ObjectiveTo investigate the therapeutic effect and mechanism of Solanum nigrum on hepatic fibrosis induced by carbon tetrachloride （CCl₄） in rats. MethodsSixty SD rats were randomly allocated into blank， model， low-， medium-， and high-dose （0.9， 1.8， 3.6 g·kg^-1， respectively） S. nigrum， and silibinin capsules （18.9 mg·kg^-1） groups. Except the blank group， the other groups were subjected to intraperitoneal injection of 40% CCl₄ solution for the modeling of hepatic fibrosis. After 4 weeks of gavage， blood was collected from the abdominal aorta following intraperitoneal anesthesia. The rats were sacrificed， and the liver was separated. The pathological changes were observed by hematoxylin-eosin staining and Masson staining. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and liver fibrosis indexes ［type Ⅲ procollagen （PCⅢ）， type Ⅳ collagen （Col Ⅳ）， laminin （LN）， and hyaluronic acid （HA）］ in the rat serum were determined. The mRNA and protein levels of B cell lymphoma-2 （Bcl-2）/Bcl-2-associated X protein （Bax）/cysteinyl aspartate-specific proteinase-3 （Caspase-3） pathway-related factors were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the blank group， the model group exhibited significant hepatocyte edema， infiltration of inflammatory cells， connective tissue proliferation， and collagen fiber deposition in the liver tissue. Compared with the model group， low-， medium-， and high-dose S. nigrum and silymarin capsules significantly improved the structure of liver cells and alleviated the edema， inflammatory cell infiltration， connective tissue proliferation， and collagen fiber deposition. Compared with those in the blank group， the serum levels of ALT， AST， PCⅢ， Col Ⅳ， LN， and HA were elevated in the model group （P<0.01）. Compared with the model group， the serum levels of ALT， AST， PCⅢ， Col Ⅳ， LN， and HA were reduced in all the treatment groups （P<0.05）. Real-time PCR and Western blot results showed that compared with the blank group， the model group had up-regulated mRNA and protein levels of Bcl-2 and down-regulated mRNA and protein levels of Bax and Caspase-3 （P<0.01）. Compared with the model group， all the treatment groups showed down-regulated mRNA and protein levels of Bcl-2 and up-regulated mRNA and protein levels of Bax and Caspase-3 （P<0.05）， with the high-dose S. nigrum group showing the best therapeutic effect. ConclusionS. nigrum modulates the progression of hepatic fibrosis in rats by regulating apoptosis through the Bcl-2/Bax/caspase-3 pathway.

OBJECTIVE To investigate the ameliorative effects and mechanisms of Miao medicine Euphorbia humifusa on hepatic fibrosis （HF） model rats. METHODS Thirty-eight rats were randomly assigned according to a random number table into control group （normal saline， n＝7）， model group （normal saline， n＝7）， E. humifusa low-， medium- and high-dose groups （0.675， 1.35， 2.70 g/kg， n＝6）， and silybin group （positive control， 18.9 mg/kg， n＝6）. All groups except the control group were subjected to HF induction via intraperitoneal injection of carbon tetrachloride. After modeling， rats were administered their respective drugs/normal saline by gavage， once a day， for 30 days. At the last medication， the liver index was calculated， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-17 （IL-17）， IL-1β， IL-6， alanine transaminase （ALT）， aspartate transaminase （AST）， and hydroxyproline （HYP） were measured. Liver morphology and HF changes were observed. Levels of transforming growth factor- β1 （TGF- β1） and α-smooth muscle actin （α-SMA）， as well as the expressions of α -SMA， proteins related to TNF- α/NF- κB signaling pathway， mRNA expressions of TNF-α and NF-κB p65 in liver tissue were determined. RESULTS Compared with model group， liver index， serum levels of TNF-α， IL-17， IL-1β， IL-6， ALT， AST and HYP， relative expression of NF-κB p65 mRNA， and the levels of TNF-α and α-SMA proteins and phosphorylated NF-κB p65 in liver tissues of rats from administration groups， the expressions of α-SMA and TGF-β1 in liver tissue of rats from E. humifusa medium-dose and high-dose groups， as well as positive staining percentage and mRNA expression of TNF- α in liver tissue of rats from E. humifusa high-dose group were all decreased significantly （P＜0.05 or P＜0.01）； IκBα protein expression from administration groups was significantly increased （P＜0.05 or P＜0.01）. Pathological changes and the degree of HF in the liver tissues of rats from administration groups were ameliorated to various extents. CONCLUSIONS E. humifusa may alleviate HF in rats by inhibiting the activation of the TNF-α/NF-κB signaling pathway.

It has been popular and challenging to undertake researches on the delay of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). As key cells for tumor initiation, cancer stem cells (CSC) play an important role in the process of resistance to EGFR-TKI. Although preliminary studies found that traditional Chinese medicine (TCM) could inhibit CSC properties and delay EGFR-TKI resistance, the specific molecular mechanism remains unclear. By summarizing the empirical syndrome treatment of EGFR-TKI resistance via TCM and combining recent researches on TCM intervention in CSC to delay EGFR-TKI resistance, this review discussed the potential molecular pathways and mechanisms of deceleration in resistance to EGFR-TKI by TCM via inhibiting CSC characteristics, in order to expand the research ideas of TCM in combination with targeted therapy.
Humans ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Medicine, Chinese Traditional ; Neoplasms/drug therapy* ; Animals ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVES: To propose a single repetition time (TR) quantitative magnetic susceptibility imaging method for the lumbar spine using bipolar readout gradient, and compare the quantitative magnetic susceptibility measurement using single TR and dual TR methods for the lumbar spine with different bone densities. METHODS: A translation correction method was proposed to correct spatial misalignment along the frequency encoding direction between positive and negative gradient readout images, and the phase difference between the images was eliminated using a phase correction method. The data of lumbar vertebrae L1-L5 were collected using single TR and dual TR methods from 6 normal individuals, 2 patients with osteopenia, and 2 patients with osteoporosis. The magnetic susceptibility map was reconstructed, the quantitative results of single TR before and after correction were compared with those of the dual TR method. RESULTS: The linear regression result of the lumbar spine magnetic susceptibility values obtained by the single TR method before calibration and the dual TR method is Y=0.64*X-11.61. The linear regression result of the lumbar spine magnetic susceptibility values corrected by the single TR method and the dual TR method is Y=1.03*X+0.25. The results of the corrected single TR method were highly consistent with those of the dual TR method, and the calibrated single TR method could effectively distinguish osteopenia and osteoporosis patients from normal individuals. CONCLUSIONS The calibrated single TR bipolar readout gradient method can generate artifact-free lumbar spine quantitative magnetic susceptibility distribution maps and reduce data acquisition time by 50%.
Humans ; Lumbar Vertebrae/pathology* ; Magnetic Resonance Imaging/methods* ; Female ; Middle Aged ; Male ; Osteoporosis/diagnosis* ; Adult ; Bone Density ; Aged ; Bone Diseases, Metabolic/diagnosis*

Hepatic fibrosis(HF)is an inevitable process for many chronic liver diseases to develop into liver cirrhosis and even liver cancer.More than 80%of hepatocellular carcinomas are formed after the process of chronic hepatitis,HF or liver cirrhosis.The immune microenvironment produced by inflammation and fi-brosis plays a significant role in promoting the occurrence and development of hepatocellular carcinoma.He-patic stellate cells(HSC),extracellular matrix(ECM),and fibroblasts are involved in the progression of HF by influencing innate immunity and adaptive immunity.This article,by analyzing the role of immune cells in HF,is expected to provide new intervention approaches and therapeutic targets for the clinical treatment of HF,thereby further enhancing the effectiveness of immunotherapy and offering safer and more effective treat-ment options for HF patients.

OBJECTIVE To investigate the improvement effects of glycyrrhizin （GL） on Helicobacter pylori （HP）-associated gastritis in rats and its mechanism. METHODS HP-associated gastritis rat model was induced by inoculating with 1×109 cfu/mL HP. The model rats were randomly divided into model group， positive control group （HP standard quadruple group）， GL low-dose， medium-dose and high-dose groups （5， 20， 50 mg/kg）， with 12 rats in each group. Another 12 healthy rats were selected as normal control group. Except the normal control group and model group were given constant volume of normal saline intragastrically， the other groups were given corresponding drugs intragastrically， once a day， for 30 consecutive days. After administration， rats received 13C urea breath test， and delta-over-baseline （DOB） was recorded； the pathological and cellular morphological changes of gastric mucosa in rats were observed， and pathological scoring was performed； the levels of interleukin-8 （IL-8）， IL-1β， tumor necrosis factor-α （TNF-α）， reactive oxygen species （ROS） and malondialdehyde （MDA） were detected in gastric mucosa of rats； mRNA expressions of high mobility group box-1 protein （HMGB1） and nuclear factor-κ-B （NF-κB）， relative expressions of nitric oxide synthases （iNOS） and HMGB1， the phosphorylation level of NF- κBp65 were also detected in rats. RESULTS Compared with normal control group， the DOB value， histopathological score of gastric mucosa， the levels of IL-8， IL-1β， TNF-α， ROS and MDA， relative expressions of HMGB1 and NF- κB mRNA， relative expressions of iNOS and HMGB1 protein and the phosphorylation level of NF-κB p65 were all increased significantly in model group （P＜0.05）； the epithelial cells of gastric mucosa in rats were incomplete in structure and decreased in the number， with an increase in cell fragments and vacuoles， and significant cell pyknosis. Compared with model group， the changes of the above indexes in GL groups and positive control group were significantly reversed （P＜0.05）； the changes in the above indicators in the GL high-dose group were more significant than GL low-dose and medium-dose groups （P＜0.05）； the pathological changes of gastric mucosal cells in rats had all improved. CONCLUSIONS GL may inhibit inflammation and oxidative stress by inhibiting the activation of HMGB1/NF-κB pathway， thus relieving HP-induced gastric mucosal injury.

Objective To explore the causal association between gut microbes and non-alcoholic fatty liver disease(NAFLD)by Mendelian randomisation analysis.Methods Genetic instrumental variables for gut microbiota were identified from a gene-wide association study of 18 340 participants,and summary statistics for NAFLD were ob-tained from the FinnGen database,which provided data on 894 NAFLD cases and 217 898 controls using the IVW method as the primary analysis.In order to test the robustness of the results,MR-Egger method,WM method,Simple Mode method,Weighted Mode method were used for Mendelian randomisation analysis,and heterogeneity test,sensitivity analysis,and multiplicity analysis were performed.Results class Gammaproteobacteria IVW re-sults showed(OR=0.621,95％CI=0.412～0.934,P=0.022);family Enterobacteriaceae IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018);genus Lachnospiraceae IVW results showed(OR=1.405,95％CI=1.036～1.904,P=0.029);genus Prevotella7 IVW results showed(OR=0.834,95％CI=0.714～0.974,P=0.021);genus Prevotella9 IVW results showed(OR=1.251,95％CI=1.025～1.527,P=0.027);order Desulfovibrionales IVW results showed(OR=0.714,95％CI=0.519～0.982,P=0.038);or-der Enterobacteriales IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018).And there was no heterogeneity in the heterogeneity test,and the sensitivity analyses all showed robustness and no pleiotropy was found.Conclusion This study implicates class Gammaproteobacteria,family Enterobacteriaceae,genus Lachno-spiraceae,genus Prevotella7,genus Prevotella9,order Desulfovibrionales,order Enterobacteriales seven species of gut microorganisms have a causal relationship with NAFLD.

OBJECTIVE To study the inhibitory effect and mechanism of total flavonoids from Melicope pteleifolia （TF-MPL） on transplanted tumor of colorectal cancer in nude mice. METHODS The transplanted tumor model of colorectal cancer was induced by injecting 0.2 mL colorectal cancer cell LoVo subcutaneously via the right armpit of nude mice. After successful modeling， nude mice were randomly divided into model group， 5-fluorouracil group （positive control， 10 mg/kg）， TF-MPL high- dose and low-dose groups （25， 12.5 mg/kg）； a normal group （normal saline containing 0.3% carboxymethyl cellulose sodium） without modeling was additionally set up， with 6 mice in each group. Each group was intraperitoneally injected with the corresponding drug solution/solvent for 21 consecutive days. The inhibitory rate of the transplanted tumor， liver and spleen index， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected after the last medication； the morphological changes of tumor tissue were observed； immunohistochemical staining was used to detect protein expressions of Toll- like receptor 4 （TLR4） and nuclear factor-κB subunit p65 （NF-κB p65） in tumor tissue of nude mice. Western blot assay was used to detect protein expressions of TLR4， myeloid differentiation factor 88 （MyD88）， TNF receptor-associated factor 6 （TRAF6）， interleukin-1 receptor-associated kinase 1 （IRAK-1）， NF-κB p65 and caspase-3 in tumor tissue of nude mice. RESULTS Compared with the model group， TF-MPL high-dose group showed a significant decrease in tumor weight （inhibitory rate of 36.91%）， liver and spleen index， serum levels of TNF-α and IL-6 and protein expressions of TLR4， MyD88， TRAF6，IRAK-1 and NF- κB p65 （P＜0.05 or P＜0.01）； the expression of caspase-3 protein was increased significantly （P＜0.05）， and more tumor cell shrinkage and deformation， nuclear pyknosis and fragmentation were observed. CONCLUSIONS TF-MPL can significantly inhibit the growth of transplanted tumor of colorectal cancer in nude mice， the mechanism of which may be associated with reducing inflammatory response， inhibiting TLR4/MyD88/NF-κB signaling pathway， and promoting apoptosis in colorectal cancer cells.

Objective To explore the relationship between peripheral blood lymphocytes and disease progression in patients with amyotrophic lateral sclerosis(ALS)in central China.Methods A total of 133 ALS patients diagnosed at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology were evaluated for disease progression,and the includ-ed patients were divided into fast progression group and slow progression group.Peripheral blood lymphocyte subsets were de-termined and compared between the two groups.Logistic regression was used to analyze the association between the statistically different lymphocyte subgroups and the rate of disease progression.Results The proportion of CD3+CD19-T lymphocytes in the slow progression group was lower than that of the fast progression group(P＜0.05).However,the NK cell count,NK cell proportion,and the proportion of CD28+helper T cells(CD28+Th cells)were higher than those of the fast progression group(all P＜0.05).In the logistic regression analysis,an increase in NK cell count(OR=0.992,P＜0.05)and an increase in the propor-tion of CD28+Th cells(OR=0.895,P＜0.05)were protective factors for the progression of ALS.Conclusion The characteris-tics of peripheral lymphocytes differed between patients with slow and fast progression.Abnormalities in the innate immune sys-tem may be involved in the progression of ALS.

Purpose: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. Methods: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry, and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis, and the AMOS 21.0 software was used to explore the mediating relationships between variables. Results: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p < .05). Social support and recurrence risk perception could affect health behavior indirectly through self-efficacy, behavioral decision-making, and worry. Behavioral decision-making acted as a main mediator between recurrence risk perception and health behavior, while the path coefficient was .47 and .37, respectively. The chain mediation effect between recurrence risk perception and health behavior was established with a total effect value of .19 (p < .01). Conclusion Most stroke survivors could be aware of recurrence risk but failed to accurately estimate their individual risk. In the mediation model of recurrence risk perception and health behavior, social support seemed to be an important external factor, while self-efficacy, behavioral decision-making, and worry seemed to act as key internal factors.