Progress in clinical research on the integration of Chinese and Western medicines for treating primary liver cancer

Primary liver cancer(PLC) is one of the most common malignant tumors in China. PLC is characterized by insidious onset, rapid progress, poor quality of life, and short survival time. Notably, current treatment strategies remain unsatisfactory. Traditional Chinese medicines(TCM) have been used to treat a variety of diseases, including liver diseases, for more than 2000 years. In this study, we performed a review of the use frequency and clinical efficacy of TCM in treating PLC. Relevant literature from January 1, 2009, to January 1, 2021 was retrieved from network databases of China National Knowledge Infrastructure(CNKI), Chongqing VIP, Wanfang, PubMed, and SinoMed. The most frequently used TCM and their efficacy in PLC treatment were summarized. Based on the inclusion and exclusion criteria, 33 articles were selected. Overall, the efficacy of the combination of TCM and Western medicines in the treatment of PLC was higher than that in the control groups(i.e. treatment with Western medicines alone)(65.11% vs.44.31%, P <.05). Among the 33 selected articles, 11 were investigated for TCM preparation(marketed drugs) and 22 for TCM formulas. In total, 102 types of TCM(single herbs) were used to treat PLC. The top five most frequently used TCM were Poria(14.71%), Astragali radix(13.73%), Atractylodis Macrocephalae Rhizoma(12.75%), Bupleuri radix(12.75%), and Glycyrrhizae radix et Rhizoma(11.76%). Of the 102 types of TCM, tonics were the most frequently used categories, followed by heat-clearing medicines, blood-invigorating medicines, and stasis-resolving medicines. Of 207 papers, 174(84.06%) could not be subjected to statistical analysis due to research quality. Further high-quality research on herb sources, formula components and dosage, toxicology, and ethics of TCM is necessary. In conclusion, TCM play a promising role in the treatment and management of PLC, although further investigations are warranted.

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma(PAAD)patients.Proper regulation could improve survival.Melatonin is an endogenous hormone that delivers multiple bioactivities.Here we showed that pancreatic melatonin level is associated with patients'survival.In PAAD mice models,melatonin supplementation suppressed tumor growth,while blockade of melatonin pathway exacerbated tumor progression.This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils(TANs),and TANs depletion reversed effects of melatonin.Melatonin induced TANs infiltration and activation,therefore induced cell apoptosis of PAAD cells.Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells.Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation.Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype,with increased neutrophil extracellular traps(NETs)causing tumor cell apoptosis through cell-to-cell contact.Proteomics analysis revealed that this reactive oxygen species(ROS)-mediated inhibition was fueled by fatty acid oxidation(FAO)in neutrophils,while FAO inhibitor abolished the anti-tumor effect.Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration.CXCL2,or TANs,combined with NET marker,can better predict patients'prognosis.Collectively,we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Clinical efficacies,underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management

Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human society worldwide.Conventional strategies,such as renin-angiotensinaldosterone system blockade,blood glucose level control,and bodyweight reduction,may not achieve satisfactory outcomes in many clinical practices for DN management.Notably,due to the multi-target function,Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment.Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines.Signaling pathways involved in glucose/lipid metabolism regulation,antioxidation,anti-inflammation,anti-fibrosis,and podocyte protection have been identified as crucial mechanisms of action.Herein,we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials,systematic reviews,and meta-analyses,with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments.We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

Chinese medicines for prevention and treatment of human hepatocellular carcinoma: current progress on pharmacological actions and mechanisms

Hepatocellular carcinoma（HCC） is one of leading causes of death in the world. Although various treatments have been developed, the therapeutic side effects are far from desirable. Chinese medicines（CMs, including plants, animal parts and minerals） have drawn a great deal of attention in recent years for their potential in the treatment of HCC. Most studies have shown that CMs may be able to retard HCC progression with multiple actions, either alone or in combination with other conventional therapies to improve quality of life in HCC patients. Additionally, CMs are used for preventing HCC occurrence. The aim of this study is to review the potential prophylactic and curative effects of CMs on human HCC and the possible mechanisms that underlie these pharmacological actions. Publications were collected and reviewed from Pub Med and China National Knowledge Infrastructure from 2000 to 2014. Keywords for literature searches include ＂Chinese medicine＂, ＂Chinese herb＂, ＂traditional Chinese Medicine＂, ＂hepatocellular carcinoma＂ and ＂liver cancer＂. CMs in forms of pure compounds, isolated fractions, and composite formulas are included. Combination therapies are also considered. Both in vitro and in vivo efficacies of CMs are being discussed and the translational potential to bedside is to be discussed with clinical cases, which show the actions of CMs on HCC may include tumor growth inhibition, antimetastatic activities, anti-inflammation, anti-liver cancer stem cells, reversal on multi-drug resistance and induction/reduction of oxidative stress. Multiple types of molecules are found to contribute in the above actions. The review paper indicated that CMs might have potential to both prevent HCC occurrence and retard HCC progression with several molecular targets involved.

PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma

Altered energy metabolism of cancer cells shapes the immune cell response in the tumor microenvironment that faclitates tumorprogression.Herein,we reported the novel of tumor cell-expressed Piwi Like RNA-Mediated Gene Silencing 1(PWL1)in mediatingthe crosstlk of fatty acid metabolism and immune response of human hepatocellular carcinoma(HCC).PlWIL1 expression in HCCwas increased compared to normal hepatic tissues and was positively correlated with the proliferation rate of HCC cell ines.PIWL1overexpression accelerated in vitro proliferation and in vivo growth of HCC tumors,while PIWL1 knockdown showed opositeeffects.PIWL1 increased oxygen consumption and energy production via fatty acid metabolism without altering aerobic glycolysis.lnhibition of fatty acid metablism abolished PWIL1-induced HCC prolferation and growth.RNA-seq analysis revealed that immunesystem regulation might be involved,which was echoed by the experimental observation that PIWL1-overexpressing HCC cellsattracted myeloid-derived suppressor cells(MDSCs)into the tumor microenvironment.MDSCs depletion reduced the prolferationand growth of PlWIL1-overexpressing HCC tumors.Complement C3,whose secretion was induced by PIWL1 in HCC cells,mediatesthe interaction of HCC cells with MDSCs by activated p38 MAPK signaling in MDSCs,which in turn initiated expression of immunosuppressive cytokine L10.Neutralizing lL10 secretion reduced the immunosuppressive activity of MDSCs in the microenvironment of PIWL1-overexpressing HCC.Taken together,our study unraveled the critical role of PIWL1 in initiating theinteraction of cancer cell metabolism and immune cell response in HCC.Tumor cell-expressed PlIWL1 may be a potential target forthe devellopment of novel HCC treatment.

Chinese integrative medicine:inclusion of a Chinese medicine programme in a conventional medical institute

To meet community demands with optimal Chinese and conventional medical treatment, the University of Hong Kong is promoting integrative medicine by developing Chinese medicine programmes that train students of both Western and Chinese medicine. The programmes emphasize multi-disciplinary training and interaction between the two therapeutic approaches, enabling students to establish reliable, consistent, and respectful mutual cooperation in their future careers.