Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

With the maturation of proteomics technologies in recent years, proteomics has made significant achievements in early detection of major diseases, disease classification, drug target discovery, and other fields. To explore the important role of proteomics, especially proteomics-based cutting-edge lifeomics technologies, in promoting the development of precision laboratory medicine and to discuss the opportunities and challenges faced during the clinical translation of innovative outcomes, the National Center for Protein Sciences-Beijing invited renowned experts and scholars in laboratory medicine, lifeomics, and precision medicine. The discussions revolved around the collaborative development of laboratory medicine and lifeomics, the future trends of new technologies in clinical laboratory testing, the innovation and development of lifeomics in laboratory medicine, the translational application of proteomics technologies in laboratory medicine, and the opportunities and challenges in the industrialization of proteomics achievements. All participants agreed that proteomics provides new directions and opportunities for precision diagnosis and treatment of diseases. However, close collaboration between academia, hospitals and industry is required. Additionally, challenges such as clinical applicability of equipment, standardization of detection methods and data, cost and quality control, talent cultivation, and the industrialization pathway need to be addressed.

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.

Objective:Age-related cataract is the most common type of adult cataract and a leading cause of blindness.Currently,there are few reports on the establishment of animal models for age-related cataract.During the experimental breeding of Microtus fortis(M.fortis),we first observed that M.fortis aged 12 to 15 months could naturally develop cataracts.This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M.fortis. Methods:The 12-month-old healthy M.fortis were served as a control group and 12-month-old cataractous M.fortis were served as an experimental group.The lens transparency was observed using the slit-lamp biomicroscope.Hematoxylin and eosin staining was used to detect pathological changes in the lens.Biochemical detection methods were applied to detect blood routine,blood glucose levels,the serum activities of superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in both groups.Finally,real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. Results:Compared with the control group,the lens of cataract M.fortis showed severely visible opacity,the structure of lens was destroyed seriously,and some pathological damage,such as swelling,degeneration/necrosis,calcification,hyperplasia,and fiber liquefaction were found in lens epithelial cells(LECs).The fibrous structure was disorganized and irregularly distributed with morgagnian globules(MGs)aggregated in the degenerated lens fibers.There was no statistically significant difference in blood glucose levels between the experimental and control groups(P＞0.05).However,white blood cell(WBC)count(P＜0.05),lymphocyte count(P＜0.01),and lymphocyte ratio(P＜0.05)were significantly decreased,while neutrophil percentage(P＜0.05)and monocyte ratio(P＜0.01)were significantly increased.The serum activities of SOD and GSH-Px(both P＜0.05)were both reduced.The mRNAs of cataract-related genes,including CRYAA,CRYBA1,CRYBB3,Bsfp1,GJA3,CRYBA2,MIP,HspB1,DNase2B,and GJA8,were significantly downregultaed in the lenses of the experimental group(all P＜0.05). Conclusion:There are significant differences in lens pathological changes,peroxidase levels,and cataract-related gene expression between cataract and healthy M.fortis.The developed cataract spontaneously in M.fortis is closely related to age,the cataract M.fortis might be an ideal animal model for the research of age-related cataract.

Objective·To explore the effects and possible molecular mechanisms of nanoplastics(NPs)on severe asthma.Methods·A mouse model of severe asthma was established by using house dust mite(HDM)and lipopolysaccharide(LPS)co-stimulation.Polystyrene nanoplastics(PS-NPs)were instilled into the severe asthma mice's airways.Subsequently,bronchoalveolar lavage fluid(BALF)was collected and lung tissue sections were prepared.Flow cytometry,hematoxylin-eosin(H-E)staining,periodic acid-Schiff(PAS)staining,immunohistochemistry,and terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,were used to observe the effects of PS-NPs on airway inflammation,mucus secretion,alveolar structure,and the proliferation and apoptosis of alveolar type Ⅱ epithelial cells(AT2 cells)in severe asthma mice.The CCK-8 assay and Annexin Ⅴ/PI double staining were performed to evaluate the effects of PS-NPs on the proliferation and apoptosis of the mouse AT2 cell line MLE-12.DNA damage in AT2 cells caused by PS-NPs was detected by using anti-γ-H2A.X immunofluorescence staining.The expression of genes in the ATR/Chk1/p53 signaling pathway was detected by real-time fluorescent quantitative polymerase chain reaction(qPCR),Western blotting,Tyramide signal amplification(TSA)multiplex immunofluorescence staining,and immunofluorescence co-localization,respectively.The ATR-specific inhibitor Ceralasertib(AZD6738)was administrated to MLE-12 cells in combination with PS-NPs to evaluate the recovery effect on cell proliferation and apoptosis.Results·Flow cytometry revealed that exposure to PS-NPs increased the total number of inflammatory cells and the number of each type of inflammatory cells in the BALF of mice with severe asthma,with a predominance of neutrophils.H-E and PAS staining showed significant increase in airway inflammatory cell infiltration and mucus secretion,as well as disruption of alveolar structure.In vitro,the CCK-8 assay demonstrated significant,dose-dependent inhibition of MLE-12 cell proliferation by PS-NPs.The Annexin V/PI double staining assay indicated a higher apoptosis rate of(56.20±3.84)%in PS-NP-exposed cells compared to(23.22±2.52)%in the control group.Immunofluorescence staining demonstrated that PS-NPs were phagocytosed by MLE-12 cells and localized around the nucleus.TUNEL staining confirmed enhanced apoptosis in AT2 cells in vivo.The immunofluorescence assay revealed that compared to the control group,the expression of the DNA damage marker γ-H2A.X increased in the experimental group.qPCR,Western blotting,and TSA multiplex staining results showed that PS-NP-induced elevated expression of mRNA and proteins was related to the ATR/Chk1/p53 pathway in MLE-12 cells.Moreover,immunofluorescence co-localization also confirmed the induction of ATR and p53 proteins in AT2 cells in vivo.The ATR-specific inhibitor Ceralasertib partially restored the PS-NP-induced inhibition of cell proliferation and enhancement of apoptosis in MLE-12 cells.Conclusion·NPs exposure leads to DNA damage in AT2 cells,activating the ATR/Chk1/p53 signaling pathway and exacerbating airway inflammation and alveolar damage in mice with severe asthma.

Objective To explore the value of computer-aided measurement of the mass-based consolidation-to-tumor ratio(CTRmass)in predicting preoperative clinical stage IA lung adenocarcinoma invasion.Methods A total of 56 patients with stage IA lung adenocarcinoma were retrospectively selected from Linfen Central Hospital and the National Lung Screening Trial(NLST)database(project number NLST-1053),and all of them were confirmed by pathology.Computer-aided software was used to automatically cal-culate parameters such as the volume-based consolidation-to-tumor ratio(CTRvol),CTRmass,average CT value,and maximum axial diameter,and its correlation with pathological results was analyzed.Results When the CTRmass≥30.95％,it indicated that lung nodules were more likely to be invasive adenocarcinoma(IAC).Conclusion CTRmass,based on computer-aided software measure-ment,can be used as one of the important indicators to evaluate the preoperative invasion of clinical stage IA lung adenocarcinoma,guiding the selection of surgical methods,and obtaining better curative effects.

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.