Autoimmune liver diseases （AILD） are a group of chronic liver diseases caused by abnormal activation of the immune system， mainly including autoimmune hepatitis， primary biliary cholangitis， primary sclerosing cholangitis， IgG4-related sclerosing cholangitis， and overlap syndrome. Clinical studies have shown that patients with AILD are often comorbid with thyroid diseases， especially autoimmune thyroid diseases （AITD）， such as Graves’ disease and Hashimoto’s thyroiditis. This article systematically reviews the epidemiological association， potential shared pathogenesis， and overlapping features between AILD and thyroid diseases. A deeper understanding of the immunological links between AILD and AITD may provide a theoretical basis for precision medicine and future research.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO₂-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL^-1 SiO₂ suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg^-1·d^-1 and 9 g·kg^-1·d^-1， respectively） ECT， and dexamethasone （0.2 mg·kg^-1·d^-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO₂-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO₂-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO₂-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.

“Zinc overload” has emerged as a promising strategy in tumor nanomedicine, wherein exogenous modulation of metal ion homeostasis selectively triggers cancer cell death. Among various bioactive ions, zinc (Zn²⁺) stands out due to its unique ability to simultaneously disrupt energy metabolism, damage mitochondria, degrade mutant p53, and activate antitumor immunity. Notably, tumor cells exhibit greater sensitivity to Zn²⁺ overload while normal cells maintain higher tolerance. This review systematically summarizes design strategies for achieving “zinc overload” using biodegradable zinc-based nanomaterials, focusing on two fundamental questions: how to specifically deliver Zn²⁺ to tumors (targeted delivery), and how to trigger controlled release at the tumor site (release strategies). Current challenges are critically analyzed and future perspectives are offered. For targeted delivery, the strategies are categorized into passive, active, and biomimetic approaches. Passive targeting relies on the enhanced permeability and retention (EPR) effect but suffers from poor enrichment efficiency and rapid clearance. Active targeting conjugates ligands (e.g., folic acid, hyaluronic acid) to recognize overexpressed receptors, significantly enhancing cellular uptake. It is emphasized that hyaluronic acid-modified ZIF-8 can co-deliver siRNA for GLUT1 silencing, achieving systematic energy exhaustion. Biomimetic delivery using cell membranes confers immune evasion, prolonged circulation, and homologous targeting, exhibiting the lowest off-target toxicity. This approach is considered to guide future nanocarrier design. For Zn²⁺ release, 4 mechanisms are discussed. Endogenous environment-responsive release exploits acidic pH to degrade materials like ZIF-8 or ZnO, causing mitochondrial dysfunction, reactive oxygen species (ROS) burst, and autophagic blockade. Incorporation of other ions (Ca²⁺, Mn²⁺, Ni²⁺) enables synergistic metabolic interference and immune activation. Exogenous responsive release using near-infrared light offers spatiotemporally precise activation. For example, a nanorobot combining black phosphorus with ZIF-8 accelerates Zn²⁺ release under dual acid and light stimuli. Ion exchange represents an elegant trigger: zinc complexes (e.g., Zn-carnosine) have higher affinity for Cu²⁺; competitive coordination releases Zn²⁺ while depleting Cu²⁺, dually inhibiting oxidative phosphorylation and glycolysis. This mechanism is proposed to hold promise for overcoming metabolic reprogramming. Finally, biological regulation—silencing the ZnT1 zinc transporter to block Zn²⁺ efflux—represents a paradigm shift from passive delivery to active homeostatic disruption. This “block and attack” strategy may prevent acquired resistance. The therapeutic consequences of zinc overload are multifaceted. Zn²⁺ causes lysosomal membrane permeabilization and impaired SNARE complex formation, blocking autophagic flux and inducing a distinct cell death termed “zincosis”. In mitochondria, Zn²⁺ inhibits glutathione reductase, causing oxidative stress and electron transport chain blockade. Meanwhile, Zn²⁺ suppresses glycolytic enzymes (GAPDH, LDHA), leading to ATP depletion and reversing drug resistance by downregulating P-glycoprotein. Moreover, zinc overload triggers immunogenic cell death, promoting dendritic cell maturation and CD8⁺ T cell infiltration. Combined with cGAS-STING activation, this reshapes the immunosuppressive tumor microenvironment and inhibits distant metastasis. These interconnected mechanisms endow zinc overload with a unique advantage over single-modality treatments. Despite remarkable preclinical efficacy, challenges remain: systemic toxicity from off-target release, potential zinc tolerance via metallothionein upregulation, and insufficient pharmacokinetic data. Future directions should prioritize: (1) intelligent stimuli-responsive materials; (2) combination with immune checkpoint inhibitors;(3) theragnostic integration; (4) deeper mechanistic studies; and (5) artificial intelligence-assisted screening. Zinc overload therapy is expected to become an indispensable component of integrated tumor treatment.

To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

OBJECTIVES: Prolonged invasive mechanical ventilation is associated with increased risks of severe complications such as retinopathy of prematurity and bronchopulmonary dysplasia. Although neonatal intensive care unit (NICU) follow the principle of early extubation, extubation failure rates remain high, and reintubation may further increase the risk of adverse outcomes. This study aims to identify risk factors and short-term prognosis associated with first extubation failure in neonates, to provide evidence for effective clinical intervention strategies. METHODS: Clinical data of neonates who received invasive ventilation in the NICU of Children's Hospital of Nanjing Medical University from January 1, 2019, to December 31, 2021, were retrospectively collected. Neonates were divided into a successful extubation group and a failed extubation group based on whether reintubation occurred within 72 hours after the first extubation. Risk factors and short-term outcomes related to extubation failure were analyzed. RESULTS: A total of 337 infants were included, with 218 males (64.69%). Initial extubation failed in 34 (10.09%) infants. Compared with the successful extubation group, the failed extubation group had significantly lower gestational age [(31.37±5.14) weeks vs (34.44±4.07) weeks], age [2.5 (1.00, 8.25) h vs 5 (1.00, 22.00) h], birth weight [(1 818.97±1128.80) g vs (2 432.18±928.94) g], 1-minute Apgar score (6.91±1.90 vs 7.68±2.03), and the proportion of using mask oxygenation after extubation (21% vs 46%) (all P<0.05). Conversely, compared with the successful extubation group, the failed extubation group had significantly higher rates of vaginal delivery (59% vs 32%), caffeine use during mechanical ventilation (71% vs 38%), dexamethasone use at extubation (44% vs 17%), the highest positive end-expiratory pressure level within 72 hours post-extubation [6(5.00, 6.00) cmH₂O vs 5 (0.00, 6.00) cmH₂O] (1 cmH₂O=0.098 kPa), the highest FiO₂ within 72 hours post-extubation [(34.35±5.95)% vs (30.22±3.58)%], and duration of noninvasive intermittent positive pressure ventilation after extubation [0.5 (0.00, 42.00) hours vs 0 (0, 0) hours] (all P<0.05). Multivariate analysis identified gestational age <28 weeks (OR=5.570, 95% CI 1.866 to 16.430), age at NICU admission (OR=0.959, 95% CI 0.918 to 0.989), and a maximum FiO₂≥35% within 72 hours post-extubation (OR=4.541, 95% CI 1.849 to 10.980) as independent risk factors for extubation failure (all P<0.05). Additionally, the failed extubation group exhibited significantly higher incidences of necrotizing enterocolitis grade II or above, moderate-to-severe bronchopulmonary dysplasia, severe bronchopulmonary dysplasia, retinopathy of prematurity, treatment abandonment due to poor prognosis, and discharge on home oxygen therapy (all P<0.05). Total hospital length of stay and total hospitalization costs were also significantly increased in the failed extubation group (all P<0.05). CONCLUSIONS Gestational age <28 weeks, younger age at NICU admission, and FiO₂≥35% after extubation are high-risk factors for first extubation failure in neonates. Extubation failure markedly increases the risk of adverse clinical outcomes.
Humans ; Infant, Newborn ; Male ; Female ; Airway Extubation/adverse effects* ; Risk Factors ; Retrospective Studies ; Respiration, Artificial/methods* ; Intensive Care Units, Neonatal ; Prognosis ; Gestational Age ; Bronchopulmonary Dysplasia ; Infant, Premature ; Treatment Failure ; Intubation, Intratracheal

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Perforin 2(MPEG 1)is a member of the MACPF(membrane attack complex/PRF membrane attack complex/perforin)superfamily,which is mainly secreted by cytotoxic T lymphocytes,natural killer cells and mac-rophages Through the formation of active pores on the target cell membrane,perforin 2 participates in altering the permeability-pressure of the target cell,or collaborates with granzymes to induce the apoptosis of target cells.Re-cently,with the development of molecular biology,MPEG 1 has been increasingly studied,and the unique gene se-quence and cell types of perforin 2 have specific functions and adaptive evolution in different immune cells,which may determine its performance and therapeutic potential in different disease states.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.