Protein-protein interactions (PPIs) are not only crucial for the assembly of protein complexes but also fundamental for maintaining normal biological functions. These interactions are vital for protein structure and biological functionality and play a central role in cellular signaling, metabolic pathways, and regulatory networks. The 14-3-3 protein, highly conserved and widely expressed in eukaryotes, primarily recognizes and binds to its partner proteins to participate in essential life processes such as cell cycle control, signal transduction, and energy metabolism. This review discusses the role of dysregulated PPIs between 14-3-3 proteins and their partner proteins such as estrogen receptor α (estrogen receptor α, ERα), RAF proto-oncogene serine/threonine-protein kinase (C-RAF/RAF-1), and p53 in the onset and progression of tumors, focusing on the research progress of 14-3-3/ERα, 14-3-3/C-RAF, and 14-3-3/p53 molecular glues. These molecular glues, by mimicking or enhancing the phosphorylation sites of serine on partner proteins, form covalent bonds, salt bridges, and hydrogen bonds with 14-3-3 proteins, thereby enhancing the stability of PPIs and effectively intervening in protein activity and signaling under pathological conditions. Additionally, this article explores the potential of this chemical intervention strategy in clinically suppressing tumor progression, providing a theoretical foundation and practical guidance for future research directions.

Objective:To explore CCR7 expression in splenic dendritic cells and its role in migration and activity of splenic dendritic cells in multiple organ dysfunction syndrome (MODS) in mice.Methods:The MODS model of mice was reproduced by Zymosan injection into peritoneal cavity.The mice were randomly divided into groups of normal,3-6 hours,24-48 hours and 10-12 days post zymosan injection.CD11c and CD205 were analysed by immunohistochemistry;The expression of CD86 and CCR7 of DCs were studied by the flow cytometry analysis.Results:In normal mice,many DC were found at the margin between the red and white pulp.In the 3-6 h and 24-48 h groups,CD86 and CCR7 were strongly up-regulated in the DC,and they distributed in T cells areas.In the 10-12 d group,DC distributed at the margin by the immature form.Conclusion:The CCR7 expression level of DC has close correlations with the migration of DC,CCR7 can be used to evaluate the migration and functional activity of DC in MODS.

Objective To investigate the effect and mechanism of soluble epoxide hydrolase inhibitor (sEHI) for NF-κB pathway and cell circle arrest of tubular epithelial cell in unilateral ureteral obstruction (UUO) mice model.Methods Thirty-two healthy C57BL/6 male mice performed UUO surgery to induce renal interstitial fibrosis.Animals were randomly divided into 4 groups:sham group (n=8),sEHI (1 mg· kg-1·d-1) group (n=8),UUO group (n=8) and UUO+sEHI (1 mg· kg-1· d-1) group (n=8).Daily sEHI [1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea,TUPS] or 2％ DMSO was applied to mice by oral gavage from day 1 to day 14 after surgery.All mice were sacrificed at day 14 and kidneys were harvested for further analysis.The changes of renal tissue morphology and pathology were observed by Hematoxylin and eosin (HE) and sirius red staining.The expressions of sEH,nuclear factor κB p65 (NF-κB p65) and IκB were measured by Western blotting.The expressions of TNF-α,IL-1β,MCP-1,IL-6,TGF-β,CTGF,collagen-Ⅳ and α-SMA were analyzed by real-time PCR.Immunofluorescence staining of phospho-histone H3 (p-HH3) and Ki67 was performed to determine the stage of cell cycle G2/M arrest.Results The expression and activity of sEH increased in UUO group (P ＜ 0.05).Administration of sEHI inhibited activity of sEH and infiltration of inflammatory cell in tubular interstitial,as well as attenuated tubular damage and tubular interstitial fibrosis.Western blotting analysis revealed administration of sEHI inhibited up-regulated NF-κB p65 and down-regulated IκB in UUO group (P ＜ 0.05).Real-time PCR demonstrated that administration of sEHI obviously decreased the mRNA expression of cytokines and fibrosis markers,including of TNF-α,IL-1 β,MCP-1,IL-6,TGF-β,CTGF,Collagen-Ⅳ,α-SMA (P ＜ 0.05).Immunofluorescence staining showed that there were much more p-HH3 and Ki67 double positive nuclear tubular epithelial cells and interstitial cells in UUO group,compared with Sham group (P ＜ 0.05).Administration of sEHI reduced the number of double positive nuclear cell only in tubular epithelial cells (P ＜ 0.05),but not in interstitial cells.Conclusions In UUO tubular interstitial fibrosis model,sEHI inhibits the activation of NF-κB pathway by down-regulating p65 and up-regulating IκB and ameliorates the infiltration of inflammatory cells.In addition,sEHI plays anti-fibrosis effect by moderating cell cycle G2/M arrest and reducing the excrete of pro-fibrosis factors of tubular epithelial cells.

Objective To analyze the clinical characteristics,pathological classification and therapy strategy of rectal carcinoid and its prognostic factors.Methods Forty four patients with rectal carcinoid were diagnosed and treated in Ruijin Hospital Shanghai Jiaotong University from January 2006 to November 2013,among whom 21 patients (19 males and 2 females) were followed-up for 1-7.5 years.The clinical data of these cases were retrospectively analyzed.Results The patients underwent colonoscopy because of changed bowel habits and/or abnormal digital rectal examination,none of them had carcinoid syndrome.Colonoscopy showed that most lesions presented yellowish in color and smooth in surface; the diameter of the tumor was ≤ 1.0 cm in 12 cases (57％) ; the tumors were located at the rectum within 8 cm from anal rim in 17cases (76％); most of them were well differentiated.Immunohistochemistry demonstrated that NSE expression was highly positive.The 1 year-and 3year-survival rate were both 100％.Among 8 cases who were followed up for over 5 year,2 relapsed.Conclusions The digital rectal examination plays a key role in detecting rectal carcinoid.Though prognosis is relatively good,we should keep close following-up to detect the recurrence.The main risk factors influencing the prognosis are tumor size,depth of invasion and clinical stage.The combination measurement of CEA,TSGF,CA19-9 and NSE will either increase the sensitivity or the specificity of early detection.

Objective To explore the clinical value of renal dynamic imaging and urinary N-acetyl-?-D-glucosaminidase(NAG),apoptosis DNA fragment(ADF) in evaluating the damage degree of hydronephrotic kidneys(HnK) in children with hydronephrosis.Methods Level of glomerular filtration rate(GFR) was detected in 41 children with congenital hydronephrosis by renal dynamic imaging,and urine NAG,ADF in pelvis in HnK and healthy kidneys (as controls) were detected by enzyme-linked immuno-sorbent assay(ELISA).Patholo-gic changes of HnK in 41 children were graded intoⅠ~Ⅴ according to Elder standard. And GFR,urinary NAG and ADF of HnK were divi-ded into subgroup according to pathologic changes ,at the same time statistical analysis was performed within each groups. And the correlations of pathologic grades with GFR,urinary NAG and ADF of HnK were analyzed.Results 1.Kindneys GFR in healthy kidneys and Hnk were (174.33?20.43)?10-3 L/min,(143.86?17.51)?10-3 L/min respectinely,and there was significant difference between healthy kidneys and Hnk (P0.05).3.There was significant negative correlation between GFR levels of HnK and pathologic grades(r=-0.814 P0.05).Conclusions For hydronephrotic kidneys,urinary NAG can eva-luate impaired nephric tubule whereas renal dynamic imaging may evaluate the damage level of glomeruli;urine ADF may not indicate the damage level of diseased kidneys in children with congenital hydronephrosis.

Objective To examine the pathological changes in the myocardial tissues such as inflammatory response and fibrosis in a rat model of acute radiation-induced heart damage (RIHD),and to explore whether NF-κB and its downstream pathway are associated with acute radiation-induced myocardial fibrosis.Methods Fourteen nale adult Sprague-Dawley rats were randomly divided into control group and radiation group.Local heart irradiation was delivered to the precordial region of rats to establish an RIHD model in a single fraction with a dose of 20 Gy generated by a 6 MV linear accelerator.At 14 days after irradiation,the histopathological changes in myocardial and interstitial tissues were examined by HE staining;the distribution of collagen fibers was observed by Masson staining,and collagen volume fraction (CVF) was used as a semi-quantitative evaluation for myocardial collagen deposition,which was defined as the percentage of collagen area occupied in total area,and was compared using the independent-samples t test.The protein and mRNA expression levels of the NF-κB members p50 and p65 and the downstream pathway members hypoxia-inducible factor 1α(HIF-1o),connective tissue growth factor (CTGF),and type I (COL-1) were quantitatively analyzed by Western blot and qPCR,respectively.Results At 14 days after local heart irradiation,the radiation group showed significant myocardial edema and derangement,rupturc of some myocardial ceils,mild nuclear pyknosis,darkened nuclear staining,a small number of irregular nuclei,and myocardial interstitial inflammatory cell infiltration accompanied by increased fibroblast,as compared with the control group.The Masson staining showed that the collagen fibers in radiation group were widely distributed at the interstitial tissue and increased significantly compared with those in the control group;normal myocardial cells were in disordered array and had a tendency to be replaced by collagen fibers.The semi-quantitative analysis showed that radiation induced a significant increase in CVF (22.05％ vs.3.76％,P =0.003).Western blot and qPCR revealed that the protein and mRNA expression of p50,p65,HIF-1 α,CTGF,and COL-1 was significantly higher in the radiation group than in the control group (all P ＜ 0.05).Conclusions The pathological features of acute RIHD include significant myocardial edema and myocardial interstitial inflammatory cell infiltration accompanied by increased fibroblasts and collagen fibers.Radiation exposure can activate NF-κB and cause the upregulation of HIF-1α and CTGF at both protein and mRNA levels,which may play an important role in the progression of radiation-induced myocardial inflammation to fibrosis.

Objective To study the effects of inhibing AKT2 by siRNA on SMMC7721 liver cancer cells proliferation,apoptosis,migration and invasion.Methods The siRNA targeting AKT2 was designedandthe SMMC7721AKT2- siRNAplasmidwasconstructed andtransfected into SMMC7721 cells.The stable cell lines were screened by G418.The effects of AKT2 by siRNA on SMMC7721 liver cancer cells,growth inhibition was evaluated by MTT assay.Cell cycle was analyzed by flowcytometry (FCM).Protein of P27 and CyclinD1 was evaluated by Western-blot.The ability of migration and invasion was evaluated by wound healing and Transwell assay.ResultsThe growth of SMMC7721 cells was significantly inhibited by siRNA (P＜0.05).Flow cytometry display that AKT2 by siRNA can induce G1 phase arrest,the ratio of G1 phase increased homologously and S phase declined homologously.The protein of CyclinD1 was declined and the protein of P27 was increased by Western-blot.Wound healing and Transwell assay show that the ability of cells,migration and invasion was inhibited by AKT2 by siRNA.Conclusion AKT2 by siRNA can significantly inhibit the growth of SMMC7721 cells,arrest cell cycle.AKT2 by siRNA can inhibit the ability of invasion and migration of SMMC7721 cells.

Objective:To analyze the incidence and risk factors of non-acute symptomatic portal vein thrombosis (PVT) after endoscopic gastric variceal injection (GVI) in the treatment of liver cirrhosis with gastric variceal bleeding (GVB).Methods:66 patients with GVB who were treated with GVI for the first time from July 2017 to October 2019 in Minhang Hospital Affiliated to Fudan University were retrospectively analyzed. The data of gender, age, preoperative Child-Pugh grade, preoperative platelet count, preoperative plasma D-dimer concentration, preoperative splenic length, preoperative portal vein velocity, preoperative splenic vein velocity, preoperative portal vein diameter, preoperative splenic vein diameter, treatment times, total number of injection points, total dose of sclerosing agent and tissue adhesive agent were collected. The patients were divided into PVT group and non-PVT group according to the occurrence of non-acute symptomatic PVT within one year after GVI. Univariate analysis was performed first, and then the factors with P<0.2 were included in the binary logistic regression model to screen the risk factors of PVT after GVI. Results:There were 25 cases (37.88%) in PVT group and 41 cases (62.12%) in non-PVT group. There were significant differences in D-dimer concentration, spleen length, Child-Pugh grade and total dose of sclerosing agent between the two groups ( P<0.05). The D-dimer concentration ( OR=2.319, 95% CI:1.359-3.956), spleen length ( OR=1.044, 95% CI:1.007-1.081) and total dose of sclerosing agent ( OR=1.075, 95% CI:1.004-1.152) were independent risk factors for PVT ( P<0.05). Conclusions:Preoperative D-dimer concentration, spleen length and total dose of sclerosing agent can predict the risk of PVT after GVI. In order to reduce the risk of PVT after GVI, the dose of sclerosing agent should be reduced as much as possible.

Objective To study the significance of the related parameters of the abduction angle ,anteversion angle and summit arc angle in the intraoperative localization of anterior column and anterior wall acetabular fractures .Methods The safety angle of abduction angle ,an-teversion angle,summit arc angle and anterior wall acetabular of 318 adult pelvic specimen(109 males and 109 females) were measured.The data was statistical analyzed.Results For the male pelvic specimen,the measured values of abduction angle of acetabulum was (43.5 ± 2.9)°, anteversion angle was (13.7 ±5.2)°,summit arc angle inside was(25.5 ±7.3)°,summit arc angle front was(37.8 ±7.2)°,sum-mit arc angle back(49.9 ±12.7)°.For female pelvic specimen,the measured values of abduction angles of acetabulum was (44.1 ±3.2)° and anteversion angle was (14.3 ±4.9)°,summit arc angle inside was(27.1 ±6.5)°,summit arc angle front was(36.3 ±9.2)°,summit arc angle back was(52.3 ±13.6)°.According to '2-7' sector method, the thickness of different point of anterior wall was measured .There were statistically significant differences in abduction angles ,anteversion angle and summit arc angle (P<0.05).And there was no statistically sig-nificant difference in the thickness of anterior column and anterior wall between the above three one angles (P>0.05),there was no signifi-cant difference in the acetabular abduction angle ,anteversion angle and summit arc angle between males and females .Conclusion The intra-operative localization of acetabulum abducted angle ,anteversion angle and summit arc angle in the acetabulum anterior column and anterior wall fractures can achieve satisfactory therapeutic effect .

Arthroplasty, Replacement, Hip ; methods ; Female ; Hip ; surgery ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods