Aged ; Female ; Histiocytoma, Malignant Fibrous ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Spleen ; chemistry ; pathology ; surgery ; Splenectomy ; Splenic Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Actins ; metabolism ; Bone Neoplasms ; blood ; complications ; diagnostic imaging ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Hypophosphatemia ; blood ; etiology ; Ilium ; Mesenchymoma ; blood ; complications ; diagnostic imaging ; pathology ; surgery ; Middle Aged ; Osteomalacia ; blood ; etiology ; Phosphates ; blood ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Tomography, X-Ray Computed

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Objective To identify the candidate genes in the vicinity of a susceptibility locus (urinary albumin 1,UA-1) contributing to the development of albuminuria in type 2 diabetic KK/Ta mice. Methods Total RNA was extracted from the kidneys of KK/Ta (n=3) and BALB/c (n=2) mice at 20 weeks of age.The gene expression profile in kidney was investigated using the Affymetrix Murine Genome U74Av2 array.Competitive RT-PCR was used to confirm the differential expression of syndecan-4 which located in the vicinity of UA-1.Genome DNA was extracted from KK/Ta and BALB/c mice.DNA sequence analysis of the coding and promotor region of syndecan-4 gene was conducted. Results In the vicinity of the susceptibility locus (UA-1)contributing to the development of albuminuria in type 2 diabetic KK/Ta mice,10 candidate genes that showed differential expression were identified.Among them,the gene expression of syndecan-4in KK/Ta kidneys at 20 weeks of age was up-regulated by 26.1 times of age-matched BALB/c kidneys.Sequence analysis revealed two synonymous polymorphisms in the coding region (A93C and T216C) and three polymorphisms in the promoter region (-T263C,-T396C and -G669A) of the syndecan-4 gene.The TATA box was found at 321 bp upstream from the transcription start site,and the T263C polymorphism was located in the binding site of transcription factor Clox.Conclusions Syndecan-4 gene is mapped in the vicinity of the susceptibility locus contributing to the development of albuminuria in type 2 diabetes.The gene expression of syndecan-4 in KK/Ta kidneys is up-regulated than that in age-matched BALB/c kidneys at 20 weeks of age.Thus syndecan-4 may be one of the potential candidate genes responsible for diabetic nephropathy.Sequence differences in the promoter region influence the expression levels of syndecan-4 genes in KK/Ta kidneys.

Objective To investigate outcome and cognitive changes of amnestic mild cognitive impairment (aMCI) in a follow-up study. Methods A cross-sectional and longitudinal parallel cohort study design was conducted among 109 aMCI patients and 104 matched normal controls. Multi-dimension neuropsychologic tests were used to extensively assess the cognitive function. Results The scores of neuropsychologic tests in aMCI patients were significantly lower than those in the normal controls( all P＜0.01 ) ,with the largest impairment on 20minutes delayed recall of the auditory verbal memory test ( AVMT), which reflects episodic memory ( aMCI pa-tients :2.50 ± 1.48, normal controls :7.85 ± 1.59, Z = - 12.697, P ＜ 0.01 ); AD was diagnosed in 15 of the 69aMCI patients with a prevalence rate of 22% ,but none was converted to AD in the normal controls. The cognitivechanges of performance in AVMT, CDT, MMSE of the patients in aMCI group (( 3.77 ± 60.83 )%, (6.89 ±28.24) %, (6.13 ± 16.89) % respectively) were significantly poorer than those of the controls group(( - 10.75 ±27.46) %, ( - 5.23 ± 14.05 ) %, ( - 1.11 ± 8.26 ) % respectively) ( all P ＜ 0.05 ). At baseline, demented aMCIperformed poorer in AVMT, CFT, TMT, SDMT, CDT, MMSE when compared to stable. During the follow-up, demented aMCI groups performed significantly poorer than did stable subjects in AVMT, CFT, DST, VFT, SDMT,MMSE ( all P ＜ 0.05 ). Conclusion aMCI is a prodromal period of AD and characterized by episodic memory impairment. The neuropsychologic test is a predictive factor for aMCI to develop AD.

Objective To investigate the current status and influencing factors of work engagement in emergency nurses, put forward a feasible strategy, improve the emergency department nurses work engagement for the emergency department to build effective human resource management to provide the reference. Methods A total 226 emergency nurses from 8 hospital of first-class in Tianjin city were recruited by the convenience sampling method and investigated with a self designed, the Medical Personnel′s Work Engagement Questionnaire. Results The total score of Medical Personnel′s Work Engagement Questionnaire was 111-166(137.32 ± 12.48) points and the scores were the highest in interpersonal concordance (4.20 ± 0.46) points and the lowest in work vigor (3.01 ± 0.61) points. Variance analysis and multiple linear regression analysis showed that gender, employment category and number of years as an emergency nurses were the influencing factors of work engagement, which could explain 51.3%of the variance. Conclusions Work engagement emergency of nurses is at a relatively moderate-to-high level, through establishing an effective incentive mechanism, increasing social benefits, accelerating the construction of emergency specialist nurse training system and paying attention to occupational development, work engagement level and quality of emergency medical care can be improved.

Objective To investigate the relationship between recurrent spontaneous abortion (RSA) and the level of interferon-γ(IFN-γ) and interleukin-4 (IL-4) in peripheral blood and gingival crevicular fluid of patients with chronic periodontitis.Methods Fifty pregnant women with recurrent spontaneous abortion(gestational age: 5-28 weeks) and 40pregnant women (gestational age: 39-41 weeks)were included and their periodontal status was examined.The level of IFN-γ and IL-4 in gingival crevicular fluid and peripheral blood was detected by enzyme-linked immunosorbent assay.Results Nine RSA women and 5 in control group had periodontitis.The prevalence of periodontitis in RSA group was 18％ (9/50) and 13％ (5/40) in the control group(P ＜0.05).The probing depth,attachment loss and bleeding index in RSA group were higher than those in the control group(P ＜0.05).The level of IFN-γwas (52.98 ± 17.56) ng/L in gingival crevicular fluid of RSA group and (25.25 ± 7.93) ng/L in control group(P ＜ 0.01).The level of IL-4 was (15.43 ± 1.77) ng/L in gingival crevicular fluid of RSA group and (19.62 ± 4.04) ng/L in control group (P ＜0.01).The content of IFN-γwas (27.79 ± 3.59) ng/L in peripheral blood of RSA group and (18.39 ±2.65) ng/L in control group(P ＜0.05).The content of IL-4 was (15.88 ± 0.95) ng/L in peripheral blood of RSA group and (22.98 ± 4.30) ng/L in control group (P ＜ 0.001).The content of cytokines in gingival crevicular fluid and peripheral blood in the same group was positively related (r ＞ 0.8,P ＜ 0.001).Conclusions Pregnant women of RSA have a higher chance of getting periodontitis.The change in the level of cytokines in periodontal tissue could result in excursion of maternal intrauterine immune environment to T-helper 1 (Th1).Periodontitis was related to RSA.

Tumor angiogenesis provides adequate oxygen and nutrition for tumor development and supports tumor growth and metastasis. Stromal cell derived factor 1 (SDF-1) and its receptor C-X-C motif chemokine receptor 4 (CXCR4) in pancreatic cancer microenvironment are involved in tumor growth such as promoting tumor cell proliferation, migration, and angiogenesis. In this study, anti-CXCR4 nanobody (CXCR4 Nb) and anti-programmed cell death ligand 1 (PD-L1) &CXCR4 bispecific nanobody (PX4 BsNb) were expressed in Escherichia coli system and purified by nickel column affinity chromatography. We investigated the anti-angiogenesis activity and mechanism of CXCR4 Nb by in vivo and in vitro experiments. Ethical approval was obtained for collection of human peripheral blood mononuclear cell (hPBMC) samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University. The results showed that CXCR4 Nb at 0.1 μmol·L^-1 could effectively inhibit the proliferation and migration of human umbilical vein endothelial cells (HUVEC) promoted by pancreatic stellate cells in vitro. CXCR4 Nb and PX4 BsNb at 0.3 mg·kg^-1 obviously decreased tumor angiogenesis and inhibited the tumor growth in NOD/SCID mice, the inhibitory rates were 28.8% and 36.1%, respectively. CXCR4 Nb significantly inhibited tumor growth and angiogenesis with great safety, which provides support for application of CXCR4 Nb and anti-angiogenesis therapy of pancreatic cancer.

The purpose of this paper is to establish big data platform for drug,linking the commonly used large databases and combining with examples to show the application of platform in pharmacokinetic/pharmacodynamic data,small molecular biological treatment target molecules,drugs,targets and adverse drug reactions.The drug big data platform is used to provide original clinical trial data for the pharmacokinetic/pharmacodynamic studies of breast cancer drug and provide data for other related researches.