OBJECTIVETo explore the mechanism of electroacupuncture scalp point-through-point therapy in the treatment of Parkinson's disease.

METHODSThirty-six Wistar rats were randomly divided into a normal group, a sham-operation group, a model group and a point-through-point therapy group. 6-()HDA was injected into left striatum to made lateralization Parkinson's disease rat model. The point-through-point therapy group was treated with electroacupuncture at "Baihui" (GV 20 )-through-"Taiyang" (EX-NH 5), once each day, 6 days constituting one course, for 2 courses, and the rats of other groups were not treated. HE staining method was used for observation of the histo-morphologic changes of the substantia nigra neurons, and RT-PCR for the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs.

RESULTSThe expressions of TH mRNA (1.22 +/- 0. 19) and DAT mRNA (0.62-0.11) in the point-through-point therapy group were significantly higher than (0.65 +/- 0.17) and (0.41 +/- 0.08) in the model group, respectively (all P < 0.05). As compared with the model group, the number of neurons in the substantia nigra increased and degeneration of the neurons relieved in the point-through-point therapy group.

CONCLUSIONThe electroacupuncture scalp point-through-point therapy can increase expressions of TH mRNA and DAT mRNA in the substantia nigra in the Parkinson's disease model rat, and promote synthesis and reuptake of dopamine, hence Parkinson's disease is cured.

Acupuncture Points ; Animals ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins ; genetics ; metabolism ; Electroacupuncture ; Female ; Gene Expression ; Humans ; Male ; Parkinson Disease ; genetics ; metabolism ; therapy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Substantia Nigra ; metabolism ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

This study was aimed to investigate the effect of cord blood dendritic cells (DCs) on the in vitro proliferation capability, immunophenotype changes, level of secreted cytokines and activity against leukemia cells of the homologous cytokine-induced killer (CIK) cells. DCs and CIK cells were induced from cord blood mononuclear cells. They were co-cultured at the ratio of 1:5, and CIK cells from cord blood or DC-CIK cells from peripheral blood were cultured as controls. Immunophenotypic changes were analyzed by flow cytometry, increased number of cells were counted by trypan-blue staining, the killing activity to leukemia cells was assayed by MTT, the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) in the cultured supernatant were detected by ELISA. The results showed that the proliferation capability of cord blood DC-CIK cells was significantly higher than that of cord blood CIK cells and peripheral blood DC-CIK cells (p < 0.05 and p < 0.05). Under the same condition, the rate of double positive cells with CD3(+)CD8(+) and CD3(+)CD56(+) in CIK cells was significantly enhanced by co-culture with cord blood DCs (p < 0.05). The level of IL-12, IFN-γ, and TNF-α in cultured supernatants of cord blood DC-CIK cells increased noticeably on day 3 as compared with CIK cells cultured alone (p < 0.01, p < 0.05, p < 0.05). Within the effector-target ratio range between 2.5:1 to 20:1, the activity of cord blood DC-CIK cells against all subtypes of acute leukemia cells was much higher than that of CIK cells (p < 0.05), and there was no significant difference among all subtypes of acute leukemia cells, which was the same with the killing effect of peripheral blood DC-CIK cells against leukemia cells. It is concluded that the proliferation capability and anti-leukemia effect of the homologous CIK cells can be enhanced by cord blood DCs. The proliferation capability of cord blood DC-CIK cells is stronger than that of peripheral blood DC-CIK cells, but there is no significant differences of cytotoxicity between DCs and CIK cells. As the cord blood is easily gained and does not easily cause a serious graft rejection, the DC-CIK cells should be clinically applied more extensively as novel immune therapy.
Cell Proliferation ; Coculture Techniques ; Cytokine-Induced Killer Cells ; cytology ; Cytotoxicity, Immunologic ; Dendritic Cells ; cytology ; immunology ; Fetal Blood ; cytology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Leukemia ; immunology ; Tumor Necrosis Factor-alpha ; metabolism

This study was aimed to investigate the effect of dendritic cells (DC) on the proliferation capability, immunophenotype changes, level of secreted cytokines and activity against leukemia of cytokine-induced killer (CIK) cells in vitro. DCs and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by trypan-blue staining; the killing activity was detected by MTT assay; immunophenotype changes were analyzed by flow cytometry; the IL-12 and INF-gamma levels of the cultured supernatants were detected by ELISA kits. The results showed that the proliferation capability of DC-CIK cells was significantly higher than that of CIK cells (p < 0.05). Under the same condition, the ratio of double positive cells such as CD3(+) CD8(+), CD3(+) CD56(+) in CIK cells was significantly enhanced by co-cultured with DC cells (p < 0.05). The levels of IL-12 and INF-gamma in cultured supernatants of DC-CIK cells increased noticeably on day 3 as compared with CIK cells cultured alone (p < 0.01, p < 0.05). Within the effector-target ratio range between 5:1 to 40:1, the activity of DC-CIK cells against leukemia cells were much higher than that of CIK cells (p < 0.05), and this effect showed a positive correlation with the effector-target ratio. It is concluded that the proliferation capability of DC-CIK cells, the level of their secreted cytokines and their activity against leukemia cells are significantly higher than those of CIK cells. This research may suggest an approach for clinical immunotherapy against leukemia with DC-CIK cells.
Cell Line, Tumor ; Cell Proliferation ; Coculture Techniques ; Cytokine-Induced Killer Cells ; cytology ; immunology ; metabolism ; Dendritic Cells ; cytology ; immunology ; metabolism ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism

To date, multiple genetic susceptible genes/loci associated with rheumatoid arthritis (RA) have been identified and confirmed through large-scale genetic association studies and genome-wide association study (GWAS). However, the heritability of RA could be not fully explained by these genetic factors, and gene-gene interaction might account for part of the missing heritability. Indeed, genetic interaction study is a critical research direction in the field of genetic epidemiology of RA, and these studies have provided novel insights into the genetic basis and pathogenesis of RA. Additionally, these studies have also provided scientific reference for risk prediction and prevention of RA. This review is aimed to present a summary of recent progress in genetic interaction study of RA, thus implicate further research in this field.

OBJECTIVETo prepare and characterize monoclonal antibodies (mAb) and polyclonal antibodies against nucleocapsid (N) protein of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and to establish antibodies-based sandwich ELISA for detecting N protein of SARS-CoV, which might apply to early diagnosis of patients with SARS-CoV infection.

METHODSBALB/c mice were immunized with purified recombinant N protein of SARS-CoV for producing mAbs, and New Zealand white rabbits were immunized for producing polyclonal antibodies. The identification of antibodies was performed using indirect enzyme-linked immunosorbent assay (ELISA), indirect fluorescent-antibody assay (IFA), and Western immunoblotting. Capturing and detecting antibodies were selected by pairing the mAbs and polyclonal antibodies one by one and an antibodies-based sandwich antigen capture ELISA was used for detecting N antigen of SARS-CoV.

RESULTSNine mAbs and hyperimmune rabbit polyclonal antibodies, specifically against SARS-CoV nucleocapsid protein were obtained. Using paired ELISA assay, three mAbs N1E8, N8E1 and N10E4 were selected as capturing antibody and rabbit polyclonal antibodies as detecting antibody then triple antibodies-based sandwich ELISA was established following horseradish peroxidase (HRP)-conjugated goat anti-rabbit immunoglobulin G. The recombinant N protein was used as a standard to establish a detection sensitivity of approximated 50 pg/ml with this assay. When tested with 420 serum specimens from serologically confirmed SARS patients, the positive rates of serum N protein were 90.1%, 23% and 0%, in which sera collected from 1 to 10 days, 11 to 20 days and beyond 21 days respectively after the onset of symptoms. The specificity of the assay was 99.86% in 715 control serum specimens. There was no cross-reaction with other respiratory viruses and coronaviruses.

CONCLUSIONSpecific and high affinity mAbs and rabbit polyclonal antibodies were obtained. By paired and optimized sandwich ELISA, a sensitive and specific antigen capture ELISA was established for detecting N antigen of SARS-CoV, which might apply to early diagnosis, source tracing and epidemiological studies of SARS.

Animals ; Antibodies, Monoclonal ; biosynthesis ; Antibodies, Viral ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mice ; Mice, Inbred BALB C ; Nucleocapsid ; immunology ; Rabbits ; SARS Virus ; immunology ; isolation & purification ; Sensitivity and Specificity ; Severe Acute Respiratory Syndrome ; virology

OBJECTIVETo evaluate the efficacy and safety of etanercept, a tumor necrosis factor (TNF)-alpha inhibitor, in the treatment of ankylosing spondylitis (AS), and investigate its effect on serum levels of matrix metalloproteinase-3 (MMP-3).

METHODSForty-eight patients with AS received etanercept 25 mg twice a week for a treatment course of 12 weeks. The patients' symptoms, signs, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and side effects were observed before and after the treatment. The serum levels of MMP-3 was determined using enzyme-linked immunosorbent assay (ELISA).

RESULTSAll the patients completed the treatment. The degree of spinal pain and pain at night, the duration of morning stiffness, the finger-to-floor distance, BASDAI and BASFI were significantly improved after the treatment (P<0.05). Etanercept treatment resulted in a significant reduction in serum MMP-3 level in the AS patients to 31.22-/+10.26 ng/ml as compared with the level before treatment (46.17-/+25.74 ng/ml, P<0.05). The reduction of serum MMP-3 was positively correlated to decrement of ESR and CRP (r=0.397 and 0.474, respectively, P<0.05). The most common adverse events of etanercept included injection site reaction and upper respiratory infection.

CONCLUSIONEtanercept treatment has obvious therapeutic effects on AS without serious adverse effects. MMP-3 may be a potentially useful indicator to assess the effect of anti-TNF-alpha treatment in AS patients.

Adolescent ; Adult ; Antirheumatic Agents ; therapeutic use ; C-Reactive Protein ; metabolism ; Etanercept ; Female ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Matrix Metalloproteinase 3 ; blood ; Middle Aged ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Spondylitis, Ankylosing ; blood ; drug therapy ; pathology ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; Young Adult

OBJECTIVETo evaluate the clinical significance of prostate-specific antigen (PSA) screening in early detection of prostate cancer in Chinese men.

METHODSPSA screening was performed in 8562 asymptomatic men who had been enrolled for health checkup and all were > or = 50 years old. Prostate biopsy was recommended for those with a serum PSA level > or = 4.0 ng/ml. The pathological and clinical features of the patients with prostate cancer detected by the PSA screening were compared with that of 82 clinically diagnosed prostate cancer patients during the same period.

RESULTSOf the 8562 asymptomatic men, 719 had PSA levels > or = 4.0 ng/ml and biopsy was performed in 295 of them. Fifty-eight prostate cancers were detected. The biopsy rate was 41.0% and positive detection rate was 19.7%. The overall age distribution in the screening group and the clinical groups was not significantly different (P = 0.176). However, 41.4% (24/58) of the patients in screening group were > 75 years old, and significantly more than that in the clinical group (25.6%, P = 0.0491). The proportion of the patients with PSA levels > or = 20 ng/ml in the screening group was significantly less than that in the patients of the clinical group (44.8% vs. 75.6%, P = 0.0002). Whether in the patients whose age was > 75 years old (P < 0.05) or < or = 75 years old (P = 0.0002), the patients in the screening group had significantly lower Gleason scores < 7 (60.3% vs. 34.1%, P = 0.002), more T1 or T2 tumor (87.9% vs. 26.8%, P < 0.0001) and more chance to receive radical prostatectomy (50.0% vs. 18.3%, P < 0.0001) than the patients in the clinical group did. However, the distributions of PSA levels at diagnosis and biopsy Gleason scores were not significantly different between the above mentioned two groups (P > 0.05).

CONCLUSIONProstate-specific antigen (PSA) screening is useful for early detection of prostate cancer in Chinese men aged > or = 50 years. The patients detected by PSA screening usually show a lower PSA level, Gleason scores and early clinical stage disease, and have more chance for radical prostatectomy than the clinically diagnosed patients.

Aged ; Aged, 80 and over ; Biopsy ; Early Detection of Cancer ; methods ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; diagnosis ; pathology

ObjectiveWorldwide, community-acquired pneumonia (CAP) is a common infection that occurs in older adults, who may have pulmonary comorbidities, including chronic obstructive pulmonary disease (COPD). Although there have been clinical studies on the coexistence of CAP with COPD, there remain some controversial findings. This review presents the current status of COPD in CAP patients, including the disease burden, clinical characteristics, risk factors, microbial etiology, and antibiotic treatment.

Data SourcesA literature review included full peer-reviewed publications up to January 2018 derived from the PubMed database, using the keywords "community-acquired pneumonia" and "chronic obstructive pulmonary disease".

Study SelectionPapers in English were reviewed, with no restriction on study design.

ResultsCOPD patients who are treated with inhaled corticosteroids are at an increased risk of CAP and have a worse prognosis, but data regarding the increased mortality remains unclear. Although Streptococcus pneumoniae is still regarded as the most common bacteria isolated from patients with CAP and COPD, Pseudomonas aeruginosa is also important, and physicians should pay close attention to the occurrence of antimicrobial resistance, particularly in these two organisms.

ConclusionsCOPD is a common and important predisposing comorbidity in patients who develop CAP. COPD often aggravates the clinical symptoms of patients with CAP, complicating treatment, but generally does not appear to affect prognosis.

Community-Acquired Infections ; epidemiology ; microbiology ; mortality ; Humans ; Pneumonia ; epidemiology ; microbiology ; mortality ; Pseudomonas aeruginosa ; pathogenicity ; Pulmonary Disease, Chronic Obstructive ; epidemiology ; microbiology ; mortality ; Risk Factors ; Streptococcus pneumoniae ; pathogenicity

OBJECTIVE To explore the effect of total flavonoids of Rhododendra simsii (TFR) on improving cerebral ischemia/reperfusion injury (CIRI) and its relationship with STIM/Orai-regulated operational Ca2+influx (SOCE) pathway. METHODS Oxygen-glucose deprivation/reoxygenation (OGD/R) PC12 cells were used to simulate CIRI in vitro, and the intracellular Ca2+ concentration and apoptosis rate of PC12 cells were detected by laser confocal microscope and flow cytometry, respectively. The regulation of STIM/Orai on SOCE was analyzed by STIM/Orai gene silencing and STIM/Orai gene overexpression. The CIRI model was established by MCAO in SD rats. The activities of inflammatory cyto?kines IL-1, IL-6 and TNF-αin serum were detected by ELISA. The pathological changes of ischemic brain tissue and the infarction of rat brain tissue were detected by HE staining and TTC staining. The protein and mRNA expression levels of STIM1, STIM2, Orai1, caspase-3 and PKB in brain tissue were detected by Western blotting and RT-qPCR, respectively. RESULTS The results of in vitro experiment showed that the fluorescence intensity of Ca2+ and apoptosis rate in PC12 cells treated with TFR were significantly lower than those in OGD/R group, and this trend was enhanced by SOCE antagonist 2-APB. STIM1/STIM2/Orai1 gene silencing significantly reduced apoptosis and Ca2+overload in OGD/R model, while TFR combined with overexpression of STIM1/STIM2/Orai1 aggravated apoptosis and Ca2+overload. In the in vivo experiment, TFR significantly reduced the brain histopathological damage, infarction of brain tissue, the contents of IL-1, IL-6 and TNF-α in the serum in MCAO rats and down-regulated the expression of STIM1, STIM2, Orai1 and caspase-3 protein and mRNA in the brain tissue, and up-regulated the expression of PKB. The above effects were enhanced by the addition of 2-APB. CONCLUSION The above results indicate that TFR may reduce the contents of inflammatory factors and apoptosis, decrease Ca2+ overload and ameliorate brain injury by inhibiting SOCE pathway mediated by STIM and Orai, suggesting that it has a protective effect against subacute CIRI.

Objective: To evaluate the prognostic significance of comprehensive geriatric assessment (CGA) in Chinese elderly acute myeloid leukemia (AML) patients. Methods: 73 AML patients over the age of 60 were enrolled. CGA stratification included the following 3 instrument assessment: activity of daily living (ADL) ; instrumental activity of daily living (IADL) ; comorbidity score according to the Modified cumulative illness rating score for geriatrics (MCIRS-G) . According to CGA and age, the enrolled patients were grouped into 'fit', 'unfit' and 'frail' categories. Results: The median age of 73 elderly AML patients were 75 years old. According to CGA, 37 (50.1%) patients were classified as 'fit', 14 (19.2%) as 'unfit', and 22 (30.7%) as 'frail'. 33 (89.2%) patients in fit group received induction chemotherapy, or demethylation treatment, as 8 (57.9%) in unfit, 10 (45.5%) in frail. The overall response rate was 68.7%、62.5%, 75.0% in fit, unfit, and frail group, respectively (χ(2)=0.615, P=0.769) .The early mortality (8 weeks) in three groups were different: 5.4%, 7.1%, 27.3%, respectively (P<0.05) . The 1-year overall survival in the 'fit', 'unfit' and 'frail' groups was 64.9%, 28.6% and 22.7%, respectively (P<0.05) . The CGA score, age, ECOG score, WHO classification (2016) were the prognostic factors of AML patients. Conclusion: CGA can be used to determine the prognosis of elderly AML patients.
Aged ; Comorbidity ; Geriatric Assessment ; Humans ; Leukemia, Myeloid, Acute ; Prognosis