N6-甲基腺苷(N6-methyladenosine, m6A)修饰是真核生物信使 RNA中最丰富的表观遗传修饰,其失调会导致mRNA异常生物学行为如翻译和降解紊乱,从而调控肿瘤发生发展。近期研究表明m6A在免疫调控过程中可发挥重要作用,其不仅可调节免疫细胞的活化,还在肿瘤微环境中免疫应答发挥重要调控作用,从而影响免疫治疗效果。越来越多的证据表明m6A修饰可能是肿瘤免疫治疗的重要潜在干预靶点。本文阐述了免疫细胞中m6A修饰调控及其在肿瘤免疫微环境中相关调节作用,并进一步探讨了靶向m6A调控蛋白在肿瘤免疫治疗中的干预策略及潜在治疗价值。
N6-methyladenosine (m6A) modification is the most abundant epigenetic modification in eukaryotic messenger RNA (messenger RNA). Its dysregulation drives abnormal transcription and translation processes, which promotes the occurrence and development of tumors. Studies have shown that m6A modification can regulate the activation of immune cells and their infiltration into the tumor microenvironment (TME), which may affect the efficiency of immunotherapy. Therefore, m6A modification may be a potential target for tumor immunotherapy. This paper describes the modification of m6A in immune cells and the antitumor immune response associated with TME, and explores the potential therapeutic value of targeting m6A regulators in tumor immunotherapy.
目的 初步研究木棉花水提取物抗炎镇痛作用。方法 采用二甲苯和醋酸作为致炎和致痛因子,通过小鼠耳廓肿胀实验、腹腔毛细血管通透性实验与扭体实验,考察灌胃高、中、低剂量的木棉花水提取物的抗炎、镇痛作用。结果 小鼠对于木棉花水提取物的最大耐受量为300 g/kg;木棉花水提取物高剂量(150 g/kg)和中剂量(100 g/kg)均能抑制小鼠耳廓肿胀,降低小鼠腹腔血管通透性;木棉花水提取液各剂量组均能有效地减少小鼠的扭体次数,且作用随剂量增加而增强。结论 木棉花水提取物具有抗炎镇痛作用。
Objective To study the anti-inflammatory and analgesic effect of water extract of Bombax malabaricum DC. Flower. Methods The xylene and acetic acid were used as inflammation and pain factors. The auricle swelling test,intraperitoneal capillary permeability test and writhing experiment were performed to study the anti-inflammatory and analgesic effect with high,medium and low dose of water extract of Bombax malabaricum DC. Flower. Results The maximum tolerated dose of mice for Bombax malabaricum DC. Flower was 300 g/kg. High dose (150 g/kg) and medium dose (100 g/kg) of water extract of Bombax malabaricum DC. Flower could both inhibit mouse auricle swelling and reduce mouse peritoneal vascular permeability. All dosages of the water extract of Bombax malabaricum DC. Flower were effective in reducing the number of writhing in mice,and the effect is strengthened with the increase of dosage. Conclusion Water extract of Bombax malabaricum DC. Flower has anti-inflammatory and analgesic effects.
目的 制备以牛血清白蛋白为模型药物的壳聚糖纳米制剂(BAS/CS NPs)及其体内外性质的研究,并通过加入羧化壳聚糖(WCS)来改善聚阳离子制备的纳米粒(CS NPs)的安全性。方法 利用油包水乳化-冻干法制备而得的CS NPs,通过激光粒度分析仪测定纳米粒粒径和电荷,用BCA法测定纳米粒包封率和载药量,并用Caco-2 cells单层膜模型评价BAS/CS NPs的细胞摄取情况和跨膜转运,以Franz扩散池法考察吸收考察BAS/CS NPs的离体各个小肠段黏膜的渗透性能,采用荧光分光光度计测定累积渗透量。结果 所制备的BAS/CS NPs平均粒径 在100～500 nm之间,电荷(-42.32±2.56)mV,包封率为88.37±6.82(%),载药量7.48±0.50(%),细胞毒性和细胞摄取实验表明羧化壳聚糖的BAS/CS NPs能降低细胞的毒性,并发现在十二指肠纳米粒具有促进BSA吸收作用(P<0.05)。结论 BAS/CS NPs是通过打开细胞紧密连接的方式增加BSA在小肠内的吸收。WCS降低BAS/CS NPs的细胞毒性,增强了兔小肠的BSA运输。作用要优于广泛研究的聚阳离子纳米粒体系,为口服蛋白类药物的传递提供了新的渠道。
目的 探讨直肠神经内分泌肿瘤的临床病理特征。方法 回顾性分析46例直肠神经内分泌肿瘤患者的临床病理资料,对不同病理分级的患者在性别、年龄、肿瘤直径、浸润深度、肝及淋巴结转移等方面进行比较。结果 直肠神经内分泌肿瘤男性多见,肿瘤多位于直肠中下段。免疫组化检测显示CgA、Syn、CD56阳性率分别为40.0%、97.8%、100%。36例Ki-67阳性指数≤2％,6例Ki-67阳性指数在3％～20％,4例Ki-67阳性指数＞20％。不同病理分级的肿瘤与患者年龄、肿瘤直径、浸润深度、淋巴结及肝转移相关,与性别不相关。结论 直肠神经内分泌肿瘤缺乏临床特异性症状,联合CgA、Syn和CD56染色可提高直肠神经内分泌肿瘤的诊断率。病理分级对预测肿瘤浸润深度、肝或淋巴结转移有重要参考价值。
Objective To investigate the pathological and clinical significance of 46 cases of rectal neuroendocrine tumors(NET). Methods Retrospectively analyzed the clinical and pathological feature of 46 patients with rectal NET, and assessed possible interactions between different pathological grades and gender, age, tumor diameter, depth of invasion, lymph node and liver metastasis. Results Rectal NET appeared more frequently in males than in females. Most tumors located in middle and distal third of rectum. The positivity rates of immunohistochemical marker CgA, Syn, CD56 were 40.0%, 97.8%, 100.0%, respectively. The cases of Ki-67 positivity rate under 2%, ranged between 3%-20%, above 20% were 36, 6, 4, respectively. Different pathological grades were significantly correlated with age, tumor diameter, depth of invasion, lymph node and liver metastasis, but not with gender. Conclusion Rectal NET had nonspecific symptoms. Combined immunohistochemical staining, such as CgA, Syn and CD56, was important in the evaluation of rectal NET. Pathological grading might be very useful for prediction of invasion depth, lymph node and liver metastasis.
目的 探讨代谢综合征(metabolic syndrome, MS)(指包括高血压,糖尿病,高脂血症和腹型肥胖的一组综合征)在中国南方老年病人的患病率、及其与心血管事件和痴呆关系。方法 本研究为一个中国南方老年人代谢综合征的横断面研究。我们采集了患者的病史、人口学和生化资料。对比生化资料、心血管事件、痴呆等疾病在MS组和非MS组中的差异,并使用Logistic回归分析来寻找MS的独立影响因子。结果 本研究共纳入206例患者。其中有92(44.66%)例患者符合代谢综合征的诊断标准。女性在MS组中35例(38.04%)明显高于在非MS组中28例(24.56%)。整体年龄(86.74± 6.10),在MS组(86.37±5.74)和非MS组(87.04±6.38)对比中无统计学意义。生化资料对比中,白细胞[(7.46±2.38) vs (6.46±2.35),P=0.003]和血肌酐[94.50(68.50, 129.33) vs 78.00(64.50, 99.75),P=0.004]在MS组中较高。Logistics单因素回归分析及多因素回顾分析提示白细胞、血肌酐和女性为MS的独立风险因子。心肌梗塞(35例,38.04%和心绞痛(28例, 24.56%)在MS组中明显高于非MS组中心肌梗塞(10例,8.77%)和心绞痛(39例,34.21%),两组比较有统计学意义,Logistics回归分析发现MS是心肌梗塞和心绞痛的独立影响因子;但是心衰和中风在两组对比中无统计学差别。痴呆(包括老年性痴呆和血管性痴呆)在MS组中明显低于非MS组:26例(28.26%)vs 50例(43.86%),提示MS可能对痴呆有预防作用。结论 MS在中国南方老年患者中普遍存在,女性、白细胞、血肌酐为MS的独立影响因子;MS是心肌梗塞和心绞痛的独立影响因子;MS中痴呆明显低于非MS组,可能对痴呆有预防保护性作用。
Objective To study the prevalence and correlation between the metabolic syndrome MS (including hypertension, diabetes, hyperlipidemia and obesity) with cardiovascular and dementia in the elderly people of south China. Methods This cross-sectional research studied metabolic syndrome of the elderly in south China. We collected the demographics and chemotic data and compared them in MS and non-MS group. And Logistic regression was used to analyze the independent factor of MS and the relationship between MS and the cardiovascular disease and dementia. Results This study included 206 patients and 92 (44.66%) of them were diagnosed as MS. 35 patients (38.04%) in MS group were female and 28 female cases (24.56%) in non-MS group. The mean age of the sample was (86.74±6.10) and the comparison between the MS group (86.37±5.74) and non-MS group (87.04±6.38) was not significantly different. White blood cell (WBC) (7.46±2.38 vs 6.46±2.35,P=0.003) and serum creatinine (Scr) was significantly [94.50(68.50,129.33) vs 78.00(64.50, 99.75),P=0.004]in MS group versus in non-MS group. Single factor and Multinomial logistic regression found WBC, serum creatinine and female gender were the independent risk factors of MS. Myocardial infarction (35, 38.04%) and angina (28, 24.56%) were significantly higher in MS group than that in non-MS group (10, 8.77%) and (39, 34.21%), respectively, with P<0.05. Logistic regression found MS was an independent risk factor of myocardial infarction and angina but not in heart failure and stroke. Dementia (including Alzheimer disease and vascular dementia) was found lower in MS group (26, 28.26%) than that in non-MS group (50, 43.86%), the difference was significant and this means MS could be protective for dementia. Conclusion MS is prevalent in the elderly of south China. Female gender, WBC and Scr were independent factors of MS; MS was the independent risk factor of myocardial infarction and angina; dementia was significantly lower in MS group, implying MS could be protective to dementia.
目的 进一步提高宫腔粘连的超声诊断准确率。方法 对476例超声诊断的宫腔粘连病例进行回顾性分析。结果 476例经阴道彩超诊断的宫腔粘连患者,超声主要表现:内膜回声连续性中断,内膜厚薄不均。超声结合临床表现,将患者分成轻度粘连、中度粘连和重度粘连。71例重度粘连患者于我院行宫腔镜治疗。经阴道彩超结合临床,对宫腔粘连的诊断准确率达100%。结论 经阴道彩色多普勒超声是诊断宫腔粘连首选的检查手段。经阴道彩超结合临床,对宫腔粘连具有很大的诊断价值,对粘连的分级有助于指导临床制定治疗计划。
Objective To improve the ultrasound diagnostic accuracy rate of Intrauterine Adhesions. Methods Retrospectively analysis of 476 intrauterine adhesions cases were diagnosed by the transvaginal color ultrasound. Results Main imaging characteristics of 476 IUA cases were endometrial echo interruption, uneven thickness, et al. Combining ultrasound with clinical performance, the data was classified into three types: mild IUA, moderate IUA, severe IUA. 71 cases of severe IUA were treated with hysteroscopy surgery. Conclusion Transvaginal ultrasound with clinical data diagnosis for the intrauterine adhesions has higher practical value. The classification is helpful for making the treatment plan.
目的 分析药源性双硫仑样反应医疗损害责任纠纷的规律及特点,为规避用药风险、促进合理用药提供参考。方法 以“双硫仑”为关键词,检索中国裁判文书网,时间截至2025年3月25日,将通过筛选的裁判文书基本情况、双硫仑样反应药物关联情况、症状表现、转归、赔偿情况等信息提取录入Excel表,建立评价数据库。结果 共检索得裁判文书81份,纳入裁判文书18例,涉及医疗机构为三级医院3例、二级医院5例、卫生院/卫生室7例、民营医院2例、诊所1例;性别构成中,男15例,女3例;怀疑引起双硫仑样反应的药物有头孢哌酮、头孢呋辛、替硝唑、头孢噻肟、甲硝唑、左氧氟沙星、头孢曲松钠、头孢替安和头孢米诺;患者饮酒和用药间隔多为1~3 d;症状表现有呼吸困难/呼吸骤停、昏迷/意识丧失/休克、面色紫绀/局部发紫/指甲发紫、抽搐/发抖、出汗、不能说话/说话不清楚等;转归结果中,15例结局为死亡,1例为神经症,1例为一级伤残（植物人）,1例为二级伤残（缺氧缺血性脑病后遗四肢功能障碍）;7例患者死亡案例因未尸检影响了结果鉴定;判决情况中,1例和解,1例未公布三审判决结果,余16例医疗机构承担了10%~70%的医疗赔偿责任,赔偿金额43 092.4~1 616 354元;医方存在的过失主要有未认真采集饮酒史、违反诊疗常规用药、违反合理注意义务、未履行知情告知义务等。结论 药源性双硫仑样反应危害大,误诊率高,发病急骤凶险,基层医疗机构对其鉴别和处置能力亟需提高;应重视饮酒史的采集和记录;合理合规处方抗生素;加强对患者的高度注意义务、知情告知义务等履行;医院药学人员应积极参与安全用药工作,做好用药教育。
Objective To analyze the regularity and characteristics of the medical damage liability dispute with drug-induced disulfiram-like reaction, to avoid the risk of medication and provide reference for clinical rational drug use. Methods China Judgements Online had been searched using the keywords of “disulfiram” from inception to March 25,2025. The evaluation table database was established with the excel table to conduct statistical analysis on the basic information of judgements, drug association, clinical performance,outcome of disease and the compensation. Results A total of 81 cases of judgements documents were retrieved,and 18 cases were enrolled. There were 3 tertiary hospitals, 5 second-class hospitals, 7 health-centers, 2 private hospitals,1 clinic among the medical establishments. Fifteen cases were male and 3 cases were female. The drugs suspected causing disulfiram-like reaction were cefoperazone, cefuroxime, tinidazole, cefotaxime, metronidazole, levofloxacin, ceftriaxone, cefotiam, cefminox. The interval between drinking and medication was usually 1-3 days. The symptoms were as follows：dyspnea/respiratory arrest, coma/loss of consciousness/shock, cyanosis /purple nails, convulsion/trembling, sweatiness, inability to speak/lack of clarity, etc. Fifteen cases ended in death, 1 was neurosis, 1 was first-degree disability (vegetative state), 1 was secondary disability (limb dysfunction after hypoxic encephalopathy). The identification of 7 cases of death was affected by the lack of autopsy. One case was settled and the outcome of the third trial was not announced in another case. The remaining 16 medical institutions took 10%-70% of the medical compensation liability, with the compensation amount ranging from 43 092. 4 yuan to 1 615 354 yuan. The main faults of the medical institutions were undetailed drinking history, irregular medication, breaches of duty of reasonable care, failure to fulfill the obligation of informed notification,etc. Conclusions Drug-induced disulfiram-like reaction has the characteristics of graveness of harm and rapid progress. Primary medical institutions need to improve their identification and disposal capacity urgently. Attention should be paid to collecting and recording of drinking history. Antibiotics should be used in a reasonable and compliant manner. Obligation of high attention to patients, information and other obligations should be fulfilled. Hospital pharmacy staff should ensure drug use safety through participating in drug education actively.
