Resumen Antecedentes: La enfermedad de injerto contra huésped (EICH) es una complicación importante después del trasplante alogénico de células madre hematopoyéticas. Objetivos: Para dilucidar el papel de TLR4, el principal receptor de LPS bacteriano, en el desarrollo de GVHD, construimos un modelo de GVHD en ratones knockout para TLR4 (TLR4-/-) y monitoreamos el quimerismo celular. Métodos: En este estudio, usamos PCR para identificar si se establecieron ratones knockout para TLR4 (TLR4-/-). Antes del trasplante, pretratamos a los ratones con irradiación para obtener la dosis de irradiación adecuada. Se aplicó citometría de flujo para medir el estado de quimerismo, las distribuciones de APC y células T en ratones receptores TLR4+/+ y TLR4-/-. Resultados: El estado general de los receptores de TLR4-/- fue mejor que el de los receptores de TLR4+/+, y los ratones receptores de TLR4-/- mostraron manifestaciones de GVHD menos graves que los ratones receptores de TLR4+/+. La mayoría de las APC y las células T en el bazo del ratón huésped se derivaron de las células del donante, y las células T CD4+, incluidas las células T de memoria, se encontraban en su mayoría en los ratones huéspedes. Conclusión: En general, nuestros datos muestran que la eliminación de TLR4 atenuó el desarrollo de GVHD, lo que sugiere que TLR4 podría usarse como un nuevo objetivo y paradigma terapéutico en las terapias de GVHD.

Abstract Background: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Objective: To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4-/-) mice and monitored the cell chimerism. Methods: In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4-/-) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4+/+ and TLR4-/- recipient mice. Results: The general condition of TLR4-/- recipients was better than that of TLR4+/+ recipients, and the TLR4-/- recipient mice showed less severe GVHD manifestations than the TLR4+/+ recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4+ T-cells, including memory T-cells, were in the majority in host mice. Conclusion: In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.

Abstract Aim: to investigate the effects of low sodium formula salt combined with the Chinese Modified Dietary Approaches to Stop Hypertension (DASH) diet on cerebrovascular function in patients with hypertension and type 2 diabetes. Methods: an eight-week single-arm trial was conducted in 66 patients with hypertension and type 2 diabetes to investigate effects of low sodium formula salt (potassium chloride 56 %, sodium chloride 23 %, 5 g/day) combined with Chinese Modified DASH diet on cerebrovascular function (measured by transcranial Doppler sonography), indicators of chronic diseases (blood pressure, blood glucose and blood lipids) and urinary excretion. The above indicators were performed before and after intervention. Results: fifty-nine subjects completed the study. Peak systolic velocity, mean flow velocity, end-diastolic velocity, pulsatility index and resistance index of internal cerebral artery and vertebral artery decreased significantly (p < 0.05); pulsatility index and resistance index of anterior cerebral artery and middle cerebral artery decreased significantly (p < 0.05); and end-diastolic velocity and pulsatility index of basilar artery decreased significantly (p < 0.05). Systolic blood pressure, diastolic blood pressure, fasting blood glucose and postprandial blood glucose decreased significantly (p < 0.001; p < 0.001; p < 0.001; p < 0.001). Blood pressure and blood glucose control rates increased significantly (p < 0.001). Conclusions: based on the study, 23 % low-sodium formula combined with CM-DASH diet pattern can improve cerebrovascular function in community patients with hypertension complicated with diabetes and has a good short-term benefit of blood pressure and glucose control.

Resumen Objetivo: investigar los efectos de una sal baja en sodio combinada con la versión china de la dieta DASH (del inglés Dietary Approaches to Stop Hypertension) modificada en la función cerebrovascular en pacientes con hipertensión y diabetes tipo 2. Métodos: en 66 pacientes con hipertensión y diabetes tipo 2 se llevó a cabo un ensayo de ocho semanas para investigar los efectos de la sal baja en sodio (cloruro de potasio 56 %, cloruro de sodio 23 %, 5 g/día) combinada con la dieta DASH en su versión china modificada en la función cerebrovascular (medido por sonografía Doppler transcraneal), los indicadores de enfermedades crónicas (presión arterial, glucosa sanguínea y lípidos sanguíneos) y la excreción urinaria. Los indicadores anteriores se midieron antes y después de la intervención. Resultados: cincuenta y nueve sujetos completaron el estudio. La velocidad sistólica máxima, la velocidad media del flujo, la velocidad diastólica final, el índice de pulsatilidad y el índice de resistencia de la arteria cerebral anterior y la arteria vertebral disminuyeron significativamente (p < 0,05); el índice de pulsatilidad y el índice de resistencia de la arteria cerebral anterior y la arteria media disminuyeron significativamente (p < 0,05); y la velocidad diastólica final y el índice de pulsatilidad de la arteria basilar disminuyeron significativamente (p < 0,05). La presión arterial sistémica, la presión arterial diastólica, la glucosa arterial en ayuno y la glucemia posprandial disminuyeron significativamente (p < 0,001, p < 0,001, p < 0,001, p < 0,001). La presión arterial y las tasas de control de glucosa en sangre aumentaron significativamente (p < 0,001). Conclusiones: la fórmula de sal con un 23 % de sodio combinada con la dieta DASH en su versión china modificada puede mejorar la función cerebrovascular en pacientes comunitarios con hipertensión complicada por la diabetes y es beneficiosa a corto plazo para la presión arterial y el control de la glucosa.

This work presented a new PEG modified calix[4]arene stationary phase (C4A-PEG-2PTSC) for gas chromatographic (GC) separations. The statically coated C4A-PEG-2PTSC column exhibited moderate polarity and column efficiency of 2224 plates m-1 determined by 1-octanol at 120 oC. The results showed that the C4A-PEG-2PTSC column exhibited the good separation performance for various types of analytes containing halogenated benzenes, benzaldehydes, phenols, alcohols, anilines isomers and showed the different retention behavior with the comparative columns. Importantly, it showed the better separation capacity of toluidine and xylidine isomers than commercial HP-35 column. Moreover, it was applied in practical sample analysis to detect the content of isomer impurities. This work exhibited the good application potential of C4A-PEG-2PTSC stationary phase in GC analyses. calix4arene calixarene calix 4 arene C4APEG2PTSC CAPEGPTSC C4A 2PTSC C A PTSC (C4A-PEG-2PTSC (GC separations 222 m1 m 1 m- 1octanol octanol 12 oC benzenes benzaldehydes phenols alcohols columns Importantly HP35 HP 35 HP-3 Moreover impurities analyses APEG CA 22 HP3 3 HP- 2

Abstract Background In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. Objective To evaluate the correlation of COX-2 with the prognosis in glioma patients. Methods Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. Results In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79–2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57–2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69–3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. Conclusion The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice. years cyclooxygenase2 cyclooxygenase 2 cyclooxygenase- COX2 COX (COX-2 CSC (CSC gliomas Nevertheless COX- controversial included ORs (ORs HRs (HRs 95 95%CIs 95CIs CIs (95%CIs estimated well 1 64 (OS n 2.26 226 26 95CI CI 1.79–2.86, 179286 1.79–2.86 , 79 86 1.79–2.86) 5 2.16 216 16 1.57–2.97 157297 57 97 nonAsian non 6 2.39 239 39 1.69–3.38 169338 69 3 38 metaanalysis. metaanalysis meta analysis. meta-analysis practice (COX- 9 2.2 22 17928 1.79–2.8 7 8 2.1 21 1.57–2.9 15729 2.3 23 1.69–3.3 16933 (COX 2. 1792 1.79–2. 1.57–2. 1572 1.69–3. 1693 179 1.79–2 1.57–2 157 1.69–3 169 17 1.79– 1.57– 15 1.69– 1.79 1.57 1.69 1.7 1.5 1.6 1.

Resumo Introdução Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. Objetivo Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. Métodos Estudos elegíveis sobre este assunto foram incluídos e foram estimadosodds ratios (ORs) ehazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. Resultados No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57–2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69–3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. Conclusão O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica. anos ciclooxigenase2 ciclooxigenase 2 ciclooxigenase- COX2 COX (COX-2 célulastronco células tronco CSC (CSC gliomas entanto COX- controverso ORs (ORs HRs (HRs 95 95%. . 95%) analisadas 1 64 (OS n 2,26 226 26 1,792,86, 179286 1,79 2,86 , 79 86 1,79-2,86) 5 2,16 216 16 1,57–2,97 157297 57 97 6 2,39 239 39 1,69–3,38 169338 69 3 38 metanálise clínica (COX- 9 2,2 22 792 1,792,86 17928 179 1,7 286 2,8 7 8 1,79-2,86 2,1 21 1,57–2,9 15729 2,3 23 1,69–3,3 16933 (COX 2, 1,792,8 1792 17 1, 28 1,79-2,8 1,57–2, 1572 1,69–3, 1693 1,792, 1,79-2, 1,57–2 157 1,69–3 169 1,792 1,79-2 1,57– 15 1,69– 1,79- 1,57 1,69 1,5 1,6

Abstract This study investigated the protective effect of dexmedetomidine (Dex) on lung injury during one-lung ventilation (OLV) in elderly patients undergoing radical esophagectomy with remote ischemic preconditioning (RIPC). Fifty-four esophageal cancer patients undergoing radical esophagectomy were divided into control, RIPC and RIPC+Dex group. During the anesthesia and ventilation in surgery, the RIPC was performed in RIPC group, and the intravenous infusion of Dex based on RIPC was conducted in RIPC+Dex group. At the time immediately before OLV beginning (T1), 60 min of OLV (T2) and end of surgery (T3), the oxygenation index (OI) and respiratory index (RI) were recorded, and the serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were determined. Results showed that, compared with RIPC group, in RIPC+Dex group the OI at T2 and T3 increased, the RI at T2 and T3 decreased, the serum SOD level at T3 increased, the serum MDA level at T3 decreased, the serum TNF-α and IL-6 levels at T2 and T3 decreased (all P < 0.05). In conclusion, for elderly patients undergoing radical esophagectomy with RIPC, Dex can effectively inhibit the oxidative stress and inflammatory response during OLV, thus alleviating the lung injury and reducing the postoperative complications. (Dex onelung one (OLV RIPC. . (RIPC) Fiftyfour Fifty four control RIPCDex T1, T1 T , (T1) (T2 T3, (T3) (OI (RI recorded SOD, (SOD) MDA, (MDA) TNFα TNF (TNF-α IL6 IL (IL-6 determined that increased IL- all 0.05. 005 0.05 0 05 0.05) conclusion complications (RIPC (T1 (T (T3 (SOD (MDA (IL- 00 0.0 (IL 0.

Abstract We sought to explore the relationship between renal lesion features and genetic mutations in tuberous sclerosis complex (TSC) patients. TSC patients with renal lesions were subjected to TSC1/2 gene next-generation sequencing (NGS). TSC1/2 mutation types and imaging examinations were screened for combined analysis of genetic and clinical features. Seventy-three probands among TSC patients with renal lesions were included. Twenty affected relatives were also included. In total, 93 patients were included. Eighty patients (86.0%) had bilateral renal angiomyolipomas (AMLs), and one had epithelioid AML. Two patients had polycystic kidney disease, one had renal cell carcinoma, and one had Wilms tumor. Among the 73 probands, four had TSC1 mutations, 53 had TSC2 mutations, and 16 had no mutations identified (NMI). There was no statistically significant difference between TSC1 mutation, TSC2 mutation and NMI group (P= 0.309), or between familial and sporadic groups (P= 0.775) when considering AML size. There was no statistically significant difference between pathogenic/likely pathogenic and benign/likely benign/NMI groups (P= 0.363) or among patients with different mutation types of TSC2 (P= 0.906). The relationship between the conditions of TSC gene mutations and the severity of renal lesions still needs more analysis. Patients with NMI, particularly those with familial disease, need more attention because the pathogenesis remains unknown.

RESUMO Objetivo: Analisar os índices subclínicos de to pografia de ceratocone utilizando as medidas feitas com Pentacam e com Orbscan-II para identificar evidências para a busca de índices sensíveis para triagem e diagnóstico de ceratocone subclínico. Métodos: Cinquenta participantes saudáveis (50 olhos) e 40 pacientes com ceratocone subclínico (40 olhos) foram incluídos. Sete parâmetros comuns, incluindo a espessura da córnea no ponto mais fino; a curvatura mínima da superfície frontal (valor mínimo da ceratometria simulada, Min de SimK); a curvatura máxima da superfície frontal (valor máximo da ceratometria simulada, Max de SimK); a superfície frontal e a superfície posterior da córnea de melhor ajuste ao raio da curvatura, a altura da superfície anterior da córnea (valor Diff anterior) e a altura da superfície corneana posterior (valor Diff posterior) medidos pelo Pentacam e pelo Orbscan-II entre os olhos normais e com ceratocone subclínico foram comparados. Resultados: As diferenças estatísticas entre os grupos saudável e com ceratocone subclínico (p<0,01) foram encontradas em todos os parâmetros corneanos medidos usando ambos os dispositivos. Diferenças na curvatura mínima da superfície frontal (Min de SimK) no ponto mais fino, no valor Diff anterior e no valor Diff posterior foram significativas entre Pentacam e Orbscan-II no grupo com ceratocone subclínico (p<0,05). Conclusão: Os achados deste estudo identificam as diferenças entre olhos normais e com ceratocone subclínico para a curvatura mínima da superfície frontal, a curvatura máxima da superfície frontal, a superfície corneana frontal e a superfície corneana posterior de melhor ajuste ao raio esférico da curvatura e as medidas de Diff anterior e posterior usando Orbscan II e o Pentacam que podem auxiliar os profissionais de oftalmologia a diagnosticar clinicamente o ceratocone subclínico.

ABSTRACT Purpose: To analyze subclinical keratoconus topography indexes using Pentacam and Orbscan-II measurements to identify evidences for seeking sensitive indexes to screen and diagnose subclinical keratoconus. Methods: Fifty healthy participants (50 eyes) and 40 patients with subclinical keratoconus (40 eyes) were included. Seven common parameters including corneal thickness at the thinnest point; minimum curvature of the front surface (minimum simulated keratometry value, SimK’s Min); maximum curvature of the front surface (maximum simulated keratometry value, SimK’s Max); the frontal corneal surface best-fit spherical radius of the curvature; the back corneal surface best-fit spherical radius of curvature; the anterior corneal surface height (anterior Diff value); and the posterior corneal surface height (posterior Diff value) measured by Pentacam and Orbscan-II between normal and subclinical keratoconus eyes were compared. Results: Statistical differences between the healthy and subclinical keratoconus groups (p<0.01) were found in all corneal parameters measured using both devices. Differences in the minimum curvature of the front surface (SimK’s Min), thinnest point, anterior Diff value, and posterior Diff value were significant between Pentacam and Orbscan-II in the subclinical keratoconus group (p<0.05). Conclusion: The findings of this study identify the differences between normal and subclinical keratoconus eyes at the minimum curvature of the front surface, maximum curvature of the front surface, frontal corneal surface best-fit spherical radius of curvature, back corneal surface best-fit spherical radius of curvature, Anterior Diff value, and Posterior Diff value measures using Orbscan II and Pentacam that can help eye care practitioners clinically diagnose subclinical keratoconus.

ABSTRACT Introduction and Objective: Several studies have focused on the treatment and recurrence of urethral diverticulum (UD). However, few investigations have addressed sexual function in patients with UD. Therefore, we sought to examine sexual function in women affected by UD. Materials and Methods: There were 108 accepted cases involving transvaginal diverticulectomy at our institution. Ultimately, 83 women were included for further analysis, only 61 of these women had sexual partners. We collected data for the Female Sexual Function Index (FSFI) from the female patients and the Male Sexual Health Questionnaire (MSHQ) from their male partners before and after surgery. Results: Preoperatively, the UD size affected the female patient's arousal and lubrication (p=0.04), and the UD location affected their satisfaction. However, no significant between-group differences were found in the total FSFI score. For all women, sexual activity improved after surgery (p=0.0087). In addition to improvements in arousal for women with a large UD, improvements in lubrication were affected by the UD size, number and shape, increases in satisfaction scores were impacted by the UD location and shape, and pain relief was linked to the UD number and shape. Analysis of the MSHQ results revealed no between-group differences among the male partners. Conclusion: Only the UD size and location affected sexual function in women with a small UD. Surgery could improve female sexual function but did not affect the sexual function of the patient's partners.

Abstract Purpose To investigate the effects of huperzine A (HupA) on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia. Methods Thirty-six Sprague Dawley rats (20-22 months old) were randomly divided into control, isofluran, and isoflurane+HupA groups; 12 rats in each group. The isoflurane+HupA group was intraperitoneally injected with 0.2 mg/kg of HupA. After 30 min, isoflurane inhalation anesthesia was performed in the isoflurane and isoflurane+HupA groups. After 24 h from anesthesia, Morris water maze experiment and open-field test were performed. Hippocampal inflammatory and neurotrophic factors were determined. Results Compared with isoflurane group, in isofluran+HupA group the escape latency of rats was significantly decreased (P < 0.05), the original platform quadrant residence time and traversing times were significantly increased (P < 0.05), the central area residence time was significantly increased (P < 0.05), the hippocampal tumor necrosis factor α, interleukin 6 and interleukin 1β levels were significantly decreased (P < 0.05), and the hippocampal nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 levels were significantly increased (P < 0.05). Conclusion HupA may alleviate the cognitive impairment in rats after isoflurane anesthesia by decreasing inflammatory factors and increasing hippocampal neurotrophic factors in hippocampus tissue.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive with poor prognosis. Long non-coding RNAs (lncRNAs), a group of non-coding RNAs, play important roles in the progression of PDAC. This study aimed to investigate the potential involvement of lncRNA CCAT2 in PDAC tumorigenesis. Methods Expression of CCAT2 was detected by quantitative real-time PCR (qRT-PCR) in 80 human PDAC tissues and three PDAC cell lines. The effects of CCAT2 silencing in PANC-1 cells on cell proliferation and invasion were studied using MTT assay and transwell assay, respectively. The effect of CCAT2 silencing on tumorigenesis was assessed by PANC-1 xenograft in vivo. Using si-KRAS, the role of KRAS to regulate CCAT2 was evaluated by qRT-PCR and luciferase reporter assay. The involvement of MEK/ERK and PI3K/AKT signaling in CCAT2 regulation was investigated by pathway inhibitors PD98059 and LY294002, respectively. Results CCAT2 was significantly elevated in high-grade PDAC tissues and higher CCAT2 expression was correlated with lower survival rate in PDAC patients. CCAT2 was up-regulated in PDAC cell lines, as compared with normal pancreatic cells. Silencing of CCAT2 inhibited cell proliferation and invasion in PANC-1 cells in vitro, and attenuated tumorigenesis of PANC-1 xenograft in vivo. Furthermore, CCAT2 was regulated by KRAS through MEK/ERK signaling pathway. Conclusions CCAT2 is an oncogenic lncRNA in PDAC likely regulated by the KRAS-MEK/ERK pathway. It could be a potential diagnostic biomarker and therapeutic target for PDAC.

The water sorption, water barrier properties and mechanical behavior of soy protein isolate (SPI) based films combined with propylene glycol alginate (PGA) and lauric acid (La) via a direct- or co-dried blending process were investigated. Higher water retention ability and a single glass transition temperature (Tg) were found when the PGA was added to form different ternary co-dried blending films by a co-drying process, indicating their compatibility. Tg was reduced in the case of higher relative humidity and incorporation of La. The response surface methodology (RSM) indicated that the effect of La content was highly significant (p < 0.05) for the water retention ability and mechanical properties, and the proposed models calculated for the tensile strength and elongation at break showed a good fit. The results revealed the importance of the interactions among lipids, protein and polysaccharide in composite films which also provided evidence for modeling film behavior.