Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

The aging trend is intensifying currently,but there is still a lack of standardized diagnosis and treat-ment schemes for severe infections in elderly people.This paper focuses on the recommendations for immune-related clinical diagnosis and treatment routes as well as the idea of risk stratified diagnosis and treatment for elderly peo-ple,aiming to effectively prevent infectious diseases in elderly people and perform stratified management through systematic and scientific means of immune function monitoring and regulation,so as to enhance the standardized level of diagnosis and treatment as well as clinical treatment effect of infection in elderly people.

Objective To explore the value of oral contrast-enhanced ultrasonography (OCEUS) combined with contrast-enhanced CT in predicting preoperative T staging in patients with gastric cancer. Methods A retrospective analysis was conducted on 80 patients with gastric cancer confirmed via endoscopic biopsy or postoperative pathology at the First People’s Hospital of Jining from January 2021 to November 2024. The cohort included 56 males and 24 females, aged 38-79 years, with a median age of 55.9 years. All patients underwent both OCEUS and contrast-enhanced CT within one week prior to surgery. T staging of gastric cancer was determined using OCEUS, contrast-enhanced CT, or their combination. The results were compared with pathological T staging, and statistical differences in accuracy were analyzed. Results Pathological T staging identified T1 in 9 cases, T2 in 16 cases, T3 in 42 cases, and T4 in 13 cases. OCEUS indicated T1 in 6 cases, T2 in 14 cases, T3 in 50 cases, and T4 in 10 cases, with an accuracy rate of 80.0%. Contrast-enhanced CT indicated T1 in 4 cases, T2 in 12 cases, T3 in 52 cases, and T4 in 12 cases, with an accuracy rate of 75.0%. The combination of OCEUS and contrast-enhanced CT indicated T1 in 6 cases, T2 in 15 cases, T3 in 47 cases, and T4 in 12 cases, with an accuracy rate of 87.5%. The combined approach demonstrated significantly higher accuracy in preoperative T staging compared to either method alone (P < 0.05). Conclusion The combination of OCEUS and contrast-enhanced CT improves the accuracy of preoperative T staging in gastric cancer patients, providing valuable support for their diagnosis and treatment.

Objective To investigate whether vertebrobasilar dolichoectasia(VBD)and three vascular endothelial injury factors correlate with white matter hyperintensity(WMH)and lacunar infarction(LI)in patients with cerebral small vessel disease(CSVD).Methods Patients with CSVD hospitalized at the Brain Disease Center of the First Affiliated Hospital of Henan University of Chinese Medicine from March 2023 to March 2024 were prospectively and consecutively included in this study.Baseline clinical data,including gender,age,body mass index,hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,hyperlipidemia,hyperhomocysteinemia,hyperuricemia,carotid plaque,history of previous stroke,smoking,alcohol consumption,and other vascular risk factors.The patients were categorized into CSVD with VBD group and CSVD without VBD group.Imaging assessments were performed within 24 h of enrollment,including evaluating the WMH severity using Fazekas scale score(mild WMH:1-2,moderate WMH:3-4,severe WMH:5-6),imaging characteristics of LI and vertebrobasilar artery parameters on three dimensional time of flight magnetic resonance angiography images(including bilateral vertebral artery diameters,basilar artery diameters,standard basilar artery length[BAL],and bending length of the basilar artery).A basilar artery diameter ≥4.5 mm or vertebral artery diameter ≥4.0 mm was defined as dilatation.BAL ≥29.5 mm was defined as elongation,and a basilar artery bending length ≥ 10.0 mm was defined as curvature.Patients meeting at least one of these criteria(dilatation,elongation,and curvature)were included in the CSVD with VBD group.Levels of interleukin-6(IL-6),soluble intercellular adhesion molecule-1(sICAM-1),and von Willebrand factor(vWF)levels were measured on the second day of enrollment.To analyze the influencing factors of VBD in CSVD patients and examine the correlation between vertebrobasilar artery imaging parameters,the levels of three vascular endothelial injury factors(IL-6,sICAM-1,vWF),and the severities of WMH and LI in patients with CSVD.Results A total of 88 patients with CSVD,aged 40-80 years,with a mean age of(64±10)years,were included in this study,with 50patients in the CSVD with VBD group and 38patients in the CSVD without VBD group.(1)Univariate analysis showed no statistically significant differences in clinical baseline data or the three endothelial injury factor levels between the two groups(all P＞0.05).After adjusting for age and gender,variables with P＜0.1 in the univariate analysis(male,smoking history)were further examined using multivariate Logistic regression analysis,which showed that neither male gender(OR,2.656,95％CI 0.647-10.907,P=0.175)nor smoking history(OR,0.992,95％CI 0.255-3.866,P=0.991)significantly increased the risk of VBD in CSVD patients.(2)There were no statistically significant differences in bilateral vertebral artery diameters or BAL among different severity of WMH or between patients with or without LI(all P＞0.05).The basilar artery bending length was significantly smaller in patients with mild and moderate WMH CSVD than those with severe WMH CSVD(2.49[1.60,4.58]mm,5.24[2.28,6.02]mm,6.99[5.19,8.93]mm,respectively;both P＜0.05).(3)Univariate analysis showed that IL-6,sICAM-1,and vWF levels were significantly higher in patients with moderate and severe WMH CSVD compared to patients with mild WMH CSVD(all P＜0.05).IL-6 and sICAM-1 levels were significantly higher in patients with severe WMH CSVD compared to patients with moderate WMH CSVD(both P＜0.05).The levels of IL-6,sICAM-1,and vWF were significantly higher in CSVD patients with LI than those in CSVD patients without LI(all P＜0.05).(4)After adjusting for confounders such as gender,age,and smoking history,the multifactorial Logistic ordered regression analysis,using patients with mild WMH CSVD as the reference indicated that high IL-6(OR,2.358,95％CI 1.268-4.387,P=0.007),sICAM-1(OR,2.077,95％CI 1.430-3.016,P＜0.01),and vWF(OR,1.437,95％CI 1.058-1.951,P=0.020)levels were significant risk factors for the occurrence of moderate WMH in patients with CSVD,as well as significant risk factors for severe WMH in patients with CSVD(IL-6[OR,5.340,95％CI 2.555-11.163,P＜0.01],sICAM-1[OR,16.004,95％CI3.692-69.379,P＜0.01],and vWF[OR,1.748,95％CI 1.267-2.412,P=0.001]);a long basilar artery bending length was an risk factor for the development of moderate(OR,1.287,95％CI 1.032-1.603,P=0.025)and severe(OR,1.639,95％CI 1.280-2.099,P＜0.01)WMH in CSVD patients.(5)After adjusting for confounding factors such as gender,age,and smoking history,multifactorial Logistic ordered regression analysis identified that high IL-6(OR,1.536,95％CI 1.074-2.198,P=0.019),sICAM-1(OR,2.066,95％CI 1.465-2.913,P＜0.01),vWF(OR,1.423,95％CI 1.078-1.879,P=0.013)levels are significant influential factors for the development of LI in CSVD patients.Conclusions Longer basilar artery bending length was associated with more severe WMH in patients with CSVD.Elevated levels of IL-6,sICAM-1,and vWF were associated with development of LI and more severe WMH in patients with CSVD.

Objective To explore the correlations of multimodal ultrasound manifestations of Hashimoto thyroiditis(HT)with normal thyroid function and serum thyroid peroxidase antibody(TPOAb)titer.Methods Data of gray-scale ultrasound,CDFI and shear wave elastography(SWE)of 100 HT patients with normal thyroid function were retrospectively analyzed.According to gray-scale ultrasound manifestations,HT was classified into focal type(type A),nodular-like type(type B),diffuse hypoechoic type(type C)and diffuse hyperechoic type(type D).Meanwhile,based on blood flow distribution shown on CDFI,HT was classified into abundant type,increased type,normal type and sparse type.Correlations of the mean Young's modulus(Emean)of thyroid gland and CDFI classification of HT with serum TPOAb titer were analyzed.Results For all 100 cases,serum TPOAb titer was(270.31±72.63)IU/ml.There were 38 cases of type A,26 cases of type B,20 cases of type C and 16 cases of type D based on gray-scale ultrasound,and 15 cases of abundant type,9 cases of increased type,69 cases of normal type and 7 cases of sparse type based on CDFI,respectively.The Emean of thyroid in all 100 cases was(22.31±7.38)kPa.Significant differences of serum TPOAb titer and thyroid Emean were found among different gray-scale ultrasound HT types(all P＜0.05).Thyroid Emean values of all 100 patients were positively correlated with TPOAb titer(rs=0.702,P=0.037).The thyroid Emean of patients with type A,B,C and D HT were positively correlated with TPOAb titer(rs=0.752,0.823,0.853,0.497,all P＜0.05),while the CDFI types of HT were negative correlated with serum TPOAb titer(rs=-0.746,P=0.035).Conclusion Both thyroid Emean and blood flow signals in HT patients with normal thyroid function were correlated with serum TPOAb titer.

Objective To explore the clinical efficacy of wrist arthroscopy assisted closed reduction with external fixation in the treatment of intra-articular comminuted fractures of the distal radius(type C3).Methods A retrospective analysis was conducted on 98 patients with type C3 intra-articular comminuted fractures of the distal radius admitted to our hospital from March 2022 to February 2023.Among them,48 patients underwent wrist arthroscopy assisted closed reduction with external fixation with a bracket(arthroscopy group),and another 50 patients underwent open reduction with steel plate internal fixation surgery(control group).The two groups were compared in terms of operation time,intraoperative bleeding volume,incision length,fracture union time,range of motion(ROM)of joint,Visual Analogue Scale(VAS),and Gartland-Werley wrist scores,as well as radiographic parameters(palmar tilt,ulnar inclination,and radial height)evaluated at various follow-up intervals.Results The arthroscopy group had an operation time of(55.3±10.5)min,which was significantly shorter than that in the control group[(83.4±14.6)min;t=-10.979,P=0.000].The intraoperative bleeding volume in the arthroscopy group was(42.3±8.6)ml,which was less than that in the control group[(71.4±10.5)ml;t=-14.953,P=0.000].The incision length of the arthroscopy group was(1.3±0.3)cm,which was shorter than that of the control group[(5.1±1.5)cm;t=-18.550,P=0.000].The arthroscopy group had a fracture healing time of(10.7±1.4)weeks,which was shorter than that in the control group[(12.2±1.6)weeks;t=-4.855,P=0.000].The palmar flexion ROM in the arthroscopy group was 68.8°±8.3°,which was significantly higher than that in the control group(61.5°±9.4°;t=4.002,P=0.000).The dorsiflexion ROM in the arthroscopy group was 63.9°±7.5°,which was significantly higher than that in the comtrol group(59.2°±8.3°;t=2.931,P=0.004).The pronation ROM in the arthroscopy group was 67.4°±10.3°,which was significantly higher than that in the control group(62.1°±9.9°;t=2.604,P=0.011).The supination ROM in the arthroscopy group was 70.5°±7.4°,which was significantly higher than that in the control group(64.4°±8.6°;t=3.777,P=0.000).The VAS score of the arthroscopy group was(1.3±0.6)points,which was significantly lower than that in the control group[(1.7±0.5)points;t=-3.941,P=0.000].After 6 months,the Gartland-Werley wrist scores of the arthroscopy group was significantly higher than that of the control group(Z=-2.614,P=0.009).The wrist joint imaging showed significantly higher radial height,palmar inclination angle,and ulnar deviation angle in the arthroscopy group than the control group(all P=0.000),while there were no significant differences in palmar inclination angle and ulnar deviation angle at different time points within each group(P＞0.05).Except for significant differences in radial height at 3 d,1 month,and 6 months after surgery(P=0.015,P=0.035),there were no significant differences between any other time points(P＞0.05).The interaction between time and group was not significant for palm inclination angle,ulnar deviation angle,and radial height(P＞0.05).Conclusion Wrist arthroscopy assisted closed reduction with external fixation for intra-articular comminuted fractures of distal radius has advantages of short operation time,less intraoperative blood loss,and good recovery of wrist joint functions.

Objective To explore the effects of long non-coding RNA LINC01772 on cell cycle,apoptosis and radiotherapy sensitivity of A549.Methods A549 cells were resuscitated and cultured for experimental pur-pose.The effects of LINC01772 knockdown on cell viability,cell cycle progression,and apoptosis were assessed using CCK-8 assays and flow cytometry,and apoptosis-related proteins were analyzed using western blotting.CCK-8 and clonogenic assays were used to measure the changes in the sensitivity of A549 cells to radiotherapy following various radiation doses,and flow cytometry to examine alterations in the cell cycle and apoptosis post-radiation treatment.Results Following lentiviral transfection that reduced LINC01772 levels in A549 cells,a significant decrease in cell viability(P<0.01)was observed alongside an increase in apoptosis(P<0.01).Notably,expres-sions of Bad and Cleaved Caspase-3 were significantly elevated(P<0.01),while Bcl-2 expression was markedly decreased(P<0.01).After exposure to different radiation doses,a dose-dependent reduction in A549 cell viability was noted(P<0.01),accompanied by a significant impairment of clonogenic ability(P<0.01),G2/M phase arrest within the cell cycle(P<0.01),and an increased incidence of apoptosis(P<0.01).Conclusion Inhibiting long non-coding RNA LINC01772 expression substantially diminishes cellular viability in A549 cells,enhances apoptotic processes,disrupts their cycling mechanisms,and augments their sensitivity to radiotherapy,suggesting that this non-coding RNA may serve as a potential target for enhancing lung cancer radiotherapy.

The aging trend is intensifying currently,but there is still a lack of standardized diagnosis and treat-ment schemes for severe infections in elderly people.This paper focuses on the recommendations for immune-related clinical diagnosis and treatment routes as well as the idea of risk stratified diagnosis and treatment for elderly peo-ple,aiming to effectively prevent infectious diseases in elderly people and perform stratified management through systematic and scientific means of immune function monitoring and regulation,so as to enhance the standardized level of diagnosis and treatment as well as clinical treatment effect of infection in elderly people.

Objective To explore the effects of long non-coding RNA LINC01772 on cell cycle,apoptosis and radiotherapy sensitivity of A549.Methods A549 cells were resuscitated and cultured for experimental pur-pose.The effects of LINC01772 knockdown on cell viability,cell cycle progression,and apoptosis were assessed using CCK-8 assays and flow cytometry,and apoptosis-related proteins were analyzed using western blotting.CCK-8 and clonogenic assays were used to measure the changes in the sensitivity of A549 cells to radiotherapy following various radiation doses,and flow cytometry to examine alterations in the cell cycle and apoptosis post-radiation treatment.Results Following lentiviral transfection that reduced LINC01772 levels in A549 cells,a significant decrease in cell viability(P<0.01)was observed alongside an increase in apoptosis(P<0.01).Notably,expres-sions of Bad and Cleaved Caspase-3 were significantly elevated(P<0.01),while Bcl-2 expression was markedly decreased(P<0.01).After exposure to different radiation doses,a dose-dependent reduction in A549 cell viability was noted(P<0.01),accompanied by a significant impairment of clonogenic ability(P<0.01),G2/M phase arrest within the cell cycle(P<0.01),and an increased incidence of apoptosis(P<0.01).Conclusion Inhibiting long non-coding RNA LINC01772 expression substantially diminishes cellular viability in A549 cells,enhances apoptotic processes,disrupts their cycling mechanisms,and augments their sensitivity to radiotherapy,suggesting that this non-coding RNA may serve as a potential target for enhancing lung cancer radiotherapy.