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.

Objective To compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P＜0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P＞0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P＜0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P＞0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P＞0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P＜0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.

Objective To explore clinical accuracy of remote sensing navigation alignment(RSNA)system in total knee arthroplasty(TKA)and its influence on postoperative clinical efficacy.Methods From May 2021 to May 2022,60 knee os-teoarthritis(KOA)patients with Kellgren-Lawrence(K-L)grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods,and 30 patients in each group.There were 6 males and 24 females in RSNA group,aged from 55 to 86 years old with an average of(68.06±8.23)years old;body mass index(BMI)ranged from 22.15 to 34.58 kg·m-2 with an average of(28.20±3.01)kg·m-2;the courses of disease ranged from 2 to 60 months with an average of(18.80±14.80)months;13 patients with grade Ⅲ and 17 patients with grade Ⅳaccording to K-L grading.In traditional operation group,there were 8 males and 22 females,aged from 57 to 85 years old with an average of(67.26±6.32)years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of(27.49±2.32)kg·m-2;the courses of disease ranged from 3 to 60 months with an average of(21.30±16.44)months;14 patients with grade Ⅲ and 16 pa-tients with grade Ⅳ according to K-L grading.Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and Knee Society score(KSS)were used to evaluate functional recovery of patients.Hip-knee-ankle angle(HKAA),distal femoral valgus angle(FVA)and distal fermoral flexion angle(DFFA)were measured before operation.HKAA and HKAA deviation angle were measured at 1 week after operation,and defective rate of lower limb force line,femur prosthesis valgus angle(FP-VA)and femoral prosthesis flexion angle(FPFA),respectively,were calculated.Results There were no serious complications such as vascular and nerve injury during operation,and wound healed at stage Ⅰ.Both groups were followed up for 6 months.There were no significant difference in WOMAC index,KSS,HKAA,FVA and DFFA between two groups before operation(P＞0.05).The force line defect rate,HKAA,HKAA deviation angle,FPVA deviation angle and FPFA of RSNA group were 6.7％,(178.74±1.56)°,(1.25±1.56)°,(1.84±0.16)° and(4.85±2.46)°,respectively;while in traditional operation group were 20％,(176.73±3.46)°,(3.27±3.46)°,(2.44±0.26)°,(6.60±1.86)°;the difference between two groups were statistically sig-nificant(P＜0.05).There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation(P＞0.05).Conclusion RSNA system could reduce defective rate of lower limb force line,FPVA deviation angle and FPFA after TKA,which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

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.

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of the right elbow reveals in a "semi-extended and pronated" elastic fixation position. Radiography and 3-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.

Objective To develop an MRI-based habitat radiomics model for the preoperative prediction of endometrial cancer(EC)molecular subtypes.Methods Patients with pathologically proven EC from two hospitals were included in the training(n=270)and testing(n=70)cohorts.All patients had preoperative MRI and histological and molecular diagnoses.First,the tumor was divided into habitat subregions based on diffusion-weighted imaging(DWI)and contrast-enhanced(CE)images.Subsequently,habitat radiomic features were extracted from different subregions of T1-weighted imaging(T1WI),T2-weighted imaging(T2WI),DWI,and CE images.Three machine learning classifiers,including logistic regression,support vector machines,and random forests,were applied to develop predictive models for p53-abnormal endometrial cancer,with model performance validated.The model demonstrating the best overall predictive performance was selected as the habitat radiomics model.Using the same procedure,a whole-region radiomics model based on T1WI,T2WI,DWI,and CE sequences and a clinical model were constructed.The performance of the models was evaluated using receiver operating characteristic curves,and DeLong's test was employed to compare differences between the models.Decision curve analysis was used to assess the clinical benefits of the models'application.Results After feature selection,eight habitat radiomic features were retained to construct the habitat radiomics model,ten features for the whole-region radiomics model,and three clinical features for the clinical model.The habitat radiomics model achieved the highest area under the curve(AUC),with 0.855(0.788-0.922)in the training cohort and 0.769(0.631-0.907)in the testing cohort.DeLong's test showed that the habitat radiomics model outperformed the whole-region radiomics model in the training cohort(P=0.001),but there was no significant difference in the testing cohort(P=0.543).In both cohorts,the habitat radiomics model outperformed the clinical model(P=0.007,training cohort;P=0.038,testing cohort).Decision curve analysis(DCA)demonstrated that this model provided clinical benefit for diagnosis within a threshold probability range of approximately 0.2-0.8.Conclusion The MRI-based habitat radiomics model can accurately predict p53-abnormal EC,outperforming both the whole-region radiomics model and the clinical model,and is useful for the non-invasive molecular subtyping of endometrial cancer before surgery.

Objective To investigate the distribution of the traditional Chinese medicine(TCM)constitution types in the patients with nonspecific low back pain(NLBP)and to explore the correlation of the thickness of ligamentum flavum with the age,body mass index(BMI),gender,the presence of diabetes mellitus,and the grading of hypertension.Methods Sixty patients with NLBP admitted to Guangdong Second Traditional Chinese Medicine Hospital from January 2023 to June 2023 were selected as the study subjects.The TCM constitution types of the patients were identified,the thickness of the ligamentum flavum at lumbar vertebrae 4/5 segment(L4/5)disc level was measured by computerized tomography(CT)scanning,and the patients'age,genders,TCM constitution types,BMI,the presence or absence of diabetes mellitus,and hypertension grading were recorded.Correlation analysis and linear regression analysis were used for the exploration of the relevant influencing factors for the thickness of the ligamentum flavum of patients with NLBP.Results(1)The average thickness of ligamentum flavum in the 60 patients with NLBP was(2.60±0.72)mm.(2)The TCM constitutions of NLBP patients were classified into four types,of which blood stasis constitution was the most common,accounting for 21 cases(35.0%),followed by 19 cases(31.7%)of damp-heat constitution,12 cases(20.0%)of phlegm-damp constitution,and 8 cases(13.3%)of qi deficiency constitution.(3)The results of correlation analysis showed that BMI,gender,TCM constitution type and the presence or absence of diabetes mellitus had no influence on the thickness of ligamentum flavum in NLBP patients(P＞0.05),while the age and hypertension grading had an influence on the thickness of ligamentum flavum(P＜0.01).(4)The results of linear regression analysis showed that the age had an influence on the thickness of the ligamentum flavum(b = 0.034,t = 6.282,P＜0.01),while the influence of the hypertension grading had no influence on the thickness of the ligamentum flavum(P＞0.05).Conclusion The TCM constitution type of NLBP patients is predominated by blood stasis constitution,the thickness of ligamentum flavum is significantly affected by the age,and hypertension may be a potential factor affecting the thickness of ligamentum flavum.

Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67％(29/30)and that of the control group was 63.33％(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P＜0.05),and the JOA scores were significantly higher than those before treatment(P＜0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P＜0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P＜0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P＞0.05).(5)The incidence of adverse reactions in the trial group was 6.67％(2/30)and that in the control group was 13.33％(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P＞0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

Objective To explore the core drugs and antidepressant molecular mechanisms of Chinese herbal compound in the clinical treatment of depression.Methods Relevant literature was searched through CNKI,Wanfang and VIP to screen and sort out the Chinese Herbal compounds used in clinical practice.By analyzing the frequency of medication and the association rules of Chinese medicines,Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix were determined as the core Chinese medicinals for the treatment of depression.The active components and target proteins of these drugs were screened by TCMSP database,and depression-related targets were obtained from TTD,OMIM,DrugBank and GeneCards.Protein-protein interaction(PPI)network and'core drug-active ingredient-intersection target'network were constructed by STRING and Cytoscape.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by Metascape.Molecular docking analysis used RCSB database,AutoDockTools and PyMOL to verify the binding activity of key active components with core targets.Results The drugs for the treatment of depression in clinical Chinese herbal compound prescriptions were mainly cold,sweet,bitter and pungent,and the liver meridian was the first.Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix had the highest frequency of medication,and the combination of"Paeoniae Radix Alba-Bupleuri Radix"and"Curcumae Radix-Paeoniae Radix Alba-Bupleuri Radix"had the highest support.In the PPI network,SLC6A4,AKT1 and CHRNA4 were the key targets.GO enrichment analysis results showed that core drugs play a role in synaptic membranes and other parts through biological processes such as chemical synaptic transmission,as well as molecular functions such as G protein-coupled receptor activity.KEGG pathway enrichment analysis results showed that core drugs may treat depression through neuroactive ligand-receptor interaction,calcium signaling pathway and other pathways.Molecular docking confirmed that there was a strong binding activity between the key active ingredients and the core target.Conclusion Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix are the core drugs for clinical treatment of depression,which can treat depression through multi-component,multi-target and multi-pathway.