BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

Phages, as obligate bacterial and archaeal parasites, constitute a virus group of paramount ecological significance due to their exceptional abundance and genetic diversity. These biological entities serve as critical regulators in Earth's ecosystems, driving biogeochemical cycles, energy fluxes, and ecosystem services across terrestrial and marine environments. Within soil microbiomes, phages function as microbial "dark matter," maintaining the soil-plant system balance through precise modulation of the microbial community structure and functional dynamics. Despite the growing research interests in soil phages in recent years, the proportion of such studies in environmental virology remains disproportionately low, which is primarily attributed to researchers' limited familiarity with the research methodologies for phage microecology, incomplete technical frameworks, and inherent challenges posed by soil environmental complexity. To address these challenges, this review synthesizes cutting-edge methodologies for soil phage investigation from four aspects: (1) tangential flow filtration (TFF)-based phage enrichment strategies; (2) integrated quantification approaches combining double-layer agar plating, epifluorescence microscopy, and flow cytometry; (3) multi-omics analytical pipelines leveraging metagenomics and viromics datasets; and (4) computational frameworks merging machine learning algorithms with eco-evolutionary theory for deciphering phage-host interaction networks. Through comparative analysis of methodological principles, technical merits, and application scopes, we establish a comprehensive workflow for soil phage research. Future research in this field should prioritize: (1) construction of soil phage resource libraries, (2) exploration of RNA phages based on transcriptomes, (3) functional characterization of unknown genes, and (4) deep integration and interaction validation of multi-omics data. This systematic methodological synthesis provides critical technical references for addressing fundamental challenges in characterizing soil phages regarding the community structure, functional potential, and interaction mechanisms with hosts.
Bacteriophages/physiology* ; Soil Microbiology ; Ecosystem ; Microbiota ; Metagenomics/methods*

Objective We propose a low-dose CT reconstruction method using partial differential equation (PDE) denoising under high-dimensional constraints. Methods The projection data were mapped into a high-dimensional space to construct a high-dimensional representation of the data, which were updated by moving the points in the high-dimensional space. The data were denoised using partial differential equations and the CT image was reconstructed using the FBP algorithm. Results Compared with those by FBP, PWLS-QM and TGV-WLS methods, the relative root mean square error of the Shepp-Logan image reconstructed by the proposed method were reduced by 68.87％, 50.15％ and 27.36％, the structural similarity values were increased by 23.50％, 8.83％ and 1.62％, and the feature similarity values were increased by 17.30％, 2.71％ and 2.82％, respectively. For clinical image reconstruction, the proposed method, as compared with FBP, PWLS-QM and TGV-WLS methods, resulted in reduction of the relative root mean square error by 42.09％, 31.04％and 21.93％, increased the structural similarity values by 18.33％, 13.45％ and 4.63％, and increased the feature similarity values by 3.13％, 1.46％ and 1.10％, respectively. Conclusion The new method can effectively reduce the streak artifacts and noises while maintaining the spatial resolution in reconstructed low-dose CT images.

Objective To explore the characteristics of response inhibition of military university students during multitasking operation. Methods Repeated measures of ANOVA as well as distribution test were employed to explore how the performance of 127 military university students in Go/No-Go test was affected by simulated driving task. Results The test results of 127 participants showed that there was a interaction between the interference task and the Go trial proportion on the hit rate and false alarm rate,that is,no significant difference was observed between the 60％ and 40％ of trial proportion without interference task (both P>0.05),but the hit rate and false alarm rate in the 60％ trial proportion condition were significantly higher than those in the 40％ trial proportion condition under interference task (both P<0.01).In addition,significant main effects of interference task were observed on hit rate,false alarm rate,and discrimination index d' (all P<0.01),that is,the interference task reduced the hit rate and discrimination,but increased the false alarm rate.Moreover,individual differences existed in the discrimination index d' changes,and the participants were divided into easily disturbed group (n=23,18.11％),undisturbed group (n=20,15.75％),and intermediate group (n=84,66.14％) by adding or subtracting 1 standard deviation from the mean of the difference. Conclusion The interference tasks increase the psychological load of military university students during multitasking operation,and impair the response inhibition;and individual differences exist in response inhibition.

Objective To investigate the key genes associated with ferroptosis in peri-implantitis and explore the potential mecha-nisms regulating peri-implantitis.Methods Several datasets were obtained from the GEO database.Differential expressed genes were screened,and GO and KEGG analyses were performed.A PPI network was constructed using the STRING website.Key genes were val-idated using a test set,and the diagnostic value of key genes was determined.The content and proportion of 22 immune cells in peri-im-plantitis tissues were obtained through immune infiltration analysis.Key genes were validated by qRT-PCR and Western Blot(WB).Results There were 1 138 differential genes between peri-implantitis tissues and normal gingival tissues,of which 29 were related to ferroptosis.The gene expression in peri-implantitis tissues mainly involved processes such as immune response activation.Five key genes in the ferroptosis-related differential genes,namely SOX2,GJA1,IL1B,GPX2 and CHAC1,were differentially expressed in peri-implantitis tissues and had high diagnostic value.Immune infiltration analysis showed significant changes in immune cells such as memory B cells and plasma cells in peri-implantitis tissues.qRT-PCR and WB confirmed significant differential expression of mRNA and the protein transcribed by key genes.Conclusion Differential genes between peri-implantitis and ferroptosis are screened using bioinformatics analysis and biological validation,providing new insights into the study on peri-implantitis.

Objective We propose a low-dose CT reconstruction method using partial differential equation (PDE) denoising under high-dimensional constraints. Methods The projection data were mapped into a high-dimensional space to construct a high-dimensional representation of the data, which were updated by moving the points in the high-dimensional space. The data were denoised using partial differential equations and the CT image was reconstructed using the FBP algorithm. Results Compared with those by FBP, PWLS-QM and TGV-WLS methods, the relative root mean square error of the Shepp-Logan image reconstructed by the proposed method were reduced by 68.87％, 50.15％ and 27.36％, the structural similarity values were increased by 23.50％, 8.83％ and 1.62％, and the feature similarity values were increased by 17.30％, 2.71％ and 2.82％, respectively. For clinical image reconstruction, the proposed method, as compared with FBP, PWLS-QM and TGV-WLS methods, resulted in reduction of the relative root mean square error by 42.09％, 31.04％and 21.93％, increased the structural similarity values by 18.33％, 13.45％ and 4.63％, and increased the feature similarity values by 3.13％, 1.46％ and 1.10％, respectively. Conclusion The new method can effectively reduce the streak artifacts and noises while maintaining the spatial resolution in reconstructed low-dose CT images.