[The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China].

OBJECTIVE: To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. METHODS: In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. RESULTS: As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. CONCLUSIONS: INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

[Association between OR2T3 gene and pulmonary arterial hypertension].

OBJECTIVE: To explore the pathogenic genes of pulmonary arterial hypertension (PAH) and validate the association between OR2T3 gene and PAH. METHODS: Whole exome sequencing was performed in four patients and one healthy person as control in two pulmonary arterial hypertension pedigree; patient-specific variations were screened by bioinformatics methods and comparison between groups. To further analyze the association between these variations and PAH, Sanger sequencing was used to analyze the genotype of patient-specific variations of 30 patients with idiopathic PAH, 90 healthy people and 30 patients with chronic thromboembolic pulmonary hypertension. RESULTS: The preliminary findings of whole exome sequencing were 57 variations may be associated with PAH; Among them, there were 6 AG heterozygotes due to OR2T3rs148748995 in the 30 idiopathic PAH patients, while no G allele carrier was found in other healthy people of two pulmonary arterial hypertension pedigree (AⅠ-1, AⅡ-3, BⅡ-1) and 90 normal control, and the difference was statistically significant (P<0.05). The variation also didn't exist in 30 chronic thromboembolic pulmonary hypertension patients. CONCLUSION: OR2T3 gene may be the pathogenic gene of PAH and OR2T3rs148748995 could have a role in the development of PAH.

Depletion and recovery of lymphoid subsets following morphine administration.

BACKGROUND AND PURPOSE: Opioid use and abuse has been linked to significant immunosuppression, which has been attributed, in part, to drug-induced depletion of lymphocytes. We sought to define the mechanisms by which lymphocyte populations are depleted and recover following morphine treatment in mice. EXPERIMENTAL APPROACH: Mice were implanted with morphine pellets and B- and T-cell subsets in the bone marrow, thymus, spleen and lymph nodes were analysed at various time points. We also examined the effects of morphine on T-cell development using an ex vivo assay. KEY RESULTS: The lymphocyte populations most susceptible to morphine-induced depletion were the precursor cells undergoing selection. As the lymphocytes recovered, more lymphocyte precursors proliferated than in control mice. In addition, peripheral T-cells displayed evidence that they had undergone homeostatic proliferation during the recovery phase of the experiments. CONCLUSIONS AND IMPLICATIONS: The recovery of lymphocytes following morphine-induced depletion occurred in the presence of morphine and via increased proliferation of lymphoid precursors and homeostatic proliferation of T-cells.

[The diagnostic value of combined detection of circulating antigens and antibodies in urine of patients with schistosomiasis japonica].

OBJECTIVE: To assess the value of detecting circulating antigens and antibodies in urine as a noninvasive method for the diagnosis of schistosomiasis. METHODS: A sandwich ELISA and ELISA using McAb were applied to detect circulating schistosomal antigens and specific antibodies in the urine of patients with acute and chronic schistosomiasis. RESULTS: When the urine samples from 10 cases of acute schistosomiasis and 61 cases of chronic schistosomiasis were examined, the positive rates of circulating antigens and specific antibodies were 60%, 40%, and 80%, 60.1%, respectively; when both detection was combined, the positive rates were 100% and 71.7% respectively, whereas a false positive rate of 3% of CAg or CAb was detected in the urine of 100 normal controls. CONCLUSION: The detection of circulating antigen in urine is a practicable and noninvasive method for the diagnosis of schistosomiasis.

Determination of membrane protein glycation in diabetic tissue.

Diabetes-associated hyperglycemia causes glycation of proteins at reactive amino groups, which can adversely affect protein function. Although the effects of glycation on soluble proteins are well characterized, there is no information regarding membrane-associated proteins, mainly because of the lack of reproducible methods to determine protein glycation in vivo. The current study was conducted to establish such a method and to compare the glycation levels of membrane-associated proteins derived from normal and diabetic tissue. We present a detailed sample preparation protocol based on the borohydride-periodate assay, modified to allow manipulation of animal tissue. Assay noise associated with extraction protocols and nonproteinaceous buffer components was eliminated by the using 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) as a membrane detergent, applying desalting columns, and including a protein precipitation step. The glycation level of membrane proteins from diabetic rats is elevated to 4.89 nmol/mg protein (standard deviation [SD] 0.48) compared with normoglycemic control tissue (2.23 nmol/mg protein, SD 0.64). This result is consistent with and correlated to the total glycated hemoglobin levels in diabetic and normoglycemic rats. Using <100 microg protein, the described methods allow further study of protein glycation effects on the function of individual transporter proteins and the role of these modifications in diabetes.

In vitro polymerization of embryonic MAP-2c and fragments of the MAP-2 microtubule binding region into structures resembling paired helical filaments.

The microtubule-associated protein Tau is widely regarded as the principal component of paired helical filaments comprising Alzheimer neurofibrillary tangles. Tau fragments containing the non-identical repeat region formed structures resembling paired helical filaments (Schweers, O., Mandelkow, M., Biernat, J., and Mandelkow, E. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8463-8467). MAP-2, the other structurally related neuronal microtubule-associated protein, has not been implicated in paired helical filament formation. We now describe the assembly of paired helical filament-like structures from MAP-2 polypeptides containing only 100 residues. A dimeric species, stabilized by an interchain disulfide, appears to be involved in the assembly reaction. We also investigated the polymerization of embryonic MAP-2c, which, except for its microtubule binding region, is structurally distinct from Tau. Full-length MAP-2c formed paired helical filament-like polymers. Polymerized MAP-2c and the microtubule binding region fragment readily bound thioflavin-S, a dye that stains paired helical filaments in the histochemical diagnosis of Alzheimer's disease. Our unprecedented finding that a small MAP-2 microtubule binding region fragment and MAP-2c can form structures resembling straight filaments or Pronase-treated paired helical filaments raises fundamental questions concerning the role of MAP-2 in the pathobiology of Alzheimer disease.

Self-assembly of the brain MAP-2 microtubule-binding region into polymeric structures resembling Alzheimer filaments.

The neuronal microtubule-associated protein known as MAP-2 has not been considered to be a subunit of paired helical filaments (PHFs) in neurofibrillary tangles seen in Alzheimer's Disease. We now describe the assembly of paired helical filament-like structures from MAP-2's 203-residue microtubule-binding region (MTBR). SDS gel electrophoresis and equilibrium ultracentrifugation suggest that a dimeric form, cross-linked by an interchain disulfide, is involved in polymerization. MAP-2 MTBR polymers bind thioflavin-S, a dye used to histochemically localize Alzheimer neurofibrillary tangles. Our finding that PHF-like structures assemble from a MAP-2 fragment raises new questions about MAP-2's role in the etiology of Alzheimer's Disease.

Heating pattern of helical microwave intracavitary oesophageal applicator.

Helical microwave intracavitary oesophageal (HMIO) applicators were designed to operate at frequencies of 433 MHz and 915 MHz. Heating patterns were studied within muscle-equivalent phantom by thermographic camera and fibreoptic thermometers. The results showed that frequency significantly influenced the microwave heating pattern. The 433 MHz applicator had a single power deposition region, the longitudinal specific absorption rate (SAR) distribution appeared to be nearly even, and the maximum SAR value occurred close to the centre of the active length of the applicator. The 915 MHz applicator had two power deposition regions, the peak SAR values occurred at about 1/4 and 3/4 of the active length respectively. The radial SAR distribution suggested that there is no obvious difference between the 433 MHz and 915 MHz applicators in that the average radial penetration of 50% surface SAR (RP50) was about 0.65 cm. It was also shown that power deposition was axially symmetric for both 433 MHz and 915 MHz HMIO applicators. It is shown that better impedance matching is more important for intracavitary hyperthermia than for external hyperthermia. Choosing HMIO applicators in clinical practice is also discussed.

[Comparative studies on diapause responses between Culex tritaeniorhynchus and Culex pipiens pallens].

By comparing the diapause responses between locally hibernating species, C. pipiens pallens, and C. tritaeniorhynchus the overwintering way of which is yet unknown, we found the relative identities of these 2 species in their ovarian diapause criteria, change of the mid-gut and the behaviour of refusing blood feeding. The increases in body weight and fatty contents in the dispersed tritaeniorhynchus were much less than those in diapause pipiens species. Moreover, their ability to resist low temperature was also found significantly weaker. In Shanghai area, the date of the critical photoperiod for C. tritaeniorhynchus was found around the 25th of September with a daylight exposure length (including twilight) of about 13 hours and 43 minutes, being 20 days earlier than that of the locally hibernating species C. pipiens pallens. The gonotrophic dissociation during critical photoperiod occurred more frequently in tritaeniorhynchus than in pipiens mosquitoes. In contrast to pipiens species, it is extremely difficult to obtain diapause tritaeniorhynchus in nature post critical photoperiod. The possibility of a seasonal migratory behaviour of C. tritaeniorhynchus was discussed.