[Retrospective analysis of BI-RADS 4 and 5 lesions additionally detected by breast MRI].

Objectives: To establish a newly-designed scoring system for breast imaging-reporting and data system (BI-RADS) 4 and 5 breast lesions only visible on MRI, and to examine their clinical pathway of biopsy. Methods: The BI-RADS 4 and 5 breast lesions only visible on MRI but not suspected on mammograms or ultrasound between June 2007 and December 2021 at Beijing Hospital were evaluated retrospectively. A total of 209 lesions from 184 patients were finally included. All patients were female, aged (50±11) years (range: 27 to 76 years). All lesions were confirmed by pathology and divided into malignancy and non-malignancy. The lesions were divided into mass and non-mass type using BI-RADS. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the new scoring system. Four types of pathology-obtaining pathway were used: biopsy guided by second-look ultrasound, local excision guided by lesion position information on MRI, intraductal lesion excision guided by methylene blue stain and mastectomy. The data between mass and non-mass lesions were compared by Mann-Whitney U test, χ2 test or Fisher exact test,respectively. Results: There were 124 malignant and 85 non-malignant lesions, while 100 mass and 109 non-mass lessions. The sizes between mass and non-mass lesions showed significant difference(M(IQR)) (7.0 (3.0) mm vs. 25.0 (25.0) mm, U=568.000, P<0.01) and their BI-RADS diagnostic accuracy had no significant difference (53.0% (53/100) vs. 65.1% (71/109), χ2=3.184, P=0.074). The areas under ROC curve of the new scoring system for evaluating mass and non-mass were 0.841 and 0.802, respectively. When taking Score 3 as threshold, it can potentially avoid 14.0% (14/100) and 4.6% (5/109) of biopsies in mass and non-mass, respectively. As to pathway of obtaining pathology, second-look ultrasound succeeded more easily in mass than non-mass (41.0% (41/100) vs.26.6% (29/109), χ2=4.851, P=0.028). More MRI-guided local excisions were performed in non-mass than mass (52.3% (57/109) vs. 34.0% (34/100), χ2=7.100, P=0.008). Conclusions: For suspicious breast lesions detected by MRI but not suspected on X-ray or ultrasound, the new scoring system can further increase diagnostic accuracy. The second-look ultrasound plays an important role for obtaining pathology, especially for mass-type lesion.

Student characteristics associated with dominant approaches to studying: Comparing a national and an international sample.

BACKGROUND: Productive approaches to studying (deep and strategic learning) are associated with a variety of favourable academic outcomes, and may be of particular importance for students in multifaceted and complex disciplines such as occupational therapy. AIM: To explore associations between student characteristics and their dominant approaches to studying in two samples of occupational therapy students: a national sample of Norwegian first-year students, and an international sample of students in different year cohorts (Australia, Hong Kong, Singapore and Norway). MATERIALS AND METHODS: A total of 180 (national sample) and 665 (international sample) students were included in the study. Approaches to studying were measured with the Approaches to Study Skills Inventory for Students (ASSIST). Data were analyzed with adjusted multinomial regression analyses. RESULTS: Age, gender and prior higher education were not associated with the dominant study approach. More time spent on independent study (international sample: OR = 1.07/1.08, p < 0.01/<0.001) and having current study program as the top priority line of education at enrolment (national sample: OR = 2.89, p < 0.05) predicted productive study approaches. CONCLUSIONS AND SIGNIFICANCE: Factors such as age, gender and prior higher education seem to be of limited importance for understanding students' dominant approaches to studying.

Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement.

The RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data have hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage and then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target modulates Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to "proofreading" capability. Lastly, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.

[Population pharmacokinetics of two recombinant human coagulation factor â § preparations in patients with hemophilia A].

Objective: To compare the differences in population pharmacokinetic (PK) parameters between two recombinant coagulation factor Ⅷ (FⅧ) preparations, Kogenate FS and Advate, in patients with hemophilia A, and to provide the theoretical basis of precise individualized treatment for those patients. Methods: Patients with moderate or severe hemophilia A who had at least one injection of Kogenate FS or Advate at 41 international hemophilia centers were enrolled as subjects from the WAPPS-Hemo project since January 2015 to December 2017. The half-lives of the two drugs and the time of FⅧ activity reaching 2% (TAT 2%) were calculated, and the differences of PK between the two drugs among different age and dose subgroups were further analyzed. Results: ①The mean age of patients in the Kogenate FS (n=117) and Advate groups (n=120) were (27.6±17.7) and (23.4±16.2) years old, respectively. All patients in the two groups were males. ②The administration doses in the Kogenate FS and Advate groups were (31.5±13.1) IU/kg and (38.17±14.83) IU/kg, respectively; the half-lives of the two drugs were (12.3±3.5) h and (10.8±2.9) h, respectively; and the TAT 2% were (65.2±21.7) h and (57.0±17.9) h, respectively. ③In the Kogenate FS group, the drug half-lives in patients aged ≥12 and <12 years old were (12.7±3.7) h and (11.1±2.5) h, respectively; the TAT 2% were (68.6±22.9) h and (55.8±14.6) h, respectively. In the Advate group, the drug half-lives in patients aged ≥12 and <12 years old were (11.4±3.1) h and (9.4±1.8) h, respectively; and the TAT 2% were (61.1±18.0) h and (45.2±11.3) h, respectively. ④In the Kogenate FS group, the drug half-lives in <20 IU/kg, (20-29) IU/kg, (30-39) IU/kg and ≥40 IU/kg groups were (13.3±4.0) h, (12.3±3.6) h, (12.2±3.5) h and (11.6±2.6) h, respectively; and the TAT 2% were (61.5±21.4) h, (63.9±22.4) h, (67.0±24.3) h and (68.0±19.5) h, respectively. In the Advate group, the drug half-lives in <20 IU/kg, (20-29) IU/kg, (30-39) IU/kg and <40 IU/kg groups were (11.5±3.8) h, (11.4±3.7) h, (11.0±2.9) h and (10.4±2.3) h, respectively; and the TAT 2% were (50.8±19.2) h, (56.7±21.0) h, (58.2±18.8) h and (58.1±15.8) h, respectively. Conclusion: The PK parameters of Kogenate FS are superior to those of Advate among different age and dose subgroups.

Clock mutant promotes osteoarthritis by inhibiting the acetylation of NFκB.

OBJECTIVES: To examine the effect of the circadian gene Clock on posttranscriptional function and pro-inflammatory mechanisms in osteoarthritis (OA). METHODS: The cartilage from Clock mutant mice was assessed using histology, (OA) score, and real-time polymerase chain reaction (PCR) quantification of key pro-inflammatory genes. Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) translocation, posttranslational state and expression levels during day and night conditions were assessed using immunoblot and IP. The regulation of transcription by Clock in cartilage tissue was assessed by using chromatin immunoprecipitation (ChIP) and luciferase assays. Total acetylation level and pattern over 24 h were quantified using immunoblot and real-time PCR. Finally, the effects of exogenous Clock nanoparticle treatment were quantified by histology and immunoblot. RESULTS: The Clock mutation significantly promoted the degradation of cartilage and the expression of the key pro-inflammatory mediators, IL-1ß, IL-6 and MCP-1. The Clock mutation significantly promoted NFκB nuclear translocation. The circadian protein CLOCK positively regulates NFκB at the transcriptional level by binding the E-box domain. The Clock mutation significantly inhibited the total lysine acetylation level in cartilage and inhibited NFκB acetylation at the Lys310 residue but promoted phosphorylation at the Ser276 residue. The forced expression of Clock in vivo inhibited NFκB activation by increasing acetylation and decreasing phosphorylation levels and by decreasing cartilage damage and inflammation. CONCLUSIONS: This study demonstrates the mutation of Clock promotes inflammatory activity by mediating the posttranscriptional regulation of NFκB in OA pathogenesis.

Systematic discovery of natural CRISPR-Cas12a inhibitors.

Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world.

Elevated miR-21 is associated with poor prognosis in non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVE: Increasing studies have investigated the prognostic value of high miR-21 expression in non-small cell lung cancer (NSCLC) with inconsistent results. We conducted this meta-analysis to explore whether the expression of miR-21 was associated with prognosis in NSCLC patients. MATERIALS AND METHODS: We systematically searched Medline, EMBASE, Web of Science and Cochrane Library for relevant studies. Studies exploring the relationship between miR-21 expression and NSCLC prognosis and clinical pathology, and reporting enough data to get the hazard ratio (HR) and 95% confidence intervals (CIs), were included. Random- or fixed-effect models were employed to calculated pooled hazard ratios (HRs) or risk ratio and 95% confidence intervals (95% CIs). RESULTS: A total of 28 eligible studies, including 24 for prognosis, 16 for clinicopathological features were identified. Our results revealed that elevated miR-21 was related to unfavorable overall survival (OS) in NSCLC (HR = 1.960, 95% CI = 1.510-2.554, p = 0.000). Similar results were found in disease-free survival, relapse-free survival, and cancer-special death. In a meta-analysis of clinical pathology, overexpressed miR-21 was significantly related to lung adenocarcinoma, larger tumor size, and advanced clinical stage. CONCLUSIONS: Our meta-analysis suggested that miR-21 may function as an unfavorable biomarker of prognosis in NSCLC patients.

[Comparison of prognosis between invasive micropapillary carcinoma and invasive ductal carcinoma of breast: a single center, retrospective case-control study].

Objective: To elucidate the clinicopathological characters and prognostic factors of invasive micropapillary carcinoma of the breast (IMPC) by compared with invasive ductal carcinoma, not otherwise specified of the breast (IDC). Methods: The retrospective study was performed with female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy from June 2008 to April 2016 in Breast Center of Beijing Hospital. Forty-seven mixed or pure IMPC patients and 93 pure IDC patients(admitted in the same center from October 2008 to January 2016 ) were matched for tumor stage, nodal status and age. Follow-up was done every 3 to 6 months postoperatively. The deadline was July 31, 2016. The curves of disease free survival and overall survival were drawn by the Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables that were identified on univariate analysis were analyzed with Cox's proportional hazards regression model for multivariate analysis. The χ(2) test or Fisher's exact test was used to compare distributions across 2 groups and the Mann-Whitney U test or t test was used to analyze the medians or means of 2 groups. Results: With exact matches, the rates of lymphovascular invasion (LVI) (29.8% vs. 12.9%, χ(2)=5.885, P=0.015)and histological grade 3 (40.4% vs. 21.5%, χ(2)=-2.690, P=0.007) were both significantly higher in patients with IMPC than that in IDC group, but the survival between the two pathological types were not significantly different (all P>0.05). The percent of IMPC component didn't influence the clinicopathologic characters (all P >0.05), but a significantly longer median disease free survival (χ(2)=11.731, P=0.001) when the patients had more than 50% of IMPC component was found. Conclusions: Higher rates of LVI and histological grade 3 were found in IMPC than that in IDC, but the survival was comparable between the two groups. A longer DFS occurred in patients with IMPC component more than 50%.

[The comparison of characters between invasive micropapillary carcinoma and invasive ductal carcinoma not otherwise specified of the breast].

Objective: To analyze the differences of clinicopathological characters and prognostic factors between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC) not otherwise specified of the breast. Methods: Patients who were treated from June 2008 to April 2016 in Breast Center of Beijing Hospital were retrospectively analyzed to evaluate the differences between IMPC (n=59) and IDC (n=1 080). Follow-up was done every 3 to 6 months postoperatively with a deadline of July 31, 2016. The curves of disease free survival (DFS) and overall survival (OS) were drawn by Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables which were identified on univariate analysis were analyzed with Cox's proportional hazards regression model for multivariate analysis. Results: More lymph nodes were involved in IMPC group (χ(2)=12.168, P=0.007) which led to more later stage in this group (χ(2)=8.950, P=0.011). IMPC group displayed a significantly increased rate of lymphovascular invasion (LVI) compared to IDC group (χ(2)=13.511, P = 0.001). The expression rate of estrogen receptor (ER) and progesterone receptor (PR) was higher in IMPC group than that in IDC group (89.8% vs. 76.3% and 88.1% vs. 70.7%, respectively, χ(2)=5.786, 8.332, all P<0.05). In multivariate analysis performed with the variables found significant in univariate analysis, the only variable found significantly affecting DFS of IMPC group was the T stage (T1-2 and T3-4, OR=5.217, 95%CI: 1.401 to 19.430, P=0.014), while in IDC group, pathological stage (stage Ⅰ to Ⅱ and stage Ⅲ to Ⅳ, OR=1.870, 95% CI: 1.262 to 2.771, P=0.002), lymph node positive ratio (LNR) (OR=2.222, 95%CI: 1.561 to 3.162, P=0.000), PR (OR=1.856, 95%CI: 1.118 to 3.082, P=0.017), and age (<50 years old and ≥50 years old, OR=0.695, 95%CI: 0.488 to 0.989, P=0.043) were prognostic factors. There were two variables found significantly affecting OS of IMPC group, which were T stage (OR=3.713, 95%CI: 1.539 to 8.959, P=0.004) and LNR (OR=2.850, 95%CI: 1.033 to 7.862, P=0.043). While in IDC group, LNR was the only variable found significantly affecting OS (OR=2.129, 95%CI: 1.324 to 3.425, P=0.002). Compared with IDC, the patients with IMPC were more likely to have local or regional recurrence (P=0.006). Although the median DFS interval was longer in IDC group (χ(2)=9.739, P=0.002), the median OS interval was comparable between the two groups (χ(2)=0.787, P=0.375). Conclusion: Although IMPC has lymphotropic feature, tendency of LVI and local or regional recurrence, it has an OS which is comparable with IDC.

Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy.

INTRODUCTION: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia. AIM: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia patients with arthropathy. METHODS: Serum from 35 haemophilia patients with varying degrees of arthropathy and 43 age- and gender-matched control subjects were analysed. Biomarkers of cartilage degradation (C2M, COMP, CTX-II, ADAMTS5), cartilage formation (PRO-C2), bone formation (PINP), bone resorption (CTX-I) and inflammation (hsCRP, CRPM) were measured by ELISA. Arthropathy was assessed by radiological evaluation (Pettersson score) and physical examination (Gilbert score). RESULTS: In patients with haemophilia, cartilage degradation, measured by C2M, CTX-II and COMP, was increased by 25% (P < 0.05) compared with control subjects. Levels of the cartilage degradation enzyme, ADAMTS5, were 10% lower in haemophilia patients (P < 0.05). Bone formation (PINP) was reduced by 25% (P < 0.05) in haemophilia patients, whereas bone resorption (CTX-I) was increased by 30% (P < 0.001). Acute inflammation (hsCRP) was increased by 50% (P < 0.01), whereas chronic inflammation (CRPM) was decreased by 25% (P < 0.0001). The hsCRP/CRPM ratio was 60% higher (P < 0.001) in haemophilia patients relative to control subjects. A biomarker panel combining C2M, CRPM, and ADAMTS5 could distinguish haemophilia patients from control subjects with 85.3% accuracy (P < 0.0001). We found no strong correlation between biomarkers and radiological and physical examination of the joint. CONCLUSION: Biomarkers detect increased cartilage and bone degradation, and altered inflammatory activity in haemophilia patients with arthropathy. These biomarkers could potentially be used to identify patients with progressing joint disease.

The assessment of the long-term effects of elective CRT-D of coronary heart disease after PCI.

OBJECTIVE: The present study was planned to evaluate the long-term effects of elective cardiac resynchronization therapy devices (CRT-D) of coronary heart disease after percutaneous coronary intervention (PCI). PATIENTS AND METHODS: We continuously selected 124 patients with chronic stable heart failure to undergo PCI, and were randomly divided into two groups viz. control group with 72 cases and observation group with 52 cases. The control group was given intensive drugs, while the observation group was treated with a combination of intensive drugs with CRT-D. Followed-up for three years and contrasted their effects. RESULTS: The survival rate of the observation group was significantly higher than that of the control group, and its major adverse cardiac events (MACE) rate was observed to be lower than that of the control group. During the follow-up of the control group, LVEDd, pro-BNP and NYHA increased but LVEF decreased. On the other hand, in the observation group, LVEDd, LVEF, NYHA showed no significant changes, but pro-BNP revealed a significant increase. The physical health, mental health, social health and total score of the observation group were significantly higher than that of the control group. CONCLUSIONS: Patients with chronic stable heart failure who have CRT-D implant testified after PCI could have significant improvement in long-term survival rate, better quality of life, improved cardiac function and reduction in the occurrence of MACE too.

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

INTRODUCTION: Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. AIM: To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. METHODS: A cross-over study on 5 IU kg-1 FVIII daily vs. 10 IU kg-1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. RESULTS: Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. CONCLUSION: Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients.

[Preliminary study for the roles and mechanisms of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles in the Lewis lung cancer mice].

OBJECTIVE: To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo. METHODS: Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group: PEG-PLGA-Rg3 nanoparticles group(Rg3-N), PEG-PLGA group (PEG), Rg3 group (Rg3), normal control group(C), saline control group(NS), and received intragastric administration for 14 days. The weights of the mice were measured every 2 days and the weight curves were obtained. At the same time, the color pattern, activity and mental status were observed. The mice were sacrificed when the administration was over, and the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight, and the tumor:weight ratios were analysed. In addition, the tumor microvessel density (MVD) was measured by immunohistochemical staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo. Furthermore, the levels of such angiogenesis and proliferation factors as MMP-9, HIF-1α, VEGF, Ki-67 were examined by RT-PCR, Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo. RESULTS: The trends of variation of the mice weights in NS group and PEG group were rising early but declining later. In contrast, the trends of the other three groups were rising early and became stable later. In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status: brighter color, more active and better spirit. Compared with NS group,the tumor weight in PEG group, Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined significantly (P<0.01). Besides, there was no significant difference between Rg3 group and Rg3-N group. At the same time, the level of VEGF mRNA, the protein expression of MMP-9, HIF-1α, VEGF in Rg3 group and Rg3-N group decreased compared with NS group. Furthermore, the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group. The expression of Ki-67 in PEG group, Rg3 group and Rg3-N group showed no significant difference compared with NS group. CONCLUSION: Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF, MMP-9 and HIF-1α in Lewis lung cancer mice, thereby indirectly contributing to their antitumor effects and alleviating the mice's general status. In addition, PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.

Coexisting congenital dysfibrinogenemia with a novel mutation in fibrinogen γ chain (γ322 Phe→Ile, Fibrinogen Beijing) and haemophilia B in a family.

INTRODUCTION: Both congenital dysfibrinogenemia and haemophilia B (HB) are rare coagulopathies caused by mutations within the fibrinogen and F9 genes respectively. AIM: To investigate the pathogenesis of combined dysfibrinogenemia with HB in a family. METHODS: Coagulation assays, factor IX (FIX) activity (one-stage method), fibrinogen activity (Clauss method), antigen (immunoturbidimetry), fibrinogen polymerization and fibrinolysis velocity were measured. The sequences of fibrinogen genes and F9 were amplified by PCR and analysed by sequencing. RESULTS: The proband, a 16-year-old boy with HB (FIX 2 IU dL(-1) ), also had persistently low Clauss fibrinogen level (0.64-0.65 g L(-1) ) with normal antigen level (2.23 g L(-1) ). The mother had a FIX 45 IU dL(-1) and similarly discrepant low Clauss fibrinogen (0.79 g L(-1) ) to antigen levels (2.23 g L(-1) ). Thrombin time for both were either slightly prolonged or at boundary value. Genetic analysis of the proband and the mother identified similar mutations in the FGG gene (heterozygous c.1042T>A resulting in p.Phe348Ile or γPhe322Ile in the mature protein) and in the F9 gene (c.1243del p.His415Metfs*11 and c.1245T>A p.His415Gln). The father had no fibrinogen or F9 gene mutations. Plasma fibrinogen polymerization was delayed, but fibrinolysis velocity was normal in the proband and his mother. CONCLUSION: To our knowledge, this is the first report of a family with combined novel dysfibrinogen (Fibrinogen Beijing) and HB with bleeding manifestations.

Comparison of changes in markers of muscle damage induced by eccentric exercise and ischemia/reperfusion.

To examine the effects of eccentric exercise (EE) and ischemia/reperfusion (I/R) on the markers of muscle damage, 72 rats were randomly assigned to the EE group, I/R group and control group (C), respectively. The rats in EE ran downhill on a treadmill with a 16 ° inclination at a constant speed for 90 min, and the rats in the I/R group underwent 90 min of four-limb ischemia, followed by 24, 48 and 72 h of reperfusion. Blood and tissue samples were collected immediately, 24, 48 and 72 h after exercise or reperfusion. Quantitative analyses showed that the I/R group had a significantly larger mitochondrial volume at 24 h after reperfusion compared with the C, and there were more disrupted Z-lines in the EE group and more disrupted mitochondria in the I/R group at 24 h after exercise or reperfusion. When compared with the C, a significantly lower total antioxidant capacity and higher interleukin-6 value were observed after exercise or reperfusion. Our data suggest that although EE and I/R result in some similar changes in the muscle damage markers, there are still some differences. The EE- and I/R-induced muscle damage may be due to different mechanisms.

Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system. Umbilical cord derived mesenchymal stem cells are immunosuppressive. We transplanted mesenchymal stem cells in a patient with refractory progressive MS, and the disease course was stabilized after the transplantation. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.

Nuclear import of influenza A viral ribonucleoprotein complexes is mediated by two nuclear localization sequences on viral nucleoprotein.

BACKGROUND: The influenza A virus replicates in the nucleus of its host cell. Thus, entry of the influenza genome into the cell nucleus is necessary for establishing infection. The genome of the influenza A virus consists of eight single-stranded, negative-sense RNA molecules, individually packed with several copies of the viral nucleoprotein (NP) into ribonucleoprotein particles (vRNPs). These vRNPs are large, rod-shaped complexes containing a core of NP, around which the RNA is helically wrapped. The vRNPs are the entities that enter the nucleus, and their nuclear import must be mediated by nuclear localization sequences (NLSs) exposed on the vRNPs. NP contains at least two putative NLSs, one at the N-terminus (NLS1) and one in the middle (NLS2) of the protein. These NP NLSs have been shown to mediate the nuclear import of recombinant NP molecules. However, it remains to be determined which NLS mediates the nuclear import of influenza vRNP complexes. RESULTS: To directly track the nuclear import of the influenza A genome, we developed an experimental assay based on digitonin-permeabilized cells and fluorescently-labeled vRNPs isolated from the influenza A virus. We used this assay to determine the contribution of the two proposed NLSs on NP to the nuclear import of influenza vRNP complexes. Peptides that mimic each of the two NLSs on NP were used to compete with vRNPs for their nuclear import receptors. In addition, antibodies against the two NP NLSs were used to block the NLSs on the vRNP complexes, and thereby inhibit vRNP nuclear import. Both peptide competition and antibody inhibition of either sequence resulted in decreased nuclear accumulation of vRNPs. The two sequences act independently of each other, as inhibition of only one of the two NLSs still resulted in significant, though diminished, nuclear import of vRNPs. Furthermore, when both sequences were blocked, vRNP nuclear import was almost completely inhibited. Antibody inhibition studies further showed that NLS1 on NP is the main contributor to the nuclear import of vRNPs. CONCLUSION: Our results demonstrate that both NLS1 and NLS2 on NP can mediate the nuclear uptake of influenza A vRNPs.

Thermodynamic modeling of a novel air dehumidification system.

A novel air dehumidification system is proposed. The proposed system incorporates a membrane-based total heat exchanger into a mechanical air dehumidification system, where the fresh air flows through the enthalpy exchanger, the evaporator and the condenser subsequently. Thermodynamic model for the performance estimation of the combined system is investigated. Processes of the fresh air and the refrigerant are studied. Two additional specific programs are devised to calculate the psychrometrics and the thermodynamic properties of the refrigerant R134a. Annual energy requirement is 4.15 × 106 kJ per person, or 33% saving from a system without energy saving measures.