ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass，strength，and function，and its occurrence and development are related to multiple factors，involving several signaling pathways. Among them，the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway，as a key pathway regulating cellular growth，survival，and metabolism，plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism，resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine （TCM），with its multi-pathway and multi-target characteristics，has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years，various monomers， extracts，and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis，reducing protein degradation，inhibiting cell apoptosis and inflammatory response，and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms， aiming to provide new insights for the treatment of sarcopenia with TCM.

ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

Regulated cell death （RCD） is a genetically determined， active and programmed form of cell death， mainly including apoptosis， autophagy， ferroptosis， pyroptosis， PANoptosis and other patterns. Dysregulation of RCD plays a pivotal role in the occurrence and progression of sarcopenia. Due to the advantages of abundant targets， diverse mechanisms of action and high safety profile， traditional Chinese medicine （TCM） has attracted considerable attention in regulating RCD， and preventing and treating sarcopenia. Through a review of the mechanisms of RCD in sarcopenia， and recent research progress on how TCM modulates RCD to improve sarcopenia， this paper reveals that single TCM herbs and their extracts （e.g.， Puerariae Lobatae Radix， and extracts of Schisandrae Chinensis Fructus， Myristicae Semen and Cistanches Herba）， active components and effective fractions of TCM （e.g.， resveratrol， polydatin， curcumin）， as well as TCM compound formulas （e.g.， Buzhong yiqi decoction， Erjing pills， Huangqi guizhi wuwu decoction， Shuanghe decoction）， can modulate RCD through multiple pathways， including the inhibition of apoptosis， pyroptosis， ferroptosis and PANoptosis， and the modulation of autophagy， thereby alleviating sarcopenia.

AIM: To investigate the effect of luteolin on tissue fibrosis in the filtering area following glaucoma trabeculectomy, and its relationship with the Wnt3a/β-catenin signaling pathway.METHODS: Rabbits were selected to establish a fibrosis model after glaucoma trabeculectomy, and randomly divided into the sham operation group, model group, luteolin-L group and luteolin-H group. Dynamic monitoring of postoperative intraocular pressure was performed in all groups. Slit-lamp biomicroscopy was used to observe postoperative conjunctival morphological changes, conjunctival healing degree, corneal integrity, and anterior chamber inflammatory responses in the filtering bleb area. HE staining was performed to evaluate conjunctival epithelial integrity, subepithelial fibrous proliferation, and inflammatory cell infiltration in the filtering tissues. Masson's trichrome staining was applied to assess collagen deposition and the degree of tissue fibrosis. The expression of α-SMA was observed by immunohistochemical staining. The mRNA and protein expression levels of Wnt3a, Wnt7a, Wnt2b, β-catenin, LC3-I, LC3-II and p62-SQSTM1 in conjunctival tissues of the operative area were quantitatively detected by RT-qPCR and Western blot, respectively.RESULTS:Postoperative dynamic monitoring showed that the luteolin-H group achieved significantly better intraocular pressure control than the luteolin-L group compared with the model group(all P<0.05). Slit lamp observations confirmed that luteolin effectively ameliorated postoperative conjunctival injury, alleviated anterior chamber inflammatory response, and maintained the structural stability of the filtering area. HE and Masson staining revealed that luteolin intervention reduced conjunctival epithelial damage and inflammatory cell infiltration, markedly inhibited fibroblast proliferation, neovascularization and excessive collagen deposition, and significantly delayed the progression of filtering bleb scarring, with stronger effects in the luteolin-H group than luteolin-L group compared with the model group. Immunohistochemical staining demonstrated that luteolin intervention decreased the positive expression rate of α-SMA. Molecular assays indicated that the luteolin-H group had lower expression levels of Wnt3a, β-catenin and LC3-II/LC3-I, and the highest p62-SQSTM1 level in the operative site relative to the model group and luteolin-L group(all PSymbol|@@0.05). No significant intergroup differences were observed in Wnt2b and Wnt7a expression. These findings suggested that luteolin could specifically regulated the Wnt3a pathway and dose-dependently suppressed the activation of the Wnt3a/β-catenin pathway after glaucoma trabeculectomy, downregulated LC3-II/LC3-I expression, upregulated p62-SQSTM1 levels, and inhibited excessive autophagy activation.CONCLUSION: Luteolin can significantly inhibit filtering bleb fibrosis after trabeculectomy, which may reduce the degree of fibrosis via the Wnt3a/β-catenin pathway.

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

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 and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult