ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Aim To investigate the effect of safflower yellow on the learning and memory of scopolamine hydrobromide-induced memory impairment model mice.Methods 6-month-old C57BL/6J mice were randomly divided into the control group,model group,SY high-dose group,SY medium-dose group,SY low-dose group,and Huperzine-A group(12 mice in each group).SCOP was used to establish a memory impair-ment model,the spatial learning,memory and cognitive ability of mice with memory impairment were evaluated by behavioral experiments,the function of the choliner-gic nervous system in the cortex of mice was measured by ELISA kit,the pathological changes of brain tissue were observed by Nissl staining,and the expression of synaptic plasticity and BDNF/TrkB/CREB pathway re-lated proteins in the cortical and hippocampus of mice in each group was detected by Western blot.Results Compared with the model group,the learning and mem-ory ability of the mice in each administration group was improved.The neurons in the hippocampus and corti-cal were neatly arranged,the cell morphology tended to be complete,and the number of normal neurons in-creased.The function of the cortical cholinergic nerv-ous system was significantly improved,the expression of synaptic plasticity-related proteins in brain tissue was increased,and the BDNF/TrkB/CREB signaling path-way was activated.Conclusions SY can significantly improve the learning and memory ability of mice with SCOP-induced memory impairment,and its mechanism may play a neuroprotective role by improving choliner-gic nervous system function,activating BDNF/TrkB/CREB signaling pathway,regulating synaptic plasticity,and reduces neuronal damage.

Objective To explore the potential value of three-dimensional fast spin echo(3D-SPACE)combined with multilayer spiral CT(MSCT)in the diagnosis of knee cruciate ligament injury,to provide a new direction for the optimization of subsequent clinical diagnosis.Methods A total of 120 patients with knee cruciate ligament injury were treated from April 2020 to April 2021,aged from 21 to 68 with an average of(41.52±4.13)years old.For all patients,separate MSCT scanner scans,3D-SPACE sequence scans alone and 3D-SPACE sequence combined with MSCT scans were used.The injury and classifica-tion of the anterior and posterior cruciate ligament of the knee were compared,the length of the anterior-medial bundle and posterolateral bundle and its angle of the knee with the horizontal plane were observed,the diagnostic value of 3 diagnostic methods in knee cruciate ligament injury were determined.Results There was no significant difference between the 3D-SPACE sequence scan alone and the MSCT test alone on the total diagnostic rate and grading total diagnostic rate(P＞0.05).The total diagnostic rate and grading total diagnostic rate of 3D-SPACE scan combined with MSCT were significantly higher than those of 3D-SPACE scan or MSCT alone(P＜0.05).The 3D-SPACE sequence scan alone and the MSCT detection alone had no signifi-cant difference in the measurement values related to the anterior and posterior cruciate ligaments of the knee joint(P＞0.05).3D-SPACE sequence scanning combined with MSCT detection on the knee joint anterior and posterior cruciate ligament related mea-surements were significantly higher than the 3D-SPACE sequence scan or MSCT detection alone(P＜0.05).The area under the ROC curve estimated by 3D-SPACE sequence scanning combined with MSCT was 0.960,which was significantly higher than that of 3D-SPACE sequence scanning and MSCT alone evaluating the area under the ROC curve line of 0.756 and 0.795.The com-bined 3D-SPACE sequence scanning and 3D-SPACE sequence scanning MSCT analysis and prediction models were statistically different(Z=2.236,P＜0.05),and MSCT alone and 3D-SPACE sequence scanning combined with MSCT analysis and prediction models were statistically different(Z=2.653,P＜0.05).Conclusion The application of 3D-SPACE sequence combined with MSCT scanning for knee cruciate ligament injury can improve the diagnosis rate of patients with knee cruciate ligament injury.It can be used as a diagnostic tool for patients with knee cruciate ligament injury and is worthy of clinical application.

Objective To compare early clinical and imaging results of domestic HURWA and imported Brainlab Knee3 surgical robot-assisted knee replacement.Methods A retrospective analysis was performed on 93 patients with knee os-teoarthritis(KOA)who underwent robot-assisted descending total knee arthroplasty(TKA)from January 2021 to July 2023,and they were divided into BRATKA group and HRATKA group according to use of robotic system.There were 40 patients in BRATKA group,including 16 males and 24 females,aged from 55 to 90 years old with an average of(64.3±7.0)years old;27 patients with grade Ⅲ and 13 patients with grade Ⅳ according to Kellgren-Lawrence(K-L);18 patients on the right side and 22 patients on the left side;the courses of disease ranged from 1 to 30 years with an average of(15.3±7.6)years;imported Brainlab Knee3 surgical robot assisted system was adopted.There were 53 patients in HRATKA group,including 18 males and 35 females,aged from 52 to 81 years old with an average of(64.4±8.5)years old;30 patients with grade Ⅲ and 23 patients with grade Ⅳ;21 patients on the right side and 32 patients on the left side;the courses of disease ranged from 1 to 32 years with an average of(16.4±7.9)years;HURWA surgical robot assisted system was adopted.Operation time,perioperative total blood loss,incision length and postoperative complications were compared between two groups.Deviation angle of hip-knee-an-kle angle(HKAA)before operation and on the first day after operation was compared between two groups.Later tibal compo-nent(LTC),frontal femoral component(FFC),later femoral component(LFC)and frontal tibal component(FTC)at 1 day af-ter on the first day after operation was compared between two groups.Knee Society score(KSS),visual analogue scale(VAS)and range of motion(ROM)of knee joint were compared between two groups before operation and on the 3rd and 90th day af-ter operation.Results Both groups were followed up for 11 to 18 months with an average of(14.4±2.1)months,and the wounds of all patients healed well.Operation time and incision length of BRATKA group were(132.1±34.6)min and(12.9±1.9)cm,while(94.1±10.8)min and(14.8±2.1)cm in HRATKA group,respectively,and the differences between two groups were statistically significant(P＜0.05).There were no significant difference in perioperative total blood loss and preoperative deviation angle of HKAA between two groups(P＞0.05).Deviation angle of HKAA,FFC angle and LFC angle in BRATKA group were(1.90±0.91)°,(87.90±1.51)°and(9.00±3.2)°,respectively;while(0.93±1.04)°,(89.03±0.96)° and(7.63±0.59)° in HRATKA group,respectively,and the differences between two groups were statistically significant(P＜0.05).There were no significant dif-ferences in FTC and LTC between two groups(P＞0.05).There were no significant differences in VAS of knee rest and exercise,KSS score and ROM of knee joint between two groups before operation and 3 days and 90 days after operation(P＞0.05).There was no significant difference in complications between two groups(P＞0.05).Conclusion Postoperative imaging of two robot systems showed good lower limb force line.The domestic HRATKA group had better LFC,FFC angle and HKA deviation angle than the imported BRATKA group,but there were no significant difference in postoperative knee function and pain relief.