BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

A 70-year-old man had radical surgery for colon cancer one year before the symptoms of memory loss and decreasing cognitive function.Subsequent magnetic resonance imaging revealed a brain mass,which was surgically resected and confirmed to be metastatic intestinal adenocarcinoma.Immunohistochemistry of the primary tumor and brain metastasis showed mismatch repair deficiency.The patient received adjuvant chemotherapy after surgery.However,the brain metastasis relapsed one month after the last chemotherapy.Genetic testing on the resected colon tumor samples confirmed microsatellite instability-high with a high tumor mutation burden by 77.7 muts/Mb.The patient was subsequently treated with programmed death-1(PD-1)monoclonal antibody pembrolizumab(keytruda).The brain metastatic lesions were completely shrunk,and a complete clinical response was achieved.

Objective:This study aimed to explore the clinical value of myostatin(MST) and follistatin(FST) as biological biomarkers in evaluating sarcopenia in elderly women.Methods:This was a retrospective cross-sectional study that enrolled 350 females aged 20-89 years who underwent physical examinations in Shanghai Huadong Hospital in 2021. Demographic characteristics, muscle mass, fat mass, bone mineral density, hand grip strength, gait speed, and serum indices of MST and FST were collected.Results:The serum levels of MST did not change significantly with age. However, the serum levels of FST increased with age. In women aged≥60 years, MST was positively correlated with total lean mass and appendicular skeletal muscle index(ASMI; r=0.236, P=0.041; r=0.289, P=0.014), while FST was negatively correlated with ASMI( r=-0.265, P=0.030). In multivariate stepwise regression analysis, after adjusting for age, body mass index, hip bone mineral density, and total fat mass, only FST was independently correlated with ASMI( β=-0.238, P=0.006), while MST was not correlated with ASMI. The receiver operating characteristic curve was plotted using muscle mass reduction as the state variable and serum FST level as the test variable. The area under the curve was 0.753. And when the FST cutoff value was 17.49 ng/mL, the maximum Jordan index was 0.46, with a sensitivity of 77.3% and a specificity of 68.7%. Women aged ≥60 years were divided into three groups based on serum FST levels. Compared to the upper third of the serum FST level group, the low third of the FST level group had a significantly reduced risk of suffering from sarcopenia( OR=0.098, P =0.036). Conclusions:Serum FST lever has a better correlation with muscle mass among elderly women, making it a promising biomarker for evaluating muscle mass.

Objective:To investigate the effect and mechanism of miR-217 targeted regulation of extracellular signal-regulated kinase 2(ERK2)expression on activity and immune escape of non-small cell lung cancer cells(NSCLC).Methods:qRT-PCR was used to detect expression levels of miR-217 and ERK2 mRNA in NSCLC tissues,adjacent tissues,and HLF-1,A549 and HCC827 cell lines.Analyzed prognosis and survival status of NSCLC patients with different miR-217 expression level.Bioinformatics and dual luciferase gene reporting experiments were used to analyze the targeting relationship between miR-217 and ERK2.Cultivated NSCLC A549 cells and divided them into NC group,miR-217 inhibitor group,miR-217 mimic group,miR-217 mimic+ERK2 NC group and miR-217 mimic+ERK2 group.Except for the NC group without any treatment,all other groups were transfected with corresponding plasmids to analyze the proliferation activity and immune escape status of A549 cells in each group,and clarified the mechanism of action.Results:Compared with adjacent tissues,expression of miR-217 in NSCLC tissue was decreased,while expression of ERK2 mRNA was increased(P<0.05).Compared with human normal lung fibroblast HLF-1 cell lines,expression of miR-217 in NSCLC cell lines A549 and HCC827 were decreased,while expression of ERK2 mRNA was increased(P<0.05).Analysis of the relationship be-tween miR-217 and prognosis of NSCLC patients based on Kaplan-Meier Plotter database showed that low expression of miR-217 was associated with poor prognosis of patients(HR=0.90,P=0.033).Dual fluorescein reporter genes showed matching sequences between the 3'UTR regions of miR-217 and ERK2.miR-217 mimic fragment could inhibit ERK2-WT signal,but had no effect on ERK2-MUT.Compared with NC group,cell proliferation activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 inhibitor group were in-creased,while CD8+T cell activity was decreased,and cell proliferation activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 mimic group were decreased,while CD8+T cell activity was increased(P<0.05).Compared with miR-217 mimic group,cell pro-liferation activity,CD8+T cell activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 mimic+ERK2 NC group had no signifi-cant changes(P>0.05),cell proliferation activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 mimic+ERK2 group were increased,while CD8+T cell activity was decreased(P<0.05).Conclusion:Overexpression of miR-217 can reduce the activity of NSCLC cell A549,inhibit the expression of PD-L1,activate CD8+T cells in tumor microenvironment,and then inhibit immune es-cape,which may play a role by targeting ERK2.

Objectives:To investigate the screening status of warning signs for mental and behavioral development (WS) and influencing factors of infants and young children (IYC) in poverty eliminated regions of Henan Province.Methods:This study was a cross-sectional study. A total of 15 680 IYC aged 6-23 months from 51 poverty eliminated counties in Henan province from June to September of 2023 were selected through a multi-stage random sampling method. IYC′s early warning signs were screened using the WS checklist (WSC). Children′s socio-demographic characteristics, maternal information, birth status, and illness conditions such as fever and diarrhea within 2 weeks were measured through a uniformly designed questionnaire. All participants also received the measurement of height, weight, and hemoglobin concentration level. Logistic regression model was used to explore the influencing factors of positive WSC and conducted sensitivity analyses.Results:Among the sample of 15 680 IYC, there were 8 462 boys (53.97%) and 7 218 girls (49.03%), with their age of (15±5) months. A total of 291 (1.86%) IYC were positive in WSC. Parenting risk ( OR=5.07, 95% CI 3.93-6.52, P<0.001) and preterm birth ( OR=1.63, 95% CI 1.06-2.52, P=0.027) were both positively associated with the odds of WSC′s positivity. Being girls ( OR=0.66, 95% CI 0.52-0.85, P=0.001), age (12-17 months, OR=0.47, 95% CI 0.35-0.62, P<0.001; 18-23 months, OR=0.40, 95% CI 0.30-0.54, P<0.001), and maternal educational level (junior high school, OR=0.46, 95% CI 0.32-0.66, P<0.001; senior high school or vocational high school, OR=0.35, 95% CI 0.23-0.56, P<0.001; college and above, OR=0.36, 95% CI 0.23-0.57, P<0.001) were all negatively associated with the risk of WSC′s positivity. Sensitivity analyses demonstrated that, after excluding anemic children, the association between preterm birth and WSC′s positivity was not significant ( OR=1.54, 95% CI 0.95-2.49, P=0.081). Despite this situation, being girls, age and maternal educational level were still negatively associated with the odds of WSC′s positivity (all P<0.05); preterm birth, parenting risk were remained positive associated with the risk of WSC′s positivity (all P<0.05) either by excluding children with protein-energy malnutrition or 2-week morbidity, or using prevalence ratio instead of OR. Conclusions:Among the IYC in poverty eliminated regions of Henan Province, the risk of positivity of WSC was higher for those IYC with parenting risk, preterm birth, boys, younger age, and lower maternal education level. These influencing factors, such as gender, age, preterm birth, parenting risk and maternal educational level, were in certain stability across different IYC characteristics and estimation models.

Objective: To investigate the screen exposure status and influencing factors among 6-12 year-old children in Hainan Province, so as to provide insights into screen exposure intervention for children. Methods: Children aged 6-12 years from 18 counties (cities) in Hainan Province were selected using multi-stage stratified cluster sampling method from December 2020 to July 2021. Demographic information, parents' educational level, family type and screen time was collected using questionnaire surveys. The screen exposure rate of children was analyzed, and factors affecting screen exposure were identified using a multivariable logistic regression model. Results: A total of 27 501 children were surveyed, including 13 901 boys (50.55%) and 13 600 girls (49.45%). The mean age was (9.22±1.86) years. Among them, 3 925 children had screen exposure, with a screen exposure rate of 14.27%. Multivariable logistic regression analysis showed that gender (female, OR=0.859, 95%CI: 0.796-0.926), age (OR=1.078, 95%CI: 1.049-1.108), ethnicity (ethnic minorities, OR=1.147, 95%CI: 1.041-1.254), place of residence (rural area, OR=0.869, 95%CI: 0.801-0.944), father's educational level (high school or technical secondary school, OR=0.879, 95%CI: 0.788-0.981; college degree or above, OR=0.686, 95%CI: 0.589-0.818), mother's educational level (college degree or above, OR=0.706, 95%CI: 0.588-0.846), family type (others, OR=1.250, 95%CI: 1.105-1.414), and annual family income (>100 000 Yuan, OR=0.741, 95%CI: 0.619-0.885) were the influencing factors for screen exposure among children aged 6-12 years. Conclusion The screen exposure among children aged 6-12 years in Hainan Province was affected by gender, age, ethnicity, place of residence, parental education level, family type and annual family income.

Objective To investigate the correlation between the expression of long non-coding ribonucleic acid growth arrest specific 5(lncRNA GAS5),phospholysine phosphohistidine inorganic pyrophosphate phos-phatase(LHPP)and epithelial-mesenchymal transition(EMT)in cancer tissues of patients with non-small cell lung cancer(NSCLC)and its clinical significance.Methods Cancer tissues and adjacent tissues of 90 patients with NSCLC who underwent surgical resection in the First Hospital Affiliated to Hebei North College from June 2018 to January 2020 were collected.The expressions of lncRNA GAS5,LHPP and EMT-associated pro-teins[E-calmodulin(E-Cad),N-calmodulin(N-Cad),and vimentin(VIM)]were detected by real-time fluores-cence quantitative polymerase chain reaction.The relationship between lncRNA GAS5 and LHPP mRNA and clinicopathological features in cancer tissues of NSCLC patients was analyzed,and the correlation between ln-cRNA GAS5 and LHPP mRNA and EMT-associated proteins expression in cancer tissues of NSCLC patients was analyzed by Pearson correlation.Kaplan-Meier method was used to plot the survival curves of NSCLC pa-tients with different lncRNA GAS5 and LHPP mRNA expressions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The expressions of lncRNA GAS5,LHPP mR-NA and E-Cad mRNA in cancer tissues of NSCLC patients were lower than those in adjacent tissues,while the expressions of N-Cad mRNA and VIM mRNA were higher than those in adjacent tissues,with statistical sig-nificance(P＜0.05).Pearson correlation analysis showed that lncRNA GAS5 in cancer tissues of NSCLC pa-tients was positively correlated with E-Cad mRNA expression(r=0.724,P＜0.001),and negatively correla-ted with N-Cad mRNA and VIM mRNA expression(r=-0.699,-0.689).P＜0.001);lncRNA GAS5 was positively correlated with LHPP mRNA expression(r=0.651,P＜0.001).The mRNA expressions of ln-cRNA GAS5 and LHPP in cancer tissues of NSCLC patients with different degrees of differentiation,tumor TNM stage and lymph node metastasis were significantly different(P＜0.05).Kaplan-Meier survival curve a-nalysis showed that the 3-year overall survival rate in the lncRNA GAS5 high expression group[68.18％(30/44)]was higher than that in the lncRNA GAS5 low expression group[36.96％(17/46)].The 3-year overall survival rate in the high LHPP mRNA expression group[67.39％(31/46)]was higher than that in the lowLHPP mRNA expression group[36.36％(16/44)],and the difference was statistically significant(x2=10.274,10.322,P＜0.05).Low differentiation,TNM stage Ⅲ and lymph node metastasis were independent risk factors for death in NSCLC patients,and lncRNA GAS5≥1.32 and LHPP mRNA≥1.12 were independ-ent protective factors(P＜0.05).Conclusion The low expression of lncRNA GAS5 and LHPP mRNA in cancer tissues of patients with NSCLC is related to EMT-associated proteins expression,differentiation de-gree,tumor TNM stage,lymph node metastasis and prognosis,and may become a new target for the diagnosis and treatment of NSCLC.