As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.

Uncaria rhynchophylla (Miq.)Miq. ex Havil (Gouteng) is a dry and hooked stem branch of Rubiaceae, which contains chemical components including alkaloids, terpenoids, flavonoids and organic acids. It has antioxidant, anti-inflammatory, and potential therapeutic effects on various diseases. The characteristics of network pharmacology are multi-component, multi-target and multi-channel, which can analyze the complex mechanism of the active ingredient group of traditional Chinese medicine and the disease markers, and clarify the relationship between drugs, targets and diseases. This review summarises the research progress of the intervention of Gouteng in neurological disorders, cardiovascular diseases, inflammation, and other diseases based on network pharmacology and provides a theoretical foundation for the clinical application of Gouteng.

ObjectiveThis study aims to develop and validate a novel multimodal predictive model， termed criss-cross network（CCNet）-directed graph neural network（DGNN）（CGN）， for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer， by integrating longitudinal chest computed tomography（CT） imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron， and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently， a DGNN was constructed to integrate heterogeneous features， where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally， model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss， facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set， achieving an area under the receiver operating characteristic curve（AUC） of 0.830， accuracy of 0.843， sensitivity of 0.657， specificity of 0.712， Cohen's Kappa of 0.417， and F₁ score of 0.544. Compared with unimodal baselines， the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components， substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine （TCM）-specific symptomatology led to an additional 5% improvement in AUC， underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis， it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model， by synergistically combining cross-attention encoding with directed graph-based feature integration， enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment， thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.

Objective To evaluate the prediction of microvascular invasion(MVI)and its grading in patients with hepatocellular carcinoma(HCC)by computed tomography(CT)and magnetic resonance imaging(MRI)features combined with laboratory indices.Methods Using plain and enhanced CT and MRI scan to examine the participants preoperatively,the features of tumor length diam-eter,shape,number,margin and tumor capsule,whether multiple nodules are fused,whether external convex nodules are visible locally,whether blood supply vessels are visible inside or degeneration or necrosis exists,and whether low density or signal exists around the tumor that are extracted from the examination results,combined with clinical indicators,such as age,preoperative alpha-fetoprotein(AFP)level,and presence of hepatitis B surface and e antigens to analyze the occurrence of MVI in patients with HCC.Results Patients with HCC and MVI were more likely to have elevated AFP;the larger the tumor length and diameter,the higher the incidence of MVI.CT and MRI showed that the features of blurred tumor edges and incomplete local capsule were independent risk factors for MVI of HCC.All the extracted image features and clinical indicators had no predictive value for MVI grading.Conclusion A few imaging features and clin-ical indicators of HCC have definite predictive value for the occurrence of MVI.