BACKGROUND:De novo adipose regeneration induced by small extracellular vesicles has become a promising method for repairing soft tissue defects.However,due to different animal models and small extracellular vesicle application dosages,it is difficult to quantitatively compare the therapeutic effect of small extracellular vesicles from various sources on adipose regeneration. OBJECTIVE:To compare the regenerative effects of small extracellular vesicles derived from stem cells and small extracellular vesicles from tissue. METHODS:Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation.The particle number,particle size,morphology,and protein expression of small extracellular vesicles were identified by nanoparticle tracking analysis,transmission electron microscopy and western blot assay.A quantitative and evaluative subcutaneous model for adipose regeneration in C57 mice was established using a customized silicone tube.The regenerative effects of induced de novo adipose were compared by cell counting and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation.Both small extracellular vesicles were round-shape in transmission electron microscopy with particle size between 50-200 nm,and abundant with the small extracellular vesicles marker protein CD81,CD63 and TSG101.(2)An equal number of small extracellular vesicles were mixed with matrigel in customized silicone tubes,implanted subcutaneously in the back of mice to establish a cell-free and quantifiable adipose regeneration model.(3)On days 3 and 7 after implantation,the results of cell counting and hematoxylin-eosin staining showed that both small extracellular vesicle groups recruited more host cells than the blank group,and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group.(4)4 weeks after implantation,hematoxylin-eosin staining of the contents in silicone tubes showed that small extracellular vesicles induced de novo adipose regeneration in vivo,and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group.The above results indicated that small extracellular vesicles derived from tissues have a superior effect on inducing de novo adipose regeneration compared to small extracellular vesicles derived from stem cells.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To investigate the expression of serum human epididymal protein 4 (HE4) in colorectal cancer patients and its relationship with recurrence and metastasis.Methods:A prospective study was conducted to collect 100 patients with colorectal cancer admitted to the First Affiliated Hospital of Hebei North University from January to December 2018 as the observation group, and 50 healthy volunteers as the control group. All patients underwent radical surgery for colorectal cancer, and serum samples were collected before surgery. Enzyme linked immunosorbent assay (ELISA) was used to detect serum HE4 levels, and the relationship between serum HE4 levels and clinical pathological characteristics in the observation group was analyzed. The relationship between preoperative serum HE4 levels and postoperative recurrence and metastasis of colorectal cancer in the observation group was also analyzed. The COX proportional risk model was used to analyze the influencing factors of postoperative recurrence and metastasis of colorectal cancer, and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of preoperative serum HE4 levels in the observation group for postoperative recurrence and metastasis of colorectal cancer.Results:The serum HE4 level in the observation group was significantly higher than that in the control group, and the difference was statistically significant ( P<0.05). The serum HE4 levels in patients with low differentiation were higher than those in patients with medium and high differentiation, while those with lymph node metastasis had higher serum HE4 levels than those without lymph node metastasis (all P<0.05). The postoperative recurrence and metastasis rate of colorectal cancer in patients with low serum HE4 levels was significantly lower than that in patients with high levels ( P<0.05). The COX proportional risk model showed that differentiation degree, lymph node metastasis, and serum HE4 levels were influencing factors for postoperative recurrence and metastasis of colorectal cancer (all P<0.05). The sensitivity and specificity of preoperative serum HE4 levels in predicting postoperative recurrence and metastasis of colorectal cancer were 72.7% and 73.1%, respectively. Conclusions:Serum HE4 is highly expressed in colorectal cancer and is closely related to postoperative recurrence and metastasis of colorectal cancer.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective To investigate the application value of Revolution CT dual-low technique coronary angiography in coronary heart disease.Methods One hundred patients with suspected coronary heart disease were retrospectively selected and randomly divided into control group and observation group,who all were examined by Revolution CT.In the control group(50 cases),the tube voltage was 120 kV,the contrast agent iohexol was 350 mg I/mL,and the dose of contrast agent was 1 mL/kg.In the observation group(50 cases),the tube voltage was 100 kV,the contrast agent iohexol was 350 mg I/mL,and the dose of contrast agent was 0.8 mL/kg.All patients underwent coronary digital subtraction angiography(DSA)examination at the same time.The image quality(subjective and objective evaluation indexes)and radiation dose of the two groups were compared,the diagnostic value of the two methods for coronary artery stenosis was compared,and the diagnostic consistency with coronary DSA between the two methods were compared using the Kappa test,as well as the typical coronary images of the two groups were analyzed.Results There were no significant differences in the sub-jective image quality grade and excellence rate between the observation group and the control group(P＞0.05).The CT value and noise of the observation group were higher than those of the control group(P＜0.05).There were no statistically significant differ-ences in the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the right coronary proximal and the left coronary main trunk between the two groups(P＞0.05).Compared with the control group,the volume CT dose index(CTDIvol),dose length product(DLP),and effective dose(ED)were lower in the observation group(P＜0.05).Compared with the results of coronary DSA,the positive predictive value,negative predictive value,sensitivity,specificity and accuracy of the two methods were＞80％,while there was no significant difference between the two groups(P＞0.05).The Kappa value of the observation group versus coronary DSA diagnosis was 0.871,the Kappa value of the control group ver-sus coronary DSA diagnosis was 0.889,and the consistency of both methods versus coronary DSA diagnosis was good.Conclusion Revolution CT dual-low technigue coronary angiography has good diagnostic value for coronary heart disease and can significantly reduce the radiation dose while ensuring image quality.

Keloids are benign skin tumors resulting from the excessive proliferation of connective tissue in wound skin. Precise prediction of keloid risk in trauma patients and timely early diagnosis are of paramount importance for in-depth keloid management and control of its progression. This study analyzed four keloid datasets in the high-throughput gene expression omnibus (GEO) database, identified diagnostic markers for keloids, and established a nomogram prediction model. Initially, 37 core protein-encoding genes were selected through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the centrality algorithm of the protein-protein interaction network. Subsequently, two machine learning algorithms including the least absolute shrinkage and selection operator (LASSO) and the support vector machine-recursive feature elimination (SVM-RFE) were used to further screen out four diagnostic markers with the highest predictive power for keloids, which included hepatocyte growth factor (HGF), syndecan-4 (SDC4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), and Rho family guanosine triphophatase 3 (RND3). Potential biological pathways involved were explored through gene set enrichment analysis (GSEA) of single-gene. Finally, univariate and multivariate logistic regression analyses of diagnostic markers were performed, and a nomogram prediction model was constructed. Internal and external validations revealed that the calibration curve of this model closely approximates the ideal curve, the decision curve is superior to other strategies, and the area under the receiver operating characteristic curve is higher than the control model (with optimal cutoff value of 0.588). This indicates that the model possesses high calibration, clinical benefit rate, and predictive power, and is promising to provide effective early means for clinical diagnosis.
Humans ; Keloid/genetics* ; Nomograms ; Algorithms ; Calibration ; Machine Learning

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Objective:To explore differences of resting brain regional homogeneity (ReHo) between patients with major depressive disorder (MDD) and their siblings.Methods:From January to December 2013, the resting-state functional magnetic resonance imaging (fMRI) data of 87 patients with MDD and 21 healthy siblings were collected.DPABI v5.1 software was used to preprocess the resting-state fMRI data, and ReHo maps of each subject was obtained. A two-sample t-test was used to compare differences between the patients with MDD and their siblings in ReHo values throughout the brain. ReHo values within the significant brain regions were extracted out, and used to calculate Spearman correlation with the total score of 17-items Hamilton depression rating scale(HAMD-17) in the patients with MDD and their siblings respectively.The software of SPSS 20.0 was used for statistical analysis. Results:The patients with MDD exhibited lower ReHo values in the precuneus extending to the posterior cingulate cortex (PCu/PCC) compared with their siblings (cluster-size=126 voxel, cluster-level PFDR=0.033; MNI: x=-4, y=-58, z=38, t=4.30). ReHo values of the PCu/PCC in patient with MDD were positively correlated with the severity of depressive symptoms ( r=0.255, P=0.021). Conclusion:Compared with the siblings, local brain activity of the PCu/PCC in the patients with MDD was decreased, and related to the severity of depressive symptoms. It is helpful to further reveal the intrinsic neural mechanism of MDD.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.