OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
Mice ; Animals ; Mitogen-Activated Protein Kinase 14/metabolism* ; Wolfiporia ; Lipopolysaccharides/pharmacology* ; Sepsis/complications* ; Signal Transduction ; Inflammation/drug therapy* ; Oxygen Radioisotopes

Objective To explore the prognostic factor and its predictive value of patients with Wilson disease-related acute-on-chronic liver failure(WD-ACLF).Methods The clinical data of 70 patients diagnosed as WD-ACLF admitted to the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1,2017 to January 1,2022 were retrospectively collected.According to the 12-week prognosis,patients were divided into survival group(n=36)and death group(n=34).The data of the two groups were analyzed by univariate and multivariate logistic analysis to screen the prognostic risk factors and evaluate their predictive value.The model coefficient is omnibus tested,and the model-fitting degree is evaluated by the Hosmer-Lemeshow test.ROC curve was used to analyze the prognostic value for WD-ACLF between the new model and chronic liver failure-sequential organ failure assessment(CLIF-SOFA)score,model for end-stage liver disease(MELD)score and Child-Turcotte-Pugh(CTP)score.Results A total of 70 WD-ACLF patients were enrolled in present study,including 36 cases in survival group[22 males and 14 females with median age of 30.0(17.3,40.0)]and 34 cases in death group[25 males and 9 females with median age of 34.0(28.8,41.0)].Univariate analysis showed that the course of disease,prothrombin time(PT),activated partial thromboplastin time(APTT)were shorter in survival group than that in death group,the white blood cells(WBC),international normalized ratio(INR),aspartate transaminase(AST),total bilirubin(TBIL),blood urea nitrogen(BUN),creatinine(Cre)and ceruloplasmin(CER)levels and the proportion of infection,ascites,and upper gastrointestinal bleeding were lower in survival group than those in death group,however,the proportion of infection,ascites and upper digestive bleeding in the survival group were lower than those in the death group.Meanwhile,the red blood cells(RBC),hemoglobin(Hb),Na+ and total cholesterol(TC)level in the survival group were higher than those in the death group(P<0.05 or P<0.01).The results of multivariate logistic regression analysis showed that disease course(OR=1.176,95%CI 1.043-1.325),INR(OR=7.635,95%CI 1.767-32.980),TBIL(OR=1.012,95%CI 1.003-1.021),and upper gastrointestinal bleeding(OR=11.654,95%CI 1.029-131.980)were independent risk factors affecting the prognosis of WD-ACLF(P<0.05).Based on the results of logistic regression analysis,a joint model for predicting the prognosis of WD-ACLF was established.The AUC of the model for evaluating the prognosis of WD-ACLF was 0.941,which was greater than the CLIF-SOFA score(AUC=0.802),MELD score(AUC=0.897),and CTP score(AUC=0.722).Conclusions The course of disease,TBIL,INR,and upper gastrointestinal bleeding are risk factors that affect the prognosis of WD-ACLF.The prognosis model established based on this can more accurately predict the prognosis of WD-ACLF patients,and its predictive value is superior to CLIF-SOFA score,MELD score,and CTP score.

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na⁺ and K⁺ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na⁺ and K⁺ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To explore the effect of Shexiang Baoxin pill on cardiac tissue angiogenesis in spontaneously hypertensive rats(SHR).Method Twenty 12 week old male SHR were randomly divided into experimental group and model group,with 12 week old male SD rats as the normal control group.The experimental group rats were orally administered with Shexiang Baoxin pill(45 mg·kg-1)daily,and their blood pressure was monitored using a non-invasive tail artery blood pressure gauge every four weeks.Eight weeks later,cardiac tissue was taken for platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)immunofluorescence staining to observe CD31 expression level.Use protein blotting to detect the expression levels of myocardial endothelial growth factor(VEGF),myocardial endothelial growth factor receptor 2(VEGF-R2),basic fibroblast growth factor(bFGF)and phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)proteins.Result There was significant increase in blood pressure between the experimental group,model group and normal group at the same time point(all P＜0.01),but there was no statistically significant difference in blood pressure changes between the experimental group and model group at the same time point(all P＞0.05).The CD31 expression rates of the normal group,model group and experimental group were(3.79±0.84)％,(2.54±0.42)％and(3.56±0.49)％;VEGF levels were 0.95±0.10,0.73±0.08 and 0.94±0.15;VEGF-R2 levels were 0.85±0.10,0.61±0.14 and 0.80±0.10;bFGF levels were 0.84±0.04,0.51±0.21 and 0.74±0.14;p-Akt/Akt levels were 0.85±0.15,0.57±0.13 and 0.80±0.20,respectively.The differences between the normal group and the model group,as well as the experimental group and the model group,were statistically significant(all P＜0.05).Conclusion Shexiang Baoxin pill can promote the neovascularization of microvessels in the heart tissue of spontaneously hypertensive rats,and its mechanism may be related to the activation of PI3K/Akt phosphorylation,upregulation of bFGF,VEGF and their receptor VEGF-R2 in myocardial tissue.

Aerobic glycolysis(AEG),as the main pathway of energy metabolism of various malignant tumor cells,is involved in the whole process of the occurrence and development of lung cancer,and plays a key role in inducing tumor proliferation,invasion and metastasis.Traditional Chinese medicine monomers and compounds can regulate the expression of related signaling pathways and key proteases and genes by interfering with AEG pathway,promote the apoptosis of lung cancer cells,inhibit the AEG process and the proliferation and growth of lung cancer cells,and thus play an anti-tumor role.Based on this,this paper summarized the biological function of AEG,the mechanism of regulating lung cancer and the intervention mechanism of traditional Chinese medicine,in order to provide new ideas and scientific basis for the development of clinical drugs for lung cancer.

Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);the above indexes in experimental-H group were significantly different from those in model group(all P＜0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.

The development status quo of Shanghai's medical device industry was described.By using SWOT analysis method the influencing factors of the industry were analyzed and the key influencing factors were determined.A SWOT strategy matrix was constructed with considerations on the strengths,weaknesses,opportunities and threats of the key influencing factors.Some suggestions were put forward based on the SWOT strategy matrix and weak links of Shanghai's medical device industry to promote the development of the industry,and references were provided for the development of Shanghai's medical device industry.[Chinese Medical Equipment Journal,2024,45(6):77-82]

Objective To explore the mechanical behavior of cancellous bone under the interaction of whole-body low-magnitude high-frequency vibration(LMHFV)parameters,in order to provide theoretical guidance for the clinical treatment of disuse osteoporosis.Methods A three-dimensional reconstruction model was established for the cancellous bone of the mid femur by Mimics software,which was then imported into Comsol software to form a three-dimensional fluid-solid coupling finite element model.Twelve scenarios with the vibration acceleration amplitude(a)being 0.015×g,0.02×g,0.03×g and vibration frequency(f)being 30,45,60 and 100 Hz were set up for the simulation study to analyze the distribution rules of the hydrodynamic microenvironment,the stresses and the deformation displacements of cancellous bone under the interaction of LMHFV parameters.Results The bone marrow flow velocity on the surface of trabeculae and deformation displacement of bone matrix increased with the rising of a and decreased with the growing of f.Trabeculae gained high mean values of deformation displacement in case of the vibration scenario(0.015×g/0.02×g/0.03×g,30 Hz),and had high von Mises stress when LMHFV parameters were restricted within(0.02×g to 0.03×g,30 Hz to 35 Hz).Conclusion Whole-body LMHFV significantly improves the force and hydrodynamic environment of cancellous bone,and force-mediated osteoblast bioactivity can be enhanced by rationally modulating LMHFV parameters during clinical processes so as to promote osteogenesis.[Chinese Medical Equipment Journal,2024,45(7):17-23]

Objective To explore the modal testing method for the three-axis manned centrifuge under elastic boundary conditions with considerations on its complicated structure and high rotational inertia.Methods Modal testing was carried out with a three-axis manned centrifuge under elastic boundary conditions as the subject and a force hammer as the excitation source according to GJB 2706A-2008 Modal tests method for spacecraft and GB/T 11349.3-1992 Experimental determination of mechnical mobility measurements using impact excitation.Four times of hammering were carried out at each excitation position,and the data of the four times of hammering underwent linear average computation.Data acquisition was implemented with a three-axis accelerometer and a 64-channel data collector,and the modal data were analyzed using a frequency response function based on the Test.Lab modal test and analysis software.Results The coherence coefficient of the excitation signal was not lower than 0.8 in the 30 Hz band;the first three orders of the system's intrinsic vibrations were all torsional vibrations,with the frequencies of 9.15,15.66 and 19.22 Hz,respectively;the first order frequency of the system was about 9.15 Hz for both Z18 and Z21 excitation positions,and each of the second and third order frequencies similar situations were observed for also had a roughly equal value for the two excitation positions.Conclusion The force hammer testing method is applicable for the modal testing of the three-axis manned centrifuge,ensuring equipment safety and subject comfort.Referen-ces are provided for the following structural optimization design.[Chinese Medical Equipment Journal,2024,45(8):38-43]