Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency.

OBJECTIVE: Melittin and its derivative have been developed to support effective gene delivery systems. Their ability to facilitate endosomal release enhances the delivery of nanoparticle-based gene therapy. Nevertheless, its potential application in the context of viral vectors has not received much attention. Therefore, we would like to optimize the rAAV vector by Melittin analog to improve the transduction efficiency of rAAV in liver cancer cells and explore the mechanism of Melittin analog on rAAV. METHODS: Various melittin-derived peptides were inserted into loop VIII of the capsid protein in recombinant adeno-associated virus vectors. These vectors carrying either gfp or fluc genes were subjected to quantitative polymerase chain reaction assays and transduction assays in human embryonic kidney 293 (HEK293T) cells to investigate the efficiency of vector production and gene delivery. In addition, the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice. Finally, the intricate details of the vector-mediated transduction mechanisms were explored by using pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle. RESULTS: A total of 76 melittin-related peptides were identified from existing literature. Among them, CMA-3, p5RHH and aAR3 were found to significantly inhibit transduction of rAAV2 vector crude lysate. The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV. Mechanistically, bafilomycin A1, a vacuolar endosome acidification inhibitor, completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors. Most importantly, p5RHH-rAAV8 vectors also increased hepatic transduction in vivo in C57BL/6 mice. CONCLUSION: The incorporation of melittin analogs into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression. While further modifications remain an area of interest, our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery. Please cite this article as: Meng J, He Y, Yang H, Zhou L, Wang S, Feng X, Al-shargi OY, Yu X, Zhu L, Ling, C. Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency. J Integr Med. 2024; 22(1): 72-82.

Oleanolic acid inhibits hypoxic tumor-derived exosomes-induced premetastatic niche formation in hepatocellular carcinoma by targeting ERK1/2-NFκB signaling.

BACKGROUND: Pulmonary premetastatic niche (PMN) formation plays a key role in the lung metastasis of hepatocellular carcinoma (HCC). Hypoxia promotes the secretion of tumor-derived exosomes (TDEs) and facilitates the formation of PMN. However, the mechanisms remain unexplored. METHODS: TDEs from normoxic (N-TDEs) or hypoxic (H-TDEs) HCC cells were used to induce fibroblast activation in vitro and PMN formation in vivo. Oleanolic acid (OA) was intragastrically administered to TDEs-preconditioned mice. Bioinformatics analysis and drug affinity responsive target stability (DARTS) assays were performed to identify targets of OA in fibroblasts. RESULTS: H-TDEs induced activation of pulmonary fibroblasts, promoted formation of pulmonary PMN and subsequently facilitated lung metastasis of HCC. OA inhibited TDEs-induced PMN formation and lung metastasis and suppressed TDEs-mediated fibroblast activation. MAPK1 and MAPK3 (ERK1/2) were the potential targets of OA. Furthermore, H-TDEs enhanced ERK1/2 phosphorylation in fibroblasts in vitro and in vivo, which was suppressed by OA treatment. Blocking ERK1/2 signaling with its inhibitor abated H-TDEs-induced activation of fibroblasts and PMN formation. H-TDEs-induced phosphorylation of ERK1/2 in fibroblasts touched off the activation NF-κB p65, which was mitigated by OA. In addition, the ERK activator C16-PAF recovered the activation of ERK1/2 and NF-κB p65 in H-TDEs-stimulated MRC5 cells upon OA treatment. CONCLUSION: The present study offers insights into the prevention of TDEs-induced PMN, which has been insufficiently investigated. OA suppresses the activation of inflammatory fibroblasts and the development of pulmonary PMN by targeting ERK1/2 and thereby has therapeutic potential in the prevention of lung metastasis of HCC.

Sanshimao formula inhibits the hypoxia-induced pro-angiogenesis of hepatocellular carcinoma cells partly through regulating MKK6/p38 signaling pathway.

OBJECTIVES: Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism. METHODS: The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo. RESULTS: The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways. CONCLUSION: SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth.

Targeting tumor-derived exosome-mediated premetastatic niche formation: The metastasis-preventive value of traditional Chinese medicine.

Tumor-derived exosome (TDE)-mediated premetastatic niche (PMN) formation is a potential mechanism underlying the organotropic metastasis of primary tumors. Traditional Chinese medicine (TCM) has shown considerable success in preventing and treating tumor metastasis. However, the underlying mechanisms remain elusive. In this review, we discussed PMN formation from the perspectives of TDE biogenesis, cargo sorting, and TDE recipient cell alterations, which are critical for metastatic outgrowth. We also reviewed the metastasis-preventive effects of TCM, which act by targeting the physicochemical materials and functional mediators of TDE biogenesis, regulating the cargo sorting machinery and secretory molecules in TDEs, and targeting the TDE-recipient cells involved in PMN formation.

Iron deficiency in hepatocellular carcinoma cells induced sorafenib resistance by upregulating HIF-1α to inhibit apoptosis.

Sorafenib is the first-line therapeutic agent for hepatocellular carcinoma (HCC), but the drug resistance has become a major impediment. Previously we found that the abnormal iron metabolism in HCC led to iron deficiency, whether it induces sorafenib resistance during the treatment of HCC is not yet disclosed. In this study, we observed the effects of iron deficiency on sorafenib resistance and explored the underlying mechanisms. The results revealed that the killing effects of sorafenib on HCC cells were weakened by iron deficiency but effectively restored by iron re-supplementation. The ferroptosis indicators, including the contents of lipid hydroperoxide (LPO) and malondialdehyde (MDA), the level of intracellular reactive oxygen species (ROS), and the expression of glutathione peroxidase 4 (GPX4), were not significantly changed by iron deficiency in sorafenib-treated HCC cells. However, the sorafenib-induced apoptosis of HCC cells was inhibited by iron deficiency. Notably, the expression of anti-apoptotic protein B-cell lymphoma-2 (BCL-2) was elevated, and the expressions of other apoptotic proteins, BCL2-associated X (Bax), caspase-3, and caspase-9, were inhibited by iron deficiency. Mechanistically, iron deficiency upregulated hypoxia-inducible factor 1 alpha (HIF-1α) to increase BCL-2. Inhibition of HIF-1α suppressed the iron deficiency-induced BCL-2 and sorafenib resistance. In summary, iron deficiency in HCC cells generated sorafenib resistance by increasing HIF-1α and BCL-2, which therefore inhibited the sorafenib-induced apoptosis of HCC cells. These results identified iron deficiency as a new factor of sorafenib resistance in HCC cells, which would be an effective target to alleviate sorafenib resistance.

Corrigendum to "The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways".

[This corrects the article DOI: 10.1155/2018/5629304.].

Knowledge about, attitude and acceptance towards, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China: A cross-sectional survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China. METHODS: A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance. RESULTS: A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients' knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the "vaccine hesitancy" population and "vaccine acceptance" population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375-2.488; P-reference [P-Ref] < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126-2.318; P-Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024-2.203; P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376-3.894; P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759-4.280; P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438-0.784; P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer (OR = 0.408; 95% CI: 0.221-0.753; P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer (OR = 0.393; 95% CI: 0.307-0.504; P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy. CONCLUSION: This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.

Impact of treatment-duration-ratio of traditional Chinese medicine on survival period of primary liver cancer -A real-world study.

Introduction: In China, traditional Chinese medicine (TCM) is regarded as an effective treatment for primary liver cancer (PLC). The present study analyzed the effect of TCM on the survival period of patients with PLC by analyzing the relationship between the treatment-duration-ratio of traditional Chinese medicine (C-TDR, (traditional Chinese medicine treatment duration)/(Overall treatment duration) × 100%) and the survival time of 1002 patients with PLC. Methods: In this study, 1002 patients with PLC admitted to TCM Oncology Department of Changhai Hospital from January, 2015 to December, 2019 were enrolled. The univariate and multivariate Cox regression equation, propensity score matching (PSM) were performed to identify independent prognostic factors for survival outcomes of PLC patients at different stages and estimate the influence of C-TDR on survival time. Results: Cox regression analysis indicated that C-TDR was an independent prognostic factor for survival outcome (P＜0.05) and a corresponding reduction of relative risk of death of 75.67% (relative risk (RR) = 0.2433; 95%Confedential Interval (CI) = 0.1747-0.3388). Similarly, it is also an independent prognostic factor for patients outcome of each stage (P＜0.05). The 251 patients of BCLC-A reduced 96.09% risk of mortality (RR = 0.0391; 95%CI = 0.0151-0.1012). The 396 BCLC-B patients decreased risk of death of 81.24% (RR = 0.1876, 95%CI = 0.1112-0.3163). Moreover, 355 patients of stage C demonstrated a 51.36% lower risk of death (RR = 1.0016, 95%CI = 0.9885-1.0149). Significant differences were found in the median overall survival (OS) both higher and lower C-TDR of all patients. Even after PSM, the overall survival of two groups were significantly improved following each stage. Conclusion: Earlier administration of traditional Chinese medicine can reduce the risk of mortality and prolong survival in patients with liver cancer.

The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment.

Invasion and metastasis are the main reasons for the high mortality of liver cancer, which involve the interaction of tumor stromal cells and malignant cells. Cancer-associated fibroblasts (CAFs) are one of the major constituents of tumor stromal cells affecting tumor growth, invasion, and metastasis. The heterogeneous properties and sources of CAFs make both tumor-supporting and tumor-suppression effects possible. The mechanisms for CAFs in supporting hepatocellular carcinoma (HCC) progression can be categorized into upregulated aggressiveness and stemness, transformed metabolism toward glycolysis and glutamine reductive carboxylation, polarized tumor immunity toward immune escape of HCC cells, and increased angiogenesis. The tumor-suppressive effect of fibroblasts highlights the functional heterogenicity of CAF populations and provides new insights into tumor-stromal interplay mechanisms. In this review, we introduced several key inflammatory signaling pathways in the transformation of CAFs from normal stromal cells and the heterogeneous biofunctions of activated CAFs. In view of the pleiotropic regulation properties of traditional Chinese medicine (TCM) and heterogeneous effects of CAFs, we also introduced the application and values of TCM in the treatment of HCC through targeting CAFs.

Effect and Molecular Mechanisms of Jiedu Recipe on Hypoxia-Induced Angiogenesis after Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma.

Transcatheter arterial chemoembolization (TACE) is one of the effective treatment methods for hepatocellular carcinoma (HCC) in middle and late phases. However, TACE-induced hypoxia may promote the angiogenesis and section of some cytokines, such as IL-8, and, thereby, lead to tumor metastasis. Therefore, we investigated the effect of Jiedu Recipe (JR), which has been demonstrated as an effective Traditional Chinese Medicine (TCM) recipe on HCC, on TACE-induced cytokines upregulation and hypoxia-induced angiogenesis. A total of 88 hepatocellular carcinoma (HCC) patients treated with TACE were enrolled and divided into a JR group or control group. TACE induced significant increases of neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), IL-1ß, IL-2R, IL-6, and IL-8. JR treatment significantly inhibited the elevation of IL-8 compared with control. In vitro, JR significantly inhibited the hypoxia-induced overexpression of IL-8, HIF-1α, and VEGF mRNA in Huh 7 cells. ELISA assay demonstrated the effect of JR on IL-8 expression. Both hypoxia and IL-8 may promote angiogenesis which was suppressed by JR. Western blot showed that IL-8 upregulated the expression of phosphorylation of AKT, ERK, NF-κB, and VEGFR, which were inhibited by JR. On the other hand, effects of IL-8 on the increase of p-AKT and p-ERK were also blocked by LY294002 and U0126, respectively. In conclusion, our results indicated that JR may inhibit hypoxia-induced angiogenesis through suppressing IL-8/HIF-1α/PI3K and MAPK/ERK pathways after TACE in HCC patients.

Mechanism for enhanced transduction of hematopoietic cells by recombinant adeno-associated virus serotype 6 vectors.

Hematopoietic gene delivery, such as hematopoietic stem/progenitor cells (HSPCs), is a promising treatment for both inherited and acquired diseases, such as hemophilia. Recently, a combined strategy to achieve more than 90% transduction efficiency was documented using recombinant adeno-associated virus serotype 6 (rAAV6) vectors. However, the mechanisms of enhanced vector transduction efficiency in hematopoietic cells are largely unknown. In this manuscript, we first reported that proteasome inhibitors, which are well-known to facilitate rAAV intracellular trafficking in various cell types, are not effective in hematopoietic cells. From the screening of small molecules derived from traditional Chinese medicine, we demonstrated that shikonin, a potential reactive oxygen species (ROS) generator, significantly increased the in vitro and ex vivo transgene expression mediated by rAAV6 vectors in hematopoietic cells, including human cord blood-derived CD34 + HSPCs. Shikonin mainly targeted vector intracellular trafficking, instead of host cell entry or endonuclear single to double strand vector DNA transition, in a vector serotype-dependent manner. Moreover, a ROS scavenger completely prevented the capability of shikonin to enhance rAAV6 vector-mediated transgene expression. Taken together, these studies expand our understanding of rAAV6-mediated transduction in hematopoietic cells and are informative for improving rAAV6-based treatment of blood diseases.

Network pharmacology suggests biochemical rationale for treating COVID-19 symptoms with a Traditional Chinese Medicine.

Chinese herbal formulas including the lung-cleaning and toxicity-excluding (LCTE) soup have played an important role in treating the ongoing COVID-19 pandemic (caused by SARS-CoV-2) in China. Applying LCTE outside of China may prove challenging due to the unfamiliar rationale behind its application in terms of Traditional Chinese Medicine. To overcome this barrier, a biochemical understanding of the clinical effects of LCTE is needed. Here, we explore the chemical compounds present in the reported LCTE ingredients and the proteins targeted by these compounds via a network pharmacology analysis. Our results indicate that LCTE contains compounds with the potential to directly inhibit SARS-CoV-2 and inflammation, and that the compound targets proteins highly related to COVID-19's main symptoms. We predict the general effect of LCTE is to affect the pathways involved in viral and other microbial infections, inflammation/cytokine response, and lung diseases. Our work provides a biochemical basis for using LCTE to treat COVID-19 and its main symptoms.

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study.

OBJECTIVE: Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC), and Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) Granule, a compound of traditional Chinese herbal medicine, side-by-side with sorafenib for the treatment of advance HCC. METHODS: Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process. RESULTS: Of the 325 patients included, 161 received JD Granule and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83-9.47) in the group receiving JD Granule and 8 months (95% CI: 6.67-9.80) in the group receiving sorafenib, with half-, 1- and 2-year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD Granule group (9.03 months; 95% CI: 6.37-14.2) and the sorafenib group (7.93 months; 95% CI: 6.5-9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD Granule group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD Granule was more cost-effective than sorafenib treatment for advanced HCC. CONCLUSION: Compared to sorafenib, JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis.

Complementary and integrative medicine (CIM) has been used for improving health-related quality of life (HRQOL) in patients with cancer. The objective of this review is to evaluate the effects of CIMs on the HRQOL of cancer patients. We identified randomized controlled trials (RCTs) involving patients with cancer at any stage by retrieving electronic databases from the inception to February 14, 2018 (Systematic Review Registration: PROSPERO CRD42018091609). The main outcomes were HRQOL scores and related domains such as physical well-being scores. The standardized mean difference was used for the analysis and heterogeneity was assessed with the I 2 statistic. A Bayesian framework was used to estimate the ranking order of efficacy in HRQOL change. Finally, 34 RCTs with 3,010 patients were included. As a whole, the results showed clearly superior efficacy of CIM in improving HRQOL. For different domains of HRQOL, different CIM interventions may play different roles. The ranking order of efficacy in change HRQOL was qigong plus mindfulness, Chinese herbal medicine, multimodal complementary medicine, qigong, nutritional supplement, mindfulness, acupuncture, yoga, and massage, and it was different among different domains. There was no evidence of publication bias. In conclusion, CIM may improve the HRQOL of cancer patients. More studies, especially focusing on male cancer patients, are needed to increase the confidence level of our findings.

Melittin Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation and Epithelial-Mesenchymal Transition through Suppression of HIF-1α/Akt Pathway in Liver Cancer.

In this study, we investigated whether melittin could suppress hypoxia-induced vasculogenic mimicry (VM) formation in liver cancer and explored the underlying mechanisms. Melittin significantly inhibited the proliferation of liver cancer cells with or without CoCl2 presence. Melittin also significantly inhibited CoCl2-induced migration, invasion, and VM formation of liver cancer cells. CoCl2 treatment suppressed the expression of E-cadherin and elevated the expression of N-cadherin and Vimentin. Melittin reversed the changes in the protein and mRNA levels of these epithelial-mesenchymal transition (EMT) markers. CoCl2-induced accumulation of HIF-1α increased the level of phosphorylated Akt and upregulated the expression of VEGF and MMP-2/9. Melittin decreased the HIF-1α level and thereby suppressed the levels of p-Akt, VEGF, and MMP-2/9. In addition, the inhibitor of PI3K/Akt also suppressed CoCl2-induced EMT and liver cancer cells migration, and the activator of Akt, SC-79, partly blocked the effect of melittin on CoCl2-induced EMT and liver cancer cells migration. In the xenograft tumor model in nude mice, melittin treatment significantly suppressed the tumor growth, VM formation, and HIF-1α expression in the tumor. In conclusion, this study indicates melittin may inhibit hypoxia-induced VM formation and EMT in liver cancer through inhibiting HIF-1α/Akt pathway.

Identification of Traditional Chinese Medicine Constitutions and Physiological Indexes Risk Factors in Metabolic Syndrome: A Data Mining Approach.

OBJECTIVE: In order to find the predictive indexes for metabolic syndrome (MS), a data mining method was used to identify significant physiological indexes and traditional Chinese medicine (TCM) constitutions. METHODS: The annual health check-up data including physical examination data; biochemical tests and Constitution in Chinese Medicine Questionnaire (CCMQ) measurement data from 2014 to 2016 were screened according to the inclusion and exclusion criteria. A predictive matrix was established by the longitudinal data of three consecutive years. TreeNet machine learning algorithm was applied to build prediction model to uncover the dependence relationship between physiological indexes, TCM constitutions, and MS. RESULTS: By model testing, the overall accuracy rate for prediction model by TreeNet was 73.23%. Top 12.31% individuals in test group (n=325) that have higher probability of having MS covered 23.68% MS patients, showing 0.92 times more risk of having MS than the general population. Importance of ranked top 15 was listed in descending order . The top 5 variables of great importance in MS prediction were TBIL difference between 2014 and 2015 (D_TBIL), TBIL in 2014 (TBIL 2014), LDL-C difference between 2014 and 2015 (D_LDL-C), CCMQ scores for balanced constitution in 2015 (balanced constitution 2015), and TCH in 2015 (TCH 2015). When D_TBIL was between 0 and 2, TBIL 2014 was between 10 and 15, D_LDL-C was above 19, balanced constitution 2015 was below 60, or TCH 2015 was above 5.7, the incidence of MS was higher. Furthermore, there were interactions between balanced constitution 2015 score and TBIL 2014 or D_LDL-C in MS prediction. CONCLUSION: Balanced constitution, TBIL, LDL-C, and TCH level can act as predictors for MS. The combination of TCM constitution and physiological indexes can give early warning to MS.

Clinical Use of Toxic Proteins and Peptides from Tian Hua Fen and Scorpion Venom.

Traditional Chinese Medicine (TCM) has been practiced in China for thousands of years. As a complementary and alternative treatment, herbal medicines that are frequently used in the TCM are the most accepted in the Western world. However, animal materials, which are equally important in the TCM practice, are not well-known in other countries. On the other hand, the Chinese doctors had documented the toxic profiles of hundreds of animals and plants thousand years ago. Furthermore, they saw the potential benefits of these materials and used their toxic properties to treat a wide variety of diseases, such as heavy pain and cancer. Since the 50s of the last century, efforts of the Chinese government and societies to modernize TCM have achieved tremendous scientific results in both laboratory and clinic. A number of toxic proteins have been isolated and their functions identified. Although most of the literature was written in Chinese, this review provide a summary, in English, regarding our knowledge of the clinical use of the toxic proteins isolated from a plant, Tian Hua Fen, and an animal, scorpion, both of which are famous toxic prescriptions in TCM.