot,respectively.CCK-8 was used to evaluate the effect of SOX4 knockdown on cell prolifer-ation.MeRIP-qPCR was used to detect the m6A modification level of SOX4 and the effect of knocking down METTL3.RNA pull-down experiments verified the interaction between SOX4 RNA fragments and ELAVL1 protein.RNA stability experiments evaluated the effect of ELAVL1 knockdown on SOX4 mRNA stability.Results:The expression of ELAVL1 in PCa cells was higher than that in normal prostate epithelial cells.The prognosis of patients with high expression of ELAVL1 was significantly worse than that of patients with low expression.In the GSE32269 dataset,the expression level of ELAVL1 in HSPC was significantly higher than that in HRPC.After knocking down of ELAVL1 in LNCaP and VCaP cells,CCK-8 experiments showed that the cell proliferation ability was significantly af-fected after knocking down ELAVL1,and overexpressed ELAVL1 promoted the proliferation of HSPC cells.The results of in vivo studies showed that knockdown of ELAVL1 significantly inhibited the tumorigenic capacity of LNCaP cells and resulted in a marked reduction in xenograft tumor mass.The levels of SOX4 mRNA and protein in LNCaP and VCaP cells were significantly higher than those in nor-mal prostate epithelial cells RWPE-1.RIP-qPCR confirmed the interaction between ELAVL1 protein and SOX4 mRNA.After knocking down of ELAVL1,the expression levels of SOX4 mRNA and protein were significantly decreased.After knocking down of SOX4,the proliferation ability of LNCaP and VCaP cells was significantly inhibited.Conclusion:ELAVL1 is highly expressed in HSPC.High expression of ELAVL1 is associated with the proliferation of HSPC.SOX4 is a downstream molecule of ELAVL1 which promotes the proliferation of HSPC.ELAVL1 enhances the stability of SOX4 mRNA through an m6A-dependent mechanism.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.

Objective:To explore the effectiveness of immersive virtual reality (VR)-guided core stability-assisted training in improving the balance of ischemic stroke survivors.Methods:Sixty-six hemiplegic ischemic stroke survivors were randomly divided into a conventional rehabilitation training group (CON) of 32 and an immersive VR-guided core stability-assisted training group (VR-TOT) of 34. In addition to basic internal medical treatment, the CON group underwent conventional rehabilitation therapy, while the VR-TOT group received VR-guided core stability-assisted training. Before and after 4 weeks of the treatments, the subjects′ balance was evaluated using the Fugl-Meyer balance scale. A three-dimensional force platform was used to collect the sway amplitude, sway speed, peripheral area and total trajectory length of the center of pressure COP of the bilateral plantar in the left-right and anterior-posterior directions while the subjects stood with the eyes open and closed.Results:After the treatments, the average Fugl-Meyer balance scores of both groups had improved significantly. In the eyes-open condition, after the treatment, there was a significant decrease in the average COP sway amplitude in the anteroposterior direction on the hemiplegic side among the CON group, as well as in both the mediolateral and anteroposterior directions on both sides in the VR-TOT group. The sway velocity in the anteroposterior direction on the hemiplegic side had decreased significantly in both groups, and the sway velocity in both the mediolateral and anteroposterior directions on the non-hemiplegic side had also decreased significantly. In the CON group the peripheral area on the non-hemiplegic side had decreased and the total trajectory length had shortened significantly. In the VR-TOT group there were significant decreases in the peripheral area on both sides and in the total trajectory length on both sides. Comparing the two groups after treatment, the peripheral area on the hemiplegic side in the VR-TOT group was significantly smaller. In the eyes-closed condition, the sway amplitude of the COP on the hemiplegic side in the anteroposterior direction and on the non-hemiplegic side in both the mediolateral and anteroposterior directions had decreased significantly in the VR-TOT group after the treatment. The average sway velocity had decreased significantly in the anteroposterior direction on the non-hemiplegic side in the CON group. In the VR-TOT group this was observed in the anteroposterior direction on the hemiplegic side and in both the mediolateral and anteroposterior directions on the healthy side. In the CON group the average peripheral area of the COP on the hemiplegic side had decreased, and the total trajectory length had shortened, both significantly. In the VR-TOT group, the peripheral area on the non-hemiplegic side had decreased significantly as well.Conclusions:Core stability-assisted training based on immersive virtual reality can effectively improve the balance of ischemic stroke survivors. It shows promise for clinical application.

Objective To evaluate the effect of donor gender on short-term survival rate of lung transplant recipients. Methods A retrospective analysis was conducted on the data of 1 066 lung transplant recipients. The log-rank test was used to evaluate the differences in short-term fatality among different donor gender groups and donor-recipient gender combination groups. Multivariate Cox regression, propensity score (PS) regression, and propensity score matching (PSM) were employed to control for confounding factors and further assess the differences in fatality. Subgroup analyses were also performed based on donor gender. Results Multivariate Cox regression analysis showed no statistically significant differences in fatality at 30 days, 1 year, 2 years and 3 years postoperatively between male and female donor groups (all P>0.05). After PS regression and PSM, univariate Cox regression analysis indicated that recipients from female donors had a higher fatality at 2 years postoperatively compared to those from male donors, with hazard ratios (95% confidence intervals) of 1.29 (1.01-1.65) and 1.36 (1.03-1.80) respectively. Multivariate Cox regression analysis also revealed no statistically significant differences in fatality at various follow-up time points among different donor-recipient gender combination groups (all P>0.05). Subgroup analyses based on donor sex showed no statistically significant differences in fatality among recipients of different gender within either male or female donor groups (all P>0.05). Conclusions Female donors may reduce the short-term postoperative survival rate of lung transplant recipients, but this negative impact is not sustainable in the long term. At present, there is no evidence to support the inclusion of sex as a factor in lung allocation rules.

OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional