ObjectiveThis paper aims to study the potential active compound components and action mechanism of Shenqi Dihuangtang in the treatment of diabetic kidney disease （DKD） through network pharmacology and in vivo experimental verification. MethodsUltra-high-performance liquid chromatography-Q-exactive orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS） technology was used to clarify the main active chemical components of Shenqi Dihuangtang， and it was combined with network pharmacology methods such as gene ontology （GO） functional annotations and Kyoto encyclopedia of genes and genome （KEGG） to predict the potential action mechanism of Shenqi Dihuangtang in treating DKD. Subsequently， the DKD model of db/db male mice was established， and the mice were randomly divided into model group， low-dose Shenqi Dihuangtang group （6.10 g·kg^-1）， medium-dose Shenqi Dihuangtang group （12.19 g·kg^-1）， high-dose Shenqi Dihuangtang group （24.38 g·kg^-1）， and daplizin group （1.25 mg·kg^-1）. During the same period， C57BL/6J male mice were selected into normal group and received drug intervention for 8 weeks， respectively. During this period， the body weight and fasting blood glucose （FBG） of the mice were dynamically monitored， and oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed at the end of dosing. The levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， uric acid （UA）， albumin （ALB）， and total protein （TP） were measured by an automatic biochemical analyzer， and 24-hour urine protein was measured by a urine protein quantitative kit. Hematoxylin-eosin （HE）， periodic-acid Schiff （PAS）， and Masson staining were employed to observe the renal histopathology. The expression of nephrotic protein Nephrin was observed by immunohistochemistry. Western blot was used to detect the expression of epithelial-mesenchymal transition （EMT）-related proteins such as TGF-β₁， Smad2/3， α-smooth muscle actin （α-SMA）， neural-cadherin （N-Cadherin）， and snail protein. ResultsUPLC-Q-Exactive Orbitrap MS identified 384 active compounds in the aqueous extract of Shenqi Dihuangtang. According to oral bioavailability≥30% and the five drug-like principles， 44 key active ingredients were screened out， and 169 intersection targets highly correlated with DKD were matched. Among them， there was a significant interaction relationship between tumor necrosis factor（TNF）， interleukin（IL）-6， protein kinase B（Akt）1， Caspase-3， Jun proto-oncogene （JUN）， hypoxia inducible factor-1α（HIF-1α）， B cell lymphoma-2（Bcl-2）， matrix metallopeptidase-9（MMP-9）， IL-1β， and TGF-β₁. GO functional annotations were significantly enriched in cellular components such as membrane rafts， membrane microdomains， and collagen-containing extracellular matrix， molecular functions such as DNA-binding transcription factor binding， R-Smad binding， and Smad protein binding， as well as biological processes such as reactions to lipopolysaccharides（LPS）， reactions to bacteria-derived molecules， and wound healing. The KEGG pathway was significantly enriched in lipids and atherosclerosis， TGF-β signaling pathway， phosphatidylinositol 3 kinase （PI3K）/Akt signaling pathway， etc. In vivo experimental results showed that the high-dose Shenqi Dihuangtang group could significantly reduce FBG levels in db/db mice （P<0.01）， improve OGTT （P<0.01） and ITT （P<0.01） levels， reduce SCr （P<0.01）， BUN （P<0.01）， UA （P<0.01） and 24-hour BUN （P<0.01）， and increase ALB （P<0.01） and TP （P<0.01） levels. Pathological staining confirmed that the high-dose Shenqi Dihuangtang group could significantly reduce the glomerular mesangial matrix area and collagen deposition （P<0.01） and upregulate the positive expression rate of Nephrin （P<0.01）. Western blot results showed that the high-dose Shenqi Dihuangtang group significantly downregulated the expression of TGF-β₁ （P<0.01） and Smad2/3 （P<0.01） signal molecules and inhibited the protein levels of α-SMA （P<0.01）， N-Cadherin （P<0.01）， and Snail （P<0.01）. ConclusionShenqi Dihuangtang can inhibit the TGF-β₁/Smad signaling axis and block the renal EMT process， thereby improving DKD renal fibrosis damage. Further analysis of its key active components and clinical transformation pathways is needed in the future.

Objective To analyze the epidemiological characteristics and spatial-temporal clustering trend of scarlet fever in Nantong from 2009 to 2023, and to provide a scientific basis for scarlet fever prevention and control. Methods The incidence data of scarlet fever in Nantong from 2009 to 2023 were analyzed. Descriptive analysis, seasonal index method and Joinpoint 5.2.0 software were used to analyze epidemiological characteristics. Spatial-temporal clustering was assessed with SaTScan 10.2.5 software. Results The average annual incidence of scarlet fever in Nantong from 2009 to 2023 was 6.54/100 000. The overall morbidity rate of scarlet fever in Nantong had an increasing trend from 2009 to 2019 with an average annual percentage change of 14.55% (t=3.36，P<0.05). The cases mainly occurred during late spring to early summer and late autumn to early winter. Students, preschool children and scattered children were the main scarlet fever population. The average annual incidence of males was significantly higher than that of females (χ²=7.00, P<0.05). Rugao City, Chongchuan District and Tongzhou District were identified as high-incidence areas, accounting for 76.51% of all reported cases. Spatial-temporal scan analysis indicated that Rugao City and Chongchuan District were primary cluster areas, spanning from 2015 to 2021 (RR=3.77, LLR=1 308.07, P<0.05). Conclusion The number of reported cases of scarlet fever in Nantong City from 2009 to 2023 shows epidemic and spatial clustering, mainly concentrated in the central urban area and adjacent counties (cities). It is necessary to strengthen health education and disease surveillance in high-incidence areas, as well as in key institutions and key populations before epidemic peaks.

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

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

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Human self-organizing cardioids, a recent breakthrough in cardiac organoid research, are constructed with the specialized cardiac lineage cells derived from human pluripotent stem cells (hPSCs) and have made rapid advancements since 2021. A key advantage of these organoids is their minimal reliance on external interventions, allowing them to more accurately replicate the heart's developmental processes through intrinsic signaling pathways, thereby closely mimicking natural cardiac characteristics. Consequently, they hold significant promise for improving drug safety evaluations, treating both congenital and acquired heart diseases, advancing eugenics practices, developing humanized cardiac disease models, conducting research in regenerative medicine, and understanding how unique environments (such as aerospace) affect human health. This review systematically describes the current various self-organizing cardioid construction techniques, comparing the structural differences caused by diverse signal stimulations, which would be instrumental in optimizing designs for more advanced and mature cardioids. Additionally, we summarize existing applications and address the challenges faced. Despite some uncertainties and challenges in current technologies and applications, this emerging cardiac organoid technology holds promise to provide new possibilities for cardiovascular medicine through continuous refinement.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

AIM:To compare the changes in diopters and axial length after 1 a of wearing defocus incorporated multiple segments(DIMS)lenses or single vision(SV)spectacle lenses in children with monocular myopia.METHODS:In this retrospective case group study, monocular myopia children aged from 6 to 14 years old in Hankou Aier Eye Hospital from October 2020 to October 2022, who were fitted with DIMS lens(n=52)or single-vision(SV)spectacle lenses(n=49)were collected. The spherical degree of myopia eyes ranged from -4.00 D to -0.50 D and the nonmyopic eyes ranged from 0 to +1.00 D, astigmatism in all eyes ranged from 0 to -2.00 D. The DIMS lens group was classified into DIMS-myopia group(the myopic eyes)and DIMS-nonmyopia group(the nonmyopic eyes). The SV lens group was also divided into SV-myopia group and SV-nonmyopia group. The changes in spherical equivalent refraction(SER)and axial length(AL)of each group were compare before and after wearing lenses for 1 a, and variations in SER and AL of both eye among groups were analzed.RESULTS: After wearing lenses for 1 a, the changes of SER in the DIMS-myopic group and the DIMS-nonmyopic group were -0.41±0.44 and -0.26±0.54 D, respectively, and the changes of AL were 0.18±0.20 and 0.15±0.15 mm, respectively. SER changes were -0.74±0.63 and -0.70±0.68 D in SV-myopic group and SV-nonmyopic group, and AL changes were 0.30±0.28 and 0.31±0.28 mm. The changes of SER and AL in the DMS-myopic and non-myopic groups were slower than those in SV group(all P<0.05). Compared with SV lenses, wearing DIMS lenses delayed and 44.6% in myopia eyes, and 62.9% in non-myopia eyes, AL delayed by 40.0% in myopia eyes and 51.6% in non-myopia eyes. The percentage of 1-year AL change ≤0.2 mm in the DIMS-myopic group and non-myopic group was 53.9% and 65.4%, respectively, which was higher than that in the SV myopic group(34.7% and 42.9%, all P<0.05). The percentage of AL change >0.4 mm in the DIMS-myopic group and nonmyopic group was 17.3% and 7.7%, respectively, which was lower than that in the SV myopic group(32.7% and 28.6%, all P<0.05). There was no significant correlation between the change of AL and age and baseline AL in the DIMS-myopic and non-myopic groups after wearing lens for 1 a(all P>0.05); the change of AL in SV-myopic group and non-myopic group was negatively correlated with age(r=-0.446, P=0.001; r=-0.312, P=0.029), and there was no significant correlation with baseline AL(all P>0.05).CONCLUSION: DIMS lens has a good effect on myopia control and prevention in both myopia and non-myopia children with monocular myopia. Children with early pre-myopia can wear DIMS to prevent myopia.