[Investigation of a cluster epidemic of COVID-19 in Ningbo].

Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

[A multicenter investigation and analysis on anemia in lymphoma patients in Shanghai].

Objective: To investigate the occurrence and influencing factors of anemia in lymphoma patients and its effect on treatment. Methods: A total of 501 lymphoma patients, who were hospitalized in four general hospitals in Shanghai from January 2017 to June 2018, were followed up for six months. The clinical data about anemia were collected and statistically analyzed. Results: Among all the enrollment patients, there were 178 patients (35.5%) had anemia. Among 289 patients whom were initially treated for lymphoma, there were 99 patients (34.3%) with anemia. In the following-up time, there were 136 new cases (42.1%) of anemia. The total prevalence of anemia was 62.7%. The univariate analysis indicated that the anemia incidence for initially treated lymphoma patients was significantly related to their age, pathological type, bone marrow infiltration, IPI scores and Ann Arbor stage. The response to initially treatment in lymphoma patients with anemia was inferior to those without anemia. The multivariate analysis indicated that IPI scores 3-5 points (P<0.001, OR=4.230, 95%CI 2.339-7.650) and chemotherapy treatment (P<0.001, OR=11.049, 95%CI 5.149-23.711) were the independent influential factors to the emerging anemia incidence. PS score used to evaluate patient physical condition was obviously related to the anemia occurrence. Conclusion: Lymphoma patients have a high prevalence and incidence of anemia. The occurrence and severity of anemia are closely related to the efficacy and physical condition of lymphoma patients.

[Prevalence of allergy in children with acute rhinosinusitis].

Objective:To explore the prevalence of allergy in patients with acute rhinosinusitis (ARS) and evaluate the severity of symptoms in ARS children with or without allergy.Method:Two hundred and seven children (4-12 years of age) with ARS and 85 children of control group were included in our research from June, 2016 to January, 2018. We use questionaire to collect the basic information of pediatric patients. The results of skin prick test (SPT) were recorded. Mothers were required to complete the Sinus and Nasal Quality-of-Life Survey (SN-5).All ARS childern were divided into allergic group and non-allergic group according to the result of SPT. We use binomial distribution to evaluate the population rate. t-test, Chi-square test and Wilcoxon rank-sum test were appropriately used to compare the parameters between two groups.Result:Among the 207 ARS participants in this study, 44.4% participants were shown to response to at least one Inhalation allergen and 40.6% participants were shown to response to at least one perennial allergen. Both ratios were significantly higher than those of the control group. Perennial allergy seems to be much more common than seasonal allergy in pediatric patients with ARS. The most troublesome symptoms among the participants with acute rhinosinusitis combined with allergic rhinitis were nasal obstruction (5.28±1.34), nasal discharge (5.07±1.04), post-nasal drip (4.63±1.31) and itchy eyes/nose (4.28±1.51). Four subscale scores of the SN-5 including nasal obstruction, allergy symptoms, emotional distress and activity limitation in the allergic group were obviously higher than those of the non-allergic group.Conclusion:Allergic factors play an important role in the pathogenesis of pediatric acute rhinosinusitis.

[Analysis of the related factors of attention deficit/hyperactivity disorder and allergic rhinitis in children].

Objective:To investigate the association between symptom of attention deficit/hyperactivity disorder (ADHD) and allergic rhinitis (AR) in children with AR at different sexes and different ages. Method:A total of 439 AR children aged 6 to 12 years were enrolled in this study. Basic information (age, gender, medical history, family history and comorbidities) of children with AR was collected. Results of prick tests on children skin were recorded. (TNSS) and Chinese version of the SNAP-Ⅳ scale, children under the guidance of independent completion of children's quality of life of children with nasal conjunctivitis scale (PRQLQ). According to the results of SNAP-Ⅳ, children were divided into AR with ADHD group ï¼»attention deficit and hyperactivity symptom score (IHS) >1.25ï¼½ and AR without ADHD group (IHS≤1.25). The differences between the two groups of children were analyzed using group t-test and χ² test, and the relationship between each parameter and IHS >1.25 was analyzed by binary logistic regression. Result:Using SPSS 22.0 software, among all the included AR children, IHS >1.25 children accounted for 26.4%, IHS >1.25 group AR symptom scores were significantly higher than HIS ≤1.25 groups. Univariate analysis showed that children with age, gender, duration of AR symptoms, skin index and PRQLQ subscales had a correlation with IHS >1.25. After controlling for age and gender, duration of AR symptoms and skin index correlated with IHS >1.25 The estimated OR values are 1.807 (95%CI: 1.350-2.419) and 1.912 (95%CI: 1.320-2.772), respectively. The estimated OR values of PRQLQ subscale and IHS >1.25 were 1.657 (nasal symptom score), 1.324 (eye symptom score), 2.48 (non-eye-nasal symptom score), 1.418 (Behavior problem score) and 2.045 (activity and sleep score). The correlation between IHS>1.25 and the skin index and PRQLQ subscales was mainly found in males with stratification of age and gender, and the association between duration of AR symptoms and HIS >1.25 was statistically significant among all groups reflected. Conclusion:The association between attention deficits and hyperactivity symptoms in AR children was correlated with the severity of AR symptoms, duration, and skin index, and this association was more pronounced in males. In children with AR and ADHD, early management of AR symptoms may improve their ADHD symptoms.

Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy.

BACKGROUND: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC. METHODS: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed. RESULTS: Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042). CONCLUSIONS: Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).

[A clinical study of antiviral therapy for patients with compensated hepatitis C cirrhosis].

Objective: To investigate the effect of antiviral therapy on the progression of liver cirrhosis and related predictive factors through a retrospective analysis of patients with compensated hepatitis C cirrhosis. Methods: The patients with compensated hepatitis C cirrhosis who were treated in our hospital from 2004 to 2015 were divided into sustained virologic response (SVR) group, non-SVR (NSVR) group, and untreated group. The baseline features of patients with or without liver cirrhosis were compared to identify the predictive factors for the progression of liver cirrhosis. The changes in platelet count, spleen sizes, Model for End-Stage Liver Disease (MELD) score, Sequential Organ Failure Assessment (SOFA) score, and Child-Turotte-Pugh (CTP) score were analyzed, and the incidence rate of liver cancer was compared between groups. A one-way analysis of variance, the Kruskal-wallis H test, the two-independent-sample t test, the chi-square test, and a multivariate logistic regression analysis were used for data analysis based on data type. Results: A total of 89 patients with compensated liver cirrhosis were enrolled, among whom 42 received the antiviral treatment with interferon and ribavirin (30 were treated with pegylated interferon-α and 12 were treated with ordinary interferon) and 47 did not receive any antiviral therapy. Among the patients who received the antiviral treatment with interferon and ribavirin, 20 achieved SVR and 22 did not achieve SVR. Compared with baseline values, platelet count in the SVR group and the NSVR group was increased by (44.93 ± 32.66)×10(9)/L and (9.73 ± 28.83)×10(9)/L, respectively, and platelet count in the untreated group was reduced by (19.76 ± 54.5)×10(9)/L; the three groups had a significant change in platelet count (F = 14.731, P < 0.001). Spleen size was reduced by 0.91 ± 1.09 cm in the SVR group and increased by 0.20±0.84 cm and 1.11 ± 1.69 cm in the NSVR group and the untreated group, respectively; the three groups had a significant change in spleen size (F = 14.943, P < 0.001). The three groups had no significant changes in MELD, SOFA, and CTP scores (P > 0.05). One patient (5.00%) in the SVR group, 5 (22.73%) in the NSVR group, and 6 (12.77%) in the untreated group progressed to liver cancer (χ (2) = 13.787, P = 0.001). The univariate analysis showed that SVR, HCV RNA, total bilirubin, and albumin were predictive factors for disease progression, and the multiple logistic regression analysis demonstrated that SVR and total bilirubin were predictive factors for disease progression. Conclusion: Interferon combined with ribavirin has a marked clinical effect in the treatment of compensated hepatitis C cirrhosis with good short- and long-term efficacy.

Gate dependence of upper critical field in superconducting (110) LaAlO3/SrTiO3 interface.

The fundamental parameters of the superconducting state such as coherence length and pairing strength are essential for understanding the nature of superconductivity. These parameters can be estimated by measuring critical parameters such as upper critical field, Hc2. In this work, Hc2 of a superconducting (110) LaAlO3/SrTiO3 interface is determined through magnetoresistive measurements as a function of the gate voltage, VG. When VG increases, the critical temperature has a dome-like shape, while Hc2 monotonically decreases. This relationship of independence between the variation of Tc and of Hc2 suggests that the Cooper pairing potential is stronger in the underdoped region and the coherence length increases with the increase of VG. The result is as for high temperature superconducting cuprates and it is different than for conventional low temperature superconductors.

[The expression of beta-tubulin gene in myelodysplastic syndrome evoluting to leukemia].

OBJECTIVE: Based on our previous established cohort of myelodysplastic syndrome (MDS), we investigated the potential effect of beta-tubulin(TUBB) gene in the transformation of MDS into acute leukemia. METHODS: From our nested case-control study cohort of MDS patients, we chose 11 paired transformed and non-transformed MDS patients. TUBB gene expression was tested by quantitative real-time PCR. TUBB-siRNA transfection was used to down-regulate TUBB gene expression in SKM-1 cell line. The function of TUBB gene in SKM-1 cell line was evaluated by cell proliferation, soft agar clone formation and electron microscope. RESULTS: TUBB gene expression in MDS patients in transformed group were significantly higher than that in control group (2.91±0.41 vs 0.90±0.23, P<0.01). After TUBB-siRNA transfection, A450/630nm of SKM-1 cells at 24 h, 48 h and 72 h were 0.299±0.045, 0.526±0.034 and 0.652±0.035, respectively, which were significantly decreased than those in negative-siRNA group(0.438±0.074, 0.858±0.064 and 0.974±0.044)(P<0.05). Soft agar clone formation in TUBB-siRNA group was (7.0±0.2)%, which was significantly reduced than that of negative-siRNA group (25.0±0.2)% (P<0.01). Electron microscope showed significant apoptotic signs in TUBB-siRNA group, including vacuoles in cytoplasm and karyorrhexis. CONCLUSION: Our results indicate that TUBB gene may play a role in the transformation of MDS into acute leukemia by affecting the proliferation of malignant clones.

F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.

Fbxl7, a subunit of the SCF (Skp-Cul1-F-box protein) complex induces mitotic arrest in cells; however, molecular factors that control its cellular abundance remain largely unknown. Here, we identified that an orphan F-box protein, Fbxl18, targets Fbxl7 for its polyubiquitylation and proteasomal degradation. Lys 109 within Fbxl7 is an essential acceptor site for ubiquitin conjugation by Fbxl18. An FQ motif within Fbxl7 serves as a molecular recognition site for Fbxl18 interaction. Ectopically expressed Fbxl7 induces apoptosis in Hela cells, an effect profoundly accentuated after cellular depletion of Fbxl18 protein or expression of Fbxl7 plasmids encoding mutations at either Lys 109 or within the FQ motif. Ectopic expression of Fbxl18 plasmid-limited apoptosis caused by overexpressed Fbxl7 plasmid. Thus, Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7 that may impact cellular processes involved in cell cycle progression.

Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection.

Neutrophil elastase (NE) and cathepsin G (CG) contribute to intracellular microbial killing but, if left unchecked and released extracellularly, promote tissue damage. Conversely, mechanisms that constrain neutrophil serine protease activity protect against tissue damage but may have the untoward effect of disabling the microbial killing arsenal. The host elaborates thrombospondin-1 (TSP-1), a matricellular protein released during inflammation, but its role during neutrophil activation following microbial pathogen challenge remains uncertain. Mice deficient in TSP-1 (thbs1(-/-)) showed enhanced lung bacterial clearance, reduced splenic dissemination, and increased survival compared with wild-type (WT) controls during intrapulmonary Klebsiella pneumoniae infection. More effective pathogen containment was associated with reduced burden of inflammation in thbs1(-/-) mouse lungs compared with WT controls. Lung NE activity was increased in thbs1(-/-) mice following K. pneumoniae challenge, and thbs1(-/-) neutrophils showed enhanced intracellular microbial killing that was abrogated with recombinant TSP-1 administration or WT serum. Thbs1(-/-) neutrophils exhibited enhanced NE and CG enzymatic activity, and a peptide corresponding to amino-acid residues 793-801 within the type-III repeat domain of TSP-1 bridled neutrophil proteolytic function and microbial killing in vitro. Thus, TSP-1 restrains proteolytic action during neutrophilic inflammation elicited by K. pneumoniae, providing a mechanism that may regulate the microbial killing arsenal.

Hepatic necro-inflammation and elevated liver enzymes: evaluation with MRI perfusion imaging with gadoxetic acid in chronic hepatitis patients.

AIM: To evaluate liver necro-inflammation and function by using gadoxetic acid-enhanced dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with histological analysis as the reference standard. MATERIALS AND METHODS: Seventy-nine subjects (21 healthy subjects; 58 chronic hepatitis patients) who received gadoxetic acid-enhanced DCE-MRI were divided into three subgroups: no (A0, n = 31), mild (A1, n = 27), and moderate-severe (A2-A3, n = 21) activities. Two DCE-MRI models were measured: (1) a dual-input single-compartment model to obtain absolute arterial, portal venous, and total blood flow, arterial fraction (ART), distribution volume, and mean transit time; (2) a curve analysis method to obtain peak, slope, and AUC (area under curve). The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels also obtained. Statistical testing included Kruskal-Wallis tests for continuous data, Pearson's correlation tests, and multiple linear regression analyses. RESULTS: Hepatic necro-inflammatory activity grades were significantly correlated with fibrotic stages, serum ALT level, ART and AUC. ART was helpful to predict the mild activity (≤ A1 versus >A1; Az = 0.728), whereas AUC could differentiate no activity from any activity (A0 versus >A0; Az = 0.703). Peak, slope and AUC were all associated with AST and ALT (p < 0.05). CONCLUSION: Gadoxetic acid-enhanced DCE-MRI parameters may be used to evaluate the severity of hepatic necro-inflammation and function.

Skp-cullin-F box E3 ligase component FBXL2 ubiquitinates Aurora B to inhibit tumorigenesis.

Aurora B kinase is an integral regulator of cytokinesis, as it stabilizes the intercellular canal within the midbody to ensure proper chromosomal segregation during cell division. Here we identified that the ubiquitin E3 ligase complex SCF(FBXL2) mediates Aurora B ubiquitination and degradation within the midbody, which is sufficient to induce mitotic arrest and apoptosis. Three molecular acceptor sites (K¹°², K¹°³ and K²°7) within Aurora B protein were identified as important sites for its ubiquitination. A triple Lys mutant of Aurora B (K¹°²/¹°³/(²°7R)) exhibited optimal resistance to SCF(FBXL2)-directed polyubiquitination, and overexpression of this variant resulted in a significant delay in anaphase onset, resulting in apoptosis. A unique small molecule F-box/LRR-repeat protein 2 (FBXL2) activator, BC-1258, stabilized and increased levels of FBXL2 protein that promoted Aurora B degradation, resulting in tetraploidy, mitotic arrest and apoptosis of tumorigenic cells, and profoundly inhibiting tumor formation in athymic nude mice. These findings uncover a new proteolytic mechanism targeting a key regulator of cell replication that may serve as a basis for chemotherapeutic intervention in neoplasia.

F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest.

Dysregulated behavior of cell cycle proteins and their control by ubiquitin E3 ligases is an emerging theme in human lung cancer. Here, we identified and characterized the activity of a novel F-box protein, termed FBXL2, belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family. Ectopically expressed FBXL2 triggered G2/M-phase arrest, induced chromosomal anomalies and increased apoptosis of transformed lung epithelia by mediating polyubiquitination and degradation of the mitotic regulator, cyclin D3. Unlike other F-box proteins that target phosphodegrons within substrates, FBXL2 uniquely recognizes a canonical calmodulin (CaM)-binding motif within cyclin D3 to facilitate its polyubiquitination. CaM bound and protected cyclin D3 from FBXL2 by direct intermolecular competition with the F-box protein for access within this motif. The chemotherapeutic agent vinorelbine increased apoptosis of human lung carcinoma cells by inducing FBXL2 expression and cyclin D3 degradation, an effect accentuated by CaM knockdown. Depletion of endogenous FBXL2 stabilized cyclin D3 levels, accelerated cancer cell growth and increased cell viability after vinorelbine treatment. Last, ectopic expression of FBXL2 significantly inhibited the growth and migration of tumorogenic cells and tumor formation in athymic nude mice. These observations implicate SCF(FBXL2) as an indispensible regulator of mitosis that serves as a tumor suppressor.

Peripheral blood mRNA expression patterns to differentiate hepatocellular carcinoma from other hepatic diseases.

Peripheral blood genes expressions profiling (GeXP) have been convinced to be more specific for the diagnosis of cancer and other diseases, and the GeXP system provides an ideal method to analyze multiple genes expression in one normalized and equable system. We aim to differentiate hepatocellular carcinoma from other hepatic diseases based on peripheral blood and the GeXP system. Fifteen selected hepatic diseases related genes with two house-keeping genes for normalization were detected by the GeXP system. The diagnosis model was based on K nearest neighbor classifier and cross validation, and software based on MATLAB software was built for differential diagnosis of hepatic diseases. Eight hepatic related genes were demonstrated to show an obvious statistic difference in expressions while the K nearest neighbors classifier showed that the accuracy for normal controls, hepatitis B, liver cirrhosis, hepatocellular carcinoma and the Other group was separately 80.57 %, 78.17 %, 84.48 %, 73.24 % and 85.85 %. The set of validation has been carried out to assess the accuracy of Model Two and the accuracy was even higher than the set of building for the model, except for the hepatitis B (HBV) group. A sensitive and specific GeXP system of eight genes has been developed for the accurate differential diagnosis of hepatic disease.

Thigh muscle volume predicted by anthropometric measurements and correlated with physical function in the older adults.

OBJECTIVES: (1) to correlate thigh muscle volume measured by magnetic resonance image (MRI) with anthropometric measurements and physical function in elderly subjects; (2) to predict MRI-measured thigh muscle volume using anthropometric measurements and physical functional status in elderly subjects. DESIGN: Cross-sectional, nonrandomized study. SETTING: Outpatient clinic in Taiwan. PARTICIPANTS: Sixty-nine elderly subjects (33 men and 36 women) aged 65 and older. MEASURMENTS: The anthropometric data (including body height, body weight, waist size, and thigh circumference), physical activity and function (including grip strength, bilateral quadriceps muscle power, the up and go test, chair rise, and five meters walk time) and bioelectrical impedance analysis data (including total body fat mass, fat-free mass, and predictive muscle size) were measured. MRI-measured muscle volume of both thighs was used as the reference standard. RESULTS: The MRI-measured thigh volume was positively correlated with all anthropometric data, quadriceps muscle power and the up and go test as well as fat-free mass and predictive muscle mass, whereas it was negatively associated with age and walk time. In predicting thigh muscle volume, the variables of age, gender, body weight, and thigh circumference were significant predictors in the linear regression model: Muscle volume (cm3) =4226.3－42.5 × Age (year)－955.7 × gender (male=1, female=2) + 45.9 × body weight(kg) + 60.0 × thigh circumference (cm) (r2 = 0.745, P < 0.001; standard error of the estimate = 581.6 cm3). CONCLUSION: The current work provides evidence of a strong relationship between thigh muscle volume and physical function in the elderly. We also developed a prediction equation model using anthropometric measurements. This model is a simple and noninvasive method for everyday clinical practice and follow-up.

Study on the relationship between meteorological conditions and acid rain in mid-eastern Fujian.

Based on the acid rain observation data and the contemporaneous historical synoptic charts of Mid-Eastern Fujian during the period of 1991 to 2003, we analyzed the distribution characteristics of acid rain in different seasons, weather types, precipitation grades and wind directions. The results showed that the acid pollution in Mid-Eastern Fujian was still serious. In winter, the precipitation pH value was 4.79, and the acid rain frequency was 60.62% which was twice higher than that in summer. The pH value of warm shear-type precipitation at 850 hPa was 4.79. Nearly half of these precipitations had the problems of acid rain pollution. The acid rain frequency of the inverted trough type was only 26.11% which was the lowest one in all types. There was no marked difference of the acid rain distribution characteristics between ahead-of-trough and behind-the-trough. The precipitation pH values of the five grades were lower than 5.30 and the acid rain frequency changed as an inverted U shape with the increasing of the rainfall. The pH values of precipitations in the eight wind directions were generally below 5.20, and the acid rain frequencies were about 40%.