【Objective】 To explore the application value of ¹⁸F-PSMA PET/CT on the detection of metastatic lesions of prostate cancer with serum total prostate specific antigen (tPSA) ≤20 ng/mL and the predictive variables affecting the imaging results, and to establish a predictive nomogram for the metastasis of prostate cancer. 【Methods】 The imaging, pathological, serum and clinical data of 175 pathologically confirmed prostate cancer patients who underwent ¹⁸F-PSMA PET/CT examination during Jan.2020 and Oct.2021 were retrospectively collected.The patients were divided into metastatic group and non-metastatic group according to PET/CT imaging results, and the positive detection rate of metastatic lesions was calculated.The independent influencing factors of ¹⁸F-PSMA PET/CT in the positive detection of metastatic lesions were determined with univariate and multivariate logistic regression analyses.The predictive nomogram was established. 【Results】 Of the 175 patients, metastatic lesions were detected in 78 cases and not detected in 97 cases, with a detection rate of 44.6% (78/175).There were statistically significant differences between the metastatic group and the non-metastatic group in urinary tract symptoms, androgen deprivation treatment (ADT) at the time of PET/CT examination and the risk level of Gleason score (GS) (P<0.05).Univariate logistic regression showed that urinary tract symptoms(OR=3.64, P<0.001), GS risk (OR=3.96, P<0.001) and concurrent ADT treatment (OR=3.71, P<0.001) were associated with the positive detection rate of metastatic lesions.Multivariate Logistic regression showed that urinary tract symptoms (OR=3.19, P=0.002), GS high-risk group (OR=2.95, P=0.005) and concurrent ADT treatment (OR=3.27, P=0.001) were independent predictors of positive detection rate. 【Conclusion】 The probability of metastasis in newly diagnosed prostate cancer patients with tPSA≤20 ng/mL is high.¹⁸F-PSMA PET/CT is of high value for the early detection of metastasis.Urinary tract symptoms, GS high-risk group and concurrent ADT treatment are independent predictors of metastatic lesions.The predictive nomogram can help assist clinical optimization of imaging examination path.

The Healthy China construction initiative highlights the concept of patient-centered value-based health care,and the value appeal of doctors'medical service is also increasing.This study attempts to introduce the concept of public service motivation in general public organizations into professional public healthcare organizations——public hospitals,and proposes the concept of"value-based medical service motivation"as an expression of public service motivation for doctors in public hospitals.Through qualitative analysis and quantitative measurement,this paper constructs the concept of"public hospital doctors'value-based medical service motivation",finds its conceptual structure,namely responsibility commitment,professional adherence,reputation maintenance,and norm compliance,and finally forms a value-based medical service motivation scale.This paper confirms that doctors in public hospitals in China have multi-dimensional value-based medical service motivation,present different motivational expressions or behavioral tendencies,and constantly deal with and balance the public value tensions in the practice of realizing the patient-centered value-based medical goal.This scale provides an effective tool for measuring doctors'value-based service motivation,and provides theoretical and practical support for further investigating the influencing factors of doctors'motivation for value-based medical services,improving the medical service capacity of public hospitals,adjusting medical behavior,and advancing doctor-patient trust.

Objective:To investigate the effect of stress-induced protein Sestrin2 (SESN2) on necroptosis of mouse dendritic cell (DC) induced by lipopolysaccharide (LPS) combined with zVAD, a panaspartate-specific cysteine protease (caspase) inhibitor.Methods:The DC2.4 cell line derived from the bone marrow of mouse in the 3rd to 10th generations was cultured. The cells were stimulated with LPS for 0 hour, 6 hours, 12 hours, and 24 hours, and grouped according to the stimulation time points. Western blotting was performed to determine the protein expression of SESN2 in each group. Overexpression empty lentivirus (NC), SESN2 gene overexpression RNA sequence lentivirus (SESN2 LV-RNA), small interfering empty lentivirus (NS), and SESN2 gene small interfering RNA sequence lentivirus (SESN2 siRNA) were transfected into DC2.4 cells. After 72 hours of transfection, cell fluorescence expression was observed under the inverted fluorescence microscope. Cells in each transfection group were stimulated with LPS for 24 hours. The blank control groups were set up and cultured with phosphate buffered saline (PBS) for 24 hours. Western blotting was performed to measure SESN2 protein expression. In the same groups as above, cells were stimulated with LPS+zVAD for 24 hours. The blank control groups were set up and cultured with PBS for 24 hours. Western blotting was used to determine the expression of mixed lineage kinase domain-like protein (MLKL) and phosphorylated-MLKL (p-MLKL). The p-MLKL levels and the number of positive cells were observed using laser scanning confocal microscopy. The necroptotic cell ratios were assessed by both flow cytometry and Hoechst staining.Results:Compared to the LPS 0 hour group, the expression of SESN2 in the LPS 24 hours group showed a significant increase. Therefore, 24 hours was chosen as the subsequent stimulation time point. After successful lentivirus transduction and 24 hours of cultivation, the MLKL phosphorylation level in the SESN2 siRNA+LPS+zVAD group was significantly higher than that in the NS+LPS+zVAD group. The MLKL phosphorylation in the SESN2 LV-RNA+LPS+zVAD group was significantly lower than that in the NC+LPS+zVAD group. The MLKL phosphorylation levels in both the NS+LPS+zVAD group and the NC+LPS+zVAD group were obviously higher than those in the NS+PBS group and the NC+PBS group, respectively. Laser scanning confocal microscopy showed that the trends in quantity and fluorescence intensity of p-MLKL protein expressions were consistent with the above results. The results from flow cytometry analysis and Hoechst staining showed that the rates of cell necrotic apoptosis in SESN2 siRNA+LPS+zVAD group were significantly higher than those in NS+LPS+zVAD group [flow cytometry analysis: (30.800±1.153)% vs. (20.800±1.114)%, Hoechst staining: (75.267±0.451)% vs. (46.267±3.371)%, both P < 0.05], indicating that knocking down SESN2 further exacerbated the occurrence of necroptosis. The necrotic apoptosis rates in SESN2 LV-RNA+LPS+zVAD group were significantly lower than those in NC+LPS+zVAD group [flow cytometry analysis: (7.160±0.669)% vs. (19.240±2.322)%, Hoechst staining: (32.433±3.113)% vs. (48.567±4.128)%, both P < 0.05], indicating that overexpressing SESN2 reversed such response and markedly reduced the proportion of necroptotic cells compared to the corresponding empty vector group. Conclusion:SESN2 exhibits an inhibitory effect on necroptosis of DC in sepsis. Targeted SESN2 expression may regulate the process of DC-mediated immune response in sepsis.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Objective:To investigate the effects of stimulator of interferon gene (STING) on ferroptosis mediated by acyl-CoA synthetase long-chain family member 4 (ACSL4) in mouse dendritic cells (DCs) under sepsis, providing a basis for improving the dysregulation of immune response in sepsis caused by factors such as wound infection.Methods:This study was an experimental research. The mouse DC line DC2.4 in the logarithmic growth phase (with passages 3-10) were divided into lipopolysaccharide (LPS) stimulation 0 h (unstimulated) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 18 h group, and LPS stimulation 24 h group according to the random number table (the same grouping method below), which were cultured with 1 μg/mL LPS (the same concentration below) for the corresponding time. The protein expressions of phosphorylated STING (p-STING), STING, and ACSL4 in cells were determined by Western blotting. DC2.4 successfully transfected with lentivirus containing STING gene small interfering RNA (hereinafter referred to as siSTING) were divided into siSTING+phosphate buffer solution (PBS) group and siSTING+LPS group. DC2.4 successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After being stimulated with PBS or LPS and cultured for 24 hours, the protein expressions of p-STING, STING, and ACSL4 in cells were determined as above. Cell lipid peroxidation degrees were observed using the lipid peroxidation assay kit, and cell apoptosis rates were detected using flow cytometry. The sample numbers in the above cell experiments were all 3. Eighty male C57BL/6J mice aged 6 to 8 weeks were divided into sham surgery+normal saline (NS) group, cecal ligation and puncture (CLP)+NS group, sham surgery+C-176 group, and CLP+C-176 group, with 20 mice in each group. Mice in the two C-176 groups were intraperitoneally injected with C-176, while mice in the two NS groups were intraperitoneally injected with an equivalent volume of NS. One hour later, sham surgery was performed on the mice in the two sham surgery groups, and CLP surgery was performed on the mice in the two CLP groups to establish a sepsis model. At 24 h post-surgery, 10 mice from each group were sacrificed to extract spleen DCs, and protein expression, lipid peroxidation, and apoptosis rates were detected as above ( n=3). Hematoxylin-eosin staining was performed to observe pathological damage in the heart, liver, lung, and kidney tissue. The remaining 10 mice in each group were observed for survival within 7 days after surgery. Results:The protein expressions of p-STING, STING, and ACSL4, as well as the p-STING/STING ratio in DC2.4 in LPS stimulation 24 h group were significantly higher than those in LPS stimulation 0 h group ( P<0.05). After 24 h of culture, the protein expressions of p-STING, STING, and ACSL4 in DC2.4 in siSTING+LPS group and empty vector+PBS group were significantly lower than those in empty vector+LPS group ( P<0.05); the lipid peroxidation degrees of DC2.4 in siSTING+LPS group and empty vector+PBS group were weaker than those in empty vector+LPS group. The apoptosis rates of DC2.4 in empty vector+PBS group, empty vector+LPS group, siSTING+PBS group, and siSTING+LPS group were (15.7±3.0)%, (37.8±2.9)%, (13.1±2.1)%, and (20.6±1.8)%, respectively. The apoptosis rates of DC2.4 in empty vector+PBS group and siSTING+LPS group were significantly lower than that in empty vector+LPS group ( P<0.05). At 24 h post-surgery, the protein expressions of p-STING and ACSL4, and the p-STING/STING ratio in spleen DCs of mice in CLP+NS group were significantly higher than those in sham surgery+NS group and CLP+C-176 group ( P<0.05); the protein expression of STING in spleen DCs of mice in CLP+NS group was significantly higher than that in sham surgery+NS group ( P<0.05); the lipid peroxidation degrees of spleen DCs of mice in CLP+C-176 group and sham surgery+NS group were weaker than that in CLP+NS group. The apoptosis rates of spleen DCs of mice in sham surgery+NS group and CLP+C-176 group were significantly lower than that in CLP+NS group ( P<0.05), and the apoptosis rate of spleen DCs of mice in CLP+C-176 group was significantly higher than that in sham surgery+C-176 group ( P<0.05). Pathological tissue damage in the heart, liver, lung, and kidney of mice in CLP+NS group was significantly worse than that in sham surgery+NS group, while such damage in the above organs of mice in CLP+C-176 group was significantly alleviated compared with that in CLP+NS group. The survival ratio of mice in CLP+NS group within 7 days after surgery was significantly lower than that in sham surgery+NS group ( χ2=8.30, P<0.05). Conclusions:Under sepsis, STING activation in mouse DCs is significant, which enhances ACSL4-mediated ferroptosis. Inhibiting STING activation can significantly reduce ACSL4-mediated ferroptosis level in mouse DCs under sepsis, thereby improving the survival rate of septic mice.

BACKGROUND:In recent years,the development of liver organoids has made it a hot spot in the field of international liver disease research,but there is still no article on the bibliometric analysis of liver organoids. OBJECTIVE:To explore the hot trends in liver organoids in the last 20 years based on bibliometrics and visualization analysis. METHODS:We searched the articles about liver organoids in the Web of Science Core Collection from January 1,2002 to November 12,2022.Origin,Office,and CiteSpace software were used for bibliometrics and visualization analysis.We statistically analyzed the number of annually published articles,countries,institutions,authors,journals,and keywords of the articles by generating charts. RESULTS AND CONCLUSION:The number of articles,citation frequency,institutions and personnel involved in the research about liver organoids showed an overall upward trend in the last 20 years,indicating that the field was growing rapidly and attention was increasing.The USA had published the most papers and had the strongest influence in this field.Although it had invested a lot of time and energy,the number of papers published by a single research institution in the USA was not the highest among many research institutions.China was second only to the USA in the number of publications,with the Chinese Academy of Sciences and Fudan University leading the list.Utrecht University in the Netherlands was the institution with the most publications.Clevers H was the author with the highest number of articles.The article with the highest co-citation frequency was"Long-term culture of genome-stable bipotent stem cells from adult human liver".The main fields of study for liver organoids were Molecular Science,Biology,and Immunology.The most frequently occurring keywords were stem cell,in vitro,and culture.The research hotspots in the liver organoids field were mainly focused on in vitro stem cell three-dimensional culture,differentiation and gene expression.

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.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.