ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

China bears a substantial disease burden of chronic hepatitis B （CHB）. Under current clinical management regimens for CHB， achieving functional cure （also termed clinical cure） is the core goal for the treatment of patients meeting treatment indications. To achieve the goal of functional cure， drug regulatory authorities in China and globally have successively issued technical criteria to provide guidance for the overall design and scientific evaluation of clinical trials for innovative drugs. However， the rapid development in scientific research， clinical practice， and new drug research and development in this field has brought new challenges， especially those concerning the assessment of the clinical value of investigational drugs. This article reviews the current status of clinical research and development of new drugs for achieving the functional cure of CHB worldwide， analyzes the characteristics of available clinical trial data， and focuses on key aspects of pivotal clinical trials for CHB functional cure drugs， including target populations （baseline HBsAg level）， HBsAg seroclearance response， HBsAg seroreversion after drug withdrawal， and clinically meaningful target threshold of functional cure response rate， in order to provide a reference for further refinement of related technical criteria.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.

Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.

Objective:To investigate the CLEC3B protein of differentially expressed proteins(DEPs)in serum of normal persons and patients with sepsis,and explore the possibility that target C-type lectin domain family 3 member B(CLEC3B)protein was used as molecular markers of sepsis.Methods:Peripheral bloods of 10 healthy persons and 18 patients with sepsis were collected,and the data of peripheral serum proteins were collected by data independent acquisition(DIA)method.The data were uploaded to iDEP online platform to analyze the DEPs in peripheral blood of patients with sepsis.Bioinformatics analysis of these DEPs was conducted to screen out the key proteins of sepsis.Enzyme linked immunosorbent assay(ELISA)was used to verify and plot the receiver operating characteristic(ROC)curves of key proteins.Results:A total of 138 differentially expressed proteins(DEPs)were screened out by using proteomics analysis,of which 34 kinds of proteins were significantly down-regulated and 104 kinds of proteins were significantly up-regulated.DEPs mostly concentrated in cellular processes,biological regulation,biological process regulation,participating binding,catalytic activation,molecular function regulation,immune system,signal transduction and so on.A protein-protein interaction network was constructed by DEPs,which screened out the key protein CLEC3B.ELISA results showed that the CLEC3B protein concentration[(297.73±22.00)ng/mL]of patients in the sepsis group was significantly lower than that[(452.42±191.72)ng/mL]in the healthy group,and the difference was statistically significant(t=13.13,P=0.000).The area under curve(AUC)value of ROC curve,sensitivity and specificity of CLEC38 protein were respectively 0.998,97.73%and 100.0%.Conclusion:CLEC3B is significantly decreased in sepsis group,which sensitivity and specificity are high.It can be used as a potentially biological diagnostic biomarker of sepsis.

Objective To investigate the initial dose and safety of intravenous infusion of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) for the displacement of cadmium. Methodsi) Efficacy test. The New Zealand male rabbits were randomly divided into model group, calcium disodium edetate (EDTA) group and GMDTC low-, medium- and high-dose groups after cadmium poisoning using 2.5 cadmium chloride dihydrate. Rabbits in EDTA group were intravenously injected with EDTA dipotassium at a dose of 93.5 mg/kg body weight, rabbits in the three doses groups were intravenously injected of GMDTC at doses of 12.0, 36.0, and 108.0 mg/kg body weight, respectively. The rabbits in the control group (separate set) and model group were intravenously injected with equal volumes of 0.9% sodium chloride solution, administered for five consecutive days per week for 1, 2, and 4 weeks. ii) Toxicity test. Specific pathogen free SD rats were randomly divided into solvent control group and low-, medium- and high-dose groups. In the acute toxicity test, the rats in the three-dose groups were intravenously injected of GMDTC at doses of 200.0, 800.0 and 3 000.0 mg/kg body weight, respectively. In the long-term toxicity test, the rats in the three-dose groups were intravenously injected GMDTC at doses of 100.0, 500.0 and 2 000.0 mg/kg body weight, respectively, once a day for four consecutive weeks, with a recovery period of four weeks. The rats in the solvent control group were given an equal volume 0.9% sodium chloride solution intravenously at the same time. The maximum tolerated dose (MTD) and no observable adverse effect level (NOAEL) were detected. Resultsi) In the one week treatment experiment, the 24 hours urinary cadmium levels of rabbits in the three doses groups were higher than those in the model group at the same time point (all P<0.05). In the two weeks treatment experiment, the 24 hours urinary cadmium levels of rabbits in medium-dose and high-dose groups at the three time points were higher than those in the model group at the same time point (all P<0.05). In the four weeks treatment experiment, the 24 hours urinary cadmium level on the 19th day of rabbits in the low-dose group was higher than that in the model group at the same time point (P<0.05), and the 24 hours urinary cadmium levels of rabbits in medium- and high-dose groups at the five time points were higher than those in the model group at the same time point (all P<0.05), except for the rabbits of fifth day of the medium-dose group. The kidney cadmium levels of rabbits in the low-dose group after four week of treatment and in the medium- and high-dose groups after one, two, and four weeks of treatment decreased compared with the model group (all P<0.05). No obvious adverse effects were observed during the treatment. ii) The MTD of GMDTC in rats administered intravenously in a single dose was 3 000.0 mg/kg body weight. During the period of intravenous infuseion with GMDTC for four consecutive weeks, the blood drug level reached the peak at the end of the first and last administrations (eight min), and no clinical adverse reactions were observed during this period of time, nor was there any apparent accumulation. The NOAEL for intravenous infusion of GMDTC for four consecutive weeks in rats was 500.0 mg/kg body weight. Conclusion The initial dose of the GMDTC injection in the cadmium poisoning rabbit was 36.0 mg/kg body weight, and the recommended initial dose for human is 480.0 mg/person. Intravenous infusion of GMDTC is characterized by rapid absorption, rapid elimination, and no accumulation.

Objective:To retrospectively analyze the feasibility of undergoing day surgery at 3rd week after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children.Methods:The clinical data from children who underwent day surgery from November 1, 2022 to February 28, 2023, with operation time ≤1 h, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, regardless of gender, aged≤14 yr, with body mass index of 10-30 kg/m 2, were divided into SARS-CoV-2 group and control group according to whether the children had been infected with the SARS-CoV-2. The main outcome measure was the incidence of respiratory system-related complications within 30 days after surgery. Secondary outcome measures included the rate of unplanned ventilation, delayed discharge and secondary admission within 30 days after surgery. Preoperative creatine kinase isoenzyme (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), white blood cell count, C-reactive protein (CRP) level, grade of oropharyngeal mucosa inflammation, operation time, emergence time, intraoperative respiratory depression, laryngeal spasm, hypoxemia, hypotension, incidence of sinus bradycardia and rate of additional rescue drugs were recorded. Results:There were 337 cases in SARS-CoV-2 group and 1 396 cases in control group. Compared with control group, CK-MB concentrations were significantly increased, and the Hb concentration was decreased before surgery in SARS-CoV-2 group ( P<0.05). There were no statistically significant differences in the incidence of respiratory system-related complications, unplanned ventilation, delayed discharge and rate of postoperative secondary admission, preoperative AST and ALT concentrations, white blood cell count, CRP concentrations, grade of oropharyngeal mucosa inflammation, operation time, intraoperative respiratory depression, laryngeal spasm, hypoxemia, hypotension, incidence of sinus bradycardia, rate of additional rescue drugs and emergence time between the two groups ( P>0.05). Conclusions:Feasibility of undergoing day surgery is good at the third week after being infected with the SARS-CoV-2 in children.

Objective:To screen key differentially expressed genes(DEGs)in dead mice with sepsis by spleen high-through-put sequencing combined with bioinformatics.Methods:①A mouse sepsis model was set up by intraperitoneal injection of lipopolysac-charide(LPS),a 7-day survival curve of mice was drawn,and the modeling doses of survival group and death group were screened out.②Expressions of TNF-α,IL-1β,IL-6 and IL-10 in peripheral blood of mice in control group,survival group and death group were verified by ELISA.③High-throughput sequencing was conducted on spleens of survival group and death group,and the key genes were screened by bioinformatics analysis of DEGs.④Expressions of key genes and proteins were detected by RT-PCR and Western blot.Results:①LPS dosage in survival group was 15 mg/kg(with a mortality of 30%),and LPS dosage in death group was 30 mg/kg(with a mortality of 80%).②Expression levels of IL-6,TNF-α and IL-1β in sepsis mice were significantly higher than those of control group,while expression level of IL-10 was decreased(P<0.05).Comparison of sepsis model groups showed that levels of pro-inflammatory factors in death group were higher than those in survival group,while level of IL-10 was lower than that in survival group(P<0.05).③A total of 2999 DEGs in survival group and death group were screened out by bioinformatics,among which 1185 genes were up-regulated and 1814 genes were down-regulated.Top 5 DEGs enrichment pathways were screened out:"hematopoietic cell lineage""primary immunodeficiency""African trypanosomiasis""leishmaniasis"and"B-cell receptor signaling pathway".Ifit1,Ifit3 and Mx1 were three key genes that were screened out.④Compared with survival group,expressions of genes and proteins of Ifit1,Ifit3 and Mx1 were down-regulated in spleen tissues of the death group(P<0.05).Conclusion:By high-throughput sequencing and bioinformatics,Ifit1,Ifit3 and Mx1 are screened out as key genes related to the death outcome of sepsis,which probably influence the outcome of sepsis through the immune mechanism related to virus infection.