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 explore the relationship between serum microRNA(miR)-122 and microRNA(miR)-558 levels and cardiac function and heart rate variability in patients with chronic heart failure(CHF).Methods A total of 100 patients with chronic heart failure who were hospitalized in Wuhan Dongxihu District Poeple's Hospital from January 2019 to January 2022 were regarded as the study group,and 100 healthy individuals who underwent physical examinations in the hospital during the same period served as the control group.The real-time fluorescence quantitative PCR method was applied to detect the expressiou levels of serum miR-122 and miR-558 in two groups.The heart rate variability and cardiac function indicators of the two groups were compared.Pearson method was applied to analyze the correlation between serum miR-122 and miR-558 expression levels,and heart rate variability and cardiac function indicators in patients with chronic heart failure.Logistic regression was applied to analyze the risk factors affecting chronic heart failure.Results Compared with the control group,the serum miR-122(0.86±0.19 vs 1.07±0.16),heart rate variability indicators,and left ventricular ejection fraction(LVEF)of patients with chronic heart failure were decreased(t=3.844～15.448),and the expression level of miR-558(1.28±0.27 vs 1.02±0.12)and left ventricular end diastolic volume index(LVEDVI),left ventricular end systolic volume index(LVESVI)were increased(t=6.794～9.358),and the differences were statistically significant(all P＜0.05).The expression level of serum miR-122(1.19±0.23,1.04±0.21)in patients with functional grades Ⅰ to Ⅱ was higher than that in patients with grades Ⅲ to Ⅳ(0.68±0.16,0.53±0.15),while the expression level of miR-558(0.93±0.24,1.21±0.26)was lower than that in patients with grade Ⅲ-Ⅳ(1.42±0.27,1.64±0.29),with significant differences(qmiR-122=3.751～14.568,qmiR-558=3.929～11.194.all P＜0.05).The serum miR-122 level in patients with chronic heart failure was positively correlated with heart rate variability indicators and LVEF(r=0.337～0.573),but negatively correlated with LVEDVI and LVESVI(r=-0.385,-0.323).Serum miR-558 was negatively correlated with heart rate variability indicators and LVEF(r=-0.646～-0.246),but positively correlated with LVEDVI and LVESVI(r=0.528,0.547).Serum miR-122[OR(95％CI)=0.528(0.328～0.850)]and miR-558[OR(95％CI)=2.845(1.364～5.933)]were influencing factors for chronic heart failure(P＜0.05).Conclusion The expression levels of serum miR-122 and miR-558 in patients with chronic heart failure were closely related to heart rate variability and cardiac function,indicating that serum miR-122 and miR-558 may be influencing factors of chronic heart failure.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

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 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.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Objective: To analyze the epidemiological characteristics of adult inpatients with gas burns in the Department of Burns of Hwa Mei Hospital of University of Chinese Academy of Sciences (hereinafter referred to as the author′s unit) , so as to provide evidence for the prevention of gas burn. Methods: Medical records of all inpatients with flame burns admitted to the author′s unit from January 2011 to December 2017 were collected. The percentage of adult inpatients with gas burns in total inpatients with flame burns in the same period, and their gender, age, injury season, accident place, burn severity, common compound injury, complication, population caliber, education, industry, as well as the pre-injury disease and prognosis of elderly inpatients with gas burns were retrospectively analyzed. In addition, the age, accident place, education, and industry of the floating population in the adult inpatients with gas burns were analyzed separately and compared with the total population of adult inpatients with gas burns in 7 years. Data were processed with chi-square test or Fisher′s exact probability test (Monte Carlo algorithm). Results: During the 7 years, 1 490 inpatients with flame burns were admitted to the author′s unit, among which 511 were adult inpatients with gas burns, accounting for 34.30%. The number of adult inpatients with gas burns increased gradually during the 7 years, but its percentage in the total inpatients with flame burns during the same period showed no significant difference (χ²=7.087, P>0.05). Among the 511 adult inpatients with gas burns (hereinafter referred to as the patients in this group), there were 315 males and 196 females, with a male/female ratio of 1.61 to 1.00, and the middle-aged patients were the most, up to 270 cases, accounting for 52.84%. The distribution of adult inpatients with gas burns during the 7 years was significantly different in gender and age (χ²=54.810, 27.832, P<0.01). Among the patients in this group, most were injured in summer, totally 251 cases, accounting for 49.12%, and the accident place was mainly at home, totally 388 cases, accounting for 75.93%. The distribution of adult inpatients with gas burns during the 7 years was significantly different in injury season (χ²=42.254, P<0.01), but not in accident place (χ²=6.782, P>0.05). The patients in this group were mainly with moderate burns (237 cases, accounting for 46.38%), and the distribution trend of burn severity of adult inpatients with gas burns was basically the same during the 7 years (χ²=19.680, P>0.05); 176 patients (34.44%) were accompanied by inhalation injury, and 30 patients (5.87%) were accompanied by blast injury of lung; post injury complications occurred in 20 patients (3.91%). In the elderly inpatients with gas burns, 44.44% (32/72) were accompanied by pre-injury basic diseases, and the proportion of death or unhealed reached 18.06% (13/72). Most of the patients in this group were permanent residents (358 cases, accounting for 70.06%) and received secondary education (304 cases, accounting for 59.49%), and the majority of them were engaged in manufacturing/construction (138 cases, accounting for 27.01%), self-employed business (90 cases, accounting for 17.61%), and catering (90 cases, accounting for 17.61%) industries. The distribution of adult inpatients with gas burns during the 7 years was significantly different in population caliber, education, and occupation (χ²=17.496, 29.898, 88.896, P<0.05 or P<0.01). Among the patients of this group, the floating population were mainly young (90 cases, accounting for 58.82%) and middle-aged (62 cases, accounting for 40.52%), with main accident place at home (97 cases, accounting for 63.40%), generally received secondary education (101 cases, accounting for 66.01%), and were mainly engaged in manufacturing/construction (71 cases, accounting for 46.41%), self-employed business (26 cases, accounting for 16.99%), and catering (20 cases, accounting for 13.07%) industries. Compared with the total adult inpatients with gas burns in 7 years, the floating population were younger, more injured in the workplace, and more concentrated in industry (χ²=42.924, 9.390, 27.819, P<0.01). Conclusions Gas burn was the leading injury cause of inpatients with flame burns in the author′s unit, which mainly occurred in summer and at home; the patients were mainly male, young and middle-aged, and permanent residents, most of which were with moderate burn, often accompanied by inhalation injury. Most of the patients were of secondary education, engaged in manufacturing/construction, self-employed business, and catering industries, among which the floating population were younger, more injured in the workplace, and more concentrated in industry. In order to prevent gas burn, we should pay more attention to the propaganda and education of gas safety among young and middle-aged men, floating population, retired old people and housewives, especially in summer, we should do a good job in gas safety inspection at home. In addition, we should urge enterprises to further strengthen the supervision of production safety.

Purpose: Four and a half LIM protein 1 (FHL1) is involved in breast cancer (BC) development, but the regulatory mechanism involved remain unclear. In the present study, we examined the role of FHL1 in BC development. Methods: The expression of FHL1, miR-183-5p, and miR-96-5p in BC tissues was analyzed using StarBase analysis. FHL1 expression in BC tissues, a normal human breast epithelial cell line, and BC cell lines was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship between FHL1 and miR-183-5p/miR-96-5p was analyzed via Pearson's rank correlation, TargetScan, and a dual-luciferase reporter assay. BT549 and MDA-MB-231 cells were transfected with either FHL1 and miR-183-5p mimics, or siFHL1 and a miR-183-5p inhibitor, respectively. The viability, colony number, migration, invasion, and tube length of BT549 and MDA-MB-231 cells were examined using cell counting kit-8, colony formation, wound-healing, Transwell, and tube formation assays, respectively. The levels of FHL1, vascular endothelial growth factor (VEGF), p53, E-cadherin, N-cadherin, and vimentin were quantified using western blotting and qRT-PCR. Results: FHL1 expression was downregulated in BC tissues and cells, whereas miR-183-5p and miR-96-5p were upregulated in BC tissues (negative correlation with FHL1 expression).FHL1 overexpression inhibited the viability, colony number, migration, and invasion of BC cells and the expression of VEGF, N-cadherin, and vimentin, and increased the expression of FHL1, p53, and E-cadherin in BT549 cells. Furthermore, a miR-183-5p mimic reversed these effects of FHL1 overexpression, whereas FHL1 silencing caused opposite results to those observed in MDA-MB-231 cells; however, this was reversed by a miR-183-5p inhibitor. Conclusion Our study suggests that miR-183-5p promotes cell proliferation, metastasis, and angiogenesis by negatively regulating FHL1 in BC.