AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

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.

Aim To investigate the effect of ACSL4 on the malignant biological behavior of esophageal cancer cells and gefitinib resistance by regulating FASN,and to explore the related mechanism.Methods Thirty-five fresh esophageal cancer tissues and adjacent nor-mal tissues,and 30 esophageal cancer tissues with ge-fitinib resistance were collected.The expressions of ACSL4 and FASN were detected by qRT-PCR and im-munohistochemistry.The expression levels of ACSL4 and FASN in human normal esophageal cells HET-1 A,esophageal cancer cell lines ECA109,EC9706,TE-1 and TE-1/GR were detected by qRT-PCR.Cells in each group were constructed by liposome transfection technique,and the drug resistance and proliferation a-bility of cells were detected by cloning and CCK-8 as-say,cell apoptosis was detected by flow cytometry,cell invasion ability was detected by Transwell,and EMT pathway protein expression was detected by Western blot.Results Compared with adjacent normal tis-sues,the expression of ACSL4 and FASN genes in cancer tissues increased,and there was a positive corre-lation.The expression of ACSL4 significantly increased in ECA109,EC9706 and TE-1 cells compared with HET-1 A cells.With the increase of gefitinib concen-tration,the expression of ACSL4 in TE-1 cells gradually increased,and the expression of ACSL4 in TE-1/GR cells was higher than that of TE-1.Compared with the control group and the si-NC group,the cell proliferation and invasion ability of si-ACSL4 group decreased,the number of apoptosis increased,the expression of E-Cadherin increased,and the expression of N-Cadherin,Vimentin and β-catenin decreased.The response ex-periment showed that compared with the si-ACSL4 group and the si-ACSL4+oe-NC group,the cells in the si-ACSL4+oe-FASN group increased drug resistance,increased proliferation and invasion ability,decreased apoptosis number and decreased expression of E-Cad-herin.The expressions of N-Cadherin,Vimentin and β-catenin increased.Conclusions By down-regulating the expression of FASN,ACSL4 reverses the resistance of esophageal cancer TE-1/GR cells to gefitinib and in-hibits the proliferation,invasion and accelerates apopto-sis of TE-1/GR cells,which may be related to the regu-lation of EMT signaling pathway.

This study investigated the mechanism of Croci Stigma in treating immune checkpoint inhibitor(ICI)-associated myocarditis based on network pharmacology and molecular docking. Network pharmacology was employed to screen the active ingredients and molecular targets of Croci Stigma in treating ICI-associated myocarditis. The "drug-ingredient-target-disease" network and protein-protein interaction network were constructed to screen the key ingredients and core targets. Gene Ontology functional enrichment analysis showed that the mechanism was related to the regulation of inflammation and apoptosis. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the treatment was related to the advanced glycation end product-receptor for advanced glycation end products(AGE-RAGE) signaling pathway. Molecular docking result showed that crocins had close associations with RAC-alpha serine/threonine-protein kinase 1(AKT1), signal transducer and activator of transcription 3, and matrix metalloproteinase 9. Crocins were then selected as the therapeutic drug. The mouse model of ICI-associated myocarditis was established by subcutaneous injection of porcine cardiac myosin combined with intraperitoneal injection of pembrolizumab. The results suggested that Croci Stigma reduced the spleen index but had no effect on the heart index. The electrocardiogram showed that Croci Stigma increased the heart rate and shortened PR and QRS intervals. Echocardiographic data indicated that Croci Stigma increased the left ventricular stroke volume, cardiac output, ejection fraction, and fractional shortening. Hematoxylin-eosin and Masson staining results showed that Croci Stigma decreased the number of inflammatory cells infiltrating in the myocardium and alleviated myocardial fibrosis. Enzyme-linked immunosorbent assay results showed that Croci Stigma decreased the serum levels of inflammatory cytokines including tumor necrosis factor-alpha, interleukin-6, interleukin-12, and regulated on activation, normal T-cell expressed and secreted and lowered the levels of creatine kinase and creatine kinase isoenzyme MB. Biochemical data suggested that Croci Stigma inhibited the activities of superoxide dismutase and lactate dehydrogenase. Western blot result showed that Croci Stigma regulated the expression of myocardial AKT. The findings demonstrate that Croci Stigma may regulate AKT expression to effectively protect the cardiac tissue from ICI-associated myocarditis through antagonizing immune responses and inflammation, inhibiting oxidative stress, alleviating cardiac fibrosis, relieving cardiac block, and improving the cardiac function.
Animals ; Molecular Docking Simulation ; Myocarditis/metabolism* ; Immune Checkpoint Inhibitors/adverse effects* ; Mice ; Network Pharmacology ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Humans ; Protein Interaction Maps/drug effects*

Objective:To investigate the clinical efficacy of trimetazidine,dopamine combined with furosemide in eld-erly patients with rheumatic heart disease(RHD)and chronic heart failure(CHF)and its effect on the levels of me-teorin-like protein(Metrnl),soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and syndecan-1.Methods:This randomized controlled study enrolled 106 elderly patients with RHD and CHF who were hospi-talized in the First People's Hospital of Xianyang between March 2022 and December 2023.Patients were divided in-to control group(n=53,routine treatment)and intervention group(n=53,additional trimetazidine,dopamine and furosemide combined treatment),and treated for 1 week.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),6-min walking distance(6MWD),Minnesota living with heart failure questionnaire(MLHFQ)score,serum levels of B-type natriuretic peptide(BNP),Metrnl,sTREM-1 and syndecan-1,and incidence of adverse reactions during treatment were compared between the two groups.Binary Logistic regression was used to analyze the association be-tween influencing factors and therapeutic effect.Results:The total effective rate of intervention group was signifi-cantly higher than that of control group(96.23％vs.83.02％,P=0.026).Compared to patients in the control group after treatment,those in the intervention group had significantly lower LVEDd[(45.27±5.95)mm vs.(50.11±4.47)mm],LVESd[(34.85±4.19)mm vs.(40.93±4.77)mm],MLHFQ score[(34.51±4.47)points vs.(45.62±5.08)points],levels of BNP[(95.29±8.31)pg/ml vs.(145.39±25.71)pg/ml],sTREM-1](43.59±4.21)pg/ml vs.(50.61±5.48)pg/ml]and syndecan-1[(7.01±1.88)μg/L vs.(11.02±2.36)μg/L],and significantly higher LVEF[(58.14±4.02)％vs.(50.61±6.15)％],6MWD[(433.48±45.74)m vs.(386.51±31.25)m]and Metrnl level[(205.08±27.45)ng/L vs.(188.52±22.37)ng/L](P＜0.001 all).Bi-nary Logistic regression analysis showed that the combination of trimetazidine,dopamine and furosemide was an in-dependent protective factor for the efficacy of elderly patients with RHD and CHF(OR=0.096,95％CI:0.011～0.837,P=0.034).There was no significant difference in the total incidence of adverse reactions between interven-tion group and control group(13.20％vs.11.32％,P=0.767).Conclusion:The combination of trimetazidine,do-pamine and furosemide could significantly improve cardiac function and exercise tolerance,reduce serum sTREM-1 and syndecan-1 levels,and increase Metrnl level with good safety in elderly patients with RHD and CHF.

Objective:To investigate the clinical efficacy of trimetazidine,dopamine combined with furosemide in eld-erly patients with rheumatic heart disease(RHD)and chronic heart failure(CHF)and its effect on the levels of me-teorin-like protein(Metrnl),soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and syndecan-1.Methods:This randomized controlled study enrolled 106 elderly patients with RHD and CHF who were hospi-talized in the First People's Hospital of Xianyang between March 2022 and December 2023.Patients were divided in-to control group(n=53,routine treatment)and intervention group(n=53,additional trimetazidine,dopamine and furosemide combined treatment),and treated for 1 week.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),6-min walking distance(6MWD),Minnesota living with heart failure questionnaire(MLHFQ)score,serum levels of B-type natriuretic peptide(BNP),Metrnl,sTREM-1 and syndecan-1,and incidence of adverse reactions during treatment were compared between the two groups.Binary Logistic regression was used to analyze the association be-tween influencing factors and therapeutic effect.Results:The total effective rate of intervention group was signifi-cantly higher than that of control group(96.23％vs.83.02％,P=0.026).Compared to patients in the control group after treatment,those in the intervention group had significantly lower LVEDd[(45.27±5.95)mm vs.(50.11±4.47)mm],LVESd[(34.85±4.19)mm vs.(40.93±4.77)mm],MLHFQ score[(34.51±4.47)points vs.(45.62±5.08)points],levels of BNP[(95.29±8.31)pg/ml vs.(145.39±25.71)pg/ml],sTREM-1](43.59±4.21)pg/ml vs.(50.61±5.48)pg/ml]and syndecan-1[(7.01±1.88)μg/L vs.(11.02±2.36)μg/L],and significantly higher LVEF[(58.14±4.02)％vs.(50.61±6.15)％],6MWD[(433.48±45.74)m vs.(386.51±31.25)m]and Metrnl level[(205.08±27.45)ng/L vs.(188.52±22.37)ng/L](P＜0.001 all).Bi-nary Logistic regression analysis showed that the combination of trimetazidine,dopamine and furosemide was an in-dependent protective factor for the efficacy of elderly patients with RHD and CHF(OR=0.096,95％CI:0.011～0.837,P=0.034).There was no significant difference in the total incidence of adverse reactions between interven-tion group and control group(13.20％vs.11.32％,P=0.767).Conclusion:The combination of trimetazidine,do-pamine and furosemide could significantly improve cardiac function and exercise tolerance,reduce serum sTREM-1 and syndecan-1 levels,and increase Metrnl level with good safety in elderly patients with RHD and CHF.

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.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.