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.

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

ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL^-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d^-1）， and low- and high-dose （crude drug 3.4， 17 g·kg^-1·d^-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL^-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.

BACKGROUND:In implant restoration in the aesthetic area,zirconium dioxide is gradually becoming the most commonly used upper restorative material and has achieved better clinical results.Resin-ceramic composite,a new type of dental restorative material,begins to try to be used as an upper restorative material in implant restoration,but there is less research on the application of this material in implant restoration. OBJECTIVE:To compare the biomechanical differences between resin ceramic crowns and zirconia all-ceramic crown implant restorations in three occlusal relationships for restoring maxillary central incisors. METHODS:The cone-beam CT image data of a patient with single-crown implant restoration of maxillary central incisor were selected,and the maxillary bone model was extracted by using Mimics 21.0 software,and the model was imported into Solidworks 2020 software.The crown,adhesive,abutment,central screw,and implant were modeled,and the model of single-crown implant restoration of maxillary central incisor was assembled.After giving the model material property parameters(resin-ceramic composite and zirconia for the upper restoration materials)in ANSYS Workbench 2021 R1 software,three occlusal relationships(edge-to-edge occlusion,normal overjet and deep overbite)were simulated and loaded to analyze the stress distribution of the resin-ceramic crown and zirconia all-ceramic crown implant restoration models. RESULTS AND CONCLUSION:(1)The stress concentration areas in the implant restoration models of the resin-ceramic crown group and the zirconia all-ceramic crown group in different occlusal relationships were distributed in the upper restoration loading point,the abutment-implant connection,the implant neck and the surrounding bone tissue.As the occlusal relationship changed from the edge-to-edge to normal and deep overbite,the peak equivalent forces of the restorative abutment,central screw,implant,and bone tissue in both the resin-ceramic and zirconia all-ceramic crown groups gradually decreased.The highest peak equivalent forces were observed for the upper restorations in deep overbite.The zirconia all-ceramic crown group had the highest peak equivalent force in the adhesive layer in the edge-to-edge relationship,and the resin-ceramic crown group had the highest peak equivalent force in the adhesive layer in the deep overbite.(2)In the edge-to-edge occlusion,the peak equivalent force of the adhesive layer and central screw in the resin-ceramic crown group was slightly smaller than that in the zirconia all-ceramic crown group,and there was no significant difference between the two groups in the peak equivalent force at the upper restoration,restoration abutment,implant,and bone tissue.The peak stresses in the upper restoration,adhesive layer,and central screw of the resin-ceramic crown group were slightly less than those of the zirconia all-ceramic crown group at normal fit,and there were no significant differences between the two groups in the peak equivalent forces at the restoration abutment,implant,and bone tissue.In deep overbite,the peak adhesive,abutment,and central screw stresses were greater in the resin-ceramic crown group than in the zirconia all-ceramic crown group,with no significant differences in the upper restorations,implants,or bone tissue.(3)The results showed that the upper restorative material had no significant effect on the stress distribution of the implant and bone tissue,and had some effects on the stress distribution of the upper restoration,adhesive,restoration abutment,and central screw,but the difference was not significant.The occlusal relationship has a significant influence on the stress distribution in all structures and bone tissue of the implant restoration.The resin-ceramic crowns have a buffering effect on the stresses in the case of edge-to-edge and normal occlusion.

Objective To observe the effect of abdominal acupuncture in treating allergic rhinitis(AR).Methods Twenty-seven AR patients who attended Fangshan Hospital,Beijing University of Chinese Medicine from August to October 2022 were selected.They were divided into treatment group(15 cases)and control group(12 cases)according to randomized numerical table method.The treatment group received abdominal acupuncture.The control group at the same point was used one-time sterile cannula acupuncture to simulate acupuncture,but no needle was inserted into the acupoint.Two groups were treated,3 times a week for 4 weeks.The visual analogue scale(VAS),rhinoconjunctivitis quality of life questionnaire(RQLQ),Pittsburgh sleep quality index(PSQI)scores,and the histamine(HIS),leukotriene D4(LTD4),immunoglobulin E(IgE)levels were compared between two groups before and after treatment.Results At each time point after treatment,the VAS,RQLQ,PSQI scores and HIS,LTD4,IgE levels of patients in treatment group were significantly lower than those before treatment(P<0.05).There were no statistically significant differences in VAS,RQLQ,and PSQI scores,the HIS,LTD4,and IgE levels after 2-week treatment in both groups(P>0.05).After 4-week treatment and follow-up 4-week,the VAS,RQLQ,and PSQI scores,the HIS,and LTD4 levels in treatment group were significantly lower than those in control group(P<0.05).Conclusion Abdominal acupuncture has good therapeutic effect on AR and significantly improves life quality of the patients,which can reduce the levels of HIS,LTD4 and IgE.The therapy is worthy of clinical application.

The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lyciumbarbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl₄). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl₄ solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl₄-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase II detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I‒V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.
Animals ; Dogs ; Antioxidants/metabolism* ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury/drug therapy* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Metabolic Networks and Pathways ; Mitochondria/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Polysaccharides/pharmacology* ; Lycium/chemistry*

The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lycium barbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl4). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl4 solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl4-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase Ⅱ detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I?V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Objective:To develop an evaluation index system for the management ability of general practice team leaders in community health service centers.Methods:Based on literature review, key insider interviews and other methods, the framework and indicator pool for management capability of general practice team leaders were formed. Two rounds of Delphi consultations with 15 experts were conducted from July to October 2021, and the evaluation index system of general practice team leaders' management ability established.Results:All 15 experts had at least 5 years of work experience, including 10 engaging in clinical general practice, 3 in public health and 2 in community management. The response rates for the two rounds of expert consultation was 15/15, and the expert authority coefficient was 0.84, with Kendall's W coefficient of 0.35 ( P<0.001) and 0.46 ( P<0.001), respectively. Finally, the evaluation index system of the management ability of general practice team leaders was established, which consisted of 5 primary indicators (personal quality, special business management, organizational management, teaching and research management, strategy and culture building), 11 secondary indicators and 37 tertiary indicators. Conclusions:The management capability evaluation index system general practitioner team leaders of the community health centers has been established in this stu, which may be used for the training and selection of general practice team leaders in the community health centers.