ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To collect and analyze outpatient prescription data for exogenous cough treatment from a hospital in Shenzhen,and to identify the characteristics and medication patterns of traditional Chinese medicine(TCM).Methods This study collected prescriptions from a hospital in Shenzhen for exogenous cough treatment in January 2024.R language for data mining were used to analyze the medication frequency,clustering patterns,and association rules in the treatment of exogenous cough by TCM and to explore the medication patterns and the usage of classic formulas in TCM for this condition.Results A total of 451 outpatient prescriptions for exogenous cough were include,the top ten most frequently used herbs were Licorice,Bitter almond,Bellflower,Ephedra,Tangerine peel,Stemonae radix,Tuckahoe,Pinellia ternata,Nepeta,Bulb of thunberg fritillary.Cluster analysis and association rules revealed that San'ao decoction,Kikyodon soup,and Zhisou powder were commonly prescribed,targeting lung function,dispersing wind,and resolving phlegm to effectively alleviate cough symptoms.Significant differences in medication usage were observed across different syndrome types.For the wind cold attacking lung pattern,the core herbs were warm in nature and focused on dispersing with acrid-warm properties.Conversely,the treatment of wind heat attacking the lung pattern typically involved cold-natured herbs,with a primary focus on clearing and draining lung heat.Stratification by age revealed that the pediatric group often used drugs with mild properties,such as Stemona and Shegan.The young adult group tended to be prescribed cold-natured drugs like Forsythia and Hogfonnel Root.The middle-aged and elderly group preferred warming and tonifying drugs such as Japanese Catnip and Perilla frutescens.Conclusion The TCM treatment of exogenous cough primarily focuses on releasing the exterior and dispersing the lung.Due to the region's subtropical monsoon climate and temperature fluctuations physicians flexibly modified classical formulas such as San'ao decoction and Zhisou powder according to individual constitutions and symptom patterns.This targeted,syndrome-based approach effectively disperses the lung qi,stops cough and transforms phlegm,and alleviates cough.

Adenoid cystic carcinoma(ACC)of the cervix is a rare and highly aggressive subtype of cervical cancer,accounting for less than 1%of all cervical cancer cases.ACC predominantly affects postmenopausal women over the age of 60,with postmenopausal vaginal bleeding being the most common symptom.Diagnosis of ACC primarily relies on histopathological examination and immunohistochemical analysis.Although there is currently no standard treatment protocol,surgical resection combined with radiotherapy or concurrent chemoradiotherapy is considered to be an effective approach.However,the effectiveness is limited,particularly in advanced cases,which generally have a poor prognosis.The treatment and prognosis of ACC are closely related to tumor staging,perineural invasion,and margin status.This paper discusses the clinical data and follow-up of six ACC patients treated at our institution,and goes through a literature review,examines its clinical features and treatment outcomes,underscores the critical importance of early diagnosis and individualized treatment.

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To collect and analyze outpatient prescription data for exogenous cough treatment from a hospital in Shenzhen,and to identify the characteristics and medication patterns of traditional Chinese medicine(TCM).Methods This study collected prescriptions from a hospital in Shenzhen for exogenous cough treatment in January 2024.R language for data mining were used to analyze the medication frequency,clustering patterns,and association rules in the treatment of exogenous cough by TCM and to explore the medication patterns and the usage of classic formulas in TCM for this condition.Results A total of 451 outpatient prescriptions for exogenous cough were include,the top ten most frequently used herbs were Licorice,Bitter almond,Bellflower,Ephedra,Tangerine peel,Stemonae radix,Tuckahoe,Pinellia ternata,Nepeta,Bulb of thunberg fritillary.Cluster analysis and association rules revealed that San'ao decoction,Kikyodon soup,and Zhisou powder were commonly prescribed,targeting lung function,dispersing wind,and resolving phlegm to effectively alleviate cough symptoms.Significant differences in medication usage were observed across different syndrome types.For the wind cold attacking lung pattern,the core herbs were warm in nature and focused on dispersing with acrid-warm properties.Conversely,the treatment of wind heat attacking the lung pattern typically involved cold-natured herbs,with a primary focus on clearing and draining lung heat.Stratification by age revealed that the pediatric group often used drugs with mild properties,such as Stemona and Shegan.The young adult group tended to be prescribed cold-natured drugs like Forsythia and Hogfonnel Root.The middle-aged and elderly group preferred warming and tonifying drugs such as Japanese Catnip and Perilla frutescens.Conclusion The TCM treatment of exogenous cough primarily focuses on releasing the exterior and dispersing the lung.Due to the region's subtropical monsoon climate and temperature fluctuations physicians flexibly modified classical formulas such as San'ao decoction and Zhisou powder according to individual constitutions and symptom patterns.This targeted,syndrome-based approach effectively disperses the lung qi,stops cough and transforms phlegm,and alleviates cough.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.