Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Objective To observe the effects of Shuangdan Mingmu Capsules on the expressions of HIF-1α and NF-κB; To explore its possible mechanism of treatment. Methods SD rats were injected with STZ (50 mg/kg) into the tail vein to induce diabetes mellitus. After the DR model was confirmed by fundus fluorescein angiography, the rats were randomly divided into model group, Shuangdan Mingmu Capsules group and positive medicine group, and normal rats were set as control group. After the last administration, the blood glucose level and retinopathy in rats were measured. The protein and gene expression of HIF-1α and NF-κB in the retina were detected by Western blot and RT-PCR respectively. Results Compared with control group, the blood glucose in the model group was significantly increased; the retinal capillaries increased; the leakage of fluorescein was obvious; the protein and gene expressions of HIF-1α,NF-κB were significantly increased.After administration of Shuangdan Mingmu Capsules,the model rats decreased blood glucose; retinal microvascular volume decreased; fluorescein leakage area was significantly reduced; protein and gene expressions of HIF-1α and NF-κB were decreased. Conclusion Shuangdan Mingmu Capsules can effectively inhibit the neovascularization of DR rats and protect the retina, which may be related to the down-regulation of the expressions of HIF-1α and NF-κB.

BACKGROUND/AIMS: No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). METHODS: We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. RESULTS: In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p<0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post-SVR albumin ≤36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. CONCLUSIONS: An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC.
Area Under Curve ; Carcinoma, Hepatocellular* ; Case-Control Studies* ; Diagnosis ; Fibrosis ; Hepatitis C, Chronic* ; Hepatitis, Chronic* ; Humans ; Risk Factors ; ROC Curve ; Sensitivity and Specificity

BACKGROUNDAmong HIV-infected patients initiating antiretroviral therapy (ART), early changes in CD4+ T-cell subsets are well described. However, HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events. Therefore, factors associated with CD4+ T-cell reconstitution need to be determined in this population, which will allow designing effective immunotherapeutic strategies.

METHODSThirty-one adult patients with baseline CD4+ T-cell count <350 cells/mm3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing, China, from October 2002 to September 2013. Changes in T-cell subsets and associated determinants were measured.

RESULTSMedian baseline CD4+ T-cell count was 70 cells/mm3. We found a biphasic reconstitution of T-cell subsets and immune activation: a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years. Baseline CD4+ T-cell count >200 cells/mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs. 27.3% respectively; P = 0.017) and normalized CD4/CD8 ratio. We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907), and 12.4% as cutoff value had a sensitivity of 84.6% and a specificity of 88.2%.

CONCLUSIONSBaseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy. Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.

Adult ; Antiretroviral Therapy, Highly Active ; methods ; CD4 Lymphocyte Count ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; metabolism ; Female ; HIV Infections ; drug therapy ; immunology ; metabolism ; HIV-1 ; drug effects ; immunology ; pathogenicity ; Humans ; Male ; Prospective Studies ; T-Lymphocyte Subsets ; immunology

H5 subtype avian influenza (AIV-H5) is a major causative agent of animalloimia a rapid and sensitive molecular biological diagnosis is crucial to the control program of AIV-H5. AIV-H5 real-time fluorescent reverse transcription loop-mediated isothermal amplification (qRT-LAMP) was established by means of heat treatment of the samples. The sensitivity, specificity and repeatability of this method were assessed and the performance of Calcein,SYBR Green I,HNB,SYTO 81 in colorimetric detection was comparatively analyzed to screen the optimum dye. The results showed the sensitivity of this method was 100 times higher than that of standard real-time fluorescent RT-PCR, and the detection limit was one copy of the gene per reaction. This method had no cross-reactivity with other common avian respiratory tract infectious disease-related pathogens such as IBV and NDV. The present study suggested Calcein was the optimum dye. Small-scale tests suggested this method was reliable for survey monitoring of AIV-H5 on the spot, indicating its potential applications in field investigation.
Animals ; Chickens ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; Influenza A Virus, H5N1 Subtype ; genetics ; isolation & purification ; Influenza in Birds ; diagnosis ; virology ; Poultry Diseases ; diagnosis ; virology ; Reverse Transcriptase Polymerase Chain Reaction ; instrumentation ; methods ; Sensitivity and Specificity

Objective To study the influence of nasal irrigations on the postoperative curative effect of patients with chronic sinusitis.Methods Total of 357 patients who suffered from chronic sinusitis received transnasal endoscopic surgery from 2008 to 2010 with 184 patients selecting nasal irrigations for the following treatments.Patients were followed up at two weeks,six weeks and four months after the surgeries via telephone.The symptoms of nasal obstruction,nasal discharge and headache were recorded and SNOT-20 was used to measure the quality of life.Results Symptoms of patients were improved,but improvement in nasal irrigations group was better than that in non-nasal irrigations group.Four months later,the average symptom score of nasal obstruction in nasal irrigations group was [0(0,1 )] which was significantly lower than [ 0( 0,1 )] in non-nasal irrigations group ( Z =- 3.176,P ＜ 0.05).The average symptom score of nasal discharge in nasal irrigations group was [0(0,2)] which was significantly lower than [0(0,2)] in non-nasal irrigations group (Z =- 4.403,P ＜ 0.05 ).The average score of headache was [ 0 ( 0,1 ) ] in nasal irrigations group and [ 0 (0,2) ] in non-nasal irrigations group,and the difference was statistically significant ( Z =- 4.539,P ＜ 0.05 ).Conclusions Nasal irrigations can improve symptoms of patients with chronic sinusitis and reduce the rectrrence.

OBJECTIVETo discuss the impact of number of retrieved lymph nodes and lymph node ratio(LNR) on the prognosis in patients with stage II and III colorectal cancer.

METHODSClinicopathological data of 507 patients with stage II and III colorectal cancer were analyzed retrospectively. Follow-up was available in all the patients.

RESULTSThe total number of retrieved lymph nodes was 5801, of which 1122 had metastasis. There was a positive correlation between metastatic lymph nodes and retrieved lymph nodes(r=0.171, P<0.01). In stage II colorectal cancer there was a significant difference in 5-year survival rate between patients with more than 12 lymph nodes retrieved and those with less than 12 lymph nodes retrieved(P<0.01). LNR also affected the 5-year survival rate of patients with stage II and III colorectal cancer(P<0.05). In patients with similar LNR, the 5-year survival rate differed significantly among different regions of lymph node metastasis(P<0.05). LNR influenced the prognosis independent of the number of lymph nodes retrieved.

CONCLUSIONSThe number of retrieved lymph nodes is a prognostic factor for stage II and III colorectal cancer. More than 12 lymph nodes should be retrieved for better staging and prognosis. LNR is also a prognostic factor in stage II and III colorectal cancer. Regions of lymph nodes metastasis should be considered when evaluating the prognosis of patients using LNR.

Colorectal Neoplasms ; diagnosis ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; pathology ; Male ; Neoplasm Staging ; Prognosis ; Retrospective Studies

OBJECTIVETo observe the effect of vascular endothelial growth factor (VEGF) on bone marrow-derived mesenchymal stem cell (MSC) proliferation and explore the signaling mechanism involved.

METHODSMSC culture was performed following the classical whole bone marrow adhering method. The characteristics of MSC were identified by induction of multi-lineage differentiation and flow cytometry for surface marker analysis (CD34, CD45, CD29, and CD90). Following the addition of 50 nmol/L wortmannin, 50 µmol/L PD98059, 30 µmol/L SB203580, 10 µmol/L H89, 20 µmol/L Y27632, 1 µmol/L rapamycin, 10 µmol/L straurosporine, 6 nmol/L Go6976, or 50 µmol/L Pseudo Z inhibitors in the cell culture, the MSC were treated with 20 ng/ml VEGF and the changes of the cell proliferation rate was measured with MTT assay.

RESULTSCultured MSC were capable of multi-linage differentiation and did not express VEGF-R, CD29 or CD90. Treatment with 20 ng/ml VEGF obviously promoted MSC proliferation, and this effect was inhibited partially by p38 mitogen-activated protein kinase (MAPK) inhibitor rapamycin, PD98059, SB203580, Go6976, and straurosporine.

CONCLUSIONSVEGF promotes MSC proliferation in close relation to the AKT-PKC pathway, in which PKC signal pathway may play the central role.

Animals ; Bone Marrow Cells ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Female ; Male ; Mesenchymal Stromal Cells ; cytology ; Protein Kinase C ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vascular Endothelial Growth Factor A ; pharmacology

Objective To evaluate the intervention effects of cognitive behavior therapy (CBT) on the patients with first episode schizophrenia. Methods A total of 80 patients with first episode schizophrenia were randomly divided into study group (n =40) and control group (n =40). The study group was treated by routine drugs and psychiatric nursing after two weeks combining with CBT while the control group was treated only by routine drugs and psychiatric nursing. Both groups were assessed with Positive and Negative Syndrome Scale (PANSS), Nurses Observation Scale for Inpatient Evaluation (NOSIE) , Scale of Social-skill for Psychiatric Inpatients (SSPI) , and Symptom Check List-90 (SCL-90) before and after CBT intervention. The scores of those scales were compared between two groups. Results There were significant differences after CBT intervention in all factors, total negative factors and total positive factors of NOSIE, total score of SSPI and PANSS (P<0.01) between two groups. Factors score of interpersonal sensitivity, depression, anxiety, panic, paranoid ideation, and psychosis of SCL-90 in the study group decreased significantly after intervention. Conclusions It is suggested that CBT can improve social function and quality of life and facilitate recovery of the first-episode schizophrenia patients.

OBJECTIVETo explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China.

METHODSGenomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C-->T, MTRR 66A-->G and the relationship between these genotypes and the risk of Down syndrome was analyzed.

RESULTSThe results show that the MTHFR 677C-->T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78 approximately 8.47). In addition, the homozygous MTRR 66A-->G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90 approximately 14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058 approximately 17.496). The two polymorphisms appear to act without a multiplicative interaction.

CONCLUSIONMTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.

Alleles ; Case-Control Studies ; China ; Down Syndrome ; diagnosis ; ethnology ; genetics ; Female ; Ferredoxin-NADP Reductase ; genetics ; Folic Acid ; metabolism ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Humans ; Lymphocytes ; metabolism ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic ; Risk Factors