Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Background and Aims:Colorectal cancer(CRC)has a complex pathogenesis,and current treatments remain limited in efficacy for advanced metastatic disease.Dasatinib is a multi-target tyrosine kinase inhibitor that has shown potential antitumor activity in various solid tumors.This study aimed to evaluate the causal relationships between dasatinib-related target genes and CRC based on genetic variation,and to explore the mediating role of immune cells,thereby providing genetic epidemiological evidence for the prevention and targeted therapy of CRC.Methods:Dasatinib-related target genes were identified through DrugBank,and the corresponding eQTLs,GWAS data for CRC(ebi-a-GCST90018808),and 731 immune-cell traits were obtained from the IEU OpenGWAS database.A two-sample Mendelian randomization(MR)framework with a two-step mediation approach was applied:first,to assess the causal relationship between dasatinib target genes(as exposures)and CRC;second,to evaluate the causal effects between target genes and immune cells,as well as between immune cells and CRC;and finally,to calculate the proportion of mediated effects.Wald ratio,inverse-variance weighted(IVW),MR-Egger,MR-PRESSO,Cochran's Q,I2,and leave-one-out analyses were used to examine heterogeneity,horizontal pleiotropy,and robustness.Results:MR results showed that dasatinib-associated inhibition of ABL1 was significantly associated with a reduced risk of CRC(OR=0.511 0,95%CI=0.323 1-0.808 0,P=0.004 1).Inhibition of YES1 was also associated with decreased CRC risk(IVW OR=0.889 9,95%CI=0.811 6-0.975 8,P=0.013 1),with no evident heterogeneity or horizontal pleiotropy among the corresponding SNPs.Further analysis revealed that dasatinib-related inhibition of YES1 significantly reduced the levels of IgD-CD24-AC level(OR=0.818 0,95%CI=0.678 2-0.986 7,P=0.035 7),and this immune cell subset itself was identified as a risk factor for CRC(OR=1.105 7,95%CI=1.029 6-1.187 5,P=0.005 7).Mediation analysis indicated that IgD-CD24-AC accounted for-9.89%and 17.31%of the mediation effects in the ABL1→CRC and YES1→CRC pathways,respectively.Conclusion:Genetic evidence from MR suggests dasatinib-target genes ABL1 and YES1 are causally linked to reduced CRC risk,with IgD-CD24-AC partially mediating the YES1-related protective effect.These findings point to immune-mediated mechanisms underlying dasatinib's potential influence on CRC risk;further experimental validation and replication across populations are warranted.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Background and Aims:Colorectal cancer(CRC)has a complex pathogenesis,and current treatments remain limited in efficacy for advanced metastatic disease.Dasatinib is a multi-target tyrosine kinase inhibitor that has shown potential antitumor activity in various solid tumors.This study aimed to evaluate the causal relationships between dasatinib-related target genes and CRC based on genetic variation,and to explore the mediating role of immune cells,thereby providing genetic epidemiological evidence for the prevention and targeted therapy of CRC.Methods:Dasatinib-related target genes were identified through DrugBank,and the corresponding eQTLs,GWAS data for CRC(ebi-a-GCST90018808),and 731 immune-cell traits were obtained from the IEU OpenGWAS database.A two-sample Mendelian randomization(MR)framework with a two-step mediation approach was applied:first,to assess the causal relationship between dasatinib target genes(as exposures)and CRC;second,to evaluate the causal effects between target genes and immune cells,as well as between immune cells and CRC;and finally,to calculate the proportion of mediated effects.Wald ratio,inverse-variance weighted(IVW),MR-Egger,MR-PRESSO,Cochran's Q,I2,and leave-one-out analyses were used to examine heterogeneity,horizontal pleiotropy,and robustness.Results:MR results showed that dasatinib-associated inhibition of ABL1 was significantly associated with a reduced risk of CRC(OR=0.511 0,95%CI=0.323 1-0.808 0,P=0.004 1).Inhibition of YES1 was also associated with decreased CRC risk(IVW OR=0.889 9,95%CI=0.811 6-0.975 8,P=0.013 1),with no evident heterogeneity or horizontal pleiotropy among the corresponding SNPs.Further analysis revealed that dasatinib-related inhibition of YES1 significantly reduced the levels of IgD-CD24-AC level(OR=0.818 0,95%CI=0.678 2-0.986 7,P=0.035 7),and this immune cell subset itself was identified as a risk factor for CRC(OR=1.105 7,95%CI=1.029 6-1.187 5,P=0.005 7).Mediation analysis indicated that IgD-CD24-AC accounted for-9.89%and 17.31%of the mediation effects in the ABL1→CRC and YES1→CRC pathways,respectively.Conclusion:Genetic evidence from MR suggests dasatinib-target genes ABL1 and YES1 are causally linked to reduced CRC risk,with IgD-CD24-AC partially mediating the YES1-related protective effect.These findings point to immune-mediated mechanisms underlying dasatinib's potential influence on CRC risk;further experimental validation and replication across populations are warranted.

Objective:To evaluate the reliability and validity of the Face, Legs, Activity, Cry, and Consolability (FLACC) Pain Behavioral Scale, the Children′s Hospital of Eastern Ontario Pain Scale (CHEOPS), and the Objective Pain Scale (OPS) during the general anesthesia recovery period in children with oral therapy, and to explore their screening ability for pain risk, so as to provide information for selecting appropriate pain assessment scales for pediatric patients.Methods:One hundred and four pediatric patients with oral therapy under general anesthesia were recruited at the Stomatological Hospital of Southern Medical University from January to May, 2024. Two researchers observed simultaneously and scored independently using three scales in random order at 15 minutes and 60 minutes after patients arrival at post anesthesia care unit (PACU). Those awake patients also used the Wong-Baker FACES Pain Rating Scale to report their pain. Internal consistency, inter-rater coefficient, construct and criterion validity of three scales were evaluated.Results:The final sample included 97 patients (50 males and 47 females), with an age of (4.88 ± 1.10) years. At 15 minutes and 60 minutes upon arrival at PACU, the Cronbach alpha coefficients for internal consistency of the FLACC, the CHEOPS, and the OPS were 0.993, 0.980, 0.990, and 0.991, 0.974, 0.989, respectively; the inter-rater correlation coefficients were 0.993, 0.985, 0.998, and 0.985, 0.984, 0.984, respectively; exploratory factor analysis extracted one factor from each scale, and cumulative variance contribution rates were 95.116%, 82.145%, 78.417%, and 89.706%, 67.652%, 75.978%, respectively. At 60 minutes upon arrival at PACU, the Spearman correlation coefficients between three scales and the Wong-Baker FACES Pain Rating scale were 0.621, 0.703, 0.588, respectively; Kappa coefficients of three scales were 0.608, 0.683, 0.520, and area under the ROC curve were 0.812, 0.839, 0.812, respectively.Conclusions:The three scales show good reliability and acceptable validity for assessing pain during the general anesthesia recovery period in children with oral therapy. The CHEOPS performs better in pain screening, followed by the FLACC, the OPS.

Objective:To evaluate the reliability and validity of the Face, Legs, Activity, Cry, and Consolability (FLACC) Pain Behavioral Scale, the Children′s Hospital of Eastern Ontario Pain Scale (CHEOPS), and the Objective Pain Scale (OPS) during the general anesthesia recovery period in children with oral therapy, and to explore their screening ability for pain risk, so as to provide information for selecting appropriate pain assessment scales for pediatric patients.Methods:One hundred and four pediatric patients with oral therapy under general anesthesia were recruited at the Stomatological Hospital of Southern Medical University from January to May, 2024. Two researchers observed simultaneously and scored independently using three scales in random order at 15 minutes and 60 minutes after patients arrival at post anesthesia care unit (PACU). Those awake patients also used the Wong-Baker FACES Pain Rating Scale to report their pain. Internal consistency, inter-rater coefficient, construct and criterion validity of three scales were evaluated.Results:The final sample included 97 patients (50 males and 47 females), with an age of (4.88 ± 1.10) years. At 15 minutes and 60 minutes upon arrival at PACU, the Cronbach alpha coefficients for internal consistency of the FLACC, the CHEOPS, and the OPS were 0.993, 0.980, 0.990, and 0.991, 0.974, 0.989, respectively; the inter-rater correlation coefficients were 0.993, 0.985, 0.998, and 0.985, 0.984, 0.984, respectively; exploratory factor analysis extracted one factor from each scale, and cumulative variance contribution rates were 95.116%, 82.145%, 78.417%, and 89.706%, 67.652%, 75.978%, respectively. At 60 minutes upon arrival at PACU, the Spearman correlation coefficients between three scales and the Wong-Baker FACES Pain Rating scale were 0.621, 0.703, 0.588, respectively; Kappa coefficients of three scales were 0.608, 0.683, 0.520, and area under the ROC curve were 0.812, 0.839, 0.812, respectively.Conclusions:The three scales show good reliability and acceptable validity for assessing pain during the general anesthesia recovery period in children with oral therapy. The CHEOPS performs better in pain screening, followed by the FLACC, the OPS.

Multiple plant lineages have independently evolved sex chromosomes and variable kary-otypes to maintain their sessile lifestyles through constant biological innovation.Morus notabilis,a dioecious mulberry species,has the fewest chromosomes among Morus spp.,but the genetic basis of sex determination and karyotype evolution in this species has not been identified.In this study,three high-quality genome assemblies were generated for Morus spp.[including dioecious M.notabilis(male and female)and Morus yunnanensis(female)]with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes.Using a combination of genomic approaches,we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes,and that sev-eral chromosome fusion events resulted in descending dysploidy(2n=2x=12).We also charac-terized a～6.2-Mb sex-determining region on chromosome 3.Four potential male-specific genes,a partially duplicated DNA helicase gene(named MSDH)and three Ty3_Gypsy long terminal repeat retrotransposons(named MSTG1/2/3),were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation.Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mul-berry.In addition,genomic areas containing selective sweeps that distinguish domesticated mul-berry from wild populations in terms of flowering and disease resistance were identified.Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.