Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVE To investigate the intervention effect of Dabufei decoction on acute lung injury in rats with high altitude hypoxia by regulating the expression of the HIF-1α/NLRP3 signaling pathway and related molecules. METHODS Sixty SPF SD rats were randomly divided into blank group, model group, positive drug group, Dabufei decoction high-dose, medium-dose, and low-dose groups with 10 rats in each group. After 3 d of adaptation to feeding, the rats in the blank group and model group were given the same amount of normal saline by gavage, and the rats in Dabufei decoction high-dose, medium-dose, and low-dose groups were given gavage for 14 d, respectively. The positive drug group was given dexamethasone by intraperitoneal injection for three consecutive days before entering the chamber. Except for the blank group, the rats in each group were exposed to hypoxia in the experimental animal low-pressure simulation chamber from the 15th day for three consecutive days. At the end of the experiment, the wet to dry ratio(W/D) of the rat lung tissue was detected. The morphology of lung tissue was observed by HE staining. ELISA detected the levels of IL-1β and IL-18 in serum. Western blotting and RT-qPCR were used to detect the protein and mRNA expressions of HIF-1α, NLRP3, GSDMD, and caspase-1 in the lung tissue of rats. RESULTS The W/D value showed that compared with the blank group, the W/D of the model group was significantly increased(P<0.01). Compared with the model group, the W/D of rats in the positive drug group, Dabufei decoction high-dose group, medium-dose, and low-dose groups was significantly decreased(P<0.01 or P<0.05). HE results showed that compared with the blank group, alveolar septum thickening, pulmonary interstitial congestion, edema, inflammatory cell infiltration, and a small amount of exudation in the alveolar cavity were seen in the lung tissue of the model group. Compared with the model group, the thickening of alveolar walls in the positive drug group, Dabufei decoction high-dose group, medium-dose, and low-dose groups were reduced, and the pulmonary interstitial congestion, edema, and inflammatory cell infiltration were significantly reduced. ELISA results showed that IL-1β and IL-18 in rat serum were significantly higher in the model group than in the blank group(P<0.01). Compared with the model group, the levels of IL-1β and IL-18 in the serum of the rats in the positive drug group, Dabufei decoction high-dose group, medium-dose, and low-dose groups were significantly decreased(P<0.05 or P<0.01). Moreover, the results of Western blotting and RT-qPCR showed that compared with the blank group, the relative protein and mRNA expressions of HIF-1α, NLRP3, GSDMD, and caspase-1 in the lung tissue of the model group were significantly increased(P<0.01). Compared with the model group, the relative protein and mRNA of HIF-1α, NLRP3, caspase-1 and GSDMD in the positive drug group and Dabufei decoction high-dose group were significantly decreased(P<0.05 or P<0.01), the relative protein of HIF-1α, NLRP3, caspase-1 and GSDMD in Dabufei decoction medium-dose group were significantly decreased and HIF-1α, caspase-1 mRNA were significantly decreased(P<0.05), the relative protein of HIF-1α and GSDMD in the low-dose group was decreased(P<0.05). The positive drug group and Dabufei decoction high-dose group had the more significant effect. CONCLUSION Dabufei decoction can regulate the HIF-1α/NLRP3 signaling pathway, inhibit pyroptosis and reduce inflammation, and has a certain protective effect on acute lung injury in rats with high altitude hypoxia.

Objective To evaluate the applicability of the comprehensive index method for assessing occupational health risks on chemical hazards in key work sites of a metal product enterprise. Methods A metal product enterprise in Beijing City was chosen as the research subject using the convenience sampling method. Occupational health investigations and chemical hazard monitoring were conducted at four work sites: grinding machine operation, welding, cutting, and painting. The comprehensive index method was used to determine the risk levels of chemical hazards. Results The grinding dust in the grinding machine operation work site was assessed as moderate risk. The nitrogen oxides and ozone in the welding (southeast) work sites were assessed as moderate risk. The nitrogen oxides ozone and welding fumes in the welding (northwest) and cutting work site were assessed as moderate risk. Benzene in the painting work site was assessed as moderate risk. All chemical hazards in other work sites were determined to pose low risks. Co-exposures to nitrogen oxides and ozone in the two welding work sites and cutting work site were classified as moderate risk. Co-exposure to ethylbenzene, xylene, methanol, ethyl acetate, and butyl acetate in the painting work site also posed moderate risk, while the co-exposure to toluene and methanol in the painting work site was assessed as low risk. Conclusion The comprehensive index method could be used for the occupational health risk assessment in the metal product enterprise. The enterprise should strengthen hazard control measures for exposure to grinding dust, welding fumes, nitrogen oxides, ozone, and benzene, and closely monitor the health risks associated with co-exposures of chemical hazards.

Objective Cirrhotic cardiomyopathy(CCM)refers to cardiac dysfunction and electrophysiological disorder caused by liver cirrhosis and is closely associated with the prognosis of patients with liver cirrhosis.Endothelial cell-specific molecule 1(endocan)can be used as a diagnostic marker for cardiovascular diseases,and it remains unclear whether it is involved in the pathogenesis of CCM.The aim of this study is to investigate the expression of serum endocan in patients with CCM and its possible role in the development of CCM.Methods This cross-sectional study was conducted among the patients with liver cirrhosis who were consecutively admitted to Beijing YouAn Hospital,Capital Medical University,from January 2019 to January 2021,and according to the presence or absence of CCM,the patients were divided into CCM group with 19 patients and non-CCM group with 106 patients.ELISA was used to measure the serum level of endocan,and its correlation with liver function and cardiac function was analyzed.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of continuous data with skewed distribution between two groups;the chi-square test was used for comparison of categorical data between groups.A Pearson or Spearman correlation analysis was used to investigate the correlation between indicators,and the receiver operating characteristic(ROC)curve was used to assess the CCM predictive model.Results The CCM group had a significantly higher expression level of serum Endocan than the non-CCM group(2.69±0.43 ng/mL vs 2.23±0.52 ng/mL,t=2.247,P=0.034).The patients with compensated cirrhosis had a significantly lower expression level of serum endocan than those with decompensated cirrhosis(2.41±0.37 ng/mL vs 2.72±0.49 ng/mL,t=3.214,P=0.02).In the CCM group,the serum level of endocan was positively correlated with Child-Pugh score(r=0.509,P=0.026)and MELD-Na score(r=0.484,P=0.036)and was negatively correlated with mean arterial pressure(r=-0.591,P=0.013)and mitral ratio of peak early to late diastolic filling velocity(r=-0.515,P=0.042).The serum endocan had an area under the ROC curve of 0.658(95%CI:0.522～0.781)in predicting CCM,when the cut-off value was 2.61 ng/mL,the sensitivity was 67.1%and the specificity was 73.7%.Conclusion There is a certain association between serum endocan and CCM,and serum endocan may be involved in the pathogenesis of CCM.

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 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 evaluate the efficacy of different interventions to the extra cranial lesions in acute ischemic stroke(AIS)due to anterior tandem lesions(TL)on reperfusion.Methods As a multi-center,cross-sectional study,AIS due to anterior TL receiving mechanical thrombectomy(MT)were retrospectively collected.Interventions to the extra-cranial stenosis were recorded.Post-procedural reperfusion was assessed using the modified thrombolysis in cerebral infarction(mTICI)score.Complete revascularization was defined as mTICI 3 and good revascularization was defined as mTICI 2b/3.The relationship between different extra-cranial intervention regi-mens and rate of re-vascularization was compared.Results Totally 117 patients were included with 92.3% reaching good recanalization and 63.2% reaching complete re-canalization.There was no significant difference in good re-canalization rates among various extra-cranial intervention regimens.The rate of complete re-canalization was significantly higher in patients receiving endovascular therapy(P＜0.05)and there was significant difference among various endovascular treatment regimens(P＜0.01):acute balloon angioplasty only group presented the highest rate of complete re-canalization(100.0% ),followed by acute stenting only group(80% ),acute stenting+balloon angioplasty group(73.7% )and conservative treatment group(54.3% ).Conclusions Endovascular inter-vention to extra-cranial stenosis contributes to complete re-canalization in AIS due to anterior TL receiving MT,and acute balloon angioplasty seems to be quite effective than acute stenting.

Objective To investigate the clinical value of high resolution vascular wall imaging(HRVWI)in the diagnosis and treatment of central nervous system vasculitis(CNSV)in children.Methods A total of 36 children with CNSV underwent HRVWI examination were selected.The HRVWI imaging features,involved vessel types and stenosis degree were analyzed retrospectively and compared with magnetic resonance angiography(MRA).Combined with some patients'follow-up and reviewed imaging after treatment.Results HRVWI showed that all of the 36 children with CNSV had cerebral arteritis,and the affected inflammatory ves-sels showed varying degrees of focal arterial wall thickening and enhancement,mainly uniform thickening and centripetal enhance-ment of the affected arterial wall.Most were mid-enhanced,and the stenosis degree was mostly at level 1(21/36).According to the type of involvement cerebrovascular,there were 26 cases of large-medium vessel type,6 cases of small vessel type and 4 cases of mixed type.Compared with MRA,HRVWI had a higher sensitivity in diagnosing CNSV(P＜0.05).13 cases were followed up after treat-ment,and HRVWI showed cerebral vasculitis relief in 8 cases and progression in 5 cases,consistent with changes in clinical symp-toms and laboratory indicators.Conclusion The imaging features of CNSV in children with different causes are different.HRVWI has a high sensitivity in the diagnosis of CNSV in children.HRVWI plays an important role in the diagnosis and treatment of CNSV in children.

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.

Objective To investigates the applicability of cutting balloon in the pretreatment of superficial coronary artery calcified lesions, so as to decrease the occurrence of serious consequences in the treatment of calcified lesions. Methods The effect of cutting balloon on calcified plaques with different curvatures, thickness, and length was analyzed using the finite element method, with normal balloon as a control. The thickness of calcified plaque was set to 0.3 mm and 0.4 mm, and the length was set to 2 mm and 4 mm. The calcification degree was set to 120°, 180°, 270°and 360° according to the intravenous ultrasound (IVUS) calcification severity grading, with a total of 16 types of calcified plaques. The brittle fracture module was used to simulate calcification fracture of calcified plaques, and virtual stent implantation was carried out based on pretreatment simulation. The effect of pretreatment was evaluated by calcification fracture condition and stent roundness. Results For superficial calcification lesions, in lesions less than 120°, the balloon could not remove the calcification plaque obstruction, and the stent roundness rate was 82.75%. In 180° calcified lesions with thickness of less than 0.3 mm, the calcification was broken by cutting balloon under 1 215.9 kPa expansion pressure, and the post-stent roundness rate was 74.42%; normal balloon could not cause calcification fracture under safe expansion pressure (1 418.55 kPa). In 270°calcified lesions with thickness less than 0.3 mm, the normal balloon produced 3 fractures under 1 013.25 kPa expansion pressure. The cutting balloon produced 2 fractures under 1 013.25 kPa expansion pressure, and the balloon could not fracture the circular calcified lesions with thickness of 0.3 mm. Conclusions Cutting balloon is recommended for 180°calcified lesions with thickness less than 0.3 mm, the normal balloon is recommended for 270°calcified lesions, and balloon pretreatment is not recommended for annular lesions with thickness greater than 0.3 mm.