[Mystery of Yiyin decoction theory: rule discovery and evaluation strategy of atypical pharmacological effects of Chinese medicinal prescription].

Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.

Improvement of Neoantigen Identification Through Convolution Neural Network.

Accurate prediction of neoantigens and the subsequent elicited protective anti-tumor response are particularly important for the development of cancer vaccine and adoptive T-cell therapy. However, current algorithms for predicting neoantigens are limited by in vitro binding affinity data and algorithmic constraints, inevitably resulting in high false positives. In this study, we proposed a deep convolutional neural network named APPM (antigen presentation prediction model) to predict antigen presentation in the context of human leukocyte antigen (HLA) class I alleles. APPM is trained on large mass spectrometry (MS) HLA-peptides datasets and evaluated with an independent MS benchmark. Results show that APPM outperforms the methods recommended by the immune epitope database (IEDB) in terms of positive predictive value (PPV) (0.40 vs. 0.22), which will further increase after combining these two approaches (PPV = 0.51). We further applied our model to the prediction of neoantigens from consensus driver mutations and identified 16,000 putative neoantigens with hallmarks of 'drivers'.

[Traditional Chinese medicine (tumor) prevention and evaluation model based on ultra-early immune response information amplification index naCTL and multidimensional immunoinformatic index TCR/BCR/HLA effective diversity].

The best time of tumor intervention is before the formation of tumor. However,due to the limited number of tumor cells,it is difficult to quantify tumor cells and immunity by the current methods available( such as CTC,ct DNA). This affects the tumor prevention in this period,and the in-depth detection,intervention and evaluation of traditional Chinese medicine( TCM)( tumor) prevention. Due to the limitations of the current detection,the evaluation system turns to detect tumor neoantigen-specific CTL( naCTL) that are directly relating to tumor cells and proliferate to high order of magnitudes after activation,and immune repertoire( TCR/BCR/HLA) effective diversity,introduces immune checkpoints,uses information of " disease" in Western medicine and " syndrome" in TCM( prevention),and sets up a multi-dimensional statistical immunity model using a variety of data analysis and related algorithms. This model can amplify the ultra-early information of tumor,indirectly evaluate the quantity and status of tumor cells,and provide quantitative measurement and new evaluation methods for the normalization of immunity and TCM( tumor) prevention. This model is not only one of important evaluation methods for resisting tumor immunity and treating TCM( tumor) prevention,but also will reveal the scientific connotation of TCM syndrome from the perspective of immunology.

[Generalized science of Chinese material medica-from preventive treatment of disease to Chinese medicine health industry].

Based on the systematic summary of the results of the fourth general survey of traditional Chinese medicine resources, the cultivation of large varieties of Chinese material medica and the latest research on health industrial development, the novel concepts and scientific connotations of generalized science of Chinese material medica are put forward, and the basic ideas and methods of a new Chinese medicine academic system, the cultivation system of large varieties of Chinese medicinal materials and the application system of the large health industry are constructed. This kind of generalized science of Chinese material medica, rooted in the traditional Chinese culture and the theory of "preventive treatment of disease", can avoid the narrow prospect induced by the increasing specialization and refinement of knowledge of science of Chinese material medica. It will play an important role in the modernization, industrialization, internationalization of traditional Chinese medicine.

[New method for evaluating pharmacodynamics of traditional Chinese medicine compounds based on its moderate regulation and principle of balanced adjustment of immunity under pan-immunomic].

For the basic research on the traditional Chinese medicine(TCM), objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds are hardly to break though. While, the modern immunology points out that the body is a counterbalance state and immune imbalance is the root of sickness. The thinking mode of treating diseases in traditional Chinese medicine is also "balance", considering disease is the result of bias which present the imbalance of "Yin counters Yang", "exterior counters interior", "cold counters heat" and "weak counters strong". The Chinese herbal compound formula preparation was applied on disease therapy based on theory of Chinese medicine, which was confirmed by long period clinical application. It is composed of multi-compounds and has the characteristic of multi-targeting. Integrative medicine has spawned pan-immunomics, and the evaluation of immune function (immune balance) has become an important basis for diagnosis and treatment models of integrative medicine. In addition, balance is the core idea of whole-systemic conception of traditional Chinese medicine. Therefore, we speculate that immune balance under pan-immunomic can bridge the traditional Chinese medicine and modern integrative medicine and is the important basis for objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds. According to the bridging theory, we attempt to utilize informatics and statistical methods to construct an evaluation system for pharmacodynamics of traditional Chinese medicine based on its moderate regulation and the balanced adjustment of immunity under pan-immunomic, which further reveal the scientific essence of the whole-systemic view of traditional Chinese medicine. This research brings out a new valuable strategy and provides a theoretical basis for accelerating the transformation of traditional Chinese medicine, especially the exploitation of Chinese herbal compound formula, and constructing the new drug innovation and review system for traditional Chinese medicine. Besides as a reference for traditional Chinese medicine objective syndrome and pharmacodynamics of traditional Chinese medicine compounds, the evaluation system can screen the immunity of sub-health population also. With the continuous accumulation of clinical sample and data, the evaluation system will be more accurate and intelligent.

Increases in PKC gamma expression in trigeminal spinal nucleus is associated with orofacial thermal hyperalgesia in streptozotocin-induced diabetic mice.

Painful diabetic polyneuropathy (PDN) at the early phrase of diabetes frequently exhibits increased responsiveness to nociception. In diabetic patients and animal models, alterations in the transmission of orofacial sensory information have been demonstrated in trigeminal system. Herein, we examined the changes of protein kinase Cγ subunit (PKCγ) in trigeminal spinal nucleus (Sp5C) and observed the development of orofacial thermal sensitivity in streptozotocin (STZ)-induced type 1 diabetic mice. With hyperglycemia and body weight loss, STZ mice exhibited orofacial thermal hyperalgesia, along with increased PKCγ expression in Sp5C. Insulin treatment at the early stage of diabetes could alleviate the orofacial thermal hyperalgesia and impaired increased PKCγ in Sp5C in diabetic mice. In summary, our results demonstrate that PKCγ might be involved in orofacial thermal hyperalgesia of diabetes, and early insulin treatment might be effective way to treat orofacial PDN.

Novel mitochondrial DNA mutations associated with Chinese familial hypertrophic cardiomyopathy.

1. Hypertrophic cardiomyopathy (HCM) is a genetic disorder that has a complex set of symptoms and potentially devastating consequences. Increasing evidence indicates that mitochondrial DNA (mtDNA) mutations are responsible for the development of HCM, but the mtDNA mutations appear to differ considerably among different populations and regions. 2. In the present study, three families with HCM were found and investigated: one in Shandong province and two in the Chongqing region of China. The entire mtDNA genome from the 18 affected and 66 unaffected family members was sequenced directly and the mtDNA mutations were determined. 3. The frequency of haplogroup M10 was significantly higher in family members with HCM (HCM group) than in unaffected family members (normal group). Three mtDNA mutations were found with a significantly higher frequency in affected individuals than in unaffected family individuals, namely G7697A in the cytochrome c oxidase subunit II gene (P < 0.0001; odds ratio (OR) 227.5; 95% confidence interval (CI) 23.6­2194.8) and T12477C (P = 0.0037; OR 5.6; 95% CI 1.8­17.6) and G13135A in the NADH dehydrogenase 5 gene (P < 0.0001; OR 26.0; 95% CI 6.9­98.3), suggesting that these mutations are probably associated with susceptibility to HCM. In addition, mitochondrial Complex I activity was markedly decreased in the HCM group, suggesting that these mutations most likely affect mitochondrial respiratory function. 4. In conclusion, the results of the present study imply that mtDNA mutations G7697A, T12477C and G13135A are genetic factors that indicate a susceptibility to HCM and that could be used for the large-scale screening of genetic markers as well as the early diagnosis of HCM.

Mitochondrial DNA haplogroups in a Chinese Uygur population and their potential association with longevity.

1. The haplogroups and polymorphisms of mitochondrial (mt) DNA are associated with longevity. This association is highly geographically dependent. The aim of the present study was to determine the relationship between mtDNA haplogroups, single nucleotide polymorphisms (SNPs) and longevity in the Chinese Uygur population. 2. Ninety-eight Uygur Chinese subjects aged over 90 years (vitality 90+) and 117 healthy young controls living in the Xinjiang Uygur Autonomous Region of China were chosen for the present study. Frequencies of mtDNA haplogroups and SNPs in the subjects were analysed using polymerase chain reaction. The entire mtDNA genome was sequenced and the mtDNA haplogroups and SNPs were determined. 3. Nine haplogroups were identified in the Chinese Uygur population and the frequency of haplogroup J was higher in control subjects than in the vitality 90+ group (odds ratio = 0.384; 95% confidence interval = 0.163-0.906; P = 0.025). Interestingly, most of the SNPs were in the D-loop region, with frequencies higher in the control group than in the vitality 90+ group. 4. In conclusion, mtDNA haplogroups are potentially associated with longevity in the Uygur Chinese population and the D-loop region is strongly involved in ageing-related events.

Novel mutations of mitochondrial DNA associated with type 2 diabetes in Chinese Han population.

Mitochondrial single nucleotide polymorphisms (mtSNPs) have been reported to associate with type-2 diabetes mellitus (T2DM), but mtSNPs appear to be considerably different among different populations and regions. To determine mtSNPs in Chinese Han patients with T2DM, the entire sequences of the mitochondrial genomes from 72 T2DM Chinese (59 +/- 4 years) and 50 age-matched healthy subjects (controls) in Chongqing region of Western China were directly sequenced and mtSNPs were analyzed. We found that M8, M9, D, G, R and A haplogroups exist in Chinese Han population and the frequency of haplogroup M9 was significantly higher in patients with T2DM than in the controls (p = 0.0006, OR 0.06 [95% CI 0.008-0.476]). MtSNPs T3394C in NADH dehydrogenase subunit 1 (ND1), G4491A in ND2, T16189C and T16519C were found with significantly higher frequency in patients with T2DM than in the controls (T16189C, p = 0.0045; T16519C, p < 0.0001; T3394C, p = 0.0015; G4491A, p = 0.0015). In contrast, the frequency of C5178A in ND2 and A10398G in ND3 was higher in the controls than in patients with T2DM (C5178A, p = 0.014; A10398G, p = 0.0011). Our results indicate that mtSNPs T3394C, G4491A, T16189C and T16519C show susceptible tendency to T2DM and mtSNPs C5178A and A10398G seem to be genetic factors for against T2DM. These mtSNPs determined in our study is useful and could be used for early diagnosis and prevention of T2DM in Chinese Han population.

Panax notoginseng saponins attenuate atherosclerosis in rats by regulating the blood lipid profile and an anti-inflammatory action.

Previous studies have reported on the anti-atherosclerotic effects of Panax notoginseng saponins (PNS). The aim of the present study was to explore the molecular mechanisms responsible for the anti-atherosclerotic effects of PNS and the inflammatory response. Thirty rats were randomly divided into three groups, namely a control group, a group, in which zymosan A was used to induce inflammation (Zym group) and a PNS-treated group. Rats in the three groups were administered liquid paraffin (i.p.), zymosan A (20 mg/kg, i.p., once every 3 days) or zymosan A and PNS (100 mg/kg, i.p., once daily), respectively. All animals were fed a high-fat diet for 9 weeks. At scheduled times, rats were killed, blood was collected and the aorta was removed. Pathological changes in aortas were observed using Sudan IV staining and transmission electron microscopy. Serum lipids were measured enzymatically. Whole-blood viscosity was observed at different shear rates. The expression of cardiovascular disease-specific genes was determined using GEArray (SuperArray, Frederick, MA, USA). Western blotting was used to evaluate the expression levels of nuclear factor (NF)-kappaB/p65 and its inhibitor IkappaBalpha in the aortic wall. In the present study, typical pathological changes associated with atherosclerosis in rats following induction by zymosan A were alleviated by PNS treatment. In the PNS-treated group, there was a marked reduction in total serum cholesterol, triglycerides and blood viscosity. In addition, PNS treatment significantly decreased the gene expression of some inflammatory factors, such as integrins, interleukin (IL)-18, IL-1beta and matrix metalloproteinases 2 and 9. The expression of NF-kappaB/p65 was attenuated, whereas the expression of IkappaBalpha was significantly increased, after treatment with PNS. In conclusion, it appears that PNS exerts its therapeutic effects on atherosclerosis through an anti-inflammatory action and regulation of the blood lipid profile and that an NF-kappaB signalling pathway is involved.

[Rapid detection of the genotyping of hepatitis C virus using DNA chip with coloration methods].

OBJECTIVE: To develop a new DNA chip with coloration, which can be used for rapid and economical detection of the genotyping of hepatitis C virus (HCV). METHODS: Probes and primers were designed according to the sequence of HCV 5' non-coding region (5' NCR) to fabricate DNA chip. Experimental group consisted of 60 positive serum samples and control group consisted of 20 negative serum samples. To obtain the aimed gene, then they were hybridized with DNA chip. Finally, the results showed in a nylon film. The results of DNA sequencing of samples were used as the control in double blind experimental. RESULTS: Using DNA chip, HCV was detected in positive of all serum specimens of experimental group and negative in control group. The determination of HCV genotype by DNA chip showed corresponding rate of 96.7% with those by sequence assay. CONCLUSION: It showed higher specialty and sensitivity using DNA chip to detect the genotype of HCV. It would be valuable for the clinical genotyping of HCV