Novel needle-type electrocoagulation and combination pharmacotherapy: Basic and clinical studies on efficacy and safety in treating keloids.

BACKGROUND AND AIM: Keloids cannot be effectively treated using monotherapy regimens. This study aimed to evaluate the efficacy and safety of ablation (a novel needle-assisted electrocoagulation technique) combined with pharmacotherapy (corticosteroid and 5-fluorouracil [5-FU] injections) in removing keloids and to investigate the underlying biological mechanisms. METHODS: The effects of energy consumption and duration of needle-assisted electrocoagulation on the ablation zone were tested in porcine liver tissue, which simulates human skin. The regulatory effects of ablation combined with pharmacotherapy on collagen deposition, cell proliferation, and angiogenesis were analyzed in a keloid-bearing nude mouse model in vivo. In a clinical trial involving six patients with keloids, the Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) scores were graded before treatment and 1 month after one cycle of ablation combined with corticosteroid and 5-FU therapy. RESULTS: Higher energy consumption and longer duration of electrocoagulation resulted in a larger ablation zone and higher surface temperature. Ablation combined with pharmacotherapy significantly reduced keloid volume in nude mice, upregulated MMP-1 and MMP-3, downregulated COL I and COL III, and inhibited angiogenesis and proliferation. This combination also significantly reduced the VSS and POSAS scores in patients with keloids after treatment without any obvious adverse events. CONCLUSION: Our findings show that electroablation combined with pharmacotherapy effectively reduces keloid volume by inhibiting collagen deposition, angiogenesis, and cell proliferation. Thus, this novel combination may serve as a safe therapeutic approach for keloid removal.

5-aminolevulinic acid photodynamic therapy protects against UVB-induced skin photoaging: A DNA-repairing mechanism involving the BER signalling pathway.

Low-dose 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been used to cope with skin photoaging, and is thought to involve DNA damage repair responses. However, it is still unknown how low-dose ALA-PDT regulates DNA damage repair to curb skin photoaging. We established a photoaging model using human dermal fibroblasts (HDFs) and rat skin. RNA-sequencing (RNA-seq) analysis was conducted to identify differentially expressed genes (DEGs) in HDFs before and after low-dose ALA-PDT treatment, followed by bioinformatics analysis. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to assess skin aging-related manifestations and Western blotting to evaluate the expression of associated proteins. A comet assay was used to detect cellular DNA damage, while immunofluorescence to examine the expression of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in cells and skin tissues. In both in vivo and in vitro models, low-dose ALA-PDT alleviated the manifestations of ultraviolet B (UVB)-induced skin photoaging. Low-dose ALA-PDT significantly reduced DNA damage in photoaged HDFs. Furthermore, low-dose ALA-PDT accelerated the clearance of the photoproduct 8-oxo-dG in photoaged HDFs and superficial dermis of photoaged rat skin. RNA-seq analysis suggested that low-dose ALA-PDT upregulated the expression of key genes in the base excision repair (BER) pathway. Further functional validation showed that inhibition on BER expression by using UPF1069 significantly suppressed SA-ß-gal activity, G2/M phase ratio, expression of aging-associated proteins P16, P21, P53, and MUTYH proteins, as well as clearance of the photoproduct 8-oxo-dG in photoaged HDFs. Low-dose ALA-PDT exerts anti-photoaging effects by activating the BER signalling pathway.

Women patients with small-cell lung cancer using immunotherapy in a real-world cohort achieved long-term survival.

BACKGROUND: Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive-stage small-cell lung cancer (ES-SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES-SCLC. METHODS: We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES-SCLC patients who received first-line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second-line therapies. Kaplan-Meier methodology was used to calculate survival analysis. Chi-squared tests were used to analyze the incidence of adverse events (AEs). RESULTS: Median progression-free survival (PFS) and median OS favored the ICI-contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second-line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first-line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). CONCLUSIONS: Our study suggested that female ES-SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

A nomogram to predict anal condyloma acuminatum recurrence in HIV-negative patients following photodynamic therapy: A decade-long retrospective clinical study at a single tertiary hospital.

BACKGROUND: Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT. METHODS: A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO2 laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling. RESULTS: Among the 176 patients included, 33 (18.75 %) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO2 laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95 % CI: 0.818-0.935) and a significant net benefit in decision curve analysis. CONCLUSIONS: The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.

Novel metalloporphyrin covalently functionalized polyphosphazene nanotubes for boosting the hydrogen evolution reaction.

Herein, we demonstrate the first example of a novel electrocatalytic hybrid system (CoTPP-PZSNT) with a push-pull motif to boost hydrogen evolution reaction (HER) activity. CoTPP-PZSNT exhibits an efficient HER activity, with overpotentials of 157 and 109 mV at 10 mA cm-2 in 1.0 M KOH and 0.5 M H2SO4 solutions, respectively. The HER performance of CoTPP-PZSNT outperforms many previously reported HER catalysts, due to efficient charge transfer between each component.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0.5 mmol/L, 3 J/cm2). Through RNA-sequencing analysis, we identified that low-dose ALA-PDT modulated autophagy-related pathways in keratinocytes and pinpointed Unc-51-like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low-dose ALA-PDT treatment upregulated the expression of autophagy-related proteins Beclin-1 and LC3-II/LC3-I ratio. Notably, low-dose ALA-PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential, and decreasing adenosine triphosphate production; all these processes functioned on the AMP-activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low-dose ALA-PDT mitigated UVB-induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3-methyladenine. Overall, these findings highlight how low-dose ALA-PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy.

Sleep quality correlates with effectiveness of ultrapulse fractional CO2 laser in the treatment of facial atrophic acne scars.

Ultrapulse fractional CO2 laser is effective for acne atrophic scars. Whether this effectiveness is affected by sleep quality remains unclear. Aiming to investigate the relationship between sleep quality and postoperative effectiveness, a retrospective clinical study was conducted, enrolling 83 patients with atrophic acne scar. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire at 3 months after the end of the first treatment. The ECCA (échelle d'évaluation clinique des cicatrices d'acné) scale was used to evaluate the clinical effectiveness before and at 3 months after treatment. The patients were divided into a mild to moderate improvement group and a good to excellent improvement group, based on whether they achieved a 50% ECCA improvement rate. PSQI score was higher in the mild and moderate improvement group than in the good to excellent improvement group (7.6 ± 4.5 vs 3.8 ± 1.7, p < 0.001). Multivariate logistic regression showed that both PSQI score (odds ratio = 0.6 [95% CI = 0.5-0.8], p < 0.001) and scar type were correlated with postfractional CO2 laser effectiveness. Pearson correlation analysis suggested that PSQI score was negatively correlated with ECCA decline score (r = -0.6139, p < 0.0001). Receiver operating characteristic curve analysis showed that PSQI score (area under the curve = 0.759) and scar type (area under the curve = 0.737) were all closely correlated with postoperative effectiveness, without statistical difference between their accuracies (p = 0.647). Decision curve analysis demonstrated that both PSQI score and scar type correlated with postoperative effectiveness. Our results demonstrated that sleep quality correlates with the postoperative effectiveness of ultrapulse fractional CO2 laser in the treatment of atrophic acne scars.

Characterization and quantification of microplastics in indoor environments.

Microplastics (MPs) have gradually attracted attention; however, people have paid limited attention to the existence of airborne microplastics, especially in indoor environments. In this study, we tracked microplastic deposition in offices, laboratories, dining halls, and dormitories. Results showed that the average microplastic abundance in the dormitory was the highest (14088.05 pcs/m3), followed by in the office (13097.13 pcs/m3), laboratory (7512.55 pcs/m3) and dining hall (4308.26 pcs/m3). The microplastics deposited at indoor environment were mostly dark, elongated and solid. The average particle size of the microplastics sampled at the four sampling points was 66.15 µm, but the size of the microplastics in the laboratory environment was smaller and more harmful. Airflow tests using air conditioners showed that turbulence increases the resuspension of microplastics. Our results also show that the frequency of human activities is one of the main factors leading to changes in the content of microplastics in indoor air, and turbulence caused by airflow will lead to the migration of microplastics in the indoor environment. In conclusion, indoor environments are prone to high microplastic concentration, which may pose certain potential risks to human health.

Experimental Study on Humidification Coagulation and Removal of Fine Particles Using an Electrostatic Precipitator.

A wet electrostatic precipitator (WESP) has much higher capture rate for fine particulate matter, PM2.5, than a traditional dry type electrostatic precipitator does. In order to make full use of existing dust removal equipment and reduce the emissions of smoke and dust to zero, a combination of chemical coagulation and humidification coagulation is proposed using a WESP. The results show that the addition of chemical coagulant can promote the coagulation of coal-fired dust particles. After the addition of pectin (PG), the median diameter of dust particles increases from 28.19 µm to 45.28 µm. Water vapor humidification can promote the coagulation of dust particles. When the water vapor injection rate increases from 0 kg/h to 3.2 kg/h, the median diameter of dust particles increases from 28.19 µm to 36.45 µm. The synergistic effect of the coagulant and water vapor can enhance the chemical coagulation effect; when 1.0 × 10-2 g/L PG and 3.2 kg/h water vapor synergize, the collection efficiency reaches 98.17%, and when 1.0 × 10-2 g/L polyacrylamide (PAM) and 3.2 kg/h water vapor synergize, the collection efficiency reaches 96.68%. Both chemical coagulation and water vapor humidification can promote the condensation of coal dust, which is beneficial to improve the efficient capture of fine particles using WESP.

Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.

BACKGROUND: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can't meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. METHODS: Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. RESULTS: A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. CONCLUSIONS: MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.

Peripheral blood CD4+ T cell count predicts recurrence of condyloma acuminatum after photodynamic therapy in HIV-positive patients.

BACKGROUND: Few studies have reported postoperative relapse of condyloma acuminatum (CA) after 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in human immunodeficiency virus (HIV) positive patients. METHODS: The clinical data of HIV-positive CA patients treated with ALA-PDT from October 2018 to December 2019 were analyzed retrospectively. Univariate and multivariate Cox regression was used to analyze the variables related to postoperative recurrence. Pearson correlation test was employed to analyze the correlation between CD4+ T cell count and postoperative recurrence rate. Kaplan-Meier method was used to compare the CA recurrence after ALA-PDT in low CD4 group and high CD4 group. RESULTS: A total of 38 HIV-positive patients with CA were included in the study. Among them, 26 patients experienced CA recurrence within 6 months, and the recurrence rate was 68.4%. CD4+ T cell count was 187.0 (79.0-596.0) cells/µl in relapsed patients and 406.0 (89.0-612.0) cells/µl in non-relapsed patients, showing a statistically significant difference (p = .005). Pearson correlation coefficient analysis revealed a negative correlation between CD4+ T cell count and postoperative recurrence rate (p = .005, r = -.443). Univariate regression analysis showed that CD4+ T cell count was correlated with postoperative recurrence, hazard ratio (HR) was 0.99 [95% Confidence interval (CI) = 0.99-1.0, p = .012]. Multivariate Cox regression analysis showed that with the low CD4+ T cell count as the reference, the high CD4+ T cell count was negatively correlated with postoperative recurrence (HR = 0.09, 95% CI 0.01-0.87, p = .038). CONCLUSIONS: Peripheral blood CD4+ T cell count can predict the CA recurrence rate after ALA-PDT in HIV-positive patients.

[Analysis of the Effcacy and Safety of Amivantamab in Non-small Cell Lung Cancer 
Patients with EGFR/MET Gene Abnormalities: A Single Center's Experience].

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS: Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.

The prevalence and real-world therapeutic analysis of Chinese patients with KRAS-Mutant Non-Small Cell lung cancer.

OBJECTIVE: Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important driver gene of non-small cell lung cancer (NSCLC). Despite a rapid progress achieved in the targeted therapy, chemotherapy remains the standard treatment option for patients with KRAS-mutant NSCLC. This study aimed to assess real-world data of Chinese patients with KRAS-mutant NSCLC undergoing chemotherapy and/or immunotherapy. METHODS: KRAS mutational status was analyzed using next-generation sequencing of 150,327 NSCLC patients from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) project (Cohort I). Treatment data were collected and analyzed retrospectively from 4348 NSCLC patients who were admitted to the Peking University Cancer Hospital and Institute between January 2009 and October 2020 (Cohort II). RESULTS: In Cohort I, 18,224 patients were detected with KRAS mutations (12.1%) of whom G12C (29.6%) was the most frequent subtype, followed by G12D (18.1%) and G12V (17.5%). In case of concomitant mutations, TP53 had the highest incidence of 33.6%, followed by EGFR (11.6%), STK11 (10.4%), KEAP1(6.2%), and CDKN2A (6.0%). Cohort II included 497 patients (11.4%) with KRAS mutations. In the first-line chemotherapeutic analysis of Cohort II, patients benefited more from the pemetrexed/platinum (PP) regimen than the gemcitabine/platinum (GP) or taxanes/platinum (TP) regimen (median progression-free survival [PFS], 6.4 vs. 4.9 vs. 5.6 months, hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.48-0.88, p = 0.033 and HR = 0.69, 95% CI 0.47-1.00, p = 0.05, respectively), with no significant difference when combined with bevacizumab. Regarding patients who received immune checkpoint inhibitors (ICIs), the objective response rate was 26% for a median PFS of 9.6 months (95% CI 6.16-13.03). Patients who received ICIs combined with chemotherapy had a significantly longer survival than monotherapy (median PFS, 13.9 vs. 5.2 months, HR = 0.59, 95% CI 0.35-0.99, p = 0.049). CONCLUSION: KRAS is an important driver gene in NSCLC, compromising 12.1% in this study, and G12C was noted as the most common subtype. Patients with KRAS-mutant NSCLC could benefit from pemetrexed-based chemotherapy and ICIs.

Evaluation of different treatment strategies between right-sided and left-sided pneumonectomy for stage I-IIIA non-small cell lung cancer patients.

BACKGROUND: This study aimed to assess the different survival outcomes of stage I-IIIA non-small cell lung cancer (NSCLC) patients who received right-sided and left-sided pneumonectomy, and to further develop the most appropriate treatment strategies. METHODS: We accessed data from the Surveillance, Epidemiology, and End Results database from the United States for the present study. An innovative propensity score matching analysis was used to minimize the variance between groups. RESULTS: For 2,683 patients who received pneumonectomy, cancer-specific survival [hazard ratio (HR) =0.863, 95% confidence interval (CI): 0.771 to 0.965, P=0.010] and overall survival (OS; HR =0.875, 95% CI: 0.793 to 0.967, P=0.008) were significantly superior in left-sided pneumonectomy patients compared with right-sided pneumonectomy patients. Cancer-specific survival (HR =0.847, 95% CI: 0.745 to 0.963, P=0.011) and OS (HR =0.858, 95% CI: 0.768 to 0.959, P=0.007) were also significantly longer with left-sided compared to right-sided pneumonectomy after matching analysis of 2,050 patients. Adjuvant therapy could significantly prolong cancer-specific survival (67 versus 51 months, HR =1.314, 95% CI: 1.093 to 1.579, P=0.004) and OS (46 versus 30 months, HR =1.458, 95% CI: 1.239 to 1.715, P<0.001) among left-sided pneumonectomy patients after the matching procedure, while adjuvant therapy did not increase cancer-specific survival for right-sided pneumonectomy patients (46 versus 42 months, HR =1.112, 95% CI: 0.933 to 1.325, P=0.236). Subgroup analysis showed that adjuvant chemotherapy could significantly improve cancer-specific survival and OS for all pneumonectomy patients. However, radiotherapy was associated with worse survival for patients with right-sided pneumonectomy. CONCLUSIONS: Pneumonectomy side can be deemed as an important factor when physicians determine the most optimal treatment strategies.

Efficacy and safety of pemetrexed maintenance chemotherapy for advanced non-small cell lung cancer in a real-world setting.

BACKGROUND: Pemetrexed maintenance therapy offers a survival benefit in patients with nonprogressive advanced nonsquamous non-small cell lung cancer (NSCLC) with good tolerability. This study was designed to analyze the efficacy and safety of pemetrexed maintenance chemotherapy in advanced nonsquamous NSCLC patients in a real-world setting. METHODS: The response rate (RR) and adverse events in 71 nonsquamous NSCLC patients treated with pemetrexed-based chemotherapy were observed until disease progression or unacceptable toxicities. Measures of survival were analyzed during follow-up. RESULTS: Of 69 efficacy-evaluable patients, the objective response rate (ORR) was 46.4% and the disease control rate (DCR) was 98.6%. ORR showed no significant difference between patients who received pemetrexed as first-line therapy and those who received pemetrexed as second-line or higher treatment. The median treatment cycle for all patients was 8. The median progression-free survival (PFS) was 9.5 months (m) and median overall survival (OS) was 30.5 m. The univariate and multivariate analyses showed that the number of chemotherapy cycles was an independent factor for PFS. The most common adverse reactions were grade 1 to 2 hematologic toxicities, gastrointestinal reactions, and liver enzyme abnormalities. Only 1 patient experienced a grade 3 gastrointestinal event. CONCLUSIONS: Pemetrexed maintenance chemotherapy can improve PFS in patients with advanced nonsquamous NSCLC with good tolerability.

Identification of serum biomarkers to predict pemetrexed/platinum chemotherapy efficacy for advanced lung adenocarcinoma patients by data-independent acquisition (DIA) mass spectrometry analysis with parallel reaction monitoring (PRM) verification.

BACKGROUND: Pemetrexed/platinum chemotherapy has been the standard chemotherapy regimen for lung adenocarcinoma patients, but the efficacy varies considerably. METHODS: To discover new serum biomarkers to predict the efficacy of pemetrexed/platinum chemotherapy, we analyzed 20 serum samples from advanced lung adenocarcinoma patients who received pemetrexed/platinum chemotherapy with the data-independent acquisition (DIA) quantitative mass spectrometry (MS). RESULTS: The 20 patients were categorized as "good response" [12 patients achieving partial response (PR)] and "poor response" [8 patients with progressive disease (PD)] groups. Altogether 23 significantly different expressed proteins were identified, which had relative ratios higher than 1.2 or lower than -0.83, with 7 proteins having an area under the curve (AUC) above 0.8. To further validate the DIA results, we used the parallel reaction monitoring (PRM) method to examine 16 candidate serum biomarkers in the study cohort of 20 patients and another cohort of 22 advanced lung adenocarcinoma patients (16 PR and 6 PD). Quantitative validation using PRM correlated well with the DIA results, and 10 promising proteins exhibited a similar up- or downregulation. It is worth noting that glutathione peroxidase 3 (GPX3) exhibits significant upregulation in the poor response group compared with the good response group, which was validated by both DIA and PRM methods. CONCLUSIONS: Our study confirmed that combined DIA MS and PRM approaches were effective in identifying serum predictive biomarkers for advanced lung adenocarcinoma patients. Further studies are needed to explore the potential biological mechanism underlying these biomarkers.

Mutation in cyp51b and overexpression of cyp51a and cyp51b confer multiple resistant to DMIs fungicide prochloraz in Fusarium fujikuroi.

BACKGROUND: Fusarium fujikuroi is a plant pathogen that causes rice bakanae disease. Prochloraz is an imidazole-class sterol, 14α-demethylase inhibitor (DMI), which has been in use for several years as a foliar spray to control Fusarium spp. on agriculturally important monocot crops. F. fujikuroi is highly resistant to prochloraz treatment, and the aim of this study was to clarify the mechanism by which F. fujikuroi renders itself resistant to prochloraz. RESULTS: Recently, prochloraz-resistant strains were identified over a vast geographical area in the agricultural regions of Zhejiang Province, China. It was found that 21.13% and 3.96% of the strains examined were highly resistant (HR) to prochloraz during 2017 to 2018. The HR strains contained a point mutation (S312T) in the FfCYP51B protein, while the strains identified with prochloraz susceptibility had no such point mutation in FfCYP51A/B/C. To confirm whether the mutations in FfCYP51B confer resistance to prochloraz, we exchanged the CYP51B locus between the sensitive strain and the resistant strain by homologous double exchange. The transformed mutants with a copy of the resistant fragment exhibited resistance to prochloraz, and the transformed mutants with a copy of the sensitive fragment exhibited sensitivity to prochloraz. Furthermore, qRT-PCR analysis of Ffcyp51a/b/c gene expression revealed that Ffcyp51a and Ffcyp51b were significantly up-regulated in the prochloraz-resistant strains relative to the sensitive strains in F. fujikuroi. Contrary to our expectation, docking of prochloraz into the modeled binding pocket of FfCYP51B indicated that the affinity between prochloraz and the FfCYP51B increased after the amino acid at codon 312 changed to Thr. CONCLUSION: The point mutation S312T in FfCYP51B and overexpression of Ffcyp51a and Ffcyp51b together lead to the prochloraz-resistant phenotype in F. fujikuroi.

Time Difference of Arrival on Contrast-Enhanced Ultrasound in Distinguishing Benign Inflammation From Malignant Peripheral Pulmonary Lesions.

INTRODUCTION: Worldwide, the incidence and mortality of lung cancer are at the highest levels, and the most lesions are located in the lung periphery. Despite extensive screening and diagnosis, the pathologic types of peripheral pulmonary lesions (PPLs) are difficult to diagnose by noninvasive examination. This study aimed to identify a novel index-time difference of arrival (TDOA)-to discriminate between benign inflammation and malignant PPLs. METHODS: Using contrast-enhanced ultrasound (CEUS), we retrospectively analyzed 96 patients with PPLs who had undergone biopsy to confirm the pathologic types. All data were collected from Dazhou Central Hospital between December 2012 and July 2019. The parameters of CEUS were analyzed by two assistant chief physicians of ultrasound diagnosis. Area under the receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the diagnostic ability of different indices. RESULTS: We found that the TDOA significantly distinguished benign inflammation from malignant lesions. The TDOA was markedly increased in patients with malignant lesions than benign inflammation lesions (P < 0.001). Compared with conventional time-intensity curve (TIC) indices, TDOA showed high diagnostic accuracy (area under the curve = 0.894). Moreover, conventional diagnostic indices did not affect the diagnostic performance of TDOA by adjusting the receiver operating characteristic curve. CONCLUSION: TDOA is feasible for the diagnosis of benign inflammation and malignant PPLs.

Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients.

BACKGROUND: Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. METHODS: This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. RESULTS: Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P < 0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs. 25.0%, P = 0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab. CONCLUSIONS: Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.