Osteosarcoma is a highly aggressive malignant bone tumor whose immuno evasion mechanisms play a pivotal role in tumor progression and therapeutic resistance. Recent studies have identified mitochondrial transfer as a novel mode of intercellular communication that significantly influences metabolic reprogramming and immune evasion in osteosarcoma cells. This mechanism operates through three principal pathways: (1) enhancing energy metabolic efficiency in tumor cells; (2) mitigating intracellular oxidative stress; and (3) modulating immune checkpoint molecule expression. Collectively, these alterations impair host immune surveillance while promoting tumor proliferation, invasion, and distant metastasis through metabolic remodeling, immune tolerance induction, and tumor microenvironment reconstruction. This review systematically elucidates the molecular mechanisms by which mitochondrial transfer regulates immune evasion in osteosarcoma and its dynamic impact on the tumor microenvironment. Furthermore, we discuss the translational potential of targeting this pathway for precision therapy and outline future research directions in this emerging field.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective To investigate the impact of continuous nebulization therapy after lung transplantation on pulmonary function and related complications in lung transplant recipients. Methods A retrospective analysis was conducted on the general data of 71 recipients who underwent allogeneic lung transplantation at the Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2024. Recipients were divided into observation group (those who continued nebulization therapy for more than 3 months after discharge) and control group (those who discontinued nebulization therapy on their own). The main observation indicators were pulmonary function indicators at 6 months after surgery, including forced expiratory volume in the first second as a percentage of predicted value (FEV₁% pred), forced vital capacity as a percentage of predicted value (FVC% pred), ratio of forced expiratory volume in the first second to forced vital capacity as a percentage of predicted value (FEV₁/FVC% pred), forced expiratory flow at 25%, 50% and 75% of forced vital capacity as a percentage of predicted value, and the percentage of predicted value of corrected carbon monoxide diffusion capacity measured by single-breath method, as well as the ratio of corrected carbon monoxide diffusion capacity to alveolar volume as a percentage of predicted value. Additionally, the annual incidence of postoperative pulmonary infections, survival rate and the rate of no severe airway complications were analyzed. Results At 6 months after lung transplantation, the FEV₁% pred and FVC% pred of the observation group were better than those of the control group [FEV₁% pred was 76% (60%, 91%) vs. 67% (62%, 78%), FVC% pred was (75 ± 13)% vs. (69 ± 11)%, both P<0.05]. The observation group had a lower annual incidence of pulmonary infections compared to the control group (P = 0.023), with a risk of 0.485 times that of the control group. There were no statistically significant differences between the two groups in median survival time and the rate of no severe airway complications (both P>0.05). Conclusions Continuous nebulization therapy after lung transplantation may effectively improve pulmonary function, reduce the annual incidence of pulmonary infections, and play a positive role in the long-term maintenance of pulmonary function.

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP＿L), and high-dose WPP group(15.5 g·kg~(-1), WPP＿H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP＿H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Lipid Metabolism/drug effects* ; Mice ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Diet, High-Fat/adverse effects* ; Liver/drug effects* ; Humans ; Disease Models, Animal ; Methionine

The efficacy mechanism of the alcoholic extract of Gnaphalium affine was investigated by observing its influence on oxidative stress and intestinal flora in rats modeled for chronic obstructive pulmonary disease(COPD). UPLC-MS was used to evaluate the quality of the alcoholic extract of G. affine, and 72 rats were randomly divided into six groups, with COPD models established in five groups by cigarette smoke combined with airway drip lipopolysaccharide, and the rats were given the positive drug of Danlong Oral Solution, as well as low-, medium-, and high-doses alcoholic extract of G. affine, respectively. After two weeks of continuous gastric gavage, the body weights and general morphology observations were performed; HE staining and Masson staining were used to verify the effects of the alcoholic extract of G. affine on alveolar inflammation and collagen deposition area in COPD rats; the oxidative stress indexes CAT and GSH in serum and SOD and MDA in lung tissue of the rats were measured, and the mRNA expression of HO-1, Nrf2, and NQO1 were determined by qRT-PCR. The protein expressions of HO-1, Nrf2, and NQO1 were determined by the Western blot method, and the mechanism by which the alcoholic extract of G. affine affected oxidative stress in COPD rats was explored. Finally, the influence of G. affine on the changes in intestinal flora caused by COPD was studied by 16S rRNA sequencing. The results showed that a total of 121 chemical components were identified by UPLC-MS, including 70 positive and 51 negative ion modes. In animal experiments, it was found that the alcoholic extracts of G. affine were able to reduce the percentage of collagen deposition, affect the oxidative stress indexes such as CAT, GSH, SOD, MDA, as well as the mRNA and protein expression of Nrf2, HO-1, and NQO1. The 16S rRNA sequencing results showed an increase in the level of Lactobacillales and a decrease in the level of Desulfovibrio and Desulfovibrionales, suggesting that the alcoholic extracts of G. affine could reverse the changes in intestinal flora caused by COPD. In conclusion, the alcoholic extracts of G. affine may exert anti-COPD effects by affecting the oxidative stress pathway and modulating the changes in intestinal flora.
Animals ; Oxidative Stress/drug effects* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Lung/metabolism*

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective:To investigate the mechanism of IL-23/STAT3/Th17 axis in severe acute pancreatitis(SAP)and the in-terventional effect of the Qingjie Huagong decoction(QJHGD).Methods:A rat model of SAP was established by injecting sodium tau-rocholate into the retrograde pancreatic duct.The blank group,model group,different doses of QJHGD administration groups and posi-tive group were set up respectively.HE staining was used to observe the pathology of pancreatic tissue.ELISA was used to detect serum lipase,α-amylase and inflammatory markers.By combining RT-qPCR,IHC,Western blot,and IF techniques,we elucidated the mechanism of QJHGD in protecting pancreatic tissue in SAP rats.Results:The levels of amylase,lipase,IL-1β,IL-6,IL-17,IL-23,TNF-α and TGF-β in the serum of SAP model rats in all dose groups of QJHGD were significantly reduced,and the effect was the best in medium dose group(P<0.05).The results of IHC and RT-qPCR revealed that the medium-and high-dose groups of QJHGD sig-nificantly reduced the expression of IL-23,STAT3,IL-17 protein and mRNA in the pancreatic tissue of this model(P<0.05).More-over,the Western blot results demonstrated that the expression of IL-23,STAT3,p-STAT3,and IL-17 proteins in SAP rats were sig-nificantly decreased in the medium-dose group of QJHGD(P<0.05);the IF assay indicated that Th17 cell differentiation in SAP rats was inhibited by all dose groups of QJHGD,with the most significant inhibition effect in the middle dose(P<0.05).Conclusion:QJH-GD regulates the activation of IL-23/STAT3/Th17 axis,thereby inhibiting Th17 cell differentiation and exerting a protective effect on pancreatic tissue.

Objective:To investigate the effect of chrysophanol(CHR)on cartilage injury in rats with osteoarthritis and its mechanism of regulating SIRT1/HMGB1/NF-κB signal pathway.Methods:Rat models of osteoarthritis were established and divided into negative control group,chrysophanol low(CHR-L,10 mg/kg),middle(CHR-M,20 mg/kg),high dose group(CHR-H,40 mg/kg),SIRT1 inhibitor(sirtinol 5 mg/kg)+chrysophanol high dose group(sirtinol+CHR-H),and normal healthy control group was set up.The degree of joint swelling was measured,and the inflammatory index was evaluated;the pain threshold(tenderness and heat pain)was measured;HE staining and safranine O staining were applied to detect the pathological changes of rat articular cartilage;the levels of serum inflammatory factors(IL-6,IL-1β,TNF-α)were detected by ELISA method;oxidative stress indexes(MDA,SOD,GSH-PX)were detected by micro method;TUNEL staining was used to detect apoptosis;Western blot was used to detect the protein expressions of SIRT1,HMGB1,NF-κB p65,p-NF-κB p65,MMP-13 and C-Caspase-3.Results:Compared with the normal healthy control group,the rats in negative control group had obvious pathological injury,such as destruction of articular cartilage structure,necrosis and reduction of chondrocytes,the joint swelling degree,arthritis index,levels of IL-6,IL-1β,TNF-α,content of MDA,chondrocyte apoptosis rate,expressions of apoptotic protein C-Caspase-3,HMGB1,NF-κB p65/p-NF-κB p65,MMP-13 proteins increased obviously,the tenderness threshold,heat pain threshold,activities of SOD,GSH-PX,and the expression of SIRT1 protein decreased obviously(P<0.05);compared with negative control group,the pathological injury of articular cartilage in CHR group improved obviously with the increase of dosage,the joint swelling degree,arthritis index,levels of IL-6,IL-1β,TNF-α,content of MDA,chondrocyte apoptosis rate,expression of apoptotic protein C-Caspase-3,HMGB1,NF-κB p65/p-NF-κB p65,MMP-13 proteins decreased obviously,the tenderness threshold,heat pain threshold,activities of SOD,GSH-PX,and the expression of SIRT1 protein increased obviously(P<0.05);compared with CHR-H group,sirtinol+CHR-H group was able to reverse the protective effect of CHR on cartilage injury to a certain extent.Conclusion:CHR can reduce the inflammation of articular cartilage,inhibit the apoptosis of chondrocytes and play a protective role in the cartilage injury of osteoarthritis rats by up-regulating the expression of SIRT1 and down-regulating the expressions of HMGB1 and NF-κB p65/p-NF-κB p65.