OBJECTIVE To investigate the effects and mechanism of total alkaloids of Corydalis Rhizoma （TAC） on the regulation of cuproptosis in rats with diabetic cardiomyopathy （DCM） based on silence information regulator 1（Sirt1）/tumor protein 53（P53）signaling pathway. METHODS DCM rat model was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. Thirty-two model rats were randomly divided into model group， TAC low-dose， medium-dose and high-dose groups （7， 10.5， 14 mg/kg）， with 8 rats in each group. An additional 8 rats were assigned to normal control group. Related drugs or normal saline were administered intragastrically in each group， once a day， for 4 weeks. After the last medication， the fasting blood glucose （FBG） levels of the rats were measured. The levels of myocardial creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in serum and myocardial tissue of rats were all detected. The pathological morphology， fibrosis degree， and Cu2+ deposition of myocardial tissue in rats were observed. The levels of Cu2+ and glutathione （GSH） in myocardial tissue， the expressions of Sirt1/P53 signaling pathway-related proteins [Sirt1， P53， solute carrier family 7 membrane 11 （SLC7A11）]， and iron-sulfur cluster-related proteins [ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， aconitase 2 （ACO2）， NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）， dihydrolipoamide acetyltransferase （DLAT）， dihydrolipoamide succinyltransferase （DLST）]， and heat shock protein 70 （HSP70） were all determined. RESULTS Compared with normal control group， the model group exhibited significantly elevated levels of FBG， CK， CK-MB and LDH in both serum and myocardial tissue， as well as increased 2+ levels of Cu in myocardial tissue and the expression of P53 and HSP70 proteins （P＜0.05）； the level of GSH and the expression levels of Sirt1， SLC7A11， FDX1， LIAS， ACO2， NDUFS8， DLAT， and DLST proteins in myocardial tissue were all significantly decreased （P＜0.05）； the myocardial tissue exhibited severe pathological damage， with numerous inflammatory cell infiltrations and significant fibrosis， as well as increased deposition of Cu2+. Compared with model group， most of the above quantitative indicators in rats were significantly reversed in TAC groups （P＜0.05）； the pathological damage to the myocardial tissue was alleviated， with reduced fibrosis and Cu2+ deposition. CONCLUSIONS TAC can ameliorate DCM in rats， and its mechanism of action may be related to activating the activity of the Sirt1/P53 signaling pathway， promoting the chelation of GSH with Cu2+， and inhibiting cuproptosis of cardiomyocyte.

Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry* ; Greenhouse Gases/metabolism* ; Carbon/analysis* ; Ecosystem ; Carbon Dioxide/metabolism* ; China ; Global Warming

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

The basic situation of the digital operating room in some hospital was introduced,and the necessity and requirements for the modification of the digital operating room were described.The overall structure and signal transmission and control mode were expounded for the modified digital operating room based on hospital LAN.The configuration schemes and application effects of the digital operating room before and after the modification were compared.It's pointed out that the modified digital operating room provided a convenient clinical environment and enhanced the quality of surgical relay and academic conferences while improving the working efficiency.References were given for the construction of digital operating rooms of other hospitals.[Chinese Medical Equipment Journal,2024,45(4):93-97]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective To investigate the effect of total alkaloids of Rhizoma Corydalis(TAC)on the expression of silencing information regulator 1(Sirt1)/tumor suppressor P53 protein signaling pathway-related proteins in the hippocampus of rats with chronic cerebral ischemia(CCH),and to explore its mechanism.Methods The rats were randomly divided into Sham operation group,model group,TAC high-dose group(14 mg/kg)and TAC low-dose group(7 mg/kg),with 6 rats in each group.A modified bilateral common carotid artery permanent occlusion method(BCCAO)was used to establish a rat model of CCH,and only bilateral common carotid arteries were separated in the Sham group.After the modeling was completed,each group was given the corresponding drug or isotonic saline by gavage,once a day,and the treatment lasted for 14 days.Hematoxycin-eosin staining was used to observe the pathological changes in the hippocampus of rats,in situ terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphate-biotin nick end labeling assay(TUNEL)was used to detect neuronal apoptosis,and Western blotting and immunohistochemistry were used to detect expression of Sirt1,P53,P53 positive apoptosis regulator(PUMA),B-cell lymphocytoma-2(Bcl-2)protein,Bcl-2-related X protein(BAX),respectively in the hippocampus of rats.Results(1)There were significant differences in the number of apoptotic cells and apoptosis rate among the four groups(F-values were 71.417 and 76.835,respectively,both P＜0.01).There were statistically significant differences in the mean integral optical density values of Sirt1,P53,PUMA,BAX and Bcl-2 protein positive expression areas among the four groups(F-values were 1 178.390,42.465,867.413,110.656 and 131.801,all P＜0.01).There were significant differences in the relative expression levels of Sirt1,P53,PUMA,BAX and Bcl-2 among the four groups(F-values were 9.497,11.863,58.552,186.855 and 12.466,all P＜0.01).(2)Compared with the Sham operation group,the neuronal arrangement of brain tissue in the hippocampus of the model group was disordered,the nuclear consolidation increased,and the glial cells and inflammatory cells increased significantly,and the number and apoptosis rate of neurons in the hippocampus of the model group increased significantly(respectively[10.8±1.5]cells vs.[2.0±0.9]cells and[35.5±4.5]％vs.[6.2±2.6]％;both P＜0.05),and the average integral optical density values of the positive expression areas of Sirt1 and Bcl-2 proteins decreased significantly(84.6±6.6 vs.244.6±4.9,138.5±6.7 vs.210.9±10.0;both P＜0.05),the average integral optical density values of P53,PUMA and BAX proteins were significantly increased(156.8±11.6 vs.93.5±11.6,151.3±3.3 vs.38.0±4.0,87.0±5.0 vs.38.4±5.5;all P＜0.05),the relative expression levels of Sirt1 and Bcl-2 proteins were significantly decreased(0.51±0.07 vs.0.74±0.07,0.36±0.03 vs.0.53±0.05;both P＜0.05),and the relative expression levels of P53,PUMA and BAX proteins were significantly increased(0.37±0.06 vs.0.21±0.02,0.62±0.06 vs.0.23±0.02,1.08±0.06 vs.0.45±0.03;all P＜0.05).(3)Compared with the model group,the hippocampal tissue structure of the high-dose and low-dose TAC groups was relatively compact and uniform,the neurons were neatly arranged,and the cell structure was relatively clear and complete,while the number of neuronal apoptotic cells and the apoptosis rate decreased significantly(respectively[3.8±0.7]cells vs.[6.2±1.2]cells,[12.4±2.8]％vs.[20.2±3.9]％;both P＜0.05),and the average integrated optical density values of the positive expression areas of Sirt1 and Bcl-2 proteins(the high-dose and low-dose TAC groups:Sirt1 150.0±4.8,131.3±1.3,and Bcl-2 207.1±7.4,169.5±3.9,respectively)were significantly increased(both P＜0.05),the average integral optical density values of P53,PUMA and BAX proteins were significantly decreased(the high-dose and low-dose TAC groups:P53 105.9±8.8,115.5±9.0,and PUMA56.8±5.1,74.4±3.9,and BAX40.5±5.6,48.4±5.0,respectively,all P＜0.05),the relative expression levels of Bcl-2 protein(the high-dose and low-dose TAC groups:0.53±0.05,0.47±0.02,respectively)were significantly increased(P＜0.05),the relative expression levels of P53(the high-dose and low-dose TAC groups:0.21±0.02,0.24±0.04,respectively),PUMA(the high-dose and low-dose TAC groups:0.36±0.02,0.28±0.04,respectively)and BAX proteins(the high-dose and low-dose TAC groups:0.52±0.02,0.54±0.03,respectively)were significantly decreased(all P＜0.05),the relative expression level of Sirt1 protein in the TAC high-dose group was significantly decreased(0.71±0.05,P＜0.05),and the relative expression level of Sirt1 protein in the TAC low-dose group was not statistically significant(0.52±0.08,P＞0.05).Conclusion TAC can alleviate neuronal damage and reduce the apoptosis rate of neurons in the hippocampus of CCH rats,and the mechanism may be related to the activation of Sirt1/P53 pathway,inhibition of P53 protein activity,and thus the expression level of apoptosis-related proteins in the downstream of TAC.

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.
Drugs, Chinese Herbal/chemistry* ; Aconitum/chemistry* ; Polysaccharides/pharmacology* ; Structure-Activity Relationship ; Technology