The pathogenesis of metabolic dysfunction-associated steatotic liver disease （MASLD） is fundamentally rooted in spleen deficiency and is closely associated with phlegm turbidity， damp-heat and blood stasis. Clinically， liver constraint with spleen deficiency and internal retention of damp turbidity represent the predominant traditional Chinese medicine （TCM） syndrome patterns. Researches have indicated intrinsic connections between the syndrome patterns and biological indicators such as gut microbiota and metabolic profiles. Regarding treatment， classical famous formulas， modern empirical formulas， and newly developed TCM drugs show positive effects in regulating glucose and lipid metabolism， improving insulin resistance， and alleviating metabolic inflammation， exhibiting multi-target mechanisms of action； acupuncture and other external therapies also provide adjunctive value. Nevertheless， current researches still have limitations such as the lack of high-quality clinical evidence and insufficient systematic elucidation of the uncerlying mechanisms. Future efforts should focus on conducting high-quality TCM clinical trials with hard endpoint outcomes such as hepatic histology outcomes， and utilizing modern technologies like multi-omics to elucidate TCM's mechanisms of action， thereby advancing the position of TCM as a first-line therapeutic strategy for MASLD.

Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Objective To evaluate the efficacy of Puerariae lobatae radix （PLR） and Anemarrhenae Rhizoma （AR） in preventing and treating Alzheimer’s disease （AD） and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride （AlCl₃） and D-galactose （D-gal） for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased （P<0.05）, while the SOD content was decreased considerably （P<0.01）. The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences （P<0.05）. The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

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

ObjectiveThis study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. MethodsUsing naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. ResultsBehavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota α‑diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e.g., L-homocitrulline), antioxidant defense (e.g., L-carnosine), neuroprotection (e.g., lithocholic acid), and DNA repair (e.g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. ConclusionThis study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammation-inhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the “microbiota-metabolite-brain” axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiota-metabolite modulation for combating neurodegenerative diseases.

Objective:To analyze the clinical efficacy of pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula for reconstructing bone defects after surgery for malignant bone tumors in children and adolescents.Methods:A retrospective analysis was performed on the data of 54 patients who underwent pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula reconstruction for bone defects after surgery for malignant bone tumors at the Bone and Soft Tissue Tumor Treatment Center of Peking University People's Hospital from September 2015 to September 2023. There were 39 males and 15 females, with an age of 12.4±5.6 years (range, 4 to 23 years). The tumor types included 33 cases of osteosarcoma, 19 cases of Ewing sarcoma, and 2 cases of soft tissue sarcoma. All cases were at Enneking stage IIB. The tumor locations were 30 cases in the femur, 19 cases in the tibia, 4 cases in the ilium, and 1 case in the humerus. The survival rate, bone healing time, tumor recurrence, and metastasis were observed. The limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score.Results:All patients successfully completed the surgery and were followed up, with a follow-up time of 44.6±27.1 months (range, 12 to 96 months). The operation time was 527±132 min (range, 150 to 730 min), and the blood loss was 730±591 ml (range, 300 to 2,800 ml). The length of inactivated tumor bone was 16.5±4.5 cm (range, 9.1 to 24.0 cm), the defect length accounted for 43.4%±12.2% of the total length of the affected bone (range, 23.8% to 75.5%), the proximal osteotomy of the long bones in the extremities was 14.1±8.3 cm from the articular surface (range, 1.9 to 31.1 cm), the distal osteotomy was 9.4±6.2 cm from the articular surface (range, 1.7 to 22.9 cm), and the length of the harvested vascularized fibula was 18.0±4.0 cm (range, 11.0 to 26.4 cm). At the last follow-up, 51 patients were alive, including 47 with no evidence of tumor and 4 with tumor; 3 patients died of tumor progression. Local recurrence occurred in 5 patients, including 4 with soft tissue recurrence in the surgical area (3 underwent surgical resection and 1 received radiotherapy) and 1 with recurrence at the site of inactivated bone. Distant metastasis occurred in 11 patients, including 5 with lung metastasis only, 2 with bone metastasis only, and 4 with combined lung and bone metastasis. Among the 5 patients with lung metastasis only, lung metastases were resected, with 3 surviving with tumor, 2 surviving without tumor; the 2 patients with bone metastasis only underwent surgical resection of bone metastases, both surviving without tumor. Among the 4 patients with combined lung and bone metastasis, 3 died of tumor progression and 1 survived with tumor. The Kaplan-Meier curve showed a 5-year survival rate of 90.8%±6.2% and a 5-year recurrence-free and metastasis-free survival rate of 68.7%±7.9%. The osteotomy healing time at the diaphysis was 8.4±2.3 months (range, 4 to 13 months), the osteotomy healing time at the metaphysis was 5.9±1.7 months (range, 3 to 10 months), and the healing time between inactivated tumor bone and fibula was 6.4±2.0 months (range, 4 to 11 months). No nonunion occurred. The MSTS-93 score at the last follow-up was 94.4%±4.8% (range, 80% to 100%).Conclusion:Pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula reconstruction for bone defects after surgery for malignant bone tumors in children and adolescents has satisfactory clinical efficacy, high bone healing rate, and low rates of local recurrence and distant metastasis.

Objective:To evaluate the preliminary clinical efficacy of minimally invasive extendable prostheses in limb-salvage treatment for distal femoral osteosarcoma in children.Methods:A retrospective analysis was conducted on 36 children who underwent reconstruction of bone defects after distal femoral osteosarcoma resection with minimally invasive extendable prostheses at Peking University People's Hospital between December 2021 and December 2023. The cohort included 22 males and 14 females, with a mean age of 10.1±2.7 years (range: 4.3-14.3 years). Among them, 27 cases were primary tumor resections with post-resection bone defects of 17.4±3.2 cm (range: 13.5-25.0 cm), and 9 cases were revision surgeries. Preoperatively, femoral limb length discrepancy (LLD) was 29.6±14.3 mm (range: -1.2-55.0 mm), tibial LLD was 16.0±11.3 mm (range: -4.8-30.0 mm), and total lower limb LLD was 45.1±23.6 mm (range: -5.5-77.0 mm). The prosthesis was modular and compatible with existing tumor prosthesis components via taper connections. Lengthening was achieved by axial screw manual expansion through a 3-4 cm parapatellar arc incision, using a specialized wrench for adjustment. X-rays were performed pre-implantation, before and after each lengthening, and at the last follow-up to assess femoral, tibial, and total lower limb LLD, as well as extension length. At the final follow-up, limb function was assessed using the Musculoskeletal Tumor Society (MSTS)-93 score, and extension-related complications were analyzed.Results:All 36 children successfully underwent implantation and subsequent extension when indicated. The mean follow-up was 14.9±8.1 months (range: 6-31 months). Eleven patients underwent 16 lengthening procedures, with a mean of 1.5±0.8 per case (range: 1-3) and an average extension of 21.1±8.3 mm (range: 9.2-42.8 mm), achieving a total mean recovery of 31.0±16.1 mm (range: 10.4-61.7 mm). Two patients reached the maximum 5 cm extension capacity and underwent minor procedures to retract the extension device and secure the prosthesis. The remaining 25 patients did not require extension as their LLD was <2 cm. At the last follow-up, femoral, tibial, and total lower limb LLDs were 10.6±11.4 mm (range: -8.6-41.4 mm), 9.1±12.7 mm (range: -9.5-39.5 mm), and 20.1±21.0 mm (range: -10.4-72.5 mm), respectively. The mean MSTS-93 score for the 11 extended patients was 90.0%±12.7% (range: 80.0%-96.7%). Complications included two cases of aseptic loosening requiring revision, one transient peroneal nerve palsy after fixed-length filling, and three cases of prosthesis segment retraction due to excessive exercise. Retractions occurred at 9.1±3.3 months (range: 5.3-11.3 months) and were corrected during subsequent extensions without revision.Conclusions:Minimally invasive extendable prostheses allow individualized limb lengthening through small parapatellar incisions based on LLD and soft tissue tension. The extension mechanism is stable, and functional recovery is favorable.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To exploring the effect of inflammatory indicators on the outcome of assisted conception of in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)in patients with ovarian endometriosis(OEM).Methods The study subjects were selected as the patients with OEM who received IVF/ICSI treatment at the Third Affiliated Hospital of Zhengzhou University from January 2019 to February 2024.Based on whether previous surgery for uterine endometriosis cyst removal had been performed,they were divided into non-surgery group(n=73)and surgery group(n=112).To explore the differences in inflammatory markers between two groups and to determine whether they have an impact on the outcome of assisted reproduction.Results The lymphocytes(L)and blastocyst formation rates of patients in surgery group were significantly higher than those in non-surgery group,platelet to lymphocyte ratio(PLR)and carbohydrate antigen 125(CA125)were significantly lower than those in non-surgery group(P＜0.05).There were no statistically significant differences in the clinical pregnancy rate and live birth rate between two groups of patients(P＞0.05).After adjusting for confounding factors,the results of multivariate Logistic regression analysis showed that L,PLR,and CA125 had no statistically significant impact on the clinical pregnancy rate and live birth rate(P＞0.05).Both maternal age and the number of embryos transferred exerted a certain influence on clinical pregnancy rates and live birth rates(P＜0.05),furthermore,the type of embryo transferred had a significant effect on clinical pregnancy rates(P＜0.05).Conclusion Compared with non-surgery group,surgery group had higher L level and lower PRL and CA125 levels,but these changes did not significantly affect clinical pregnancy or live birth outcomes in OEM patients undergoing IVF/ICSI assisted reproduction.