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BackgroundPrimary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.MethodsThe peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions.ResultsGenome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While CyTOF analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.ConclusionDNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.

目的 探讨急性髓系白血病（AML）自发缓解的临床特点及可能的机制。 方法 回顾性分析郑州大学第一附属医院诊治的1例伴有MLL-AF9基因重排和肝功能损伤的AML自发缓解患者的临床资料，并进行相关文献报道病例汇总分析。 结果 该患者伴有MLL-AF9基因重排，经历了肺部感染、发热、肝功能损伤，治疗上给予抗感染、输注血制品，未经化疗，患者获完全缓解（CR），随访35个月，仍处于CR，期间伴有轻度间接胆红素升高。1990年至2021年6月文献报道的有骨髓检测支持的AML（非急性早幼粒细胞白血病）自发缓解患者56例，与本次报道的1例汇总分析，共57例患者，其中男37例，女20例，中位年龄51（20～83）岁，中位缓解时间为5个月，52例患者获得CR，5例具有染色体核型资料的长期缓解且至今未复发的病例，3例为正常染色体核型，2例伴有t（9;11）（q21;q23）异常。 结论 AML自发缓解罕见，可能与免疫抑制、基因均有关。

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies, and patients with established rheumatoid arthritis (RA) by applying an integrative multi-omics approach where we investigated changes at the level of DNA methylation and gene expression and its relation to disease pathogenesis. We performed genome-wide DNA methylation and gene expression profiling of synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66) where patients with SJC66 of 9 or more displayed reasonable separation from the rest. Specifically, combined DNA methylation and gene expression patterns of patients with SJC66 ≥ 9 displayed activation of the immune response as well as dysregulation of cell adhesion pathways. Through an integrative analysis framework, we reveal differences in both methylation and expression at 59 genes associated with the difference between SJC66 ≥ 9 and 0 < SJC66 ≤ 8, for which we identify specific transcripts correlated with differential methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of the changes associated with an increasing number of swollen joints in RA patients, and point to novel candidate targets for the treatment of the disease. Funding Statement: AYFLY was funded by the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. ITN-2014-EID-641665. Declaration of Interests: AYFLY, KM, GR, EC, HDL, DFT, CL, DG, and RB are employees of GSK. EF and PPT are employees of Novartis and Kintai Therapeutics, respectively. WJJ is financially supported by GSK and Mead Johnson. All declarations are correct for the time of writing and/or conducting this study. Ethics Approval Statement: All subjects provided written informed consent and the collection and use of the samples received Institutional Review Board review and approval. Characteristics of patients included in this study are listed in Table S1.

Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.

To investigate the expression of human myozenin 2 (MYOZ2) in cancer tissues and its effect on the prognosis of patients with gastric cancer.Gastric cancer tissue and adjacent normal tissue specimens were obtained from a total of 258 patients together with complete clinicopathological data. Those patients were treated in Harbin Medical University Cancer Hospital from March 2007 to March 2012. Quantitative Real Time-Polymerase Chain Reaction (RT-PCR) was used to detect the expression of MYOZ2 messenger RNA (mRNA) in gastric cancer tissues and normal gastric tissues, and correlations between the expression level of MYOZ2 in gastric cancer tissues and the clinicopathological parameters of patients were analyzed. MYOZ2 protein expression levels in different gastric cancer cells were detected by Western blotting; transwell chamber assay was used to detect the effect of MYOZ2 expression on the in-vitro migration and invasion abilities of gastric cancer cells; 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to examine the in-vitro proliferation and growth abilities of gastric cancer cells.The expression level of MYOZ2 mRNA in gastric cancer tissues was significantly higher than that in cancer-adjacent tissues in 258 cases (p0.05). Western blotting results showed that the expression level of MYOZ2 protein in gastric cancer tissues was significantly increased compared with that in the corresponding adjacent healthy tissues (p0.05). In-vitro growth, migration and invasion abilities of MYOZ2 positive gastric cancer cells were significantly higher than those of normal tissue cells. Univariate analysis showed that the high expression level of MYOZ2 in gastric cancer tissues was closely related to tumor size, lymph node metastasis, and pathological tumor-node-metastasis (pTNM) staging (p0.05), but not associated with gender, age, differentiation degree, and tumor location (p0.05). The 1-, 3- and 5-year survival rates of patients with low expression level of MYOZ2 (n=130) were higher than those of patients with high expression level of MYOZ2 (n=128). Multivariate analysis revealed that the expression level of MYOZ2 (p=0.000), lymph node metastasis (p=0.002), and pTNM staging (p=0.015) were independent risk factors influencing the prognosis of gastric cancer.Our results showed that the expression level of MYOZ2 may play an important role in the occurrence and development of gastric cancer, and can also provide references for the clinical diagnosis and treatment of gastric cancer.

目的 评估含门冬酰胺酶方案化疗桥接自体造血干细胞移植（auto-HSCT）治疗鼻型结外NK/T细胞淋巴瘤（ENKTL）的疗效及安全性。 方法 回顾性分析2012年1月至2017年6月期间接受含门冬酰胺酶方案诱导化疗桥接auto-HSCT的16例进展/复发ENKTL患者的临床资料。 结果 ①全部16例患者中男12例、女4例，中位年龄35.5（14~61）岁，移植前处于第1、2次完全缓解（CR1、CR2）期的患者分别为11、5例。移植前EB病毒（EBV）DNA（EBV-DNA）阴性、阳性患者分别为13、3例。②16例患者均获得造血重建，中性粒细胞植入中位时间为12（8~17）d，血小板植入中位时间为15.5（12~24）d。③至随访截止，未发生移植相关死亡，3例患者因疾病进展死亡，7例患者总生存（OS）期及无进展生存（PFS）期均超过2年。④移植前CR1、CR2患者的OS及PFS差异无统计学意义（P=0.162，P=0.123）。移植前EBV-DNA阴性、阳性患者的OS、PFS差异无统计学意义（P=0.280，P=0.244）。 结论 含门冬酰胺酶方案化疗桥接auto-HSCT治疗进展/复发ENKTL具有较好的疗效和安全性。

We aimed at investigating the functions of endothelial progenitor cells (EPCs) in the pathophysiology of coronary artery spasm (CAS) and coronary artery disease (CAD), as well as to evaluate the correlation of these diseases with the number and function of EPCs, the plasma concentration of vascular endothelial growth factor 165 (VEGF165) and stromal cell-derived factor 1 (SDF-1).Participants were recruited into three groups, CAS, CAD and the control. The number and functions of early EPCs and outgrowth endothelial cells (OECs) were determined in peripheral blood samples, and the endothelial function was evaluated by measuring endothelium-dependent flow-mediated vasodilation (FMD).No differences of baseline characteristics were found among CAS, CAD, and the control groups. The OECs isolated from CAS and CAD exhibited significant decrease in the percentage of CD34+/CD45- population, OEC colony formation, OEC proliferation and OEC tubulogenesis, nitric oxide (NO) production, endothelial nitric oxide synthase (eNOS) activity, and the phosphorylation level at Ser1177 of eNOS, compared with OECs isolated from control participants. Meanwhile, FMD was significantly reduced in CAS and CAD (CAS, 4.1% ± 1.9%; CAD, 4.3% ± 1.8%; control, 11.2% ± 3.5%). FMD was positively correlated to OEC functions including NO production, eNOS phosphorylation, colony formation, and proliferation. No differences of plasma VEGF165 and SDF-1 concentrations were recorded among these three groups. Similarly, there was no correlation between plasma VEGF165 (and SDF-1) concentration and EPC number and function.EPCs show the potential of repairing damaged endothelium in CAS and CAD.

SUMMARYIn the near future, the inactivated enterovirus 71 (EV71) vaccine is expected to become available on the market in China. Since EV71 is a major cause of hand, foot and mouth disease (HFMD), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. However, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of EV71 HFMD infection. Based on the 2011 population data, we estimated the clinical and economic effect of EV71 HFMD infection in children aged 0–9 years in Shanghai, China. The annual cost related to HFMD is >US$7.66 million for a population of 1·42 million children aged 0–9 years with an average cost of US$208.2/case. The extrapolated cost for EV71 HFMD infection was US$3.53 million, comprising 46·1% of the overall cost associated with HFMD. Around 97% of all of the HFMD-related expenses were paid for by the families creating a considerable economic burden. Our findings could provide the necessary recommendations on the most effective national EV71 vaccine implementation, as well as a baseline data for assessing the cost-effectiveness of the vaccine in China.

To investigate the in vitro and in vivo effects of hydrogen sulfide (H2S) on activated hepatic stellate cells (HSCs) and carbon tetrachloride (CCl4)-induced hepatic fibrosis rats. To explore the in vitro and in vivo expression of Phospho-p38, Phospho-Akt and NF-kB in HSCs treated with H2S.HSC-T6 cells were incubated and activated with 500 µg/L ferric nitrilotriacetate (Fe-NTA), and then were incubated with NaHS, an H2S-releasing molecule for 6, 12, 24 and 48 h. MTT assay was performed to detect cell viability. Propidium iodide (PI) staining was used to determine cell cycle by flow cytometry. Apoptosis was detected with Annexin-V FITC (fluorescein isothiocyanate) and PI (propidium iodide) double staining. Western blotting was performed to detect protein expressions of Phospho-p38, Phospho-Akt and NF-kB. Hepatic fibrosis model was established by intraperitoneal injection of CCl4 in male Wistar rats, and rats were randomly divided into three groups, including healthy control, rats treated with CCl4 + saline, and rats treated with CCl4 + NaHS. Immunohistochemistry analysis was performed to measure protein expression of Phospho-p38 and Phospho-Akt in rat hepatic samples.NaHS inhibited the proliferation of Fe-NTA (nitrilotriacetic acid)-induced HSC-T6 cells in a dose-dependent way at 6, 12, 24 and 48 h. NaHS (500 µmol/L) induced G1 phase cell cycle arrest and promoted survival in Fe-NTA-induced HSC-T6 cells. NaHS decreased Phospho-p38 and increased Phospho-Akt expressions in Fe-NTA-induced HSC-T6 cells and CCl4-induced liver fibrosis rats.Exogenous H2S inhibits activated HSC-T6 cells and induces cell cycle arrest and apoptosis. Decreased Phospho-p38 and increased Phospho-Akt expressions may mediate the anti-fibrosis effect by exogenous H2S.

Portal hypertension and splenomegaly are common in patients with cirrhosis. However, there is limited previous in vivo research on the correlation between spleen stiffness and stages of liver fibrosis. This study aimed to evaluate the diagnostic value of spleen stiffness measurement (SSM), using acoustic radiation force impulse (ARFI) technology, for liver fibrosis assessment. Eligible patients with chronic hepatitis B or C (n = 163) underwent concurrent liver stiffness measurement (LSM), SSM and percutaneous liver biopsy. Receiver operating characteristic curves estimated the diagnostic performance of SSM, with multiple linear regression models for LSM and SSM determining the significance of explanatory factors. Results indicated significant correlation between LSM and SSM (R(2) = 0.574, P0.0001). Using SSM to classify METAVIR fibrosis (METAVIR F) scores, the areas under curves were 0.839 (95% CI: 0.780-0.898) for METAVIR F1 vs F2-4, 0.936 (95% CI: 0.898-0.975) for F1-2 vs F3-4 and 0.932 (95% CI: 0.893-0.971) for F1-3 vs F4, all P0.001. Multiple linear regression models identified BMI, spleen stiffness, METAVIR F3 and F4, serum alanine aminotransferase, international normalized ratio of prothrombin time, sodium and platelet count as significant independent explanatory factors for liver stiffness (adjusted R(2) = 0.724, P0.001). Male gender, liver stiffness, METAVIR F2, F3 and F4 also significantly and independently explained spleen stiffness (adjusted R(2) = 0.647, P0.001). ARFI SSM is potentially useful as a single or adjunct predictor of stages of liver fibrosis.

SUMMARYWe retrospectively analysed the epidemiological data of all hand, foot, and mouth disease (HFMD) cases from the largest paediatric infectious diseases centre in Shanghai between 2007 and 2010. A total of 28 058 outpatients were diagnosed with HFMD, of which 3948 (14·07%) were hospitalized, 730 (2·60%) had complications with neurological disorders and pulmonary oedema/haemorrhage, and 11 (0·04%) died. The peak season was the summer months. Boys were more affected than girls. Since 2008, the major population group affected has shifted from native Shanghainese children attending preschool to migrant children and younger children cared for at home. Children aged 1–4 years constituted 82·27% of cases. EV-A71 was tested in clinical samples taken from severe cases in 2009 and 2010, and from most inpatients in 2010. EV-A71 was positive in 99·17% and 86·31% of severe cases, respectively in 2009 and 2010. All 12 cases with pulmonary oedema or haemorrhage were infected with EV-A71. Ten (90·90%) of 11 fatal cases were attributable to EV-A71 infection. In 2010, EV-A71-positive cases accounted for 54·12% of inpatients. The dominant circulation of EV-A71 led to the outbreak of HFMD and occurrence of severe and fatal cases.

Background In this study, we assessed the prognostic value of the lymph node ratio (LNR), established a hypothetical tumor–ratio–metastasis (TRM) staging system and compared it with the 7th edition International Union Against Cancer pathological N (pN) and tumor–node–metastasis (TNM) system. Patients and methods A total of 1343 gastric cancer patients undergoing D2 resection were staged using the TRM staging system and the 7th edition TNM system. Optimal cut points of LNR were calculated using X-tile software and validated by bootstrapping. Homogeneity, discriminatory ability, and monotonicity of gradients of the TRM and TNM systems were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. Results Optimal cut points classified patients into LNR0 (0%), LNR1 (1%–30%), LNR2 (31%–60%), and LNR3 (61%–100%) groups. In univariate, multivariate and stratified analyses, the LNR staging showed superiority to the 7th edition pN staging. The TRM staging system had higher linear trend and likelihood ratio χ2 scores and smaller AIC values compared with those for the TNM system, which represented the optimum prognostic stratification. Conclusions The novel TRM staging system predicts survival of gastric cancer more accurately than the 7th edition TNM system. It may be considered as an alternative to TNM system.

To estimate the biological doses for two severely exposed subjects (A and B) in a radiation accident in Shandong Jining, China in 2004.Conventional chromosome aberration analysis and cytokinesis-block micronuclei (CBMN) assay were performed in peripheral blood and bone marrow samples on two subjects after the accident. A new dose-effect curve and the nuclear division index (NDI) obtained from in vitro irradiation experiments using high dose of (60)Co gamma-rays were used to estimate the exposed doses.No metaphases or binucleated cells were observed in the peripheral blood cultures from either of the subjects. However, metaphases and binucleated cells were obtained from both subjects after bone marrow cultures. Both dicentric/ring and micronuclei yields were very high. The dose estimated for A and B were 20.0 Gy and 8.8 Gy, respectively, by dicentric/ring scoring, similar to the data by combination of the CBMN and NDI (CBMN + NDI) assay. The estimated doses by the two methods were in accordance with the clinical symptoms.The new curve, together with the CBMN + NDI assay, are reliable for estimating higher doses of irradiation. In future radiation accidents, the accuracy and significance of these methods can be further tested.

44 cases of adrenal hemorrhage (AH) were analyzed. The forensic autopsy showed that AH occurred mainly in male aged from 20 to 40 years old. The traumatic AH was more often seen in young men and the pathologic AH was mostly seen in elderly persons. AH were more likely found in bilateral adrenal corticomedullary junction. The pathological grade of AH was not related to the interval time of survival. The pathologic mechanism of AH was discussed as well.

To observe the dynamic variations of blood lipids and circulatory endocrine factors in acute myocardial infarction(AMI) patients.We determined plasma levels of ET-1, ANP, insulin and serum lipids on the 1st, 3rd, 7th and 14th day in 41 patients with acute myocardial infarction.The serum levels of TC, LDL-C obviously decreased from the 3rd to the 7th day, and gradually elevated on the 14th day. The serum level of TG elevated gradually and showed significant difference after one week. HDL-C had no significant difference. The levels of ET-1 and insulin increased to highest level on the 1st day and decreased gradually since then. However, ANP reached the highest value on the 3rd day, and decreased markedly in fourteen days later. On the 1st day, only the concentration of insulin was negatively related with serum levels of TC, LDL-C(r = -0.376, -0.388, respectively, P0.05). The concentrations of blood lipids weren't related with circulatory endocrine factors during other phases.The primary characteristics of blood lipids dynamic variations are the decrement of TC, LDL-C and the increment of TG during acute phase of AMI. Meanwhile, the concentrations of ET-1, ANP and insulin present dynamic variations and may effect the metabolism of blood lipids through some cytokines.

To observe the effect of puerarin on heart function and serum oxidized-LDL(ox-LDL) in patients with chronic cardiac failure.Seventy-eight patients with chronic cardiac failure were randomly divided into two groups, regular group (R) and regular + puerarin group (P). All patients in two groups received conventional treatment with inotropic agents, diuretic, and vasodilator, etc. The patients in the P group took puerarin 400 mg.d-1 for 10 days.After treatment, the clinical heart function of the patients in the two groups was improved, but there was no significant difference between them; the left ventricular ejection fraction (EF) of patients in the P group was higher than that in the R group(P0.05); and serum ox-LDL level was significantly decreased in the P group patients, but that was no change in the R group patients(P0.05).Puerarin may improve the clinical heart function, increase the left ventricular ejection, meanwhile, it may decrease the level of ox-LDL.

To investigate the repairing result for the massive bony defects of upper and middle tibia and lower femur.Since 1974, four types of pedicled-fibula transposition were performed to repair the massive bone defect of tibia and femur in 25 cases, which included; 9 cases with benign tumor of upper part of tibia were performed muscle-pedicled fibula transposition and knee fusion after tumor resection; 9 cases with extensive benign tumor or tumoroid lesion of tibia shaft were performed muscle-pedicled fibula transposition and tibia-fibula fusion after tumor resection; 2 cases with extensive benign tumor or tumoroid lesion of middle and lower parts of tibia were performed vascular pedicled fibula transposition and tibia-fibula fusion; 5 cases with benign tumor of distal femur were performed vascular pedicled fibula reversal transposition and knee fusion.After 3 months to 11 years follow-up, 23 cases showed bone healing at 6 months postoperatively. The other 2 cases showed bone healing at 12 months postoperatively. All cases had satisfactory functional rehabilitation.Pedicled-fibula transposition is a choice method for repairing massive defects of tibia and femur.

To explore the antistress effect of Morinda officinalis (Chinese medicine "Bajitian") oligosaccharides (MW-97) in mice.Male mice and rats were subjected to a variety of unpredictable stressors on a daily basis over 15 d period and then the Vidiomex-V image pattern analytic system was used to observe the spontaneous motor activity. Meanwhile, regular method was used to prepare pathologic section of adrenal gland and blood cells analytic system was used to detect white blood cell (WBC) count (including relative WBC percentages) in peripheral blood. On the end, the serum level of stress hormone was detected using radioimmunoassay.Chronic stress resulted in diffuse hyperplasia of the adrenal cortex and atrophy of the adrenal medulla in mice, which suggested that stress-adaption failure of the adrenal gland occurred, while adrenal gland of the mice pretreated with MW-97 (100 mg/kg, ip) prior to each stressor for 15 d did not occur any pathologic changes. In addition, chronic stress also significantly reduced the WBC count and relative WBC percentages in the peripheral blood, including the percentage of lymphocytes, monocytes, neutrophils, however, MW-97 (25 and 100 mg/kg) reversed these changes and raised WBC count, along with relative WBC percentages significantly. Furthermore, the serum concentration of testosterone was decreased and corticosterone was increased significantly in chronically stressed animals. MW-97 also declined the serum level of corticosterone and raised level of testosterone. MW-97 had no effects on the spontaneous motor activity in the stressed mice.MW-97 had antistress effect against chronic stress, moreover, MW-97 had no excitatory or inhibitory effects on the CNS, which suggested that MW-97 might become a new kind of antistress agent.

The alteration of cardiac beta-adrenoceptor (beta-AR) and subtypes in Wistar rats of 48 and 10 weeks old were investigated by radioligand binding assay and functional determination of isolated perfused left atria. The results indicated that: (1) The density of cardiac total beta-AR was downregulated about 28% in 48 weeks old rats as compared with rats of 10 weeks old for both beta 1- and beta 2-AR; (2) The sensitivity of beta-AR and subtypes to isoproterenol in isolated perfused atria was significantly lowered in rats of 48 weeks old; (3) The beta-AR mediated contractile effect of 10 weeks old rat hearts was mainly attributed to beta 1 type, but equally to both beta 1 and beta 2 types in 48 weeks old rat hearts; (4) The two receptor subtypes showed mutually potentiation effect in 10 weeks old rat hearts when stimulated simultaneously, but only additive in 48 weeks old rat hearts.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a (CAG)n array in the MJD1 gene. We analyzed the sizes of the (CAG)n array using DNA samples from 61 members of four Chinese MJD families and 18 Chinese normal control subjects and confirmed that the (CAG)n array in 15 MJD chromosomes was expanded to 72-86 repeat units. There were no subjects with (CAG)n array sizes intermediate between those of normal and MJD affected groups. Meanwhile, we found a significant negative correlation between the age of onset of symptoms and (CAG)n array size. The largest (CAG)n array of 86 repeat units was in the youngest patient, whose age of onset was 5 years. The intergenerational increase in number of CAG repeat units was associated with the clinical phenomenon of anticipation.

To study the effect of the angiotensin-converting enzyme (ACE) inhibitors perindopril (Per) and enalaprilat (Ena) on the reactivity of the endothelium in normal rats.Male rats were treated intragastrically with Per (2 mg.kg-1.d-1) or placebo (n = 18) for 6 wk. Aorta was isolated for experiment. Another set of isolated aortic rings with and without endothelium were incubated with Ena (0.1 mumol.L-1) for 30 min. Responses to acetylcholine, serotonin, phenylephrine, sodium nitroprusside (SN), and nitroglycerin (Nit) were observed.Endothelium-dependent relaxation to acetylcholine was augmented in aortic rings from rats treated with Per in comparison with control. The IC50 value (95% confidence limits) decreased from 3.8 (0.56-26.1) mumol.L-1 (control group) to 0.98 (0.28-3.41) mumol.L-1 (Per-treated group). The maximal relaxation was augmented from 62 +/- 9% to 78 +/- 10% (P0.01). However, the responses to the endothelium-independent vasodilators, SN and Nit, were similar. Serotonin- and phenylephrine-induced contractions were decreased, which were influenced by basal release of endothelium-derived relaxing factor (EDRF). EC50 values was 6.1 (2.6-14.4) nmol.L-1 vs 8.3 (3.6-18.8) nmol.L-1 in comparison with control group and Per-treated group. The maximal contraction was decreased from 2.42 +/- 0.29 g (control group) to 1.96 +/- 0.25 g (treated group) (P0.01). Similar results were found in incubation with Ena.Ena and Per enhanced the basic release of EDRF from vascular endothelium.

Our previous work showed that a lymphocyte proliferation suppressing factor could be found in the serum of restraint mice. In the present work, it was found that intracerebroventricular (icv) injection of IL-1 receptor antagonist (IL-1Ra) was found capable of suppressing the production of such a serum protein under restraint stress. Nearly complete suppression could be achieved by 5.0 micrograms IL-1Ra. Intracerebroventricular injection of IL-1 beta (1 pg), however, increased the generation of the supressive protein. Neither intraperitoneal (ip) injection of IL-1Ra or IL-1 beta had any effect on the generation of the protein. The fact that icv. injection of a very small dose of IL-1 beta (0.06 fmol) was effective on the generation of the supressive protein led us to suggest that IL-1 in brain might act as an important mediator between CNS and the immune system.

Our previous work showed that a suppressive factor (a protein with large molecular weight) in serum was induced by restraint stress in mice and rats, which suppressed Con A induced lymphocyte proliferation. It was also found that the generation of serum suppressive factor was under control of the central nervous system. Our further study showed that intracerebroventricular (icv) injection of interleukin 1 receptor antagonist (IL-1Ra) antagonised the generation of serum suppressive factor induced by restraint stress and icv injection of interleukin-1 beta (IL-1 beta) increased the generation of the suppressive factor. Our experiment also showed that the serum suppressive factor induced by restraint stress was first made in lymph tissue and then released into blood. The present work was designed to investigate the role of IL-1 in the brain in generation of the suppressive factor in lymph node in mice. Icv injection of IL-1 beta (1 pg/mouse) was shown to significantly increase the generation of the suppressive factor in lymph node. Icv injection of IL-1Ra, however, antagonised generation of the suppressive factor. In mice without restraint stress, both the suppressive factor in serum and in lymph node were found to be induced in dose-dependent manner by icv injection of IL-1 beta. Taken together, these results suggest that IL-1 beta in brain played a very important role in generation of the suppressive factor in lymph node. The positive correlation between the suppressive action of lymph node and of serum added to the evidence that lymph tissue is probably the source of the serum suppressive factor.

Ninety two patients with unexplained syncope and 52 normal controls without history of syncope were divided into three groups respectively. Baseline tilt table test (BTTT), multistage isoproterenol tilt table test (MITTT), and single stage isoproterenol tilt table test (SITTT) were performed in all of them. Logistics regression was used with the result of TTT as independent variable; dependent variables included sex, age, basal heart rate, basal blood pressure, the index of syncope (i) and the difference between basal heart rate and the rate before tilting (h12). The results were as follows: (1) According to the regression for the total population tested, the main factors influencing the result of TTT were i and h12 (P = 0.012 and P = 0.001). Similar result was found in the patient group (P = 0.052 and P = 0.032). (2) In the control group, sex and h12 were the predictors of the result (P = 0.090 and P = 0.016). It is concluded that: (1) The result of TTT is mainly affected by the frequency and degree of syncope, as well as by the use of isoproterenol; (2) Isoproterenol increases the sensitivity of TTT, but decreases the specificity; (3) Sex is probably an important factor affecting the result of TTT.

Selective ablation of slow pathway by radiofrequency (RF) current in 34 patients with atrioventricular (AV) node pathways and tachycardia was performed with two methods in our section; posterior approach was used in the first 12 patients, the slow pathways were ablated successfully. Inferior approach was performed in the other 22 patients. Slow pathways were interrupted in 14 patients. Retrograde fast pathways and/or slow pathways were ablated in 6 patients. Retrograde fast pathways and slow pathways were abolished and antegrade fast pathways were injured transitorily in 2 cases. The total procedure time was shorter, RF applications were fewer by inferior approach than by posterior approach (P0.05). Both antegrade and retrograde conduction of fast pathways had not been affected after slow pathways were ablated (P0.05). After a mean of 8 months follow-up, two patients recurred and were ablated successfully again. We come to the conclusion that inferior approach might be a preferable method compared with posterior approach; the slow pathways is the compact node and its posterior input of transitional cells; the retrograde fast pathway may be the anterior superficial group of transitional cells and is not always in the same location of antegrade fast pathway.

By using French's method TBSA in CSFs of 43 patients with tuberculous meningitis and 40 patients with non-tuberculous meningitis were performed. All the patients with tuberculous meningitis were positive and all the patients with non-tuberculous meningitis were negative. So the results showed that the method is a rapid, sensitive and accurate for diagnosis of tuberculous meningitis.

The authors report extraction of cupric intraocular foreign bodies in 108 cases with a success rate of 99.07%. The methods utilized and improvements made in localizing the foreign bodies and the procedures of operation were described. Suggestions were also made concerning the timing of operation and the treatment of preoperative and postoperative complications.

To determine the possibility that asymptomatic bronchial hyperresponsiveness (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in a 3,067 population survey (BHR group). Eighty-eight age-matched students (48 male, 40 female) with normal bronchial responsiveness served as control subjects. Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24 h when symptoms occurred. Histamine inhalation tests were performed at the beginning of the study and at the end of the first and the second year. In the BHR group, 58 students remained bronchial hyperresponsive at the end of follow-up. Nine of 31 students with initially diagnosed bronchial asthma had their symptoms relieved entirely, but ten asymptomatic students developed asthma. The incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5 percent) in the BHR group were significantly higher than those (2.27 percent, 2.27 percent) in the control group. FVC and FEV1 showed no significant difference between two groups. PD20 FEV1 values in newly diagnosed asthmatics were significantly lower than those in asymptomatic students both at the beginning (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p0.05) or the end (3.47 +/- 1.73 mumol vs 6.55 +/- 1.51 mumol, p0.05). The percentage of early respiratory illness was significantly higher in those with newly diagnosed asthma (80 percent) than in asymptomatic students (22.3 percent), but atopic index and the percentage of parental asthma showed no difference between two groups. In nine asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20 FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the remaining six. The higher the BHR, the more likely the students developed asthma. About 45 percent of asymptomatic students with PD20or = 3.2 mumol developed asthma in the following two years and 80 percent of them had a history of early respiratory illness, suggesting that they may have subclinical or potential asthma.

We have evaluated the effect of various autonomic drugs on the electromyographic activity of the sphincter of Oddi and the small intestine of seven opossums. Hexamethonium bromide and atropine sulfate abolished and bethanechol increased the frequency of spike bursts in the sphincter of Oddi and duodenum. Phenylephrine and epinephrine increased the number of spike bursts in the sphincter of Oddi after a short period of stimulation. No spike potentials were seen in the duodenum after infusion of norepinephrine. Clonidine and dobutamine decreased spike burst activity in the sphincter of Oddi and duodenum. Terbutaline also decreased the frequency of spike bursts in the sphincter of Oddi but did not change the number in the duodenum. Prior infusion of antagonists blocked partially or totally the effect of all respective agonists except for yohimbine, which did not inhibit the effect of clonidine. These findings suggest that the sphincter of Oddi may have cholinergic, alpha 1, alpha 1, beta 1 and beta 2-adrenergic receptors. Cholinergic agonists stimulate and alpha 2, beta 1 and beta 2-adrenergic agonists inhibit the motility of the sphincter of Oddi and the small intestine. Alpha-adrenergic agonists stimulate the motility of the sphincter of Oddi and inhibit the motility of the small intestine.

Mixed longitudinal data of length and weight growth from 595 rural and 337 urban infants were analysed. Count models were fitted to the means of length and weight in different ages, sexes and feedings separately. The curve fitting to the data was rather satisfactory. Comparison of model parameters between urban and rural infants suggested that rural infants had a higher length level at birth but lower accelerative growth afterwards than urban ones, which was even more obvious in breast-fed infants. The difference in birth weight between them was not significant; and the urban infants had a faster linear growth velocity than rural ones. These results might be caused by the fact that food supplementing in urban infants was significantly earlier and better than in rural ones.