Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Parkinson's disease is a neurodegenerative disease associated with abnormal copper metabolism in the brain,which leads to misfolding and aggregation of α-synuclein-copper complexes,which is an important pathological sign of Parkinson's disease.Copper metabolism,i.e.,cellular metabolic processes involving copper ions,is closely related to the pathogenesis of α-synuclein aggregation,dopamine metabolism,mitochondrial dysfunction,oxidative stress,and ferroptosis in Parkinson's disease.In this review,we summarize the molecular metabolic mechanism of copper toxicity by studying the pathological role of copper metabolism in Parkinson's disease,to support our further understanding of the mechanism of action and drug development.

Aim To investigate the dynamic changes of neuronal cells at different time points following acute cerebral ischemia-reperfusion injury by establishing a model of brain ischemia-reperfusion injury.Methods Thirty male Sprague-Dawley(SD)rats were ran-domly divided into six groups:sham group and cere-bral ischemia-reperfusion injury(IR)groups at differ-ent time points.Focal cerebral ischemia-reperfusion injury model was established using the middle cerebral artery occlusion(MCAO)technique.The Longa sco-ring method was used to assess neurobehavioral scores in rats.After successful model preparation,routine paraffin sections were made,and TUNEL staining and immunohistochemistry staining with NeuN antibody were performed to observe cell apoptosis and neuronal cell survival,respectively.Immunohistochemistry stai-ning was also performed to investigate the changes in glial fibrillary acidic protein(GFAP)as a marker for astrocytes,ionized calcium-binding adapter molecule 1(IBA-1)as a marker for microglia,and CD31 as a marker for endothelial cells at different time points.Results No significant changes were observed in neu-ronal cells of the sham group at different time points.In the cerebral ischemia-reperfusion injury groups,cell apoptosis was activated at IR3h and increased in quan-tity with morphological damage as time progressed.Ne-uN+neurons showed signs of ischemic injury after IR3h,with abnormal cell morphology.From 12 h,Ne-uN+neurons decreased in a time-dependent manner and reached their peak severity at 24 h.GFAP+astro-cytes decreased significantly after IR3h,while poorly labeled GFAP+astrocytes increased at IR 6 h and al-most disappeared in the infarcted area at 24 h and 48 h.The number of IBA-1+microglia-positive cells de-creased at IR3h,and their volume increased at IR6h.Microglial cell death was observed in the infarcted area at IR12h.CD31+endothelial cells around the infarc-ted cortex and striatum increased significantly after IR3h and persisted until 48 h.Conclusions After cerebral ischemia-reperfusion injury,the number of ap-optotic cells increases with the prolongation of time,and NeuN+neurons exhibit the most severe damage at 24 h.GFAP+astrocytes and microglial cells gradually die over time.The number of CD31+endothelial cells increases significantly around the infarcted cortex and striatum after 3 h of reperfusion and persists until 48 h.

Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
Cinnamomum camphora/enzymology* ; Alkyl and Aryl Transferases/chemistry*

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.
DNA Methylation/genetics* ; Drugs, Chinese Herbal ; Hematologic Neoplasms/genetics* ; Humans ; Materia Medica ; Medicine, Chinese Traditional

ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics， so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb₁ were determined by high performance liquid chromatography （HPLC）， to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol （2∶1∶1） with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb₁ was acetonitrile-0.1% phosphoric acid aqueous solution （31∶69） with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established， and mice were randomly divided into five groups， namely sham operation group， model group， domperidone group （3.9 mg·kg^-1） and high- and low-dose groups of Jiaojiang cataplasms （6.2， 3.1 g·kg^-1， measured by crude drug dosage）， to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool， 6-gingerol and ginsenoside Rb₁ at 24 h were 16.41， 4.23， 4.15 μg∙cm^-2∙h^-1， the average transdermal rates of them at 24 h were 2.31， 0.64， 0.29 μg∙cm^-2∙h^-1， their skin retention values were 19.56， 3.59， 1.61 μg， respectively. According to the Ritger-Peppas equation， the release of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb₁ was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury， and promote intestinal peristalsis and small intestinal propulsion rate （P<0.05）. ConclusionJiaojiang cataplasms has in vitro release and transdermal properties， the in vitro release conforms to Higuchi equation， and transdermal absorption behavior conforms to zero-order kinetic equation， which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.

ObjectiveTo study the effects of Toddalia asiatica alcohol extract on autophagy and apoptosis of non-small cell lung cancer A549 cells， and to explore its possible mechanism. MethodA549 cells were cultured in vitro. Cell counting kit-8 （CCK-8） was used to detect the proliferation of A549 cells， and cell survival rate was calculated to screen the drug concentration. The apoptosis in each dose group and that after the use of 3-methyladenine （3-MA）， an autophagy inhibitor， were detected by flow cytometry combined with Annexin V-FITC/PI double staining. Western blot was used to detect the expression levels of apoptosis-related proteins such as B cell lymphocytoma-2（Bcl-2）， Bcl-2-associated X protein（Bax）， microtubule-associated protein 1 light chain 3 （LC3）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， activated poly （Adenosine diphosphate） ribonucleotide polymerase （cleaved PARP1）， PARP1， activated death activator （t-Bid）， Bid， and ubiquitin-binding protein p62 in each group and those after the use of 3-MA. ResultCompared with the conditions in the control group， the cell survival rate in 0.25 g·L^-1 group （P<0.05）， and 0.5， 1， 2， 4 g·L^-1 groups （P<0.01） was decreased after 24 h intervention. Additionally， the cell survival rate was reduced in a concentration-dependent manner at 48 h and it was less than 10% at 4 g·L^-1 （P<0.01）. Compared with the conditions in the control group， the total apoptosis rate in 0.5 g·L^-1 group was increased （P<0.05）， and the apoptosis rate in 1 and 2 g·L^-1 groups was also increased （P<0.01）. Compared with the 2 g·L^-1 group and 3-MA group， the 3-MA combined with T. asiatica alcohol extract had significantly decreased apoptosis rate （P<0.01）. Compared with the conditions in the control group， elevated expression of pro-apoptotic proteins cleaved PARP1， Bax and t-Bid in 1 and 2 g·L^-1 groups （P<0.05， P<0.01）， and reduced expression of Bid in the 2 g·L^-1 group （P<0.01） were found. Compared with the conditions in the control group， the expression of anti-apoptotic protein Bcl-2 （P<0.05， P<0.01） and the level of p62 （P<0.01） were down-regulated in 0.5， 1， 2 g·L^-1 groups， while the level of LC3 Ⅱ protein was up-regulated （P<0.01）， with certain concentration dependence. ConclusionT. asiatica alcohol extract could significantly inhibit the proliferation of A549 cells， which might be related to promoting autophagy and inducing apoptosis.

Objective:To obtain ancient traditional Chinese medicine（TCM）literatures relating to tumor and visual analysis by an automatic framework tool， in order to systematically sort out the development of ancient Chinese medicine oncology. Method:Based on the database platform of ancient TCM books，names of tumor-related diseases in ancient TCM books were retrieved by Selenium WebDriver， an automation framework tool under Python 3.8. Lxml's etree library was used to parse the data. Statistics was made for "classification"， "authors"， "completion time" and "summary" of relevant ancient books automatically. After the data was checked and processed， Tableau 2019.2 software was used for data visualization analysis. And ancient Chinese medicine literatures relating to tumor were consulted at the database manually，with the dynasties as the clue，and the symptoms，etiology，pathogenesis and prognosis as the emphasis，this paper explores the development process of TCM oncology. Result:A total of 774 349 bytes of text data of 1 128 entries in 242 ancient books were included automatically. According to the findings， there were simple classification and time distribution of tumor diseases in ancient TCM books in the pre-Qin period， with a simple view on the pathogenesis of tumor diseases. From the Han dynasty to the Tang dynasty， the number of relevant literature records and the types and disease names had gradually increased，which further enriched the cognition of tumor nature，signs，classification methods，differential diagnosis；in Song and Ming dynasties，the proportion of Chinese prescription books and surgery books had increased gradually，with the largest number of abdominal organ tumor names among all dynasties；from Qing dynasty to the Republic of China，literatures relating to tumor name and classification were the most improved，and then the TCM tumor syndrome differentiation and treatment system had been formed. Conclusion:It was found that TCM oncology originated in the pre-Qin dynasty，and was improved in the Han and Tang dynasties， mature in the Song and Ming dynasties and completed in the Qing dynasty and the Republic of China. The data visualization method with integrated automation framework and parsing tools is helpful to analyze the subdivision characteristics of ancient TCM literatures，which is convenient，efficient and innovative，in the expectation to provide a classic reference for contemporary TCM studies.

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg
Animals ; Drugs, Chinese Herbal ; Metabolome ; Quality of Life ; Rats ; Stomatitis ; Tablets ; Transcriptome