Biliary tract cancer (BTC) is a disease entity comprising diverse epithelial tumors with features of cholangiocyte differentiation, and it includes cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Depending on its anatomical location, cholangiocarcinoma is categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Nearly two-thirds of patients with biliary tract cancer present with advanced disease at diagnosis and in 68-86% of resections the cancer eventually recurs either locoregionally or at a distance. Chemotherapy is the first-line therapy for advanced or recurrent BTC. With the development of next-generation sequencing (NGS)-guided molecular targeted therapy, more options are available for treatment of advanced BTC. Chemotherapy, and especially a triplet regimen based on gemcitabine/cisplatin/nab-paclitaxel, has had the most significant effect, and fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) combined with bevacizumab is promising. Molecular targeted therapy should be based on genome sequencing and appears essential to precision medicine. Fibroblast growth factor receptor (FGFR) inhibitors and isocitrate dehydrogenase (IDH) inhibitors are promising emerging targeted therapies mainly for iCCA. Other targeted therapies such as anti-human epidermal growth factor receptor-2 (HER2) therapies, MEK inhibitors, BRAF inhibitors, and poly ADP ribose polymerase (PARP) inhibitors had tentatively displayed efficacy. Further evaluations of combination strategies in particular are needed. An immune checkpoint inhibitor (ICI) alone is less efficacious, but an ICI in addition to chemotherapy or radiotherapy has resulted in a response according to many case series. However, ICIs are still being evaluated in several ongoing studies. Combination therapies have garnered attention because of interactions between signaling pathways of carcinogenesis in BTC.
Tetramethylpyrazine is the main component of Ligusticum chuanxiong. Studies have found that tetramethylpyrazine has a good protective effect against cardiovascular diseases. In the heart, tetramethylpyrazine can reduce myocardial ischemia/reperfusion injury by inhibiting oxidative stress, regulating autophagy, and inhibiting cardiomyocyte apoptosis. Tetramethylpyrazine can also reduce the damage of cardiomyocytes caused by inflammation, relieve the fibrosis and hypertrophy of cardiomyocytes in infarcted myocardium, and inhibit the expansion of the cardiac cavity after myocardial infarction. In addition, tetramethylpyrazine also has a protective effect on the improvement of familial dilated cardiomyopathy. Besides, the mechanisms of tetramethylpyrazine on blood vessels are more abundant. It can inhibit endothelial cell apoptosis by reducing oxidative stress, maintain vascular endothelial function and homeostasis by inhibiting inflammation and glycocalyx degradation, and protect vascular endothelial cells by reducing iron overload. Tetramethylpyrazine also has a certain inhibitory effect on thrombosis. It can play an anti-thrombotic effect by reducing inflammatory factors and adhesion molecules, inhibiting platelet aggregation, and suppressing the expression of fibrinogen and von Willebrand factor. In addition, tetramethylpyrazine can also reduce the level of blood lipid in apolipoprotein E-deficient mice, inhibit the subcutaneous deposition of lipids, inhibit the transformation of macrophages into foam cells, and inhibit the proliferation and migration of vascular smooth muscle cells, thereby reducing the formation of atherosclerotic plaque. In combination with network pharmacology, the protective mechanism of tetramethylpyrazine on the cardiovascular system may be mainly achieved through the regulation of phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), hypoxia-inducible factor 1(HIF-1), and mitogen-activated protein kinase(MAPK) pathways. Tetramethylpyrazine hydrochloride and sodium chloride injection has been approved for clinical application, but some adverse reactions have been found in clinical application, which need to be paid attention to.
Background: The changes before and after fluid resuscitation in patients with septic shock and their relationship with prognosis have rarely been reported. Objectives: We aimed to observe the correlation between pulmonary vascular permeability index (PVPI), shock index (SI), and severity of septic shock. Methods: This case-control study retrospectively analyzed the clinical data of 154 patients with septic shock treated at our hospital (Weifang, China) from October 2016 to October 2018. They were divided into a survival group or a death group according to the 28-day prognosis. Univariate analysis was performed for vital signs, the acute physiology and chronic health evaluation II (APACHE-II) score, the sequential organ failure assessment (SOFA) score at admission, SI at admission (SI1), SI at 3 h after fluid resuscitation (SI2), PVPI at admission (PVPI1), PVPI at 3 h after fluid resuscitation (PVPI2), and lactate clearance rate (LCR). The correlations of PVPI and SI with the APACHE-II score, SOFA score, and LCR were analyzed by plotting the receiver operating characteristic curves. Results: Among the 154 cases, 70 survived after 28 days and 84 died. We observed that SI1, SI2, PVPI1, PVPI2, APACHE-II score, and SOFA score were significantly lower in the survival group than in the death group, while LCR was significantly higher (P < 0.05). Also, SI1, SI2, PVPI1, and PVPI2 were positively correlated with APSCHE-II and SOFA scores of patients with septic shock, but negatively correlated with LCR (P < 0.05). Moreover, SI2 predicted the prognosis of patients with septic shock significantly better than SI1, PVPI1, and PVPI2 did. When SI2 was 1.22, the Youden index was 0.822, the sensitivity was 91.23%, the specificity was 89.47%, the positive predictive value was 0.912, and the negative predictive value was 0.924. The positive and negative likelihood ratios were 0.897 and 0.375, respectively. Conclusions: Based on the study, SI after fluid resuscitation was more valuable for evaluating the prognosis of patients with septic shock than SI at admission, as well as PVPI values at admission and after fluid resuscitation.
Histone deacetylases (HDACs) remove acetyl groups from lysine residues of histones and the deacetylation allows for tighter electrostatic interactions between DNA and histones, leading to a more compact chromatin conformation with limited access for transactivators and the suppression of transcription. HDAC mRNA and protein overexpression was observed in endometrial and ovarian cancers. Numerous in vitro studies have shown that HDAC inhibitors, through their actions on histone and nonhistone proteins, are able to reactivate the tumor suppressor genes, inhibit cell cycle progression and induce cell apoptosis in endometrial and ovarian cancer cell cultures. Results from mouse xenograft models also demonstrated the potency of HDAC inhibitors as anticancer reagents when used as single agent or in combination with classical chemotherapy drugs.
Objective
To investigate the diagnosis and treatment of autoimmune pancreatitis (AIP).
Methods
The clinical data of 25 patients with AIP who were admitted to the Cancer Hospital of Tianjin Medical University between January 2009 and December 2013 were retrospectively analyzed. Patients received the test of serum γ-globulin and IgG4 and abdominal imaging examination. The revised HISORt or results of postoperative pathological examination were performed as diagnostic criteria. Patients who were unable to tolerate surgery were treated by oral prednisone. The focal masses were apparent in the pancreas by imaging examination, which cannot exclude the possibility of malignancy because of ambiguous pathologic characters of masses. Patients who received ineffective hormonal therapy and were able to tolerate surgery underwent surgery. All the patients were followed up by outpatient examination and telephone interview up to December 2014.
Results
Primary symptoms: jaundice was detected in 16 patients, obvious weight loss (weight loss >10% standard body mass) in 4 patients, chronic diarrhea (duration of diarrhea >2 months or 2 weeks
The aim of this study was to select specific targets locating on the surface of epithelial ovarian cancer cells.Peptide phage display library was used to isolate specific ligand to ovarian cancer cell receptors. The diluted library was incubated with the normal ovarian cells that primarily cultured before hand, and then the supernatant of nonbonding phage was added to the first epithelial ovarian cancer cell line A2780. Phage that binds to the cell surface are eluted and then amplified to be used in the next round. After the third round of panning, the elute was used as input phage for the next cell line biopanning. Four epithelial ovarian cancer cell lines were used one by one in this way. Finally the positive clones were identified by ELISA assay. Sequencing analysis was carried out for further identification.10 positive clones were chosen and one was regarded as target clone. A candidate sequence (YYGLAEVDAGGS) was identified by amino acid sequence assay.The phage peptide library provides an efficient selection system for searching special targets locating on the cell surface.
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