BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

Plague, infectious disease in modern medicine, refers to a type of disease with strong pathogenicity and infectiousness, it refers to the infectious diseases of western medicine. Due to its wide variety, the knowledge and understanding of plagues of Traditional Chinese Medicine (TCM) doctors in different stages have evolved and developed with the times. This article, via collating ancient documents, differentiatesthe classification in TCM and analyzes itsrelated theories to perfect the type of plagues in TCM, providing the theoretical basis for the research of plague in modern times.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective To evaluate the prognostic value of anemia in patients diagnosed with extranodal nasal-type natural killer (NK)/T cell lymphoma (NKTCL).Methods Clinical data of 1 225 NKTCL patients receiving the first course of treatment from 10 medical institutions in China were retrospectively analyzed.According to the diagnostic criteria in China,anemia was defined as the hemoglobin (Hb) level＜ 120 g/L for the male and＜ 110 g/L for the female from the sea-level area.The severity of anemia was classified into the extremely severe anemia (Hb ≤ 30 g/L),severe anemia (31-60 g/L),moderate anemia (61-90 g/L) and mild anemia (＞90 g/L).Results Among 1 225 patients,199(16.2％) were complicated with anemia,who had more adverse prognostic factors compared with their counterparts without anemia.Among NKTCL patients with anemia,the proportion of patients with stage Ⅱ-ⅣV,a median age＞ anemia,Eastern Cooperative Oncology Group (ECOG) score of 2-4 and NK/T-cell lymphoma prognostic index (NKTCLPI) ≥ 2 was relatively high.Patients with anemia obtained worse clinical prognosis than those without anemia.The 5-year overall survival (OS) and progression-free survival (PFS) in NKTCL patients with anemia were calculated as 49.4％ and 35.4％,significantly lower compared with 63.3％ and 56.0％ in their counterparts without anemia (both P＜0.01).Single factor analysis demonstrated that anemia,age,ECOG score,group B symptom,lactate dehydrogenase,primary tumor site,primary tumor invasion and staging were the prognostic factors of OS and PFS.Multivariate analysis revealed that anemia was still the independent prognostic factor.Conclusions Anemia is not common in patients with NKTCL and these patients obtain poor clinical prognosis.Anemia is an independent prognostic factor for patients with NKTCL.

Objective There is still a lack of effective clinical prognostic factors for predicting outcomes and guiding treatments in extranodal nasal-type NK/T-cell lymphoma (NKTCL).This study was aimed to investigate the clinical features and prognostic role of primary tumor burden (PTB).Methods A total of 1383 patients were recruited from ten hospitals, including 947 stage Ⅰ patients (68.5%), 326 stage Ⅱ patients (23.6%), and 110 stage Ⅲ-IV patients (8.0%).There were 751 patients (54.3%) presenting with high PTB (H-PTB).The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was conducted for survival difference analysis.Meanwhile, a multivariate analysis was performed using the Cox regression model.Results H-PTB was associated with high invasive potential, high frequency of B symptoms, advanced stage, regional lymph node involvement, lactate dehydrogenase elevation, and poor performance status.The patients with H-PTB had significantly lower 5-year overall survival (OS) and progression-free survival (PFS) rates than those with low PTB (L-PTB)(OS:50.2% vs.72.1%, P=0.000;PFS:41.8% vs.62.5, P=0.000).PTB was an independent prognostic factor for both OS (HR=1.851) and PFS (HR=1.755) according to the Cox multivariate analysis.Moreover, H-PTB was associated with significantly lower locoregional control (LRC) in early-stage NKTCL, and the 5-year LRC rate was 71.6% in patients with H-PTB and 84.3% in those with L-PTB (P=0.000).Conclusions H-PTB is associated with multiple adverse clinical features in NKTCL, and it is an independent indicator for poor outcomes and LRC.H-PTB can be used as a reliable indicator for risk stratification and treatment decision.

Objective To evaluate the clinical features, treatment outcome, and prognostic factors in patients with primary Waldeyer’ s ring diffuse large B?cell lymphoma (WR?DLBCL). Methods This study included 200 patients with a confirmed diagnosis of primary WR?DLBCL admitted to our hospital from 2000 to 2013, who consisted of 50 stage I patients, 125 stage II patients, and 25 stage III?IV patients. Most patients received 4?6 cycles of CHOP or CHOP?based chemotherapy with or without involved field radiotherapy (Waldeyer′s ring+cervical lymph node region). Results The 5?year sample size was 71. The 5?year overall survival (OS), progression?free survival (PFS), and locoregional control (LRC) rates for the whole group were 78%, 72%, and 87%, respectively. In the 175 early stage patients, chemoradiotherapy resulted in significantly higher OS, PFS, and LRC than chemotherapy alone (86% vs. 70%, P= 0?? 001;84% vs. 58%, P= 0?? 000;97% vs. 66%, P= 0?? 000). Univariate analysis showed that age, tumor size, stage, lactate dehydrogenase level, and International Prognostic Index were prognostic factors for OS, PFS, and LRC ( P= 0?? 000?0?? 036), while the prognostic factors for PFS also included Eastern Cooperative Oncology Group score and cervical nodal involvement (P= 0?? 018). Multivariate analysis showed that age and stage were prognostic factors for OS and LRC (P= 0?? 003?0?? 022), and age was the prognostic factor for PFS (P= 0?? 000). Conclusions WR?DLBCL has distinct clinical features and favorable prognoses. For early stage patients, combined?modality therapy results in significantly higher OS, PFS, and LRC.

Objective To evaluate the value of radiotherapy following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone ( R?CHOP )?based chemotherapy for patients with early?stage Waldeyer’ s ring diffuse large B?cell lymphoma ( WR?DLBCL). Methods Eighty?three patients diagnosed with early?stage WR?DLBCL who were admitted to our hospital from 2000 to 2013 were enrolled in the study. In these patients, twenty?five had stageⅠdisease and fifty?eight had stageⅡdisease. All patients received R?CHOP?based chemotherapy with ( n= 62 ) or without ( n= 21 ) involved?field radiotherapy ( Waldeyer’ s ring plus cervical lymph nodes ) . The overall survival ( OS ) , progression?free survival ( PFS) , and local?regional control ( LRC) rates were calculated using the Kaplan?Meier method. The univariate analysis was performed using the log?rank method. The multivariate analysis was performed using the Cox regression model. Results In all patients, the 5?year sample size was 18;the 5?year OS, PFS, and LRC rates were 89%, 84%, and 90%, respectively. According to the univariate analysis, patient age greater than 60 years, an increased lactate dehydrogenase level, Eastern Cooperative Oncology Group ( ECOG ) performance status no less than 2, and International Prognostic Index ( IPI ) no less than 2 were poor prognostic factors. Patient age greater than 60 years, a tumor size no less than 5 cm, ECOG performance status no less than 2, and IPI no less than 2 were influencing factors for PFS and LRC rates. In addition to the treatment with rituximab, patients treated with consolidative radiotherapy had significantly higher PFS and LRC rates (94% vs. 58%, P=0?003;100% vs. 61%, P=0?000) as well as slightly higher OS rate ( 9 4%vs . 7 1%, P=0?0 6 3 ) than those treated without radiotherapy . Conclusions Consolidative radiotherapy following R?CHOP?based chemotherapy significantly improves PFS, LRC, and probably OS rates for early?stage WR?DLBCL. This conclusion still needs to be confirmed by prospective studies with a large sample size.

Objective To evaluate the clinical effects and experiences of short stem ceramic-on-ceramic total hip arthroplasty in the treatment of young and middle-aged patients with femoral head necrosis.Methods From December 2009 to March 2011,40 patients with femoral head necrosis were treated primarily with short stem ceramic-on-ceramic hip arthroplasty (43 hips) through posterior-lateral or anterior-lateral approach.There were 23 males,17 females； with the mean age of 40.5 years (range,27-55 years).All cases were stage Ⅳ or more according Steinberg stage.The patients were followed up at the 3,6,12 months after operation,and then once each year.Standard X-ray films were taken at the follow-ups.Femoral prosthesis subsidence was assessed through X-ray films.Harris scores system and WOMAC Osteoarthritis Index were recorded before and after operation to evaluate clinical effects of surgery.Results Thirty-eight patients (41 hips) were followed up for 21-36 months,with an average of 31.3 months.The femoral stem subsided 0.68±2.90 mm at the last follow-up.After operation,hip pain of patients was relieved obviously.The Harris score improved from 38.7±12.1 (15-66) preoperatively to 95.2±4.49 (83-100) postoperatively,WOMAC Index from 66.7±12.0 (49-94) to 12.8±5.6 (0-24).During follow-up period,there was no serious complication such as femoral neck fracture,infection of wound,pulmonary embolism,et al.No dislocation,implant prosthesis failure and infection were observed.Conclusion The short stem hip arthroplasty preserves bone stock to a great extent.The short stem implant showed a good stability and osseous integration.The wear rate of ceramic-on-ceramic bearing surface is extremely low.Short stem hip arthroplasty plus ceramic-on-ceramic bearing surface might be a good option for the young and middle-aged patients with femoral head necrosis.