Disseminated intravascular coagulation (DIC) triggered by sepsis is a major challenge in the emergency and critical care of severely ill patients. The inflammasome is an essential component of the human immune system, and its activation can mediate pyroptosis and then release interleukin (IL)-1β and IL-18, which further activates platelets and the coagulation system and exacerbates inflammatory responses and coagulation processes, thus creating great uncertainty for the treatment and prognosis of sepsis. This article aims to review the correlation between the inflammasome and pyroptosis, as well as their impact on coagulation function, in hope of providing new insights for the clinical treatment of DIC.

In recent years， the potential anti-tumor effects of metformin have attracted widespread attention in the field of cancer treatment. This article summarizes the research progress of metformin in the treatment of malignant tumors，finding its potential application in the treatment of malignant tumors in the digestive system （biliary tract cancer，gastric cancer，esophagus cancer，colorectal cancer，pancreatic cancer，liver cancer） and reproductive system （prostate cancer，ovarian cancer，breast cancer， cervical cancer），non-small cell lung cancer，renal cell carcinoma，and melanoma. Metformin can inhibit the proliferation of tumor cells and extend the overall survival of patients. Its mechanisms of action include，but are not limited to，inhibiting the activity of mitochondrial complex Ⅰ，activating adenosine monophosphate-activated protein kinase/p53 signaling pathway，and blocking the cell cycle. Additionally，the combined use of metformin with chemotherapy drugs has shown potential for reducing toxicity and enhancing efficacy. It can enhance the sensitivity of biliary tract cancer，ovarian cancer，and melanoma cells to chemotherapy drugs， improve the drug resistance of gastric and colorectal cancer cells to chemotherapy，and reduce the toxic reactions of breast cancer patients during chemotherapy. Metformin is also used as an immunomodulator，applied in the immunotherapy of patients with esophagus cancer，colorectal cancer，cervical cancer，non-small cell lung cancer，and melanoma.

BACKGROUND:Osteoarthritis is one of the most common senile chronic degenerative diseases in China.Due to its complex pathogenesis and cellular molecular communication pathways,there is currently no effective method to slow down the progression of osteoarthritis.Studies have found that transforming growth factor-β is one of the key factors in the maintenance and regulation of joint stability and plays a significant role in the formation of early joints,as well as the development of bone and cartilage,and the remodeling of joints at various stages. OBJECTIVE:To review the regulatory role of the transforming growth factor-β subfamily in the occurrence and development of osteoarthritis,both domestically and internationally in recent years,to analyze the impacts it has at different stages of osteoarthritis,and to explore the potential application prospects of transforming growth factor-β in the clinical treatment of osteoarthritis,with a view to informing clinical treatment protocols.. METHODS:The relevant articles were searched by computer from CNKI Database and PubMed Database.The search terms were"osteoarthritis,transforming growth factor,signaling pathway,bone remodeling,cartilage degeneration,angiogenesis,treatment"in Chinese and English,respectively.Finally,57 articles were included for review. RESULTS AND CONCLUSION:The pathogenesis of osteoarthritis remains a subject of ongoing exploration with no unified consensus.Numerous studies highlight the close correlation between osteoarthritis and cytokines,focusing on the transforming growth factor-β superfamily as a pivotal mechanism and therapeutic breakthrough.Transforming growth factor-β plays a crucial role in early joint cartilage formation and maintenance,promoting cartilage repair.However,post-joint formation,its protective effect weakens,leading to potential destructive consequences.This dual regulatory role is a current clinical treatment focus,necessitating further research to delineate its application scope for standardized protocols.Highly active transforming growth factor-β participates in the regulation of bone cells,osteoblasts,and osteoclasts under mechanical stress,and intervenes in the subsequent remodeling of bone microstructure.Specific inhibitors present potential targeted therapeutics,yet their safety and efficacy in clinical settings require refinement.Vascular proliferation may serve as a potential disruptive pathway in transforming growth factor-β-mediated cartilage degeneration and subchondral bone remodeling.Abnormal communication pathways can further disrupt the homeostasis of the microenvironment of osteochondral units,thereby accelerating key pathological progressions of osteoarthritis.Research on transforming growth factor-β in osteoarthritic contexts is comprehensive,holding broad clinical application prospects.Drugs related to transforming growth factor-β are in clinical trial phases,but addressing potential impacts on other tissues and precise control of targeted delivery are critical concerns.As research advances,there is optimism for innovative breakthroughs in slowing the progression of osteoarthritis in the future.

Disseminated intravascular coagulation (DIC) triggered by sepsis is a major challenge in the emergency and critical care of severely ill patients. The inflammasome is an essential component of the human immune system, and its activation can mediate pyroptosis and then release interleukin (IL)-1β and IL-18, which further activates platelets and the coagulation system and exacerbates inflammatory responses and coagulation processes, thus creating great uncertainty for the treatment and prognosis of sepsis. This article aims to review the correlation between the inflammasome and pyroptosis, as well as their impact on coagulation function, in hope of providing new insights for the clinical treatment of DIC.

Objective To grasp the main environmental factors affecting the growth of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao;To predict the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province;To provide references for the rational distribution of the resources in Shanxi Province.Methods This study utilized the sample point longitude and latitude information collected in the"Fourth Survey of Chinese Materia Medica Resources"database in Shanxi Province.The data were supplemented by searching the China Digital Herbarium and retrieving related literature records.347 sample points distribution data and environmental factors were added to the MaxEnt model.The main environmental factors and contribution rates affecting the geographical distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao were screened out.The ArcGIS software was used to divide the ecological suitable area of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province.Results The area under the ROC curve of the established MaxEnt model was 0.909,indicating that the model prediction results were accurate.The model screened 19 environmental factors.Among them,climate factor was the most important environmental factor,followed by biological factor and topographic factor,and soil factor had the least influence.The potential suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province were mainly distributed in the northern mountainous areas,presenting a trend of gradually decreasing suitability levels from north to south.Under the current climate conditions,the most suitable area for Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province was 15 424 km2,the suitable area was 19 856 km2,the sub suitable area was 59 436 km2,and the unsuitable area was 61 894 km2.Conclusion Based on MaxEnt model and ArcGIS software,this study predicts the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province,which has certain reference value for the protection and rational distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao resources in Shanxi Province.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.

Objective:To corelate thromboelastography (TEG)-related parameters and D-dimer and fibrinogen levels with the severity of preeclampsia and pregnancy outcomes in patients with preeclampsia.Methods:A case-control study was conducted involving 92 patients with preeclampsia who received treatment at Northwest Women's and Children's Hospital between March 2022 and September 2023 (patient group) and 92 healthy pregnant women who underwent routine check-ups during the same period (control group). All participants underwent TEG tests, and D-dimer and fibrinogen levels were measured. Intergroup comparisons were performed, and patients were categorized based on the severity of their condition. TEG parameters and D-dimer and fibrinogen levels were compared among patients with varying severities of preeclampsia. TEG-related parameters were correlated with D-dimer and fibrinogen levels. Adverse pregnancy outcomes in the patient group were statistically analyzed, and risk factors for these adverse outcomes in women with preeclampsia were identified.Results:In the patient group, the R and K values were (3.06 ± 0.36) minutes and (1.21 ± 0.14) minutes, respectively, both of which were significantly lower than those in the control group [(5.44 ± 0.61) minutes, (1.79 ± 0.21) minutes, t = 32.22, 22.04, both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in the patient group were (71.31 ± 7.63)°, (3.89 ± 0.41), (65.71 ± 7.01) mm, (2.22 ± 0.24) mg/L, and (4.51 ± 0.49) g/L, respectively, all of which were significantly higher than those in the control group [(64.85 ± 6.79)°, (2.19 ± 0.23), (58.96 ± 6.09) mm, (1.92 ± 0.21) mg/L, (3.75 ± 0.40) g/L, t = -6.06, -34.68, -6.97, -9.02, -11.52, all P < 0.001]. In the patient group, severe cases had significantly lower R and K values compared with mild cases, while the α angle, CI value, MA value, and D-dimer and fibrinogen levels were significantly higher in severe cases than in mild cases ( t = 11.06, 7.16, -8.01, -12.05, -3.91, -13.74, -8.269, all P < 0.001). In patients with preeclampsia, the R and K values were negatively correlated with D-dimer levels, and the R value was negatively correlated with fibrinogen level ( r = -0.504, -0.612, -0.493, all P < 0.05). In addition, the MA and CI values were positively correlated with D-dimer level, and the α angle was positively correlated with fibrinogen level ( r = 0.436, 0.534, 0.492, all P < 0.05). Among the participants, 41 women experienced adverse pregnancy outcomes. In patients with adverse pregnancy outcomes, the R and K values were (2.48 ± 0.25) minutes and (1.12 ± 0.14) minutes, which were significantly lower than those in patients without adverse pregnancy outcomes [(2.75 ± 0.29) minutes, (1.28 ± 0.13) minutes, t = 4.71, 5.67; both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in patients with adverse pregnancy outcomes were (76.62 ± 8.01)°, (4.42 ± 0.46), (69.77 ± 7.06) mm, (2.57 ± 0.27) mg/L, and (4.97 ± 0.51) g/L, all of which were significantly higher than those in patients without adverse pregnancy outcomes [(67.04 ± 7.01)°, (3.46 ± 0.37), (62.45 ± 6.82) mm, (1.94 ± 0.21) mg/L, (4.14 ± 0.43) g/L, t = -6.11, -5.03, -11.09, -12.25, -8.46, all P < 0.001]. Logistic regression analysis indicated that R and K values were protective factors for adverse pregnancy outcomes ( OR < 1, P < 0.05), while MA value, α angle, CI value, and D-dimer and fibrinogen levels were independent risk factors ( OR > 1, P < 0.05). Conclusion:TEG-related parameters differ significantly between patients with preeclampsia and healthy pregnant women. These parameters are correlated with the severity of preeclampsia, as well as with D-dimer and fibrinogen levels. TEG-related parameters are risk factors for adverse pregnancy outcomes in patients with preeclampsia.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.