Non-targeted TCM metabolomic techniques were employed to explore the potential effective substances of Shuangshen Fuzheng San.The inhibitory effects of Shuangshen Fuzheng San and its effective substances on human lung adenocarcinoma A549 cells in vitro were evaluated by using CCK-8 assays,colony formation assays,flow cytometric analysis of apoptosis,and Western blot analysis of apoptosis-related proteins.This study aims to explore the optimal effective substance combination,further analyze,and verify the potential action mechanisms underlying the inhibitory effects of Shuangshen Fuzheng San and its effective substances on the lung adenocarcinoma through network pharmacology analysis.The results demonstrate that ginsenoside Rg3,ginsenoside Ro,and notoginsenoside Fe can simultaneously enter into the mice's serum and lung tissues and are identified as the key effective substances of Shuangshen Fuzheng San responsible for inhibiting A549 cell proliferation.The combination of ginsenoside Rg3 and notoginsenoside Fe exhibits the strongest inhibitory effect on A549 cell proliferation and is determined to be the optimal effective substance combination.The optimal effective substance combination can inhibit clonogenic formation of A549 cells,significantly promote the apoptosis of A549 cells,and markedly upregulate the expression of apoptosis-related proteins,with the effective substance combination showing a superior effect compared with the drug-containing serum.The interleukin(IL)-17 signaling pathway is strongly associated with the inhibitory effects of Shuangshen Fuzheng San on lung adenocarcinoma.Consistently,both the optimal effective substance combination of Shuangshen Fuzheng San and drug-containing serum can significantly downregulate the expression levels of key IL-17 pathway-related proteins,including IL-17A,IL-6,and matrix metalloproteinase-9(MMP-9),in A549 cells.Collectively,ginsenoside Rg3,ginsenoside Ro,and notoginsenoside Fe are the key effective substances of Shuangshen Fuzheng San.The combination of ginsenoside Rg3 and notoginsenoside Fe constitutes the optimal effective substance combination of Shuangshen Fuzheng San,which together with drug-containing serum,inhibits lung adenocarcinoma progression via the IL-17 signaling pathway and exhibits superior inhibitory effects on lung adenocarcinoma in vitro compared with drug-containing serum.

ETHNOPHARMACOLOGICAL RELEVANCE:It is well known that Shaoyao Decoction (SYD), as a commonly used formula of traditional Chinese medicine (TCM), has a beneficial effect on the treatment of ulcerative colitis (UC). It is found that SYD can also prevent colitis-associated colorectal cancer (CAC). However, its potential anti-cancer mechanism is still waiting to be revealed. AIM OF THE STUDY:The aim of this study is to investigate the underlying mechanisms of SYD in inhibiting CAC through silico analysis as well as animal experiment validation. MATERIALS AND METHODS:The primary active compounds, potential therapeutic targets and intervening signaling pathways, which SYD might inhibit the CAC process were predicted by network pharmacology analysis combined with our previous research result of high performance liquid chromatography (HPLC). We attempted to validate the acquired hub targets from molecular docking combined with the Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), and the cBioPortal database comprehensively. Subsequently, an animal model of CAC mice induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) was constructed and treated with SYD for 14 weeks, and tumor-related physical indicators were evaluated after sacrificed. In addition, samples of colon tissues were obtained for histologic and protein level studies to verify the predicted mechanism. RESULTS:We obtained 166 active ingredients of SYD and predicted 148 potential targets through network pharmacology analysis, among which quercetin, berberine, kaempferol, wogonin and naringenin were selected as core drug ingredients, and TP53, AKT1, CASP3, PTGS2 and CCND1 were identified and included into the range of core targets. GO and KEGG analyses suggested that the PI3K-Akt signaling pathway might hold a crucial role in CAC prevention and treatment by promoting apoptosis and inhibiting tumor proliferation. In the animal experiment, both SYD and SASP treatments improved the inflammatory condition and pathological damage of the colon tissues in mice. After treatments with SYD and SASP, it was found that decreases of Cyclin D1 and Survivin expression levels and increases of p53 and Cleaved caspase-3 expression levels could be mediated by decreasing the phosphorylation levels of PI3K and Akt proteins in the colon tissues of mice. CONCLUSION:The results of our study provide supports that SYD effectively inhibits CAC based on modulating PI3K-Akt signaling pathway to suppress tumor proliferation process as well as to promote tumor apoptosis process.

BACKGROUND Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated. AIM To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved. METHODS Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A “drug-ingredient-target” network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers. RESULTS Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1 , identifying PI3K , AKT , and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro . Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K , p-Akt , and survivin, which likely contributed to CRC apoptosis. CONCLUSION Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Background:Shuangshen granule s(SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects.Therefore,it is crucial to understand the precise mechanism.Building upon the findings of our previous study,the objective of the present study was to explore the impact of S SGs on the sphingosine-1-phosphate receptor-1(S1PR1)/signal transducer and activator of transcription 3(STAT3) axis,as well as the recruitment of myeloid-derived suppressor cells(MDSCs) during the formation of the premetastatic niches(PMNs).Methods:In a mouse xenograft model utilizing Lewis lung carcinoma(LLC) cells that express green fluorescent protein(GFP),the initiation of lung metastasis was monitored every three days until day 35 following transplantation.Lung metastasis,MD SC recruitment,the expression of PMN and S1PR1/STAT3 axis biomarkers,as well as the blood levels of granulocyte-mac rophage colony-stimulating factor(GM-CSF) and transforming growth factor-β(TGF-β) were assessed in the SSG treatment and control groups.Results:The LLC cells did not reach the lung until 14-17 days following subcutaneous implantation,which was concurrent with the formation of lung PMNs.S SG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs.S SG also suppre ssed the S1PR1/STAT3 axis in tumor tissue s,bone marrow,and lung PMNs.Additionally,SSG suppres sed the blood levels of GM-CSF and TGF-β,as well as the PMN markers,matrix metalloproteinase-9 and versican.Conclusion:Our findings suggested that SSG suppressed the development of MD SC-mediated PMNs by inhibiting the S1PR1/STAT3 axis,consequently postponing the initiation of lung metastasis.

Background: The inflammatory microenvironment created by chronic inflammation is a key factor in tumor development and poses a significant challenge to global health. This study aims to assess the trends in the burden of inflammation-related diseases of the digestive system among adolescents and adults aged 15 to 49 at global, regional, and national levels from 1990 to 2021, as well as to predict the prevalence of these diseases over the next 15 years. Methods: We utilized the analytical tools from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to calculate the age-standardized rates, annual percentage changes (APC), and the average annual percentage changes (AAPC) of inflammation-related diseases of the digestive system among the population aged 15 to 49 years. These diseases included chronic hepatitis B including cirrhosis, chronic hepatitis C including cirrhosis, gastritis and duodenitis, pancreatitis, and inflammatory bowel disease. We analyzed the trends of these diseases based on age, sex, region, and socio-demographic index (SDI), identified the years with the most significant changes, visualized these trends on world maps, and examined the effects of population growth, aging, and epidemiological changes on disease burden. Finally, we projected the prevalence of inflammation-related diseases for the next 15 years. Findings: From 1990 to 2021, the age-standardized rates of chronic hepatitis B including cirrhosis, chronic hepatitis C including cirrhosis, gastritis and duodenitis, pancreatitis, and inflammatory bowel disease among the 15 to 49 age group showed a decline. However, in 2021, the number of cases of inflammation-related diseases increased compared to 1990, with chronic hepatitis B including cirrhosis (170,642,543.25 per 100,000 population), chronic hepatitis C including cirrhosis (67,505,399.19 per 100,000 population), gastritis and duodenitis (15,262,169.84 per 100,000 population), pancreatitis (2,060,258.85 per 100,000 population), and inflammatory bowel disease (1,684,616.35 per 100,000 population). The reasons for these changes can be categorized into three main factors: population growth, aging, and epidemiological changes. Population growth and aging primarily contributed to the increase in the number of cases, while epidemiological changes generally led to a decrease in cases. Collectively, these factors resulted in a rise in overall case numbers, with the burden of inflammation-related diseases worsening alongside decreasing SDI. Using the Norpred model to project the prevalence of inflammation-related diseases over the next 15 years, we found that while the prevalence decreased across all age groups, the total number of cases exhibited a polarization effect, with younger individuals showing a decline and older individuals an increase, with a notable inflection point around the age of 40. Interpretation: Inflammation-related diseases, which carry the risk of cancer transformation, are primarily concentrated in economically underdeveloped regions. Although there have been some improvements in disease prevalence, overall levels remain high. Given the differing natures of these diseases, there is an urgent need to develop tailored prevention and control policies to alleviate the disease burden on adolescents and adults and prevent transformation into cancer. Funding: This work was funded by the National Nature Science Foundation of China (82174464), and the Central High-level Traditional Chinese Medicine Hospital Clinical Research Business Fee Subsidy (HLCMHPP2023085) Declaration of Interest: We declare no competing interests.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

骨髓源性抑制细胞(MDSC)可形成能够影响慢性结肠炎相关癌变(CAC)进程的免疫抑制微环境.炎症条件下,异常的线粒体代谢与缺氧状态参与调控MDSC并影响CAC的进展.而AMP依赖的蛋白激酶的激活会抑制MDSC对缺氧诱导因子-1 α基因的表达调控.本文拟从免疫代谢途径探究MDSC如何调控和影响慢性肠炎的癌变,以期为结直肠癌的防治提供思路和证据支撑.

The wingless-related integration site (Wnt) signaling pathway plays an essential role in embryonic development and nervous system regulation. It is critically involved in multiple types of neuropathic pain (NP), such as HIV-related NP, cancer pain, diabetic neuralgia, multiple sclerosis-related NP, endometriosis pain, and other painful diseases. Wnt signaling is also implicated in the pain induced by sciatic nerve compression injury and selective spinal nerve ligation. Thus, the Wnt signaling pathway may be a potential therapeutic target for NP.

目的 运用现代信息技术挖掘现代中药复方治疗慢性偏头痛的组方用药规律.方法 检索2013年1月至2020年12月维普资讯中文科技期刊数据库、中国期刊全文数据库、万方医学网数据库关于中药复方治疗慢性偏头痛的文献,对符合纳排标准的文献进行预处理,运用Excel 2019对数据库里的中药使用频次、功效类别、性味归经等进行统计分析;运用SPSS Modeler 18.0、SPSS Statistics 20软件分别进行关联规则分析、聚类分析.结果 筛选符合标准的文献236篇,涉及255组方剂,录入中药165味,筛选出高频中药(频次≥27次):川芎、甘草、白芍、天麻等36味.对高频中药进行统计,药物分类以活血化瘀、平肝息风、补益气血药居多;药性以温性药物居多;药味以辛味药居多;归经以肝、脾经居多.高频中药的关联规则分析、聚类分析分别形成了 23组药对组合、5类聚类组合.结论 慢性偏头痛用药以活血化瘀、平肝息风、补益气血药为主,大多选择药性偏温、味辛、归肝脾经的药物.

Background Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan–Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

目的:观察三才封髓丹加减治疗气阴两虚型2型糖尿病合并汗证的疗效.方法:采用回顾性研究方法,将68例2型糖尿病合并汗证患者分为对照组和观察组,每组34例.对照组患者在常规治疗基础上予甲钴胺片口服,观察组患者在对照组基础上加用三才封髓丹加减,两组均治疗8周.比较两组治疗前后中医证候评分、空腹血糖、餐后2 h血糖、糖化血红蛋白水平.比较两组疗效、不良反应发生情况.结果:观察组总有效率为88.2％,高于对照组的47.1％,差异有统计学意义(P<0.05).治疗后,观察组自汗、盗汗主症评分及气短乏力、口干多饮次症评分均优于治疗前,且明显优于对照组,差异有统计学意义(均P<0.05).两组不良反应发生率比较,差异无统计学意义(P>0.05).结论:常规治疗联合三才封髓丹内服治疗气阴两虚型2型糖尿病合并汗证患者,可改善糖代谢指标,临床疗效较好.

对2010-2019年度国家自然科学基金中医学领域糖尿病相关项目申请与资助情况进行回顾和分析,介绍了面上、青年、地区科学基金项目的申请和资助项目数及资助率,并对资助病种进行总结.分析后发现,近10年国家自然科学基金资助的糖尿病相关项目具有围绕中医优势病种,面向临床需求,聚焦前沿科学问题,重视中医药防治糖尿病基础研究,推动多学科交叉,加强原始创新等特点;但也存在缺乏中医理论支撑,科学问题属性不明确等问题.

目的 探讨非布司他治疗G3期慢性肾脏病(CKD)伴无症状高尿酸血症(HUA)的临床效果及对患者肾功能的保护作用.方法 选取2017年2月至2020年1月收治的186例G3期CKD-HUA患者作为研究对象,采用随机数字表法分为观察组和对照组,各93例.对照组予别嘌醇(日剂量100～300 mg,po)治疗,观察组予非布司他(日剂量20～40 mg,po)治疗,疗程均为6个月.检测2组患者治疗前后血尿酸(SUA)、肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白定量和肾小球滤过率(eGFR)水平,评估2组治疗有效率、SUA达标率、氧化应激指标变化和不良反应发生率.结果 观察组治疗3、6个月的SUA达标率分别为53.76％和68.82％,高于对照组的38.71％和53.76％(P ＜ 0.05);观察组治疗有效率高于对照组(96.77％vs 89.25％,P ＜ 0.05).治疗后,2组SUA、Scr、BUN、24h尿蛋白和eGFR水平均低于同组治疗前,且观察组上述指标均显著低于对照组(P＜0.05).治疗后,观察组丙二醛(MDA)水平低于对照组,超氧化物歧化酶(SOD)水平高于对照组(P ＜ 0.05).2组不良反应发生率比较差异无统计学意义(P＞0.05).结论 非布司他对G3期CKD-HUA的疗效较别嘌醇更显著,可降低患者SUA水平,改善氧化应激指标水平,减轻肾功能损伤,安全性较高.

从总体资助情况、连续资助项目情况、资助项目研究特点及申请建议4个方面对国家自然科学基金医学科学部中医学科2010-2020年中医妇科领域面上项目、青年项目以及地区项目的 申请与资助情况进行分析,希望为广大中医妇科领域科研和医务工作者申报国家自然科学基金提供参考.

炎性微环境对于肠癌的发病进程有着重要影响.慢性炎性微环境存在的炎性细胞因子、炎性趋化因子、炎性信号通路调控以及炎性状态下的肠上皮细胞高甲基化都会影响慢性肠炎癌变.中医认为炎性相关肠癌的病机为脾虚湿热,具有清热燥湿作用以及健脾益气作用的中药可以通过抑制或者调控炎症相关因子及其信号通路进而抑制肠炎癌变进程,并抑制肠癌细胞增殖、减低肠道肿瘤负担进而防治肠炎癌变.

对2019年度国家自然科学基金医学科学部中医循证研究领域申请的项目,从临床研究与方法学研究两个方面分析其项目申请领域分布与资助情况,分析中医循证研究存在的主要问题,探讨中医循证研究在提高中医药临床研究质量、突出中医药特色和揭示其作用规律、中医循证方法学研究等方面的研究思路.

目的 芍药汤可有效治疗溃疡性结肠炎,炎症细胞中ROS水平的增加可能会加重癌症的发展,Nrf2已成为预防结直肠癌的新靶点.评估了芍药汤的细胞保护作用.方法 在H2O2诱导的氧化应激模型和棕榈酸诱导的炎症模型中评估芍药汤对结直肠癌的细胞保护作用,芍药汤通过调控HT-29细胞系中的蛋白质表达来激活Nrf2的信号传导途径来分析芍药汤诱导Nrf2激活的靶标,通过蛋白质印迹和酶联免疫吸附测定法测定蛋白质表达和炎性细胞因子水平.结果 10％体积分数的高剂量(37 g/kg)芍药汤血清增加Nr12表达、核转位和下游Ⅱ期抗氧化酶的表达,并通过Nrf2/ARE途径降低H2O2诱导的氧化应激,5％体积分数高剂量的芍药汤含药血清能够抑制炎性细胞因子水平和NF-κB表达.结论 研究结果表明,芍药汤可以激活Nrf2通路,可以预防氧化应激诱导的肠癌细胞损伤并减少炎症.芍药汤中药治疗可能是结肠炎相关结直肠癌的替代疗法.

1例53岁男性因黏膜相关淋巴组织型结外边缘区B细胞淋巴瘤接受利妥昔单抗联合环磷酰胺、长春新碱、泼尼松(R-CVP)方案治疗,第二周期治疗后3周出现活动后气促.入院行全身CT示双肺炎症,双侧胸腔少量积液.考虑为利妥昔单抗及/或环磷酰胺致间质性肺炎可能性大,予大剂量激素冲击治疗后,间质性肺炎明显好转.

目的:选取氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)诱导的慢性肠炎癌变小鼠模型,动态探究具有清热燥湿、调气和血功效的芍药汤调控抗氧化应激信号通路Keap1/Nrf2/ARE发挥抗氧化作用对肠“炎-癌”转化进展的保护机制.方法:病理学评价AOM/DSS诱导的肠炎癌变情况;定量RT-PCR检测结直肠组织中抗氧化信号通路核因子E-2-相关因子2(Nrf2)关键指标的表达;免疫组化检测结直肠组织炎症和肿瘤形成指标核因子κB(NF-κB)、Ki-67抗原(Ki-67)、Nrf2的表达;ELISA法检测结直肠组织炎性细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素1β (IL-1β)以及氧化应激蛋白超氧化物歧化酶(SOD)和丙二醛(MDA)的表达.结果:与AOM模型组比较,芍药汤各组小鼠体质量减轻较少、均能明显抑制结肠缩短、显著减少肿瘤数量(P＜O.01).与AOM组比较,芍药汤高剂量组各时间点谷胱甘肽还原酶(GR)、硫氧还蛋白还原酶(TR)、血红素氧合酶-1(HO-1)、苷二磷酸葡萄糖醛酸基转移酶1A1 (UGT1A1)的mRNA表达水平,第63、98天时,醌NADH脱氢酶1(NQO-1) mRNA及第28、63天时尿苷二磷酸葡萄糖醛酸基转移酶1A10(UGT1A10)、γ-谷氨酰半胱氨酸合成酶c(γ-GCSc)mRNA表达水平均显著升高(P＜ 0.05,P＜0.01);芍药汤各剂量组第98天NF-κB、Ki-67表达水平显著降低(P＜0.01),第63、98天TNF-α及IL-1 β表达水平显著降低(P＜ 0.05,P＜0.01);芍药汤高、中剂量组各时间点SOD活性增强(P＜0.05,P＜0.01),芍药汤各剂量组各时间点MDA含量减少(P＜0.01).结论:芍药汤对AOM/DSS诱导的肿瘤发生具有一定程度的预防作用,能够抑制氧化应激诱导的炎性损伤,通过调控抗氧化应激信号通路Keap 1/Nrf2/ARE发挥抗氧化和抗炎作用.