[Blastic plasmacytoid dendritic cell tumor treated with DVT regimen: a case report and literature review].

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy, there is no standard treatment and the prognosis is very poor. Affiliated Zhongshan Hospital of Dalian University report a case of 85-year-old BPDCN male patient treated with DVT regimen (decitabine combined with Venetoclax and thalidomide) and achieved complete remission. The patient with skin nodules and the pathology diagnosed BPDCN, the next generation sequencing of skin nodules showed mutations of IDH2 and ASXL1. DVT (decitabine combined with Venetoclax and thalidomide) has significant efficacy with rapid and deep remission for BPDCN, and the adverse effects is less, especially suitable for elderly patients who cannot tolerate intense chemotherapy.

[The anti-proliferative and anti-inflammatory mechanisms of JAK1 inhibitor SHR0302 versus Ruxolitinib in SET2 cell line and primary cells].

Objective: To explore the effects and molecular mechanism of the selective JAK1inhibitor SHR0302 and Ruxolitinib on myeloproliterative neoplasms (MPN) cell line SET2 and primary cells in vitro. Methods: Cell proliferation was detected by CCK8 kit. Colony forming experiment was conducted to evaluate erythroid burst colony formation unit (BFU-E) of primary cells from MPN patients. Multi-factor kits were used to detect six inflammatory cytokines. Phosphorylated proteins of Jak-Stat signaling pathway were tested by Western blot. Results: At different time points after treated with SHR0302 and Ruxolitinib, the inhibition of cell proliferation was dose dependent by both drugs (P<0.01) . The inhibitory rates of 2.5 µmol/L SHR0302 and 0.1 µmol/L Ruxolitinib on SET2 cells for 72 h were comparable, i.e. (59.94±0.60) % and (64.00±0.66) %, respectively, suggesting that the inhibitory effect of SHR0302 was weaker than that of Ruxolitinib. Similarly, both SHR0302 and Ruxolitinib inhibited BFU-E in primary marrow cells from MPN patients in a dose-dependent manner. SHR0302 1.0 µmol/L produced similar degree of inhibition compared to Ruxolitinib 0.2 µmol/L. Except IL-12, the expression of other 5 cytokines (IL-6, TNF-α, IL-1ß, IL-2, IL-8) was significantly inhibited by 1.6 µmol/L SHR0302 in SET2 cells at 24 h (P<0.01) , while Ruxolitinib 1.0 µmol/L had the same effect. Several phosphorylated molecules of Jak-Stat signaling pathway were significantly inhibited by SHR0302 in SET2 cells only for 3 h. P-stat1 (Tyr701) , p-stat3 (Tyr705) were down-regulated when treated with SHR0302 1.0 µmol/L (P<0.05) , p-jak1 (tyr1022/1023) and p-stat5 (Tyr694) were inhibited at 5.0 µmol/L (P<0.05) . Ruxolitinib significantly inhibited the downstream STAT protein at 0.1 µmol/L. Again, the inhibitory effect of SHR0302 on protein expression was weaker than that of Ruxolitinib. Conclusion: SHR0302 can effectively inhibit the proliferation of MPN cell line and patients' primary cells, as well as the expression of inflammatory factors. The molecular mechanism is possibly related to the down-regulation of phosphorylated proteins of Jak-Stat signaling pathway. Overall, the anti-proliferative and anti-inflammatory effects of SHR0302 are weaker than those of Ruxolitinib.

[Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma].

Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender(P=0.215), age(P=0.828), primary tumor site(P=0.927), LR(P=0.126), DFS(P=0.710), and OS(P=0.402) between the two groups, while the RR(χ(2)=5.640, P<0.05) and distant metastasis(χ(2)=10.363, P<0.01) showed significant differences between the two groups. Conclusion: The ICT+ PND+ CCRT treatment model has benefit on regional control of locally advanced head and neck squamous cell carcinoma.

[The 459th case: arthralgia, fever, rash, and thrombocytopenia].

The differential diagnoses of reactive arthritis presenting as arthralgia should be considered as diverse disorders, especially when the symptoms cannot be fully explained by some definite diseases. Do not ignore the indication of bone marrow aspiration. We reported a 50-year-old woman who complained of arthralgia, recurrent fever and rash 9 months ago. Laboratory exams showed mild leukopenia, anemia, thrombocytopenia and increased lymphocyte proportion. She was treated with glucocorticoid after the diagnosis of connective tissue disease was suspected. Until platelet count abruptly decreased to very low level, the final diagnosis of acute lymphoblastic leukemia was made through bone marrow morphology, flow cytometry, and chromosome examination. Therefore, a small number of leukemia is not easily diagnosed by routine operations. Thus when diagnoses are not determined with recurrent symptoms, cautious observation and further examination are required to avoid misdiagnoses or missed diagnoses of acute leukemia.

[Peripheral blood circulating tumor cells in local advanced head and neck squamous cell carcinoma].

Objective: To investigate the value of detecting circulating tumor cells (CTCs) in patients with local advanced head and neck squamous cell carcinoma (LAHNSCC). Methods: Twenty cases of LAHNSCC and eight healthy cases as the negative control were collected. The clinicopathological factors were evaluated. The LAHNSCC CTCs were enriched by specific antibody nanofluidic chip immunoassay using CytoSorter CTCs sorting system. LAHNSCC CTCs were identified by immunofluorescence staining. The relationships between CTCs and the clinicopathological features of LAHNSCC were analyzed. The numbers of CTCs were monitored and compared two weeks after inductive chemotherapy and at the end of the treatment. Results: CTCs were detect in 15 (75%) 20 patients with LASHNCC, with an average number of 22.4 CTCs. There was a correlation between the numbers of CTCs and age or N staging (P<0.05). Among the 15 cases with CTCs, 13 cases received inductive chemotherapy, for whom CTCs were detected again after inductive chemotherapy in all of these 13 patients, with an average number of 9.5 CTCs. Ten of the fourteen cases (71.4%) were still CTCs detected After whole treatments CTCs were detected in 14 patients, of them, 10 (71.4%) patients showed positive CTCs, with an average 1.6 CTCs. The numbers of CTCs decreased after either inductive chemotherapy or the whole treatment. The number of detected CTCs after whole treatment decreased nearly to background levels. Conclusions: CTCs have a high detection rate in the peripheral blood of patients with LAHNSCC, especially in patients ≥60 years old and with ≥ N2 stage before treatment. Real-time detection of dynamic change of CTCs may assist to evaluate therapeutic effect.

Differential expression of CYB5A in Chinese and European pig breeds due to genetic variations in the promoter region.

Cytochrome b5 (CYB5A) is an important electron transfer protein with homologues in a number of different organisms. In pigs, CYB5A is related to boar taint because of its role in androstenone biosynthesis. To determine the variety of CYB5A expression in pig breeds, genetic variations in the porcine CYB5A promoter region in both Chinese and European pig breeds were examined. Three single nucleotide polymorphisms (NC_010443.4:g.165901487delG, g.165901767T>C and g.165902078C>T) were identified in the porcine CYB5A promoter region. These SNPs occurred in different frequencies in Chinese and European pigs. Chinese pigs were primarily haplotype B (denoted as delG-C-T: the position of nt 165901487 of the CYB5 gene is a G deletion, nt 165901767 is C and nt 165902078 is T), except for Licha black pigs, which were primarily haplotype A (denoted as G-T-C: nt 165901487 is G, nt 165901767 is T and nt 165902078 is C), similar to European pigs. Quantitative PCR data from liver tissues demonstrated that haplotype B individuals had higher CYB5A expression than did those with haplotype A. This was confirmed by in vitro cell transfection assays, in which haplotype B individuals had higher reporter activity than did those with haplotype A. In silico analysis predicted that Myc-associated zinc-finger protein (MAZ) is a potential transcription factor at position 165901767. Electrophoretic mobility shift assays showed this polymorphism affects the stable binding of transcription factors to the CYB5A promoter, which in turn affects the expression levels of this gene. Therefore, this variation of the porcine CYB5A promoter region may explain the differences in androstenone accumulation between Chinese and European pig breeds and may also prove useful as a genetic marker to distinguish the origin of different pig breeds.

Effect of SB203580 on pathologic change of pancreatic tissue and expression of TNF-α and IL-1ß in rats with severe acute pancreatitis.

OBJECTIVE: This study aimed to investigate the effect of SB203580 which is the inhibitor of p38 mitogen-activated protein kinase on pathologic change of pancreatic tissue and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1b) in rats with severe acute pancreatitis (SAP), Hematoxylin-eosin (HE) staining and immunohistochemistry were carried out in the present study. METHODS: Forty-five male Wistar rats were divided into three groups: the SAP group (N=15), SB203580-treated group (SB group) (N=15), and the control group (N=15). Severe acute pancreatitis was induced by injection of sodium taurocholate into the pancreatic duct. For SB203580-treated group, SB203580 were administered via intraperitoneal injection (10 mg/kg). Serum amylase activity was measured 6, 12 and 24 hours respectively after the operation. The pancreas tissue were stained with HE for histopathological evaluation and the expression of TNF-α and IL-1b in the pancreatic tissue were determined through inferior vena cava. RESULTS: The results show that the level of amylase in SAP group was higher than that in the other groups. Further, the pancreas tissues of SB group rats were observed more mildly edematous, hemorrhagic and with monocytes infiltration. Based on immunohistochemical staining, the expression of TNF-α and IL-1ß in SAP rats were significantly increased than those of the control group. However, those of SB203580-treated group were more significantly reduced than those of SAP group (p < 0.05). CONCLUSIONS: Those data suggest that SB203580, down regulating the expression of pro-inflammatory mediators such as TNF-α and IL-1ß, then through p38 MAPK signaling pathway inhibition, plays an important role in the treatment of SAP.

Prognostic and predictive significance of plasma hepatocyte growth factor and carcinoembryonic antigen in non-small lung cancer after surgery.

OBJECTIVES: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a polypeptide growth factor with a number of biologic activities, including cell scattering, stimulation of cell motility, mitogenesis, morphogenesis, angiogenesis, and cellular invasiveness, it is thought to be important in the growth and spread of several carcinomas. We assessed whether preoperative plasma levels of HGF and carcinoembryonic antigen (CEA) can enhance the accuracy of standard models for predicting pathologic features and clinical outcomes. PATIENTS AND METHODS: The study comprised 45 consecutive patients treated with surgery for clinically localized non-small-cell lung cancer. HGF and CEA were measured using the commercially available immunoassay. Multivariate logistic regression was used to assess the relationship between plasma HGF/CEA and pathologic features. Multivariate Cox regression was used to predict disease recurrence. RESULTS: Patients with lung squamous cell cancer (SCC) more frequently had higher plasma HGF, whereas CEA levels were significantly elevated in patients with non-SCC histology. Preoperative plasma HGF and CEA levels were not the independent predictors of overall survival. CONCLUSIONS: Preoperative plasma levels of HGF and CEA are not the independent predictors of non-small lung cancer disease recurrence and metastasis after surgery; HGF is a predictor of lung squamous cell cancer. Use of HGF may help in therapeutic decision-making and estimate the histological type of NSCLC.