Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

Objective To investigate the effects and underlying mechanisms of down-regulating m6A demethylase fat mass and obesity-associated protein(FTO)on proplatelet formation in the MEG-01 megakaryocytic cells.Methods ①MEG-01 cells were treated with 1 nmol/L phorbol myristate acetate(PMA)(treatment group)or DMSO(control group)for 72 h.FTO expression was measured by Western blotting and RT-qPCR.② MEG-01 cells were infected with targeted FTO shRNA(knockdown group,sh-FTO)or negative control shRNA(negative control group,sh-NC)viruses.FTO knockdown group and negative control group MEG-1 cells were treated with 1 nmol/L PMA for 72 h,and the protein and mRNA expression levels of FTO were detected by Western blotting and RT-qPCR.Cell cycle,viability and apoptosis were assessed by propidium iodide(PI)DNA staining,CCK-8 assay and Annexin V-FITC/PI double staining and TUNEL staining.The expression of cleaved Caspase-3 protein was determine by Western blotting.Megakaryocyte maturation was assessed by CD41/CD61 staining.Proplatelet formation was observed under bright field and detected by CD61 immunofluorescence assay.The expression of apoptosis-related molecules(Caspase3,BAD,BAK1,BCL2 and MCL1)was detected by RT-qPCR,and the protein change of BCL2 was further verified by Western blotting.The dataset was screened out from the gene expression omnibus(GEO)database,and then analyzed with University of California,Santa Cruz(UCSC)genome browser to compare the methylation sequencing peaks on BCL2 mRNA,and m6A methylated RNA immunoprecipitation(m6A-RIP)was used to assess the m6A methylation levels of BCL2 target gene mRNAs in MEG-01 megakaryocytes.Then,the changes in the m6A methylation enrichment level of BCL2 mRNA were observed between the sh-NC group and the sh-FTO group.mRNA stability and ribosome profiling assays were performed to assess translational efficiency of target genes.Results ①PMA treatment upregulated the expression of FTO at protein(P＜0.05)and mRNA(P＜0.01)levels.② FTO shRNA resulted in reduced FTO expression at both mRNA and protein levels(P＜0.01).Compared to the negative control group,the FTO knockdown group showed more cells arrested at the G1/S phase[(60.80±1.29)%vs(72.13±1.18)%,P＜0.01],significantly reduced cell viability[(1.17±0.03)%vs(0.69±0.05)%,P＜0.01],increased Annexin V-FITC/PI positive cells[(12.87±0.83)%vs(17.45±1.58)%,P＜0.01],more TUNEL positive cells[(1.03±0.27)%vs(17.49±9.91)%,P＜0.01],enhanced protein level of cleaved Caspase-3(P＜0.01),decreased proportion of CD41/CD61 positive cells[(51.63±1.13)%vs(34.08±0.53)%,P＜0.01],and less proplatelet formation in MEG-01 megakaryocytes[(26.49±6.73)%vs(13.31±5.97)%,P＜0.01].③Compared to sh-NC group,the FTO knockdown group had significantly decreased protein and mRNA expression of anti-apoptotic molecule BCL2(P＜0.01).UCSC GEO sequencing data revealed there were m6A methylation modification sites on BCL2 mRNA,which was verified through m6A-RIP experiment in MEG-01 megakaryocytes.Compared with GAPDH mRNA,BCL2 mRNA exhibited a significantly enriched m6A signal(P＜0.01).Compared to sh-NC group,a significant increase in m6A methylation modification was observed on BCL2 mRNA.BCL2 mRNA stability was significantly decreased,and its translation efficiency significantly was decreased(P＜0.01).Conclusion m6 A demethylase FTO rgulates BCL2 mRNA stability and translation efficiency,thereby promoting proplatelet formation in MEG-01 megakaryocytes.

Objective:To investigate the effect of tumor necrosis factor α (TNF-α) on the permeability of blood labyrinth barrier in C57BL/6J male mice and its possible mechanism.Methods:As for the design of animal experiment, twenty male C57BL/6J mice aged 6-8 weeks were randomly divided into control group and cisplatin group with 10 mice in each group by software method. The control group was intraperitoneally injected with normal saline every day, and the cisplatin group was intraperitoneally injected with 4 mg/kg cisplatin for 4 consecutive days. After administration, auditory brainstem response (ABR) was used to detect hearing changes in mice. HE staining was used to observe the morphological changes of mouse cochlea vasculature. The expression of TNF-α was detected by immunohistochemistry and ELISA. The permeability of the blood labyrinth barrier was observed by Evans blue staining. With respect to the design of cell experiment, primarily cultured cochlea pericytes (PC) and endothelial cells (EC) were divided into EC group, EC+TNF-α group, EC+PC group, EC+PC+TNF-α group, EC+PC+TNF-α+SB-3CT (MMP-9/MMP-2 secretion inhibitor) group, PC group, PC+TNF-α group, PC+TNF-α+LY294002 (PI3K/AKT pathway inhibitor) group, PC+LY294002 group. The protein expressions of ZO-1, VE-cadherin, MMP-9, MMP-2, PI3K, p-PI3K, AKT, and p-AKT were detected by Western blot. TEER and FITC-dextran penetration experiment were used to detect EC resistance and monolayer EC permeability, respectively. The data were statistically analyzed using GraphPad Prism 8 software.Results:In animal experiment, compared with control group, the ABR response threshold of mice in cisplatin group was increased ( P<0.01). The vaccine ular structure of the cochlea was disordered red, wrinkled and vacuole increased. The extravasation of vascular red fluorescent dye increased ( P<0.05), and also, levels of serum TNF-α and cochlear veins increased ( P<0.01). In cell experiment, by treatment of EC with different concentrations of cisplatin, 20 μmol cisplatin led to the highest expression of TNF-α ( P<0.01). The expression of TNF-α was the highest after 3 h intervention in EC ( P<0.05). Compared with those in EC+PC group, the resistance value of EC was decreased, the permeability of monolayers EC was increased, the expression of ZO 1 and VE cadherin proteins was decreased, and however, the resistance value was increased and the permeability of EC was decreased after the intervention of SB-3CT in EC+PC+TNF-α group. The expressions of ZO-1 and VE-cadherin proteins were increased ( P<0.05). The expression of MMP-9 increased after TNF-α intervention ( P<0.05), the expression of MMP-2 had no significant change, and the expression of p-PI3K/PI3K and p-AKT/AKT were increased ( P<0.05). The expression of MMP-9 decreased in PC+TNF-α+LY294002 group ( P<0.05). Conclusion:The hearing loss of C57BL/6J male mice induced by cisplatin may be related to the increased release of TNF-α from the blood labyrinth barrier EC in the cochlear stria vascularis, and the activation of PI3K/AKT signaling pathway by TNF-α in PC, which increases the secretion of MMP-9 from PC, ultimately leads to the increased permeability of the blood labyrinth barrier.

OBJECTIVE To observe the effect of Jiangqi Pingxiao Formula on airway inflammation in mice with acute asthma and explore its possible mechanism.METHODS A total of 36 BALB/c mice were randomly divided into normal group,model group,dexamethasone group,low-dose,medium-dose and high-dose groups of Jiangqi Pingxiao Formula,with 6 mice in each group.Except for the normal group,the other groups were given ovalbumin to establish the acute asthma attack mouse model.The normal group and the model group were given distilled water by gavage,and the Jiangqi Pingxiao Formula groups were given Jiangqi Pingxiao Formula by gavage at the corresponding dose,once a day,for 5 consecutive days.Whole Body Plethysmography was used to measure the changes of enhanced respiratory interval(Pehn)of bronchial contraction parameters in mice.HE staining was used to observe the pathological changes of lung tissue in mice.ELISA method was adopted to detect the expression levels of interleukin 1β(IL-1β),interleukin 18(IL-18)and tumor necrosis factor α(TNF-α)in lung tissue homogenate of mice.Immunohistochemistry method was used to detect the expression level of NOD-like receptor pyrin domain-associated protein 3(NLRP3)in lung tissue of mice.Western blot method was employed to detect the expression of NLRP3 inflammasome activation-associated protein κ gene binding nuclear factor-κB(NF-κB),NOD-like receptor pyrin domain-associated protein 3(NLRP3),NIMA-associated kinase 7(NEK7),Caspase 1(Cleaved-Caspase 1)and apoptosis-associated speck-like protein(ASC)in lung tissue of mice.RESULTS Compared with the normal group,the Penh level of mice in the model group was increased(P<0.001),and the pathological results of lung tissue showed that the number of inflammatory cells around the airway increased,the inflammatory score increased(P<0.001),the expression of IL-1β,IL-18,and TNF-α in lung tissue homogenate increased(P<0.001),and the expression of NF-κB,NLRP3,NEK7,Cleaved-Caspase 1,and ASC proteins in lung tissue increased(P<0.05,P<0.01,P<0.001).Compared with the model group,the Penh level of mice in the Jiangqi Pingxiao Formula groups and the dexamethasone group was reduced(P<0.05,P<0.001),the number of inflammatory cells in lung tissue decreased,and the inflammatory score decreased(P<0.001);the expression of IL-1β,IL-18,and TNF-α in lung tissue homogenate decreased(P<0.05,P<0.01,P<0.001);the expression of NF-κB,NLRP3,NEK7,Cleaved-Caspase 1,and ASC pro-teins in lung tissue decreased(P<0.05,P<0.01,P<0.001).CONCLUSION Jiangqi Pingxiao Formula can improve lung function and airway inflammation in asthma model mice,and its mechanism may be related to regulating NLRP3 inflammasome-mediated IL-1β secretion.

Objective To investigate the relationship between the early neutrophil-to-lymphocyte ratio(NLR)in peripheral blood,poor prognosis and early neurological deterioration(END)in patients with acute ischemic stroke(AIS)following intravenous thrombolysis treatment.Methods The retrospective study included 221 AIS patients who underwent intravenous thrombolysis therapy.Demographic information,medical history,clinical and imaging data were collected.Peripheral venous blood samples were drawn before treatment for routine blood tests,and NLR was calculated.The primary endpoint was poor prognosis or death at 3 months after onset,and the secondary endpoint was symptomatic intracranial hemorrhage(SICH)or END within 24 hours after thrombolysis.Logistic regression was used to analyze factors associated with the primary and secondary endpoint events.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of NLR for clinical outcomes.Results Logistic regression analysis revealed that female,hypertension,higher baseline NLR(OR=1.968,95%CI:1.516-2.555,P＜0.001)and NIHSS scores were independent risk factors for 3-month poor outcomes in AIS patients.Female,a history of stroke or transient ischemic attack(TIA),higher random blood glucose,elevated baseline NLR(OR=1.317,95%CI:1.028-1.688,P=0.030)and NIHSS scores were independent risk factors for 3-month mortality.Hypertension,elevated homocysteine,higher baseline NLR(OR=1.420,95%CI:1.180-1.709,P＜0.001)and NIHSS scores were independent risk factors for END.There was no significant difference in NLR level between the SICH group(n=5)and the non-SICH group(n=216).ROC curve analysis showed that baseline NLR had high predictive value for 3-month poor outcomes,3-month mortality and END in AIS patients,with AUCs of 0.748(95%CI:0.679-0.817),0.738(95%CI:0.622-0.853)and 0.730(95%CI:0.656-0.804),respectively.There was no predictive value for SICH.Patients in the high NLR group(NLR≥2.63,n=89)had significantly higher baseline NIHSS scores,random blood glucose levels and rates of hypertension,coronary artery disease,END,3-month poor outcomes and 3-month mortality compared to those in the low NLR group(NLR＜2.63,n=132).Conclusion Elevated baseline NLR is associated with the occurrence of END and 3-month poor outcomes in AIS patients following intravenous thrombolysis therapy,suggesting its potential as a biomarker for predicting clinical outcomes in AIS patients.

Objective The optimum formulation process was selected to prepare the ethosomes of Cortex Dictamni-Fructus Kochiae,and its prescription was verified and its properties were studied.Methods The formulation was optimized by single factor and response surface test.The appearance,particle size,Zeta potential and stability were investigated.The encapsulation rate was used as the evaluation index.Results The optimum preparation process of ethosomes of Cortex Dictamni-Fructus Kochiae is as follows:Using the dosage of lyophilized powder 409.06 mg,soybean lecithin 258.07 mg,cholesterol 90.87 mg,ethanol volume fraction 22.76％,stirred for 2 hours at 700 r·min-1 at 50 ℃ water bath temperature,The appearance of the prepared ethosomes suspension was light yellow,and the particles were nearly spherical in shape.The average particle size was(103.1±0.78)nm,the Zeta potential was(-36.0±3.65)mV,and the average encapsulation rates of Xibutanone,ash,and saponin Ⅰc were(89.25±0.91)％,(80.16±1.52)％,(86.59±0.58)％,respectively.After 14 days of storage at room temperature,the results showed that:The ethosomal suspension is still a light yellow,uniform,and stable liquid,and there is no stratified precipitation phenomenon.Conclusion The method of ethanol injection is easy to operate,high encapsulation rate and good stability,which lays a foundation for further study on the skin administration of this preparation.

Objective:To summarize the best evidence for frailty management in patients undergoing postoperative chemotherapy for gastric cancer, so as to provide reference for alleviating patient frailty.Methods:Guidelines, expert consensus, evidence summaries, systematic reviews, and randomized controlled trials and other articles on the frailty management of patients with postoperative chemotherapy for gastric cancer were electronically searched in computerized decision-making systems such as UpToDate, BMJ Best Practice, and Guidelines International Network, in comprehensive databases such as PubMed, Embase, and Web of Science, and in the websites of professional societies. The search period was from database establishment to September 15, 2024. Two researchers independently screened the literature and evaluated the quality of the included literature, combining professional judgment to extract and summarize the best evidence.Results:A total of 18 papers were included, including two clinical decisions, one evidence summary, eight guidelines, two expert consensus, one systematic review, one randomized controlled trial, two quasi-experimental studies, and one observational study. The best evidence included a total of 34 pieces in seven aspects of comprehensive screening, nursing plan construction, preoperative prehabilitation, nutritional interventions, Chinese medicine interventions, exercise interventions, and psychological interventions for frailty.Conclusions:The summary of the best evidence for frailty management in patients undergoing postoperative chemotherapy for gastric cancer may provide an evidence-based basis for frailty interventions by clinical medical and staff.

Objective The optimum formulation process was selected to prepare the ethosomes of Cortex Dictamni-Fructus Kochiae,and its prescription was verified and its properties were studied.Methods The formulation was optimized by single factor and response surface test.The appearance,particle size,Zeta potential and stability were investigated.The encapsulation rate was used as the evaluation index.Results The optimum preparation process of ethosomes of Cortex Dictamni-Fructus Kochiae is as follows:Using the dosage of lyophilized powder 409.06 mg,soybean lecithin 258.07 mg,cholesterol 90.87 mg,ethanol volume fraction 22.76％,stirred for 2 hours at 700 r·min-1 at 50 ℃ water bath temperature,The appearance of the prepared ethosomes suspension was light yellow,and the particles were nearly spherical in shape.The average particle size was(103.1±0.78)nm,the Zeta potential was(-36.0±3.65)mV,and the average encapsulation rates of Xibutanone,ash,and saponin Ⅰc were(89.25±0.91)％,(80.16±1.52)％,(86.59±0.58)％,respectively.After 14 days of storage at room temperature,the results showed that:The ethosomal suspension is still a light yellow,uniform,and stable liquid,and there is no stratified precipitation phenomenon.Conclusion The method of ethanol injection is easy to operate,high encapsulation rate and good stability,which lays a foundation for further study on the skin administration of this preparation.

OBJECTIVE To observe the effect of Jiangqi Pingxiao Formula on airway inflammation in mice with acute asthma and explore its possible mechanism.METHODS A total of 36 BALB/c mice were randomly divided into normal group,model group,dexamethasone group,low-dose,medium-dose and high-dose groups of Jiangqi Pingxiao Formula,with 6 mice in each group.Except for the normal group,the other groups were given ovalbumin to establish the acute asthma attack mouse model.The normal group and the model group were given distilled water by gavage,and the Jiangqi Pingxiao Formula groups were given Jiangqi Pingxiao Formula by gavage at the corresponding dose,once a day,for 5 consecutive days.Whole Body Plethysmography was used to measure the changes of enhanced respiratory interval(Pehn)of bronchial contraction parameters in mice.HE staining was used to observe the pathological changes of lung tissue in mice.ELISA method was adopted to detect the expression levels of interleukin 1β(IL-1β),interleukin 18(IL-18)and tumor necrosis factor α(TNF-α)in lung tissue homogenate of mice.Immunohistochemistry method was used to detect the expression level of NOD-like receptor pyrin domain-associated protein 3(NLRP3)in lung tissue of mice.Western blot method was employed to detect the expression of NLRP3 inflammasome activation-associated protein κ gene binding nuclear factor-κB(NF-κB),NOD-like receptor pyrin domain-associated protein 3(NLRP3),NIMA-associated kinase 7(NEK7),Caspase 1(Cleaved-Caspase 1)and apoptosis-associated speck-like protein(ASC)in lung tissue of mice.RESULTS Compared with the normal group,the Penh level of mice in the model group was increased(P<0.001),and the pathological results of lung tissue showed that the number of inflammatory cells around the airway increased,the inflammatory score increased(P<0.001),the expression of IL-1β,IL-18,and TNF-α in lung tissue homogenate increased(P<0.001),and the expression of NF-κB,NLRP3,NEK7,Cleaved-Caspase 1,and ASC proteins in lung tissue increased(P<0.05,P<0.01,P<0.001).Compared with the model group,the Penh level of mice in the Jiangqi Pingxiao Formula groups and the dexamethasone group was reduced(P<0.05,P<0.001),the number of inflammatory cells in lung tissue decreased,and the inflammatory score decreased(P<0.001);the expression of IL-1β,IL-18,and TNF-α in lung tissue homogenate decreased(P<0.05,P<0.01,P<0.001);the expression of NF-κB,NLRP3,NEK7,Cleaved-Caspase 1,and ASC pro-teins in lung tissue decreased(P<0.05,P<0.01,P<0.001).CONCLUSION Jiangqi Pingxiao Formula can improve lung function and airway inflammation in asthma model mice,and its mechanism may be related to regulating NLRP3 inflammasome-mediated IL-1β secretion.

Objective To investigate the relationship between the early neutrophil-to-lymphocyte ratio(NLR)in peripheral blood,poor prognosis and early neurological deterioration(END)in patients with acute ischemic stroke(AIS)following intravenous thrombolysis treatment.Methods The retrospective study included 221 AIS patients who underwent intravenous thrombolysis therapy.Demographic information,medical history,clinical and imaging data were collected.Peripheral venous blood samples were drawn before treatment for routine blood tests,and NLR was calculated.The primary endpoint was poor prognosis or death at 3 months after onset,and the secondary endpoint was symptomatic intracranial hemorrhage(SICH)or END within 24 hours after thrombolysis.Logistic regression was used to analyze factors associated with the primary and secondary endpoint events.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of NLR for clinical outcomes.Results Logistic regression analysis revealed that female,hypertension,higher baseline NLR(OR=1.968,95%CI:1.516-2.555,P＜0.001)and NIHSS scores were independent risk factors for 3-month poor outcomes in AIS patients.Female,a history of stroke or transient ischemic attack(TIA),higher random blood glucose,elevated baseline NLR(OR=1.317,95%CI:1.028-1.688,P=0.030)and NIHSS scores were independent risk factors for 3-month mortality.Hypertension,elevated homocysteine,higher baseline NLR(OR=1.420,95%CI:1.180-1.709,P＜0.001)and NIHSS scores were independent risk factors for END.There was no significant difference in NLR level between the SICH group(n=5)and the non-SICH group(n=216).ROC curve analysis showed that baseline NLR had high predictive value for 3-month poor outcomes,3-month mortality and END in AIS patients,with AUCs of 0.748(95%CI:0.679-0.817),0.738(95%CI:0.622-0.853)and 0.730(95%CI:0.656-0.804),respectively.There was no predictive value for SICH.Patients in the high NLR group(NLR≥2.63,n=89)had significantly higher baseline NIHSS scores,random blood glucose levels and rates of hypertension,coronary artery disease,END,3-month poor outcomes and 3-month mortality compared to those in the low NLR group(NLR＜2.63,n=132).Conclusion Elevated baseline NLR is associated with the occurrence of END and 3-month poor outcomes in AIS patients following intravenous thrombolysis therapy,suggesting its potential as a biomarker for predicting clinical outcomes in AIS patients.