Automated Design of Collaboration-Based Hybrid Metaheuristics.

Hybridization plays a prominent role in bolstering the performance of optimization algorithms (OAs), yet designing efficient hybrid OAs tailored to intricate optimization problems persists as a formidable task. This article introduces a novel top-down methodology for the automated design of hybrid OAs, treating algorithm design as a meta-optimization problem. A general design template for collaboration-based hybrid OAs is developed, integrating a multitude of hybridization strategies for the first time. Besides, a mathematical model is built to formulate the meta-optimization problem of algorithm design. To address the meta-optimization challenge, an improved multifactorial evolutionary algorithm is proposed to automatically design efficient hybrid metaheuristics in a multitasking environment for the given instances with diverse features. To verify the effectiveness of the proposed design methodology, it is applied to the CEC2017 benchmark functions and the binary knapsack problem. Numerical results have demonstrated the feasibility and effectiveness of the proposed methodology for both continuous and combinatorial optimization benchmarks.

Multifaceted complications and surgical management of bronchobiliary fistula with associated pneumonia and intrahepatic stones: A case report.

Background: Bronchobiliary fistulas (BBFs), primarily stemming from choledocholithiasis, present considerable diagnostic and treatment challenges. Their prolonged nature can lead to life-threatening situations without timely management, often complicated by lung abscesses. Case presentation: A 64-year-old man, presenting with fever, chills, and a cough initially misdiagnosed as a common cold, developed severe respiratory distress and delirium upon admission. Urgent intensive care unit (ICU) admission was prompted by a computed tomography (CT) scan revealing a right lung abscess. Enhanced CT scans and elevated bilirubin levels confirmed the biliary origin of the BBFs. Comprehensive treatment included laparoscopic partial hepatectomy, choledochojejunostomy, stone extraction, choledochoscopy, T-tube drainage, and BBFs closure. The patient was discharged with a T-tube. Follow-up CT after two months showed no recurrence. Conclusions: Managing BBFs, especially with concurrent lung abscesses in choledocholithiasis patients, remains challenging but feasible. Early diagnosis and intervention are crucial to improving survival rates and quality of life, highlighting the need for vigilance. This case underscores the importance of early detection and comprehensive treatment for successful outcomes in such complex conditions.

Neoadjuvant chemotherapy followed by surgery versus concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma: a retrospective cohort study.

PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.

HAX-1 interferes in assembly of NLRP3-ASC to block microglial pyroptosis in cerebral I/R injury.

Acute cerebral ischemia has a high rate of disability and death. Although timely recanalization therapy may rescue the ischemic brain tissue, cerebral ischemia-reperfusion injury has been shown to limit the therapeutic effects of vascular recanalization. Protein HAX-1 has been reported as a pro-survival protein that plays an important role in various disorders, particularly in association with the nervous system. However, the effects and mechanisms of HAX-1 in cerebral IR injury have yet to be elucidated. So, we aimed to investigate the effect of HAX-1 on microglial pyroptosis and explore its potential neuroprotective effects in ischemia-reperfusion injury. Our results show that the expression of HAX-1 decreased after cerebral IR injury, accompanied by an increase in pyroptosis pathway activation. In addition, HAX-1 could inhibit microglial pyroptosis both in vivo and in vitro and reduce the release of inflammatory mediators. The above neuroprotective effects might be partially mediated by inhibiting of interaction of NLRP3 and ASC through competitive binding, followed by the attenuation of NLRP3 inflammasome formation. In conclusion, Our findings support that HAX-1 exhibits a protective role in cerebral I/R injury, and further study on HAX-1 expression regulation will contribute to cerebral infarction therapy.

Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study.

OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.

Related factors associated with the prognosis of children undergoing liver transplantation under the enhanced recovery after surgery nursing concept.

This study aimed to investigate factors associated with the clinical outcomes of patients who underwent pediatric liver transplantation (LT) and received enhanced recovery after surgery (ERAS) nursing. A cohort of 104 pediatric patients was studied at our hospital. Data on 8 indicators and 2 clinical outcomes, including length of hospital stay (LOS) and 30-day readmission rates, were collected. Linear and logistic regression analyses were employed to examine the associations of the 8 indicators with hospital-LOS and readmission risks, respectively. The predictive value of these indicators for the outcomes was determined using the receiver operating characteristic (ROC) curve, decision curve analysis, and importance ranking through the XGBoost method. A comprehensive model was developed to evaluate its predictive accuracy. Regression analyses identified donor age, donor gender, and intensive care unit (ICU)-LOS of recipients as significant predictors of hospital LOS (all P < .05), whereas no indicators were significantly associated with readmission risk. Further, ROC analysis revealed that 3 indicators provided superior prediction for 28-day hospital LOS compared to the median LOS of 18 days. ICU-LOS demonstrated the highest clinical net benefit for predicting 28-day hospital-LOS. Multivariable regression analysis confirmed the independent predictive value of donor age and ICU-LOS for the hospital-LOS (all ß > 0, all P < .05). Although the comprehensive model incorporating donor age and ICU-LOS showed stable predictive capability for hospital-LOS, its performance did not significantly exceed that of the individual indicators. In pediatric LT, hospital LOS warrants greater emphasis over readmission rates. Donor age and ICU-LOS emerged as independent risk factors associated with prolonged hospital LOS.

Treatment patterns and survival in T4b esophageal cancer: a retrospective cohort study.

PURPOSE: This study aims to evaluate the efficacy of various treatment approaches in stage T4b esophageal cancer patients. MATERIALS AND METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results databases, covering patients diagnosed with esophageal cancer between 2000 and 2020. Kaplan-Meier analysis was used to assess cancer-specific survival (CSS) and overall survival (OS) across different treatment patterns. RESULTS: The study included 482 patients: 222 (46.1%) received chemoradiotherapy, 58 (12.0%) underwent radiotherapy alone, 37 (7.7%) received chemotherapy alone, 50 (10.4%) underwent surgery, and 115 (23.8%) received no treatment. Median CSS were 12, 4, 6, 18, and 1 month for chemoradiotherapy, radiotherapy alone, chemotherapy alone, surgery, and non-treatment groups. Median OS for these groups were 11, 3, 6, 17, and 1 month, respectively. Multivariable proportional hazard regression analysis revealed that patients who underwent surgery experienced significantly improved CSS (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.24-0.72; P = 0.002) and OS (HR = 0.45, 95% CI: 0.28-0.74; P = 0.002) compared to those receiving chemoradiotherapy after propensity score matching. CONCLUSIONS: Esophagectomy, with or without radiotherapy and/or chemotherapy, results in better survival outcomes than chemoradiotherapy in patients with stage T4b esophageal cancer.

Immune checkpoint inhibitors combined with concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

Purpose: This study aims to evaluate the efficacy of immune checkpoint inhibitors (ICIs) combined with concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. Materials and methods: This retrospective cohort study included patients diagnosed with locally advanced esophageal squamous cell carcinoma who received either CCRT alone or CCRT combined with ICIs from April 2019 to February 2023. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS). Results: A total of 101 patients were enrolled, with 58 undergoing CCRT alone and 43 receiving CCRT+ICI. The CCRT+ICI group demonstrated a higher complete response rate compared to the CCRT alone group (11.6% vs. 1.7%, P = 0.037). However, no significant difference was observed in 1-year PFS (58.9% vs. 55.2%; hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 0.70-2.26; P = 0.445) or 1-year OS (70.8% vs. 75.9%; HR = 1.21, 95% CI: 0.58-2.53; P = 0.613) between CCRT+ICI and CCRT alone groups. The CCRT alone group experienced a higher incidence of leukopenia of any grade (93.1% vs. 76.7%, P = 0.039) but a lower incidence of pneumonitis of any grade (36.2% vs. 65.1%, P = 0.008). Conclusion: CCRT+ICI may not lead to improved survival outcomes compared to CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. These findings indicate the need for further investigation into this treatment approach.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

Role of Postoperative Radiotherapy on High-Risk Stage pIIIA-N2 Non-Small Cell Lung Cancer Patients After Complete Resection and Adjuvant Chemotherapy: A Retrospective Cohort Study.

Background: The aim of the study was to assess the effectiveness of postoperative radiotherapy in high-risk patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy. Methods: Data from NSCLC patients within the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. The study examined the association between lymph node ratio (LNR) and both cancer-specific survival (CSS) and overall survival (OS) using restricted cubic spline curves. Patients were categorized into high- and low-risk groups based on established LNR cut-off values, and survival outcomes were compared between those receiving postoperative radiotherapy and those who did not within the high-risk group. Results: The study included 1,690 patients. An LNR threshold of 0.29 was identified for both CSS and OS. Patients with an LNR ≥ 0.29 demonstrated significantly worse CSS (hazard ratio (HR) = 1.56, 95% confidence interval (CI): 1.37 - 1.78; P < 0.001) and OS (HR = 1.44, 95% CI: 1.28 - 1.62; P < 0.001) compared to those with an LNR < 0.29. In the high-risk group (LNR ≥ 0.29), postoperative radiotherapy did not significantly affect CSS (HR = 0.98, 95% CI: 0.82 - 1.17; P = 0.809) or OS (HR = 0.95, 95% CI: 0.81 - 1.11; P = 0.533). Conclusions: LNR is a significant prognostic factor in patients with stage pIIIA-N2 NSCLC post complete resection and adjuvant chemotherapy. A higher LNR (≥ 0.29) is associated with poorer CSS and OS. However, postoperative radiotherapy does not confer survival benefits in these high-risk patients. Our findings suggest that postoperative radiotherapy should not be routinely performed in this subgroup. Further research is required to explore effective treatment strategies for these patients.

Adjuvant treatment patterns for pT3N0M0 esophageal cancer undergoing surgery.

To assess adjuvant treatment patterns on survival in patients with pT3N0M0 esophageal cancer who underwent esophagectomy without neoadjuvant chemoradiotherapy. Stage pT3N0M0 esophageal cancer patients were assessed between 2000 and 2020 from the Surveillance, Epidemiology, and End Results databases. Kaplan-Meier analysis was used to compare overall survival (OS) among various treatment patterns. We identified 445 patients: 252 (56.6%) received surgery alone, 85 (19.1%) received surgery+chemoradiotherapy, 80 (18.0%) underwent surgery+chemotherapy, and 28 (6.3%) received surgery+ radiotherapy. For squamous cell carcinoma, surgery+chemoradiotherapy ([hazard ratio] HR = 1.04, 95% confidence interval (CI): 0.65-1.66; P = 0.873), surgery+chemotherapy (HR = 0.72, 95% CI: 0.42-1.22; P = 0.221), and surgery+radiotherapy (HR = 1.33, 95% CI: 0.74-2.39; P = 0.341) had similar OS compared to surgery alone. For adenocarcinoma, surgery+chemoradiotherapy (HR = 0.51, 95% CI: 0.36-0.74; P < 0.001) and surgery+chemotherapy (HR = 0.61, 95% CI: 0.42-0.87; P = 0.006) had better OS compared to surgery alone. However, surgery+radiotherapy had a comparable OS (HR = 0.81, 95% CI: 0.44-1.49; P = 0.495).Adjuvant treatments did not improve survival in stage pT3N0M0 esophageal squamous cell carcinoma patients. In contrast, adjuvant chemoradiotherapy and chemotherapy were recommended for esophageal adenocarcinoma patients.

Bioactive 5/5/5/6 Four-Ring System Iridoids from Plumeria alba L.

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

Efficacy of treatment patterns based on concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma.

PURPOSE: To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods. RESULTS: A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41-2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45-12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14-25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29-2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55-42.26; P = 0.157) compared to CCRT. CONCLUSION: AC did not improve survival in patients with stage IIB CSCC receiving CCRT.

Lymph Node Ratio Enhances Predictive Value for Treatment Outcomes in Patients with Non-Small Cell Lung Cancer Undergoing Surgery: A Retrospective Cohort Study.

Purpose: To compare the prognostic value of lymph node ratio (LNR) and pN in patients with non-small cell lung cancer (NSCLC) undergoing surgery. Materials and methods: NSCLC patients were investigated between 2004 and 2015 from the Surveillance, Epidemiology, and End Results databases. The X-tile software was used to determine LNR cut-off values. Kaplan-Meier analysis was employed to assess cancer-specific survival (CSS) and overall survival (OS). Results: The identified cut-off values of LNR were 0.19 and 0.73. Median CSS for LNR1 (LNR < 0.19), LNR2 (0.19 ≤ LNR ≤ 0.73), and LNR3 (LNR > 0.73) were 71, 41, and 17 months. Both LNR2 (HR = 1.46, 95% CI: 1.36-1.57; P < 0.001) and LNR3 (HR = 2.85, 95% CI: 2.58-3.15; P < 0.001) demonstrated poorer median CSS compared to LNR1. Similarly, median OS for LNR1, LNR2, and LNR3 were 50, 35, and 16 months. LNR2 (HR = 1.36, 95% CI: 1.27-1.45; P < 0.001) and LNR3 (HR = 2.60, 95% CI: 2.37-2.85; P < 0.001) exhibited worse median OS compared to LNR1. A revised pN (r-pN) classification incorporating LNR and pN demonstrated superior penalized goodness-of-fit and discriminative ability in predicting CSS and OS compared to both LNR and pN. Conclusion: LNR outperformed pN in predicting CSS and OS in NSCLC patients undergoing surgery, potentially leading to more precise adjuvant treatment decisions.

Treatment Patterns and Survival Outcomes in Patients With Stage T1-2N0M0 Small Cell Lung Cancer Undergoing Surgery: A Retrospective Cohort Study.

Background: The aim of the study was to delineate the treatment modalities and survival outcomes in patients with stage T1-2N0M0 small cell lung cancer (SCLC) who underwent surgery. Methods: SCLC patients from the Surveillance, Epidemiology, and End Results databases between 2000 and 2020 were investigated. Kaplan-Meier survival analysis was employed to assess cancer-specific survival (CSS) and overall survival (OS) across diverse therapeutic strategies. Results: The study included 190 patients. Treatment modalities included surgery alone in 65 patients (34.2%), surgery + chemotherapy in 70 patients (36.8%), surgery + radiotherapy in three patients (1.6%), and surgery + chemoradiotherapy in 52 patients (27.4%). The median CSS remained undetermined for the surgery alone group, whereas it was 123 and 113 months for the surgery + chemotherapy and surgery + chemoradiotherapy groups. Median OS was 47, 84, and 50 months for these groups. Multivariate Cox regression analysis revealed that patients receiving surgery + chemotherapy exhibited a significantly enhanced OS (hazard ratio (HR) = 0.60, 95% confidence interval (CI): 0.38 - 0.94; P = 0.028) compared to those undergoing surgery alone. However, the integration of radiotherapy did not improve OS compared to surgery alone (HR = 0.72, 95% CI: 0.44 - 1.15; P = 0.170). Conclusion: Adjuvant chemotherapy improved OS compared to surgery alone. However, the addition of radiotherapy did not prolong OS.

Multifunctional In-MOF and Its S-Scheme Heterojunction toward Pollutant Decontamination via Fluorescence Detection, Physical Adsorption, and Photocatalytic REDOX.

A novel doubly interpenetrated indium-organic framework of 1 has been assembled by In3+ ions and highly conjugated biquinoline carboxylate-based bitopic connectors (H2L). The isolated 1 exhibits an anionic framework possessing channel-type apertures repleted with exposed quinoline N atoms and carboxyl O atoms. Owing to the unique architecture, 1 displays a durable photoluminescence effect and fluorescence quenching sensing toward CrO42-, Cr2O72-, and Cu2+ ions with reliable selectivity and anti-interference properties, fairly high detection sensitivity, and rather low detection limits. Ligand-to-ligand charge transition (LLCT) was identified as the essential cause of luminescence by modeling the ground state and excited states of 1 using DFT and TD-DFT. In addition, the negatively charged framework has the ability to rapidly capture single cationic MB, BR14, or BY24 and their mixture, including the talent to trap MB from the (MB + MO) system with high selectivity. Moreover, intrinsic light absorption capacity and band structure feature endow 1 with effective photocatalytic decomposition ability toward reactive dyes RR2 and RB13 under ultraviolet light. Notably, after further polishing the band structure state of 1 by constructing the S-scheme heterojunction of In2S3/1, highly efficient photocatalytic detoxification of Cr(VI) and degradation of reactive dyes have been fully achieved under visible light. This finding may open a new avenue for designing novel multifunctional MOF-based platforms to address some intractable environmental issues, i.e., detection of heavy metal ions, physical capture of pony-sized dyes, and photochemical decontamination of ultrastubborn reactive dyes and highly toxic Cr(VI) ions from water.

Treatment patterns and survival analysis in patients with unresectable stage III EGFR-mutated non-small cell lung cancer.

PURPOSE: To investigate the treatment patterns and survival outcomes in patients with unresectable Stage III EGFR-mutated non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective analysis was conducted on patients with unresectable Stage III EGFR-mutated NSCLC spanning from 2012 to 2022. Treatment patterns were outlined, and survival comparisons between different treatment groups were performed using Kaplan-Meier methods. RESULTS: A total of 88 patients were included: 62.5% received TKI alone, 26.1% received TKI+chemotherapy, 4.5% received radiotherapy, 4.5% participated in clinical trials, and 2.4% received TKI+antiangiogenic drugs. Prior to propensity score matching, TKI+chemotherapy and TKI alone groups demonstrated similar progression-free survival (hazard ratio [HR] = 1.56, 95% confidence interval [CI]: 0.87-2.80; P = 0.134), overall survival (HR = 1.12, 95% CI: 0.59-2.13; P = 0.733), and locoregional-free survival (HR = 1.46; 95% CI: 0.75-2.81; P = 0.267). However, TKI+chemotherapy showed reduced distant metastasis-free survival compared to TKI alone (HR = 2.39, 95% CI: 1.11-5.18; P = 0.022). After propensity score matching, no significant differences were observed in progression-free survival (P = 0.435), overall survival (P = 0.205), locoregional-free survival (P = 0.706), and distant metastasis-free survival (P = 0.171) between the TKI+chemotherapy and TKI alone groups. CONCLUSIONS: The addition of chemotherapy to TKI did not enhance survival outcomes compared to TKI monotherapy in patients with unresectable Stage III EGFR-mutated NSCLC.

Novel compound heterozygous mutations of the FBP1 gene in a patient with hypoglycemia and lactic acidosis: A case report.

BACKGROUND: Fructose-1,6-bisphosphatase (FBPase) deficiency, caused by an FBP1 mutation, is an autosomal recessively inherited metabolic disorder characterized by impaired gluconeogenesis. Due to the rarity of FBPase deficiency, the mechanism by which the mutations cause enzyme activity loss still remains unclear. METHODS: We report a pediatric patient with typical FBPase deficiency who presented with hypoglycemia, hyperlactatemia, metabolic acidosis, and hyperuricemia. Whole-exome sequencing was used to search for pathogenic genes, Sanger sequencing was used for verification, and molecular dynamic simulation was used to evaluate how the novel mutation affects FBPase activity and structural stability. RESULTS: Direct and allele-specific sequence analysis of the FBP1 gene (NM_000507) revealed that the proband had a compound heterozygote for the c. 490 (exon 4) G>A (p. G164S) and c. 861 (exon 7) C>A (p. Y287X, 52), which he inherited from his carrier parents. His father and mother had heterozygous G164S and Y287X mutations, respectively, without any symptoms of hypoglycemia. CONCLUSION: Our results broaden the known mutational spectrum and possible clinical phenotype of FBP1.

Simultaneous Growth Strategy of High-Optical-Efficiency GaN NWs on a Wide Range of Substrates by Pulsed Laser Deposition.

Here, we explore a catalyst-free single-step growth strategy that results in high-quality self-assembled single-crystal vertical GaN nanowires (NWs) grown on a wide range of common and novel substrates (including GaN, Ga2O3, and monolayer two-dimensional (2D) transition-metal dichalcogenide (TMD)) within the same chamber and thus under identical conditions by pulsed laser deposition. High-resolution transmission electron microscopy and scanning transmission electron microscopy (HR-STEM) and grazing incidence X-ray diffraction measurements confirm the single-crystalline nature of the obtained NWs, whereas advanced optical and cathodoluminescence measurements provide evidence of their high optical quality. Further analyses reveal that the growth is initiated by an in situ polycrystalline layer formed between the NWs and substrates during growth, while as its thickness increases, the growth mode transforms into single-crystalline NW nucleation. HR-STEM and corresponding energy-dispersive X-ray compositional analyses indicate possible growth mechanisms. All samples exhibit strong band edge UV emission (with a negligible defect band) dominated by radiative recombination with a high optical efficiency (∼65%). As all NWs have similar structural and optical qualities irrespective of the substrate used, this strategy will open new horizons for developing III-nitride-based devices.

Efficacy of First-Line Immunotherapy Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients With Different Brain Metastases Status: A Systematic Review and Meta-Analysis.

Background: This study aims to evaluate the efficacy of first-line immunotherapy combined with chemotherapy in extensive-stage small cell lung cancer (ES-SCLC) patients with differing brain metastasis statuses. Methods: We conducted a comprehensive search in public databases, such as PubMed, EMBASE, and the Cochrane Library, to identify randomized controlled trials involving ES-SCLC patients, with or without brain metastases, who underwent first-line immunotherapy combined with chemotherapy. The primary outcome measure was progression-free survival (PFS), and the secondary outcome measure was overall survival (OS). Results: Our analysis incorporated seven high-quality randomized controlled trials, encompassing 398 patients with brain metastases and 3,533 without. Among patients without brain metastases, the combination of immunotherapy and chemotherapy led to significantly improved PFS (hazard ratio (HR) = 0.72, 95% confidence interval (CI): 0.62 - 0.84, P < 0.001) and OS (HR = 0.77, 95% CI: 0.67 - 0.88, P < 0.001) in comparison to chemotherapy alone. Conversely, for patients with brain metastases, the addition of immunotherapy to chemotherapy did not result in a significant improvement in PFS (HR = 1.03, 95% CI: 0.66 - 1.61, P = 0.887) or OS (HR = 1.03, 95% CI: 0.82 - 1.31, P = 0.776) when compared to chemotherapy alone. Conclusions: In ES-SCLC patients without brain metastases, first-line immunotherapy combined with chemotherapy demonstrated improved PFS and OS in contrast to chemotherapy alone. However, patients with brain metastases did not experience similar benefits.