This study employs ultra-performance liquid chromatography(UPLC) to analyze the differences in alkaloid content of Commelina communis from various geographical origins, exploring its feasibility as a quality evaluation indicator. A total of 57 batches of C. communis samples from 23 provinces, autonomous regions, and municipalities in China were selected. The MicroPulite HSS T3(2.1 mm×50 mm, 1.8 μm)column was used with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(20∶80), detection wavelength at 254 nm, and a flow rate of 0.3 mL·min~(-1) to measure the content of 1-deoxynojirimycin(DNJ) and deoxymannojirimycin(DMJ). The MicroPulite XP tC_(18)(2.1 mm×100 mm, 1.7 μm)column was employed with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(4∶96), detection wavelength at 254 nm, and a flow rate of 0.4 mL·min~(-1) to measure the content of norharmine(NHM) and harmanme(HM). Chemometric methods were applied to study the relationships and differences among the 57 batches of C. communis. Significant differences in alkaloid content were observed among C. communis from different regions, with the average total content decreasing in the order of North China, Northeast China, Northwest China, East China, Southwest China, Central China, and South China. Cluster analysis(CA) and principal component analysis(PCA) further revealed the quality differences of C. communis from various origins, and partial least squares discriminant analysis(PLS-DA) identified DNJ as a marker compound to distinguish the quality differences between different geographical sources of C. communis. It is recommended that the content limit of DNJ be set at no less than 0.055 9%, providing a reference for the quality evaluation and clinical application of C. communis medicinal materials.
Alkaloids/analysis* ; Drugs, Chinese Herbal/chemistry* ; China ; Chromatography, High Pressure Liquid ; Chemometrics/methods* ; Quality Control

A 12-year-old boy was admitted with symptoms of cough and fever lasting over a month, accompanied by weight loss 2 kg. Prior anti-infective treatments proved ineffective in alleviating the symptoms. Chest imaging revealed diffuse interstitial pulmonary edema in the right lung with obstructed lymphatic drainage. Combined with histopathological examinations, the diagnosis was confirmed as lung cancer with pulmonary lymphangitic carcinomatosis. The patient underwent chemotherapy with docetaxel and carboplatin, yet the disease progressively worsened, resulting in death three months after diagnosis. This case highlights lung cancer should not be overlooked in patients with persistent respiratory symptoms of unknown etiology. Early imaging examinations, along with necessary pathological evaluations, are crucial for timely detection and diagnosis. The presence of pulmonary lymphangitic carcinomatosis often indicates an advanced-stage of cancer, associated with a poor prognosis.
Humans ; Male ; Lung Neoplasms/complications* ; Child ; Carcinoma/drug therapy*

Research in photodynamic therapy (PDT) primarily focuses on enhancing light penetration depth, improving oxygen supply, and optimizing photosensitizer delivery. Notably, the delivery efficiency of the photosensitizer is crucial for therapeutic efficacy. Carboxyl-substituted phthalocyanines, as important photosensitizing molecules, possess unique chemical modification sites that enable direct targeted delivery or integration into diverse delivery systems. Their synthesis predominantly employs mixed- or cross-condensation, selective synthesis, and axial modification strategies to introduce carboxyl groups. However, their inherent hydrophobicity significantly hinders effective delivery. To address this limitation, modifications with peptides or quaternary ammonium salt derivatives may facilitate precise delivery to tumor cells and pathogens. With advances in nanotechnology, carboxyl-substituted phthalocyanines can serve as key photosensitizer modules, effectively integrated into nanomaterials such as biomacromolecules, inorganic metals, and polymers for both active and passive delivery. Recently, researchers have exploited the π-π stacking and other intermolecular forces among carboxyl-substituted phthalocyanine molecules to drive their self-assembly into nano-micelles, enabling carrier-free delivery or co-delivery with other therapeutic agents for synergistic effects. This review systematically outlines the synthesis strategies for carboxyl-substituted phthalo-cyanines. Taking mono-carboxyl-substituted zinc phthalocyanine as a model molecule, the performance of three delivery modalities were compared: single-molecule targeted delivery, nanocarrier-encapsulated delivery, and carrier-free self-assembled delivery, in terms of PDT efficacy, biocompatibility, and imaging-guided tracing capabilities, to provide a systematic technical framework for the rational design of novel modular photosensitizers and to advance the clinical translation of PDT in precision oncology and anti-infective therapy.
Photochemotherapy/methods* ; Indoles/administration & dosage* ; Isoindoles ; Photosensitizing Agents/administration & dosage* ; Drug Delivery Systems ; Humans

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

OBJECTIVES: To explore the mechanism of Circ-MYOCD back-splicing and its regulatory role in myocardial hypertrophy. METHODS: Sanger sequencing and RNase R assays were performed to verify the circularity and stability of Circ-MYOCD, whose subcellular distribution was determined by nuclear-cytoplasmic fractionation. Bioinformatics analysis and mass spectrometry from pull-down assays were conducted to predict the RNA-binding proteins (RBPs) interacting with Circ-MYOCD. In rat cardiomyocytes H9C2 cells, the effects of HNRNPH1 and HNRNPL knockdown and overexpression on Circ-MYOCD back-splicing were evaluated. In a H9C2 cell model of angiotensin II (Ang II)-induced myocardial hypertrophy, the expression of HNRNPH1 was detected, the effects of HNRNPH1 knockdown and overexpression on progression of myocardial hypertrophy were assessed, and the regulatory effect of HNRNPH1 on Circ-MYOCD back-splicing was analyzed. RESULTS: Sanger sequencing confirmed that the junction primers could amplify the correct Circ-MYOCD sequence. RNase R and nuclear-cytoplasmic fractionation assays showed that Circ-MYOCD was stable and predominantly localized in the cytoplasm. Bioinformatics analysis and mass spectrometry from the Circ-MYOCD pull-down assay identified HNRNPH1 and HNRNPL as the RBPs interacting with Circ-MYOCD. In H9C2 cells, HNRNPH1 knockdown significantly enhanced while its overexpression inhibited Circ-MYOCD back-splicing; HNRNPH1 overexpression obviously increased the expressions of myocardial hypertrophy markers ANP and BNP, while its knockdown produced the opposite effect. In Ang II-induced H9C2 cells, which exhibited a significant increase of HNRNPH1 expression and increased expressions of ANP and BNP, HNRNPH1 knockdown obviously increased Circ-MYOCD expression, decreased MYOCD expression and lowered both ANP and BNP expressions. CONCLUSIONS HNRNPH1 regulates Circ-MYOCD back-splicing to influence the progression of myocardial hypertrophy.
Animals ; Rats ; RNA, Circular/genetics* ; Cardiomegaly/metabolism* ; Myocytes, Cardiac/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism* ; Cell Line ; RNA Splicing ; Angiotensin II ; RNA-Binding Proteins

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

AIM:To investigate the mechanism by which the Z-DNA-binding protein 1(ZBP1)/receptor-in-teracting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)pathway modulates the necroptosis of neurons in a mouse model of Alzheimer disease(AD).METHODS:Thirty mice were randomly divided into three groups:normal control(NC)group,APP/PS1 model(MOD)group,and necroptosis inhibitor necrostatin-1(Nec-1)group,each with 10 mice.The learning and memory capacities of mice were assessed using the Morris water maze assays.The pathological morphology of hippocampal tissue was examined based on the HE staining assay.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in serum samples were measured by ELISA.The phosphory-lation of amyloid precursor protein(APP),Tau protein and the expression levels of proteins related to the ZBP1/RIPK1/MLKL pathway in hippocampal tissue were measured by Western blot.Immunofluorescence analysis was performed to de-tect the positive expression of p-RIPK1,while the mRNA level of ZBP1 was measured by RT-qPCR.RESULTS:Com-pared with NC group,the escape latency of mice in the MOD group was significantly longer(P<0.05),the number of crossing platforms was reduced(P<0.05),and the arrangement of hippocampal neurons was disordered accompanied with nuclear condensation.The concentration of TNF-α in serum was increased,whereas the concentration level of IL-10 was decreased(P<0.05).The expression levels of APP,p-Ttau and ZBP1 proteins in the hippocampal tissue and the ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly upregulated(P<0.05).Similarly,the positive expression level of p-RIPK1 and the mRNA level of ZBP1 in hippocampal tissue were significantly upregulated(P<0.05).Compared with the MOD group,the cognitive function of AD mice,pathological damage of hippocampal tissue,and the levels of TNF-α and IL-10 in serum were reversed in the Nec-1 group(P<0.05).Moreover,the Nec-1 treatment signifi-cantly downregulated the expression levels of the above proteins(P<0.05),and the positive expression of p-RIPK1 and the mRNA level of ZBP1 were significantly decreased(P<0.05).CONCLUSION:The ZBP1/RIPK1/MLKL pathway is involved in the occurrence of neuronal necroptosis and the pathological process of AD mice.Inhibition of this pathway sig-nificantly ameliorates cognitive dysfunction and neuroinflammatory responses in AD mice.

Antimicrobial resistance(AMR)has become a global public health crisis,posing a serious threat to the achievement of sustainable development goals(SDGs)of the United Nations.This article explores the potential con-sequences and far-reaching impacts of AMR on the global health system,economic development,and social well-being from the perspective of SDGs.This article analyzes the current situation and challenges of AMR prevention and control globally and domestically,proposes comprehensive response suggestions,such as establishing a global collaborative governance mechanism for AMR,deepening the"One Health"practice framework,perfecting survei-llance as well as infection prevention and control system on AMR,accelerating the development of new vaccines,ex-ploring AMR innovative response technologies,and strengthening AMR literacy education for all people.The re-search findings can provide reference globally,especially for developing countries to comprehensively respond to the threat of AMR and promote the SDGs process.

During sudden outbreaks of major infectious diseases,traditional vaccine clinical trials often fail to deliver timely and meaningful outcomes.To address this,innovative trial designs are essential to accelerate or restructure the traditional three-phase clinical trial process while maintaining adherence to scientific principles of drug candidate safety and efficacy.This paper presents various innovative vaccine clinical trial designs and concepts,along with critical considerations for their application,to serve as a methodological reference for related research.Adaptive designs provide flexibility by dynamically adjusting trial parameters—such as dose selection,population stratification,and sample size reestimation—based on interim analysis results.Bayesian designs incorporate historical data and prior information,reducing sample size requirements.Master protocol designs enable the evaluation of multiple treatments or target populations within a unified framework,significantly improving efficiency.Additionally,real-world data(RWD),including electronic health records vaccination records and insurance claims,supports the creation of virtual control groups,addressing ethical concerns while enhancing trial feasibility.A hybrid design combining randomized controlled trials(RCTs)with RWD is also proposed to leverage the strengths of both methodologies.These innovative designs optimize the research process,accelerating vaccine development and regulatory approval.By integrating these approaches,robust evidence-based insights can be generated,advancing precision medicine goals and strengthening public health responses to emerging infectious diseases.