ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the association between serum fasting triglyceride glucose-body mass index （TyG-BMI） and new-onset metabolic dysfunction-associated fatty liver disease （MAFLD） within 10 years. MethodsA retrospective analysis was performed for the data of individuals who underwent physical examination in The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University in 2013， 2018， and 2023 and were not diagnosed with MAFLD in 2013， and a total of 1 340 valid subjects were enrolled according to the inclusion and exclusion criteria. The gbmt package in R 4.3.0 was used to construct the dynamic change trajectory model of TyG-BMI， and four different TyG-BMI trajectory groups were determined， i.e.， the low-level group （n=352）， the medium-level group （n=517）， the high-level group （n=314）， and the extremely high-level group （n=157）. The data on general information and blood biochemical parameters were collected from all subjects and were then compared between groups. The chi-square test was used for comparison of categorical data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data with heterogeneity of variance between multiple groups. The Cox regression analysis was used to investigate the association between different TyG-BMI trajectories and the risk of MAFLD， and the receiver operating characteristic （ROC） curve was used to assess the value of TyG-BMI in the diagnosis of MAFLD. ResultsThe cumulative incidence rate of MAFLD increased with the increase in the level of TyG-BMI trajectory， with a cumulative incidence rate of 4.83% in the low-level group， 29.98% in the medium-level group， 61.15% in the high-level group， and 83.44% in the extremely high-level group （P<0.001）， and the cumulative incidence rate of MAFLD in men was significantly higher than that in women （51.34% vs 20.67%， P<0.001）. The multivariate Cox regression analysis showed that increases in the levels of TyG-BMI trajectory， uric acid， diastolic blood pressure， hemoglobin， and alanine aminotransferase were independent risk factors for the onset of MAFLD （all P<0.05）， while the increase in high-density lipoprotein cholesterol was an independent protective factor against MAFLD （P<0.001）. After adjustment for confounding factors， the medium-， high-， and extremely high-level groups had a hazard ratio of 4.430 （95% confidence interval ［CI］： 2.660 — 7.377， P<0.001）， 6.937 （95%CI： 4.110 — 11.708， P<0.001）， and 7.989 （95%CI： 4.616 — 13.827， P<0.001）， respectively. The ROC curve analysis showed that TyG-BMI had the highest diagnostic value， with an area under the ROC curve of 0.859 （95%CI： 0.840 — 0.879）， a sensitivity of 79.8%， and a specificity of 76.3%. ConclusionThe risk of MAFLD increases with the increase in the level of TyG-BMI trajectory， and TyG-BMI can be used as a predictive indicator for MAFLD.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

Objective:To investigate the effect of ear acupoint bean pressing on gastrointestinal motility and related hormones after laparoscopic surgery in patients with hysteromyoma,and to explore the therapeutic mechanism of ear acupoint bean pressing.Methods:Patients undergoing laparoscopic myomectomy in the Department of Gynecology of The People's Hospital Affiliated to Fujian Univer-sity of Traditional Chinese Medicine from May 2022 to December 2023 were randomly divided into an experimental group and a control group,with 57 patients in each group.The experimental group was treated with postoperative routine nursing and ear acupoint bean pressing(targeting the spleen,stomach,and sympathetic),and the control group was treated with postoperative routine nursing and sham ear acupoint bean pressing(containing no Vaccaria seed,targeting the spleen,stomach,and sympathetic).After the intervention,the time to first postoperative passing of flatus and defecation,clinical efficacy,and changes in gastrointestinal hormone levels were compared between the two groups.Results:The time to first postoperative passing of flatus[20.31(17.52,22.38)h vs.21.51(18.53,28.15)h]and defecation[35.32(31.47,39.17)h vs.38.12(33.44,42.78)h]in the experimental group was lower than that in the control group(P<0.05),and the clinical efficacy was better than that in the control group(P<0.05).There were no significant differ-ences in motilin(MTL),gastrin(GAS),somatostatin(SS),and substance P(SP)levels between the two groups before operation(P>0.05).The MTL and GAS levels were increased and the SS and SP levels were decreased after operation.The MTL[(451.52±54.33)pg/mL vs.(476.24±56.35)pg/mL]and GAS[150.50(133.93,164.52)pg/mL vs.173.44(154.45,184.63)pg/mL]levels at 24 h after operation in the experimental group were lower than those in the control group(P<0.05),and the SS[38.34(33.24,40.23)pg/mL vs.33.36(29.13,38.76)pg/mL]level at 24 h after operation was higher than that in the control group(P<0.05),with no significant change in the SP level(P>0.05).The results of repeated measures analysis of variance and generalized estimation equation showed that there were significant differences in the time effect and interaction effect of MTL(P<0.05),a significant difference in the time effect of SP(P<0.05),and significant differences in the time effect,intergroup effect,and interaction effect of GAS and SS(P<0.05).Conclusion:Ear acupoint bean pressing has significant effect on abdominal distension after laparoscopic surgery in patients with hysteromyoma,ef-fectively regulates the level of gastrointestinal motility related hormones,and promotes the recovery of gastrointestinal function.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Objective:To explore the factors influencing ethical sensitivity of oncology nurses.Methods:Using purposive sampling, 15 oncology nurses from 13 tertiary general hospitals in Foshan, Guangdong Province were selected as research participants from July to September 2023. In-depth semi-structured interviews were conducted, and Colaizzi's seven-step content analysis method was applied to organize and analyze the collected data.Results:A total of 4 themes were summarized: insufficient clinical experience and knowledge reserve; lack of ethical education and management system processes; high-pressure working environment and communication barriers; and the constraints of the cultural concept of "valuing life over death".Conclusions:Oncology nurses have insufficient ethical sensitivity. Nursing managers should establish a systematic ethical education system, improve ethical management systems, optimize the clinical working environment, and integrate cultural sensitivity education to jointly enhance nurses' communication skills. Attention should also be paid to the inheritance of clinical experience from senior nurses, so as to improve the ethical sensitivity of oncology nurses in a multidimensional way.

Objective To explore and analyze the characteristics and transmission routes of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains in intensive care unit(ICU).Methods From January to October 2023,17 clinical infection isolates(clinical infection group),5 active screening isolates(active screening group),and 7 envi-ronmental isolates(environmental group)of CRKP in the liver surgery ICU of a hospital were selected and analyzed by whole-genome sequencing.The differences in resistance genes,virulence genes,and sequence typing(ST)were compared,and transmission routes were analyzed based on the phylogenetic tree.Results 29 strains of CRKP car-ried 4-18 resistance genes and 52-98 virulence genes,respectively.There were no statistically significant diffe-rences in genotype distribution of resistance genes,the number of virulence genes,and gene types among three groups of CRKP(all P＞0.05).ST showed that 29 CRKP strains mainly consisted of two categories:ST11 and ST15.Based on the phylogenetic tree constructed from the core genome,there were 7 highly homologous groups of CRKP,among which 4 groups had clear epidemiological associations.Conclusion CRKP in ICU carries more re-sistance and virulence genes,and some strains are highly homologous in ST and phylogenetic tree,which may lead to cross transmission.In the future,prevention and control measures should be strengthened to reduce the trans-mission of CRKP.