Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

It is proposed that cold pathogen plays an important promoting role in the onset and progression of hyperlipidemia. External exposure to cold， the gradual generation of internal cold， and the covert consumption of yang qi caused by modern lifestyle factors may all provide a pathological basis for the development of hyperlipidemia. Based on the pathogenic characteristics of cold， namely its tendency to damage yang， induce stagnation， and cause contraction， this paper suggests that the treatment of hyperlipidemia should focus on warming and tonifying， warming and resolving， and warming and unblocking， respectively. This provides a theoretical reference for the diagnosis and treatment of hyperlipidemia with traditional Chinese medicine.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Recent studies have revealed a significant association between Porphyromonas gingivalis(P.gingivalis)infection and poor prognosis in esophageal squamous cell carcinoma(ESCC).Although cer-tain circular RNAs(circRNA)have been shown to suppress ESCC tumorigenesis and progression,their regulatory mechanisms in P.gingivalis infection-associated ESCC remain elusive.In this study,RT-qPCR analysis demonstrated that P.gingivalis infection downregulated hsa_circ_0057552 expression in ESCC cells and tissues in a time-and dose-dependent manner.Actinomycin D assays further confirmed that P.gingivalis infection reduced the RNA stability of hsa_circ_0057552 in ESCC cells(P＜0.05).Functional assays in vitro and a subcutaneous tumor xenograft model in vivo revealed that hsa_circ_0057552 overexpression significantly inhibited ESCC cell proliferation,migration,invasion,and tumor growth(P＜0.05).Additionally,PCR array screening combined with RT-qPCR and Western blotting in-dicated that P.gingivalis infection markedly upregulated human antigen R(HuR)expression at both RNA and protein levels(P＜0.05).Mechanistic investigations demonstrated that HuR knockdown signifi-cantly increased hsa_circ_0057552 expression(P＜0.01),whereas hsa_circ_0057552 overexpression had no regulatory effect on HuR.Finally,si-HuR treatment reversed the inhibitory effect of P.gingivalis on hsa_circ_0057552 transcription.This study demonstrated that P.gingivalis may promote the progression of ESCC through a novel mechanism involving the regulation of HuR/hsa_circ_0057552,thereby identif-ying a novel therapeutic target and molecular marker for P.gingivalis-associated ESCC.

Objective To investigate the effects of miR-1 on the proliferation,migration and invasion of esophageal squamous cell carcinoma.Methods miR-1 mimics,inhibitors and their corresponding controls were transfected into ESCC cells ECa109 and KYSE410.The efficiency of cell transfection was validated by SYBR-green quantitative PCR.The proliferation,migration and invasion ability of ESCC cells were assessed by MTT,foci formation,wound healing and Matrigel invasion assays,respectively.Statistical analysis was carried out using SPSS 22.0software for Windows.Results Overexpression of miR-1 markedly inhibited the cell growth rate and the colony-forming ability of the ESCC cells.While,downregulation of miR-1 promoted the cell growth rate and foci formation(P＜0.05).And upregulation or downregulation of miR-1 significantly suppressed or promoted tumor cell invasion and migration(P＜0.05).Conclu-sion miR-1 inhibited ESCC cell proliferation,invasion and migration,suggesting that miR-1 functions as a tumor suppressor in the tumorigenesis and progression of ESCC and may be a potential therapeutic target.

Recent studies have revealed a significant association between Porphyromonas gingivalis(P.gingivalis)infection and poor prognosis in esophageal squamous cell carcinoma(ESCC).Although cer-tain circular RNAs(circRNA)have been shown to suppress ESCC tumorigenesis and progression,their regulatory mechanisms in P.gingivalis infection-associated ESCC remain elusive.In this study,RT-qPCR analysis demonstrated that P.gingivalis infection downregulated hsa_circ_0057552 expression in ESCC cells and tissues in a time-and dose-dependent manner.Actinomycin D assays further confirmed that P.gingivalis infection reduced the RNA stability of hsa_circ_0057552 in ESCC cells(P＜0.05).Functional assays in vitro and a subcutaneous tumor xenograft model in vivo revealed that hsa_circ_0057552 overexpression significantly inhibited ESCC cell proliferation,migration,invasion,and tumor growth(P＜0.05).Additionally,PCR array screening combined with RT-qPCR and Western blotting in-dicated that P.gingivalis infection markedly upregulated human antigen R(HuR)expression at both RNA and protein levels(P＜0.05).Mechanistic investigations demonstrated that HuR knockdown signifi-cantly increased hsa_circ_0057552 expression(P＜0.01),whereas hsa_circ_0057552 overexpression had no regulatory effect on HuR.Finally,si-HuR treatment reversed the inhibitory effect of P.gingivalis on hsa_circ_0057552 transcription.This study demonstrated that P.gingivalis may promote the progression of ESCC through a novel mechanism involving the regulation of HuR/hsa_circ_0057552,thereby identif-ying a novel therapeutic target and molecular marker for P.gingivalis-associated ESCC.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

AIM:To investigate the protective effects of Klotho protein against hypoxia/reoxygenation(H/R)-in-duced damage in rat cardiomyocytes,and to elucidate its underlying mechanisms.METHODS:Rat cardiomyocyte H9c2 cells were divided into 4 groups:control,H/R,low-concentration(1 μmol/L)Klotho+H/R,and high-concentration(10 μmol/L)Klotho+H/R groups.Cells were pretreated with Klotho at specified concentrations before induction of H/R injury.Flow cytometry was used to determine cardiomyocyte apoptosis rates,while reactive oxygen species(ROS)levels were measured using the DCFH-DA probe.Additionally,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were assessed using biochemical assay kits.Mitochondrial membrane potential was evaluated using the JC-1 as-say,and activity of caspase-3 and caspase-9 was quantified.Western blot analysis was conducted to measure the protein expression of cytochrome C(Cyt-C),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in cardio-myocytes from each group.RESULTS:Compared with the control group,the H/R group exhibited significantly increased apoptosis rates(P<0.05),elevated ROS levels and MDA content,decreased SOD activity(P<0.05),reduced mitochon-drial membrane potential(P<0.05),increased caspase-3 and caspase-9 activity(P<0.05),decreased mitochondrial Cyt-C and Bcl-2 protein expression(P<0.05),and increased cytoplasmic Cyt-C and Bax protein expression(P<0.05).In comparison with the H/R group,both low-and high-concentration Klotho treatments significantly reduced cardiomyocyte apoptosis(P<0.05),lowered ROS levels and MDA content(P<0.05),increased SOD activity(P<0.05),restored mito-chondrial membrane potential(P<0.05),decreased caspase-3 and caspase-9 activity(P<0.05),increased mitochondrial Cyt-C and Bcl-2 expression(P<0.05),and decreased cytoplasmic Cyt-C and Bax expression(P<0.05).Notably,the high-concentration Klotho group demonstrated more pronounced protective effects(P<0.05).CONCLUSION:Klotho protein exerts protective effects against H/R-induced cardiomyocyte injury,possibly by inhibiting mitochondria-mediated apoptosis.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Objective To investigate the effects of miR-1 on the proliferation,migration and invasion of esophageal squamous cell carcinoma.Methods miR-1 mimics,inhibitors and their corresponding controls were transfected into ESCC cells ECa109 and KYSE410.The efficiency of cell transfection was validated by SYBR-green quantitative PCR.The proliferation,migration and invasion ability of ESCC cells were assessed by MTT,foci formation,wound healing and Matrigel invasion assays,respectively.Statistical analysis was carried out using SPSS 22.0software for Windows.Results Overexpression of miR-1 markedly inhibited the cell growth rate and the colony-forming ability of the ESCC cells.While,downregulation of miR-1 promoted the cell growth rate and foci formation(P＜0.05).And upregulation or downregulation of miR-1 significantly suppressed or promoted tumor cell invasion and migration(P＜0.05).Conclu-sion miR-1 inhibited ESCC cell proliferation,invasion and migration,suggesting that miR-1 functions as a tumor suppressor in the tumorigenesis and progression of ESCC and may be a potential therapeutic target.