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Background: This study aimed to compare the efficacy and safety of rezivertinib (BPI-7711) and gefitinib as first-line therapies in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC)., Methods: This multicentre, double-blind, randomised, phase 3 study (REZOR) included eligible patients from 50 hospitals across China. Those who had been histologically or cytologically confirmed as having NSCLC with EGFR exon 19 deletion or exon 21 Leu858Arg mutation by central laboratory were randomly assigned (1:1) to receive once daily either rezivertinib 180 mg or gefitinib 250 mg, until unacceptable toxicity occurred, disease progression, or other treatment discontinuation criteria were met. Each cycle lasted for 21 days. The primary endpoint was progression-free survival evaluated by masked independent central review (MICR) in the intention-to-treat set. This trial is registered with ClinicalTrials.gov, NCT03866499 and follow-up is ongoing., Findings: Between July 15, 2019, and Feb 14, 2022, 695 patients were screened. Among them, 369 eligible patients were randomly assigned to receive either rezivertinib 180 mg/day plus placebo (n=184) or gefitinib 250 mg/day plus placebo (n=185) in a 1:1 ratio; all of eligible participants were included in the intention-to-treat set. Median MICR-assessed progression-free survival was 19·3 months (95% CI 13·8-22·1) in the rezivertinib group and 9·6 months (8·4-11·3) in the gefitinib group (hazard ratio [HR] 0·48, 95% CI 0·36-0·63; p<0·0001) and the prespecified subgroup efficacy analysis showed consistent results. Median duration of exposure was 16·0 months (95% CI 0·0-29·7) in the rezivertinib group and 11·0 months (0·0-28·9) in the gefitinib group. Grade 3 or higher treatment-emergent adverse events (82 [45%] of 184 in the rezivertinib group; 80 [43%] of 185 in the gefitinib group) and treatment-related adverse events (TRAEs; 43 [23%] of 184 in the rezivertinib group; 43 [23%] of 185 in the gefitinib group) were similar in both groups. One patient died from a TRAE in the rezivertinib group, due to pneumonia and interstitial lung disease., Interpretation: Our findings suggested that rezivertinib is a potential choice for patients with EGFR-mutated locally advanced or metastatic NSCLC as first-line therapy, owing to the superior overall efficacy and subgroup progression-free survival compared with gefitinib in targeted patients. No new safety signals were identified., Funding: Beta Pharma (Shanghai) and the China National Science and Technology Major Project for Key New Drug Development., Competing Interests: Declaration of interests DZ and JP are employees of Beta Pharma (Princeton, NJ, USA). HS, FG, TW, and AZ are employees of Beta Pharma (Shanghai, China). All other authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study., Methods: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS)., Results: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed., Conclusions: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases., Trial Registration: ClinicalTrials.gov number, NCT03849768., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

Tobacco is one of the vital economic crops in China. Nevertheless, tobacco diseases cause substantial economic losses each year. Tobacco target spot is a fungal disease which commonly found on the leaves. While both sexual and asexual reproduction can occur, asexual reproduction is much more common in tobacco. In June 2022, target spot was found on tobacco leaf samples from Yibin, Sichuan Province and Meitan, Guizhou Province, China. The typical symptoms were light brown tissue with concentric ring marks, and the necrotic part of the disease spot was fragile and forming perforation after falling off. The diseased tissue in the sample was cut off and sterilized in 75% ethanol for 1 min, and rinsed three times in sterilized distilled water. Finally, the tissues were placed on potato glucose agar (PDA) medium with kanamycin (0.1 mg/mL). After incubation at 28 °C in darkness for 3 days,the culture of the isolate grew in the form of radial mycelium on PDA dishes, the mycelium was white initially, turned brown generally at the later stage, and finally thickened and separated with the growth of the culture. Nine pathogenic strains were isolated, including four isolates from Yibin and five from Meitan. They were all used for pathogen identification. Genomic DNA of each isolate was extracted using the CATB method, and PCR analysis was performed with primers specifically designed to detect individual fusion groups or fusion subgroups of solani: AG-1 IA, IB, and IC; AG-3 PT; AG-4 HG-I, HG-II and HG-III; AGs-5-6 and P-21-22. Among the 11 specific primer pairs, only AG-5-specific primer amplified the fungal DNA, indicating that the nine isolates tested all belonged to the R. solani AG-5 fusion group. BLASTn search was performed on the gene sequences obtained from these strains and they deposited in GenBank under accession no. OP647851-OP647859. These gene sequences were aligned with the voucher specimen R. solani AG-5, with more than 99% similarity . The nine isolates were then tested for mycelial anastomosis reactions using the R. solani AG-5 standard strain following the method described by Ogoshi (1987). A decrease in the diameter of the mycelia at the anastomosis site and death of adjacent cells were observed, indicating their anastomosis response. Therefore, these nine strains were identified as R. solani AG-5 based on morphological and genetic analysis. Subsequently, one pathogenic strain from Meitan and another one from Yibin were selected for pathogenicity verification. Mycelial PDA blocks (6 mm in diameter) of the two isolates were inoculated on healthy tobacco plants, while leaves containing only PDA blocks were used as controls. A total of 6 replicates were conducted. After inoculation, they were incubated at 85% relative humidity and 15 to 25 °C. Koch's hypothesis was confirmed by reisolating pathogens from diseased leaves 5 days after inoculation. Typical symptoms were observed on tobacco plants inoculated with the pathogen strains but not on control tobacco plants. To the best of our knowledge, tobacco target spot has been reported caused by R. solani AG-3, AG-6 and AG-2.1 groups in the field in China and in Argentina. Up until now, this is the first report of R. solani AG-5 causing tobacco target spot on tobacco in the field in China. It was also found to be highly virulent to chickpea in Turkey. Due to serious damages caused by this disease in the last five years in China, more attention should be paid in disease control measures to avoid economic losses. In addition, it also provides some theoretical help for the damage caused by this pathogen on other hosts and helps people to better understand Rhizoctonia solani AG-5.

The interfaces between the absorber and charge transport layers are shown to be critical for the performance of perovskite solar cells (PSCs). PSCs based on the Spiro-OMeTAD hole transport layers generally suffer from the problems of stability and reproducibility. Inorganic hole transport materials CuCrO 2 have good chemical stability and high hole mobility. Herein, we reported the preparation of the delafossite-type CuCrO 2 nanocrystals with a template-etching-calcination method and the incorporation of the as-obtained CuCrO 2 nanocrystals at the perovskite/Spiro-OMeTAD interfaces of planar PSCs to improve the device efficiency and stability. Compared with the traditional hydrothermal method, the template-etching-calcination method used less calcination time to prepare CuCrO 2 nanocrystals. After the CuCrO 2 interface modification, the efficiency of PSCs improved from 18.08% to 20.66%. Additionally, the CuCrO 2 -modified PSCs showed good stability by retaining nearly 90% of the initial PCE after being stored in a drybox for 30 days. The template-etching-calcination strategy will pave a new approach for the synthesis of high-performance inorganic hole-transporting materials.

Background: Response evaluation of neoadjuvant chemotherapy (NACT) in patients with osteosarcoma is significant for the termination of ineffective treatment, the development of postoperative chemotherapy regimens, and the prediction of prognosis. However, histological response and tumour necrosis rate can currently be evaluated only in resected specimens after NACT. A preoperatively accurate, noninvasive, and reproducible method of response assessment to NACT is required. In this study, the value of multi-parametric magnetic resonance imaging (MRI) combined with machine learning for assessment of tumour necrosis after NACT for osteosarcoma was investigated., Methods: Twelve patients with primary osteosarcoma of limbs underwent NACT and received MRI examination before surgery. Postoperative tumour specimens were made corresponding to the transverse image of MRI. One hundred and two tissue samples were obtained and pathologically divided into tumour survival areas (non-cartilaginous and cartilaginous tumour viable areas) and tumour-nonviable areas (non-cartilaginous tumour necrosis areas, post-necrotic tumour collagen areas, and tumour necrotic cystic/haemorrhagic and secondary aneurismal bone cyst areas). The MRI parameters, including standardised apparent diffusion coefficient (ADC) values, signal intensity values of T2-weighted imaging (T2WI) and subtract-enhanced T1-weighted imaging (ST1WI) were used to train machine learning models based on the random forest algorithm. Three classification tasks of distinguishing tumour survival, non-cartilaginous tumour survival, and cartilaginous tumour survival from tumour nonviable were evaluated by five-fold cross-validation., Results: For distinguishing non-cartilaginous tumour survival from tumour nonviable, the classifier constructed with ADC achieved an AUC of 0.93, while the classifier with multi-parametric MRI improved to 0.97 (P = 0.0933). For distinguishing tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.83, while the classifier with multi-parametric MRI improved to 0.90 (P < 0.05). For distinguishing cartilaginous tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.61, while the classifier with multi-parametric MRI parameters improved to 0.81(P < 0.05)., Conclusions: The combination of multi-parametric MRI and machine learning significantly improved the discriminating ability of viable cartilaginous tumour components. Our study suggests that this method may provide an objective and accurate basis for NACT response evaluation in osteosarcoma.

Background: Differentiating glioma recurrence from treatment-related changes can be challenging on conventional imaging. We evaluated the efficacy of quantitative parameters measured by dual-energy spectral computed tomographic (CT) for this differentiation., Methods: Twenty-eight patients were examined by dual-energy spectral CT. The effective and normalized atomic number (Z eff and Z eff-N, respectively); spectral Hounsfield unit curve (λ HU ) slope; and iodine and normalized iodine concentration (IC and IC N , respectively) in the post-treatment enhanced areas were calculated. Pathological results or clinicoradiologic follow-up of ≥2 months were used for final diagnosis. Nonparametric and t-tests were used to compare quantitative parameters between glioma recurrence and treatment-related changes. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and accuracy were calculated using receiver operating characteristic (ROC) curves. Predictive probabilities were used to generate ROC curves to determine the diagnostic value., Results: Examination of pre-contrast λ HU , Z eff , Z eff-N , IC, IC N , and venous phase IC N showed no significant differences in quantitative parameters (P > 0.05). Venous phase λ HU , Z eff , Z eff-N , and IC in glioma recurrence were higher than in treatment-related changes (P < 0.001). The optimal venous phase threshold was 1.03, 7.75, 1.04, and 2.85 mg/cm 3 , achieving 66.7, 91.7, 83.3, and 91.7% sensitivity; 100.0, 77.8, 88.9, and 77.8% specificity; 100.0, 73.3, 83.3, and 73.3% PPV; 81.8, 93.3, 88.9, and 93.3% NPV; and 86.7, 83.3, 86.7, and 83.3% accuracy, respectively. The respective areas under the curve (AUCs) were 0.912, 0.912, 0.931, and 0.910 in glioma recurrence and treatment-related changes., Conclusions: Glioma recurrence could be potentially differentiated from treatment-related changes based on quantitative values measured by dual-energy spectral CT imaging.

New immunotherapeutic approaches are urgently needed for gastric cancer due to its poor survival and unsatisfactory treatment. Here we applied the humanized chA21 scfv based chimeric antigen receptor (CAR) modified T cells approach to the HER2 overexpressing gastric cancer treatment. The chA21-4-1BBz CAR T cells specifically exerted Th1 skewed cytokine response and efficient cytolysis of HER2 overexpressing human gastric cancer cells in vitro . Both the cytokine production and cytotoxicity levels were correlated with the level of HER2 surface expression by tumor cells. In established subcutaneous xenograft and peritoneal metastasis models, chA21-4-1BBz CAR T cells dramatically facilitated regression of HER2 overexpressing tumor and prolonged survival of tumor-bearing mice, whereas spared the progression of HER2 low-expressing tumor. Additionally, the capability of these CAR T cells to persist in circulation, as well as specifically home to, and accumulate in tumor sites were identified. Taken together, these results provide the basis for the future clinical investigation of the humanized chA21 scFv based, 4-1BB costimulated CAR T cells for the treatment of gastric cancer, and other HER2-expressing solid tumors., Competing Interests: None.

Long-term uninterrupted therapy is essential for maximizing clinical benefits of antiangiogenic drugs (AADs) in cancer patients. Unfortunately, nearly all clinically available AADs are delivered to cancer patients using disrupted regimens. We aim to develop lifetime, nontoxic, effective, orally active, and low-cost antiangiogenic and antitumor drugs for treatment of cancer patients. Here we report our findings of long-term maintenance therapy with orally active, nontoxic, low cost antiangiogenic chemotherapeutics for effective cancer treatment. In a sequential treatment regimen, robust antiangiogenic effects in tumors were achieved with an anti-VEGF drug, followed by a low-dose chemotherapy. The nontoxic, low dose of the orally active prodrug capecitabine was able to sustain the anti-VEGF-induced vessel regression for long periods. In another experimental setting, maintenance of low-dose capecitabine produced greater antiangiogenic and antitumor effects after AAD plus chemotherapy. No obvious adverse effects were developed after more than 2-mo of consecutive treatment with a low dose of capecitabine. Together, our findings provide a rationalized concept of effective cancer therapy by long-term maintenance of AAD-triggered antiangiogenic effects with orally active, nontoxic, low-cost, clinically available chemotherapeutics., Competing Interests: The authors declare no conflict of interest.

Purpose: Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands., Methods: Expression of NKG2D ligands including MICA, MICB, and ULBP1-3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity., Results: Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells., Conclusion: These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis.

Aberrant tumor cell expression of B7-H3, a member of the B7-family that stimulates interleukin-10 (IL-10) secretion, contributes to tumor immune evasion and tumor progression. The aim of this study was to investigate the expression of B7-H3 and IL-10 in ductal and lobular breast cancer tissues. Using immunohistochemistry, B7-H3 and IL-10 protein expression in tumor specimens of primary human breast cancer was investigated. The association between B7-H3 or IL-10 expression and clinicopathological variables was analyzed. The correlation between the expression of B7-H3 and IL-10 was also evaluated. In tumor tissues, the expression of B7-H3 and IL-10 was identified on the cell membrane and in the cytoplasm. Expression of B7-H3 was observed in 90.60% (106/117) of the specimens and 80.34% (94/117) expressed IL-10. Patients with a positive B7-H3 or high IL-10 expression were more likely to have positive lymph node metastasis (N1-3; P=0.018 or 0.035, respectively) and advanced disease (stage II-IV; P=0.011 or 0.039, respectively) compared to those with a negative or low expression. Furthermore, B7-H3 expression was correlated with IL-10 in tumor cells (R=0.545, P=0.000). High B7-H3 expression in human breast cancer tissues may be important in tumor progression and invasiveness. This expression appeared to be correlated with the ability of B7-H3 to promote IL-10 secretion.

Objective: To gain a primary understanding of the prevalence of 21-hydroxylase deficiency(21-OHD) heterozygote (carrier) among androgen excess women of Chinese Han nationality, compare the molecular genetic changes therein revealed with the results of adrenocorticotropic hormone (ACTH) stimulating test, and assess the carriers' phenotype-genotype correlation., Methods: Eighty-two androgen excess cases and 14 healthy women underwent ACTH stimulating test during the follicular phase. Molecular genetic analysis of CYP21 for 9 common mutations was performed with the method of amplification-created restriction sites., Results: In androgen excess group, the basal level of F0 (P<0.01), as well as basal 17-OHP0 and the ACTH stimulated concentrations of 17-OHP60 were much higher than controls (P<0.01), and there was no obvious discrepancy in F60 (P>0.05). The net increase of 17-OHP and the ratio of net increase of 17-OHP to net increase of F were also higher than controls (P<0.01). No CYP21 gene mutations were found in control group. Four patients of the androgen excess group were identified as heterozygous carriers of CYP21 mutations. The ACTH stimulating test results from gene normal patients and from carriers overlapped to a certain extent., Conclusion: Among 82 patients of Chinese Han nationality androgen excess women, 4.9% were 21-OHD heterozygous. The response of serum 17-OHP is not useful for predicting CYP21 gene mutation carrier status. Genotyping is the most reliable method to detect carrier.