OBJECTIVEParkinson's disease (PD), a neurodegenerative disorder, has been reported to be associated with brain neuroinflammation in its pathogenesis. Herein, changes in peripheral immune system were determined to better understand PD pathogenesis and provide possible target for treatment of PD through improvement of immune disorder.

METHODS1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected into mice to prepare PD model. Expression levels of pro-inflammatory and anti-inflammatory cytokines and transcription factors of CD4+ T lymphocyte subsets in spleen and mesenteric lymph nodes and concentrations of the cytokines in serum were examined on day 7 after MPTP injection. Percentages of CD4+ T lymphocyte subsets were measured by flow cytometry.

RESULTSMPTP induced PD-like changes such as motor and behavioral deficits and nigrostriatal impairment. Expression levels of the pro-inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-17 and IL-22, in spleen and mesenteric lymph nodes were upregulated and their concentrations in serum were elevated in PD progression. But, the concentrations of the anti-inflammatory cytokines including IL-4, IL-10 and transforming growth factor (TGF)-β were not altered in the two lymphoid tissues or serum of PD mice. In addition, expression of T-box in T cells (T-bet), the specific transcription factor of helper T (Th) 1 cells, was downregulated, but expression of transcription factor forkhead box p3 (Foxp3), the transcription factor of regulatory T (Treg) cells, was upregulated. In support of the results, the numbers of IFN-γ-producing CD4+ cells (Th1 cells) were reduced but CD4+CD25+ cells (Treg cells) were elevated in both the lymphoid tissues of PD mice.

CONCLUSIONPD has a dysfunction of peripheral immune system. It manifests enhancement of proinflammatory response and CD4+ T cell differentiation bias towards Treg cells away from Th1 cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; CD4-Positive T-Lymphocytes ; pathology ; Cell Differentiation ; Cytokines ; blood ; Disease Models, Animal ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukins ; blood ; Lymph Nodes ; cytology ; Lymphocyte Activation ; Mice ; Parkinson Disease ; immunology ; physiopathology ; Spleen ; cytology ; T-Box Domain Proteins ; metabolism ; T-Lymphocytes, Regulatory ; Th1 Cells ; Transforming Growth Factor beta ; blood

OBJECTIVEWe used an animal model of collagen-induced arthritis (CIA) to study changes and roles of tyrosine hydroxylase (TH) expressed by CD4+ T cell subsets, and then explore the relationship between CD4+ T cell subset-derived catecholamines and inflammatory responses in CIA.

METHODSThirty-six male DBA/1 mice were randomly divided into control group, CIA model group (day 35) and CIA model group (day 55) (n = 12). CIA model was induced by type II collagen (CII) in DBA/1 mice. On the 35th and 55th day following primary immunization, the joints of the mice were observed for clinical score of swelling and the level of anti-CII IgG antibody in serum was examined. Expression of specific transcription factors and cytokines of Th1, Th17, Th2 and Treg cells and TH in mesenteric lymph nodes was measured by means of Western blot. The changes of TH expressed by CD4+ T cell subsets in mesenteric lymph nodes were determined by flow cytometry.

RESULTSClinical score and anti-CII antibody level increased in CIA compared with that in intact mice. Specific transcription factors and cytokines expressed by Th1 and Th17 cells were upregulated and cytokines expressed by Th2 and Treg cells were downregulated in mesenteric lymph nodes in CIA mice. Expression of TH was upregulated and the increased expression of TH in CD4+ T cells was attributed to Th1 and Th17 cells in mesenteric lymph nodes of CIA.

CONCLUSIONThe increase in catecholamines from CD4+ T cell subsets in mesenteric lymph nodes of CIA may be related to inflammatory alleviation in CIA progression.

Animals ; Arthritis, Experimental ; immunology ; CD4-Positive T-Lymphocytes ; enzymology ; Collagen Type II ; adverse effects ; Cytokines ; metabolism ; Disease Models, Animal ; Lymph Nodes ; immunology ; Male ; Mice ; Mice, Inbred DBA ; T-Lymphocyte Subsets ; immunology ; Transcription Factors ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism

Objective To study the effect of topiramate(TPM) on serum level of leptin and the expression of neuropeptide Y(NPY) in arcuate nucleus and their relationship with weight changes in pentetruzole-induced epileptic rats,and to explore the mechanism that TPM could reduce the weight.Methods One hundred and fifteen Wistar rats were randomly divided into 4 groups:blank control group,TPM contrast group,pentylenetetrazol(PTZ) model group,and TPM group.Weight changes were measured every 3 days.Serum leptin level was detected with rodioimmunity method and hypothalamic arcuate nucleus NPY expression was measured by immunohistochemical ABC technique at the 2~(nd),4~(th),6~(th) weekend,respectively.Results In TPM control group and TPM group weight loss appeared in the 4~(th) week compared with other groups at the 3~(rd) weekend and fell to the lowest at 4~(th) weekend(P

BACKGROUNDRecently, the number of patients with prostate cancer who needed to be treated with radical prostatectomy increased rapidly in China. There is still a difference between clinical staging and the post-operative final pathologic staging; hence, an excellent tool for accurately predicting the pathologic stages of prostate cancer is needed urgently in clinical practice. The Partin tables are the most popular and widely used tool for predicting the pathologic stages of prostate cancer because of its high accuracy and ease of implementation. The aim of this study was to externally validate the accuracy of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer.

METHODSWe retrospectively analyzed the data from 203 patients with prostate cancer who underwent radical prostatectomies between June 2000 and May 2012. The accuracies of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer were evaluated using the area under the receiver operating characteristic curve (AUC).

RESULTSUsing the 1997, 2001, and 2007 Partin tables for predicting the current cases, the AUC of organ confinement (OC) was 0.877, 0.788, and 0.726; the AUC of extracapsular extension (ECE) was 0.525, 0.615, and 0.608; the AUC of seminal vesicle invasion (SVI) was 0.875, 0.649, and 0.820; and the AUC of pelvic lymph node invasion (LNI) was 0.808, 0.758, and 0.735 respectively.

CONCLUSIONSThe accuracies of the three versions of Partin tables in predicting OC, SVI, and LNI were good, especially the 2001 Partin table for SVI. In contrast, the accuracy of the three versions of the Partin tables in predicting ECE was fair. The 1997 Partin table was much better than the 2007 table in predicting OC, and the 2001 table in predicting SVI. The 2007 Partin table did not show any advantages.

Aged ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Nomograms ; Prostate-Specific Antigen ; blood ; Prostatectomy ; Prostatic Neoplasms ; pathology ; surgery ; Retrospective Studies

OBJECTIVETo summarize clinical experience in the treatment of low rectal cancer with anterior perineal plane for ultra-low anterior resection of the rectum(APPEAR).

METHODSClinical and follow-up data of 26 patients with low rectal cancer undergoing the APPEAR operation in Department of General Surgery at Peking Union Medical College from September 2009 to August 2011 were retrospectively analyzed.

RESULTSThe 26 cases consisted of 19 male and 7 female patients with an average age of (63.4 ± 9.5) years. The average tumor distance from the anal verge was (4.6 ± 0.7) cm according to preoperative examinations. Fourteen patients received neoadjuvant radiochemotherapy before the operation. All the 26 patients had successful sphincter-preserving operations. The average operative time was (170 ± 21) min and the average intra-operative blood loss (140 ± 69) ml. Complications included one case of intraoperative injury to the rectal wall and 4 cases of postoperative perineal wound infection. Postoperative pathological examination showed well to moderately differentiated adenocarcinomas(n=10), moderately differentiated adenocarcinomas with partial mucinous adenocarcinomas (n=7), poorly differentiated adenocarcinoma(n=1), villous adenoma with high-grade intraepithelial neoplasia (n=1), and rectal villous adenoma(n=1). In 6 cases no residual tumor cells were detected in the surgical specimens. All the patients were followed-up for an average period of(11.4 ± 5.6) months. No impaired urinary function or tumor recurrence was observed during the follow-up. Eighteen patients had the transverse colon stoma closure six months after the operation. The average Wexner continence score was 5.5 after colostomy reversal surgery. The anorectal manometry tests showed that maximum squeeze pressure of the anal sphincter was(224.0 ± 59.3) mm Hg. The maximum resting pressure was (42.5 ± 11.8) mm Hg, and the maximum tolerable volume of the rectum was (120.0 ± 27.4) ml. Anorectal reflexes were present in all these patients.

CONCLUSIONThe APPEAR technique can be applied in the sphincter-preserving operations for low rectal cancer patients with satisfactory anal function.

Aged ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Perineum ; surgery ; Rectal Neoplasms ; surgery ; Rectum ; surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo compare the differences of two recommended diagnostic criteria for metabolic syndrome (MS) in a health check-up population aged 12-19 years in Taiwan province.

METHODThe study data were supplied by the MJ Health Screening Center, which is a private membership chain clinic with 4 health screening centers around the Taiwan Island and provides periodic health examination to its members. The database included a self-administered questionnaire for health history, asking about demographic, socioeconomic, medical, and lifestyle information, and clinical and laboratory measures for every member. A total of 1629 members (873 boys and 756 girls, respectively) received a health check-up first time at MJ centers were recruited from 2005 to 2006. MS detection rate and agreement rate was calculated according to two definitions, respectively. The distributions of MS components and the aggregation of risk factors were further analyzed.

RESULT(1) The range of age-adjusted detection rate of MS for two definitions were 4.05% (5.84% for boys, 1.98% for girls) and 8.35% (10.42% for boys, 5.95% for girls), respectively. It was 0.94% , 14.20% and 36.59% for criterion I among adolescents who were overweight (BMI over 95th percentile), at risk of overweight (BMI between 85th and 95th percentile) and normal weight (BMI below the 85th percentile), respectively; while 3.61%, 25.93% and 53.66% for criterion II. (2) The range of five MS components were 9.09% (low-HDL-C)-16.39% (high blood pressure) for definition I, while 0.98% (high FBG)-27.13% (high WC) for definition II. (3) Of the total subjects, 2.76%, 1.04% and 0.25% were presented with three, four and five MS risk factors for definition I; while 6.69%, 1.60% and 0.34% for definition II, separately. (4) The most common clinical symptom complex of MS was "obesity, hypertension and low-HDL-C" for criterion I, "high TG, obesity and low-HDL-C" for criterion II. (5) The MS diagnostic criterions of I and II were in moderate accordance with agreement rate of 94.35%, Kappa index was 0.518.

CONCLUSIONOur findings reveal that there were relatively large differences in detection and aggregation of risk components on MS when using two recommended definitions, the detection rate of MS in adolescents depends strongly on the parameters chosen and their respective cut-off points. In order to avoid possible relevant under- or over-estimation of the prevalence, it seems advisable that the use of unversally specific cut-off values seems to be more appropriate to give more reliable results.

Adolescent ; Adult ; Child ; Cross-Sectional Studies ; Diagnostic Techniques and Procedures ; standards ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; Reference Standards ; Taiwan

OBJECTIVETo study the effect and the possible mechanism of IL-6 on NMDA-excited neuronal discharges of rats in vitro.

METHODSThe cerebellar slices were prepared and spontaneous discharges of single cerebellar interposed nuclear (IN) neurons were recorded by extracellular recordings. The cerebellar slices were perfused with artificial cerebral spinal fluid (ACSF) containing N-methyl-D-aspartate (NMDA), IL-6, JAK inhibitor AG490. The changes in firing activities of the neurons treated with the drugs were recorded. The levels of phosphorylation at serine 897 site of NMDA receptor subunit 1 (NR1) in the neurons treated with various drugs mentioned above were detected by Western blot.

RESULTSThe discharge rates of the neurons that were treated with IL-6 together with NMDA were significantly lower than those of the neurons treated with NMDA alone. AG490 partially blocked the inhibitory effect of IL-6 on the NMDA-stimulated neuronal firing activity. The treatment of the neurons with IL6 and NMDA led to a concentration-dependent suppression of the phospho-NR1 expression relative to those neurons treated with NMDA alone. AG490 blocked the effect of the IL-6-induced depression of phospho-NR1 expression.

CONCLUSIONIL-6 inhibits NMDA-stimulated neuronal firing activity, and simultaneously down-regulates the phosphorylation of NR1 at serine 897 site.

Animals ; Cerebellum ; drug effects ; metabolism ; In Vitro Techniques ; Interleukin-6 ; pharmacology ; N-Methylaspartate ; pharmacology ; Nerve Growth Factors ; metabolism ; Neurons ; drug effects ; metabolism ; physiology ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism

Objective To explore whether Th17 cells play a role in the neuroinflammatory process of Parkinson's disease (PD).Methods C57BL/6 mice were injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models.Saline-injected and naive mice were used as controls.In substantia nigra compact (SNc) part,double-immunofluorescence staining was used to observe glucose transporter (Glut 1+) and CD4+ T cells or retinoic acid-related orphan nuclear receptor γt (ROR γt) and intedeukin (IL)-17.Real-time PCR was employed to examine the mRNA expressions ofIL-17 and IL-22 in the SNc.Results PD models were successfully induced in the mice; CD4+ T cells invaded into the brain parenchyma of PD mice models.Besides,the mount of CD4+ T cells on the seventh day of MPTP injection was more than that of the second day of MPTP injection.The expressions ofROR γt and IL-17 increased in the SNc of the PD mice; a co-localization ofROR γt and IL-17 in SNc indicated that invasive CD4+ T cells contained Thl7 cells.There was evident up-regulation in the expressions ofIL-17 and IL-22 mRNAs in PD mice as compared with the saline-injected or intact mice,which was much more evident in the late phase of disease (the seventh day of MPTP) than in the early stage (the second day of MPTP injection).Conclusion Neuroinflammation induced by infiltration of Th17 cells participates in the process of PD.

Objective To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and efficacy and adverse drug reactions of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) in Chinese population.Methods Retrieved from CNKI,VIP,Wanfang,China biology medicine(CBM),PubMed,EmBase and Cochrane Library,case control studies about the relationship between MTHFRC677T and A1298C genetic polymorphisms and efficacy and adverse drug reactions of MTX in the treatment of rheumatoid arthritis were collected.Meta-analysis was performed by software of RevMan 5.3.Results Five studies involving 449 participants were included,and five involved MTHFR C677T,three involved A1298C.The Meta-analysis showed that compared with 1298AC/CC,1298AA had a lower clinical efficacy (P ＜0.05);and compared with 677CT/TT,677CC had a lower risk of adverse drug reactions (P ＜ 0.05).Conclusion MTHFR C677T and A1298C polymorphisms seem to be influence the efficacy and adverse drug reactions of methotrexate in the treatment of rheumatoid arthritis in Chinese population.However,the evidence was not strong due to the quantity of the studies.Further study for association of MTHFR polymorphisms with MTX efficacy and toxicities should be needed in larger RA population.

Objective Exploring the occurrence and clinical characteristics of adverse drug reactions caused by the treatment of malignant hematological diseases in children with pegaspargase,in order to provide reference for safe drug use in clinical practice.Methods Summarize and organize 24 cases of adverse reactions related to pegaspargase reported in the pediatric hematology ward of our hospital from January 2016 to June 2023 for analysis and re evaluation.The basic information,severity of adverse drug reaction(ADR),dosage,route of administration,clinical manifestations,occurrence time and outcome of ADR were analyzed statistically.Results Among the 24 ADR reports,there were 15 males(62.50％)and 9 females(37.50％).The age ranged from 2 to 15 years,with an average age of(7.79±4.68)years.There were 16 children under 10 years old(66.67％).The primary disease is acute lymphocytic leukemia(87.50％).The administration mode of 24 patients was intramuscular injection,and the dosage was 1200-3 750 U.A total of 30 AD Rs occurred in 24 patients,10 of which were serious ADRs.The most common organ involved in ADR was gastrointestinal system damage(8 cases,27.59％),followed by systemic(6 cases,20.69％)and skin and Subcutaneous tissue(5 cases,17.24％).The shortest occurrence time of ADR is 5 minutes after medication,and the longest is 56 days after medication.Conclusion Clinical attention should be paid to the occurrence characteristics of asparaginase ADR.After medication,patients need to be monitored for safety over a long period of time,closely monitoring their clinical symptoms and related test indicators,especially in young children,to reduce the damage caused by ADR to patients.