Chemotherapeutic drugs, such as cisplatin and phenanthriplatin (PhenPt), as STING agonists to induce DNA damage and activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway provides a potential strategy for clinical chemo-immunotherapy. However, treatment with Pt-based drugs leads to irreversible ectopia of phosphatidylserine (PS), a major component of the intracellular membrane, to the surface of the cancer cells by enzymes (Xkr8). Exposed PS can bind to immune cell receptors and inhibit the presentation of tumor antigens, leading to immunosuppression and attenuation of chemotherapy. Herein, we report a novel approach to enhance chemo-immunotherapy by constructing siRNA targeted Xkr8 (siXkr8)-mediated tetrahedral framework nucleic acid nanogel structure concurrently loaded with PhenPt (siXkr8-FNG/PhenPt) for co-delivery of siRNA and Pt-based drugs. The results showed that siXkr8-FNG/PhenPt can not only be used as an efficient delivery carrier to deliver siXkr8, block the expression of Xkr8, reduce the exposure of PS on the cancer cells surface, but also act as an immune stimulant to activate cGAS-STING pathway, effectively improve the immunosuppressive microenvironment, produce antitumor immune response, and inhibit tumor growth and metastasis. Overall, this new delivery system is important for improving the effect of Pt-based drug chemotherapy, inducing immune enhancement and nucleic acid drug delivery.

To investigate the impact of miR-142-5p on intestinal epithelial cells,an expression vector for overexpressing miR-142-5p lentivirus was constructed and administered to mice to observe pathological changes in their colon tissue.The miR-142-5p gene was integrated into the green fluo-rescent lentiviral vector plenti-CMV/TO eGFP-Puro(plenti),and the resulting recombinant vec-tor was named plenti miR-142-5p following confirmation through sequencing.293T cells were transfected with the recombinant plasmid and packaging-assisted plasmid,yielding a packaged miR-142-5p overexpressing lentiviral vector(LV-miR-142-5p).The recombinant lentivirus suspen-sion was collected and concentrated via ultrafast centrifugal precipitation.Virus titer was deter-mined using real-time PCR.The virus suspension was then injected into the tail vein of 6-8-week-old BALB/c mice,after which their colonic tissues were dissected for HE staining and microscopic observation.The results showed that miR-142-5p homologous recombination into plenti vector and sequencing results were consistent with the expected sequence.plenti-miR-142-5p was co-transfect-ed with the packaging helper plasmid in 293T cells,and the successful transfection was confirmed based on the green fluorescence expression,and the real-time PCR results showed that the lentiviral titer was 1.23 × 109 IU/mL.Colon tissue slices from infected mice exhibited compromised colon integrity and significant inflammatory response.It was proved that LV-miR-142-5p was suc-cessfully constructed,and miR-142-5p caused damage to intestinal epithelial cells of mice.

Migraine is a common neurological disorder with a complex pathogenesis that is currently not fully understood;however,the role of mitochondrial function in migraine pathogenesis has recently attracted widespread attention.This review considers the latest research progress on the relationship between mitochondrial dysfunction and migraine,including mitochondrial energy metabolism,oxidative stress,calcium homeostasis,and neuroinflammation.We introduce the epidemiological and clinical characteristics of migraine,and provide a detailed exploration of the key role of mitochondria in these processes.Mitochondrial dysfunction may lead to increased neuronal excitability,abnormal vasoconstriction,and inflammatory responses,thereby inducing migraine.Based on the evidence of mitochondrial involvement in the pathogenesis of migraine,we propose future research directions and potential treatment strategies,with the aim of providing new ideas for the prevention and treatment of migraine.

Migraine is a common neurological disorder with a complex pathogenesis that is currently not fully understood;however,the role of mitochondrial function in migraine pathogenesis has recently attracted widespread attention.This review considers the latest research progress on the relationship between mitochondrial dysfunction and migraine,including mitochondrial energy metabolism,oxidative stress,calcium homeostasis,and neuroinflammation.We introduce the epidemiological and clinical characteristics of migraine,and provide a detailed exploration of the key role of mitochondria in these processes.Mitochondrial dysfunction may lead to increased neuronal excitability,abnormal vasoconstriction,and inflammatory responses,thereby inducing migraine.Based on the evidence of mitochondrial involvement in the pathogenesis of migraine,we propose future research directions and potential treatment strategies,with the aim of providing new ideas for the prevention and treatment of migraine.

To investigate the impact of miR-142-5p on intestinal epithelial cells,an expression vector for overexpressing miR-142-5p lentivirus was constructed and administered to mice to observe pathological changes in their colon tissue.The miR-142-5p gene was integrated into the green fluo-rescent lentiviral vector plenti-CMV/TO eGFP-Puro(plenti),and the resulting recombinant vec-tor was named plenti miR-142-5p following confirmation through sequencing.293T cells were transfected with the recombinant plasmid and packaging-assisted plasmid,yielding a packaged miR-142-5p overexpressing lentiviral vector(LV-miR-142-5p).The recombinant lentivirus suspen-sion was collected and concentrated via ultrafast centrifugal precipitation.Virus titer was deter-mined using real-time PCR.The virus suspension was then injected into the tail vein of 6-8-week-old BALB/c mice,after which their colonic tissues were dissected for HE staining and microscopic observation.The results showed that miR-142-5p homologous recombination into plenti vector and sequencing results were consistent with the expected sequence.plenti-miR-142-5p was co-transfect-ed with the packaging helper plasmid in 293T cells,and the successful transfection was confirmed based on the green fluorescence expression,and the real-time PCR results showed that the lentiviral titer was 1.23 × 109 IU/mL.Colon tissue slices from infected mice exhibited compromised colon integrity and significant inflammatory response.It was proved that LV-miR-142-5p was suc-cessfully constructed,and miR-142-5p caused damage to intestinal epithelial cells of mice.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective To investigate the application effects of different myocardial protective solutions in total thoracoscopic minimally invasive aortic valve replacement surgery.Methods The clinical data of 72 patients with total thoracoscopic minimally invasive aortic valve replacement surgery in this hospital from May 2020 to January 2024 were analyzed retrospectively.The patients were divided into the St Thomas cardioplegia group(STH group,n=13),del Nido cardioplegia group(DN group,n=24),histidine tryptophan ketoglutar-ate solution group(HTK group,n=35)according to the different myocardial protective solutions.The levels of lactate(Lac)before and during surgery,the highest levels of myocardial creatine kinase isoenzyme(CK-MB),high-sensitivity troponin T(TnT)and creatinine(Cr)before operation,on the operative day and after surgery as well as the duration of extracorporeal circulation,aortic cross-clamping time,maximum flow rate,minimum bladder temperature,cardioplegia perfusion times,number of defibrillation after aortic de-clamping,postoperative ventilator assisted time,ICU stay duration and postoperative hospitalization duration were com-pared among the three groups.Results Except for 1 case of HTK was discharged automatically after surgery,the other 71 cases recovered and discharged according to the doctor's advice.There were no statistically signif-icant differences in the age,body weight,extracorporeal circulation time,aortic blocking time,maximum flow volume of extracorporeal circulation,minimum bladder temperature of extracorporeal circulation,Lac before extracorporeal circulation,highest Lac during extracorporeal circulation,assistant time of postoperative venti-lator,ICU stay duration,postoperative hospitalization duration,serum Cr before operation,Cr on operative day,preoperative TnT,postoperative TnT on operative day,postoperative highest TnT,preoperative CK-MB,postoperative CK-MB on operative day and postoperative highest CK-MB among the three groups(P＞0.05).There were statistically significant differences in the defibrillation ratio after aortic de-clamping and perfusion frequency of myocardial protective solution(P＜0.05).There was statistically significant difference in the perfusion frequency of myocardial protective solution in pairwise comparison among groups(P＜0.05),and the defibrillation ratio after aortic de-clamping had statistical difference between the DN group and HTK group(P＜0.05).Conclusion DN,STH and HTK all have good myocardial protective effect in total thoraco-scopic minimally invasive aortic valve surgery.HTK has the advantages of less perfusion times and decreasing the operative procedures compared with DN and STH;DN has the advantage of lower use for electrical defib-rillation correcting arrhythmias after aortic opening over HTK.

Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective To investigate the effect and mechanism of long non-coding RNA(lncRNA)maternally expressed gene 3(MEG3)on the alleviation of myocardial ischemia-reperfusion(IR)injury by sponging miR-21 in rats after ovariectomy(OVX).Methods A total of 108 female SD rats were subjected,and 48 of them were randomly divided into sham group,OVX group,IR group and combined group 1(OVX+IR),with 12 rats in each group.And the remaining 60 rats were given an injection with blank adeno-associated virus(AAV,negative control),lncRNA MEG3 AAV and miR-21 AAV,respectively through the tail vein before OVX and myocardial IR modeling,and then consequently assigned into negative sham group,negative model group,lncRNA MEG3 group,miR-21 group,and combined group 2(lncRNA MEG3+miR-21),with 12 rats in each group.Myocardial infarction size,left ventricular ejection fraction(LVEF),left ven-tricular fractional shortening(LVFS),serum lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)content,cardiomyocyte apoptotic rate and expression level of cleaved Caspase-3 were determined.Dual luciferase reporter gene assay was used to detect lncRNA MEG3 targeting miR-21 in H9c2 cardiomyocytes.Results Compared with the sham group,the expression of lncRNA MEG3 was decreased and that of miR-21 was increased in the OVX group,IR group and combined group 1(P＜0.05).The combination group 1 had significant-ly lower lncRNA MEG3 expression and higher miR-21 expression than the OVX group and IR group(P＜0.05).Compared with the negative model group,the myocardial infarction size,serum LDH,CK,CK-MB,cardiomyocyte apoptotic rate,and cleaved Caspase-3 expression were de-creased,while LVFS and LVEF were increased in the lncRNA MEG3 group(P＜0.05).Compared with the lncRNA MEG3 group,myocardial infarction size,serum LDH,CK,CK-MB content,car-diomyocyte apoptotic rate,Cleaved Caspase-3 expression were increased,while LVFS and LVEF were decreased in the combined group 2[(43.58±3.32)％vs(50.37±4.29)％,(57.12±4.28)％vs(68.47±5.61)％,P＜0.05].Conclusion Overexpression of lncRNA MEG3 alleviates the myo-cardium IR injury in OVX rats by sponging miR-21.

Objective To investigate the effect and mechanism of long non-coding RNA(lncRNA)maternally expressed gene 3(MEG3)on the alleviation of myocardial ischemia-reperfusion(IR)injury by sponging miR-21 in rats after ovariectomy(OVX).Methods A total of 108 female SD rats were subjected,and 48 of them were randomly divided into sham group,OVX group,IR group and combined group 1(OVX+IR),with 12 rats in each group.And the remaining 60 rats were given an injection with blank adeno-associated virus(AAV,negative control),lncRNA MEG3 AAV and miR-21 AAV,respectively through the tail vein before OVX and myocardial IR modeling,and then consequently assigned into negative sham group,negative model group,lncRNA MEG3 group,miR-21 group,and combined group 2(lncRNA MEG3+miR-21),with 12 rats in each group.Myocardial infarction size,left ventricular ejection fraction(LVEF),left ven-tricular fractional shortening(LVFS),serum lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)content,cardiomyocyte apoptotic rate and expression level of cleaved Caspase-3 were determined.Dual luciferase reporter gene assay was used to detect lncRNA MEG3 targeting miR-21 in H9c2 cardiomyocytes.Results Compared with the sham group,the expression of lncRNA MEG3 was decreased and that of miR-21 was increased in the OVX group,IR group and combined group 1(P＜0.05).The combination group 1 had significant-ly lower lncRNA MEG3 expression and higher miR-21 expression than the OVX group and IR group(P＜0.05).Compared with the negative model group,the myocardial infarction size,serum LDH,CK,CK-MB,cardiomyocyte apoptotic rate,and cleaved Caspase-3 expression were de-creased,while LVFS and LVEF were increased in the lncRNA MEG3 group(P＜0.05).Compared with the lncRNA MEG3 group,myocardial infarction size,serum LDH,CK,CK-MB content,car-diomyocyte apoptotic rate,Cleaved Caspase-3 expression were increased,while LVFS and LVEF were decreased in the combined group 2[(43.58±3.32)％vs(50.37±4.29)％,(57.12±4.28)％vs(68.47±5.61)％,P＜0.05].Conclusion Overexpression of lncRNA MEG3 alleviates the myo-cardium IR injury in OVX rats by sponging miR-21.