Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.

Objective To explore the influencing factors of microcirculation dysfunction in patients with anterior wall acute myocardial infarction(AMI)and to establish a relevant prediction model.Methods A total of 130 patients with anterior wall AMI,whose microcirculation function was assessed by caIMR after receiving percutaneous coronary intervention(PCI)at Shanghai Sixth People's Hospital of China from January 2017 to September 2020,were enrolled in this study.The patients were divided into abnormal microcirculation resistance group(n=52)and normal microcirculation resistance group(n=78).The clinical data were compared between the two groups.The regression analysis was used to analyze the influencing factors of microcirculation dysfunction.Results In the abnormal microcirculation resistance group the contrast agent consumption,the onset-to-operation time,the Gensini total score and the LAD Gensini score were(121.92±31.37)mL,(10.51±5.12)min,(97.91±31.77)points and(69.36±13.15)points respectively,which were significantly higher than(109.03±28.2)mL,(4.94±2.94)min,(81.05±35.22)points and(54.45±23.48)points respectively in the normal microcirculation resistance group,the differences in the above indexes between the two groups were statistically significant(all P＜0.05).A prediction model covering interventional strategies was established,and its accuracy was higher than that of a conventional model,its AUC compared with the conventional model was 0.91 to 0.87,indicating that this model could well predict the risk of microcirculation dysfunction in patients with AMI after receiving PCI.Conclusion This prediction model can promptly identify high-risk microcirculation dysfunction patients with anterior wall AMI after receiving PCI.

Objective To investigate the clinical value of matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS)in rapid detection of carbapenemase produced by Klebsiella pneumoniae and Pseudomonas aeruginosa.Methods A total of 60 strains of Klebsiella pneumoniae and 80 strains of Pseudomonas aeruginosa isolated from Pizhou People's Hospital affiliated to Xuzhou Medical University from January 2022 to October 2023 were collected,including 30 strains of carbapenem-resistant Klebsiella pneumoniae(CRKP),30 strains of carbapenem-sensitive Klebsiella pneumoniae(CSKP),50 strains of carbapenem-resistant Pseudo-monas aeruginosa(CRPA)and 30 strains of carbapenem-sensitive Pseudomonas aeruginosa(CSPA).Three detection methods were applied,i.e.,modified carbapenem inactivation method(mCIM),colloidal gold immunochromatography and Autof MS 1000 mass spectrometry identification system to evaluate the ability of Autof MS 1000 mass spectrometry identification system in detecting carbape-nase production of Klebsiella pneumoniae and Pseudomonas aeruginosa.Results The results of Autof MS 1000 mass spectrometry iden-tification system were consistent with those of both mCIM and colloidal gold immunochromatography.Carbapenemase was detected in 28 of the 30 CRKP strains,and it was negative in 2 CRKP strains.Carbapenamase was detected in 15 of the 50 CRPA strains and it was negative in 35 CRPA strains.Thirty strains of CSKP and 30 strains of CSPA were all Carbapenemase negative.The coincidence rate of the results of the three methods in the detection for carbapenase was 100％.Conclusion The result of Autof MS 1000 mass spectrome-try identification system has been consistent with those of mCIM and colloidal gold immunochromatography.It not only has the charac-teristics of cost-saving compare with of mCIM method,but also hold the advantages of fast speed and high accuracy of colloidal gold im-munochromatography method.Thus,Autof MS 1000 system can be used for the rapid identification of carbapenemase produced by Kleb-siella pneumoniae and Pseudomonas aeruginosa.

BACKGROUND:Currently,electrospun nanofibers,which are biomimetic materials of natural extracellular matrix and contain a three-dimensional network of interconnected pores,have been successfully used as scaffolds for various tissue regeneration,but are still faced with the challenge of extending the biomaterials into three-dimensional structures to reproduce the physiological,chemical as well as mechanical properties of the tissue microenvironment. OBJECTIVE:To summarize the process and principles of electrostatic spinning and to explore the applications of the resulting electrospun nanofibers in tissue regeneration of skin,blood vessels,nerves,bone,cartilage and tendons/ligaments. METHODS:With"electrospinning,electrospun nanofibers,electrospun nanofiber scaffolds,tissue regeneration"as the Chinese and English search terms,Google Academic Database,PubMed,and CNKI were searched,and finally 88 articles were included for review. RESULTS AND CONCLUSION:(1)The electrospun nanofibers are a natural fibrous extracellular matrix mimetic material and contain a three-dimensional network of interconnected pores that have been successfully used as scaffolds for a variety of tissue regeneration applications.(2)Several papers have described the great potential of electrospun nanofiber scaffolds applied to the regeneration of skin,blood vessels,nerves,bones,cartilage and tendons/ligaments,providing a solid theoretical basis for its final application in clinical disease treatment,or for its transformation into practical products to enter the market.(3)However,the current research results are mostly based on cell experimental research results in vitro,and whether it can be finally applied to human body still needs clinical verification.(4)At present,many kinds of electrospun products for various clinical needs have been commercialized in and outside China,indicating that the research field of electrospun nanofiber scaffolds for soft and hard tissue regeneration has great research value and application potential.

BACKGROUND:Pauwels Ⅲ femoral neck fracture is a typical unstable fracture characterized by high vertical shear force and high incidence of postoperative complications.At present,there are many fixation methods for Pauwels Ⅲ fracture,and there is no clear conclusion as to which internal fixation is the best fixation method for Pauwels Ⅲ femoral neck fracture in young adults. OBJECTIVE:To compare the clinical effect of three inverted triangle cannulated screws assisted transverse lag screws and femoral neck system in fixing Pauwels Ⅲ femoral neck fractures of young adults. METHODS:From May 2021 to December 2022,21 young and middle-aged patients with Pauwels Ⅲ femoral neck fracture were treated with three inverted triangle cannulated screws assisted by transverse lag screws and femoral neck system in Affiliated Hospital of Southwest Medical University.Of them,9 patients were treated with three inverted triangle cannulated screws and one transverse lag screws perpendicular to the fracture line as the 3+1 cannulated screw group and 12 patients were treated with femoral neck system as the femoral neck system group.The two fixation methods were compared in terms of operation time,intraoperative blood loss,total incision length,intraoperative fluoroscopy times,fracture healing time,and limb function. RESULTS AND CONCLUSION:(1)All patients were followed up.Patients in the 3+1 cannulated screw group were followed up for 10-25 months,with a mean of(17.44±4.30)months.The patients in the femoral neck system group were followed up for 8-24 months,with a mean of(15.58±4.68)months.(2)The intraoperative fluoroscopy times and Harris score at 3 months postoperatively in the femoral neck system group were better than those in the 3+1 cannulated screw group,and the difference was statistically significant(P<0.05).The intraoperative blood loss,total incision length,and femoral neck shortening distance in the 3+1 cannulated screw group were better than those in the femoral neck system group,and the differences were statistically significant(P<0.05).There was no significant difference in operation time,fracture healing time,and Harris score at the last follow-up between the two groups(P>0.05).(3)It is indicated that three inverted triangle cannulated screws assisted transverse lag screw and femoral neck system can achieve good clinical effects in the treatment of young and middle-aged Pauwels Ⅲ femoral neck fracture.The femoral neck system has fewer intraoperative fluoroscopy times and better early overall stability,while the 3+1 cannulated screw is more minimally invasive,easier to operate.Both fixation methods are worthy of clinical application and promotion,and can be selected according to the actual clinical situation.

Objective:To analyze the effect of panax notoginseng saponins(PNS)on mTORC1-HIF1α signaling pathway,and to explore its effect and mechanisms on the differentiation balance of Th17/Treg cells in CD4+T cells.Methods:Isolate the spleens of C57BL/6 mice,then select CD4+T cells by magnetic beads and cultured in vitro.The optimal concentration of PNS was screened by the CCK-8,and then these cells were divided into control group and PNS treatment group(5,10 and 20 μg/ml),each gives correspond-ing drug treatment after 48 h.Afterwards,flow cytometry was used to detect differentiation of Th17/Treg cells.Real-time quantitative fluorescent PCR was used to detect the expressions of RORγt,Foxp3,mTOR,Raptor,HIF1α mRNA.ELISA was used to detect the levels of IL-17A and IL-10 in the supernatant of cell culture.Western blot was used to detect the expressions and phosphorylation levels of 4EBP1,S6K and HIF1α proteins.Results:5,10,20 μg/ml PNS could significantly inhibit Th17 cells differentiation and promote Treg cells differentiation;5,10,20 μg/ml PNS could significantly reduce the expression of RORγt mRNA,and then reduce the level of IL-17A;20 μg/ml PNS could significantly promote the expression of Foxp3 mRNA and increase the level of IL-10;10,20 μg/ml PNS could significantly decrease the phosphorylation of 4EBP1 and S6K;5,10,20 μg/ml PNS could significantly reduce the expression of HIF1α mRNA and inhibit the expression of HIF1α protein.Conclusion:Certain concentrations of PNS can inhibit the differentiation of Th17 cells in CD4+T cells,and promote the differentiation of Treg cells,which is related with modulating mTORC1-HIF1α signaling pathway.

Objective:To explore the influence of deviation of the bolt in femoral neck system (FNS) on the short-term outcomes in young and middle-aged patients with displaced femoral neck fracture.Methods:A retrospective analysis was conducted of the 114 young and middle-aged patients with displaced femoral neck fracture who had been treated with FNS at Department of Orthopaedics, Suzhou Municipal Hospital from December 2019 to January 2023. Based on the postoperative measurements of the deviation of the bolt tip to the central axis of the femoral head and neck (W), the patients were divided into a central group (W≤20%) and a deviation group (W>20%). In the central group of 63 cases, there were 27 males and 36 females with a mean age of (46.4±8.0) years. In the deviation group of 51 cases, there were 20 males and 31 females with a mean age of (45.1±9.8) years. The 2 groups were compared in terms of weight-bearing time, fracture healing time, tip-apex distance, degree of femoral neck shortening, Harris Hip Score and EuroQol five-dimensional questionnaire-5L (EQ-5D-5L) utility value at the last follow-up, as well as complications and revision surgeries.Results:There was no statistically significant difference in the preoperative general information, auxiliary reduction or quality of fracture reduction between the 2 groups, showing comparability between groups ( P>0.05). There was no significant difference in the partial weight-bearing time between the 2 groups ( P>0.05). In the central group, the full weight-bearing time [15.0 (14.0, 16.0) weeks] and fracture healing time [14.0 (12.0, 15.0) weeks] were significantly shorter than those in the deviation group [16.0 (15.0, 19.0) weeks; 15.0 (13.0, 17.0) weeks], the tip-apex distance [(21.4±3.4) mm] was significantly shorter than that in the deviation group [(23.5±2.7) mm], the Harris Hip Score [(90.6±6.1) points] and EQ-5D-5L utility value [0.9 (0.8, 0.9)] at the last follow-up were significantly higher than those in the deviation group [(87.7±6.2) points; 0.9 (0.8, 0.9)], and the incidences of moderate and severe femoral neck shortening [25.4% (16/63)], avascular necrosis of the femoral head [0 (0/63)] and revision surgery [0 (0/63)] were significantly lower than those in the deviation group [66.7% (34/51), 7.8% (4/51), 9.8% (5/51)] (all P< 0.05). Conclusion:A closer positioning of the FNS bolt to the central axis of the femoral head and neck favors satisfactory short-term outcomes and a lower revision surgery rate in young and middle-aged patients with displaced femoral neck fracture.

Objective:To explore the prognostic value of peripheral blood lymphocyte subsets in lymphoma patients with different infection status of Epstein-Barr virus (EBV).Methods:A retrospective cohort study. A total of 333 lymphoma patients newly diagnosed from November 2012 to August 2023 in the Affiliated Hospital of Xuzhou Medical University were included in the study, including 185 patients with Diffuse Large B-cell Lymphoma (DLBCL), 100 patients with Natural Killer/T-cell Lymphoma (NKTCL), and 48 patients with Hodgkin Lymphoma (HL). Clinical data and laboratory indicators of patients were collected, including lymphocyte subset ratios detected by flow cytometry and EBV-DNA levels measured by real-time quantitative polymerase chain reaction. The survival status of patients was recorded through referring to medical records and telephone follow-up. The Kaplan-Meier method was used to plot survival curves and compare the survival rates among different groups. The Cox proportional hazards model was applied to analyze factors related to overall survival in lymphoma patients.Results:In the NKTCL group, 73.0% (73/100) were positive for EBV-DNA, which was higher than 43.8% (81/185) in the DLBCL group and 35.4% (17/48) in the HL group ( P<0.001). Kaplan-Meier survival curves showed that lower overall survival rates in the DLBCL group with abnormal levels of CD19 +B cells and CD16 +CD56 +NK cells (defined as either high or low referring to the reference intervals), with EBV-DNA negative and abnormal levels of CD19 +B cells, or with EBV-DNA positive and abnormal levels of CD16 +CD56 +NK cells, compared with the normal level group ( P<0.05). Multivariable analysis suggested that the abnormal level of CD19 +B cells was an independent adverse prognostic factor for DLBCL patients ( HR=2.098, 95% CI 1.181-3.727, P=0.011). EBV-DNA positivity ( HR=17.623, 95% CI 2.397-129.565, P=0.048) and Ann Arbor stage (Ⅲ/Ⅳ) ( HR=2.770, 95% CI 1.335-5.750, P=0.006) were adverse prognostic factors for NKTCL patients. Conclusion:There are differences in peripheral blood lymphocyte subsets among lymphoma patients with different EBV infection status, and CD19 +B cell levels may serve as an independent prognostic factor for DLBCL patients.

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

BACKGROUND/OBJECTIVES: To identify modifiable risk factors for type 2 diabetes mellitus and explore the relationship between diet sodium intake and blood glucose levels.MATERIALS/METHODS: Based on inclusion and exclusion criteria, we extracted, analyzed, and assessed the available crossover studies of dietary salt intake restriction and insulin resistance in PubMed, Web of Science, MEDLINE, Embase, Wanfang, and CNKI databases. RESULTS: We included 6 studies with 8 sets of data, covering 485 subjects. I2 statistics results showed insignificant heterogeneity among all data (I 2 = 39.2% < 50%). Thus, a fixed-effect model was adopted for the final pooled effect size. Weighted mean difference and its 95% confidence interval (CI) value was 0.193 (95% CI, 0.129–0.257), and the test of the overall effect showed P < 0.001. The results revealed that the blood glucose levels in the subjects in the low-salt intake group were significantly higher than those in the normal or high-salt intake groups. We also found no significant change occurred after the removal of any study through sensitivity analysis, which confirmed that the outcome we calculated was prudent and credible. The quantitative Egger’s test (P = 0.109 > 0.05) indicated that insignificant publication bias existed. CONCLUSION This meta-analysis highlights the relationship between dietary sodium intake and blood glucose levels. Our findings show that higher blood glucose levels might be expected in hypertensive or normal people with low-salt consumption compared to those with normal or high-salt consumption, although these differences were not clinically significant.Trial Registration: PROSPERO Identifier: CRD42021256998