Background: Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value. Methods: During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data. Results: The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence. Conclusions HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.

BackgroundSleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.

MethodsWe recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.

ResultsThe mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO(r = -0.323, -0.315, both P = 0.001) in PD patients.

ConclusionsThe level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Aged ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Parkinson Disease ; blood ; physiopathology ; Polysomnography ; Sleep Wake Disorders ; blood ; physiopathology

Objective: To investigate the current status of antithrombotic strategy for elderly patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) after stent implantation in Beijing area and to study the safety and efficacy of different therapeutic strategy. Methods: A total of 467 relevant patients were enrolled by re-travelling electronic medical records from 12 hospitals in Beijing area. The patients' mean age was (78.70±3.32) years and they were divided into 2 groups by antithrombotic therapy condition: Triple therapy group, n=17 (3.64％), Double therapy group, n=450 (96.36％). The incidence of major adverse cardiac and cerebral events (MACCE) including all-caused death, non-fatal myocardial infarction, stent thrombosis, target vessel revascularization (TVR), stoke and bleeding was compared between Triple therapy group and Double therapy group.Results: The medication in Double therapy group included aspirin+ticagrelor, aspirin+clopidogrel, clopidogrel+warfarin and cilostazol+clopidogrel; in Triple therapy group was aspirin+clopidogrel+warfarin. Patient with HAS-BLED score≥3 was defined as high risk of bleeding and they were all treated by double therapy; HAS-BLED<3 was defined as low risk of bleeding, only 5.03％ patients were treated by triple therapy. 3 patients in Triple therapy group and 33 in Double therapy group suffered from gastrointestinal bleeding, P=0.338; 6 patients in Triple therapy group and 128 in Double therapy group had MACCE, P=0.589; 3 and 80 patients died in Triple therapy group and Double therapy group, P=0.766. Conclusion: Triple therapy was rarely used in elderly AF and ACS patients after stent implantation, double therapy was the main strategy; the incidence of MACCE and mortality were similar between triple and double therapies; patients with triple therapy had the higher incidence of gastrointestinal bleeding.

Objective To know the status of heavy metal (Pb,Cd,Cr,Ni,Cu,Zn,Hg and As)contents and level of pollution in soils of vegetable plantation bases in Yongkang City.Methods A total of 84 samples from 5 vegetable plantation bases was collected and determined.Pb,Cd,Cr,Ni,Cu and Zn were determined by AAS.Hg and As were determined by AFS.And results were evaluated by using cumulative degree level,a single pollution index and Nemerow pollution index according to Safety Qualification of Agricultural Product -Environmental Requirements for Origin of Non -environmental Pollution Vegetable and Soil Environmental Quality Standard.Results The content of Cd was higher than the standard,while the other 7 heavy metals were in line with national standards.The Pb,Ni,Cu,As in vegetable plantation bases located on level one (fundamental change,clean),and Cd,Cr,Zn,Hg were level two (mild change, low accumulation).The integrated pollution index of vegetable plantation soils in Yongkang City was 0.86 (level two, warning limit).Conclusion The heavy metal contents in soils of vegetable plantation bases in Yongkang City are in line with national standards except Cd.

Objective To know the contents of heavy metal (Pb,Cd,Cr,Ni,Cu,Zn,Hg and As) in home -grown vegetables in a city for providing evidences in vegetable planting.Methods A total of 248 samples from 5 vegetable plantation bases in four seasons were collected and the contents of heavy metal were determined and analyzed.Pb,Cd,Cr, Ni,Cu and Zn were determined by AAS,Hg and As were determined by AFS.The results were evaluated according to the national food sanitation standard limits.Results The exceeding rate of Ni in home -grown vegetables of root leaf and fruit was 48.48%,9.29% and 5.33% respectively,the exceeding rate of Cd was 12.12%,0.71 % and 8.00%,the exceeding rate of Pb was 0.00%,16.43% and 5.33%.The exceeding rate of other heavy metal were all below 5% or in line with the standard.The degree of heavy metal pollution decreased with season's order of autumn,summer,spring and winter.The content of As in leafy -vegetables was in significant association with the contents of AS in soil.Conclusion The heavy metal pollution of Ni,Pb and Cd in vegetables in the city is serious,and more attention should be paid to the heavy metal pollution.

OBJECTIVETo explore the association of spermatogenic arrest with the expression of estrogen receptor alpha (ERalpha) in human testes.

METHODSWe examined the testicular biopsy specimens of 120 infertile men by HE staining, detected the expression of ERalpha in the specimens of those with spermatogenic arrest by the two-step immunohistochemical method, and compared the results with those of 10 healthy men.

RESULTSOf the 120 specimens from the infertile men, 31 (25.8%) met the diagnostic criteria of spermatogenic arrest. In the testis tissue of normal men, ERalpha expressed in Sertoli, myoid and Leydig cells, but not in spermatogenic cells, while in the testis tissues of those with spermatogenic arrest, ERalpha expressed lowly in Sertoli, myoid and Leydig cells, with statistically significant differences in immunostaining intensity between the two groups (P < 0.05).

CONCLUSIONAndrogen receptor (AR) and ERalpha may play a coordinating role in facilitating spermatogenesis. Spermatogenic arrest may be related to a complex series of disorders in cell signal transduction involving AR, ERalpha and HSP90.

Adult ; Case-Control Studies ; Estrogen Receptor alpha ; metabolism ; Humans ; Infertility, Male ; etiology ; metabolism ; pathology ; Male ; Spermatogenesis ; Testis ; metabolism ; pathology ; Young Adult

Objective To evaluate the effcacy and side effects of [~(90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)~0,Tyr3]octreotate (~(90)Y-DOTATATE) combined with lysine as a renal protective agent.Methods Twenty-five patients with advanced neuroendocrine tumors were confirmed as somatostatin receptor subtype-2 (SSTR2)-positive by somatostatin receptor scintigraphy (SRS).Each patient received 1-5 cycles of treatment and the interval between two cycles of treatment was 6-9 weeks.~(90)Y-DOTATATE was administered intravenously within 30 min.Lysine was injected before and after the administration of ~(90)Y-DOTATATE.After each treatment cycle.the side effects were assessed according to National Cancer Institute Grading Criteria(NCIGC).The etticacy was evaluated by the WHO criteria 8 weeks after the last treatment.Results Pattial remission was found in 1 patient (4%).minor response in 3 patients(12%),stable disease in 16 patients (64%)and tumor progression in 5 patients (20%).Two patients suffered from renal functional injuries and 3 patients developed leukocytopenia.Three patients showed nausea while another 3 patients presented vomiting.Conclusions ~(90)Y-DOTATATE in association with lysine may be a promising treatment method for the patients with metastatic and inoperable neuroendocrine tumors.More research work may be directed to reduce renal injury.

Objective To study post antibiotic effect (PAE), post β-lactamase inhibitor effect (PLIE) and post antibiotic sub-MIC effect (PASME) of ceftriaxone/tazobactam on β-lactamase-producing Escherichia coli in vitro. Methods The minimal inhibitory concentration (MIC) of ceftriaxone/tazobactam against 4 types of β lactamase producing E. colis strains, was measured by two-fold agar dilution method. The numbers of CFU on plates were counted by micro-inoculation colony counting method. The growth kinetics curves of the bacteria were drawn according to CFU counts, from which the PAE. PLIE and PASME were calculated. Results The MIC of the ceftriaxone/tazobactam combination was eight times more than ceftriaxone alone. No longer PAE (-0. 59-0. 85 h) was found in the ceftriaxone/tazobactam combination or any of them alone. The PLIE and PASME varied according to the type of β-lactamase but similar results were observed for the strains producing the same type β-lactamase. All PLIEs (0. 62-3. 22 h) and most PASMEs (0.12-5. 61 h) were longer than PAEs. The lower MIC of ceftriaxone the strain had, the longer the PAE, PLIE and PAMSE were. Conclusion The duration of PLIE and PASME may concerned with the type of β-lactamase. With both longer PLIE and PASME, longer dosing interval should be recommended. The PAE, PLIE and PASME provide an important instrument for pharmacodynamic studies of antibiotics, in particular for the design of dosing schedules.

OBJECTIVESTo evaluate the feasibility and effectiveness of stent placement in treating hepatic artery stenosis after orthotopic liver transplantation (OLT).

METHODSFrom November 2003 to September 2005, 14 patients who had hepatic artery stenosis after OLT underwent stent placement in their narrowed hepatic arteries. This included early interventional treatment in 10 patients and delayed interventional treatment in 4 patients. The technical results, clinical outcomes, and the hepatic artery patencies were reviewed.

RESULTSTechnical and immediate success was 100%. After a mean follow-up of 146 days (range, 9-345 days), all patients' hepatic arteries were patent, except that hepatic arterious restenosis occurred in 2 patients at 26 and 45 days after the stent placement. Of the 10 patients who received early treatment, 8 survived with normal results of liver function test and 2 patients died of septic multiple-organ failure at 9 and 30 days after the stent procedure. One patient received a retransplantation because of refractory biliary infection. Of the 4 patients who received a delayed interventional treatment, 1 patient survived for 345 days but with abnormal liver functional test results, the other 3 patients died of septic multiple-organ failure resulting from liver abscesses biliary infection.

CONCLUSIONHepatic artery stenosis after OLT can successfully be treated with stent placement and an early interventional treatment is the key for a good clinical outcome.

Adult ; Constriction, Pathologic ; therapy ; Female ; Graft Occlusion, Vascular ; etiology ; therapy ; Hepatic Artery ; surgery ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Stents ; Vascular Diseases ; etiology ; therapy

OBJECTIVETo study the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV) like virus in animals at a live animal market of Guanzhou in 2004 before and after culling of wild animal action taken by the local authority, in order to predict the re-emerging of SARS from animal originals in this region.

METHODSAnimals at live animal market were sampled for rectal and throat swabs in triplicate. A single step realtime reverse transcription-polymerase chain reaction (RT-PCR) diagnostic kit was performed for screening SARS-CoV like virus, the manual nested RT- PCR and DNA sequencing were performed for confirmation. Only specimens which tested positive for both of the N and P genes by nested RT-PCR were scored as positive.

RESULTSIn 31 animals sampled in January 5 2004 before culling of wild animals at Guangdong Province, including 20 cats (Felis catus), 5 red fox (Vulpes vulpes) and 6 Lesser rice field rats (Rattus losea), 8 (25.8%) animals were tested positive for SARS-CoV like virus by RT-PCR methods, of which 4 cats, 3 red fox and one Lesser rice field rats were included. However, two weeks after culling of animals and disinfection of the market were implemented, in 119 animals sampled in January 20 2004, including 6 rabbits (Oryctolagus cuniculus), 13 cats, 46 red jungle fowl (Gallus gallus), 13 spotbill duck (Anas platyrhynchos), 10 greylag goose (Anser anser), 31 Chinese francolin (Franclinus pintadeanus), only rectal swab from one greylag goose was tested positive for SARS-CoV like virus. Furthermore, in 102 animals that including 14 greylag gooses, 3 cats, 5 rabbits, 9 spotbill duck (Anaspoecilorhyncha), 2 Chinese francolin (Franclinus pintadeanus), 8 common pheasant (Phasianus colchicus), 6 pigeons, 9 Chinese muntjac (Muntiacus reevesi), 19 wild boar (Sus scrofa), 16 Lesser rice field rats, 5 dogs, 1 mink (Mustela vison), 3 goats, 2 green peafowl (Pavo muticus) sampled in April, May, June, July, August and November, only rectal swab from one pig was tested positive. However, of 12 and 10 palm civets sampled in November and December including five of which had been at the live animals market for 2 days, none of them was tested positive.

CONCLUSIONThis findings revealed that animals being sampled in April, May, June, July, August and November of 2004, only one rectal swab from a pig was tested positive as SARS-CoV like virus, much lower than the results from the previous year, suggesting that the possibility of re-emerging of human infection from animal origins is low for the winter of 2004-2005.

Animals ; Animals, Wild ; virology ; China ; DNA, Viral ; analysis ; Felidae ; virology ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; isolation & purification