Objective A phase Ⅱ trial of anti-programmed death-1 (PD-1) monoclonal antibody CT-011,an anti PD-1 humanized monoclonal antibody combined with rituximab therapy in patients with relapsed follicular lymphoma (FL) were conducted.Methods In order to evaluate the safety and efficacy of CT-011,the impacts of CT-011 on immune cells both from the peripheral blood (PB) samples and tumor microenvironment were examined.PB and core needle biopsies from involved lymph nodes were collected prior to and on day 14 after the first infusion of CT-011.PB mononuclear cells (PBMC) were analyzed by multiparametric flow cytometry to determine various immune cell subsets.Whole genome gene expression profiling (GEP) was performed on core needle biopsies.Results A significant increase in the absolute number of PB immune cells were observed in day 14 samples compared with baseline including total lymphocyte count (P ＜ 0.01),CD+3 T cells (P =0.01),CD+4 T cells (P ＜ 0.01).Comparison of GEP from core needle biopsies obtained pretreatment and day 14 (n =8 pairs) showed up regulation of several genes associated with T cell activation.Conclusion Administration of CT-011 was associated with increase in the numbers of CD+4 T cells and resulted in activation of T cells in the PB and the tumor microenvironment in FL.These results provide insight into the mechanism of action of CT-011 and offer a predictive biomarker for selection of patients for future clinical trials with this class of agents in FL.

Objective:To evaluate the effectiveness of esketamine during perioperative anesthesia for acute and chronic pain after cesarean section.Methods:One hundred and fifty patients scheduled for elective cesarean section under spinal anesthesia were randomly assigned into 2 equal groups ( n=75) using a random number table: esketamine group (group E) and control group (group C). Subarachnoid block was administered with 9-11 mg of hyperbaric bupivacaine with 0.33% glucose concentration. After the delivery of the fetus, 0.15 mg/kg (1 mg/ml) esketamine was pumped intravenously for 30 min in the group E, while the same dosage of normal saline was administered in the group C. Furthermore, patients received an intravenous patient controlled intravenous analgesia (PCIA) pump after surgery (100 μg sufentanil + 1.25 mg/kg esketamine + 8 mg ondansetron for the group E, 100 μg sufentanil + 8 mg ondansetron for the group C). Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded in the initial time of esketamine administration, and 5, 15 min, and 30 min after administration. The pain Numerical Rating Scale (NRS) score at rest and during coughing were recorded at 2, 6, 12, 24 h and 48 h after surgery. The first analgesic time and cumulative sufentanil consumption were recorded at 0-12 h, 12-24 h, 24-48 h, 0-24 h and 0-48 h after surgery. Moreover, we recorded the incidence of chronic pain at 3 and 6 months after surgery. Results:There were no significant differences in HR, SBP and DBP between the two groups immediately after administration of esketamine and 5, 15 min and 30 min after administration (all P>0.05). At rest or during coughing, the pain NRS score were significantly lower at 2, 6 h, and 12 h postoperatively in group E compared to group C (all P<0.05). The time to first analgesia in group E was significantly longer than the group C [(176.8±18.3)min vs (148.5±16.9)min, P<0.05]. The cumulative sufentanil consumption was significantly lower in group E during 0-12 h, 12-24 h, 0-24 h and 0-48 h postoperatively than in group C (all P<0.05), but there was no statistical significance between the two groups at 24-48 h ( P>0.05). There were no significant difference between the two groups in the incidence of chronic pain at 3 months and 6 months after surgery ( all P>0.05). The incidence of chronic pain in group E was lower than that in group C at 3 months [13.4%(9/67) vs 18.8%(13/69), P=0.392] and 6 months [10.7%(6/56) vs 16.1%(10/62), P=0.391], but the difference was not statistically significant. Conclusions:Perioperative administration of esketamine provided superior short-term analgesia after cesarean section and did not increase the psychotomimetic adverse event rate. However, the development of chronic pain was not restrained.

OBJECTIVETo study the surgical reconstruction of unilateral Craniofacial Atrophy and Hypoplasia.

METHODSAccording to the etiological factors and severity of the facial deformities, different methods are employed, including bone framework reconstruction, soft tissue transplantation, orthognathic surgery.

RESULTSFrom September 1998 to August 2004, 42 cases were treated, Include: Hemifacial Microsomia 22 cases, Hemifacial Atrophy 16 cases, unilateral facial hypoplasia due to radiation 4 cases. Miniplate and transplants extrusion occurred on 2 post radiation patients due to poor soft tissue coverage, infection occurred on 1 patient after mandibular ramus reconstruction using autogenous rib and contralateral mandibular outer cortex. The leaving patients recovered well and the facial asymmetry were improved greatly.

CONCLUSIONSFacial asymmetry due to unilateral Craniofacial Atrophy or Hypoplasia is a common and complex condition for surgical management, The surgical plan should be delicated made individually according to the severity of the soft tissue and the underlying bone framework.

Adolescent ; Adult ; Craniofacial Abnormalities ; surgery ; Facial Asymmetry ; surgery ; Facial Hemiatrophy ; surgery ; Female ; Humans ; Male ; Reconstructive Surgical Procedures ; methods ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the effects of Scutellaria barbata extract (ESB) in suppressing tumor growth and modulating the immune functions in mice bearing tumors derived from hepatocarcinoma H22 cells.

METHODSFifty mice inoculated subcutaneously with H22 cells were equally divided into the model group, high-, moderate-, and low-dose ESB groups, and 5-Fu group, with corresponding treatments for 10 days. Another 10 mice with only saline injection served as the normal control group. The body weight, tumor mass, thymus index and spleen index of the mice were measured, and the lymphocyte proliferation activity, NK cell activity and interleukin-2 (IL-2) production by the splenocytes were detected.

RESULTSModerate- and high-dose ESB significantly suppressed the tumor growth with tumor inhibition rate of 28.68% and 36.98%, respectively. ESB treatment at moderate and high doses significantly increased the thymus index and spleen index (P < 0.01), which were decreased significantly in 5-Fu group. The lymphocyte proliferation activity, NK cell activity and IL-2 production by the splenocytes were significantly lower in the model group than in the normal group (P < 0.05). Compared with the model group, ESB at the high dose obviously increased the three indexes above mentioned. The NK cell activity was also significantly improved in moderate-dose ESB group (P < 0.05).

CONCLUSIONESB can suppress the growth of H22 implant tumor and enhance the immune function of the tumor-bearing mice.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Interleukin-2 ; metabolism ; Killer Cells, Natural ; immunology ; Liver Neoplasms, Experimental ; immunology ; pathology ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred ICR ; Random Allocation ; Scutellaria ; chemistry

OBJECTIVETo investigate the reliability and feasibility of sentinel lymph node biopsy (SLNB) of papillary thyroid carcinoma using combination of lymphoscintigraphy, the gamma probe and methylene blue staining techniques.

METHODSTwenty-three consecutive patients with thyroid papillary carcinoma were entered in the study between August 2007 and August 2009. All cases were without clinical evidence of cervical lymph node involvement. The (99)Tc(m)-dextran of 74 MBq (2mCi) was injected intratumorally under ultrasound guidance about 2 h to 5 h prior to surgery. Methylene blue was injected around the tumor during surgery. Preoperative lymphoscintigraphy, intra-operative hand-held gamma probe detecting and methylene blue staining techniques were used to detect the sentinel lymph node (SLN). SLN biopsies were sent to prepare frozen sections and the results were compared with specimen of routine selective neck dissection.

RESULTSThe SLNs were identified in all cases with the combination techniques. The SLN identification rates were 87.0% and 100% with methylene blue staining and lymphoscintigraphy plus probe scanning, respectively. Metastases in SLNs were revealed by frozen-section histology in 12 patients. In one case, SLNs frozen-section were negative, but metastasis was detected in routine histology. In other case both SLN and routine histology were negative, but metastasis was detected in non-SLN (level VI) neck dissection. The overall accuracy of the SLN biopsy was 91.3%, positive predictive value 100% and negative predictive value 81.8%.

CONCLUSIONThe results seem the SLN biopsy technique is a feasible and valuable method for detecting cervical lymph node metastasis and is helpful to decide performing neck dissection in patients with cN0 papillary thyroid carcinoma.

Adult ; Aged ; Carcinoma, Papillary ; diagnostic imaging ; pathology ; surgery ; Dextrans ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; diagnostic imaging ; pathology ; Lymphatic Metastasis ; Male ; Methylene Blue ; Middle Aged ; Neoplasm Staging ; Organotechnetium Compounds ; Radionuclide Imaging ; Sentinel Lymph Node Biopsy ; Thyroid Neoplasms ; diagnostic imaging ; pathology ; surgery ; Young Adult

OBJECTIVETo study the clinicopathologic features of intravascular large B-cell lymphoma (IVLBCL).

METHODSTwo autopsy cases of IVLBCL were retrieved from the archival file. The clinicopathologic features, immunohistochemistry and molecular findings were studied.

RESULTSThe deceased were 70-year-old and 50-year-old males. Both of them had complained of a sudden onset of weakness and numbness of lower extremities. The clinical course deteriorated rapidly, with multi-organ failure. They died 85 days and 44 days after the presentation, respectively. Post-mortem examination did not reveal any mass lesion, except the presence of multiple skin and epicardium nodules, ranging from 0.5 cm to 2.5 cm in diameter, in the first patient. Pericardial effusion, ascites and pleural effusion were also observed. Histologically, neoplastic lymphoid cells filled up the small vessel lumina in many organs, including brain, hypophysis, spinal cord, spinal nerve roots, heart, lungs, kidneys, liver, spleen, digestive tract, pancreas, adrenal, thyroid, testes and lymph nodes. The tumor cells were relatively monotonous and of medium to large in size with round vesicular nuclei and 1 to 3 small basophilic nucleoli. Immunohistochemical study showed that the lymphoma cells expressed B-cell markers CD20 and CD79a, occasionally positive for CD5 and bcl-2 but negative for CD3, bcl-6, CD10, CD30, myeloperoxidase and cytokeratin. In-situ hybridization for Epstein-Barr virus-encoded RNA was negative. The proliferative index, as demonstrated by Ki-67 staining, was about 80%. Molecular study showed the presence of immunoglobulin heavy chain gene rearrangement in both cases, T-cell receptor-gamma gene rearrangement was not found.

CONCLUSIONSIVLBCL may present as neurological disturbance and carries distinctive morphologic characteristics, immunophenotype and molecular findings. The prognosis of this disease is often dismal.

Aged ; Antigens, CD20 ; analysis ; Autopsy ; B-Lymphocytes ; pathology ; virology ; CD79 Antigens ; analysis ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell ; immunology ; pathology ; virology ; Lymphoma, Large B-Cell, Diffuse ; immunology ; pathology ; virology ; Male

OBJECTIVETo study the depression symptoms in chronic prostatitis (CP) patients, and explore the correlation between depression symptoms and CP.

METHODSThe Zung self-rating depression scale (SDS) , NIH-CPSI, IIEF-5, and a self-designed questionnaire were employed in 1500 cases of CP patients.

RESULTSA total of 1426 effective questionnaires were collected. The mean score of SDS was (44.24 +/- 10.20), significantly higher than that of the domestic norm (P = 0.000). With the score limitation set at > or = 53, 309 (21.7%) of the CP patients had symptoms of depression, of whom 176 (12.3%) were rated by SDS as in the mild, 114 (8.0%) in the moderate and 19 (1.3%) in the severe state of depression. The dominating symptoms as listed in SDS were exactly the stimulating and provoking factors of CP. The scores of SDS were significantly correlated with disease course, CPSI score, IIEF score and times and cost of treatment (P < 0.01), while no correlation was observed with age and WBC counts in EPS.

CONCLUSIONCP patients mostly have depression problems, which are closely correlated with CP and contribute to the recurrence, refractoriness and discontinued outcome of the disease.

Adolescent ; Adult ; Aged ; Chronic Disease ; Depressive Disorder ; epidemiology ; etiology ; Epidemiologic Studies ; Humans ; Male ; Middle Aged ; Prostatitis ; epidemiology ; psychology ; Surveys and Questionnaires

OBJECTIVEWhether statins can slow down the progression of chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to evaluate the effects of statin therapy on disease progression in adult patients with CKD who did not require dialysis therapy.

METHODSWe searched the electronic databases for relevant randomized controlled trials (RCTs) published by February 2015. Random-effects meta-analysis of RCTs was used to pool the renal outcomes of the patients.

RESULTSTwenty-eight studies (30 RCTs) involving a total of 45 688 participants were included in the analysis. Compared with the control groups, statins produced no effects in preventing end-stage renal disease (ESRD) [relative risks (RR) 0.98, 95% confidence intervals (CI): 0.91-1.05] and in reducing the risk of doubling of the serum creatinine level (RR 1.43, 95% CI: 0.26-7.79). Statin therapy was associated with a lowered risk of estimated glomerular filtration rate (eGFR) reduction by 25% or more (RR 0.91, 95% CI: 0.83-0.99) and delayed the reduction of eGFR [standardized mean differences (SMD) 0.04, 95% CI: 0.02-0.07]. In subgroup analyses, the benefit of statins on changes in eGFR was statistically significant in patients with moderate CKD (SMD 0.09, 95% CI 0.04-0.13). Among different statins, atorvastatin was associated with a beneficial effect on kidney function (SMD 0.10, 95% CI 0.03-0.17). Patients who received high-intensity statin therapy showed significant changes in eGFR (SMD 0.12, 95% CI: 0.02-0.21).

CONCLUSIONStatin therapies may not prevent ESRD or doubling of serum creatinine level, but can improve GFR or delay the reduction of GFR in CKD patients. The therapeutic effects are associated with the patients' baseline eGFR levels, statin types and therapy intensity.

Adult ; Disease Progression ; Glomerular Filtration Rate ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic ; drug therapy

OBJECTIVETo study CXCR3 and CCR5 chemokine receptor expression in spleens of patients with primary immune thrombocytopenia (ITP) and its clinical significance.

METHODSThe splenectomy specimens from 10 ITP patients (ITP group) and 8 patients with traumatic splenic rupture (normal control group) were studied. Immunohistochemistry (IHC) was used to study the positive rate of CXCR3 and CCR5. Western blot was performed to detect CXCR3 and CCR5 protein expression, while real-time polymerase chain reaction (RT-PCR) was conducted to analyze their mRNA expression.

RESULTSThe positive rate of CXCR3 and CCR5 were both higher in ITP group (90% and 100%, respectively) than those in control group (75% and 87.5%, respectively)(P < 0.05). The differences were statistically significant (P < 0.05). Protein and mRNA level of CXCR3 in ITP group were 3.0 and 3.5 times as high as those in control group, respectively. Those of CCR5 in ITP group were 1.2 and 1.7 times as high as those in control group, respectively.

CONCLUSIONHigh expression of CXCR3 and CCR5 may play a part in the splenic immune disorders in patients with ITP.

Adolescent ; Adult ; Case-Control Studies ; Child ; Female ; Humans ; Male ; Middle Aged ; Receptors, CCR5 ; metabolism ; Receptors, CXCR3 ; metabolism ; Spleen ; metabolism ; Thrombocytopenia ; immunology ; metabolism ; Young Adult

OBJECTIVETo detect the disparity of three cytokines interleukin-6 (IL-6), interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).

METHODSerum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen patients with no marked arthritis symptom or only temporary arthralgia were enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were examined for cytokine levels.

RESULT(1) The statistically significant difference in serum IL-6 was detected between sJIA and healthy control group [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically significant differences between sJIA group and healthy control group in serum concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05], yet compared to healthy control group, no significant difference in concentration level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2) ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4-111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01, respectively], but there was only significant difference in IL-17 between pJIA SF and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01].

CONCLUSIONIL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may be the biomarker associated with arthritis in early JIA stage. Both autoinflammation and autoimmune response may be involved in the pathogenesis of sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB may not be significantly increased. The prominent expression gradient between SF and PB of IP-10 maybe the basis of performing chemotaxis and further causing joint damage.

Adolescent ; Arthritis, Juvenile ; blood ; immunology ; metabolism ; Case-Control Studies ; Chemokine CXCL10 ; blood ; metabolism ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-17 ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Knee Joint ; metabolism ; Male ; Synovial Fluid ; immunology ; metabolism