The function of the glutathione peroxidase family and the possibility of its members as immunotherapeutic markers for glioma / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨谷胱甘肽过氧化物酶（GPX）家族在胶质瘤发生发展中的生物学功能和预后价值。方法：利用TCGA、GTEx和CGGA等多个数据库数据分析胶质瘤中GPX各亚型基因的表达及其相关性、蛋白之间的相互作用、基因突变、GPX表达与胶质瘤患者预后的关系以及GPX7、8的基因集富集分析；GPX8与胶质瘤中免疫细胞浸润以及免疫检查点分子表达的相关性分析，胶质瘤中GPX8表达与化疗药物IC50的相关性分析。采用qPCR法、WB法和免疫荧光技术检测国人胶质瘤组织和对照组织（标本收集自2022年10月20日至12月20日间在上海奉贤区中心医院神经外科手术切除的5例胶质瘤和3例严重脑外伤的病灶组织）中GPX mRNA、蛋白以及相关免疫检查点分子的表达进行验证。结果：数据库分析显示胶质瘤中GPX各亚型蛋白之间存在相互作用、基因表达水平存在相关性（P<0.05或P<0.01），胶质瘤组织中多个GPX亚型存在单核苷酸变异和拷贝数变异；不同类型胶质瘤组织的免疫细胞和肿瘤细胞中主要表达的GPX亚型有明显不同，在胶质瘤组织中GPX1、4、7、8均呈高表达（均P<0.05）且与胶质瘤患者预后不良相关（P<0.01）。qPCR法、WB法检测中国人胶质瘤组织中GPX7、8均呈高表达验证了数据库信息的正确性。在胶质瘤中GPX7、8表达具有独立预后预测价值；富集分析显示GPX7、8与胶质瘤细胞周期和免疫途径有关，在GBM和LGG中GPX8表达与免疫评分呈明显相关（P<0.01）、GPX8可能在胶质瘤中诱导抑制性免疫细胞浸润导致免疫抑制、GPX8表达与胶质瘤中多个免疫检查点分子表达正相关（均P<0.01）、GPX8表达与化疗药物IC50呈明显正相关（均P<0.01）且其高表达可导致胶质瘤对化疗药物的耐药。结论：GPX8在胶质瘤中呈显著高表达，GPX8高表达能诱导胶质瘤中抑制性免疫细胞的浸润其与多个免疫抑制点、与多个化疗药物IC50和患者预后密切相关，可作为胶质瘤免疫治疗的潜在靶点。

The relationship between PM20D1 gene and hypoxia and prognosis in diffuse large B-cell lymphoma was analyzed by integrating multiple databases / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨肽酶M20结构域1（peptidase M20 domain containing 1，PM20D1）在人弥漫大B细胞淋巴瘤（diffuse large B-cell lymphomas，DLBCL）细胞中的表达及其与缺氧相关性和预后的关系。方法：通过GDC、TCGA、GTEx公共数据库分析PM20D1表达对DLBCL细胞增殖、迁移和凋亡的影响及其与患者预后的关系。通过对不同分组患者的富集分析及PM20D1与CD274相关性分析验证PM20D1是否为DLBCL的缺氧相关基因；采用ChEA、ENCODE和hTFtarget数据库分析上游调控PM20D1表达的转录因子（TF）和miRNA，以及差异表达PM20D1与化疗药物敏感性的关系。采用WB法检测PM20D1在正常淋巴细胞和DLBCL细胞中的表达水平，通过设计PM20D1的siRNA序列敲减目的基因，并采用qPCR和WB法检测验证SUDHL2和SUDHL10细胞中PM20D1的敲减效率，采用CCK-8法和Transwell实验分别检测敲减PM20D1对细胞增殖和迁移能力的影响，流式细胞术检测细胞凋亡水平。结果：PM20D1在DLBCL组织中高表达且患者预后差（P<0.05或P<0.01）；富集分析显示，PM20D1高表达组与ssGSEA高分组主要涉及细胞电耦合通讯、甘油三酯代谢过程调节和细胞质翻译起始复合物过程，且PM20D1表达与免疫检查点CD274表达呈正相关（P<0.01，r=0.757）。在SUDHL2和SUDHL10细胞中敲减PM20D1后，细胞的增殖和迁移均显著降低（均P<0.05），细胞凋亡明显增加（P<0.05）。结论：PM20D1基因在DLBCL组织和细胞中高表达且与患者预后密切相关；PM20D1可能通过促进DLBCL细胞的增殖、迁移并抑制凋亡，从而促进DLBCL的发生发展。

Clinical efficacy of traditional Chinese medicine therapy for female stress urinary incontinence: a meta-analysis / Eficácia clínica da terapia da medicina tradicional chinesa para a incontinência urinária de esforço feminina: uma meta-análise / Eficacia clínica de la terapia de medicina tradicional china para la incontinencia urinaria de esfuerzo femenina: un metaanálisis

ABSTRACT Objectives: To investigate the efficacy of traditional Chinese medicine (TCM) in the treatment of female stress urinary incontinence (SUI). Method: PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang, and VIP databases were searched for articles published up to September 2022. Variables were analyzed using weighted mean difference (WMD), standardized mean difference (SMD), odds ratios (OR), and 95% confidence interval (CI). Results: Eight studies containing 744 patients were included in this study. The results demonstrate that TCM therapy had more advantages in improving the clinical outcome of SUI patients (OR = 2.90, 95%CI:1.92-4.37, P = 0.000), reducing the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score (WMD = -2.41, 95%CI:-2.83- -1.98, P = 0.000), reducing 1-h urinary pad leakage urine volume (WMD = -1.86, 95%CI:-2.23- -1.49, P = 0.000) and increasing Maximum urethral closure pressure (MUCP) (SMD = 0.86, 95%CI: 0.61-1.11, P = 0.000). Conclusion: TCM therapy is effective in improving urinary incontinence symptoms, urodynamics, and quality of life in patients with SUI. This article provides a reference for the application of TCM therapy in women with urinary incontinence.

RESUMEN Objetivo: Investigar la eficacia de la medicina tradicional china (MTC) en el tratamiento de la incontinencia urinaria de esfuerzo (IUE) femenina. Método: Se llevaron a cabo búsquedas de artículos publicados hasta septiembre de 2022 en las bases de datos PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang y VIP. Las variables se analizaron mediante la diferencia de medias ponderada (DMP), la diferencia de medias estandarizada (DME), la razón de momios (RM) y el intervalo de confianza (IC) del 95%. Resultados: Este estudio incluyó ocho investigaciones con la participación de 744 pacientes. Los resultados indican que la terapia de medicina tradicional china (MTC) presentó mejoras significativas en los resultados clínicos de pacientes con incontinencia urinaria de esfuerzo (IUE) (RM = 2.90, IC del 95%: 1.92-4.37, P = 0.000), al reducir la puntuación del Cuestionario Internacional sobre la Incontinencia y su impacto en la calidad de vida (ICIQ-SF) (DMP = -2.41, IC del 95%: -2.83- -1.98, P = 0.000), así como la disminución del volumen de orina a la 1 hora de fuga de la almohadilla urinaria (DMP = -1.86, IC del 95%: -2.23- -1.49, P = 0.000) y el aumento de la presión de cierre uretral máxima (PCUM) (DME = 0.86, IC del 95%: 0.61-1.11, P = 0.000). Conclusión: La terapia de medicina tradicional china (MTC) resulta efectiva en la mejora de los síntomas de la incontinencia urinaria, la urodinámica y la calidad de vida en pacientes con incontinencia urinaria de esfuerzo (IUE). Este artículo ofrece una referencia para la aplicación de la terapia de MTC en mujeres con incontinencia urinaria.

RESUMO Objetivo: Investigar a eficácia da medicina tradicional chinesa (MTC) no tratamento da incontinência urinária de esforço (IUE) feminina. Método: Foram realizadas pesquisas de artigos publicados até setembro de 2022 nas bases de dados PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang e VIP. As variáveis foram analisadas por meio da diferença de média ponderada (DMP), da diferença média padronizada (DMP), da razão de chances (RC) e do intervalo de confiança (IC) de 95%. Resultados: Esta pesquisa envolveu oito estudos, contando com a participação de 744 pacientes. Os resultados indicam que a terapia da medicina tradicional chinesa (MTC) apresentou melhorias significativas nos resultados clínicos de pacientes com incontinência urinária de esforço (IUE) (RM = 2.90, IC de 95%: 1.92-4.37, P = 0.000), ao reduzir a pontuação do Questionário Internacional sobre a Incontinência Urinária - Versão Breve (ICIQ-SF) (Diferença de Média Ponderada = -2.41, IC de 95%: -2.83- -1.98, P = 0.000), assim como na diminuição do volume de urina na 1 hora de vazamento do absorvente urinário (Diferença de Média Ponderada = -1.86, IC de 95%: -2.23- -1.49, P = 0.000) e no aumento da pressão máxima de encerramento uretral (PMCU) (Diferença Média Padronizada = 0.86, IC de 95%: 0.61-1.11, P = 0.000). Conclusão: A terapia da medicina tradicional chinesa (MTC) é eficaz na melhoria dos sintomas da incontinência urinária, na urodinâmica e na qualidade de vida em pacientes com incontinência urinária de esforço (IUE). Este artigo fornece uma referência para a aplicação da terapia da MTC em mulheres com incontinência urinária.

Repair of large traumatic tympanic membrane perforation using ofloxacin otic solution and gelatin sponge / Reparo de grande perfuração da membrana timpânica traumática utilizando solução otológica de ofloxacina e curativo de Gelfoam®

Abstract Introduction Traumatic large tympanic membrane perforations usually fail to heal and require longer healing times. Few studies have compared the healing and hearing outcomes between gelatin sponge patching and ofloxacin otic solution. Objectives To compare the healing outcomes of large traumatic tympanic membrane perforations treated with gelatin sponge, ofloxacin otic solution, and spontaneous healing. Methods Traumatic tympanic membrane perforations >50% of the entire eardrum were randomly divided into three groups: ofloxacin otic solution, gelatin sponge patch and spontaneous healing groups. The healing outcome and hearing gain were compared between the three groups at 6 months. Results A total of 136 patients with large traumatic tympanic membrane perforations were included in analyses. The closure rates were 97.6% (40/41), 87.2% (41/47), and 79.2% (38/48) in the ofloxacin otic solution, gelatin sponge patch, and spontaneous healing groups, respectively (p = 0.041). The mean times to closure were 13.12 ± 4.61, 16.47 ± 6.24, and 49.51 ± 18.22 days in these groups, respectively (p < 0.001). Conclusions Gelatin sponge patch and ofloxacin otic solution may serve as effective and inexpensive treatment strategies for traumatic large tympanic membrane perforations. However, ofloxacin otic solution must be self-applied daily to keep the perforation edge moist, while gelatin sponge patching requires periodic removal and re-patching.

Resumo Introdução As grandes perfurações traumáticas da membrana timpânica geralmente apresentam falha de cicatrização e requerem tempos de cicatrização mais longos; poucos estudos compararam os resultados de cicatrização e a audição dessas perfurações obtidos com curativo de Gelfoam® e solução otológica de ofloxacina. Objetivo Comparar os resultados de cicatrização de grandes perfurações traumáticas da membrana timpânica tratadas com Gelfoam®, solução otológica de ofloxacina e cicatrização espontânea. Método Perfurações traumáticas de > 50% de todo o tímpano foram divididas aleatoriamente em três grupos: tratamento com solução otológica de ofloxacina, com curativo de Gelfoam® e grupo de cicatrização espontânea. O resultado da cicatrização e o ganho auditivo foram comparados entre os três grupos após 6 meses. Resultados Foram incluídos nas análises 136 pacientes com grandes perfurações traumáticas de membrana timpânica. As taxas de cicatrização foram de 97,6% (40/41), 87,2% (41/47) e 79,2% (38/48) com a solução otológica de ofloxacina, curativo de Gelfoam® e grupos de cicatrização espontânea, respectivamente (p = 0,041). O tempo médio de cicatrização foi de 13,12 ± 4,61, 16,47 ± 6,24 e 49,51 ± 18,22 dias nesses grupos, respectivamente (p < 0,001). Conclusões O curativo de Gelfoam® e a solução otológica de ofloxacina podem servir como estratégias de tratamento eficazes e de baixo custo para grandes perfurações traumáticas de membrana timpânica. Entretanto, a solução otológica de ofloxacina deve ser autoaplicada diariamente para manter a borda da perfuração úmida, enquanto o curativo de Gelfoam® requer sua remoção e reaplicação periódicas.

Research progress on the correlation between herpangina and hand⁃foot⁃mouth disease / 口腔疾病防治

@# As acute enterovirus⁃induced infections, herpangina(HA) and hand⁃foot⁃mouth disease(HFMD) are simi⁃lar in many aspects. Although these diseases vary with time and region, many studies have shown that the viruses caus⁃ing HA and HFMD are consistent, and there is no notable difference in partial VP1 gene sequences between different vi⁃ruses. HA and HFMD also resemble each other in epidemiological features. Both infections show significant summer⁃time seasonality, have a strong connection with certain environmental conditions and are most prevalent in young chil⁃dren and infants. Herpangina is thought to be a mild disease, defined as vesicular enanthem and then ulcers of the fau⁃ces and soft palate with presentation of feve r, sore throat, and decreased appetite. HFMD, which could lead to severe symptoms, is also characterized by oral ulcers, although they are chiefly on the buccal mucosa and tongue, and typical vesicular rashes, which are most commonly found on the hands, feet, knees and buttocks. While HA is generally be⁃ lieved to be self⁃limited and has a favorable prognosis, HA with certain clinical characteristics, such as diarrhea, vomit⁃ing, limb jitter and sleepiness, can evolve into HFMD, according to some literature in recent years. However, HA is an independent risk factor for HFMD, and severe cases only present with herpes appearing at the isthmus of the fauces at an early stage, which indicates a strong correlation between them. Clinical manifestations of HA should be considered by medical staff to identify potential children with HFMD as early as possible to prevent its further development or transformation.

Impact of chrysosplenetin, per se or in combination with artemisinin, on breast cancer resistance protein (Bcrp)/ABCG2 mRNA expression levels in mice small intestine

ABSTRACT Our previous work revealed that chrysosplenetin in combination with artemisinin inhibited in vivo P-glycoprotein (P-gp, one of classic multi-drug resistance proteins) mediated digoxin transportation activity by reversing the upregulated P-gp/Mdr1 mRNA expression levels by artemisinin. Therefore, chrysosplenetin might be a potential artemisinin-resistance reversal agent as a P-gp inhibitor. But it still remains unknown if chrysosplenetin has an impact on another pivotal multi-drug resistance protein, breast cancer resistance protein (Bcrp), which is co-expressed with P-gp in apical membrane of intestinal epithelial cell and overlaps some of the substrates and inhibitors. This study, therefore, further addressed the impact of chrysosplenetin, per se or in combination with artemisin, on Bcrp/ABCG2 mRNA expression levels in mice small intestine determined by western blot and real time-quantitative polymerase chain reaction (RT-qPCR) assay. The drugs were intragastrically administrated once per day for 7 days. Novobiocin, a known Bcrp inhibitor, was observed to have no impact on Bcrp/ABCG2 levels with or without artemisinin versus vehicle. Interestingly, artemisinin alone attenuated Bcrp level while chrysosplenetin alone increased it (p < 0.05). Relative mRNA level was significantly decreased when co-used with artemisinin and chrysosplenetin in ratio of 1:2 (p < 0.05). The discrepant results for chrysosplenetin on Bcrp/ABCG2 mRNA expressions might be closely related to the transcriptional or posttranscriptional regulation.

Chrysosplenetin, in the absence and presence of artemsininin, alters breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate

ABSTRACT The present study describes the impact of chrysosplenetin, in the absence and presence of artemisinin, on in vitro breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate. We observed that novobiocin, a known breast cancer resistance protein active inhibitor, increased Papp (AP-BL) of aristolochic acid I 3.13 fold (p < 0.05) but had no effect on Papp (BL-AP). Efflux ratio (PBA/PAB) declined 4.44 fold (p < 0.05). Novobiocin, consequently, showed a direct facilitation on the uptake of AAI instead of its excretion. Oppositely, both artemisinin and chrysosplenetin alone at dose of 10 µM significantly decreased Papp (BL-AP) instead of Papp (AP-BL). Chrysosplenetin alone attenuated the efflux ratio, which was suggestive of being as a potential breast cancer resistance protein suppressant. Oddly, Papp (BL-AP) as well as efflux ratio were respectively enhanced 2.52 and 2.58 fold (p < 0.05), when co-used with artemisinin and chrysosplenetin in ratio of 1:2. The potential reason remains unclear; it might be relative to binding sites competition between artemisinin and chrysosplenetin or the homodimer/oligomer formation of breast cancer resistance protein bridged by disulfide bonds, leading to an altered in vitro breast cancer resistance protein-mediated efflux transport function.

Development of a UPLC–MS/MS method for determination of pimavanserin tartrate in rat plasma:Application to a pharmacokinetic study / 药物分析学报

A simple, rapid and sensitive method based on an ultra-performance liquid chromatography–tandem mass spectrometry(UPLC–MS/MS)has been developed and validated for the determination of pimavanserin in rat plasma.The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C18column(100 mm×2.1 mm,1.7μm;Waters,USA),with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 min. The analyte and clarithromycin (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 428.2 → 223.0 for pimavanserin and m/z 748.5 → 589.5 for clarithromycin. Relative coefficient (r) for the calibration curve was more than 0.9980. The intra-day and inter-day precisions(relative standard deviation,RSD%)were less than 13.3% and 10.5%,respectively,and the accuracy(relative error,RE%)was within ± 11.5%.The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg.