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

Objective:To investigate the expression of SLIT2/ROBO1 in prostate cancer and its clinical significance.Methods:A total of 100 cases of radical prostatectomy paraffin specimens at Department of Clinical Pathology, the average age of the patients was (71.8±7.8) years, the People?s Hospital of Baoan Shenzhen from January 2015 to December 2019 were collected and immunohistochemical staining was used to analyze the correlation between SLIT2/ROBO1 expression and clinicopathological features in prostate cancer.COX regression was used to analyze the influencing factors of biochemical recurrence in patients with prostate cancer after radical treatment.Prostate cancer cells PC3 and LNCaP were used as research objects, ROBO1 was silenced by small interfering RNA specific to human ROBO1, and its effect on the growth rate of prostate cancer was observed by CCK8 assay.Transwell cell migration and invasion assay was used to detect the effect of ROBO1 knock-down on the migration and invasion ability of prostate cancer cells.Protein immunoimprinting assay was used to detect the expression of TGF-β/SMAD pathway-related proteins after ROBO1 knockdown.Results:The expressions of SLIT2 and ROBO1 in prostate cancer were increased with the increase of prostate cancer Gleason score system (Gleason score) and International Society of Urology Pathology score (ISUP)( P<0.05). The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis ( P<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer ( P<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. Conclusions:The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of prostate cancer.At the same time, ROBO1 can inhibit the migration and invasion of prostate cancer cells by regulating the TGF-β/SMAD signaling pathway.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Objective To investigate the clinical value of baseline 18F-fluorodeoxyglucose(18F-FDG)PET/CT metabolic parame-ters and certain clinical indicators in predicting the prognosis of patients with diffuse large B-cell lymphoma(DLBCL).Methods A retrospec-tive analysis was conducted on the baseline 18 F-FDG PET/CT data of 73 DLBCL patients who received R-CHOP treatment.Patients were divided into progression group(24 cases)and non-progression group(49 cases)based on disease progression within 2 years post-treatment.The lesion maximum standardized uptake value(SUVmax),tumour-to-liver blood pool SUVmax ratio(LLR)and tumour-to-mediastinal blood pool SUVmax ratio(L-BPR)were analyzed using receiver operating characteristic(ROC)curves.Kaplan-Meier(K-M)survival curves analysis were performed based on the optimal thresholds of SUVmax,LLR and L-BPR.x2 tests were used to analyze and compare the relationship between each parameter and disease progression.Indicators that were significant in the x2 tests were included in the multivariate Cox regression analysis.Results The area under the curve(AUC)for LLR,L-BPR,and SUVmax were 0.920,0.914,and 0.848,respectively,with optimal thresholds of 7.41,10.67,and 14.70.Based on these thresholds,K-M survival curves analysis showed that the 2-year progression-free survival(PFS)rates for DLBCL patients were 79.2％vs 30.8％(P＜0.001),74.3％vs 22.0％(P=0.009),and 79.5％vs 51.6％(P=0.002),respectively.Significant differences were observed between the progression and non-progression groups in terms of LLR,L-BPR,SUVmax,extranodal involvement,international prognostic index(IPI)score,lactate dehydrogenase(LDH)level,Eastern Cooperative Oncology Group(ECOG)score,and β2-microglobulin(β2-MG)levels(P＜0.05).Multivariate Cox regression analysis revealed that the IPI score and LLR were independent predictors affecting the 2-year PFS of DLBCL patients(P＜0.05).Conclusion Baseline 18F-FDG PET/CT metabolic parameter LLR and IPI score are inde-pendent factors for predicting the prognosis of DLBCL patients.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objective:To analyze the iodine nutrition status of children and adolescents and influencing factors in Zhejiang Province, providing scientific basis for optimizing iodine deficiency disorders (IDD) prevention and control strategies.Methods:In June 2022, a multistage stratified sampling method was used to divide 16 counties (cities, districts, abbreviated as counties) in Zhejiang Province into three categories based on their geographical locations (average distance from the coastline): coastal areas (including Dinghai District, Jiaojiang District, Sanmen County, Cixi City and Lucheng District), sub-coastal areas (including Wuxing District, Haining City, Linping District, Fuyang District and Fenghua District), and inland areas(including Suichang County, Changshan County, Shengzhou City, Jindong District, Dongyang City and Yongjia County). One county was selected from each category, and one township (street) was selected from each county. Two administrative villages (neighborhood committees) were selected from each township (street). Ten households including all children and adolescents aged 6-17 in each household were selected from each administrative village (neighborhood committee). Demographic information and personal dietary characteristics were collected via questionnaires, while household salt and a random urine sample were tested for iodine level. Trend analysis was conducted using a χ 2trend test, and a multivariate logistic stepwise regression model was used to analyze the influencing factors of urinary iodine levels. Results:A total of 755 children and adolescents aged 6-17 were selected, including 387 males (51.26%) and 368 females (48.74%), with an age of (11.24 ± 3.32) years. There were 269 children and adolescents in coastal areas (35.63%) and 409 children and adolescents in urban areas (54.17%). A total of 755 household salt samples were collected, with a median salt iodine concentration of 21.80 mg/kg. These included 263 non-iodized salt samples, 38 unqualified iodized salt samples, and 454 qualified iodized salt samples. The coverage rate of iodized salt was 65.17% (492/755), and the consumption rate of qualified iodized salt was 60.13% (454/755). The distribution of salt iodine quality among children and adolescents in different geographical locations showed statistically significant differences (χ 2 = 111.95, P < 0.001), with the proportion of non-iodized salt gradually decreasing from coastal areas to inland areas (χ 2trend = 90.17, P < 0.001). A total of 755 urine samples were collected, with a median urinary iodine concentration of 186.60 μg/L. The proportions of urinary iodine < 100, 100-199, 200-299, and ≥300 μg/L were 16.95% (128/755), 37.62% (284/755), 24.37% (184/755), and 21.06% (159/755), respectively. The χ 2trend test revealed a nonlinear positive correlation between salt iodine level and urinary iodine level (χ 2regression = 21.98, P < 0.001; χ 2partial = 6.96, P < 0.001). The frequency distribution of urinary iodine in children and adolescents from different geographical locations and between urban and rural areas showed statistically significant differences (χ 2 = 29.63, 16.56, P < 0.001). Among them, the proportion of children and adolescents with urinary iodine < 100 μg/L gradually decreasing from coastal areas to inland areas (χ 2trend = 6.15, P = 0.013). The results of multivariate logistic regression analysis revealed that sub-coastal regions, inland regions, and urban-rural regions ( OR = 1.57, 1.53, 1.64, 95% CI: 1.11-2.24, 1.03-2.27, 1.17-2.32, P < 0.05) were significantly associated with urinary iodine levels in children and adolescents aged 6-17. Conclusions:In 2022, the iodine nutrition of children and adolescents in Zhejiang Province is generally suitable, but there is a risk of iodine deficiency among coastal children and adolescents. Geographic location and urban/rural areas are influencing factors on iodine nutrition status of children and adolescents in Zhejiang Province.

Objective To investigate the clinical characteristics and outcomes of Coronavirus Dis-ease 2019 in immunocompromised hosts.Methods A retrospective analysis was conducted on the clinical data of 230 hospitalized patients diagnosed with Coronavirus Disease 2019 at Nanjing Yimin Hospital from December 2022 to November 2023.The patients were divided into three groups based on their immune status:immunocompromised group(n=59),relatively immunocompromised group(n=129),and immunocompetent group(n=42).The clinical characteristics(such as clinical manifesta-tions,imaging features,and laboratory examinations)and outcomes(such as length of hospital stay and in-hospital mortality)were compared among three groups.Results Compared with there latively immunocompromised and immunocompetent groups,the immunocompromised group showed no obvious specific clinical manifestations.However,the proportions of patients with symptoms such as cough and expectoration were lower,and the occurrences of symptoms such as myalgia and fatigue were less fre-quent in the immunocompromised group(P＜0.05).The chest CT findings in the immunocompro-mised group also lacked specific changes,mainly presenting as subpleural ground-glass opacities and consolidations with multilobar distribution,but fibrotic changes were more common(P＜0.05).The proportion of patients with decreased absolute lymphocyte counts in the immunocompromised group was higher than that in the immunocompetent group,and the proportion of patients with elevated procalcitonin levels was higher than that in the other two groups(P＜0.05).The proportion of severe case sand the length of hospital stay in the immunocompromised group were higher and longer than those in the relatively immunocompromised and immunocompetent groups(P＜0.05).The in-hospital mortality rates in the immunocompromised,relatively immunocompromised,and immunocompetent groups were 10.17％,6.98％,and 2.38％,respectively,with no statistically significant difference(P＞0.05).Conclusion After Coronavirus Disease 2019,immunocompromised hosts do not show obvi-ous clinical and imaging features.However,they have a prolonged length of hospital stay,a signifi-cantly higher proportion of severe cases,and a tendency towards increased in-hospital mortality,which should be given high clinical attention.

Objective To evaluate the diagnostic value of positron emission tomography(PET)/computed tomography(CT)and bone marrow biopsy(BMB)for bone marrow infiltration in common non-Hodgkin lymphoma(NHL).Methods We retrospectively analyzed data from 197 patients with NHL and compared the diagnostic value of PET/CT and BMB for bone marrow infiltration.Differences in PET/CT parameters and serological test results were compared between PET/CT-positive and PET/CT-negative patients as well as between BMB-positive and BMB-negative patients.Results In patients with diffuse large B-cell lymphoma(DLBCL),the sensitivities of PET/CT and BMB for detecting bone marrow infiltration were 90.5%and 66.7%,and the specificities were 95.1%and 100.0%,respectively.In patients with follicular lymphoma(FL),the sensitivities were 63.6%and 81.8%,and the specificities were 98.1%and 100.0%,respec-tively.In patients with T-cell lymphoma(TCL),the sensitivities were 60.0%and 80.0%,and the specificities were 88.0%and 100.0%,respectively.Among patients with DLBCL and TCL,significant differences were observed in platelet count and lactate dehydrogenase levels between PET/CT-positive and PET/CT-negative patients(P<0.05).Conclusion PET/CT showed excellent diagnostic perfor-mance for evaluating bone marrow infiltration in DLBCL.PET/CT had limited sensitivity for FL and TCL and might serve as a supplemen-tary tool for BMB.Platelet count and lactate dehydrogenase levels may aid in the diagnosis of bone marrow infiltration in DLBCL and TCL.