目的:观察脐部敷贴通便膏联合服用乳果糖口服溶液对晚期癌痛阿片类药物相关性便秘(OIC)患者的临床疗效.方法:将129例晚期癌痛OIC患者按照随机数字表法随机分为治疗组68例和对照组61例,对照组予乳果糖口服溶液口服,治疗组在对照组治疗的基础上加用通便膏脐部敷贴,2组均治疗14?d后进行疗效观察.比较2组患者治疗前后粪便性状评分(BSFS评分)、便秘情况评分(CCS评分)、生活质量评分(PAC-QOL评分)、中医证候积分等指标改变情况,治疗后比较2组患者中医证候疗效.结果:治疗后治疗组患者BSFS评分、CCS评分、PAC-QOL评分均较治疗前明显降低(P<0.01),且均明显低于同期对照组(P<0.01,P<0.05);治疗后对照组患者BSFS评分较治疗前略有下降,但差异无统计学意义(P>0.05),CCS评分、PAC-QOL评分均明显低于治疗前(P<0.05,P<0.01).治疗后治疗组患者排便不尽感、肠鸣、腹胀、矢气等单项证候评分以及总分均明显低于治疗前(P<0.01),且均明显低于同期对照组(P<0.01);对照组患者除矢气外,其余单项证候评分及总分均明显低于治疗前(P<0.05,P<0.01).治疗组患者中医证候总有效率为98.53％,明显高于对照组的50.82％(P<0.01).结论:在乳果糖口服溶液治疗的基础上加用通便膏脐部敷贴能进一步改善晚期癌痛OIC患者的粪便性状、便秘程度和临床症状,提高患者的生活质量.

Triple-negative breast cancer (TNBC) is ineligible for hormonal therapy and Her-2-targeted therapy due to the negative expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Although targeted therapy and immunotherapy have been shown to attenuate the aggressiveness of TNBC partially, few patients have benefited from them. The conventional treatment for TNBC remains chemotherapy. Chemoresistance, however, impedes therapeutic progress over time, and chemotherapy toxicity increases the burden of cancer on patients. Therefore, introducing more advantageous TNBC treatment options is a necessity. Metabolic reprogramming centered on glucose metabolism is considered a hallmark of tumors. It is described as tumor cells tend to convert glucose to lactate even under normoxic conditions, a phenomenon known as the Warburg effect. Similar to Darwinian evolution, its emergence is attributed to the selective pressures formed by the hypoxic microenvironment of pre-malignant lesions. Of note, the Warburg effect does not disappear with changes in the microenvironment after the formation of malignant tumor phenotypes. Instead, it forms a constitutive expression mediated by mutations or epigenetic modifications, providing a robust selective survival advantage for primary and metastatic lesions. Expanding evidence has demonstrated that the Warburg effect mediates multiple invasive behaviors in TNBC, including proliferation, metastasis, recurrence, immune escape, and multidrug resistance. Moreover, the Warburg effect-targeted therapy has been testified to be feasible in inhibiting TNBC progression. However, not all TNBCs are sensitive to glycolysis inhibitors because TNBC cells flexibly switch their metabolic patterns to cope with different survival pressures, namely metabolic plasticity. Between the Warburg effect-targeted medicines and the actual curative effect, metabolic plasticity creates a divide that must be continuously researched and bridged.

目的 从c-JUN调控的糖基化角度探究追毒方逆转三阴性乳腺癌(TNBC)耐药的机制.方法 MTT检测细胞增殖,采用Western blot检测c-JUN、β3GnT8和ppGalNAc-T1/2、CD147、耐药蛋白BCRP和MDR1的表达.采用转染c-JUN质粒建立过表达c-JUN的MDA-MB-231/ADR细胞.体内实验采用耐药TNBC原位移植裸鼠模型.结果 追毒方可显著抑制MDA-MB-231/ADR细胞的增殖(P<0.01),具有时效和量效关系;可明显抑制耐药TNBC原位移植裸鼠的肿瘤质量(P<0.01);降低耐药蛋白BCRP和MDR1表达(P<0.01),并同时明显降低c-JUN、β3GnT8和ppGalNAc-T1/2、CD147蛋白的表达(P<0.05).过表达c-JUN后,与空白质粒对照组比较,β3GnT8、ppGalNAc T1/2、CD147、BCRP和MDR1的表达均显示增加(P<0.05,P<0.01).而空白质粒对上述蛋白的表达无影响.追毒方可以显著降低过表达c-JUN后的上述蛋白的表达,但其表达水平还是显著高于空白质粒加药组(P<0.05,P<0.01).结论 追毒方通过作用于调控因子c-JUN,下调β3GnT8和ppGalNAc-T1/2的激活,从而抑制CD147的糖基化修饰,导致耐药蛋白BCRP和MDR1下调而逆转TNBC耐药.

The brain-gut axis (BGA) is a significant bidirectional communication pathway between the brain and gut. Traumatic brain injury (TBI) induced neurotoxicity and neuroinflammation can affect gut functions through BGA. N-6-methyladenosine (m(6)A), as the most popular posttranscriptional modification of eukaryotic mRNA, has recently been identified as playing important roles in both the brain and gut. However, whether m(6)A RNA methylation modification is involved in TBI-induced BGA dysfunction is not clear. Here, we showed that YTHDF1 knockout reduced histopathological lesions and decreased the levels of apoptosis, inflammation, and oedema proteins in brain and gut tissues in mice after TBI. We also found that YTHDF1 knockout improved fungal mycobiome abundance and probiotic (particularly Akkermansia) colonization in mice at 3 days post-CCI. Then, we identified the differentially expressed genes (DEGs) in the cortex between YTHDF1-knockout and WT mice. These genes were primarily enriched in the regulation of neurotransmitter-related neuronal signalling pathways, inflammatory signalling pathways, and apoptotic signalling pathways. This study reveals that the ITGA6-mediated cell adhesion molecule signalling pathway may be the key feature of m(6)A regulation in TBI-induced BGA dysfunction. Our results suggest that YTHDF1 knockout could attenuate TBI-induced BGA dysfunction.

在全球范围内,肝癌是目前癌症最常见的死亡原因之一,其高复发率和高转移率都是导致患者高死亡率的最终原因,因此需要寻求一种更好的治疗方式,以提高患者的生存质量,延长生存时间.胸腺基质淋巴细胞生成素(TSLP)可作用于肿瘤细胞,并且高表达的TSLP可以诱导肿瘤的发生.辅助性T细胞(Th1、Th2)具有抗肿瘤的作用,但在肝癌患者体内,TSLP水平的升高会导致Th1/Th2失衡,增加肝癌的复发率.本文将阐述TSLP在肝癌中基于Th1/Th2平衡的相关信号通路的机制研究,以提供新的临床治疗思路.

目的 探讨乳腺癌患者血清中B7-同源物2(B7-H2)和B7-同源物3(B7-H3)的表达及临床意义.方法 选择2018年1月至2019年6月南京中医药大学附属苏州市中医医院收治的乳腺癌患者45例为乳腺癌组,另选择同期于本院体检中心体检健康者25例为对照组.采用酶联免疫吸附法检测2组受试者血清中B7-H2、B7-H3表达水平;通过查阅病历采集乳腺癌患者的年龄、肿瘤直径、TNM分期、病理类型、远处转移、淋巴结转移及雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER-2)表达等临床病理特征,分析乳腺癌患者血清中B7-H2、B7-H3表达水平与患者临床病理特征的关系;采用受试者操作特征(ROC)曲线分析B7-H2、B7-H3单独及联合检测对乳腺癌的诊断价值.结果 乳腺癌组患者血清中B7-H2、B7-H3表达水平显著高于对照组(P<0.05).乳腺癌患者血清B7-H2表达水平与患者的年龄、肿瘤直径、TNM分期、病理类型、远处转移、淋巴结转移及ER、PR、HER-2表达均无关(P>0.05);B7-H3表达水平与患者的TNM分期、淋巴结转移、远处转移有关(P<0.05),与年龄、肿瘤直径、病理类型及ER、PR、HER-2表达无关(P>0.05).乳腺癌患者血清中B7-H2与B7-H3表达呈正相关(r=0.307,P<0.05).血清中B7-H2、B7-H3单独检测诊断乳腺癌的灵敏度分别为75.6％、91.1％,特异度分别为96.0％、84.0％;B7-H2与B7-H3联合检测诊断乳腺癌的灵敏度为93.3％,特异度为88.0％.血清中B7-H2、B7-H3单独和联合检测诊断乳腺癌的ROC曲线下面积(AUC)分别为0.866、0.895、0.959;B7-H2联合B7-H3诊断乳腺癌的AUC显著高于B7-H2(Z=2.348,P<0.05),B7-H2联合B7-H3与B7-H3单独检测诊断乳腺癌的AUC比较差异无统计学意义(Z=1.938,P>0.05),B7-H2与B7-H3单独检测诊断乳腺癌的AUC比较差异无统计学意义(Z=0.466,P>0.05).结论 B7-H2、B7-H3可能参与乳腺癌的发生、发展,血清中B7-H3表达水平可反映乳腺癌患者的恶性程度,可作为判断乳腺癌预后的一个指标;B7-H2、B7-H3对诊断乳腺癌具有较高的灵敏度和特异度,B7-H2联合B7-H3能提高对乳腺癌的诊断效能.

Background. Oxaliplatin-induced peripheral neuropathy (OIPN) is one of the most common side effects of oxaliplatin, which can cause reduction and cessation of oxaliplatin-based chemotherapy and significantly affect patients’ quality of life. However, no drug has got recognition to prevent or treat OIPN. Yiqi-Wenjing-Fang (YWF) is a joint name of Chinese medicine prescriptions with similar effects of tonifying qi and warming meridians, represented by Huangqi Guizhi Wuwu decoction (HGWD) and Danggui Sini decoction (DSD), both from “Treatise on Cold Pathogenic and Miscellaneous Diseases.” YWF granules, including HGWD granules and DSD granules, have been, respectively, demonstrated to be effective in preventing OIPN in previous small-sample observations. The purpose of this study is to enlarge the sample size for further evaluation of the preventive efficacy and safety of YWF granules on OIPN. Methods and Analysis. This study is a randomized, double-blind, placebo-controlled, and multicenter clinical trial. 360 postoperative patients with stage IIa-IIIc colorectal cancer will be randomly assigned into placebo-control group, intervention group I, and intervention group II, taking the mimetic granules of YWF as placebo, HGWD granules and DSD granules, respectively. All subjects will receive oxaliplatin-based chemotherapy regimen at the same time. EORTC QLQ-CIPN20 will be used to assess the degree of OIPN as the primary outcome measure. The grades of OIPN, quality of life, chemotherapeutic efficacy, and the number of completed chemotherapy cycles are selected as the secondary outcome measures. Discussion. Based on the condition of no recognized effective drugs in preventing OIPN, evidence-based medical study will be conducted for seeking a breakthrough in the field of Chinese herb medicine. This protocol could provide reliable and systemic research basis about the efficacy of YWF granules and the differentiation of two classical prescriptions of YWF on preventing OIPN objectively. Trial Registration. This study was registered at ClinicalTrials.gov on 26 December 2020 (ID: https://clinicaltrials.gov/ct2/show/NCT04690283).

三阴性乳腺癌(triple-negative breast cancer,TNBC)指雌激素受体(ER)、孕激素受体(PR)、人类表皮细胞生长因子受体-2(HER-2)均不表达的一种乳腺癌亚型.正因为缺乏有效受体靶点,所以目前没有特效治疗药物,并且与其他基底细胞癌比较,其更容易转移和复发,因此生存率较低.越来越多的研究表明,免疫疗法是一种有希望的治疗策略,被誉为对抗癌症的突破,所以对TNBC的免疫治疗研究十分重要.本文从免疫检查点阻断、过继性免疫治疗、肿瘤疫苗以及中医药治疗等方面对TNBC近期的免疫治疗做一综述.

大菱鲆(Scophthalmus maximus)是我国北方的重要经济鱼种,为研究运输胁迫对大菱鲆生理免疫的影响,并确定大菱鲆的优选运输方案,采用体长为4.65±1cm(幼体组)和14.50±1cm(成体组)2种规格的大菱鲆为研究对象,在实验室模拟运输条件,分析其非特异性免疫、呼吸排泄及死亡率变化,并探究活鱼苗运输的优选方案,结果显示:(1)过氧化氢酶(CAT)、碱性磷酸酶(AKP)、超氧化物歧化酶(SOD)、溶菌酶(LZM)呈现降低趋势并明显低于对照组,随着模拟运输中温度的升高、密度的增加和震动强度的增加而降低,谷草转氨酶(GOT)、谷丙转氨酶(GPT)、丙二醛(MDA)呈现升高趋势并明显高于对照组,随着模拟运输中温度的升高、密度的增加和震动强度的增加而升高;(2)大小2种规格的大菱鲆在运输胁迫下表现出了不同的免疫能力,幼体组中的GOT、GPT、SOD、MDA的表现优于成体组,成体组中的CAT、AKP、LZM优于幼体组;(3)耗氧率和排氨率随着模拟运输中温度的升高、密度的增加和震动强度的增加而升高,幼体组的耗氧率和排氨率的升高程度要低于成体组;(4)实验结束后的幼体组与成体组大菱鲆死亡率均随时间变化先升高后降低,在实验结束时的死亡率极低,而在0～24h死亡率达总死亡率的50％以上,24～48h内的死亡率又开始下降.随着模拟运输中温度的升高、密度的增加和震动强度的增加,2种规格的大菱鲆的总死亡率呈现上升趋势,成体组的总死亡率的升高程度要低于幼体组;(5)通过正交实验极差分析法得出综合考虑成本及运输效果前提下,幼体组与成体组大菱鲆的优选运输方案均为A1B1C2,即温度为15℃、密度为ind·L-1、震动强度为200RPM.

Background: Postoperative central nervous system infections (PCNSIs) are serious complications following neurosurgery. Effective management of the infections depends on the identification of causative pathogens and the antibiotic sensitivities. The aim of this study was to investigate the clinical features, causative organisms and their antimicrobial susceptibility testing results, which could help clinicians to initiate appropriate empirical antibiotic therapy.Methods: This was a retrospective study conducted over a period of 3.5 years (from January 2016 to July 2019). All in-patients admitted neurosurgery and ICU meeting the inclusion criteria of PCNSIs were included in the study. Demographic characteristics, type of neurosurgery, laboratory data, causative organisms and antimicrobial susceptibility testing results were analyzed.Results: A total of 1500 patients underwent operation during this study. Twenty-three patients with 34 isolates out of 79 patients with 157 CSF culture samples were available for data analysis. The estimated incidence and culture-positive rate of PCNSIs were approximately 1.5% and 29.1%, respectively. The predominant organism was coagulase-negative staphylococci, of which most were methicillin-resistant coagulase-negative staphylococci (MRCoNS). All were susceptible to vancomycin, linezolid, and rifampicin. Acinetobacter baumannii was the most frequent causative Gram-negative agent and was resistant to 14 out of 17 antimicrobials tested. The sensitivity rates for amikacin, sulfamethoxazole-trimethoprim and minocycline were only 44, 44, and 11%, respectively.Conclusions: The MRCoNS were the predominant organism for PCNSIs. The management of Acinetobacter baumannii could be a major clinical challenge with few effective antimicrobials in PCNSIs.

β-1,3-N-Acetylglucosaminyltransferase 8 (β3GnT8) is a key enzyme that catalyzes the formation of polylactosamine glycan structures by transferring GlcNAc to tetra-antennary β1-6-branched N-glycans, and it has been reported to participate in tumor invasion and metastasis by regulating the expression of matrix metalloproteinases (MMPs), cluster of differentiation 147 (CD147) and polylactosamine. By contrast, the role of transcription factor c-Jun in cell cycle progression has been well established. c-Jun has an important role in tumor cell invasion and metastasis. However, the precise molecular mechanisms by which c-Jun regulates these processes in colorectal carcinoma cells are not fully elucidated. In the present study, c-Jun had a significant effect on the invasive and migratory abilities of SW480 and LoVo cells. Additionally, overexpression of c-Jun was able to increase the expression of β3GnT8, MMPs, CD147 and polylactosamine. Similarly, knockdown of c-Jun was able to decrease the expression of β3GnT8, MMPs, CD147 and polylactosamine. These results suggest that c-Jun is able to regulate colorectal carcinoma cell invasion and metastasis via β3GnT8. A chromatin immunoprecipitation assay indicated that c-Jun is able to bind directly to the promoter regions of β3GnT8 in SW480 and LoVo cells. This leads to transcriptional activation of β3GnT8, which in turn regulates the expression of tumor invasion and metastasis-associated genes. The results of the present study demonstrate a novel mechanism underlying colorectal carcinoma cell invasion and metastasis, where β3GnT8 is transcriptionally activated via c-Jun binding to its promoter.

目的:观察清热解毒中药对小鼠Lewis 肺癌瘤组织金属蛋白酶基因MMP-9 及其抑制基因TIMP-1 表达的影响.方法:将荷Lewis 瘤肺癌小鼠随机分为5 组,分别给予清热药、养阴药、补肾药、健脾药,对照组予生理盐水灌胃,连续20 天,第22 天处死小鼠,检测不同治法的抑瘤率,对小鼠的移植瘤体积、重量和肺部转移灶数目的影响,并采用RT-PCR法检测MMP-9、TIMP-1 值.结果:各给药组与对照组相比,在抑瘤率、移植瘤体积、肿瘤重量方面无明显差别;各给药组转移灶数目低于对照组,且有统计学差异;清热组具有下调MMP-9 表达及上调TIMP-1 表达的作用,与对照组相比有显著性差异.结论:清热解毒法能降低肺癌组织MMP-9 表达,上调TIMP-1 表达,从而抑制小鼠Lewis 肺癌的转移;各组药物均能不同程度地抑制荷瘤小鼠肺转移灶数目,但其作用机理有待进一步研究.

Objective: Study on the curative effect of treating non-small cell lung cancer malignant pleural effusion by pouring the Ade injection into the thoracic cavity.Method: A total of 46 patients with non-small cell lung cancer were randomized into the 2 groups: treatment group 23 examples by pouring the Adye injection into the thoracic cavity,and the control group 23 examples by pouring CTX into the thoracic cavity.Result:The curative effect of two groups was similar,but the treatment groups without toxic and side effect.Conclusion: The curative effect of treating non-small cell lung cancer by pouring Adye injection to the thoracic cavity were affirmed,and without toxic and side effect.

采用中医益气养阴法治疗210例恶性肿瘤术后患者,平均年龄61.2岁,结果显示:益气养阴法治疗5年生存率为56.7%,与国内文献报道相仿,与辅助化疗组比较,无明显差异.结果提示:中医益气养阴法治疗也具有一定的抗恶性肿瘤转移的作用,认为恶性肿瘤患者术后坚持服药2年以上,可获得较好的远期生存率.