This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Aim To evaluate the toxicity and mecha-nism of Epimedium sagittatum(Sieb.et Zucc.)Maxim aqueous extract(ESMAE)on HepaRG cells based on serum toxicology.Methods MTT assay was used to detect the activity of HepaRG cells after treatment with the serum containing ESMAE from SD rats.Western blot was used to detect the effects of the serum contai-ning drug on the expression of endoplasmic reticulum stress-related proteins(PERK,eIF-2α,ATF-4,GRP78,CHOP)and pyroptosis related proteins(NL-RP1,caspase-1,cleaved caspase-1,GSDMD,GSDMD-N).MTT assay was used to detect the activity of Hep-aRG cells after treatment with the liver homogenate containing ESMAE from SD rats.Results Twenty percent serum containing drug significantly decreased the viability of HepaRG cells,with the cells exhibiting swelling,rupture,and vesicle-like pyroptosis.The ex-pression levels of endoplasmic reticulum stress-related proteins PERK,eIF-2α,ATF-4,GRP78,and CHOP significantly increased.The expression levels of pro-teins involved in the NLRP1-mediated classical pyrop-tosis pathway were significantly increased.Finally the liver homogenate containing drug decreased the cell ac-tivity,and cells exhibited swelling,rupture,and vesicle-like pyroptosis.Conclusions After administration of ESMAE,the serum containing drug and the liver ho-mogenate containing drug of rats show toxicity to Hep-aRG cells,and can induce endoplasmic reticulum stress and activate the NLRP1/caspase-1/GSDMD pyroptosis pathway in HepaRG cells.

Objective:To investigate the effect of tolerogenic dendritic cells(tolDC)on autophagy of synovial cells in collagen-induced arthritis(CIA)rats.Methods:Bone marrow mononuclear cells of rats were extracted and induced into tolDC using IL-4,GM-CSF and NF-κB oligonucleotide decoy,and loaded with BⅡC to become BⅡC-tolDC.SD rats were randomly divided into normal control group,CIA model group and BⅡC-tolDC intervention group,with 3 rats in each group.Normal female SD rats were immunized with bovine type Ⅱ collagen solution to construct CIA model.Rats in BⅡC-tolDC intervention group were infused with BⅡC-tolDC via tail vein on the 21st day after initial immunization for two weeks,arthritis indexes were recorded weekly.On the 35th day,the rats were sacrificed,and synovial histopathology of ankle joint of rats in each group were observed by HE staining;the number of osteo-clasts in cartilage of rats in each group were observed by TRAP staining.The number of autophagic of ankle synovial cells of rats in each group were observed by transmission electron microscopy.Levels of serum TNF-α and IL-1β of rats in each group were detected by ELISA.LC3,Beclin-1 and ATG5 proteins of synovial cells of ankle joints of rats in each group were detected by Immunohistochemical staining.Results:CIA rats were constructed successfully by immunization with bovine type Ⅱ collagen.BⅡC-tolDC intervention re-duced the arthritis index of CIA rats,inhibited synovial inflammation and abnormal proliferation of synovial tissue,improved joint bone and cartilage injury,and reduced the number of osteoclasts in cartilage tissue and the number of autophagosomes in synovial cells.At the same time,reduced levels of serum TNF-α,IL-1β,and protein expressions of LC3,Beclin-1 and ATG5 of synovial cell of CIA rats.Conclusion:BⅡC-tolDC may alleviate arthritis lesions of CIA rats by inhibiting synovial cell autophagy of CIA rats.

Objective:To investigate the changes in accommodative facility after implantation of V4c implantable collamer lens (ICL) using the intelligent flipper (iFLIP).Methods:A serial case-control study was conducted.Forty patients (80 eyes) who underwent ICL implantation of V4c for myopia correction and completed the follow-up were enrolled at the Affiliated Hospital of Guizhou Medical University from April 2022 to April 2023.Monocular and binocular accommodative facility, adjustment time, and relaxation time were measured with iFLIP before operation and at 1 week, 1 month, 3 months, and 6 months after operation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (No.2023-983).Written informed consent was obtained from each subject.Results:Monocular and binocular uncorrected visual acuity at 1 week, 1 month, 3 months and 6 months after surgery were significantly improved compared with before surgery, and the differences were statistically significant (all P<0.05).Monocular and binocular postoperative accommodative facility gradually increased over time, and the increase gradually decreased and gradually stabilized.Before operation and 1 week, 1 month, 3 months, and 6 months after operation, the monocular accommodative facility was (7.99±3.42), (10.19±4.25), (12.03±4.24), (13.10±4.66) and (13.64±4.40)cpm, and the binocular accommodative facility was (9.01±3.63), (9.56±3.38), (11.58±4.00), (13.31±3.64), and (14.03±3.72)cpm, respectively, with statistically significant overall differences ( F=24.02, 14.46; both P<0.001).Monocular accommodative facility was higher than before surgery at each time point after surgery, and was higher than 1 week after surgery at 1, 3, and 6 months after surgery, with statistically significant differences (all P<0.05).Binocular accommodative facility was higher at 1, 3, and 6 months after surgery than that before surgery and 1 week after surgery, and higher at 3 and 6 months after surgery than that at 1 month after surgery, with statistically significant differences (all P<0.05).With the extension of postoperative time, the monocular and binocular adjustment time and relaxation time gradually shortened, and the shortening gradually decreased and stabilized.Monocular adjustment time and relaxation time were shorter than before surgery at all time points after surgery.The monocular adjustment time was shorter at 1, 3 and 6 months after surgery than that at 1 week after surgery and shorter at 3 and 6 months after surgery than that at 1 month after surgery, and the monocular relaxation time was shorter at 3 and 6 months after surgery than that at 1 week after surgery, and the differences were statistically significant (all P<0.05).The binocular adjustment time was shorter at 1, 3 and 6 months after surgery than before surgery and at 1 week after surgery, shorter at 3 and 6 months after surgery than at 1 month after surgery and the binocular relaxation time was shorter at all time points after surgery than that before surgery, showing statistically significant differences (all P<0.05). Conclusions:After ICL implantation, uncorrected visual acuity, accommodative facility, adjustment time and relaxation time all improve throughout the preoperative period and eventually stabilize.

Objective To explore the mechanism of S100A9 derived from non-small cell lung cancer(NSCLC)in regulating invasion,metastasis and activating the brain microvascular endothelium of the metastatic niche.Methods R language was used to extract RNAseq data from the TCGA database and a paired-sample T-test was employed to analyze the expression of S100A9 in NSCLC tissues and normal lung tissues.Visualization was conducted using the ggplot2 package;the proportional hazards assumption test and survival regression were performed using the survival package to compare the prognosis between the high/low expression groups of S100A9,and visualization was carried out using the survminer package and ggplot2 package.RT-qPCR and Western Blot were used to detect the expression differences of S100A9 in NSCLC cell lines(A549,NCI-H1299)and normal lung epithelial cells(BEAS-2B).An in vitro co-culture of A549 cells and human brain microvascular endothelial cells(hCMEC/D3)was established to construct a blood-tumor barrier(BTB)model.Additionally,siS100A9 knock-down A549 cell strains were constructed.Scratch healing and Transwell assays were performed to assess the changes in the migration and invasion abilities of A549 cells in different treatment groups.CCK-8 and flow cytometry were used to examine the proliferative activity and cell cycle effects of HCMEC/D3 cells treated with varying concen-trations of S100A9.RT-qPCR and Western Blot were employed to investigate the expression changes of receptors for advanced glycation endproducts(RAGE),Toll-like receptor 4(TLR4),and tumor transendothelial migration-related adhesion molecules(ICAM-1,VCAM-1,ALCAM)in hCMEC/D3 cells treated with different concen-trations of S100A9.Furthermore,CCK-8,RT-qPCR,and Western Blot were utilized to assess the recovery of proliferative activity and adhesion molecule expression in hCMEC/D3 cells stimulated with different concentrations of S100A9 after pretreatment with FPS-ZM1 and TAK242 to block RAGE and TLR4 pathways,respectively.Results The RNAseq data mining and analysis from the TCGA database revealed that the expression of S100A9 in lung cancer tissue samples was significantly higher than that in normal lung tissue samples(P=0.03).The Kaplan-Meier survival curve graph showed that the survival probability of the S100A9 high-expression group was lower than that of the S100A9 low-expression group,suggesting that the high expression of S100A9 was significantly associated with a poorer overall survival period for patients(HR=1.46(1.10-1.95),P=0.01).In the cell experiments,S100A9 was highly expressed in NSCLC(P<0.05).Knockdown of S100A9 inhibited the migration and invasion of A549 cells(P<0.05).The average migration inhibition rate of the knockdown group at 6,12,24,36,and 48 hours was 80.61%,75.70%,73.78%,69.54%,and 56.96%respectively,and the average invasion inhibition rate was 57.38%(at 48 hours).Meanwhile,the proliferative activity and cell cycle of hCMEC/D3 cells in the BTB model were regulated positively(P<0.05).Mechanistically,S100A9 promoted the crosstalk between A549 and hCMEC/D3 cells through RAGE and TLR4,upregulating the expression of ICAM-1,VCAM-1,and ALCAM in hCMEC/D3 cells(P<0.05).Recovery experiments confirmed that the S100A9-RAGE/TLR4 regulatory axis could affect the endothelial adhesion process during lung cancer brain metastasis(P<0.05).Conclusion The S100A9-RAGE/TLR4 axis is associated with the progression of lung cancer brain metastasis.Knockdown of S100A9 can inhibit the invasion and metastasis of lung cancer cells.Blocking downstream RAGE and TLR4 receptors can attenuate the proliferative growth of brain microvascular endothelium and inhibit the formation of a pre-metastatic adhesive microenvironment between lung cancer cells and brain microvascular endothelium.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.