Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

BACKGROUND:Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury;however,the specific mechanism is still not clear.Therefore,revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE:To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS:Allen's impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group.The serum of rats of each group was collected.H9c2 cells were divided into a blank control group,a sham operated rat serum group,a spinal cord injury rat serum group and a luteolin pretreatment group.The cells in blank control group were only cultured with ordinary culture medium.The cells in the sham operated rat serum group were treated with medium containing 10%serum from sham operated rat.The cells in the spinal cord injury rat serum group were treated with medium containing 10%serum from spinal cord injury rat.The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10%rat serum from spinal cord injury rat.After 24 hours of culture,the survival rate of each group of H9c2 cells was measured by CCK-8 assay.Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION:Compared with the blank control group,there was no significant change in cell survival rate in the sham operated rat serum group(P>0.05).Compared with the sham operated rat serum group,the cell survival rate(P<0.01)and the expression of LC3 protein(P<0.05)in spinal cord injury rat serum group was significantly reduced,and the expression of p62 protein was significantly increased(P<0.05).Compared with the spinal cord injury rat serum group,the survival rate of cells in the luteolin pretreatment group significantly increased(P<0.000 1);the expression of LC3 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05).The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.

OBJECTIVES: This study aimed to explore the potential target and molecular mechanism of Eclipta prostrata L-Ligustrum Lucidum Ait (EPL-LLA) in the treatment of periodontitis by using network pharmacology and molecular docking technology, and to explore its biocompatibility, regulatory effects on inflammatory factors, and antioxidant acti-vity through in vitro experiments. METHODS: The active components and potential targets of EPL-LLA were screened and predicted through a variety of databases, and the intersection of EPL-LLA and periodontitis targets was selected. The protein interaction network (PPI) was analyzed by the string platform. The Metascape database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The active ingredients from the top 6 degrees were docked with the core targets, and the results of binding energy were visualized. An in vitro cell model was established to evaluate the biocompatibility, modulation of inflammatory factors, and antioxidative effects of EPL-LLA through cell counting kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe assays. RESULTS: Screening revealed 13 active components in EPL corresponding to 220 potential targets, 10 active components in LLA corresponding to 283 potential targets, and 1 643 periodontitis-related targets, with 91 shared targets among the three. GO analysis of the shared targets yielded 5 271 entries, while KEGG enrichment analysis indicated involvement in 253 signaling pathways. Molecular docking confirmed stable binding between the top 6 active components and core targets. CCK-8 assays demonstrated good biocompatibility of EPL-LLA at concentrations 0.02 mg/mL (P<0.05). qRT-PCR showed that EPL-LLA reduced the mRNA expression of pro-inflammatory factors in macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide while upregulating anti-inflammatory factor mRNA expression (P<0.05). DCFH-DA fluorescence probe assays confirmed the reactive oxygen species (ROS)-scavenging capacity of EPL-LLA (P<0.05). CONCLUSIONS EPL-LLA may treat periodontitis through multi-component, multi-target, and multi-pathway mechanisms, providing a theoretical basis for further research on its therapeutic potential.
Periodontitis/drug therapy* ; Molecular Docking Simulation ; Eclipta/chemistry* ; Humans ; Protein Interaction Maps ; Ligustrum/chemistry* ; Antioxidants/pharmacology* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology

ObjectiveTaking the oligosaccharides in Rehmanniae Radix（RR） as the research object， the content determination method based on high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） and thin layer chromatography（TLC） identification method were established to explore the content and distribution of oligosaccharides in different RR herbs and decoction pieces. MethodA total of 10 batches of fresh and raw RR， 12 batches of RR decoction pieces and Rehmanniae Radix Praeparata（RRP） were collected. A TLC identification method for fructose， sucrose， manninotriose， raffinose and stachyose in RR was established by using silica gel G thin-layer plates with ethyl acetate-water-anhydrous formic acid-glacial acetic acid（12∶6∶5∶4） as the developing agent and 10% sulfuric acid-ethanol solution as chromogenic agent. A HPLC-ELSD was used to determine the contents of fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose in different RR herbs and decoction pieces. Then principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to analyze the contents of 7 kinds of saccharides in RR herbs and decoction pieces， and the differential components were screened with the value of variable importance in the projection（VIP）>1. ResultThe results of TLC identification showed that fresh RR， raw RR and its decoction pieces showed spots of the same color on the corresponding positions with the control products of stachyose， raffinose and sucrose， while the TLC of RRP showed spots of the same color at corresponding positions to manninotriose and fructose controls. The results of methodological investigations of 7 analytes met the requirements of determination. Only glucose， sucrose， raffinose and stachyose were detected in 10 batches of fresh RR and 10 batches of raw RR herbs， the average contents of which were 0.84%， 4.62%， 2.42% and 57.90% in fresh samples， while those were 3.16%， 9.36%， 7.05% and 38.10% in raw samples， respectively. In 12 batches of RR decoction pieces， the contents of the above seven sugars（fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose） were 1.68%， 4.27%， 9.96%， 0.53%， 6.85%， 3.05% and 37.52%， respectively. In 12 batches of RRP， the contents of the above seven sugars were 10.62%， 11.01%， 1.25%， 3.35%， 1.12%， 28.16% and 6.39%， respectively. The results of multivariate statistical analysis showed that fresh RR， raw RR and RRP could be distinguished from each other by the contents of the 7 sugars， and the main differential components were stachyose， sucrose， raffinose and manninotriose. ConclusionIn terms of oligosaccharides， the contents and types of saccharides in different herbs and decoction pieces of RR are quite different， and the TLC identification method based on this can be used to distinguish raw RR from RRP， which can lay a foundation for improving the quality standard of RR and developing and applying oligosaccharides in different processed products of RR.

Objective:To analyze the dietary patterns of Chinese adults and explore the relationship with serum uric acid (SUA) and hyperuricemia (HUA).Methods:A total of 9 358 adults were selected in the 2018 China Health and Nutrition Survey. Dietary intake data were collected by three consecutive 24-hour dietary recalls and weighing method. The social demographic information of the survey subjects was obtained through questionnaire surveys. The dietary patterns were extracted using factor analysis, and the relationship between dietary patterns and SUA was analyzed using multiple linear regression analysis. The correlation between HUA and dietary patterns was analyzed using logistic regression analysis models.Results:Four dietary patterns were identified: northern (high intakes of wheat, other cereals,and tubers); modern (high intakes of fruit, dairy, eggs, and nuts); southern (high intakes of rice and vegetables);animal food-wine (high intake of organ meats, seafood, and wine). The multiple linear regression analysis results showed that the northern pattern was negatively correlated with SUA ( β=-0.438, 95% CI: -0.500--0.376); the modern pattern was negatively correlated with SUA ( β=-0.134, 95% CI: -0.219--0.049); the southern model was significantly correlated with higher SUA ( β=0.146, 95% CI: 0.079-0.214); the animal food-wine pattern was positively correlated with SUA ( β=0.188, 95% CI: 0.123-0.252). Logistic regression analysis showed that compared with the northern model score Q1 group, the risk of developing HUA was reduced in Q3 and Q4 groups, with ORs values of 0.777 (95% CI: 0.650-0.929) and 0.509 (95% CI: 0.423-0.613), respectively; and compared with the modern model score Q1 group, the higher the scores in Q3 and Q4 groups, the HUA was lower, with ORs of 0.793 (95% CI: 0.660-0.953) and 0.768 (95% CI: 0.631-0.934), respectively. Compared with the animal food-wine pattern score Q1 group, the risk of developing HUA was increased in both Q3 and Q4 groups ( Q3 group: OR=1.224, 95% CI: 1.012-1.480; Q4 group: OR=1.312, 95% CI: 1.086-1.584). Conclusions:Dietary patterns are associated with HUA. The northern and modern patterns are related to lower SUA levels and reduced risk of HUA, while the animal food-wine pattern increases the risk of HUA.

Hydration status refers to the balance between the intake and discharge of water in the body. When the ingested and discharged water are roughly equal and the body is in water balance, it is the normal hydration status, and when the water intake is too little or too much, it is the "dehydration" or "overhydration status". The hydration status of the body not only affects metabolism, but also affects the functions of the urinary system, cardiovascular system, nervous system, etc. In order to further clarify the relationship between body hydration status and decompression sickness (DCS), this paper reviewed relevant studies and analyzed the interaction between hydration and decompression safety during diving. The primary causes of dehydration in diving are "hyperbaric diuresis", "immersion diuresis", breathing dry gas, heat, and cold. Dehydration not only promotes the occurrence of DCS but also reduces the aerobic work efficiency and athletic performance of divers, as well as affects cognition and mood. A study found that appropriate rehydration before and during diving can reduce the risk of DCS, which possibly associates with the increase of blood volume, plasma surface tension, and vasoconstriction. Fluid therapy is also important for those who already have DCS. This paper analyzed the amount, nature, timing, and effect of rehydration involved in the above links, comprehensively sorted out the relationship between hydration and diving safety, summarized the existing problems, and provided reference for practical application and future research.