ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

Objective To develop a prognostic risk model for anoikis-related genes(ANRs)in bladder cancer,calculate risk scores,and analyze the relationship between bladder cancer patients with high and low risk scores and the tumor microenvironment.Methods Prognosis-related ANRs and clinically independent risk factors were screened by public database information and Cox regression analysis.Prognostic risk modeling was performed by least absolute shrinkage and selection operator(LASSO)analysis and column-line diagrams.Prognostic risk model accuracy was validated by kaplan-meier survival analysis and area under receiver operating characteristic curve(ROC)curve(AUC).The relationship between risk score and tumor microenvironment was explored by CIBERSORT(https://cibersortx.stanford.edu/)and single sample gene set enrichment analysis(ssGSEA).Results The prognostically relevant ANRs were B-lymphoblastoma-2-associated promoter(BAD),cell cycle protein-dependent kinase inhibitor 3(CDKN3),and proliferating cell nuclear antigen(PCNA),and the clinically independent risk factors were gender,age,clinical stage(T,N),and risk score.The prognostic risk model was expressed as risk score=(0.155 2 × BAD expression)+(0.2286 × CDKN3 expression)+(0.0114×PCNA expression)and column line graph.The lower the risk score the better the prognosis of bladder cancer patients,the AUC of the survival curves for 1,3 and 5 years were 0.732,0.620 and 0.541,respectively,and the column line graphs of the 1-,3-and 5-year calibration curves almost corresponded diagonally,reflecting the accuracy of the model.The high and low risk groups of the prognostic risk model showed great differences in immune cell infiltration in the tumor microenvironment of bladder cancer.Conclusion The established prognostic risk model for bladder cancer loss of apoptosis-related genes is highly accurate and can better assess the prognosis of bladder cancer patients,and bladder cancer patients with high and low risk scores are closely related to the tumor microenvironment.

Objective:To investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 435 men of childbearing age and 87 men of infertile age.The patients were divided into the varicocele group(n=116)and non-varicocele group(n=406)according to clinical diagnosis.The differences of seminal plasma nORP,DFI,sperm high DNA stain ability(HDS)and semen parameters were analyzed between the two groups.The relationship among general clinical data,seminal plasma nORP,semen parameters,DFI and HDS in patients with varicocele were further analyzed.According to the severity of varico-cele,the patients were divided into three groups,including mild,moderate and severe.And the differences of seminal plasma nORP and semen parameters,DFI and HDS among all groups were analyzed.The differences of seminal plasma nORP,semen parameters,DFI and HDS were compared between the varicocele and non-varicocele groups.Results:The total sperm count,sperm concentra-tion,progressive motility sperm percentage(PR％)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P＜0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly higher than those in control group(P＜0.05).Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm,sperm concentration and NSMR(P＜0.05),and significantly positively correlated with DFI and HDS(P＜0.05).There were significant differences in nORP,total sperm count,sperm concentration,PR％,DFI and HDS among mild,moderate and severe varicocele groups(P＜0.05).Seminal plasma nORP,sperm concentration,PR％and DFI in severe group were significantly lower than those in mild and moderate groups(P＜0.05).Sperm count and HDS in severe group were significantly lower than those in mild group(P＜0.05).In infertile patients,seminal plasma nORP,DFI and HDS in varicocele group were significantly higher than those in control group(P＜0.05).And PR％in varicocele group was significantly lower than that in control group(P＜0.05).Conclusions:Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.

Objective To evaluate the effects of low-dose intrathecal morphine(ITM)combined with liposomal bupivacaine adductor canal block(LB-ACB)on postoperative analgesia and opioid-sparing efficacy in patients undergoing total knee arthroplasty(TKA).Methods In this randomized,double-blind,controlled trial,80 TKA patients were allocated to either an intervention group(ITM 0.1 mg+LB-ACB,n=40)or a control group(intrathecal saline+LB-ACB,n=40).Primary outcomes included resting/movement visual analog scale(VAS)scores at 6,12,24,48,and 72 hours postoperatively,48-hour morphine consumption,time to first rescue analgesia,and incidence of complications.Results(1)The intervention group showed significantly lower resting and movement VAS scores at 6,12,24,and 48 hours postoperatively compared with controls(all P<0.05),except at 72 hours(P>0.05).(2)The intervention group had a significant reduction in 48-hour morphine consumption(4.58±1.0 mg vs.9.34±4.8 mg,P=0.027),a significantly lower rescue analgesia rate(15.0%vs.47.5%,P=0.002),and a significantly prolonged time to first rescue analgesia(48.8±7.5 h vs.14.5±5.5 h,P<0.001).(3)The intervention group demonstrated a significant decrease in the incidence of nausea(from 15.0%to 35.0%,P=0.039)and vomiting(from 10.0%to 27.5%,P=0.045),but no significant differences were observed in the incidences of pruritus,urinary retention,or motor block(all P>0.05).Conclusion Low-dose ITM(0.1 mg)combined with LB-ACB significantly enhances early postoperative analgesia,reduces opioid consumption,and decreases nausea/vomiting risk,without increasing the risks of other complications.This regimen aligns with enhanced recovery after surgery(ERAS)principles.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.