Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.
Animals ; Chloroquine ; toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Etanercept ; therapeutic use ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pruritus ; chemically induced ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Receptors, Tumor Necrosis Factor, Type I ; deficiency ; genetics ; Receptors, Tumor Necrosis Factor, Type II ; deficiency ; genetics ; Signal Transduction ; drug effects ; Skin ; drug effects ; metabolism ; Spinal Cord ; drug effects ; metabolism ; Thalidomide ; therapeutic use ; Time Factors ; Tumor Necrosis Factor-alpha ; adverse effects ; genetics ; metabolism ; p-Methoxy-N-methylphenethylamine ; toxicity

Objective To investigate the mutations of epigenetic regulation factor ASXL1 gene in myelodysplastic syndrome(MDS).Methods Mutation analysis of ASXL1 gene in 53 de novo MDS patients and 20 healthy persons was performed by using polymerase chain reaction(PCR)followed by sequence analysis at DNA level.The clinical and laboratory characteristics were compared in MDS patients with ASXL1 gene mutation and ASXL1 wild type.ASXL1 mutation in mRNA level was detected by using reverse transcription PCR(RT-PCR)followed by sequence analysis.Results ASXL1 gene mutations were observed in 9 cases(16.9%)of 53 MDS patients.6 mutation types were detected,including 4 frameshift mutations types(2 cases with p.Glu635ArgfsX15,3 cases with p.Gly646TrpfsX12,1 case with p.Ala640GlyfsX14 and 1 case with p.Gly790TrpfsX10)and 2 nonsense mutation types(1 case with p.Gln1063X and 1 case with p.Gln695X).All the mutations were heterozygous,and p.Gly790TrpfsX10 and p.Gln695X were new mutation types.In addition,a single nucletide polymorphism(SNP)p.Gly652Ser was also detected in 4 cases with MDS.5 cases of p.G652S SNP and 1 case of p.Leu1173Leu SNP were detected in 20 healthy people.Frameshift mutation(p.Gly646TrpfsX12)could be detected at mRNA level by using RT-PCR.Differences were not observed in red blood cell counts,white blood cell counts,platelet counts,hemoglobin levels,reticulocyte,neutrophil granulocyte,the peripheral blood lymphocytes percentage,T-cell subsets in the peripheral blood,the proportion of primitive cell in the marrow and MDS types between the patients with ASXL1 gene mutation and ASXL1 wild type patients(P >0.05).Conclusion There is a high frequency of ASXL1 gene mutation in MDS patients,which can be detected at mRNA level.

Objective To evaluate the effect of dexmedetomidine on the tolerance to endotracheal tube, on agitation and other complications of patients undergoing transnasal transsphenoidal pituitary tumor resection.Methods One hundred and twenty-four patients aged 18-65 years, ASA physical status Ⅰ or Ⅱ) were randomly assigned to dexmedetomidine group (group D, n=60) and control group (group C, n=62).Group D were given intravenous infusion of dexmedetomidine during the operation and group C with saline.The extubation time, observation time in the post-anesthesia care unit (PACU), the incidence of emergence agitation, cough, postoperative sore throat and hoarseness were analyzed.Results The extubation time [(29.7±11.5) min vs (22.2±8.5) min] and the length of stay in PACU [(41.5±11.8) min vs (35.3±10.0) min] were significantly longer in group D than those in group C (P<0.05).There was no significant difference of the incidence of emergence agitation (26.3% vs 32.3%), cough (49.1% vs 53.2%), postoperative sore throat (14.0% vs 24.2%) and hoarseness (10.5% vs 19.4%) between two groups.Conclusion Intraoperative intravenous administration of dexmedetomidine can prolong the extubation time and the length of stay in PACU.The incidence of agitation, cough, postoperative sore throat and hoarseness was not affected by dexmedetomidine.

Objective To evaluate the treatment outcome, prognostic factors, radiation dose, and toxicities in patients with early-stage primary diffuse large B-cell lymphoma of Waldeyer's ring (WR-DLBCL) treated with intensity-modulated radiotherapy (IMRT).Methods This study included 80 patients with a confirmed diagnosis of stage Ⅰ-Ⅱ primary WR-DLBCL who were admitted to our hospital from 2008 to 2015.Only 3 patients received radiotherapy alone, and the other patients received radiotherapy and chemotherapy.After chemotherapy, 24 patients achieved complete remission (CR), and 53 patients achieved partial remission (PR).IMRT was given to the primary lesion and cervical lymphatic drainage region.Survival analysis was performed using the Kaplan-Meier method and log-rank test.The Cox model was used for analysis of prognostic factors.The toxicities were scored using the RTOG criteria.Results The median follow-up was 64 months.The 5-year locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) rates were 94%, 88%, and 84%, respectively.The dose-volume histogram showed that the maximum, mean, and minimum doses to primary gross tumor volume were 54.47 Gy, 52.27 Gy, and 38.83 Gy, respectively.Prognostic analysis showed that age>60 years and increased lactate dehydrogenase (LDH) were influencing factors for OS (P=0.009 and 0.002), and that aged>60 years, IPI ≥2, and increased LDH were influencing factors for PFS (P=0.001, 0.035, and 0.007).Among all patients, 12, 53, and 8 experienced grade 1-3 radiation-induced acute oral mucositis, respectively, and 16 and 13 experienced grade 1 and 2 xerostomia as the late toxicity, respectively.Conclusions For patients with early-stage primary WR-DLBCL, IMRT results in satisfactory OS, PFS, and LRC and has tolerable early or late radiation-induced toxicities.

Objective To explore the value of the plasma miR-193a-5p level on diagnosis and monitoring the response to treatment in acute myeloid leukemia (AML). Methods Peripheral blood samples were obtained from AML patients enrolled in hematology department of the Second Hospital of Shanxi Medical University from July 2015 to December 2015, including 30 de novo AML patients, 9 patients in complete remission (CR) and 6 patients in relapse. Peripheral blood samples from 15 healthy people were randomly choosed as the health control group. Plasma miR-193a-5p expression levels were detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Results The plasma miR-193a-5p relative expression level of AML patients group [0.465 6 (0.103 1-5.000 2)] was obviously lower than that of health control group [0.766 1 (0.052 1-3.134 4)] (U= 122, P= 0.018 7). The plasma miR-193a-5p relative expression levels of de novo group and relapse AML group were significantly lower than those of CR group and health control group (P<0.05), and there was no significant difference between the CR group and health control group (U= 56, P= 0.511 9). No significant correlation was found between the plasma miR-193a-5p level and age, gender, blast percentage of the bone marrow, peripheral blood leukocyte count, platelet count, CD34+cells'percentage and so on. Conclusion The decreased plasma miR-193a-5p expression level can be served as a new and noninvasive biomarker for the evaluation of diagnosis and treatment in AML.

Objective To observe the clinical efficacy ofXing Nao Kai Qiao (brain-awakening and orifice-opening) needling plus thunder-fire moxibustion in treating vertebrobasilar ischemia.Method Fifty-five patients with vertebrobasilar ischemia were randomized into a treatment group of 26 cases and a control group of 29 cases. The treatment group was intervened byXing Nao Kai Qiao needling plus thunder-fire moxibustion, while the control group was by oral administration ofYangxue Qingnao granules. The blood flow of vertebrobasilar arteries were observed by using ultrasonic Doppler blood-flow detector before and after intervention, and the clinical efficacies were compared between the two groups.Result The recovery and markedly-effective rate and total effective rate were respectively 61.5% and 96.2% in the treatment group, versus 34.5% and 89.7% in the control group, and the differences were statistically significant (P<0.01,P<0.05). The VS and VD of vertebral arteries and VS of basilar arteries were significantly changed after intervention in the treatment group (P<0.05). The VS of basilar arteries was significantly changed after intervention in the control group (P<0.05). After treatment, The VS of vertebral and basilar arteries in the treatment group was significantly different from that in the control group (P<0.05).ConclusionXing Nao Kai Qiao needling plus thunder-fire moxibustion is an effective approach in treating vertebrobasilar ischemia.

Mechanisms of perineural invasion may include the effect of microenvironment, the interaction of cancer cell and nerve, the action of stromal cell and cancer cell, signal transduction between the cancer cell and nerve by the involvement of the neurotrophin and its receptor, chemokines and its receptor.Its impacts on early cervical cancer include surgery, adjuvant therapy, prognosis and so on.

Objective To investigate the epidemiological and clinical characteristics and prognosis of 31 children with hand foot and mouth disease(HFMD) complicated with acute flaccid paralysis(AFP).Methods Thirty-one HFMD children complicated with AFP served as study objective,who were admitted to Tangshan Maternity and Children Health Hospital from Jun 2011 to Dec 2014.The clinical manifestations and follow-up outcomes of 31 children with HFMD followed by AFP were retrospectively reviewed.Results Participants in this study consisted of 31 children(16 males,15 females,age from 3 months to 9 years) who met the criteria for HFMD with AFP.Among the 31 cases,27(87.1％)cases were less than 3 years old and 29(93.5％) cases were from countryside.Eleven cases (35.5％)were infected by enterovirus 71,1 case (3.2％) was infected with coxsackieviruses A16 and 19 cases(61.3％) were infected by other enteroviruses.AFP developed(7.1 ±2.9) days after the onset of fever and progressed to maximum severity within 1-2 days.All of the cases presented with fever and skin rash,38.7％ cases presented with limbs tremor and 87.1％ cases presented with startle and skip.Besides AFP of limbs, 100％ cases complicated with encephalitis.Thirty-one cases showed poliomyelitis-like syndrome(20 cases with one flaccid limb,5 cases with lower limbs,4 cases with upper limbs and 2 cases with left hemiplegia).In these cases, the muscle power varied from level 0 to level 4.The muscle strengthen and muscle tone in 21 patients were recovered within 2 weeks,and the other cases showed recovery 2 to 3 weeks later.After four weeks, the muscle strengthen in 19 cases recovered to 5 level(10 cases with single lower limb,5 cases with single upper limb,3 cases with two lower limbs and 1 case with two upper limbs).Conclusion HFMD complicated with AFP most commonly occurs in children aged less than 3 years old.The majority of cases were from countryside.Enterovirus 71 is still relatively common pathogen.All the 31 cases complicated with encephalitis.Cases clinically presented one flaccid limb, lower limbs, upper limbs and hemiplegia.AFP may be to some degree reversible in HFMD cases.In most cases described here, paralysis occurred in a single lower extremity and recovered more rapidly than those with two fimbs affected or with single upper extremity impairment.

Objective To study the characteristic findings of computer tomography (CT) and magnetic resonance imaging (MRI) in hepatobiliary cystadenocarcinoma.Methods CT,MRI and clinical data were analysed retrospectively.Plain,dynamic CT and MRI were performed in all patients.Results There were 8 patients,7 female,1 male,aged 48-74 years,with a median age of 58.Five lesions were in the left liver,and 3 lesions were in the right liver.One lesion was multilocular cysts with septations.Seven lesions were solitary.The lesions showed low or mixed density on plain CT.Two cysts showed evidence of hemorrhage,while 3 cysts showed fluid levels.There were different signal intensities in the cystic wall nodules which could appear as slightly low intensity on T1WI or slightly high intensities on T2WI.The cyst wall and septations appeared as slightly low intensity on T1WI and T2WI.The cystic fluid signal intensity changed with liquid ingredients.The nodularities showed obviously high signal intensity on DWI,and the fluid showed slightly high signal,while the cystic wall and separations showed slightly low signal intensity.On CT and MRI dynamic enhancement scanning,the nodularities showed obvious enhancement on the arterial phase,while the cystic wall and separations showed no enhancement.The nodularities showed persistent enhancement on the portal venous and delayed phases while the cystic wall and separation showed slight enhancement.Conclusions Hepatobiliary cystadenocarcinoma showed characteristic features on MSCT and MRI.MSCT combined with MR is an important method in the diagnosis and differential diagnosis of hepatobiliary cystadenocarcinoma.