Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

OBJECTIVE To analyze the chemical constituents of the active parts of Piper wallichii. METHODS The petroleum ether-extract fraction was prepared from the methanol extract of P. wallichii. Separation and purification were performed using semi-preparative high-performance liquid chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS Nineteen compounds were isolated from the petroleum ether-extract fraction from the methanol extract of P. wallichii， identified as 3-acetoxybenzyl benzoate （1）， 2-acetoxybenzyl benzoate （2）， 2-methoxybenzyl benzoate （3）， 3-methoxybenzyl benzoate （4）， 4-hydroxy-3-methoxybenzyl benzoate （5）， 3-hydroxybenzyl benzoate（6）， benzyl benzoate （7）， ganschisandrine （8）， lancifolin A （9）， （7R，8R，3′R）-7-acetoxy-3′，4′-dimethoxy-3，4-methylenedioxy-6′-oxo- Δ1′，4′，8′-8.3′-lignan （10）， （7S，8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （11）， （7R， 8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （12）， isodihydrofutoquinol A （13）， licarin A （14）， licarin B （15）， 2-（2′，5′-dimethoxyphenyl）-3，4- dimethyl-5-（3″，4″-dimethoxyphenyl）- tetrahydrofuran （16）， galgravin （17）， velutin （18）， and piyunin A （19）. CONCLUSIONS Compound 1 is a new benzyl benzoate compound. Compounds 3-5， 8 and 9 are isolated from the Piper genus for the first time， while compounds 2， 6， 10-13 and 15-19 are isolated from P. wallichii for the first time.

Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

Objective:To construct a quality analysis model by combining the strengths-weaknesses-opportunities-threats(SWOT)analysis method and analytic hierarchy process(AHP),and to explore its application value in the quality management for operation of first aid equipment of hospital.Methods:The advantages,disadvantages,opportunities and threats of management for equipment were analyzed according to SWOT model,and the operation quality of equipment was positioning analyzed by AHP,and comprehensive management countermeasures were formulated from the aspects of personnel,system,preventive maintenance,information management and cooperation between institutes and enterprises.A total of 215 first aid equipment in clinical use in Qilu Hospital of Shandong University from January 2021 to December 2024 were selected.In these equipment,171 equipment from January 2021 to December 2022 were managed by using the conventional management mode,and 195 equipment(including 151 using equipment under the conventional management mode and 44 newly added equipment)from January 2023 to December 2024 were managed by using the strategic management mode with quality analysis model.The operation quality and management level of the two management modes for the equipment were compared.A self-made survey questionnaire was used to investigate the satisfaction scores of nurses of operating equipment,doctors of clinical department,medical engineers and administrators for the service effects of equipment under the two management modes,who use and manage the first aid equipment in hospital.Results:The average failure rate,risk rate,alarm rate and unqualified rate of first aid equipment in hospitals,which adopted the strategic management mode,were respectively(0.72±0.42)%,(1.08±0.70)%,(1.18±0.48)%and(1.33±0.63)%,all of which were lower than those of the conventional management mode,and the differences were statistically significant(t=3.629,2.792,2.179,2.396,P<0.05).The management level scores of monitors,ventilators,defibrillators,high-frequency electrosurgical knives and other first aid equipment,which adopted the strategic management mode,were respectively(94.69±1.68),(95.84±2.52),(95.38±2.85),(95.69±2.02)and(94.17±4.89)points,all of which were higher than those of the conventional management mode,and the differences were statistically significant(t=4.797,2.403,2.390,3.825,2.196,P<0.05).The satisfaction scores of nurses of operating equipment,doctors of clinical department,medical engineers and administrators for first aid equipment of adopting strategic management mode were all higher than those of adopting conventional management mode,and the difference were statistically significant(t=3.666,3.336,4.275,4.292,P<0.05).Conclusion:The quality analysis model of first aid equipment of hospital can improve the operation quality and management level of first aid equipment,and reduce the equipment's failure rate and the unqualified rate of quality inspection,and improve the service effect of first aid equipment.

Objective:To construct a quality analysis model by combining the strengths-weaknesses-opportunities-threats(SWOT)analysis method and analytic hierarchy process(AHP),and to explore its application value in the quality management for operation of first aid equipment of hospital.Methods:The advantages,disadvantages,opportunities and threats of management for equipment were analyzed according to SWOT model,and the operation quality of equipment was positioning analyzed by AHP,and comprehensive management countermeasures were formulated from the aspects of personnel,system,preventive maintenance,information management and cooperation between institutes and enterprises.A total of 215 first aid equipment in clinical use in Qilu Hospital of Shandong University from January 2021 to December 2024 were selected.In these equipment,171 equipment from January 2021 to December 2022 were managed by using the conventional management mode,and 195 equipment(including 151 using equipment under the conventional management mode and 44 newly added equipment)from January 2023 to December 2024 were managed by using the strategic management mode with quality analysis model.The operation quality and management level of the two management modes for the equipment were compared.A self-made survey questionnaire was used to investigate the satisfaction scores of nurses of operating equipment,doctors of clinical department,medical engineers and administrators for the service effects of equipment under the two management modes,who use and manage the first aid equipment in hospital.Results:The average failure rate,risk rate,alarm rate and unqualified rate of first aid equipment in hospitals,which adopted the strategic management mode,were respectively(0.72±0.42)%,(1.08±0.70)%,(1.18±0.48)%and(1.33±0.63)%,all of which were lower than those of the conventional management mode,and the differences were statistically significant(t=3.629,2.792,2.179,2.396,P<0.05).The management level scores of monitors,ventilators,defibrillators,high-frequency electrosurgical knives and other first aid equipment,which adopted the strategic management mode,were respectively(94.69±1.68),(95.84±2.52),(95.38±2.85),(95.69±2.02)and(94.17±4.89)points,all of which were higher than those of the conventional management mode,and the differences were statistically significant(t=4.797,2.403,2.390,3.825,2.196,P<0.05).The satisfaction scores of nurses of operating equipment,doctors of clinical department,medical engineers and administrators for first aid equipment of adopting strategic management mode were all higher than those of adopting conventional management mode,and the difference were statistically significant(t=3.666,3.336,4.275,4.292,P<0.05).Conclusion:The quality analysis model of first aid equipment of hospital can improve the operation quality and management level of first aid equipment,and reduce the equipment's failure rate and the unqualified rate of quality inspection,and improve the service effect of first aid equipment.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

Objective:Methamphetamine(METH)is an illicit psychoactive substance that can damage various organs,with the urinary system being one of its significant targets.This study aims to explore the role of microtubule affinity-regulating kinase 4(MARK4)in METH-induced acute kidney injury(AKI). Methods:A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group,5 mice in each group.The METH group was administered METH(20 mg/kg,intraperitoneally,once daily for 3 consecutive days),while the control group received an equal volume of physiological saline.The mice were executed 24 hours after the final injection,and the success of the AKI model was detected by blood serum creatinine,blood urea nitrogen,and renal HE staining.Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and bioinformatics analysis.The accuracy of proteomic data was validated using Western blotting,and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured.We further explored the role of MARK4 in METH-induced AKI.Firstly,a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment;the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. Results:The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins,of which 11 were up-regulated and 6 were down-regulated(all P＜0.05).The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice(both P＜0.05).The activity of BUMPT cells gradually decreased with increasing METH treatment concentration(all P＜0.05),where the viability of BUMPT cells decreased to about 60％after METH treatment at 4 mmol/L.Compared with the control group,expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration-and time-dependent manner(all P＜0.05).Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity,down-regulated the expression of cleaved caspase-3,and decreased the apoptosis of BUMPT cells induced by METH. Conclusion:MARK4 is highly expressed in a mouse model of METH-induced AKI,and MARK4 mediates METH-induced AKI by regulating cell apoptosis.