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.

Ferroptosis is a unique regulated form of cell death that is distinct from apoptosis, necrosis, and other well-characterized regulated cell death types, and plays an important role in the occurrence and development of chronic metabolic diseases, including diabetes, hypertension, hyperlipidemia, and non-alcoholic steatohepatitis. Recently, increasing evidence has supported traditional Chinese medicine (TCM) as a new hot spot for the treatment of chronic metabolic diseases by mediating ferroptosis. Unfortunately, few systematic reviews have described the importance of TCM in treating chronic metabolic diseases through the ferroptosis pathway. In the current review, the mechanism of ferroptosis and the roles of ferroptosis in chronic metabolic diseases are summarized. Additionally, this review illustrates that the regulation of ferroptosis by TCM could be an effective approach for treating chronic metabolic diseases based on experimental evidence and clinical application. In summary, this work will improve the understanding of ferroptosis and the ability of TCM to regulate ferroptosis in chronic metabolic diseases, thereby promoting the development and application of natural TCM.

Cancer， one of the deadliest diseases caused by cells escaping homeostasis， abnormal proliferation， and abnormal differentiation， is fast becoming one of the most burdensome diseases of this century. With decades of human research and cognitive changes in cancer， cancer treatment is also developing rapidly， but there is still a lack of effective treatment and countermeasures. Especially， the search for safe， efficient， and non-toxic drugs has become a long-term goal in the field of cancer. Saponins extracted and separated from traditional Chinese medicine can improve cancer through various pathways and have almost no toxic side effects. Therefore， the research on the anti-cancer effect of saponins is heating up. It is found that saponins play anti-tumor roles by inhibiting proliferation， metastasis， and angiogenesis of cancer cells， promoting apoptosis of cancer cells， inducing autophagy of tumor cells， and regulating miRNA expression and immune functions. Chinese herbal medicine saponins can regulate secretory glycoprotein /β-catenin （Wnt/β-catenin）， adenylate activated protein kinase （AMPK）， nuclear transcription factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Janus kinase/activator of signal transduction and transcription 3 （JAK/ STAT3）， hypoxia-inducible factor-1α （HIF-1α）， Toll-like receptor （TLR）， and other related signaling pathways to get involved in the proliferation， metastasis， angiogenesis， apoptosis， autophagy， and other processes of cancer cells， thus interfering with the progression of cancer. Therefore， the focus of this review is to update the discovery and evaluation of Chinese herbal medicine saponins with anti-cancer properties， clarify their mechanism of action， including the progress of related signaling pathways， and deepen the understanding of the anti-cancer function of Chinese herbal medicine saponins， so as to provide a new perspective and direction for the prevention and treatment of tumors by traditional Chinese medicine and better promote the development and utilization of resources.

OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides （BCP） on acute liver injury （ALI） in mice. METHODS Overall 40 mice were randomly divided into normal group， model group， positive control group （Baogan tablet， 550 mg/kg）， BCP high-dose and low-dose groups （400， 100 mg/kg）， with 8 mice in each group. The drug was administered intragastrical once a day for 7 days. One hour after the last administration， except for the normal group， mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model. After injection of concanavalin A solution for 12 h， the liver and spleen indexes of mice were measured， and the pathological changes of liver and spleen tissue were observed； the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） were detected， and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissue were detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum and liver tissue of mice were determined， as well as the protein expression levels of nuclear factor-κB （NF-κB）， Toll-like receptor 4 （TLR4）， nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were also detected. RESULTS Compared with the normal group， the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells； spleen enlargement， increased bleeding and decreased lymphocytes were observed， liver and spleen indexes were increased significantly （P＜0.01）； the serum levels of AST， ALT and LDH， the levels of TNF-α， IL-6 and IL-1β in serum and liver tissue， as well as the MDA level， protein expressions of TLR4， NF- κB and HO-1 in liver tissue were all increased significantly （P＜0.05 or P＜0.01）. The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly （P＜0.05）. Compared with the model group， the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups， and most of liver and spleen indexes， the above indexes of serum and liver tissue were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS BCP has a protective effect on ALI， the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.

To revise GBZ 188 Technical Specification for Occupational Health Surveillance based on national laws, regulations, standards, specifications and legal documents of occupational disease, and combination with the actual situation in China. The main modifications are as follows: the occupational health surveillance for workers exposed to toluene (xylene may implement by reference), bromopropane, methyl iodide, ethylene oxide, chloroacetic acid, indium and its compounds, coal tar, coal tarasphalt, asphalt, β-naphthylamine, dust of metal and its compounds(tin, iron, antimony, barium and its compounds), hard metal dust, erionite dust, low temperature, laser, tick-borne encephalitis virus, Borrelia burgdorferi, and human immunodeficiency virus, for scraper or grind operators, and underground workers using squatting or kneeling position, crawling position, side-lying position, or shoulder position for a long period of time are included. The emergency health screening for workers exposed to arsenic, fluorine and its inorganic compounds, and acrylamide are included. The occupational medical examination (OME) for workers exposed to amino and nitro compounds of benzene, phosgene, monomethylamine, organic fluorine and dimethyl sulfate has been adjusted and made mandatory, with corresponding assessments required upon leaving the job. The special occupational health surveillance for workers exposed to mycobacterium tuberculosis and hepatitis virus is removed. The OME conclusion of reexamination is removed, and standardize recheck/additional inspection requirements. The optional items in OME performed before, during and after leaving post are removed, but the optional items in emergency medical examination are retained. Additional OME items are added. The Guideline for OME Summary Reports is added as informative appendix, and so on. The revised GBZ 188 Technical Specification for Occupational Health Surveillance is more scientific and practical.

Epilepsy is a chronic brain disease characterized by seizures， and is one of the most common nervous system diseases in clinic practice with the recurrent， transient， and refractory characteristics. Clinically， western medicine therapy is mainly adopted in the treatment of epilepsy， but it is not conducive to long-term use for patients on account of severe side effects， which can result in abnormalities in the digestive system， central nervous system， hematopoietic system， urinary system， and liver function to varying degrees. Syndrome differentiation is usually used for the treatment of epilepsy by traditional Chinese medicine （TCM）， which can avoid the side effects of western medicine treatment on the basis of improving patients' syndromes. The literature on TCM in the treatment of epilepsy in China and abroad indicates that the syndrome differentiation in TCM is often based on phlegm， blood stasis， wind， and deficiency， and the treatment methods include acupuncture， acupoint catgut embedding， moxibustion， Chinese medicine monomer， drug pair， and compound decoction. The various treatments of TCM play an important role in the comprehensive treatment of epilepsy through multiple channels and links， such as reducing the degree and number of seizures. This paper comprehensively summarized the clinical experience of TCM in the treatment of epilepsy， systematically expounded various treatment methods and ideas of TCM in the treatment of epilepsy， and deeply discussed the mechanism of TCM in the treatment of epilepsy， aiming to provide a theoretical basis for the clinical formulation of a reasonable individualized treatment plan for epilepsy and diversified ideas for the more effective treatment of epilepsy by TCM.

Traditional Chinese medicine has the characteristics of multiple components， pathways， and targets in the treatment of fracture healing， and has good therapeutic advantages and potential for fractures with complex pathological mechanisms. Based on this， the author summarized the mechanism of promoting fracture healing by the monomer components and compound formulas of traditional Chinese medicine and found that visfatin A， puerarin， and others can activate the mitogen-activated protein kinase （MAPK） signaling pathway； Xugudan， Guben zenggu formula and others can activate bone morphogenetic protein （BMP） signaling pathway； baicalin， Achyranthes bidentata polysaccharides and others can activate Wnt/β -catenin signaling pathway； apigenin， notoginsenoside and others can activate receptor activator of nuclear factor-κB （NF-κB）/receptor activator of NF-κB ligand/osteoprotegerin （RANK/RANKL/OPG） signaling pathway； Compound huoxue jiegu capsule， Jiangu granule and others can inhibit phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway； icariin can activate Notch signaling pathway； Taohong siwu decoction， crocin and others can activate Hippo signaling pathway； jujuboside A and osthole can inhibit NF-κB signaling pathway， and thus promote fracture healing.

Objective:To investigate the effects of mixed probiotics on food allergy and the underlying mechanism.Methods:BALB/c mice on the 15 th day of pregnancy were randomly (random number table method) classified into the control group, food allergy model group and mixed probiotics group.Mice in the food allergy model and mixed pro-biotics group were subjected to ovalbumin (OVA) sensitization after birth, and those in the mixed probiotics group were then given probiotic solution by gavage from day 21 to day 35.Mice in control group were similarly given 9 g/L saline.Twenty-four hours after the last OVA sensitization, intestinal histopathological sections were prepared to observe intestinal pathological changes.Blood smears were prepared to detect eosinophil count.In addition, serum samples were collected to measure cytokine levels and OVA specific antibodies.The number of dendritic cells (DCs) and regulatory T cells (Tregs) in mouse mesenteric lymph nodes was calculated.Differences among 3 groups were compared by the One- Way ANOVA or Kruskal- Wallis H test. Results:Compared with those of food allergy model group, diarrhea score, the ratio of eosinophils and serum levels of interleukin(IL)-4, IL-5, IL-13, mast cell protease 1 (MCPT-1), and OVA specific antibodies IgE and IgG were significantly lower in mixed probiotics group[(2.00±0.71) points vs.(3.22±0.97) points, (2.28±1.61)% vs.(10.99±2.26)%, (413.68±22.81) ng/L vs.(708.78±27.66) ng/L, (36.64±3.74) ng/L vs.(46.05±4.95) ng/L, (201.37±65.61) ng/L vs.(495.22±96.66) ng/L, (31 924.15±1 177.77) ng/L vs.(36 175.77±618.29) ng/L, (9.10±8.08) ng/L vs.(19.69±0.84) ng/L, (30.50±8.81) ng/L vs.(190.32±6.40) ng/L], while IL-10 level was significantly higher[(164.12±3.88) ng/L vs.(123.90±7.31) ng/L] ( t=3.37, 8.72, 16.07, 3.90, 7.40, 7.95, 3.91, 44.00 and 7.76, respectively, all P<0.01). Compared with those of food allergy model group, programmed cell death ligand 1 (PD-L1) level on the surface of CD 103+ DCs and CD 103+ CD 80-CD 40-DCs, the proportion of Tregs in CD4 + T cells, and the level of programmed cell death 1 (PD-1) on the surface of Tregs were significantly higher in mixed probiotics group[(75.59±0.45)% vs.(45.60±4.73)%, (67.56±1.87)% vs.(37.12±6.07)%, (8.24±0.69)% vs.(6.20±0.66)%, (11.25±3.12)% vs.(4.08±2.33)%]( t=7.88, 4.48, 3.63 and 3.71, all P<0.01). Conclusions:Mixed probiotics can alleviate the symptoms of food allergy and inflammatory response of young rats through mediating Tregs via the PD-1/PD-L1 pathway.