Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective: To systematically analyzes the impact of blood donor characteristics on red blood cell (RBC) quality and transfusion outcomes, and to provide a scientific basis for optimizing donor selection criteria and developing personalized transfusion strategies. Methods: A literature search was conducted across electronic databases including CNKI, VIP, Wanfang Data, PubMed, and Embase using combinations of keywords such as "donor characteristics", "blood storage lesion", "blood quality", and "transfusion outcomes" for summary and analysis. Results: Factors associated with the blood donor characteristics including demographic characteristics (sex, age, body mass index), lifestyle habits (smoking, alcohol consumption, exercise), and dietary or pharmacological exposures significantly influence blood storage stability and transfusion efficacy by modulating erythrocyte metabolism, oxidative stress levels, and immune properties. Conclusion: The complexity and diversity of the blood donor characteristics are associated with blood quality and transfusion outcomes. Future efforts should focus on refining donor selection criteria and establishing personalized transfusion strategies to enhance blood product quality and improve patient outcomes.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective: To explore the association between mental health status and adverse childhood experiences (ACEs) among sexual minority college students, so as to provide a scientific basis for mental health education and health promotion in universities. Methods: From January to February 2024, convenience and cluster sampling methods were used to select 1 792 college students from 11 colleges in Guangxi. A self reporting method was applied to identify 476 sexual minority individuals. The Symptom Check-List 90 (SCL-90) and the Simplified Chinese Adverse Childhood Experiences International Questionnaire (SC-ACE-IQ) were employed to assess mental health and ACEs. Multivariate Logistic regression analysis was conducted to examine the associations. Results: The detection rates of all psychological issues among sexual minority college students in Guangxi were significantly higher than those of non sexual minority college students ( χ 2=56.01-91.39, all P <0.01). Except for physical neglect, bullying, and community violence, sexual minority students exhibited higher reporting rates of other ACEs types compared to nonsexual minority students ( χ 2= 4.52-13.34, all P <0.05). The total ACEs score for college students was 1.00 (1.00, 2.00), while the SCL-90 total score was 96.00 (113.00, 160.00). Spearman correlation analysis revealed a positive correlation between ACEs total scores and SCL-90 total scores ( r=0.29, P <0.05). Additionally, all ACEs subscales, including emotional neglect, physical neglect, emotional abuse, sexual abuse, parental loss, domestic violence, and community violence were positively correlated with corresponding SCL-90 subscale scores ( r =0.05-0.22, all P <0.05). Multivariate Logistic regression analysis showed that family violence increased the risk of mental health issues for sexual minority students ( OR=1.61, 95%CI =1.26-2.09); emotional neglect ( OR= 1.05 , 95%CI =1.00-1.10), physical neglect ( OR=1.20, 95%CI =1.06-1.35), sexual abuse ( OR=1.49, 95%CI =1.15-1.93) increased mental health risks for non sexual minority students (all P <0.05). The cumulative effects of ACEs were all statistically significant in the total sample and both subgroups (all P <0.05). Conclusion Mental health status among sexual minority college students in Guangxi is associated with ACEs, and their well being requires active attention

Objective To investigate the microstructural changes of white matter in patients with relapsing-remitting multiple sclerosis(RRMS)and its correlation with clinical functional scores.Methods A total of 20 patients with RRMS(RRMS group)and 20 healthy controls(HC)(HC group)were selected and underwent diffusion tensor imaging(DTI)and expanded disability status scale(EDSS)scores.Patients with RRMS were categorized into two groups based on their EDSS scores,including MS-1 group(motor dysfunction with visual impairment)and MS-2 group(motor dysfunction).Image processing was performed via tract-based spatial statistics(TBSS).Group comparisons were executed using the t-test,while correlations were analyzed utilizing Spearman correlation.Results In the RRMS group,reduced fractional anisotropy(FA)values were accompanied by increased mean diffusivity(MD)and radial diffusivity(RD)values in the forceps major,forceps minor,bilateral cingulum,bilateral uncinate fasciculus,bilateral superior longitudinal fasciculus,bilateral inferior longitudinal fasciculus,bilateral inferior fronto-occipital fasciculus,bilateral corticospinal tract and bilateral anterior thalamic radiation compared with the HC group.Additionally,In the RRMS group,increased axial diffusivity(AD)values were noted in the forceps major,forceps minor,bilateral superior longitudinal fasciculus(temporal),right inferior fronto-occipital fasciculus,bilateral corticospinal tract and right anterior thalamic radiation compared with the HC group.Compared with the MS-2 group,the MS-1 group exhibited higher FA values in the right cingulum(cingulate gyrus part)and higher AD values in the left cingulum(cingulate gyrus part).Correlation analysis revealed negative correlations between the FA values of the forceps major,right superior longitudinal fasciculus and the motor function scores in RRMS group.Conversely,positive correlations were identified between the MD values of the forceps minor,right superior longitudinal fasciculus,right inferior fronto-occipital fasciculus,left corticospinal tract and the RD values of the forceps minor,right cingulum(hip-pocampus),right superior longitudinal fasciculus,and left corticospinal tract,as well as the motor function scores.Conclusion RRMS patients exhibit microstructural damage in white matter and are associated with motor dysfunction,which provides imaging support for the pathological mechanisms underlying motor dysfunction in RRMS patients.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective To construct an enhancer-based prognostic risk prediction model for non-small cell lung cancer (NSCLC) by integrating DNA methylome data and transcriptome data. Methods The weighted gene co-expression network analysis (WGCNA) was used to identify NSCLC related genes from the differentially methylated positions (DMPs) of enhancers. Based on the transcriptome data,the prognostic risk prediction model was constructed using LASSO-Cox regression algorithm. Results Through the analysis on DNA methylome data of NSCLC,19784 DMPs were obtained and their distribution patterns were characterized,including 6089 DMPs of enhancers. WGCNA analysis screened 79 highly correlated DMPs of enhancer with NSCLC from the 6089 DMPs. After analyzing the target genes of 79 DMPs with LASSO-Cox regression based on the transcriptome data,10 genes were used to construct a prognostic risk prediction model. The prognostic risk prediction model was evaluated by calculating the areas under the curve (AUC) of 3-,5-,and 10-year time-dependent receiver operating characteristic (ROC) curves in training set and validation set;and the results showed that the 3-,5-,and 10-year AUC in training set and validation set were all higher than 0.7. Finally,a nomogram was constructed to predict the 3-,5-,and 10-year survival probabilities of NSCLC. Conclusion This study provides new insights into the role of enhancers in NSCLC and has the potential to improve the prognosis by guiding personalized treatment decisions.

Objective:To design a special device for limiting position of boat-shape headrest of breast brackets,and explore its application value in radiotherapy post-radical mastectomy.Methods:1 cm plex glass plate was cut as T-shape base plate,and the top of the T-shape base plate was drilled to obtain four holes for limiting position.A 2 mm acrylic plate was cut as horse hoof-shape and strip-shape pieces for limiting position,which were adhered respectively to the top and bottom of the T-shape base plate to form a boat-shape headrest with groove structure for limiting position.Self-made pillars with limiting position were used to connect the T-shape base plate with the backplane of breast bracket,so as to realize rigid connection between conventional boat-shape headrest and breast bracket.A total of 60 female patients who received radiotherapy after radical mastectomy for breast cancer at Changzhou Cancer Hospital during January and December 2023 were selected.They were randomly divided into an observation group and a control group(with 30 cases in each group)by using a random number table.The observation group adopted breast bracket combined with self-made boat-shape headrest for limiting position device+boat-shape headrest to conduct fixation,while the control group adopted rotundity headrest of breast bracket to conduct fixation.Both groups adopted hybrid intensity-modulated radiotherapy(IMRT)technique to formulate plan,and the exposure dose was 50Gy/25 fractions,and patients received radiotherapy as 5 times per week,and the treatment course was 5 weeks.Cone-beam computed tomography(CBCT)was used to conduct verification for position before the first 3 treatments.During the treatment duration between the 2nd and the 5th week,CBCT verification for position was conducted in each week.The positioning error and positioning time on left-right direction(x),head-foot direction(y)and abdomen-back direction(z)at each time between two groups were compared.Results:The positioning errors on x,y,z direction of three dimension at each time in observation group were lower than those in control group,and the differences were significant(Z=-7.666,-11,672,-6.311,P<0.05).The average positioning time at first time and the total average positioning time were respectively(222.4±12.9)s and(212.2±15.1)s in observation group,all of which were lower than(262.9±12.5)s and(254.0±15.7)s in control group,and the differences were significant(t=12.364,27.783,P<0.05).Conclusion:The combination of breast bracket and self-made device with boat-shape for limiting position can increase precision and efficiency of positioning,and improve comfort through individually chooses the type of boat-shape headrest,and set the position of headrest,which has favorable clinically application value.