OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

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 explore the effects of sigma-1 receptor(Sig-1R)on brain function in rats after cardiopulmo-nary resuscitation and its protective role in brain injury.Methods Rats were randomly assigned to four groups with 20 in each:sham-operated control(sham group),6-hour post-resuscitation(PR 6 h group),12-hour post-resuscitation(PR 12 h group)and 24-hour post-resuscitation(PR 24 h group).In the latter three groups,cardiac arrest was induced by as-phyxiation,and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest.The rats were scored for neu-rological deficits at 6,12 and 24 hrs after resuscitation,respectively;after that,the rats were executed,and the expres-sion of Sig-1R protein,mitochondrial function index,and endoplasmic reticulum stress index apoptosis index were detec-ted by Western blot and immunohistochemistry.The correlation between Sig-1R and mitochondrial,endoplasmic reticulum stress and apoptosis indexes was evaluated.Results Compared with the sham-operated group,the rats in test group showed a gradual decrease in neurological deficit scores,Sig-1R protein expression,brain tissue adenosine triphos-phate(ATP)concentration and mitochondrial membrane potential(MMP)levels at 6,12,and 24 hrs of PR(P＜0.05);CHOP protein,activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated(P＜0.05).In addition,Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05)but positively correlated with mitochondrial membrane potential level(P＜0.05).Conclusions Sig-1R ex-pression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.

Objective To explore the correlation between serum vitamin D(VD3)level differences and immune inflammatory markers in elderly sepsis patients.Methods A total of 103 elderly patients with sepsis(aged 65-99 years)in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency:VD3 deficiency group(n=32)and VD3 severe deficiency group(n=71).Correlation analysis was conducted by comparing the differences in serum 25-(OH)-D3(VD3)levels,immune function-related indicators upon admission(blood routine,infection-related proteins,combined detection of 12 cytokines,absolute count analysis of lymphocytes and subgroups,quantitative determination of infection-related immune cells,immunoglobulin,and complement),illness severity,and prognostic indicators(APACHE-II score,SOFA score,duration of ICU stay,and 28-day mortality rate).Result(1)Serum VD3 levels were lower in elderly patients with sepsis.No patient was in the VD3 normal or insufficient group.Patients with severe VD3 deficiency had higher APACHE-II scores,SOFA scores,and 28-day mortality rates than those with VD3 deficiency,and these scores were negatively correlated with serum VD3 levels(P<0.001),while the difference in ICU stay duration between the two groups was not statistically significant(P>0.05);(2)WBC,PCT,CRP,and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group(P<0.05),while IL-6,IL-10,CD45+,CD3+/CD45+,and CD19+Abs were all higher than those in the VD3 severe deficiency group(P<0.05);In the VD3 deficiency group,VD3 levels were positively correlated with CD45+(P<0.05 for all),while negatively correlated with IL-6,IL-10,PCT,and CRP(P<0.05 for all);In the VD3 severe deficiency group,there were fewer corre-lation indicators and the correlation strength was not as strong as that in the VD3 deficiency group.Conclusion(1)Elderly patients with sepsis generally have lower levels of VD3,with lower levels associated with more severe illness and poorer prognosis;(2)In elderly sepsis patients,compared to patients with severe VD3 deficiency,patients with VD3 deficiency have lower levels of inflammation,stronger cellular immune response,and stronger correlation,suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Intraluminal thrombus(ILT)at the vertebral artery origin is rare and often missed due to atypical symptoms.However,it poses a high risk of artery-to-artery embolism and severe posterior circulation ischemia.This article reports a case of missed diagnosis of ILT to improve the diagnostic ability.The patient,a 49-year-old male was admitted to emergency department with sudden dizziness accompanied by nausea for 12 hours.Head CT suggested posterior circulation ischemia.Patient was given aspirin 0.2 g/d and atorvastatin 20 mg/d orally and discharged from the hospital.Head MRI in the outpatient department showed a recent infarct in the right cerebellar hemisphere next day.On the 28th,dizziness recurred,accompanied by unsteady walking and right-sided hemisensory numbness.The symptoms persisted and did not improve.He was admitted to the hospital on the 29th.Cervical CTA showed severe stenosis at the origin of the right vertebral artery,filling defect in the distal lumen combined with the Donut sign.Thus,ILT was diagnosed.The drug treatment regimen was adjusted to aspirin 100 mg/d combined with clopidogrel 75 mg/d for a total of 15 weeks.High-resolution MRI of the cervical blood vessels in the outpatient department showed occlusion of the V1-V2 segment of the right vertebral artery.On November 2,endovascular treatment was performed under local anesthesia.At 90 days and 6 months of follow-up after the operation,no recurrence of cerebral ischemia events occurred,and the mRS score was 0.This case highlights the need for vigilance toward ILT in posterior circulation ischemia when initial imaging is inconclusive.Early dynamic CTA(5-7 days)combined with dual antiplatelets may prevent thrombus progression and improve outcomes.

Objective:To investigate the anti-inflammatory action and mechanism of action of rosmarinic acid(RA),a Chi-nese monomeric herbal compound based on the NF-κB/NLRP3 pathway in a rat model of acute gouty arthritis(AGA).Methods:Forty healthy male SD rats were randomly assigned to five groups,and the model and drug administration groups were established a rat model of AGA by injecting a suspension of sodium urate crystals(MSU)into the joint cavity of the right paw of the rats.The degree of ankle joint swelling was measured using vernier calipers and stained with hematoxylin-eosin(HE).The inflammatory infiltration of the ankle joint and chondrocyte shedding was observed by staining with Safranine O-fast green(SOFG)and Mankin's score.The levels of IL-6,IL-1β and TNF-α in the right ankle joint of rats were determined by ELISA and the expression of NF-κB/NLRP3 pathway-associated proteins in the ankle joint were measured by Western blot.Results:Injection of MSU suspension into the ankle successfully induced AGA in rats.Compared with control group,the rats in model group showed significantly increased ankle swelling(P<0.01),greater in-flammatory infiltration,significant chondrocyte detachment,significantly increased secretion of IL-1β,IL-6 and TNF-α(P<0.01)and increased expressions of NF-κB/NLRP3 pathway-related proteins.Compared with model group,RA showed greater anti-inflamma-tory effects,dose-dependently inhibiting the development of ankle swelling in rats(P<0.01,P<0.001)and inhibited inflammatory cy-tokine infiltration.RA inhibited the secretion of inflammatory cytokines IL-6,IL-1β,TNF-α(P<0.01)and inhibited the expressions of proteins associated with the NF-κB/NLRP3 pathway(P<0.01).Conclusion:RA shows potent anti-inflammatory effects in a mouse model of AGA,and the mechanism is associated with regulation of the NF-κB/NLRP3 pathway.

Background and Aims:Laparoscopic pancreaticoduodenectomy(LPD)has become a preferred approach for periampullary tumors,yet delayed gastric emptying(DGE)remains a frequent complication that hampers postoperative recovery.The nasojejunal feeding tube(NJT)is commonly used for early enteral nutrition,but its impact on DGE is controversial.This study aimed to evaluate whether intraoperative NJT placement increases the risk of DGE after LPD and to assess its influence on postoperative recovery outcomes.Methods:A retrospective cohort of 319 patients who underwent LPD at Provincial Hospital Affiliated to Shandong First Medical University from April 2017 to November 2023 was analyzed.Patients were divided into two groups based on intraoperative NJT placement(NJT group,n=200;non-NJT group,n=119).The incidence of DGE and postoperative outcomes were compared.Multivariate logistic regression and propensity score matching(PSM)were performed to identify independent risk factors for DGE.Results:The incidence of grade B/C DGE was significantly higher in the NJT group than in the non-NJT group(36.5%vs.21.8%,P=0.006).NJT placement was associated with longer postoperative hospital stay and higher hospitalization costs(both P<0.05).Multivariate analysis revealed intraoperative NJT placement(OR=1.960,95%CI=1.142-3.363,P=0.015)and intraoperative blood loss>400 mL(OR=1.921,95%CI=1.155-3.194,P=0.012)as independent risk factors for DGE.These findings were consistent after PSM.Conclusions:Prophylactic intraoperative NJT placement confers no additional benefit for postoperative recovery after LPD and is associated with a higher risk of DGE,prolonged hospitalization,and increased medical costs.Routine NJT placement should therefore be avoided,and individualized strategies should be adopted to minimize postoperative complications and enhance recovery.

Background and Aims:Laparoscopic pancreaticoduodenectomy(LPD)has become a preferred approach for periampullary tumors,yet delayed gastric emptying(DGE)remains a frequent complication that hampers postoperative recovery.The nasojejunal feeding tube(NJT)is commonly used for early enteral nutrition,but its impact on DGE is controversial.This study aimed to evaluate whether intraoperative NJT placement increases the risk of DGE after LPD and to assess its influence on postoperative recovery outcomes.Methods:A retrospective cohort of 319 patients who underwent LPD at Provincial Hospital Affiliated to Shandong First Medical University from April 2017 to November 2023 was analyzed.Patients were divided into two groups based on intraoperative NJT placement(NJT group,n=200;non-NJT group,n=119).The incidence of DGE and postoperative outcomes were compared.Multivariate logistic regression and propensity score matching(PSM)were performed to identify independent risk factors for DGE.Results:The incidence of grade B/C DGE was significantly higher in the NJT group than in the non-NJT group(36.5%vs.21.8%,P=0.006).NJT placement was associated with longer postoperative hospital stay and higher hospitalization costs(both P<0.05).Multivariate analysis revealed intraoperative NJT placement(OR=1.960,95%CI=1.142-3.363,P=0.015)and intraoperative blood loss>400 mL(OR=1.921,95%CI=1.155-3.194,P=0.012)as independent risk factors for DGE.These findings were consistent after PSM.Conclusions:Prophylactic intraoperative NJT placement confers no additional benefit for postoperative recovery after LPD and is associated with a higher risk of DGE,prolonged hospitalization,and increased medical costs.Routine NJT placement should therefore be avoided,and individualized strategies should be adopted to minimize postoperative complications and enhance recovery.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.