Advances in the comprehensive treatment of pancreatic cancer / 国际外科学杂志

Pancreatic cancer is one of the most malignant digestive cancer with high morbidity and mortality. Surgical treatment is considered the only way to cure pancreatic cancer. For resectable pancreatic cancer, the principles of "artery-frst approach" and "systematic mesopancreas dissection" have improved the increase the local radicality and reduce the local recurrence rate. For borderline resectable pancreatic cancer and locally advanced pancreatic cancer, neoadjuvant chemotherapy can be used before surgical resection. Although there are no targeted and immunotherapeutic drugs for pancreatic cancer, clinical studies on monoclonal antibodies are ongoing. Chimeric antigen receptor T cell therapy and irreversible electroporation are emerging therapies in the treatment of pancreatic cancer. In the present study, the status and progress of comprehensive treatment for pancreatic cancer are reviewed.

Cathepsin B in hepatic Kupffer cells regulates activation of TLR4-independent inflammatory pathways in mice with lipopolysaccharide-induced sepsis / 南方医科大学学报

OBJECTIVE@#To investigate the role of cathepsin B in hepatic Kupffer cells (KCs) in activating Toll-like receptor 4(TLR- 4)-independent inflammatory pathways in mice with lipopolysaccharide (LPS)-induced sepsis.@*METHODS@#Eighteen wild-type (WT) mice and 18 TLR4-knockout (TLR4) mice were both divided into 3 groups for intraperitoneal injections of a lethal dose (54 mg/kg) of LPS, LPS and CA-074(a cathepsin B inhibitor), or normal saline, and the survival of the mice were observed. Another 36 WT mice and 36 TLR4mice were also divided into 3 groups and subjected to intraperitoneal injections of normal saline, 20 mg/kg LPS, or LPS with CA-074 pretreatment.After the treatments, KCs were collected from the mice for assessing the protein level and activity of cathepsin B.The histopathological changes of the liver were observed with HE staining, and the serum levels of IL-1α, IL-1β, TNF-α and IL-18 were detected.@*RESULTS@#Compared with the WT mice,TLR4mice receiving the lethal dose of LPS had significantly longer survival time (up to 84 h) after the injection,but were still unable to fully resist LPS challenge.CA-074 pretreatment prolonged the survival time of WT mice and TLR4mice to 60 h and 132 h,respectively.In the mouse models of sepsis,20 mg/kg LPS induced significantly enhanced activity of cathepsin B without affecting its expression level in the KCs (<0.05) and increased the serum levels of the inflammatory cytokines.CA-074 pretreatment of the mice obviously lessened the detrimental effects of LPS in TLR4mice by significantly lowering cathepsin B activity in the KCs,alleviating hepatocyte apoptosis and reducing the serum levels of inflammatory cytokines.@*CONCLUSIONS@#Cathepsin B plays an important role in activating TLR4-independent inflammatory pathways in mice with LPS-induced sepsis.

Changes of Foxo3a in PBMCs and its associations with stress hyperglycemia in acute obstructive suppurative cholangitis patients.

OBJECTIVE: The levels of Foxo3a in the peripheral blood mononuclears cells (PBMCs) before and after treatment were detected in acute obstructive suppurative cholangitis (AOSC) patients to evaluate the associations between Foxo3a and stress hyperglycemia (SHG). METHODS: PBMCs were obtained from AOSC patients (n=28) on admission (AP), from patients at 1 week after cure (RP) and from healthy volunteers (HV) (n=14) to evaluate the relationship between the protein levels of Foxo3a and the serum levels of glucose. Signaling pathways, which link inflammation and glycometabolism, simultaneously affecting the expression of Foxo3a, were detected. In addition, cytokines were detected in PBMCs and AOSC mouse models, which were pre-treated with Foxo3a agonist. RESULTS: The levels of glucose and p-Foxo3a in the AP were significantly higher than those in the RP and HV, where as the levels of Foxo3a in the AP were lower than those in the RP and HV. Foxo3a levels in the AP normalized against RP were strongly negatively correlated with the glucose levels in the AP normalized against RP. The levels of sphingosine-1-phosphate receptor 2 (S1PR2) in the AP were higher than those in the RP and HV. In addition, inhibition of Foxo3a phosphorylation, coupled with the down-regulation of S1PR2, attenuated the LPS-induced inflammatory response in the PBMCs and AOSC mouse models. CONCLUSIONS: Foxo3a is correlated with the dysregulation of glucose homeostasis in the pathogenesis of AOSC-induced sepsis by inhibiting the activation of PI3K/Akt-S1PR2 and NF-κB pathways, hinting at a switched role and therapeutic potentialities in the early stage of sepsis.

Role of Pellino-1 Overexpression on Ubiquitin of Tumor Necrosis Factor Receptor-associated Factors 3 and MAPK Signaling Pathway in Endotoxin-tolerant Kupffer Cells / 中山大学学报(医学科学版)

[Objective]To investigate the effect of pellino-1 gene overexpression by lentivirus vector on the ubiquitin of tumor necrosis factor receptor-associated factors 3 (TRAF3) and the activation of mitogen-activated protein kinases (MAPK) signaling pathway in endotoxin-tolerant kupffer cells (KCs).[Methods]Isolated KCs of C57BL/6 mouse were randomly divided into two groups:control group,which transfected with control lentivirus vector for 48 h,then pretreated with 10 ng/mL lipopolysaccharide (LPS)for 24 h,and next treated with 300 ng/mL LPS;overexpression group,which transfected with pellino-1 gene overexpression lentivirus vector for 48 h,then pretreated with 10 ng/mL lipopolysaccharide(LPS)for 24 h,and next treated with 300 ng/mL LPS. The protein expressions of pellino-1,K48-Ub,TRAF3,p38,p-p38,c-Jun N-terminal kinase(JNK)and p-JNK were analyzed by Western blot. The level of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in superna-tants were measured by enzyme linked immunosorbent assay(ELISA).[Results]Compared with control group,the protein expres-sions of pellino-1,K48-Ub,p-JNK and p-p38 and the levels of IL-1β(P < 0.05),TNF-α(P < 0.05)in supernatants was in-creased in overexpression group,while the protein levels of TRAF3 and the levels of IL-10(P < 0.05)in supernatants were de-creased.[Conclusion]Overexpression of pellino-1 can promote TRAF3 K48 ubiquitination degradation,decrease the protein expres-sion of TRAF3,activate the downstream MAPK signaling pathway,and thus impair the formulation of endotoxin tolerance.

Stress ulcer survey of anti-ulcerative drug use in patients undergoing arthroscopic operation / 实用医学杂志

Objective To investigate anti-ulcerative drug use in patients undergoing arthroscopic operation against stress ulcer. Methosds A total of 297 patients undergoing arthroscopic operation during Jan. to Aug. 2013 in our hospital were recruited and retrospectively analyzed with Excellspreadsheet. Results Among 297 patients in the study, ninety-four patients (31.6%) used AUD before operation, most (94.9%) administered by intravenous, and drug utilization index was 1.35. Ninety-eight point nine patients used proton pump inhibitors (PPIs) in which Lansoprazole was prescribed most. Conclusion This study highlights the overuse of PPIs in patients undergoing arthroscopic operation.

Expression and purification of fusion protein CTP-SOD in Pichia pastoris and antioxidant capacity analysis / 生物工程学报

Cytoplasmic transduction peptide (CTP) is a newly designed transduction peptide, by which special molecules can be carried out and localized into cytoplasmic compartment. Superoxide dismutase (SOD) is a protein that is difficult to go into cytoplasm. In this study, CTP-SOD fusion gene was amplified from human cDNA by PCR, and the active recombinant protein was successfully expressed in Pichia pastoris. HeLa cells pretreated with CTP-SOD showed a significantly improved survival against the pyrogallol-induced oxidative stress, suggesting CTP-SOD could cross the cell membrane more efficiently and protect cells from oxidative stress.

The impact of night work near the day of ovulation on outcome of pregnancy / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of night work near the day of ovulation on outcome of pregnancy.</p><p><b>METHODS</b>Daily early morning urine samples were collected from eligible shift women workers, and human chorionic gonadotropin(hCG), follicle-stimulating hormone(FSH), the urinary steroid metabolites of estrogen and progesterone(PDG, E1C) were measured to confirm the day of ovulation and early fetal loss(EFL). Questionnaires were used to know workshift, other occupation exposures, and related information.</p><p><b>RESULTS</b>12 clinical spontaneous abortion(SAB), 18(EFL) and 44 clinical living birth were analyzed in relation to SAB, EFL and night shift near the day of ovulation by using single factor and multi-factor logistic regression. The result showed that night shift on the day of ovulation and the day before or after ovulation was related with SAB both in single- and muti-factorial analysis(single factor: OR = 2.48, 95% CI 1.10-5.60; multi-factor; OR = 3.90, 95% CI 1.28-11.90).</p><p><b>CONCLUSION</b>Night shift near the day of ovulation may be related to SAB.</p>

PRELIMINARY STUDY ON ANTI-IMPLANTATION AND ANTI-EARLY FERTILITY EFFECT OF CHINESE HERBAL MEDICINE HERBA LEONURI(益母草) UPON MICE / 西安交通大学学报(医学版)

Mice were orally administered Herba Leonuri decoction once 0.1 ml(containing about 50 mg drz drug of Herba Leonuri decoction) totally 4 or 5 times.The results showed that Herba Leonuri exhibits some anti-implanatation and antiearly fertility effect on mice.The effect mechanism and toxity were discussed on the basis of the obtained experimental data.