This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

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

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To observe the value of nomogram based on echocardiographic functional parameters of left atrium(LA)for identifying atrial fibrillation(AF).Methods Sixty-six adult patients with AF and 65 individuals without AF were retrospectively enrolled and randomly divided into training set(n=79)and test set(n=52).Four-dimensional LA volumetric echocardiography was performed,and LA volume and strain parameters were measured using four-dimensional left atrial automatic quantification(4D LAQ)technology.Echocardiographic parameters were compared between AF group(n=38)and non-AF group(n=41)in training set,and a logistic regression model for identifying AF was constructed.The performance of the model was evaluated with receiver operating characteristic(ROC)curve and the area under the curve(AUC).Then a nomogram was developed based on the logistic regression model,and the calibration was assessed using a calibration curve,as well as the clinical net benefit was evaluated through decision curve analysis(DCA).Results In training set,compared to those in non-AF group,LA diameter(LAD),the minimum LA volume(LAVmin),the maximum LA volume(LAVmax)and the maximum LA volume index(LAVImax)increased,while the left ventricular ejection fraction(LVEF),LA emptying volume(LAEV),LA emptying fraction(LAEF),and the magnitude of LA reservoir longitudinal strain(LASr)and LA reservoir circumferential strain(LASr_c)decreased in AF group(all P＜0.05).LASr(OR[95％CI]=0.780[0.636,0.956])and LAEF(OR[95％CI]=0.850[0.757,0.954])were both independently associated with AF.The logistic regression model constructed for identifying AF achieved an AUC of 0.950 in training set and 0.955 in test set.The nomogram demonstrated good calibration and provided a certain level of net clinical benefit.Conclusion Nomogram constructed on basis of LASr and LAEF was effective for identifying AF.

Objective To observe the value of nomogram based on echocardiographic functional parameters of left atrium(LA)for identifying atrial fibrillation(AF).Methods Sixty-six adult patients with AF and 65 individuals without AF were retrospectively enrolled and randomly divided into training set(n=79)and test set(n=52).Four-dimensional LA volumetric echocardiography was performed,and LA volume and strain parameters were measured using four-dimensional left atrial automatic quantification(4D LAQ)technology.Echocardiographic parameters were compared between AF group(n=38)and non-AF group(n=41)in training set,and a logistic regression model for identifying AF was constructed.The performance of the model was evaluated with receiver operating characteristic(ROC)curve and the area under the curve(AUC).Then a nomogram was developed based on the logistic regression model,and the calibration was assessed using a calibration curve,as well as the clinical net benefit was evaluated through decision curve analysis(DCA).Results In training set,compared to those in non-AF group,LA diameter(LAD),the minimum LA volume(LAVmin),the maximum LA volume(LAVmax)and the maximum LA volume index(LAVImax)increased,while the left ventricular ejection fraction(LVEF),LA emptying volume(LAEV),LA emptying fraction(LAEF),and the magnitude of LA reservoir longitudinal strain(LASr)and LA reservoir circumferential strain(LASr_c)decreased in AF group(all P＜0.05).LASr(OR[95％CI]=0.780[0.636,0.956])and LAEF(OR[95％CI]=0.850[0.757,0.954])were both independently associated with AF.The logistic regression model constructed for identifying AF achieved an AUC of 0.950 in training set and 0.955 in test set.The nomogram demonstrated good calibration and provided a certain level of net clinical benefit.Conclusion Nomogram constructed on basis of LASr and LAEF was effective for identifying AF.

Background and objective hTere are incresing lung cancer patients detected and diagnosed at the in-termediate stage when the pre-malignant or early lesions are amenable to resection and cure, owing to the progress of medical technology, the renewal of detection methods, the popularity of medical screening and the improvement of social health con-sciousness. hTe aim of this study is to investigate the risk factors of the occurrence of postoperative cardio-pulmonary compli-cations in stage I non-small cell lung cancer (NSCLC) patients, based on routine laboratory tests, basic characteristics, and in-traoperative variables in hospital.Methods hTe 421 patients atfer lobectomy in patients with stage I NSCLC at the West China Hospital of Sichuan University from January 2012 to December 2013 were included into the study and stratiifed into complica-tion group and non-complication group, according to whether to occur postoperative cardio-pulmonary complications atfer lobectomy in 30 days.Results Of them, 64 (15.2%) patients were ifnally identiifed and selected into the complication group, compared with 357 (84.8%) in non-complication group: pneumonia (8.8%, 37/421) was the primary complication, and other main complications included atelectasis (5.9%, 25/421), pleural effusion (≥middle) (5.0%, 21/421), persistent air leak (3.6%, 15/421); hTe operation time (P=0.007), amount of blood loss (P=0.034), preoperative chronic obstructive pulmonary disease (COPD) (P=0.027), white blood cell (WBC) count (P<0.001), neutrophil-lymphocyte ratio (NLR) (P<0.001) were signiif-cantly different between the two groups. According to the binary logistics regression analysis, preoperative COPD (OR=0.031, 95%CI: 0.012-0.078,P<0.001) and WBC count (OR=1.451, 95%CI: 1.212-1.736,P<0.001) were independent risk factors for postoperative cardio-pulmonary complications.Conclusion Among an array of clinical variables in hospital, operation time, preoperative white blood cell count, preoperative COPD, may be the independent risk factors of the occurrence of postopera-tive cardio-pulmonary complications.

Animals ; Athletic Performance ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Morinda ; Myocardium ; metabolism ; Physical Conditioning, Animal

OBJECTIVETo observe the morphological and molecular biological peculiarities of the experimental autoimmune prostatitis (EAP) rat model made by SC purified prostate protein twice with immune adjuvant.

METHODSMale rats were intradermally immunized with a saline extract of male rat prostate glands (RPG) in Freund's complete adjuvant (FCA) and Pertussis-Diphtheria-Tetanus vaccine 0.5 ml i.p. at the 0 and 30th day, and the concentrations of the extract were respectively 5 mg/ml, 10 mg/ml and 15 mg/ml. At the 45th day, the rats were sacrificed and the morphological and molecular biological changes of the prostate specimens were observed to determine the effective concentration of RPG for a successful model.

RESULTSThe expression of inflammation genes such as TNF-alpha, IL-1beta, IL-2 and iNOS obviously increased in the high-dosage model group; LM, EM and in situ hybridization revealed appearant chronic inflammation response, but this was not the case in the other two dosage groups.

CONCLUSION15 mg/ml RPG mixed with FCA (1:1) 1.0 ml SC with Pertussis-Diphtheria-Tetanus vaccine 0.5 ml i.p. was an effective dosage for the successful model in our experiment.

Animals ; Autoimmune Diseases ; immunology ; metabolism ; pathology ; Diphtheria-Tetanus-Pertussis Vaccine ; administration & dosage ; Disease Models, Animal ; Freund's Adjuvant ; administration & dosage ; Injections, Intraperitoneal ; Male ; Prostate ; metabolism ; pathology ; Prostatitis ; immunology ; metabolism ; pathology ; Proteins ; administration & dosage ; Rats ; Rats, Wistar