Broadband near-infrared (NIR) emitting Cr3+ -doped La3 Ga5 SnO14 phosphor with long persistent and photostimulated persistent luminescence.

Recently, long persistent phosphors (LPPs) have attracted significant attention as promising candidates for biomedical applications. However, the serious decrease in luminescence intensity in tissue still remains a major challenge. Therefore, exploring more competitive LPPs and achieving reproducible tissue imaging is crucial. In this study, a new series of near-infrared (NIR) phosphors La3 Ga5 Sn1-x O14 :xCr3+ (x = 0.005-0.05) were synthesized using a high-temperature solid-state method. The as-synthesized samples were characterized using X-ray diffraction, diffuse/photoluminescence spectroscopy, fluorescence decay curves, and thermoluminescence spectroscopy. Upon excitation with ultraviolet light, strong emission bands were observed in the range 600-1200 nm with an optimal doping concentration of x = 0.02 mol. Moreover, La3 Ga5 SnO14 :Cr3+ exhibits persistent luminescence due to the presence of suitable energy traps, which prompted the phosphor to emit NIR light even after the removal of the excitation source.

[Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis]. / CHI3L1åœ¨å·å´Žç— æ ·è¡€ç®¡ç‚Žå°é¼ æ¨¡åž‹å† çŠ¶åŠ¨è„‰æŸä¼¤ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. METHODS: Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. RESULTS: The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). CONCLUSIONS: In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Gamma-Glutamyl Transpeptidase-to-Platelet ratio predicts liver fibrosis in patients with concomitant chronic hepatitis B and nonalcoholic fatty liver disease.

OBJECTIVES: The aim of this study was to compare the correlation of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index-4 (FIB-4), and liver stiffness measurement (LSM) in the diagnosis of liver fibrosis, and perform a diagnostic value of GPR for predicting fibrosis in CHB patients with NAFLD. METHODS: A retrospective study was conducted on CHB patients concurrent with NAFLD between September 2019 and December 2020. They were divided into control group (LSM ≤ 9.7 kpa) and fibrosis group (LSM ≥ 9.8 kpa). Demographic data were collected; ALT, AST, and PLT were also detected. LSM was measured by transient elastography (TE). The GPR, APRI, and FIB-4 were calculated. The correlation between GPR, APRI, FIB-4, and LSM was compared. The accuracy of predicting liver fibrosis using GPR, APRI, and FIB-4 was assessed. RESULTS: Eighty-five CHB patients with NAFLD were enrolled. Multivariate analysis showed that age (p = 0.005), GGT (p = 0.001), and PLT (p = 0.013) were the independent risk factors for LSM. The GPR (p = 0.008), APRI (p = 0.001), and FIB-4 (p = 0.001) values in fibrosis group were higher than control group. Pearson linear correlation was used to analyze the correlations between LSM and GPR, APRI, and FIB-4. LSM was correlated with GPR, APRI, and FIB-4. The AUCs of GPR, APRI, and FIB4 were 0.805, 0.766, and 0.826 in assessing liver fibrosis, respectively. No significant differences in the areas of GPR were comparable to that of APRI and FIB-4. CONCLUSION: GPR has a good correlation with LSM in assessing liver fibrosis and can be used as a noninvasive index for the assessment of liver fibrosis in patients with concomitant CHB and NAFLD.

[Association between duration of fever before treatment and intravenous immunoglobulin resistance in Kawasaki disease]. / å·å´Žç— æ²»ç–—å‰å‘çƒ­æ—¶é—´ä¸Žä¸™ç§çƒè›‹ç™½è€è¯çš„ç›¸å ³æ€§ä¸´åºŠç ”ç©¶.

OBJECTIVES: To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD). METHODS: A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance. RESULTS: In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05). CONCLUSIONS: IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.

Diagnostic accuracy of red blood cell distribution width to platelet ratio for predicting liver fibrosis in patients with chronic hepatitis B: A meta-analysis / Precisión diagnóstica del ancho de distribución de glóbulos rojos a la proporción de plaquetas para predecir la fibrosis hepática en pacientes con hepatitis B crónica: un metaanálisis

Objective: This study aims to systematically review the performance of red blood cell distribution width to platelet ratio (RPR) in the diagnosis of significant or advanced fibrosis, and cirrhosis associated with hepatitis B virus (HBV). Methods: The relevant studies were comprehensively searched in English databases such as Web of Science, PubMed, EMBASE, Cochrane Library, as well as Chinese databases such as China National Knowledge Infrastructure, Wanfang Data from the inception to March 2021. Accuracy of RPR in diagnosing significant or advanced fibrosis and liver cirrhosis was assessed by area under the curve (AUC), pooled sensitivity and specificity, as well as positive and negative likelihood ratios. Stata 15.0 software was applied to analyze the data. Results: In total, 13 literature met the requirements, including patients with significant fibrosis (n=1890), advanced fibrosis (n=645), and cirrhosis (n=499). The prevalence rates of significant fibrosis, advanced fibrosis and cirrhosis were 49.31% (range: 17.25–84.21%), 37.07% (range: 9.60–58.20%) and 2.18% (range: 2.78–44.19%), respectively. The AUCs for predicting significant fibrosis, advanced fibrosis, and cirrhosis by RPR were 0.73 (95%CI: 0.69–0.76), 0.80 (95%CI: 0.77–0.84) and 0.80 (95%CI: 0.76–0.83), respectively. Conclusion: RPR is of some diagnostic value to the prediction of HBV-related significant fibrosis, advanced fibrosis and cirrhosis. This conclusion is urgently needed to be verified by further multi-center studies of large sample size and rigorous design.(AU)

Objetivo: Este estudio tiene como objetivo revisar sistemáticamente la capacidad del cociente entre el ancho de distribución de los glóbulos rojos y el recuento plaquetario (RPR) para discriminar en pacientes con infección crónica por virus de la hepatitis B la existencia de fibrosis significativa, avanzada y cirrosis. Métodos: Se realizaron búsquedas exhaustivas de los estudios relevantes en bases de datos en inglés, como Web of Science, PubMed, EMBASE y Cochrane Library, así como en bases de datos chinas, como China National Knowledge Infrastructure y Wanfang Data, desde el inicio hasta marzo de 2021. La precisión de RPR en el diagnóstico de fibrosis avanzada y cirrosis hepática se evaluó mediante el área bajo la curva, la sensibilidad y la especificidad combinadas, así como las razones de probabilidad positiva y negativa. Se aplicó el software Stata 15.0 para analizar los datos. Resultados: Un total de 13 publicaciones cumplieron con los requisitos, incluyendo pacientes con fibrosis significativa (n=1.890), fibrosis avanzada (n=645) y cirrosis (n=499). Las tasas de prevalencia de fibrosis significativa, fibrosis avanzada y cirrosis fueron del 49,31% (rango: 17,25-84,21), 37,07% (rango: 9,60-58,20) y 2,18% (rango: 2,78-44,19), respectivamente. El área bajo la curva para predecir fibrosis significativa, fibrosis avanzada y cirrosis por RPR fue 0,73 (IC 95%: 0,69-0,76), 0,80 (IC 95%: 0,77-0,84) y 0,80 (IC 95%: 0,76-0,83), respectivamente. Conclusión: La RPR tiene algún valor diagnóstico para la predicción de fibrosis significativa relacionada con el virus de la hepatitis B, fibrosis avanzada y cirrosis. Y esta conclusión debe ser verificada con urgencia mediante más estudios multicéntricos de gran tamaño de muestra y diseño riguroso.(AU)

Diagnostic accuracy of red blood cell distribution width to platelet ratio for predicting liver fibrosis in patients with chronic hepatitis B: A meta-analysis.

OBJECTIVE: This study aims to systematically review the performance of red blood cell distribution width to platelet ratio (RPR) in the diagnosis of significant or advanced fibrosis, and cirrhosis associated with hepatitis B virus (HBV). METHODS: The relevant studies were comprehensively searched in English databases such as Web of Science, PubMed, EMBASE, Cochrane Library, as well as Chinese databases such as China National Knowledge Infrastructure, Wanfang Data from the inception to March 2021. Accuracy of RPR in diagnosing significant or advanced fibrosis and liver cirrhosis was assessed by area under the curve (AUC), pooled sensitivity and specificity, as well as positive and negative likelihood ratios. Stata 15.0 software was applied to analyze the data. RESULTS: In total, 13 literature met the requirements, including patients with significant fibrosis (n=1890), advanced fibrosis (n=645), and cirrhosis (n=499). The prevalence rates of significant fibrosis, advanced fibrosis and cirrhosis were 49.31% (range: 17.25-84.21%), 37.07% (range: 9.60-58.20%) and 2.18% (range: 2.78-44.19%), respectively. The AUCs for predicting significant fibrosis, advanced fibrosis, and cirrhosis by RPR were 0.73 (95%CI: 0.69-0.76), 0.80 (95%CI: 0.77-0.84) and 0.80 (95%CI: 0.76-0.83), respectively. CONCLUSION: RPR is of some diagnostic value to the prediction of HBV-related significant fibrosis, advanced fibrosis and cirrhosis. This conclusion is urgently needed to be verified by further multi-center studies of large sample size and rigorous design.

LncRNA AFAP1-AS1 regulates proliferation and apoptosis of endometriosis through activating STAT3/TGF-ß/Smad signaling via miR-424-5p.

AIM: Endometriosis is a common gynecological disorder characterized by chronic pelvic pain and infertility, which negatively affects women's health worldwide. AFAP1-AS1 has been implicated in endometriosis lesions recently, but its mechanism of endometriosis progression remains unclear. METHODS: Endometrial stromal cells (ESCs) were used to identify the role of AFAP1-AS1 in endometriosis. The migratory capability was determined by transwell. Gene and protein expressions were identified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability and apoptosis were detected by MTT assays and flow cytometry, respectively. Luciferase report assays were used to identify the interaction of AFAP1-AS1, miR-424-5p and signal transducer and activator of transcription 3 (STAT3). RESULTS: AFAP1-AS1 knockdown or miR-424-5p overexpression inhibited proliferation and migration, and promoted apoptosis in ESCs. In addition, knockdown of AFAP1-AS1 repressed the expression of ki-67 and Bcl-2, and promoted the levels of cleaved caspase-3 and Bax. Furthermore, knockdown of AFAP1-AS1 inhibited the conversion of E-cadherin to N-cadherin and the expression of Snail. Moreover, AFAP1-AS1 activated the STAT3/transforming growth factor-ß1 (TGF-ß1)/Smad2 axis via directly targeting miR-424-5p. The regulatory effect of AFAP1-AS1 silencing in ESC migration, proliferation, and apoptosis was reversed by miR-424-5p inhibition or STAT3 overexpression. CONCLUSIONS: AFAP1-AS1 silencing could inhibit cell proliferation and promote apoptosis by regulating STAT3/TGF-ß/Smad signaling pathway via targeting miR-424-5p in ESCs. AFAP1-AS1 may be a potential therapeutic target of controlling the progression of endometriosis.

Mitigating COVID-19 Transmission in Schools With Digital Contact Tracing.

Precision mitigation of COVID-19 is in pressing need for postpandemic time with the absence of pharmaceutical interventions. In this study, the effectiveness and cost of digital contact tracing (DCT) technology-based on-campus mitigation strategy are studied through epidemic simulations using high-resolution empirical contact networks of teachers and students. Compared with traditional class, grade, and school closure strategies, the DCT-based strategy offers a practical yet much more efficient way of mitigating COVID-19 spreading in the crowded campus. Specifically, the strategy based on DCT can achieve the same level of disease control as rigid school suspensions but with significantly fewer students quarantined. We further explore the necessary conditions to ensure the effectiveness of DCT-based strategy and auxiliary strategies to enhance mitigation effectiveness and make the following recommendation: social distancing should be implemented along with DCT, the adoption rate of DCT devices should be assured, and swift virus tests should be carried out to discover asymptomatic infections and stop their subsequent transmissions. We also argue that primary schools have higher disease transmission risks than high schools and, thereby, should be alerted when considering reopenings.

[Clinical features of children with recurrent Kawasaki disease: a Meta analysis].

OBJECTIVE: To study the clinical features of children with recurrent Kawasaki disease (KD). METHODS: PubMed, Web of Science, Embase, CNKI, Wanfang Med Online, and Weipu Data were searched for case-control studies on the clinical features of initial and recurrent KD. The articles were screened according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the Meta analysis. Effect models were selected based on the results of heterogeneity test, and then pooled OR or weighted mean difference (WMD), and their 95% CI were calculated. RESULTS: A total of 9 case-control studies were included, with 12 059 children with KD in total, among whom 206 children had recurrent KD (127 boys/61.7%; 79 girls/38.3%). The results of the Meta analysis showed that compared with the initial KD onset, the children with recurrent KD had a shorter duration of fever (WMD=-1.81, 95%CI:-2.99 to -0.64) and a lower proportion of children with swelling of the hands and feet (OR=0.46, 95%CI:0.26 to 0.80). There was no significant difference in the incidence rate of coronary artery lesions between recurrent KD and initial KD (OR=1.34, 95%CI:0.84 to 2.14). CONCLUSIONS: Current evidence shows that children with recurrent KD tend to have a shorter duration of fever and a lower incidence of swelling of the hands and feet. KD recurrence is more common in boys. Current evidence does not show an increased risk of developing coronary artery lesions in children with recurrent KD.

The relationship between endothelial progenitor cells and pulmonary arterial hypertension in children with congenital heart disease.

BACKGROUND: Pulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD. METHODS: In this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /µL of peripheral blood was calculated using the following formula: EPCs /µL = WBC /L × lymphocytes % × EPCs % × 10- 6. RESULTS: The median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/µL, 1.30 /µL and 0.98/µL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16-0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05). CONCLUSION: The findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.

Long-term follow-up and clinical implications in Chinese patients with aortic intramural hematomas.

BACKGROUND: Intramural hematomas (IMHs) are reported to dynamically evolve into different clinical outcomes ranging from regression to aortic rupture, but no practice guidelines are available in China. OBJECTIVE: To determine the evolution of IMHs after long-term follow-up and to identify the predictive factors of IMH outcomes in the Chinese population. METHODS: A total of 123 IMH patients with clinical and imaging follow-up data were retrospectively studied. The primary endpoints were aortic disease-related death, aortic dissection, penetrating aortic ulcer (PAU), thickening of the aortic hematoma and aortic complications requiring surgical or endovascular treatment. RESULTS: All 123 IMH patients were monitored clinically. The follow-up duration ranged from 1.4 to 107 months (median, 20 months). Thirty-nine patients had type A IMH, and 84 had type B. The multivariate analysis showed that a baseline MAD ≥ 44.75 mm (2.9% vs 61.4%, P < 0.001) and acute PAUs (2.9% vs 34.1%, P = 0.008) were independent predictors of aorta-related events. CONCLUSIONS: Medication and short-term imaging are recommended for Chinese IMH patients with a hematoma thickness < 10.45 mm and a baseline MAD < 44.75 mm. Rigorous medical observation should also be performed during the acute phase of IMH.

Influence of distal extension of false lumen on adverse aortic events after TEVAR in patients with acute type B aortic dissection.

OBJECTIVE: To investigate the clinical outcomes influenced by distal extension of false lumen in acute type B aortic dissection (TBAD) patients following thoracic endovascular aortic repair (TEVAR). METHODS: From April 2002 to January 2013, 264 TBAD patients treated with TEVAR were retrospectively enrolled. The IIIa group exhibited a distal false lumen above the diaphragm (n = 70), and the IIIb group exhibited a distal false lumen under the diaphragm (n = 194). The morphological characteristics and adverse events (30-day and >30 days) were recorded and evaluated. RESULTS: There were no significant differences between the two groups regarding the demographics, comorbidity profiles, or initial feature of computed tomography angiography. The incidence of true lumen compression and branch involvement were significantly increased in the IIIb group compared with the IIIa group (8.6% vs. 25.3%, respectively; 15.7% vs. 36.1%, respectively, both P < 0.05). The 30-day mortality rate was 1.0% (2/194) in the IIIb group, whereas the IIIa group was zero. The incidence of early adverse events, the 5-year cumulative freedom from adverse events, and the 5-year cumulative freedom from all-cause mortality rate were not significantly different between the IIIa and IIIb groups (2.9% vs. 6.7%, 81.4%, and 80.4%, and 95.7% vs. 93.8%, respectively, all P > 0.05). Log-rank tests also indicated there was no significant difference. CONCLUSIONS: There was no significant difference between the IIIa and IIIb groups in the 5-year morality and adverse aortic events following TEVAR. The distal extension of false lumen prior to TEVAR does not influence the long-term morality and adverse aortic events in acute TBAD.

Association of TNF-α gene variations with thoracic aortic dissection risk in a Chinese Han population.

BACKGROUND: Chronic inflammation may be involved in pathogenesis of thoracic aortic dissection (TAD). Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays an important role in pathological TAD progression. In this study, we determined wether genetic variants of TNF-α were associated with TAD. METHODS: Frequency distributions of TNF-α promoter polymorphisms (-1031C/T,-857C/T,-308G/A, and -238G/A) were determined by direct sequencing. TNF-α plasma levels were measured by enzyme-linked immunosorbent assay. Plasma levels of TNF-α mRNA in peripheral-blood mononuclear cells were analyzed by real-time quantitative polymerase chain reaction amplification. RESULTS: We found the TNF-α promoter -857C/T polymorphism is associated with disease progression susceptibility in TAD patients. The CC homozygote of TAD patients had a significantly higher risk of TAD than did T allele carriers (P< 0.05). Plasma TNF-α concentrations were also significantly higher in TAD patients than control subjects (P<0.05), and CC genotype carriers showed increased TNF-α levels compared with T allele carriers (P<0.05). Moreover, peripheral-blood mononuclear cells carrying the CC genotype showed increased TNF-α mRNA levels compared with cells carrying the T allele. CONCLUSIONS: The -857C/T polymorphism of TNF-α promoter plays a role in the genetic variation underlying susceptibility of individuals to TAD progression. The CC genotype is associated with increased TNF-α expression in TAD patients, and may be an independent predictive factor for TAD.

Disruption of Circadian Rhythms and Sleep in Critical Illness: Potential Implications for Angiogenesis After Myocardial Infarction. A Review.

Angiogenesis plays an important role in the treatment of acute myocardial infarction (MI). Formation of micro-vessels has the potential to prevent apoptosis of the ischemic myocardium and to improve cardiac function after MI. Delivery of growth factors or administration of stem/progenitor cells (mainly from bone marrow) are the dominant therapies to induce angiogenesis after MI. Nevertheless, clinical trials have shown that delivery of a single growth factor or single type of cell does not provide sufficient angiogenesis to promote cardiac repair. Circadian rhythms control many physiological and pathological processes in mammals. Many studies show a close relationship between circadian rhythms and MI. Disruption of the circadian rhythms in humans leads to increased incidence of MI. The onset and infarct area of MI are markedly elevated at certain time points. Determining the mechanisms of angiogenesis and vessel maturation in the ischemic heart under the control of circadian rhythms could help in the development of novel and angiogenesis- targeted therapeutics for the treatment of MI.

Inhibition of heat shock protein 90 suppresses squamous carcinogenic progression in a mouse model of esophageal cancer.

PURPOSE: Heat shock protein 90 (Hsp90), a potential therapeutic target, has been widely recognized in vitro and in vivo in immunodeficient mice. Here, we aimed to evaluate the role of Hsp90 in an immunocompetent mouse model of esophageal squamous cell cancer (ESCC). METHODS: The carcinogen 4-nitroquinoline 1-oxide (4NQO) was used to induce ESCC in C57BL/6 mice. Cancer progression was analyzed through observation of appearance, hematoxylin-eosin staining, immunohistochemical detection, and terminal dUTP nick-end labeling analysis. RESULTS: 4NQO led to the progressive appearance of preneoplastic and tumoral lesions in the esophagus, with 100 % incidence of ESCC in situ occurring only after 16 weeks of carcinogen exposure. Most of these lesions evolved spontaneously into highly invasive ESCC even after 4NQO withdrawal (weeks 16-22). Interestingly, there was marked upregulation of Hsp90 and its client proteins in tumoral lesions at 22 weeks. Hsp90 inhibition by intraperitoneal injection of SNX-2112 over the following 2 weeks downregulated AKT and cyclin D1 expression, leading to significant reduction in tumor incidence and prevention of ESCC progression. Moreover, SNX-2112 treatment decreased proliferating cell nuclear antigen expression and increased the number of apoptotic cells in ESCC tissues. CONCLUSIONS: Our in vivo findings support the contribution of Hsp90 to ESCC progression, which was achieved by stimulating apoptosis and inhibition of cell proliferation, and provide a strong rationale for further evaluation of Hsp90 inhibitors for treating ESCC.

SNX-25a, a novel Hsp90 inhibitor, inhibited human cancer growth more potently than 17-AAG.

17-Allylamino-17-demethoxygeldanamycin (17-AAG), a typical Hsp90 inhibitor derived from geldanamycin (GA), has entered Phase III clinical trials for cancer therapy. However, it has several significant limitations such as poor solubility, limited bioavailability and unacceptable hepatotoxicity. In this study, the anticancer activity and mechanism of SNX-25a, a novel Hsp90 inhibitor, was investigated comparing with that of 17-AAG. We showed that SNX-25a triggered growth inhibition more sensitively than 17-AAG against many human cancer cells, including K562, SW-620, A375, Hep-2, MCF-7, HepG2, HeLa, and A549 cell lines, especially at low concentrations (<1 µM). It showed low cytotoxicity in L-02, HDF and MRC5 normal human cells. Compared with 17-AAG, SNX-25a was more potent in arresting the cell cycle at G2 phase, and displayed more potent effects on human cancer cell apoptosis and Hsp90 client proteins. It also exhibited a stronger binding affinity to Hsp90 than 17-AAG using molecular docking. Considering the superiority effects on Hsp90 affinity, cell growth, cell cycle, apoptosis, and Hsp90 client proteins, SNX-25a is supposed as a potential anticancer agent that needs to be explored in detail.

[Sequencing analysis and identification of a novel HLA-B(*)40:162 allele].

The aim of this study was to identify a novel HLA-B allele in Chinese population. The HLA typing of bone marrow donors was performed by PCR-SBT. The ambiguous novel HLA allele was confirmed with GSSP and single stranded SBT method. The result indicated that there was a sample, the sequence of which was different from all alleles in the HLA databases. The sequence analysis showed that it differed from the closet matching allele B(*)40:06:01 in one nucleotide substitution, 272 C>T in Exon 2, which resulted in an amino acid change from Serine (Ser) to Phenylalanine (Phe) at codon 63. It is concluded that the novel allele has been identified and is named HLA-B(*)40:162 by the WHO Nomenclature Committee.

Phosphorylation and anti-tumor activity of exopolysaccharide from Lachnum YM120.

Phosphorylated polysaccharide PLEP-1a, with the PO4³â» content of 6.39%, was prepared from LEP-1a by phosphorylation. IR, (13)C NMR and (31)P NMR results of PLEP-1a showed that the original basic structure of the polysaccharide was not changed, and the -H2PO3 group was linked at C6 of LEP-1a. The results of anti-tumor experiments in vivo showed that 100 mg/kg and 400 mg/kg of LEP-1a could significantly improve the food consumption, body weight, tumor inhibition rate and thymus index of S180 sarcoma mice, and increase the levels of SOD, IL-2 and TNF-α in mice blood serum, indicating that LEP-1a had an excellent anti-tumor activity. Furthermore, PLEP-1a had a significantly enhanced inhibitory effect on S180 sarcoma mice than LEP-1a, suggesting that phosphorylation is an effective way of improving the biological activity of LEP-1a.

Efficacy of entecavir treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life.

OBJECTIVE: To analyze the efficacy and safety of entecavir (ETV) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life. METHODS: We retrospectively analyzed 230 nucleos(t)ide naïve chronic hepatitis B patients who received ETV 0.5 mg/day monotherapy for at least 3 months, of whom 113 were HBeAg positive and 117 were HBeAg negative. The primary endpoints was cumulative probability of achieving a virological response (undetectable serum HBV DNA, <100IU/mL). Secondary endpoints were rates of ALT normalization (ALT < upper limit of normal), HBeAg seroconversion, resistance, and safety. RESULTS: The median follow-up duration was 27.5 months (3-73 months) and mean age was 42 years. With 230, 214, 180, 142, 88, 42 and 11 patients followed-up for at least 3 months,6 months, 1, 2, 3, 4 and 5 years, respectively. In all, Incremental increases were observed in the rates of undetectable HBV DNA. 67.0%, 85.0%, 89.4%, 94.4%, 95.5%, 97.6%, 100% had undetectable HBV DNA at month 3, month 6, 1 year, 2 years, 3 years, 4 years and 5 years. Proportions of patients achieving normal ALT were 73.9%, 85.5%, 82.8%, 89.4%, 80.7%, 85.7%, 100%, respectively. The rate of HBeAg seroconversion reached 21.4% and 15.4% at year2, 3, respectively. One patient achieved HBsAg seroclearance after 1 year, and achieved anti-HBs seroconversion at year 3. Of 180 patients, HBV DNA was detectable (partial virological response, PVR) in 19 patients at year 1 of follow-up, twelve of 14 (85.7%) patients with PVR need more than 1 year of continuous ETV therapy to achieved VR. At baseline, no ETV-resistance was detected in 25 ETV-naïve patients. One patient developed ETV-resistance mutations due to noncompliance. No serious adverse event was reported. CONCLUSION: Long-term ETV treatment of nucleos(t)ide-naïve was effective and safe in real life. Adjustment of ETV monotherapy in nucleos(t)ide-naïve patients with a partial virological response at 1 year may be unnecessary.

Antibacterial properties of PES/CuCl(2) three-bore hollow fiber UF membrane.

In this study, a three-bore polyethersulfone (PES) hollow fiber ultrafiltration (UF) membrane with antibacterial properties was prepared by phase inversion, using PES as the membrane material, N,N-dimethylacetamide (DMAC) as solvent, polyvinylpyrrolidone (PVP) and CuCl(2) as additives. The effect of CuCl(2) content on the water flux and rejection was studied and the antibacterial properties of PES hollow fiber UF membrane were also investigated. The water flux results indicated that the hydrophilic properties of PES UF membranes were improved after adding CuCl(2). The rejection of PVA-50000 was expected to drop slightly but remain high above 96%. The membranes showed good antibacterial activity against Escherichia coli (E. coli) after adding CuCl(2) and the antibacterial rate of PES/CuCl(2) UF membranes was close to 100% after running for 48 h. PES hollow fiber UF membranes with antibacterial properties were prepared through the formation of the water-soluble PVP/Cu(2+) complex with spatial network structure, which have good antibacterial and hydrophilic properties. Therefore, this study could provide an effective method for membrane antifouling.