OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective:To evaluate the association between body temperature and duration of mechanical ventilation in the intensive care unit (ICU) among patients after coronary artery bypass grafting (CABG).Methods:Clinical data from patients, aged >18 yr, undergoing primary isolated CABG, between 2008 and 2019, were extracted from the Medical Information Mart for Intensive Care Ⅳ version 2.0 database. Participants were stratified into 3 groups based on the mean body temperature in ICU: hypothermia group (<36.0 ℃), normothermia group (36.0 ℃ ≤ temperature <37.3 ℃), and hyperthermia group (≥37.3 ℃). Multivariable linear regression and linear curve fitting were performed to assess the association between body temperature and duration of mechanical ventilation.Results:A total of 4, 588 patients were finally included in the statistical analysis, including 133 cases in hypothermia group, 4, 177 cases in normothermia group and 278 cases in hyperthermia group. The duration of mechanical ventilation was significantly prolonged in both hypothermia and hyperthermia groups compared with normothermia group ( P<0.05). The results of multivariable linear regression demonstrated that each 1 ℃ increase in body temperature was associated with a 2.43 h reduction in the duration of mechanical ventilation in hypothermia group ( P<0.001), and each 1 ℃ temperature elevation corresponded to a non-significant reduction of 0.12 h in hyperthermia group ( P=0.851). The results of linear curve fitting revealed a U-shaped relationship between body temperature and duration of mechanical ventilation, and an inflection point was identified at 36.71 ℃, with duration of mechanical ventilation prolonged with temperatures either below or above this threshold ( P<0.05). Conclusions:Hypothermia during ICU stay following CABG may lead to prolonged mechanical ventilation in patients.

Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective: : The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). Methods: : A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. Results: : The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. Conclusion : High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Objective To investigate the mechanism of E26 transformation-specific sequence 4(ETV4)affecting the proliferation and migration of colon cancer cells through the nuclear factor-κB(NF-κB)signaling pathway.Methods The expression level of ETV4 in normal colon tissues and cancer tissues was analyzed by the user-friendly interactive cancer transcriptome data analysis resource(UALCAN)database.Reverse transcription quantitative polymerase chain reaction(qRT-PCR)and Western blot were used to detect the expression level of ETV4 in normal intestinal epithelial cells and colon cancer cell lines.After silencing ETV4 in SW480 cells,qRT-PCR and Western blot were per-formed to detect the expression of ETV4 to assess transfection efficiency;colony formation and Tran-swell assays were conducted to explore the effects of ETV4 silencing on the proliferation and migration of colon cancer cells;the Western blot was used to detect the effects of ETV4 silencing on the protein expression of protein 65(p65)and phosphorylated protein 65(p-p65)in the NF-κB pathway.Results The UALCAN database analysis revealed high expression of ETV4 in colon cancer tissues.The qRT-PCR and Western blot showed that ETV4 expression was significantly higher in the colon cancer cell lines SW480,Lovo,Caco-2,and SW620 than in normal intestinal epithelial cells HIEC-6,with the highest expression in SW480 cells(P＜0.001).Colony formation and Transwell assay results indicated that silencing ETV4 significantly inhibited the proliferation and migration of colon cancer SW480 cells(P＜0.001).Western blot results showed that silencing ETV4 significantly inhibited the expression of p-p65 protein in the cells(P＜0.001).Conclusion Silencing ETV4 may inhibit the activation of the NF-κB signaling pathway,thereby inhibiting the proliferation and migration of colon cancer cells.

OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure （RHF） based on the Hippo/Yes-associated protein （YAP） signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group， low-dose group of Wenyang lishui formula （4.25 g/kg）， high-dose group of the Wenyang lishui formula （17.00 g/kg）， furosemide group （20 mg/kg）， and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group （17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60）， with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection， once a day， for 4 consecutive weeks. During the experiment， the general conditions of the rats in each group were observed； after the last administration， the right ventricular diameter， right atrial diameter， end-diastolic volume， pulmonary artery blood flow acceleration time （PAAT） and its ratio to ejection time （ET） （PAAT/ET）， pulmonary artery pressure and its ratio to pulmonary arterial flow velocity （pulmonary artery pressure/velocity） were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ （Ang Ⅱ） were detected. The pathological changes of the right ventricular tissue were observed， and the collagen volume fraction， the phosphorylation levels of the large tumor suppressor 1/2 （LATS1/2） and YAP， and the protein expression of the transcriptional coactivator of PDZ-binding motif （TAZ） were also detected. RESULTS Compared with the RHF group， the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color， movement， diet， and mental state. The atrophy of right ventricular myocardial cells， the increase of inflammatory cells， collagen deposition， and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter， right atrial internal diameter， end-diastolic volume， pulmonary artery pressure， pulmonary artery pressure/velocity， the plasma levels of brain natriuretic peptide and AngⅡ ， collagen volume fraction， the phosphorylation level of YAP and protein expression of TAZ were significantly decreased， while the PAAT， PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased （P＜0.05）. PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators （P＜ 0.05）. CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats， reduce their pulmonary artery pressure， alleviate the pathological changes in their cardiac tissues， and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation.

Objective To investigate the differences in clinical characteristics,surgical outcomes,and prognosis between sporadic intracranial hemangioblastoma(IC-HB)and von Hippel-Lindau(VHL)syndrome-associated IC-HB.Methods A retrospective consecutive series of patients who underwent microsurgical resection at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,between April 2014 and January 2024,with postoperative pathological confirmation of IC-HB,was included.Clinical and imaging data were collected,including demographics(sex,age),preoperative clinical manifestations(asymptomatic,headache,dizziness,vertigo or imbalance,blurred vision or papilledema,nausea or vomiting,other symptoms),number of symptoms,lesion type(solid or solid-cystic),lesion size(volume,longest diameter,anteroposterior diameter,superoinferior diameter,transverse diameter),lesion location(cerebellar region:hemisphere,vermis;brainstem region:medulla oblongata,fourth ventricle;skull base region:cerebellopontine angle,jugular foramen,petroclival region),Karnofsky performance status(KPS)score(preoperative,postoperative;KPS score＞70 and 70),surgical information,and follow-up data.Based on past medical history,family history,and VHL gene test results,patients were classified into sporadic IC-HB and VHL syndrome-associated IC-HB groups.Differences in clinical characteristics,surgical outcomes,and follow-up status were compared between the groups.Improved outcomes were defined as increases in KPS scores over 0 at 6-month follow-ups in comparison with preoperative KPS,while non-improved outcomes were defined by unchanged or decreased(＞0 point)KPS scores.Survival outcomes,including postoperative recurrence(newly occurring abnormally enhancing nodules at the surgical site or periphery with continuous development during follow-ups.Recurrence could be verified through the combination of imaging enhancement features,clinical manifestations and post-operative pathological examinations),postoperative KPS improvement,and death of any cause during follow-up.The outcomes of postoperative KPS improvement versus non-improvement(unchanged or worsened)were analyzed through univariate analysis with the Firth penalized maximum likelihood Logistic regression model.Variables meeting the criteria(P＜0.05 in univariate analysis,clinical importance,statistical model feasibility)were included in a multivariate Logistic regression model to identify independent factors influencing functional outcomes.Survival outcomes were analyzed using Cox proportional hazards regression models.Kaplan-Meier survival analysis was used to assess recurrence-free survival rates between groups with the Log-rank test.Furthermore,univariate and multivariate Logistic regression analyses were performed separately for the sporadic IC-HB and VHL syndrome-associated IC-HB subgroups to explore independent factors for postoperative KPS improvement.Results A total of 82 IC-HB patients(41 male,41 female),aged 11-73 years(mean[42±15]years),were included.Among which,68 had sporadic IC-HB and 14 had VHL syndrome-associated IC-HB.39 patients had improved postoperative KPS and 43 patients showed no improvements in KPS scores.(1)For clinical characteristics,the age of onset was younger in the VHL syndrome-associated IC-HB group([35±14]years vs.[44±15]years,P=0.044).Lesions in VHL syndrome-associated IC-HB patients were more likely to involve the brainstem and adjacent critical structures(8/14 of which involved medulla oblongata),while sporadic IC-HB was more common in the cerebellar hemispheres(70.6％[48/68]).The distribution of lesion location across cerebellar,skull base,and brainstem regions differed significantly between groups(P=0.015),while other characteristics showed no significant differences(all P＞0.05).(2)For treatment and follow-ups,all patients underwent gross total microsurgical resection.Preoperative angiography via femoral artery was performed in 22 patients,with partial preoperative embolization in 4 patients.Postoperatively,KPS improved in 39 patients,remained unchanged in 33 patients,and worsened in 10 patients.The change in KPS scores pre-to post-operatively did not differ significantly between groups(P=0.707).The recurrence rate was higher in the VHL syndrome-associated IC-HB group(4/14 vs.5.9％[4/68],P=0.026),but there was no significant difference in mortality(P=0.999).(3)For analysis of factors influencing postoperative KPS improvement,univariate Logistic regression showed preoperative asymptomatic(OR,0.05,95％CI0.00-0.39,P=0.002),preoperative dizziness(OR,2.62,95％CI 1.09-6.47,P=0.031),vertigo/imbalance(OR,3.60,95％CI 1.04-15.45,P=0.043),nausea/vomiting(OR,4.49,95％CI 1.65-13.53,P=0.003),preoperative symptoms(OR,2.27,95％CI 1.46-3.86,P＜0.01)and preoperative KPS ≤70(OR,7.65,95％CI 1.60-74.47,P=0.009)were strongly associated with KPS improvement.Multivariate Logistic regression only identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,2.44,95％CI 1.04-6.32,P=0.049).(4)For survival outcome analysis,no significant differences in the risk of postoperative recurrence,KPS improvement,or death were observed between the VHL syndrome-associated and sporadic IC-HB patients(recurrence:HR,4.88,95％CI 0.97-24.69,P=0.055;KPS improvement:HR,0.60,95％CI 0.25-1.43,P=0.246;mortality:P=0.999).Kaplan-Meier curves showed no statistically significant difference in recurrence-free survival rate between groups(P=0.053).(5)In the subgroup analysis,in sporadic IC-HB patients,multivariate Logistic regression identified the number of preoperative symptoms as an independent predictor of postoperative KPS improvement(OR,1.97,95％CI 1.14-3.68,P=0.021).Due to the small sample size,reliable parameter estimation was not possible for the VHL syndrome-associated IC-HB subgroup due to the small sample size.Conclusions VHL syndrome-associated IC-HB patients have a higher risk of recurrence in comparison with sporadic IC-HB patients.The number of preoperative symptoms can guide survival ending assessment.