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Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance 黄连温胆汤单用或联合西药治疗痰热内乱致失眠的疗效及安全性meta分析
Q3 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.dcmed.2022.10.010
Y.A.N.G. Lei , H.E. Liyun , C.H.E.N. Xiao , W.A.N.G. Kaiyue , F.A.N.G. Yongjun , L.I.A.N.G. Zhuang , Y.A.N.G. Zhao

Objective

To evaluate the efficacy and safety of Huanglian Wendan Decoction (黄连温胆汤, HLWDD) alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance in recent 10 years.

Methods

The randomized controlled trials of HLWDD alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance from January 1, 2012 to April 1, 2022 were searched in China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, China BioMedical Literature Database (CBM), PubMed, Web of Science, Embase, and Cochrane Library databases. After being screening, the included literature was analyzed to evaluate the effective rate, Pittsburgh Sleep Quality Index (PSQI) score, traditional Chinese medicine (TCM) syndrome score, and adverse reactions of HLWDD on insomnia caused by phlegm-heat internal disturbance. The subgroup analyzed the effect of HLWDD after different treatment courses, and compared the therapeutic effects of HLWDD alone and HLWDD combined with western medicine.

Results

Twenty-seven randomized controlled trials were finally included, with a total of 2 395 patients. The results of the meta-analysis showed that the curative effect of HLWDD alone or combined with the western medicine group was better than that of the western medicine group [RR = 1.14, 95% CI (1.06, 1.22), P = 0.000]. The PSQI score [SMD = – 0.31, 95% CI (– 0.42, – 0.20), P = 0.000], TCM syndrome score [SMD = – 0.40, 95% CI (– 0.67, – 0.12), P = 0.005], and adverse reaction rate [RR = 0.21, 95% CI (0.15, 0.29), P = 0.000] of HLWDD alone or combined with western medicine group were significantly reduced compared with the western medicine group. The subgroup’s analysis showed that the curative effect of HLWDD alone or combined with western medicine group of 4 weeks treatment course was better than that of the western medicine group [RR = 1.14, 95% CI (1.03, 1.26), P < 0.05]. The TCM syndrome score of HLWDD alone or combined with the western medicine group of 4 weeks treatment course decreased more obviously than that of the western medicine group [SMD = – 0.60, 95% CI (– 0.96, – 0.25), P < 0.05]. There were no significant differences between HLWDD alone or combined with western medicine group and western medicine group with different treatment courses based on PSQI score and adverse reaction rate. Based on the effective rate, the comparison between the HLWDD alone group and the western medicine group [RR = 1.09, 95% CI (1.00, – 1.20) P < 0.05], and between the HLWDD combined with western medicine group and the western medicine group [RR = 1.15, 95% CI (1.03, 1.29), P < 0.05] was the same. PSQI score [SMD = – 0.44, 95% CI (– 0.59, – 0.30), P < 0.05] and TCM syndrome score [SMD = – 1.10, 95% CI (– 1.59, – 0.61)

目的评价近10年来黄连温胆汤单用或联用西药治疗痰热内邪性失眠的疗效和安全性。方法检索2012年1月1日至2022年4月1日中国知网(CNKI)、中国科技期刊库(VIP)、万方数据库、中国生物医学文献库(CBM)、PubMed、Web of Science、Embase、Cochrane Library等数据库中单用或联合西药治疗痰热内乱型失眠的随机对照试验。筛选后,对纳入的文献进行分析,评价其有效率、匹兹堡睡眠质量指数(PSQI)评分、中医证候评分及对痰热内耗型失眠的不良反应。亚组分析不同疗程后高脂泻泻的疗效,比较单用高脂泻泻与西药联用高脂泻泻的疗效。结果最终纳入27项随机对照试验,共纳入患者2 395例。meta分析结果显示,单用或联用西药组患者的疗效均优于西药组[RR = 1.14, 95% CI (1.06, 1.22), P = 0.000]。单用或联用西药组的PSQI评分[SMD = - 0.31, 95% CI (- 0.42, - 0.20), P = 0.000]、中医证候评分[SMD = - 0.40, 95% CI (- 0.67, - 0.12), P = 0.005]、不良反应率[RR = 0.21, 95% CI (0.15, 0.29), P = 0.000]均显著低于西药组。亚组分析显示,单用或联合西药组治疗4周疗效优于西药组[RR = 1.14, 95% CI (1.03, 1.26), P <0.05]。治疗4周后,高肝郁单药组或联合西药组中医证候评分较西药组下降更明显[SMD = - 0.60, 95% CI (- 0.96, - 0.25), P <0.05]。在PSQI评分及不良反应发生率方面,高脂寡糖单用或联用西药组与不同疗程西药组比较差异无统计学意义。基于有效率,单药组与西药组比较[RR = 1.09, 95% CI (1.00, - 1.20) P <差异有统计学意义(RR = 1.15, 95% CI (1.03, 1.29), P <0.05]相同。PSQI评分[SMD = - 0.44, 95% CI (- 0.59, - 0.30), P <0.05]和中医证候评分[SMD = - 1.10, 95% CI (- 1.59, - 0.61), P <[0.05]与西药联合治疗组相比,显著低于西药治疗组。两组患者不良反应发生率差异无统计学意义[RR = 0.08, 95% CI (0.04, 0.17), P <[0.05]和HLWDD联合西药组[RR = 0.36, 95% CI (0.24, 0.53), P <0.05]。结论中西医结合治疗痰热内邪失眠有效,有效率高,显著降低PSQI评分和中医证候评分,且安全性较好。最佳疗程为4周。
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引用次数: 0
Exploring the phytoconstituents targeting TNF-α as potential lead compounds to treat inflammatory diseases: an in-silico approach 探索靶向TNF-α的植物成分作为治疗炎症性疾病的潜在先导化合物:一种计算机方法
Q3 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.dcmed.2022.10.003
Sumit Arora (Assistant Professor) , Pallavi Rushiya , Kalpana Tirpude , Nidhi Sapkal , Subhash Yende , Abhay Ittadwar , Sapan Shah

Objective

To explore the anti-inflammatory phytoconstituents from various plant sources as tumour necrosis factor-α (TNF-α)-inhibitor, a mediator involved in the inflammatory disorder, by in silico molecular docking.

Methods

Based on previous findings, we performed the in silico assessment of anti-inflammatory phytoconstituents from different medicinal plants to understand their binding patterns against TNF-α (PDB ID: 6OP0) using AutoDock Vina. Molecular docking was performed by setting a grid box (25 × 25 × 25) Å centered at [– 12.817 × (– 1.618) × 19.009] Å with 0.375 Å of grid spacing. Furthermore, Discovery Studio Client 2020 program was utilized to assess two- and three-dimensional (2D and 3D) hydrogen-bond interactions concerning an amino acid of target and ligand. Physicochemical properties were reported using the Lipinski’s rule and SwissADME database to support the in silico findings. Results From the selected medicinal plants, more than 200 phytocompounds were screened against TNF-α protein with binding scores in the range of – 12.3 to – 2.5 kcal/mol. Amongst them, emodin, aloe-emodin, pongamol, purpuritenin, semiglabrin, ellagic acid, imperatorin, α-tocopherol, and octanorcucurbitacin A showed good binding affinity as – 10.6, – 10.0, – 10.5, – 10.1, – 11.2, – 10.3, – 10.1, – 10.1, and – 10.0 kcal/mol, respectively. Also, the absorption, distribution, metabolism, excretion, and toxicology (ADMET) profiles were well within acceptable limits.

Conclusion

Based on our preliminary findings, we conclude that the selected phytoconstituents have the potential to be good anti-inflammatory candidates by inhibiting the TNF-α target. These compounds can be further optimized and validated as new therapeutic components to develop more effective and safe anti-inflammatory drugs.

目的通过硅分子对接,探索多种植物源中具有抗炎作用的肿瘤坏死因子-α (TNF-α)抑制剂。方法基于已有研究成果,利用AutoDock Vina软件对不同药用植物抗炎成分进行了计算机评价,了解其对TNF-α (PDB ID: 6OP0)的结合模式。通过设置以[- 12.817 × (- 1.618) × 19.009] Å为中心,网格间距为0.375 Å的网格框(25 × 25 × 25) Å进行分子对接。此外,利用Discovery Studio Client 2020程序来评估涉及靶和配体氨基酸的二维和三维(2D和3D)氢键相互作用。使用Lipinski规则和SwissADME数据库报告了物理化学性质,以支持计算机上的发现。结果从所选药用植物中筛选出200多种抗TNF-α蛋白的化合物,结合分数在- 12.3 ~ - 2.5 kcal/mol之间。其中,大黄素、芦荟大黄素、蒲加酚、紫皮素、半红素、鞣花酸、欧前胡素、α-生育酚和辛酸葫芦素A的结合亲和力分别为- 10.6、- 10.0、- 10.5、- 10.1、- 11.2、- 10.3、- 10.1、- 10.1和- 10.0 kcal/mol。此外,其吸收、分布、代谢、排泄和毒理学(ADMET)指标均在可接受范围内。结论根据我们的初步研究结果,我们得出结论,所选择的植物成分可能通过抑制TNF-α靶点而成为良好的抗炎候选者。这些化合物可以进一步优化和验证为新的治疗成分,以开发更有效和安全的抗炎药物。
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引用次数: 0
Tongue image segmentation and tongue color classification based on deep learning 基于深度学习的舌图像分割和舌色分类
Q3 Medicine Pub Date : 2022-09-01 DOI: 10.1016/j.dcmed.2022.10.002
L.I.U. Wei, C.H.E.N. Jinming, L.I.U. Bo, H.U. Wei, W.U. Xingjin, Z.H.O.U. Hui

Objective

To propose two novel methods based on deep learning for computer-aided tongue diagnosis, including tongue image segmentation and tongue color classification, improving their diagnostic accuracy.

Methods

LabelMe was used to label the tongue mask and Snake model to optimize the labeling results. A new dataset was constructed for tongue image segmentation. Tongue color was marked to build a classified dataset for network training. In this research, the Inception + Atrous Spatial Pyramid Pooling (ASPP) + UNet (IAUNet) method was proposed for tongue image segmentation, based on the existing UNet, Inception, and atrous convolution. Moreover, the Tongue Color Classification Net (TCCNet) was constructed with reference to ResNet, Inception, and Triple-Loss. Several important measurement indexes were selected to evaluate and compare the effects of the novel and existing methods for tongue segmentation and tongue color classification. IAUNet was compared with existing mainstream methods such as UNet and DeepLabV3+ for tongue segmentation. TCCNet for tongue color classification was compared with VGG16 and GoogLeNet.

Results

IAUNet can accurately segment the tongue from original images. The results showed that the Mean Intersection over Union (MIoU) of IAUNet reached 96.30%, and its Mean Pixel Accuracy (MPA), mean Average Precision (mAP), F1-Score, G-Score, and Area Under Curve (AUC) reached 97.86%, 99.18%, 96.71%, 96.82%, and 99.71%, respectively, suggesting IAUNet produced better segmentation than other methods, with fewer parameters. Triplet-Loss was applied in the proposed TCCNet to separate different embedded colors. The experiment yielded ideal results, with F1-Score and mAP of the TCCNet reached 88.86% and 93.49%, respectively.

Conclusion

IAUNet based on deep learning for tongue segmentation is better than traditional ones. IAUNet can not only produce ideal tongue segmentation, but have better effects than those of PSPNet, SegNet, UNet, and DeepLabV3+, the traditional networks. As for tongue color classification, the proposed network, TCCNet, had better F1-Score and mAP values as compared with other neural networks such as VGG16 and GoogLeNet.

目的提出基于深度学习的舌头图像分割和舌头颜色分类两种新的计算机辅助舌头诊断方法,提高其诊断准确率。方法采用labelme软件对舌膜和Snake模型进行标记,优化标记效果。构建了一个新的舌图像分割数据集。对舌色进行标记,建立分类数据集用于网络训练。本研究在现有UNet、Inception和Atrous卷积的基础上,提出了Inception + Atrous空间金字塔池(ASPP) + UNet (IAUNet)舌头图像分割方法。此外,参考ResNet、Inception和Triple-Loss构建了舌色分类网(TCCNet)。选择了几个重要的测量指标来评价和比较新的和现有的舌头分割和舌头颜色分类方法的效果。将iunet与UNet、DeepLabV3+等现有主流舌头分割方法进行比较。将TCCNet与VGG16和GoogLeNet进行舌色分类比较。结果该方法能准确地从原始图像中分割出舌形。结果表明,IAUNet的平均相交度(MIoU)达到96.30%,平均像素精度(MPA)、平均平均精度(mAP)、F1-Score、G-Score和曲线下面积(AUC)分别达到97.86%、99.18%、96.71%、96.82%和99.71%,表明IAUNet的分割效果优于其他方法,且参数较少。在TCCNet中应用三重损耗来分离不同的嵌入颜色。实验取得了理想的结果,TCCNet的F1-Score和mAP分别达到88.86%和93.49%。结论基于深度学习的iaunet对舌语的分割效果优于传统方法。IAUNet不仅可以产生理想的舌段分割,而且比PSPNet、SegNet、UNet、DeepLabV3+等传统网络的舌段分割效果更好。在舌色分类方面,与VGG16、GoogLeNet等神经网络相比,本文提出的网络TCCNet具有更好的F1-Score和mAP值。
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引用次数: 3
Visualization analysis of the international standard ISO/TC 249 for traditional Chinese medicine 中药国际标准ISO/TC 249的可视化分析
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.001
Zhao Shuting , Zhong Yanmei , Hu Yuanzhang , Sun Tao , Wu Chunjie , Wen Chuanbiao

Objective

This study proposes to visually review the current situation and progress of standards sets by the International Organization for Standardization/Technical Committee on Traditional Chinese Medicine (ISO/TC 249). The review aims to explore the development strategies of the standards, which will exhibit the considerable impact on the economy, trade and exchanges, and cooperation in the area of traditional Chinese medicine (TCM).

Methods

ISO/TC 249 standards were searched on the ISO website, and their title, proposed time, current stage, scope, and classification were obtained for further summarization. Gephi was utilized to portray the co-occurrence network graph of the ISO/TC 249 standards subject.

Results

In ISO/TC 249, there were 116 standards, including 81 published standards and 35 developing standards by April 30, 2022. Two withdrawal standards were published after revision, which were not counted in the total standards. The number of published standards has been increasing since the first standard was published in 2014, whose title was “Sterile acupuncture needles for single use”. Among these standards, 17.24% (20/116) standards were in review, 56.03% (65/116) in publication, 3.45% (4/116) in approval, 5.17% (6/116) in enquiry, 3.45% (4/116) in committee, and 14.66% (17/116) in preparation, respectively. With 116 standards, most of the research focused on the medicament, as its classification of the International Classification for Standards (ICS) showed the proportion reaching 49.54%. The network analysis data revealed that the top five most frequent words were “materials” “root” “requirements” “products” and “system”, after removing the noise data, such as prepositions, conjunctions, and pronouns. Additionally, the word “system” co-exists with the terms “computerized” “coding” “image” “tongue” and “analysis”; the word “requirement” co-exists with “manufacturing” “decoction” “process” and “materials”; whereas the word “devices” co-exists with “pulse” “electric” “skin” and “measurement”.

Conclusion

With the increased diversification and complexity of problems, the development of standards is also oriented to multidisciplinary fields to cultivate the interdisciplinary talents, and especially the international standardization talents of compound TCM. Multi-angle analysis, formulation, and demonstration of standards, in line with industry needs in different disciplines, enhance the availability of standards and the ability to serve the industry.

目的对国际标准化组织/中医药技术委员会(ISO/ tc249)标准制定的现状和进展进行综述。审查旨在探讨标准的发展战略,这将对经济、贸易和交流以及中医药领域的合作产生重大影响。方法在ISO网站上检索ISO/ tc249标准,获取其标题、拟制定时间、目前阶段、范围、分类等信息,进行进一步总结。采用Gephi来描绘ISO/TC 249标准主题的共现网络图。结果截至2022年4月30日,ISO/TC 249共有116项标准,其中已发布标准81项,正在制定标准35项。修订后发布了两个退出标准,不计入总标准。自2014年第一个标准《一次性使用无菌针灸针》发布以来,已发布的标准数量不断增加。其中,17.24%(20/116)的标准处于评审阶段,56.03%(65/116)的标准处于公布阶段,3.45%(4/116)的标准处于批准阶段,5.17%(6/116)的标准处于调查阶段,3.45%(4/116)的标准处于委员会阶段,14.66%(17/116)的标准处于准备阶段。该药物的研究以116项标准为主,其在国际标准分类(ICS)中的分类比例达到49.54%。网络分析数据显示,除去介词、连词、代词等噪音数据后,使用频率最高的前5个词分别是“材料”、“根”、“要求”、“产品”和“系统”。此外,“系统”一词与“计算机化”、“编码”、“图像”、“语言”和“分析”共存;“需”字与“制”、“煮”、“制”、“料”共存;然而,“设备”一词与“脉冲”、“电子”、“皮肤”和“测量”共存。结论随着问题的日益多样化和复杂化,标准的制定也应面向多学科领域,培养复合型人才,特别是复方中药国际化标准化人才。多角度分析、制定、论证标准,符合行业不同学科的需求,增强标准的可用性和服务行业的能力。
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引用次数: 1
Protective effects of Zuogui Jiangtang Jieyu Formula on hippocampal neurons in rats of diabetes complicated with depression via the TRP/KYN metabolic pathway 左归降糖解郁方通过TRP/KYN代谢途径对糖尿病合并抑郁症大鼠海马神经元的保护作用
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.010
Ling Jia , Liu Jian , Jin Shi , Zou Manshu , Jiang Yajie , Wang Yuhong

Objective

To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZGJTJYF) on hippocampal neurons in rats of diabetes complicated with depression (DD) via the TRP/KYN metabolic pathway.

Methods

(i) In vivo experiments: 60 specified pathogen free (SPF) grade male Sprague-Dawley (SD) rats were randomly divided into six groups with 10 rats in each groups: control, DD model, positive (1.8 mg/kg fluoxetine + 0.18 g/kg metformin), high-dose ZGJTJYF (ZGJTJYF-H, 40.500 g/kg ZGJTJYF), middle-dose ZGJTJYF (ZGJTJYF-M, 20.250 g/kg ZGJTJYF), and low-dose ZGJTJYF (ZGJTJYF-L, 10.125 g/kg ZGJTJYF) groups. Except for the control group, other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin (STZ) and four weeks of chronic unpredictable mild stress (CUMS). All drug administration groups were treated by gavage during CUMS modeling, and the control and model groups were given equal amount of distilled water. After four weeks, the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF. Moreover, the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF. Changes in 5-hydroxytryptamine (5-HT) level were detected via high-performance liquid chromatography with electrochemical detection (HPLC-ECD); the levels of tryptophan (TRP), kynurenine (KYN), and indoleamine 2,3-dioxygenase (IDO) in the hippocampus were detected using enzyme-linked immunosorbent assay (ELISA); the protein expression levels of synaptophysin (SYN) and postsynaptic density material-95 (PSD-95) were detected via immunohistochemistry (IHC); and the protein expression levels of N-methyl-D-aspartate receptor (NR) 2A and NR2B were detected using Western blot. (ii) In vitro experiments: five SPF grade SD pregnant rats (E16 – 18) were used to obtain primary hippocampal neurons (Ne), six SD new-born rats were used to collected primary astrocytes (As) and microglia (MG), and to establish a Ne-As-MG co-culture system. All co-culture systems were divided into six groups: control (PBS), model [150 mmol/L glucose + 200 μmol/L corticosterone (G&P) + PBS], blank (G&P + blank serum), positive (G&P + positive drug-containing serum), ZGJTJYF (G&P + ZGJTJYF serum), and 1-methyl-D-tryptophan (1-MT, IDO inhibitor) (G&P + 1-MT) groups. After 18 h of intervention by corresponding treatment, immunofluorescence was used to analyze the protein expression levels of SYN, PSD-95, NR2A, and NR2B; ELISA was performed to measure the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α , and TRP/KYN metabolic pathway-related factors [TRP, KYN, kynurenine acid (KYNA), quinolinic acid (QUIN)].

Results

(i) In vivo experimental<italic/> results showed that ZGJTJYF-M and ZGJTJYF-L significantl

目的探讨左归降糖解郁方(ZGJTJYF)通过TRP/KYN代谢途径对糖尿病合并抑郁症(DD)大鼠海马神经元的保护作用及其机制。方法(i)体内实验:选取SPF级雄性SD大鼠60只,随机分为6组,每组10只;对照组、DD模型、阳性组(氟西汀1.8 mg/kg +二甲双胍0.18 g/kg)、高剂量组(ZGJTJYF- h、40.500 g/kg ZGJTJYF)、中剂量组(ZGJTJYF- m、20.250 g/kg ZGJTJYF)、低剂量组(ZGJTJYF- l、10.125 g/kg ZGJTJYF)。除对照组外,其余各组均采用高脂乳剂饲喂单尾静脉链脲佐菌素(STZ)和慢性不可预测轻度应激(CUMS) 4周建立DD模型。各给药组均在CUMS造模期间灌胃,对照组和模型组灌胃等量蒸馏水。4周后,测定血清血糖和糖化血红蛋白水平,以确定ZGJTJYF的降糖作用。另外,采用开放场试验和Morris水迷宫试验来评价ZGJTJYF的抗抑郁作用。采用高效液相色谱-电化学检测(HPLC-ECD)检测5-羟色胺(5-HT)水平的变化;采用酶联免疫吸附法(ELISA)检测海马组织中色氨酸(TRP)、犬尿氨酸(KYN)、吲哚胺2,3-双加氧酶(IDO)水平;免疫组化(IHC)检测突触物理素(SYN)和突触后密度物质-95 (PSD-95)蛋白表达水平;Western blot检测n -甲基- d -天冬氨酸受体(NR) 2A和NR2B的蛋白表达水平。(ii)体外实验:取5只SPF级SD孕鼠(E16 ~ 18)获取海马原代神经元(Ne),取6只SD新生大鼠收集原代星形胶质细胞(As)和小胶质细胞(MG),建立Ne-As-MG共培养体系。共培养体系分为6组:对照组(PBS)、模型组[150 mmol/L葡萄糖+ 200 μmol/L皮质酮(G&P) + PBS]、空白组(G&P +空白血清)、阳性组(G&P +阳性含药血清)、ZGJTJYF组(G&P + ZGJTJYF血清)和1-甲基- d -色氨酸(1-MT, IDO抑制剂)(G&P + 1-MT)组。相应处理干预18 h后,采用免疫荧光法分析SYN、PSD-95、NR2A、NR2B蛋白表达水平;ELISA法检测各组大鼠血清中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α和TRP/KYN代谢途径相关因子[TRP、KYN、犬尿氨酸(KYNA)、喹啉酸(QUIN)]的水平。结果显示,ZGJTJYF-M和ZGJTJYF-L可显著改善DD大鼠的血糖升高状态(P <0.01和P <分别为0.05);ZGJTJYF-H、ZGJTJYF-M和ZGJTJYF-L均提高了自主活动、学习和记忆能力(P <0.01, P <0.01, P <分别为0.05)。5-羟色胺和色氨酸水平显著升高(P <0.01),海马KYN、IDO水平显著降低(P <0.01)。海马神经元中SYN和PSD-95蛋白表达水平显著上调(P <0.01),而海马NR2A和NR2B的异常激活明显受到抑制(P <0.05)。(ii)体外实验结果显示,含zgjtjyf血清显著提高海马神经元SYN和PSD-95蛋白表达水平(P <0.01), IL-1β水平降低(P <0.01), IL-6 (P <0.05), TNF-α (P <0.01), IDO (P <0.05), KYN (P <0.05), QUIN (P <0.01), TRP和KYNA水平升高(P <0.01)在模拟DD状态下。ZGJTJYF对神经元中NR2A和NR2B的异常激活也有显著抑制作用(P <0.05),处于受激DD状态。结论ZGJTJYF可通过抑制IDO表达和调节TRP/KYN代谢途径,有效改善大鼠海马5-HT缺乏症,对DD所致海马神经元损伤具有良好的保护作用,是一种预防和治疗DD的潜在有效治疗药物。
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引用次数: 1
Screening influencing factors of blood stasis constitution in traditional Chinese medicine 中医瘀血体质影响因素的筛选
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.006
Zhou Xiaoying , Yang Shengwen , Ou Jintao , Wang Zhuo , Wang Guangrong , Luo Yue

Objective

To study the influencing factors of blood stasis constitution and provide a basis for treating blood stasis-related diseases by traditional Chinese medicine (TCM) constitution identification.

Methods

Data were collected using the self-developed TCM constitution identification platform based on B/S model by the project team. The obtained data were divided into blood stasis constitution and normal constitution groups. The differences of the categorical type influencing factors (gender, birth mode, feeding mode within four months of birth, family history, marital status, eating habits, sleeping habits, exercise habits, emotional state, stress situation, and living environment) and the quantitative type influencing factors (sleep time, age, and mother's age at birth) on the constitution of the two groups were analyzed. In the single-factor analysis, the Pearson's chi-square test was selected for the categorical variable, and the independent sample t test and Mann-Whitney U nonparametric test were selected for the quantitative variables according to whether they conformed to the positive-terrestrial distribution; the binary logistic stepwise regression method was selected for the multi-factor analysis.

Results

The data of 318 cases were collected from the TCM composition identification platform, and 159 cases of blood stasis constitution were used as the experimental group and 159 cases of normal constitution were used as the control group. The Pearson's chi-square test yielded significant differences (P < 0.05) in the effects of gender, pressure situation, family history, living environment, emotional state, exercise habits, and dietary habits on blood stasis constitution. The independent samples t test yielded differences in sleep duration between the blood stasis constitution and normal constitution populations (P < 0.05), which meant sleep duration of the blood stasis constitution population was less than that of the normal constitution population. The Mann-Whitney U nonparametric test results accepted the original hypothesis that there was no difference in the distribution of age and mother’s age at birth across constitution types (P > 0.05). Binary logistic regression analysis showed that gender, family history, marital status, living environment, exercise habits, and emotional state were risk factors for blood stasis constitution (P < 0.05).

Conclusion

Gender, family history, living environment, emotional state, and exercise habits were significant influencing factors of blood stasis constitution. Blood stasis constitution populations can pay more attention to these influencing factors in their daily life for the prevention and reconciliation of blood stasis constitution.

目的探讨血瘀体质的影响因素,为中医体质鉴定治疗血瘀相关疾病提供依据。方法采用项目组自行开发的基于B/S模式的中药体质识别平台进行数据采集。将所得数据分为血瘀体质组和正常体质组。分析两组儿童的分类型影响因素(性别、出生方式、出生后4个月内的喂养方式、家族史、婚姻状况、饮食习惯、睡眠习惯、运动习惯、情绪状态、应激状况、生活环境)和定量型影响因素(睡眠时间、年龄、母亲出生年龄)对体质的影响差异。单因素分析中,分类变量采用皮尔逊卡方检验,定量变量根据是否符合正大地分布采用独立样本t检验和Mann-Whitney U非参数检验;采用二元logistic逐步回归法进行多因素分析。结果从中药成分鉴定平台收集318例患者资料,其中血瘀体质者159例为实验组,正常体质者159例为对照组。皮尔逊卡方检验显示显著差异(P <性别、压力状况、家族史、生活环境、情绪状态、运动习惯、饮食习惯对血瘀体质的影响0.05)。独立样本t检验显示血瘀体质与正常体质人群的睡眠时间存在差异(P <0.05),说明血瘀体质人群睡眠时间少于正常体质人群。Mann-Whitney U非参数检验结果接受了最初的假设,即不同体质类型的年龄和母亲出生年龄的分布没有差异(P >0.05)。二元logistic回归分析显示,性别、家族史、婚姻状况、生活环境、运动习惯、情绪状态是血瘀体质的危险因素(P <0.05)。结论性别、家族史、生活环境、情绪状态、运动习惯是血瘀体质的重要影响因素。血瘀体质人群在日常生活中可多注意这些影响因素,以预防和调和血瘀体质。
{"title":"Screening influencing factors of blood stasis constitution in traditional Chinese medicine","authors":"Zhou Xiaoying ,&nbsp;Yang Shengwen ,&nbsp;Ou Jintao ,&nbsp;Wang Zhuo ,&nbsp;Wang Guangrong ,&nbsp;Luo Yue","doi":"10.1016/j.dcmed.2022.06.006","DOIUrl":"10.1016/j.dcmed.2022.06.006","url":null,"abstract":"<div><h3>Objective</h3><p>To study the influencing factors of blood stasis constitution and provide a basis for treating blood stasis-related diseases by traditional Chinese medicine (TCM) constitution identification.</p></div><div><h3>Methods</h3><p>Data were collected using the self-developed TCM constitution identification platform based on B/S model by the project team. The obtained data were divided into blood stasis constitution and normal constitution groups. The differences of the categorical type influencing factors (gender, birth mode, feeding mode within four months of birth, family history, marital status, eating habits, sleeping habits, exercise habits, emotional state, stress situation, and living environment) and the quantitative type influencing factors (sleep time, age, and mother's age at birth) on the constitution of the two groups were analyzed. In the single-factor analysis, the Pearson's chi-square test was selected for the categorical variable, and the independent sample <em>t</em> test and Mann-Whitney U nonparametric test were selected for the quantitative variables according to whether they conformed to the positive-terrestrial distribution; the binary logistic stepwise regression method was selected for the multi-factor analysis.</p></div><div><h3>Results</h3><p>The data of 318 cases were collected from the TCM composition identification platform, and 159 cases of blood stasis constitution were used as the experimental group and 159 cases of normal constitution were used as the control group. The Pearson's chi-square test yielded significant differences (<em>P</em> &lt; 0.05) in the effects of gender, pressure situation, family history, living environment, emotional state, exercise habits, and dietary habits on blood stasis constitution. The independent samples <em>t</em> test yielded differences in sleep duration between the blood stasis constitution and normal constitution populations (<em>P</em> &lt; 0.05), which meant sleep duration of the blood stasis constitution population was less than that of the normal constitution population. The Mann-Whitney U nonparametric test results accepted the original hypothesis that there was no difference in the distribution of age and mother’s age at birth across constitution types (<em>P</em> &gt; 0.05). Binary logistic regression analysis showed that gender, family history, marital status, living environment, exercise habits, and emotional state were risk factors for blood stasis constitution (<em>P</em> &lt; 0.05).</p></div><div><h3>Conclusion</h3><p>Gender, family history, living environment, emotional state, and exercise habits were significant influencing factors of blood stasis constitution. Blood stasis constitution populations can pay more attention to these influencing factors in their daily life for the prevention and reconciliation of blood stasis constitution.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377722000337/pdfft?md5=fbab4fbab72bf52951db93fd3b2de3d0&pid=1-s2.0-S2589377722000337-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73889084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preventive and therapeutic effects of Aerva lanata (L.) extract on ethylene glycol-induced nephrolithiasis in male Wistar albino rats 鹿茸提取物对乙二醇致雄性Wistar白化大鼠肾结石的防治作用
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.009
Ankul Singh S, Chitra Vellapandian, Gowri Krishna

Objective

Nephrolithiasis is a common urological disease. This study aims to evaluate the preventive and therapeutic effects of hydro-alcoholic extract of Aerva lanata (L.) roots (HAEAL) on ethylene glycol-induced nephrolithiasis in rats.

Methods

Fifty grams of shade-dried coarsely powdered Aerva lanata (L.) root was successively extracted with organic solvents in increasing order of polarity [petroleum ether (60 −80 °C), chloroform, and ethanol] using a Soxhlet apparatus, and then concentrated. Physical tests including nature, color, odor, and texture were performed on the herbal suspension. In vitro nephrolithiasis assessment was performed by nucleation assay, aggregation assay, and crystal growth assay. Thirty adult male Wistar albino rats were randomly divided into five groups (six rats in each group). Group 1: negative control group without induction or treatment till day 28. Group 2: positive control group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and mixed with distilled water till day 28. Group 3: standard group receiving a daily oral solution of 0.75% ethylene glycol till day 14 and Cystone (750 mg/kg) from day 15 to day 28. Group 4: low dose HAEAL group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and 400 mg/kg HAEAL from day 15 to day 28 (1 mL per day). Group 5: high dose HAEAL group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and 800 mg/kg HAEAL from day 15 to day 28 (1 mL per day). Urine (urine volume, pH value, appearance, odor, and turbidity) examination and serum test were performed. On day 29, the kidneys were dissected, and histopathology examination was performed to determine the degree of tubular injury.

Results

The suspension showed stability and aroma with no turbidity at room temperature. The suspension did not show changes in color and odor until day 3, indicating that the preparation was stable for 72 h. Body weight decreased in the positive control group indicating stone formation and changes in water intake. Both standard and HAEAL treatments restored the body weight to normal levels after treatment, indicating the beneficial effects of the treatment. Histopathological examination revealed no significant findings in the negative control group, whereas the positive control group showed inflammation in the kidney parenchyma. Compared with positive control group, there was increase in urine volume and excretion of urinary constituents such as calcium and oxalate (P < 0.01) as well as improved clearance rate (P < 0.05) in HAEAL treatment groups, in addition, the urine pH value of HAEAL groups was increased.

Conclusion

HAEAL reduced nephrolithiasis formation and had a diuretic effect, which could be used to promote the expulsion of stones. Further studies are needed to enhance the stability of the suspension

目的肾结石是泌尿系统常见病。本研究旨在探讨银叶根水酒精提取物(HAEAL)对乙二醇所致大鼠肾结石的预防和治疗作用。方法采用索氏装置,用极性依次为石油醚(60 ~ 80℃)、氯仿、乙醇的有机溶剂分别提取50 g阴凉干燥的粗粉雪芹根,然后浓缩。对草药悬浮液进行了性质、颜色、气味和质地等物理测试。体外肾结石评估采用成核试验、聚集试验和晶体生长试验。选取成年雄性Wistar白化大鼠30只,随机分为5组,每组6只。第1组:阴性对照组,不进行诱导或治疗至第28天。组2:阳性对照组每日口服0.75%乙二醇溶液至第14天,并与蒸馏水混合至第28天。组3:标准组每日口服0.75%乙二醇溶液至第14天,第15天至第28天口服赛石(750 mg/kg)。第4组:低剂量HAEAL组每日口服0.75%乙二醇溶液至第14天,第15天至第28天每日口服400 mg/kg HAEAL(每天1ml)。第5组:高剂量HAEAL组每日口服0.75%乙二醇溶液至第14天,第15天至第28天每日口服800 mg/kg HAEAL(每天1ml)。进行尿液(尿量、pH值、外观、气味和浊度)检查和血清试验。第29天,解剖肾脏,进行组织病理学检查以确定肾小管损伤程度。结果该悬浮液稳定性好,常温下无浑浊,香气良好。悬浮液直到第3天才出现颜色和气味的变化,表明制剂在72小时内是稳定的。阳性对照组体重下降,表明结石形成和饮水量的变化。治疗后,标准和HAEAL治疗均使体重恢复到正常水平,表明治疗的有益效果。阴性对照组组织病理检查未见明显变化,阳性对照组肾实质可见炎症。与阳性对照组相比,尿量增加,尿液成分如钙和草酸盐的排泄量增加(P <0.01)和提高的清除率(P <治疗组尿pH值显著高于对照组(0.05),且各组尿液pH值均升高。结论haeal可减少肾结石的形成,具有利尿作用,可促进肾结石的排出。需要进一步的研究来提高悬浮液的稳定性,以生产更好的药物制剂。
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引用次数: 4
MEDICLOUD: a holistic study on the digital evolution of medical data MEDICLOUD:医疗数据数字化演进的整体研究
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.002
Astha Modi , Nandish Bhayani , Samir Patel , Manan Shah

The Corona Virus Disease 2019 (COVID-19) pandemic has taught us many valuable lessons regarding the importance of our physical and mental health. Even with so many technological advancements, we still lag in developing a system that can fully digitalize the medical data of each individual and make it readily accessible for both the patient and health worker at any point in time. Moreover, there are also no ways for the government to identify the legitimacy of a particular clinic. This study merges modern technology with traditional approaches, thereby highlighting a scenario where artificial intelligence (AI) merges with traditional Chinese medicine (TCM), proposing a way to advance the conventional approaches. The main objective of our research is to provide a one-stop platform for the government, doctors, nurses, and patients to access their data effortlessly. The proposed portal will also check the doctors’ authenticity. Data is one of the most critical assets of an organization, so a breach of data can risk users' lives. Data security is of primary importance and must be prioritized. The proposed methodology is based on cloud computing technology which assures the security of the data and avoids any kind of breach. The study also accounts for the difficulties encountered in creating such an infrastructure in the cloud and overcomes the hurdles faced during the project, keeping enough room for possible future innovations. To summarize, this study focuses on the digitalization of medical data and suggests some possible ways to achieve it. Moreover, it also focuses on some related aspects like security and potential digitalization difficulties.

2019冠状病毒病(COVID-19)大流行给我们上了许多关于身心健康重要性的宝贵教训。即使有了如此多的技术进步,我们在开发一个能够将每个人的医疗数据完全数字化并使患者和卫生工作者在任何时间点都能方便地访问这些数据的系统方面仍然落后。此外,政府也没有办法确定特定诊所的合法性。本研究将现代技术与传统方法相结合,从而突出了人工智能(AI)与传统医学(TCM)相结合的场景,提出了一种推进传统方法的方法。我们研究的主要目的是为政府、医生、护士和患者提供一个一站式的平台,让他们毫不费力地访问他们的数据。拟议中的门户网站还将检查医生的真实性。数据是组织最重要的资产之一,因此数据泄露可能会危及用户的生命。数据安全至关重要,必须优先考虑。该方法基于云计算技术,保证了数据的安全性,避免了任何形式的泄露。该研究还解释了在云中创建这样一个基础设施所遇到的困难,并克服了项目中面临的障碍,为未来可能的创新保留了足够的空间。综上所述,本研究的重点是医疗数据的数字化,并提出了一些可能的实现方法。此外,本文还重点讨论了一些相关方面,如安全性和潜在的数字化困难。
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引用次数: 0
Mechanisms of Dihuang (Rehmanniae Radix) in treating diabetic nephropathy complicated with depression based on network pharmacology 地黄治疗糖尿病肾病伴抑郁的网络药理学机制
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.007
Lei Xing , Chen Qingyao , Wang Xiaoping , Xu Jie , Gao Yazhen , Lin Qiaohong , Ye Zuwen , Zhang Jieyan , Si Qin , Wang Fang

Objective

To predict the molecular mechanism of Dihuang (Rehmanniae Radix) in the treatment of diabetic nephropathy (DN) complicated with depression based on network pharmacology.

Methods

The components of Dihuang (Rehmanniae Radix) were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and relevant literature. The component targets were detected by combining the SwissTargetPrediction and PubChem databases. Disease targets were collected from the Therapeutic Target Database (TTD), DisGeNET, and Ensembl databases with “diabetic nephropathy” and “depression” as keywords. The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape 3.7.2. The co-expression genes of the key targets were collected based on the COXPRESdb 7.3. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for potential targets using R language. Target-component docking was verified and evaluated using Discovery Studio 4.5.

Results

According to the databases and literature reports, Dihuang (Rehmanniae Radix) contained 65 active components, and had 155 related targets for the treatment of DN complicated with depression. PPI screening showed that the key targets included serine/threonine protein kinase 1 (AKT1), signal transducer and activator transcription 3 (STAT3), interleukin 6 (IL-6), mitogen-activated protein kinase 1 (MAPK1), and vascular endothelial growth factor A (VEGFA), etc. GO enrichment analysis mainly involved biological processes, such as lipid metabolism, protein secretion regulation, cell homeostasis, and phosphatidylinositol 3 kinase activity. KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements, insulin resistance (IR), neurotrophin signal path, Toll-like receptor signaling pathway, relaxin signaling pathway, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), etc. Molecular docking showed that the target had high affinity for stachyose, manninotriose, verbascose, nigerose, etc.

Conclusion

Based on network parmacology, this study preliminarily predict the effects of Dihuang (Rehmanniae Radix) in treating DN complicated with depression by regulating inflammation, glucose metabolism, nution nerve, etc.

目的基于网络药理学,探讨地黄治疗糖尿病肾病(DN)合并抑郁的分子机制。方法通过中药综合药理学研究平台(TCMIP)、中药系统药理学数据库与分析平台(TCMSP)及相关文献对地黄进行成分鉴定。通过结合SwissTargetPrediction和PubChem数据库检测组件目标。从治疗靶点数据库(TTD)、DisGeNET和Ensembl数据库中收集疾病靶点,以“糖尿病肾病”和“抑郁症”为关键词。利用Venny 2.1.0软件绘制疾病组分靶点,获取潜在靶点。利用Search Tool for Retrieval of Interacting Genes/Proteins (STRING)数据库和Cytoscape 3.7.2构建蛋白-蛋白相互作用(PPI)网络。基于COXPRESdb 7.3收集关键靶点的共表达基因。利用R语言对潜在目标进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用Discovery Studio 4.5对目标组件对接进行验证和评估。结果根据数据库和文献报道,地黄中含有65种有效成分,155个相关靶点治疗DN合并抑郁症。PPI筛选显示,关键靶点包括丝氨酸/苏氨酸蛋白激酶1 (AKT1)、信号传导与激活因子转录3 (STAT3)、白细胞介素6 (IL-6)、丝裂原活化蛋白激酶1 (MAPK1)、血管内皮生长因子A (VEGFA)等。氧化石墨烯富集分析主要涉及脂质代谢、蛋白质分泌调节、细胞稳态和磷脂酰肌醇3激酶活性等生物学过程。KEGG通路富集分析包括AGE-RAGE信号通路在糖尿病补体、胰岛素抵抗(IR)、神经营养因子信号通路、toll样受体信号通路、松弛素信号通路、表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)等中的作用。分子对接表明,该靶点对水苏糖、甘露糖、毛蕊糖、黑糖等具有较高的亲和力。结论基于网络药理学,本研究初步预测地黄通过调节炎症、糖代谢、神经等作用治疗DN合并抑郁。
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引用次数: 2
Intra-set correlation analysis of medical records of thyroid cancer treated by traditional Chinese medicine Master ZHOU Zhongying 中医大师周忠英治疗甲状腺癌病历集内相关分析
Q3 Medicine Pub Date : 2022-06-01 DOI: 10.1016/j.dcmed.2022.06.004
Xu Ziyuan , Zhu Yao , Lu Ming , Zhou Zhongying

Objective

Based on intra-set correlation analysis, this paper deconstructs the clinical medical records of traditional Chinese medicine (TCM) Master ZHOU Zhongying in treating thyroid cancer, and analyzes the experience in “mechanism-syndrome-medicine-prescription” for thyroid cancer.

Methods

Through Medcase data processing platform, based on Frequent Pattern (FP)-Growth enhanced correlation analysis algorithm, the medical records of Professor ZHOU Zhongying for the treatment of thyroid cancer from June 1, 2001 to February 28, 2015 were analyzed within the set.

Results

This study involved 43 medical records, 43 patients, and 167 visits. After processing intra-set correlations, 28 groups of highly correlated symptoms, 21 groups of highly correlated tongue images, 10 groups of highly correlated pulse conditions, 28 groups of highly correlated pathogenesis, 34 groups of highly correlated herbs, and 26 groups of highly correlated western medicine diagnosis were selected. Professor ZHOU Zhongying treats thyroid cancer according to syndrome differentiation. Symptoms with more association rules included neck swelling, neck pain, cough, and dry mouth; tongue images with more association rules included dark purple tongue, dark red tongue, and fissured tongue; pulse conditions with more association rules were wiry pulse, thready pulse, small pulse, and slippery pulse; the pathogenesis with more association rules was phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin; herbs with more association rules were Chaihu (Bupleuri Radix), Zeqi (Sun Euphoribiae Herb), and Tiandong (Asparagi Radix); western medicine diagnosis with more association rules included thyroid cancer, insomnia, and chronic gastritis.

Conclusion

Thyroid cancer mostly presents as deficiency in origin and excess in manifestations. The basic pathogenesis is phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin, which are closely related to liver, kidney, and spleen. Professor ZHOU Zhongying adopts both attack and supplement approaches as the general treatment principle, with a strong emphasis on regulating Qi and relieving depression, eliminating phlegm and resolving stagnation, eliminating dampness and turbidity, clearing fire and destroying poison, moistening dryness and softening hard mass, invigorating Qi and nourishing Yin, and paying attention to nourishing liver and kidney, invigorating spleen and stomach, while protecting the heart and lungs.

目的通过集内相关分析,对中医大师周忠英治疗甲状腺癌的临床病历进行解构,分析其“机-证-药-方”治疗甲状腺癌的经验。方法通过Medcase数据处理平台,基于频繁模式(FP)-增长增强相关分析算法,对周忠英教授2001年6月1日至2015年2月28日治疗甲状腺癌的病历进行集内分析。结果本研究涉及43份医疗记录,43名患者,167次就诊。经组内相关性处理后,选取28组高相关症状、21组高相关舌像、10组高相关脉象、28组高相关病机、34组高相关中药、26组高相关西药诊断。周忠英教授以辨证论治甲状腺癌。关联规则较多的症状包括颈部肿胀、颈部疼痛、咳嗽和口干;联想规则较多的舌象包括深紫色舌、深红色舌和裂隙舌;关联规则较多的脉象为细脉象、细脉象、小脉象和滑脉象;关联规律较多的病机为痰血瘀、湿热积存、气阴双全;关联规则较多的中药有柴胡、泽七、天冬;西医诊断关联规则较多的有甲状腺癌、失眠、慢性胃炎等。结论甲状腺癌多表现为源虚多亢。其基本病机为痰瘀瘀、湿热积存、气阴双损,与肝、肾、脾密切相关。周忠英教授以攻补并作为主的治疗原则,强调调气解郁、化痰化瘀、祛湿浊、清火解毒、润燥柔硬团、益气养阴,注意养肝养肾、健脾益胃、护心肺。
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引用次数: 0
期刊
Digital Chinese Medicine
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