Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China: an integrated data analysis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.

Identification of a major quantitative trait locus for ear size induced by space flight in sweet corn.

The development of molecular markers has contributed to progress in identifying the gene(s) responsible for favorable variations in maize studies. In this study, quantitative trait locus (QTL) mapping was conducted using simple sequence repeat markers in an F2 sweet corn population from a cross between parental line 1132 and space flight-induced mutant line 751 to identify the loci contributing to an increase in some yield traits. A primary mutated genomic region was located on chromosome 9. In total, 26 QTL were detected for eight yield-related traits and assembled into three clusters on chromosome 9. The largest QTL cluster at bin 9.02/03, primarily contributing to >10% of the phenotypic variation in ear and cob diameters, was likely due to a major QTL. Desired alleles of these QTL were provided by the mutant line 751. The primary action of the major mutant allele was an additive effect. Another mutant locus, which was induced in bin 9.01, increased cob and ear diameters by dominant genetic action.

Anomalous Josephson current through a topological noncoplanar ferromagnetic trilayer.

We present an anomalous Josephson effect in a TI-based Josephson junction with a ferromagnetic insulator (FI) trilayer which has noncoplanar magnetizations. It is shown that there exist equal fractional spin-singlet and -triplet correlations due to the magnetism-tuning chiral Dirac energy band structure. The consequent anomalous Josephson supercurrent is exhibited, in which a 0-πor similar 0-πstate transition through phase shift is induced only by exchange field strength of the first FI region, while theϕ0supercurrent and the maximum one gradually drop with the increase of exchange field strengths of the second and third FI regions without relative state transitions. With the increase of the FI region length, theϕ0supercurrent and the maximum one are also both decreased, are found, which is different from the situation for increasing the exchange filed strength. In addition, the corresponding free energies are presented and discussed.

Platelet-derived growth factor-AA mediates oligodendrocyte lineage differentiation through activation of extracellular signal-regulated kinase signaling pathway.

Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for the proliferation of oligodendrocyte progenitor cells (OPCs). Whether it plays a role in oligodendrocyte lineage differentiation of neural stem cells (NSCs) is unclear. Here we report that PDGF-AA is an instructional signal required for the differentiation of embryonic forebrain NSCs into O4-positive oligodendrocytes. Moreover, such PDGF-AA-induced oligodendrocyte differentiation appears to be mediated by the extracellular signal-regulated kinases 1 and 2 (Erk1/2) but not phosphatidylinositol-3 kinase (PI3K) pathway. Finally, PDGF-AA treatment resulted in a significant increase in the expression of the oligodendrocyte-specific transcriptional factor Olig2 in an Erk1/2-dependent mechanism at early stages of oligodendrogliogenesis. Together, our studies provide cellular and molecular evidence to suggest that PDGF-AA is a key molecule that regulates the differentiation of embryonic NSCs into oligodendrocytes. The action of PDGF-AA is mediated by the activation of Erk pathway which involves the downstream upregulation of transcriptional factor Olig2.

Discrimination of novel bunyavirus infection using routine laboratory test.

The wide epidemic and high case fatality rate have made severe fever with thrombocytopenia syndrome (SFTS) a significant public health problem. The diagnosis and discrimination of SFTS virus (SFTSV) infection at an early stage of the disease is important for treatment choice. A prospective study was performed in an SFTS reference hospital during 2011-2013. Suspected SFTS patients were recruited and prospectively observed. Comparison between SFTSV-positive and -negative patients was made to identify the parameters that were related to positive detection by discriminant and classification tree analysis. A total of 538 SFTSV-positive and 396 negative patients were recruited and observed. Multiple logistic regression models demonstrated the significant parameters associated with positive detection, including decreased platelet counts and elevated aspartate aminotransferase (AST) level during the first stage (1∼4 days), decreased white blood cell and platelet counts, elevated creatine kinase (CK) and AST levels during the second stage (5∼7 days), and older age, decreased consciousness and elevated CK and AST during the third stage (8-11 days). The classification trees disclosed that the significant predictors for positive SFTSV detection were AST >50.6 U/L and AST/alanine transaminase (ALT) >1.3 at the first stage, CK >257 U/L or 57.7 U/L < CK ≤98.5 U/L with AST/ALT >1.6 at the second stage, as well as CK >630.7 U/L or 114.3 U/L < CK ≤630.7 U/L with decreased consciousness at the third stage. In making the clinically probable diagnosis of SFTS, the supplementation of AST and CK evaluations might remarkably improve the diagnostic capacity of routine laboratory tests, while the leukopenia is of limited use.

Potassium conductances in cultured bovine and human retinal pigment epithelium.

PURPOSE: To identify K+ conductances on the apical and basolateral membranes in cultured monolayers of fetal bovine and human retinal pigment epithelium (RPE). METHODS: Bovine and human RPE cells were grown on a permeable substrate for an average of 4 and 25 months, respectively, mounted in a modified Ussing chamber that allowed rapid solution changes at both membranes, and perfused with modified Ringer's solutions. Conventional microelectrode recording techniques were used to record intracellularly from RPE cells. RESULTS: Electrical parameters under control conditions for bovine (n = 11) and human (n = 7) cultures respectively, were: transepithelial potential, 0.6 +/- 0.2 and 3.2 +/- 0.5 mV; Rt, 70 +/- 12 and 227 +/- 30 ohm.cm2; and Vap, -61 +/- 3 and -51 +/- 2 mV (mean +/- SEM). The relative K+ conductance (TK) was estimated from responses to 10-fold increases in [K+]o. For the apical and basal membranes, the values for TK were 0.65 and 0.37, respectively, in bovine and 0.33 and 0.45, respectively, in human RPE. Barium applied to either surface of the cultures produced membrane depolarizations and suppressed the responses significantly to K+. In bovine, a 10-fold decrease in basal [K+]o hyperpolarized Vba by 2 +/- 1 mV; a similar decrease in apical [K+]o hyperpolarized Vap by 14 +/- 1 mV. At both membranes, perfusion with Ba2+ unmasked a significant membrane depolarization induced by lowering [K+]o; this phenomenon, observed previously at the apical membrane in fresh explant bovine, frog, and toad RPE, appears to be an unmasking of Na+/K+ pump modulation by K+. CONCLUSIONS: These results indicate the presence of Ba2+ sensitive K+ conductances at the apical and basal membranes of confluent monolayers of cultured fetal human and bovine RPE and the presence of Na+/K+ pump sites at both membranes of cultured bovine cells.

Localization of NaK ATPase on cultured human retinal pigment epithelium.

PURPOSE: To localize NaK ATPase sites on cultured human retinal pigment epithelium (RPE). METHODS: Cultured human RPE from fetal, 2-year-old, and 21-year-old donors was grown to confluence in microporous culture wells for 4 months to 2 years, mounted in a small-volume Ussing chamber, and perfused with growth medium. Ouabain (10(-5)-M) was applied to the basal and apical sides of the RPE. Changes in transepithelial resistance (Rt), transepithelial potential (TEP), and apical and basal membrane potentials were measured. RESULTS: Application of ouabain to the basal side of RPE produced a small sustained increase in TEP after 6 minutes and, simultaneously, small depolarizations of both apical and basal membranes. During the continued presence of ouabain on the basal side, application of ouabain to the apical side produced a significantly larger TEP decrease and greater depolarization of both membranes. Significant changes in Rt were not observed. CONCLUSIONS: These results indicate that NaK ATPase sites are present on both the apical and basolateral membranes of cultured human RPE. The greater effect of ouabain when applied to the apical side suggests that functional NaK ATPase sites are more abundant on the apical membrane.

[Timing of radical operation on Hirschsprung's disease in newborns].

From June 1987 to June 1993, 42 neonates with Hirschsprung's disease (NHD) were treated with modified Duhamel's procedure. The follow-up from 2 months to 5 years (mean 30 mons) showed satisfactory results in all survivors. Comparing with 21 infants with Hirschsprung's disease treated (IHD) with modified Swenson's method showed that: (1) The follow-up results of NHD were better than IHD; (2) The extent and degree of hypertrophy and dilatation of proximal and transitional segment were less serious in NHD and the length of resection was shorter than that of IHD (NHD: 14.5-24.1 cm, IHD: 33-40.5 cm); (3) The degree of pathological changes such as mucosal inflammation, ulcer formation, and degeneration of ganglion cells was related to the age, duration and the length of agangliosis. Hirschsprung's disease has a chronic progressive course. Early operation can decrease the secondary structural and functional damage to the intestine.

Modified thoracoscopic versus minimally invasive oesophagectomy in curative resection of oesophageal cancer.

Conventional thoracoscopic oesophagectomy is time-consuming and requires sophisticated endoscopic skills. To reduce these problems we have modified the operating procedure, first by anastomosis of the oesophagus with the tubular stomach pulled up via the retrosternal route, followed by thoracoscopic oesophagectomy (modified thoracoscopic oesophagectomy). Outcomes were compared between the modified procedure and minimally invasive oesophagectomy. There were no significant differences in general preoperative clinical characteristics between the two patient groups. The modified thoracoscopic oesophagectomy group had significantly lower hospitalization expenses, significantly shorter operation times and significantly more lymph nodes removed compared with the minimally invasive oesophagectomy group, but there were no significant group differences in lengths of hospital and intensive care unit stays, morbidity and mortality. These results indicate that modified thoracoscopic oesophagectomy is feasible, simplifies operating procedures and reduces hospitalization expenses with acceptable morbidity.

Studies on the optimal immunization schedule of experimental animals. VI. Antigen dose-response of aluminum hydroxide-aided immunization and booster effect under low antigen dose.

The dose-response relationships of a viomycin (VM) immunogen for total immunoglobulin (Ig) G and anti-VM antibody response of mouse using aluminum hydroxide as adjuvant was studied. The condition required to absorb a protein on aluminum gel was first established. The effective immunogen dose for total and specific IgG response of mouse using aluminum hydroxide as the adjuvant was found to be in the narrow range of 5 to 20 micrograms, and 10 micrograms per mouse was optimal. The most effective number and intervals of booster injections were studied; when mice were immunized with a lower antigen dose than the optimal, both the number and interval period of booster injections greatly affected the immune response; the more boosters were given, the higher was the response level of specific IgG. The results are contrary to those obtained by immunizing with the optimal or a higher antigen dose.

[Surgical treatment of 219 cases of primary tumor and cyst of the mediastinum].

Two hundred and nineteen patients with primary tumor and cyst in the mediastinum were retrospectively analysed. All patients received surgical treatment and pathologic examination. Results showed that: (1) the commonest mediastinal tumors was the thymoma (42.0%) (2) The second teratoma (20.1%). The incidence of neurogenic tumors was 16.4%. The over-all incidence of these three tumors was 78.5%. A total excision of the tumor was performed in 198 patients; incomplete excision was performed in 18 patients; 3 patients underwent biopsy only. The anatomic locations, clinical manifestations, complication and mortality of surgical treatment of these tumors were analysed.

[Surgical treatment of congenital heart defect complicating severe pulmonary infection in infants and young children].

OBJECTIVE: To review the experience of surgical management of left to right shunt congenital heart defect complicating severe pulmonary infection. METHOD: Twenty patients aged 4-17 months who weighed 3.6-11.6 kg were analysed. Among them, 16 underwent surgical treatment. RESULTS: The mortality rate of 4 who received conservative therapy was 75% (3/4). The mortality rate of the operative group 16 Cases, was 12. 5% (2/16), 14 were doing well by follow-up of 8-24 months. CONCLUSION: Infants of Congenital heart defect Complicating Severe Pulmonary infection, Should be performed operation actively.

[Surgical treatment for mitral valve prolapse].

OBJECTIVE: To determine the excellent operative procedure to treat mitral valve prolapse (MVP). METHODS: Fifty seven patients with MVP were divided into three groups: Group I received traditional chordal reconstruction; Group II underwent chordal replacement using expanded polytetrafluorethylene(e-PTFE) sutures and artificial ring valvuloplasty reconstruction; Group III submitted mitral valve replacement. RESULTS: Mitral regurgitation volume was reduced significantly in Group II [(1.3 +/- 3.8) ml] and Group III [(1.2 +/- 3.4) ml] than that in Group I [(4.7 +/- 7.7) ml] (P < 0.05). CONCLUSION: The utilization of e-PTFE sutures as artificial chordae and artificial ring valvuloplasty for MVP is a more reliable and safe procedure than traditional mitral valve reconstruction, and can avoid the complications of long term anticoagulant therapy after mechanical valve replacement.

[Repair of cardiac defects by minimal incision without aortic cross-clamp].

From July 1998 to June 1999, seventy two patients underwent repair of congenital heart defects by a partial sternal split and a limited skin incision(4-8 cm) under cardiopulmonary bypass without aortic cross-clamp at our institution. The average age of these patients was 4 years and 5 months(range: 7 months to 12 years), and the average weight was 15.6 kg(range: 7 kg to 30 kg). Fifty six patients had simple ventricular septal defects, sixteen suffered from atrial septal defects. The average bypass time was (21 +/- 20) min (range: 8-58 min). All patients recovered rapidly from the operation in an uneventful postoperative course. Our experience demonstrates that this technique is feasible and can be performed easily in young children with simple cardiac defects, and has excellent cosmetic results.

[Effects of aprotinin on TNF-alpha levels after cardiopulmonary bypass].

OBJECTIVE: This study evaluates the anti-inflammatory activity of full-dose and pump-prime-only(low-dose) aprotinin by means of comparing tumor necrosis factor alpha(TNF-alpha) levels of both groups after CPB. METHODS: Twenty-nine adults with rheumatic heart disease were randomized into three groups: (1) full-dose aprotinin-treated group(Group A, n = 10); (2) pump-prime-only aprotinin-treated group(Group B, n = 10), and (3) control group(Group C, n = 9). Plasma concentrations of TNF-alpha were measured by enzyme-linked immunosorbent assay technique at baseline(before operation), and at 2, 24 hours after CPB termination. RESULTS: A significant(P < 0.05) increase of TNF-alpha occurred in all three groups at 2 and 24 hours after CPB termination when compared with the same group at baseline. In Group A, TNF-alpha level was significantly lower than that in group C(P < 0.05) at 24 hours after CPB, but not in group B(P > 0.05). CONCLUSIONS: Both CPB and operative stimulus induce the increase of cytokine TNF-alpha after CPB. Full-dose aprotinin has the anti-inflammatory effect by means of reducing TNF-alpha level after CPB. Low-dose aprotinin dose not reduce TNF-alpha level. So it no significant anti-inflammatory effect.

Studies on the optimal immunization schedule of experimental animals. V. The effects of the route of injection, the content of Mycobacteria in Freund's adjuvant and the emulsifying antigen.

The effects of several conditions for the immunization of mice was studied using an aliquot of a viomycin (VM) protein conjugate as the common primary or booster antigen. Responses of the mice were assessed by measuring mouse serum levels of total immunoglobulin G (IgG) and anti-VM antibody responses using the newly improved two assay methods. The choice of route was found to be a very important factor in immunization and intraperitoneal injection was the most optimal among the four routes studied. The effect of the concentration of Mycobacteria in Freund's complete adjuvant (FCA) was also studied, and it was found that a diluted FCA was more effective than a commercial FCA. The effect of the controlled release of the antigen was studied and three important phenomena were observed: The mice immunized by the mini-osmotic pump-aided controlled release of the antigen responded with similar small amounts of both total IgG and anti-VM antibody regardless of the presence or absence of FCA in the antigen; emulsifying the antigen with FCA was a very important condition for the effective elicitation of the specific antibody; a mixture of antigen and FCA without emulsifying produced little specific antibody and a large amount of total IgG. The more effectively immunized mice responded with a larger decrease in body weight soon after the primary injection.

Studies on the optimal immunization schedule of experimental animals. IV. The optimal age and sex of mice, and the influence of booster injections.

To establish the optimal condition for preparing mouse antiserum specific to a drug, the optimal age and sex of mice for the immune response were studied by measuring the mouse serum levels of total immunoglobulin G (IgG) and specific antibody to viomycin, as well as the changes in weight of mice immunized with a viomycin immunogen. It was observed that age was a more important factor than sex, and strongly affected productions of both total and specific IgGs of mice. The mice aged 8 weeks yielded the highest levels of both total IgG and the specific antibody. In the study on the influence of booster schedule, the number of boosters given had a larger influence on the immune response than the interval between priming and boosters. The greater the number of booster shots given, the less was the production of total and specific antibodies. The decrease in the weight of mice after immunization was also studied in more detail; it was found that it only occurred in the first week after priming but not after a booster injection. The mice aged eight weeks showed the largest weight loss.