Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

With the rapid development of deep learning(DL)technology,its potential applications in the medical field have become increasingly prominent.As a refractory disease,osteonecrosis of the femoral head(ONFH)has certain limitations in traditional diagnostic and therapeutic approaches.The application of DL technology is expected to overcome these limitations and improve diagnosis and treatment outcomes.At present,the applications of DL models-including enhancing image clarity,improving diagnostic accuracy and efficiency,conducting prognostic evaluations,optimizing preoperative planning,assisting intraoperative imaging,and customizing personalized treatment plans-have fully demonstrated their tremendous potential in the diagnosis and treatment of ONFH.This review summarizes the current application status of DL in ONFH diagnosis and treatment,aiming to provide references and insights for future related research.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Objective To understand the current status of healthcare-associated infection(HAI)management for transesophageal echocardiography(TEE)examination in China,and provide a scientific basis for formulating guide-lines and standards for infection prevention and control in ultrasound diagnosis and treatment.Methods A stratified sampling survey was conducted in 162 medical institutions(MIs)in 14 provinces(autonomous regions,municipali-ties)in China.A unified questionnaire was designed,and on-site surveys were conducted in the TEE examination room of each MI,with questionnaires filled out based on the results of the on-site survey.Results 162 MIs were surveyed,out of which 114(70.4％)carried out TEE examination.TEE examination was undertaken by ultrasound medicine department(66.7％)and cardiology department(36.0％)in most MIs,and 91.0％of HAI departments had specially-assigned infection prevention and control professional to responsible for the management of HAI rela-ted to examination.32.4％(n=36)of TEE examinations used ultrasound probe isolation sleeves,mainly sterilized isolation membranes.The overall high-level disinfection or sterilization rate of TEE probes was 79.3％,19.8％of MIs chose medium-level disinfection.However,based on the number of equipped probes,the interval between pa-tient examination,and the disinfection method of probes,it was inferred that the proportion of effective high-level disinfection was only 67.6％.The most commonly adopted sterilization,high-level disinfection and medium-low le-vel disinfection methods for probes were low-temperature hydrogen peroxide sterilization,o-phthalaldehyde disinfec-tion and quaternary ammonium wiping disinfection,respectively.92.8％of examination rooms stored the probes in special storages cabinets(boxes)after disinfection.32.4％of examination rooms cleaned and disinfected ultrasound devices other than TEE probe between each patient examination,all were with medium-level disinfection.Most exa-mination rooms equipped complete hand hygiene(HH)facilities and ventilation,59.5％of the operators had the HH compliance rate of more than 90％.The wearing of disposable medical rubber examination gloves and glove changing for each patient was ideal.However,the change of bedding and the change of medical operators'overalls for each patient were not ideal.Conclusion TEE examination is generally carried out in large MIs across the coun-try,but the high-level disinfection rate of TEE probes still needs to be improved,and the appropriate disinfection methods still need further discussion and research.The disinfection awareness of ultrasound devices other than TEE probes still needs to be enhanced,and the compliance of hand hygiene of operators,the awareness of timely chan-ging of bedding of patients'examination beds,and the awareness of changing of overalls of diagnosis and treatment operators need to be enhanced.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

Objective To establish human colorectal cancer(CRC)organoids and to evaluate the efficacy of chem-otherapy drugs.Methods Patient-derived CRC cells were cultured to form organoids.The CRC organoids and origi-nal tissues were stained with molecular markers of CRC immunohishtochemically.CRC organoids were used to test drug sensitivity and different concentrations of chemotherapy drugs 5-fluorouracil,oxaliplatin and irinotecan were given respectively;Organoid activity before and after drug treatment was measured by 3D cell viability assay.Results The patient-derived organoids(PDO)from 5 CRC tissues were successfully established.The expression of CK20,Ki67 and Villin proteins was similar in organoids and in original tumor.The organoids retained histologcial features similar to those of the original tumors.Different PDO showed differential sensitivity to different chemothera-py drugs.Conclusions CRC-PDO can dispaly their different sensitivities to different chemotherapy drugs,and could provide valuble reference for personalized treatment for CRC patients.

Objective To explore the effect and predictive value of ultrasound-guided needling assisted motor evoked potentials(MEP)and electromyography(EMG)monitoring on neurological recovery in spinal surgery.Methods A retrospective analysis was conducted on the clinical data of 80 patients who underwent spinal surgery at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2024.A total of 41 patients in the observation group received ultrasound-guided needling assisted MEP and EMG monitoring,and 39 patients in the control group received conventional method for MEP and EMG monitoring.The operative time,intraoperative blood loss,and the proportions of intraoperative MEP and EMG warnings were compared between the two groups,and the sensitivity and specificity of intraoperative MEP monitoring were compared between the two groups.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to analyze the efficiency of MEP warning in predicting the dysfunction of postoperative spinal cord.Results There were no significant differences in the operative time,intraoperative blood loss,or the proportions of intraoperative MEP and EMG warnings(P>0.05).The sensitivity,specificity and AUC of intraoperative MEP monitoring in the observation group were significantly higher than those in the control group,with statistically significant differences(P<0.05).The sensitivity,specificity,and AUC of postoperative MEP warning in predicting the dysfunction of spinal cord in the observation group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Ultrasound-guided needling assisted MEP and EMG monitoring can effectively enhance the intraoperative neural monitoring accuracy,and postoperative MEP warning demonstrates superior predictive value for postoperative neurological dysfunction.

Objective To understand the current status of healthcare-associated infection(HAI)management for transesophageal echocardiography(TEE)examination in China,and provide a scientific basis for formulating guide-lines and standards for infection prevention and control in ultrasound diagnosis and treatment.Methods A stratified sampling survey was conducted in 162 medical institutions(MIs)in 14 provinces(autonomous regions,municipali-ties)in China.A unified questionnaire was designed,and on-site surveys were conducted in the TEE examination room of each MI,with questionnaires filled out based on the results of the on-site survey.Results 162 MIs were surveyed,out of which 114(70.4％)carried out TEE examination.TEE examination was undertaken by ultrasound medicine department(66.7％)and cardiology department(36.0％)in most MIs,and 91.0％of HAI departments had specially-assigned infection prevention and control professional to responsible for the management of HAI rela-ted to examination.32.4％(n=36)of TEE examinations used ultrasound probe isolation sleeves,mainly sterilized isolation membranes.The overall high-level disinfection or sterilization rate of TEE probes was 79.3％,19.8％of MIs chose medium-level disinfection.However,based on the number of equipped probes,the interval between pa-tient examination,and the disinfection method of probes,it was inferred that the proportion of effective high-level disinfection was only 67.6％.The most commonly adopted sterilization,high-level disinfection and medium-low le-vel disinfection methods for probes were low-temperature hydrogen peroxide sterilization,o-phthalaldehyde disinfec-tion and quaternary ammonium wiping disinfection,respectively.92.8％of examination rooms stored the probes in special storages cabinets(boxes)after disinfection.32.4％of examination rooms cleaned and disinfected ultrasound devices other than TEE probe between each patient examination,all were with medium-level disinfection.Most exa-mination rooms equipped complete hand hygiene(HH)facilities and ventilation,59.5％of the operators had the HH compliance rate of more than 90％.The wearing of disposable medical rubber examination gloves and glove changing for each patient was ideal.However,the change of bedding and the change of medical operators'overalls for each patient were not ideal.Conclusion TEE examination is generally carried out in large MIs across the coun-try,but the high-level disinfection rate of TEE probes still needs to be improved,and the appropriate disinfection methods still need further discussion and research.The disinfection awareness of ultrasound devices other than TEE probes still needs to be enhanced,and the compliance of hand hygiene of operators,the awareness of timely chan-ging of bedding of patients'examination beds,and the awareness of changing of overalls of diagnosis and treatment operators need to be enhanced.