Silk fibroin (SF) hydrogel has been popular in the wound dressing and tissue engineering fields for its good biocompatibility, biodegradation and water retention ability. The development of functional SF-based hydrogels has gained attention in recent decades in medical fields. Multifunctional SF hydrogel is prepared by the addition and combination of therapeutic agents with cell growth promoting, antibacterial, antioxidant and anti-inflammatory properties. In particular, the antibacterial activity of SF-based hydrogel is essential in clinical practice. Despite this growing interest in functional silk protein hydrogels and their potential antimicrobial applications, a comprehensive review on this topic is currently lacking. Therefore, this review aims to provide an in-depth understanding of the advanced status of the antibacterial application of SF-based hydrogel, mainly focused on different components loaded. The review begins by briefly introducing the preparation methods of SF-based hydrogel. Subsequently, the review summarizes diverse components loaded into the hydrogel to provide a comprehensive understanding in the antibacterial field. Furthermore, the article reviews the biomedical applications of antibacterial aspects including tissue engineering, sustained drug release, wound repair and adhesive use. Also the challenges associated with developing SF-based hydrogels are analyzed alongside future prospects. We hope that this study will contribute to promoting the application and innovation of SF material in the clinical antibacterial field. © 2024 Society of Chemical Industry.

BackgroundHepatic cancer is a common cancer in clinical practice. Current drug therapies for this condition include targeted therapy, chemotherapy, and immunotherapy. Tumor lysis syndrome (TLS) is the most serious complication of oncology treatment. According to the literature, several cases reported TLS occurred with targeted therapies for hepatic cancer.MethodsReporting odds ratio and information component were used to measure the disproportionate signals for TLS associated with targeted therapies, using data from the FDA's Adverse Event Reporting System (FAERS). A stepwise sensitivity analysis was conducted to test the robustness of signals. Time-to-onset analysis was used to describe the latency of TLS events associated with targeted therapies. The Bradford Hill criteria were used to perform a global assessment of the evidence.ResultsSorafenib, lenvatinib, cabozantinib, and bevacizumab showed higher disproportionate signals for TLS than chemotherapy. The median number of days to TLS occurrence after drug therapy was 5.5, 6.5, and 6.5 days for sorafenib, lenvatinib, and bevacizumab, respectively.ConclusionsThere is a significant association between tumor lysis syndrome and targeted therapies for hepatic carcinoma, with particularly strong signals for sorafenib and lenvatinib. Clinicians should be aware of the potential for tumor lysis syndrome in targeted therapies for hepatic carcinoma.

ObjectiveWith the rapid advancement of Chat Generative Pre-Trained Transformer (ChatGPT) in medical research, our study aimed to identify global trends and focal points in this domain.MethodAll publications on ChatGPT in medical research were retrieved from the Web of Science Core Collection (WoSCC) by Clarivate Analytics from January 1, 2023, to January 31, 2024. The research trends and focal points were visualized and analyzed using VOSviewer and CiteSpace.ResultsA total of 1,239 publications were collected and analyzed. The USA contributed the largest number of publications (458, 37.145%) with the highest total citation frequencies (2,461) and the largest H-index. Harvard University contributed the highest number of publications (33) among all full-time institutions. The Cureus Journal of Medical Science published the most ChatGPT-related research (127, 10.30%). Additionally, Wiwanitkit V contributed the majority of publications in this field (20). “Artificial Intelligence (AI) and Machine Learning (ML),” “Education and Training,” “Healthcare Applications,” and “Data Analysis and Technology” emerged as the primary clusters of keywords. These areas are predicted to remain hotspots in future research in this field.ConclusionOverall, this study signifies the interdisciplinary nature of ChatGPT research in medicine, encompassing AI and ML technologies, education and training initiatives, diverse healthcare applications, and data analysis and technology advancements. These areas are expected to remain at the forefront of future research, driving continued innovation and progress in the field of ChatGPT in medical research.

气虚体质之人,易于遭受外界毒邪侵袭,引发疾病,尤以在鼻咽癌的病机演变过程最为典型.其发生发展过程,源于易感人群具有遗传易感性或基因多态性所致的特殊病理体质状态,即禀赋决定的先天性气虚体质,这些人群或个体对致病因素"毒邪"甚为敏感,导致内外合邪,促进病机演变而发病.此即课题组提出的鼻咽癌发病"气虚染毒"病机学说.这一理论的依据,是基于对鼻咽癌高危人群病理体质及其与细胞免疫功能相关性的临床流行病学调查结果.

目的 探究核因子κB(NF-κB)抑制剂(BAY11-7082)联合核因子E2相关因子2(Nrf2)抑制剂(ML385)对人结肠癌细胞HCT116的作用机制.方法 体外培养人结肠癌细胞HCT116,将细胞分为4组:空白对照组、NF-κB抑制剂组、Nrf2抑制剂和联合组.空白对照组以RPMI-1640培养基进行培养,NF-κB抑制剂组以10μmol·L-1 BAY 11-7082干预,Nrf2抑制剂组以5μmol·L-1 ML385干预,联合组以10μmol·L-1 BAY 11-7082+5μmol·L-1 ML385干预,干预时间为24 h.MTT法检测人结肠癌细胞HCT116增殖抑制率,以流式细胞术和Hoechst 33342染色法检测细胞凋亡状况,以蛋白质印迹法检测凋亡相关蛋白及Nrf2、NF-κB通路相关蛋白表达水平.结果 ML385、BAY 11-7082均能显著抑制人结肠癌细胞HCT116增殖(均P<0.05);干预24 h,空白对照组、Nrf2抑制剂组、NF-κB抑制剂组和联合组的细胞凋亡率分别为(1.77±0.60)％,(19.41±1.87)％,(21.55±2.33)％和(39.84±1.22)％;这4组的B细胞淋巴瘤-2相关X蛋白(Bax)的相对表达量分别为1.00,1.53±0.28,1.43±0.30和3.47±0.70;这4组的生存素蛋白的相对表达量分别为1.00,0.60±0.11,0.32±0.10和0.32±0.12;这4组的X连锁凋亡抑制蛋白(XIAP)的相对表达量分别为1.00,0.50±0.11,0.19±0.06和0.25±0.04.空白对照组、Nrf2抑制剂组和NF-κB抑制剂组的NF-κB蛋白的相对表达量分别为1.00,0.71±0.10和0.44±0.06;这3组的IκB蛋白分别为1.00,0.37±0.15和0.33±0.13;这3组的Nrf2蛋白分别为1.00,0.14±0.09和0.75±0.08.Nrf2抑制剂组、NF-κB抑制剂组和联合组与空白对照组比较,上述指标的差异均有统计学意义(均P<0.05).结论 NF-κB抑制剂联合Nrf2抑制剂可协同诱导人结肠癌细胞HCT116凋亡,该效应可能与下调Survivin和XIAP的表达、上调Bax表达有关.

结直肠癌(CRC)是全球第三大常见恶性肿瘤,已严重威胁人类健康.尽管近年来在结直肠癌的治疗方面已经取得一定进展,但是迫切需要找到能够早期诊断和有效治疗患者的新靶标,故针对肿瘤前后微环境的分子作用机制和关键控点进行系统研究,是研究结直肠癌防治的重点.对核因子κB(NF-κB)和核因子E2相关因子2(Nrf2)信号通路转导与结直肠癌发生发展的关系,以及它们之间错综复杂的交互作用(Crosstalk)进行综述,以期进一步了解结直肠癌发生发展机制,最后归纳中医药以其为靶点防治结直肠癌的已有研究成果,为结直肠癌的中医药防治提供思路与方向,为相关药物研发与应用提供参考依据.

目的 探讨黄芩苷(baicalin)对鼻咽癌CNE2细胞增殖及TGF-β1/ERK1/2信号通路的作用.方法 采用CCK8法检测不同浓度黄芩苷(2.5、5、10、20、40、80μmol·L-1)、顺铂(4μg·mL-1)在24、36、48 h对CNE2细胞增殖的作用;细胞成像多功能检测系统(CytationTM 5)实时监测黄芩苷对CNE2增殖数量的变化;Western blot检测黄芩苷对CNE2细胞增殖相关蛋白PCNA、Survivin及TGF-β1/ERK1/2信号通路关键蛋白TGF-β1、p-ERK1/2的影响.结果 CCK8结果显示,黄芩苷可抑制CNE2增殖(P<0.05或P<0.01),且随着浓度升高,抑制作用增强;CytationTM 5监测结果显示,黄芩苷可抑制CNE2细胞数量增多(P<0.05或P<0.01);Western blot结果表明,黄芩苷下调了增殖相关蛋白PCNA(P<0.05)、Survivin(P<0.05)及TGF-β1/ERK1/2信号通路关键蛋白TGF-β1(P<0.05)、p-ERK1/2(P<0.05)的表达水平.加入TGF-β1(TGF-β1/ERK1/2信号通路激活剂)后,黄芩苷对TGF-β1、p-ERK1/2、PCNA、Survivin的抑制作用降低(P<0.05),同时降低了黄芩苷对CNE2细胞增殖的抑制作用.结论 黄芩苷能够抑制鼻咽癌CNE2细胞增殖,并通过抑制TGF-β1/ERK1/2信号通路进一步降低下游蛋白PCNA、Survivin的表达发挥作用.

目的 研究益气解毒方水提物对结肠癌HCT116细胞凋亡及B细胞淋巴瘤-2相关X蛋白(Bax)、X连锁凋亡抑制蛋白(XIAP)、生存素(Survivin)和NF-κB信号通路相关蛋白表达的影响.方法 采用噻唑蓝(MTT)比色法检测不同浓度(1,0.5,0.25,0.125 g·L-1)益气解毒方水提物对HCT116细胞活性的影响;采用Hoechst 33342染色法及流式细胞术检测其对HCT116细胞凋亡的影响;采用蛋白免疫印迹法(Western blot)检测其对HCT116细胞凋亡相关蛋白Bax、XIAP、Survivin及NF-κB通路相关蛋白NF-κB、IκK、IκB的影响.结果 MTT结果提示益气解毒方水提物能抑制HCT116细胞活性,呈时间-剂量关系(P<0.01);与对照组比较,Hoechst 33342染色及流式细胞术结果显示益气解毒方水提物处理后,凋亡率升高(P<0.01);XIAP、Survivin表达下降(P<0.01),Bax表达上升(P<0.05,P<0.01),NF-κB、IκK、IκB表达均下降(P<0.05,P<0.01).结论 益气解毒方水提物可抑制结肠癌HCT116细胞增殖,诱导其凋亡,其机制可能与抑制NF-κB信号通路相关蛋白NF-κB、IκK、IκB表达,下调XIAP、Survivin表达,上调Bax表达有关.

目的 探讨益气解毒方对中晚期鼻咽癌患者Th17细胞活性的干预效应.方法 40例中晚期鼻咽癌患者,于治疗开始前应用流式细胞术检测外周血Th17细胞数值比例,ELISA法检测血清细胞因子IFN-γ、IL-17含量水平,并以10例健康人作为对照,分析各指标的组间差异及其意义.然后,将40例中晚期鼻咽癌患者随机分为常规治疗组和联合治疗组各20例;常规治疗组予以标准化常规放化疗,联合治疗组在常规治疗基础上加用益气解毒方;两组患者均于放疗疗后3个月时分别应再次检测外周血Th17细胞数值比例,ELISA法检测血清细胞因子IFN-γ、IL-17水平,比较分析其组间差异及意义.结果 中晚期鼻咽癌患者治疗前外周血中Th17细胞数量(IL-17+/CD3+2.89±1.06,IL-17+/CD4+0.47±0.19)、血清IFN-γ(124.95±4.22)、IL-17(4.61±0.09),均分别显著低于健康对照组的(细胞比值11.03±2.53和1.69±0.28)、(细胞因子水平220.36±18.76和7.71±0.34)(P＜0.05);经过系统治疗后,联合治疗组患者外周血Th17细胞数值比例(分别为IL-17+/CD3+11.10±2.84,IL-17+/CD4+2.09±0.34)、IFN-γ及IL-17水平(分别为321.60±41.19和5.54±0.14)均较常规治疗组显著升高(分别为3.55±1.11,0.63±0.20,155.26±4.99,2.97±0.14),组间差异具有显著性统计学意义(P＜0.05).结论 益气解毒方能促进Th17细胞分化,增强效应细胞因子IFN-γ和IL-17分泌.

目的 探讨益气解毒方中苯丙素类化合物异欧前胡素、阿魏酸、绿原酸对人鼻咽癌CNE2细胞增殖效应的抑制作用及机制研究.方法 使用实时无标记细胞功能分析技术(RTCA)动态监测不同浓度的3种苯丙素类化合物对离体人鼻咽癌CNE2细胞生长曲线的影响;CytationTM 5高通量活细胞成像分析检测系统分别监测3种不同浓度苯丙素类化合物对人鼻咽癌CNE2细胞形态改变;Western blot法检测3种苯丙素类化合物对人鼻咽癌CNE2细胞增殖相关蛋白增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、X连锁的凋亡蛋白抑制剂(X-linked inhibitor of apoptosis protein,XIAP)、Survivin表达的影响.结果 RTCA实时监测结果显示异欧前胡素、阿魏酸、绿原酸均能不同程度地抑制CNE2细胞增殖,存在药物浓度越高抑制效应越明显的趋势.Cyta-tionTM 5检测结果显示,与对照组相比,3种苯丙素类化合物作用36 h后,大量CNE2细胞出现细胞漂浮死亡,细胞膜破溃、细胞结构模糊等形态变化.Western blot检测结果显示,与对照组相比,异欧前胡素、阿魏酸、绿原酸能明显抑制CNE2细胞中增殖相关蛋白PCNA、XIAP、Survivin的表达(P<0.05).结论 益气解毒方中主要苯丙素类化合物异欧前胡素、阿魏酸、绿原酸均可以不同程度抑制人鼻咽癌CNE2细胞增殖,其机制可能与下调增殖相关蛋白PCNA、XIAP、Survivin的表达有关.

目的:研究氧化苦参碱(OMT)对鼻咽癌CNE2细胞增殖和凋亡的影响及作用机制.方法:采用MTT法检测OMT对CNE2细胞增殖的影响;流式细胞术测细胞凋亡率;Western Blot法检测增殖、凋亡相关蛋白及MAPK/ERK信号通路关键蛋白的表达水平.结果:OMT对鼻咽癌CNE2细胞增殖的抑制率随时间(24、48、72h)和药物浓度(5、10、20、40、80μmol/L)的增加而增加.与溶剂对照组比较,OMT能诱导CNE2细胞凋亡(P＜0.01),降低增殖相关蛋白PCNA,抗凋亡蛋白Survivin、XIAP和Bcl-2的表达水平(P＜0.01),提高促凋亡蛋白Bax表达水平(P＜0.01),降低Bcl-2/Bax比值和MAPK/ERK信号通路蛋白p-c-Raf、p-MEK和p-ERK表达水平(P＜0.01).结论:OMT能抑制鼻咽癌CNE2细胞增殖和诱导其凋亡,可能与其下调MAPK/ERK通路的表达水平,继而调控增殖和凋亡相关蛋白的表达水平有关.

目的 探讨结肠癌肺转移患者外周血CD4+CD25+调节性T细胞和血清TGF-β1、IL-10的临床意义.方法 分别应用流式细胞仪(FCM)、逆转录聚合酶链反应(RT-PCR)、酶联免疫吸附测定(ELISA)方法检测结肠癌肺转移患者、健康人外周血CD4+CD25+调节性T细胞占总CD4+调节性T细胞的比例、叉头状螺旋转录因子(Foxp3)表达水平和血清转化生长因子β1(TGF-β1)、白细胞介素10(IL-10)含量.结果 结肠癌肺转移患者外周血CD4+CD25+调节性T细胞占总CD4+的比例、Foxp3表达水平及TGF-β1及IL-10的浓度均明显高于健康人(P<0.001或P<0.05).结论 结肠癌肺转移患者外周血CD4+CD25+调节性T细胞占总CD4+调节性T细胞的比例明显升高,可能是通过Foxp3基因控制的抑制性细胞因子TGF-β1和IL-10而参与结肠癌肺转移的免疫耐受.

通过从肠治咳的临床实践,秉着实践升华真理的思维导图,及对"肺与大肠相表里"的理论探讨,根据理论基础、理论源头,结合自己临床实践与他山之石,从胚胎早期同源性、物质基础共同性、黏膜免疫相关性、信号通路多源性、生态菌落协调性、经脉通路延续性、证候表现关联性等七个微观方面的现代研究及存在的问题进行阐述,并从宏观角度提出该理论再实践、再应用的方向与设想.

细胞焦亡(pyroptosis)是由半胱氨酸天冬氨酸特异性蛋白酶(Caspase)介导,并伴随炎症反应和参与机体免疫应答的一种程序性细胞死亡方式.研究发现细胞焦亡有抑制和促进肿瘤发生发展的双重作用,本文就细胞焦亡的机制及其与肿瘤的关系作一综述.

[目的]通过观察模型大鼠肺组织和结肠组织中NF-κb蛋白及其mRNA水平的变化,探讨与"肺与大肠相表里"相关联的可能信号通路.[方法]实验设正常对照组、COPD模型组、便秘模型组、COPD合便秘模型组4组,取各组大鼠的肺和结肠组织,用免疫组化方法检测NF-κb蛋白的含量,用RT-PCR法检测其NF-κb mRNA的表达,分析不同肺肠病理模型动物中肺组织和结肠组织NF-κB蛋白及其mRNA水平的变化情况.[结果]与正常对照组比较,COPD模型组、便秘模型组、COPD合便秘模型组的大鼠肺组织及结肠组织中NF-κb蛋白及其mRNA水平均显著升高(P<0.05);与COPD模型组、便秘模型组比较,COPD合便秘模型组,大鼠肺组织及结肠组织中NF-κb蛋白及其mRNA的表达均有显著升高(P<0.01).[结论]COPD状态下结肠组织NF-κb mRNA水平升高,便秘时肺组织NF-κb mRNA水平亦升高,NF-κb信号通路可能是"肺与大肠相表里"相关联的物质基础之一.

Objective To investigate the effects of Qi-Boosting Toxin-Resolving Formula (QBTRF) on CD4+CD25+ regulatory T cells and Th17 cells of patients with middle to late staged nasopharyngeal carcinoma (NPC). Methods Flow cytometry was performed to detect the ratio of CD4+CD25+ regulatory T cells and Th17 cells in the peripheral blood mononuclear cells (PMBC) among 18 patients with middle to late stage of NPC treated by QBTRF added to conventional therapy (treatment group), Foxp3 mRNA and ROR-γt mRNA in PMBC was determined by RT-PCR technique. Furthermore, serum levels of IL-6 and TGF-β were assayed by ELISA. Meanwhile, 15 patients with NPC treated by conventional therapy were taken as the control group. Results The ratio of CD4+CD25+ regulatory T cells to the total CD4+ T cells and the transcriptional level of Foxp3 mRNA in PMBC were significantly lower in treatment group than that of control group (P<0.05), the ratio of Th17 cells to the total CD4+T cells and the transcriptional level of ROR-γt mRNA in PMBC were significantly higher in treatment group than that of control group (P<0.05). However, the serum level of IL-6 was obviously higher in treatment group than that of control group (P<0.05), and the serum leve of TGF-βwas obviously lower in treatment group than that of control group (P<0.05). Conclusion QBTRF can significantly affect the number ratio and functional activity of CD4+CD25+ regulatory T cells and enforce the differentiation of Th17 cells among patients with middle to late staged NPC, which it may be reversed the immune tolerance of NPC through regulating the level of IL-6 and TGF-β.

Objective To investigate the implications of Th17 cells and its regulatory cytokines in patients with middle to late staged nasopharyngeal carcinoma (NPC) based on a clinical trial. Methods The ratio of Th17 cells in the peripheral blood mononuclear cells (PMBC) was detected among 28 patients with middle to late stage of NPC by the procedures of flow cytometry, and ROR-γt mRNA in PMBC was determined by RT-PCR technique. Furthermore, serum levels of IL-10, IL-7 and IFN-γ were assayed by the use of ELISA Meanwhile, 15 healthy persons were taken as the normal controls, all with these indicators detected at the same time. Results The ratio of Th17 cells to the total CD4+T cells and the transcriptional level of ROR-γt mRNA in PMBC were significantly lower in middle to late staged NPC patients than that of healthy controls, with the serum levels of IL-17 and IFN-γ being in the same tendency as compared with that of normal persons(P<0.05). However, the serum leve of IL-10 was obviously higher in these patients than that of healthy controls (P<0.05). This suggested that a negative relationship was present in the functional activity of Th17 cells with the severity of lesion for cases with middle to late staged NPC. Conclusion Decrease in the number ratio and functional activity of Th17 cells may be one of the important factors responsible for existing immune tolerance phenomenon that inducing immune escape in the tumor microenvironment among patients with middle to late staged NPC. Therefore, it may be taken as a new target for intervention and treatment once such a situation identified.

Objective To investigate the implications of ratio of the CD4+ and CD25+ positive regulatory T cells (CD4+CD25+Tregs) in peripheral blood mononuclear cells (PBMC) and its associated regulatory factors such as forkhead transcription factor 3 (Foxp3) mRNA transcriptional activity in PBMC,serum levels of transforming growth factor beta-1 (TGF-β1),and interleukin 10 (IL-10) in the immunopathology of patients with middle to late staged nasopharyngeal carcinoma (NPC) based on a clinical trial.Methods In this study,18 NPC cases at middle to late stage as observing group and 10 healthy persons as control group were included to detect their ratio of the CD4+CD25+Tregs in the PBMC with flow cytometry (FCM) technique,transcriptional activity of Foxp3 with RT-PCR procedure,and serum levels of TGF-β1 and IL-10 with enzyme-linked immunosorbent assay (ELISA) method.A comparative analysis was used to explore their implications in the immunopathological correlation of NPC cases with their lesion.Results The ratio of the CD4+CD25+Tregs to total CD4+T cells in PBMC was significantly increased [(4.23 ±0.53)％ vs (2.65 ±0.31)％,t =8.60,P ＜0.01],accompanied with significantly elevated levels of Foxp3 transcription in PBMC (3.699 ± 0.309 vs 1.109 ± 0.146,t' =31.08,P ＜ 0.05],and serum contents of TGF-β1 [(645.56 ± 39.61) pg/ml vs (488.82 ± 36.91) pg/ml,t =10.27,P ＜ 0.01] and IL-10 [(1.27 ± 0.21) pg/ml vs (0.68 ± 0.08) pg/ml,t' =10.61,P ＜ 0.05] in these patients,when compared with that of healthy controls.Conclusions It may be true that CD4 + CD25 + Tregs,transcriptional regulatory factor Foxp3,and cytokines TGF-β1 as well as IL-10 altogether were composed of a regulating system in a positive feedback way to promote the developing process of immunotolerance phenomena in the tumor microenvironment and the initiation of immunoescape among patients with middle to late staged nasopharyngeal carcinoma.

Objective:To investigate the effect of qi-tonifying and detoxicating prescription on CD4 + CD25 + regulatory T cells(Tregs) in patients with advanced nasopharyngeal carcinoma.Methods:Thirty patients with advanced nasopharyngeal carcinoma were randomly divided into control group(n = 15) and observation group(n = 15).The control group received conventional treatment,while the observation group received conventional treatment plus qi tonifying and detoxicating prescription of traditional Chinese medicine.In the first week of treatment and in the first week after 3 months of treatment,the percentage of CD4 + CD25 + Tregs in CD4 + T cells in peripheral blood was measured by flow cytometry,and serum levels of interleukin(IL)-10 and transforming growth factor(TGF)-β were measured by ELISA.Results:Compared with the control group,the observation group had a significantly lower percentage of CD4 + CD25 + Tregs in CD4 + T cells in peripheral blood than the control group(P 0.05) and significantly lower serum levels of IL-10 and TGF-β(P 0.05).Conclusion:Qi-tonifying and detoxicating prescription can decrease the percentage of CD4 + CD25 + Tregs in patients with advanced nasopharyngeal carcinoma.It may affect the immune tolerance of nasopharyngeal carcinoma by regulating serum levels of IL-10 and TGF-β.