Renal ischemia-reperfusion injury （RIRI） is a major cause of acute kidney injury during kidney transplantation and peri-operative settings， and there is still a lack of safe and effective targeted preventive and therapeutic drugs in clinical practice. Specifically， xanthohumol， luteolin， dracorhodin C， naringin， senkyunolide Ⅰ， verbascoside， and shikonin enhance antioxidant defenses， and inhibit lipid peroxidation and ferroptosis via the nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 pathway. Apigenin， nobiletin， tanshinone Ⅱ A ， and salidroside activate the phosphatidylinositol 3-kinase/protein kinase B pathway to inhibit mitochondria- dependent apoptosis and facilitate renal repair. Quercetin， methyleugenol， cyanidin-3-glucoside， and platycodin D promote autophagy and improve mitochondrial homeostasis through the adenosine monophosphate-activated protein kinase（AMPK）/mTOR or AMPK/phosphatase and tensin homolog-induced kinase 1/Parkin pathways. In addition， hesperidin， curcumin， ganoderic acid， pulsatilla saponin B4， capsaicin， and diosgenin mitigate inflammatory responses and decrease renal tubular injury markers by inhibiting the Toll-like receptor 4/nuclear factor κB， high mobility group box 1， Janus kinase/signal transducer and activator of transcription pathways， thereby exerting multi-target， multi-stage renoprotective effects.

Objective To compare and analyze the changes in the use of lung cancer therapeutic drugs before and after the national initiation of health insurance negotiations, and to study the impact of a series of policies on the use of lung cancer drugs. Methods Descriptive statistical methods were used analyze the basic situation of lung cancer patients and the changes of corresponding therapeutic drugs in Peking University People's Hospital from 2014 to 2020, as well as to the hospital procurement data of lung cancer therapeutic drugs in the database of the Chinese Medicine Economic Information. Results From 2014 to 2020, the total cost per capita of lung cancer patients showed a trend of first increasing and then decreasing, increasing before the national drug negotiation and gradually decreasing after the negotiation. After 2017, the use of small ATC categories such as VEGF/VEGFR inhibitors and EGFR tyrosine kinase inhibitors increased significantly, along with a rise in the number of monoclonal antibody varieties. The DDDs of osimertinib, anlotinib, alectinib, crizotinib and other drugs in the medical insurance list increased significantly, and the average daily cost decreased significantly. Conclusion The number of hospitalization days for lung cancer patients had continued to shorten in recent years, and the structure of drug use had changed significantly. The adjustment of the medical insurance catalog had led to more innovative lung cancer drugs showing the trend of volume up and price down.

Objective To investigate the predictive value of serum vasoactive intestinal peptide(VIP)and 5-hydroxytryptamine(5-HT)levels on the outcome of spinal cord electrical stimulation(SCS)in patients with postherpetic neuralgia(PHN).Methods A total of 96 PHN patients who received SCS treatment in Ziy-ang Central Hospital from January 2022 to December 2023 were selected.According to the disease outcomes of all PHN patients after 6 months of treatment,a good group(n=71)and a poor group(n=25)were set up.The clinical data of the two groups were collected and the serum VIP and 5-HT levels were detected in all pa-tients before treatment.The predictive value of serum VIP and 5-HT on disease outcome after SCS treatment in PHN patients was evaluated by receiver operating characteristic(ROC)curve,and the influencing factors of disease outcome after SCS treatment in PHN patients was explored by multivariate Logistic steppe gression a-nalysis.Results The levels of serum VIP and 5-HT in poor group were higher than those in good group(P＜0.05).The area under the curve(AUC)of serum VIP and 5-HT for predicting the disease outcome of PHN patients after SCS treatment were 0.829(95％CI:0.779-0.874)and 0.743(95％CI:0.693-0.793),respec-tively,and the AUC of combined prediction was 0.941(0.891-0.986).There were no significant differences in age,gender,body moss index,education,location of onset,hypertension and drinking history between the two groups(P＞0.05).The time of initial hospital admission in the poor group was longer than that in the good group,skin rash area in the poor group was larger than that in the good group,and diabetes mellitus and smoking history in the poor group were higher than those in the good group(P＜0.05).The time of admis-sion for initial treatment＞3 d(OR=2.188,95％CI:1.383-3.461),skin rash area＞10 cm2(OR=2.018,95％CI:1.283-3.173),diabetes mellitus(OR=2.264,95％CI:1.379-3.717),serum VIP level ≥41.78 ng/L(OR=3.022,95％CI:1.685-5.420),serum 5-HT level ≥99.27 ng/mL(OR=3.579,95％CI:1.885-6.793)were the influencing factors of disease outcome after SCS treatment in PHN patients(P＜0.05).Con-clusion The elevated levels of serum VIP and 5-HT before treatment are associated with poor outcomes after SCS in patients with PHN,and could be used as potential markers to predict the outcomes of SCS in patients with PHN.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe(BOC2)on the expression of six types of mitochondrial N-formyl peptides(NFPs)in blood and two formyl peptide receptors(FPRs)in pancreatic tissue of rats with severe acute pancreatitis(SAP),and to explore its mechanism of alleviating inflammatory damage of SAP.Methods Forty male SD rats were randomly divided into four groups:the sham group,the SAP model group,the BOC2 low-dose and the BOC2 high-dose group(0.1 and 0.2 mg/kg),with 10 animals in each group.The SAP model was prepared by retrograde injection of 5%sodium taurocholate(50 mg/kg)into biliary and pancreatic ducts in the last 3 groups.BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling,and samples were taken 4 hours after modeling.HE staining was used to observe pathological changes in pancreas.Western blot assay was used to detect the expression of NFPs in plasma.IHC staining was used to detect the expression of FPRs in pancreatic tissue.ELISA was used to detect interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α levels in plasma.qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue.Results Compared with the model group,the BOC2 high-dose group and the BOC2 low-dose group showed improvement in pathological phenomena,such as pancreatic bleeding,acinar cell necrosis,inflammatory cell infiltration and edema.The pancreatic injury score,pancreatic FPRs expression,plasma MT-ND1,MT-ND2,MT-ND3,MT-ND5,MT-ND6 expression,as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue,were significantly reduced(P＜0.05).Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway.

Objective To screen and analyze the differentially expressed genes(DEGs)in basal cell carcinoma(BCC)of the eyelid using RNA sequencing technology.Methods Six patients who underwent extended resection and primary eyelid reconstruction for BCC of the eyelid in Hebei Eye Hospital from July to November 2021 were selected.Part of the excised cancer tissues and the adjacent normal tissues trimmed during the repair of the defect were sampled for the study.The library construction for sequencing was performed using RNA sequencing technology.The threshold for DEGs was set using the DESeq2 software:P＜0.05 and|log2(foldchange)|＞1,to identify DEGs.Gene Ontology(GO)and Kyo-to Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the clusterProfiler software,and the biological significance of these DEGs was further analyzed.Results DESeq2 software was used to analyze the differential expression between cancer tissues and adjacent tissues,and 1 317 DEGs were screened out.In the cancer tis-sues of the 6 patients,906 DEGs were up-regulated,and 411 DEGs were down-regulated.GO enrichment analysis showed that the top 30 up-regulated DEGs were mainly concentrated in humoral immune response,immunoglobulin complex,B cell receptor signaling pathway,extracellular matrix,antigen binding,and receptor modulator activity,and the top 10 down-regulated genes were mainly related to epidermal development in biological process,cell composition,and molecular func-tion.KEGG pathway analysis revealed that DEGs were mainly enriched in the melanogenesis signaling pathway,WNT sig-naling pathway,and immune-related signaling pathway,and there were 8 related gene pathways.According to the signifi-cance of gene up-regulation,the core genes identified finally were FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2.Conclusion The occurrence of BCC is closely related to the interaction and synergy of various pathways.Among the highly expressed genes,the up-regulation of FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2 expression in the tissues of patients with BCC of the eyelid is the most significant,which is closely related to the occurrence and development of BCC of the eyelid.

Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.