Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.

Objective To noninvasively predict isocitrate dehydrogenase(IDH)status of glioma via combining imaging and clini-cal features before surgery,so as to provide basis for individualized clinical treatment decision.Methods A total of 47 patients with glioma confirmed by pathological and molecular genetic tests were included,including 20 with IDH mutant type and 27 with IDH wild type.After diffusion tensor imaging(DTI)scanning,fractional anisotropy(FA)and mean diffusivity(MD)values of tumor paren-chyma were calculated.Combining DTI parameters with MRI morphological features of tumor,blood neutrophil/lymphocyte ratio(NLR)and patient's age,binary logistic regression model was established to effectively predict IDH status of glioma patients before surgery.Results There were significant differences in FAmean/FANAWM,MDmin,NLR,tumor location and age between IDH mutant type and IDH wild type groups(P<0.05).The binary logistic regression model concluding,FAmean/FANAWM,MDmin,cystic degeneration,NLR and age,predicted IDH status of glioma with area under the curve(AUC)of 0.961 and 95%confidence interval(CI)of 0.914-1.00.Conclusion The regression model established via combining DTI,MRI morphological features and blood NLR has great performance in classifying IDH status of glioma,and can help predict IDH status noninvasively before surgery,so as to assist clinical individualized treatment.

Depression's high recurrence rate and severe consequences pose significant challenges to public health.To address this issue effectively,this review explores the innovative application of wearable devices in monitoring and intervening in depression,surpassing the limitations of traditional subjective assessments and patient self-reports.The paper systematically analyzes recent studies utilizing wearable devices to monitor physiological and behavioral indicators of depression,categorizing them by different technological types and evaluating their practical effectiveness in early diagnosis and intervention.The findings indicate that wearable devices can continuously monitor physiological indicators and behavioral patterns related to depression,potentially enabling early detection of depressive episodes and supporting timely interventions.Despite challenges such as data privacy and user acceptance,wearable technology holds immense potential in enhancing clinical outcomes in depression treatment.

Objective To explore the clinical efficacy of ginseng schisandra decoction in children with lobar pneumonia(lung spleen deficiency syndrome)induced by mycoplasma pneumoniae infection and improvement of inflammatory indicators.Method 84 children with lobar pneumonia(lung spleen deficiency syndrome)caused by mycoplasma infection admitted to the First Clinical Hospital of Jilin Academy of Traditional Chinese Medicine from January 2020 to July 2022 were selected and randomly divided into two groups with 42 cases each.The conventional group was treated according to the traditional treatment plan,while the combined group was treated with ginseng and schisandra decoction in addition to the traditional treatment plan.After 7 days,compare the differences in traditional Chinese medicine syndrome scores,clinical efficacy,inflammatory indicators,and total incidence of adverse reactions between the two groups of children.Result The results showed that the traditional Chinese medicine syndrome score and inflammatory indicators in the combined group were lower than those in the conventional group(P<0.05),and the clinical efficacy level distribution was better than that in the conventional group(P<0.05).The total effective rate was higher than that in the conventional group(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion In the treatment of children with lobar pneumonia(lung spleen deficiency syndrome)caused by Mycoplasma pneumoniae infection,the modified Ginseng Wuweizi decoction has a positive therapeutic effect and good safety,and is worth promoting.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Electroacupuncture treatment of primary insomnia is widely used and with confirmed efficacy. The factors influencing the therapeutic effect of electroacupuncture include waveform selection, treatment frequency, stimulation intensity, stimulation time and acupoint selection. The mechanism of electroacupuncture in treating this disease mainly includes regulating the levels of excitatory neurotransmitters, γ-aminobutyric acid, melatonin and interleukin cytokines.

ObjectiveTo explore the mechanism of Shenqi Gualou Xiebai Banxia Decoction （参芪瓜蒌薤白半夏汤， SGXBD） in the treatment of atherosclerosis. MethodsThirty Apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into five groups： model group， rosuvastatin group， low-， moderate-， and high-dose SGXBD， with six mice in each group. They were fed a high-fat diet to prepare for atherosclerosis model. Another six C57BL/6J wild-type mice were set as the blank group. After modeling， the low-， moderate-， and high-dose SGXBD groups were gavaged with 6.46， 12.92， and 25.84 g/（kg·d） of SGXBD， respectively. The rosuvastatin group was given 1.55 mg/（kg·d） of rosuvastatin tablets by gavage. The blank group and model group were given 0.5 ml saline by gavage. After four weeks， the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum of each group were detected， as well as TC and TG in the liver. The serum bile acid level was detected by enzyme cycling colorimetry. The mRNA and protein expression of peroxisome proliferator-activated receptor γ （PPARγ）， sterol regulatory element-binding protein 2 （SREBP2）， 3-hydroxy-3-methylglutaryl-CoA reductase （HMGCR）， and cholesterol 7α-hydroxylase （CYP7A1） in the liver were detected by real-time RT-PCR and Western blot. ResultsCompared with the blank group， the model group showed significant increases in serum TG， TC， and LDL-C levels， and significant decreases in HDL-C and bile acid levels； the levels of TG and TC in the liver， as well as the expression of SREBP2 and HMGCR proteins and mRNA in the liver significantly increased， while the expression of PPARγ and CYP7A1 proteins and mRNA significantly decreased （all P＜0.01）. Compared with the model group， the rosuvastatin group and high-dose SGXBD group showed significant decreases in serum TG， TC， and LDL-C levels and liver TG and TC levels， and significant increases in bile acid levels； the expression of PPARγ and CYP7A1 proteins and mRNA increased， while the expression of SREBP2 and HMGCR proteins and mRNA decreased； the low-dose SGXBD group showed significant decreases in serum TC and LDL-C levels and liver TC level （P＜0.05 or P＜0.01）. Compared with the rosuvastatin group， the low-dose SGXBD group had a significantly higher liver TC level， while the high-dose SGXBD group had a significantly lower liver TC level， CYP7A1 mRNA level， and PPARγ protein expression level， and a significantly higher SREBP2 protein expression level （P＜0.05 or P＜0.01）. Compared with the low- and moderate-dose groups， the high-dose SGXBD group had significantly lower serum TG and liver TC levels （P＜0.05）. ConclusionSGXBD may improve blood lipid levels and exhibit anti-atherosclerotic effects by regulating the protein level of PPARγ and simultaneously affecting the synthesis of liver cholesterol and the conversion of cholesterol to bile acids.

Objective : To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis． Methods : Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results: Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ． Conclusion The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.