Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy. METHODS: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment. FINDINGS: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported. INTERPRETATION: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings. FUNDING: BeiGene.

Prognostic value of L4 lymph node dissection during video-assisted thoracoscopic surgery in patients with left-sided non-small cell lung cancer: a single-center, retrospective cohort study.

Background: Lymph node dissection (LND) is crucial procedure during radical resection of non-small cell lung cancer (NSCLC), but the prognostic value of L4 LND remains elusive. To investigate the prognostic value of L4 LND in patients with left-side NSCLC who underwent video-assisted thoracoscopic surgery (VATS). Methods: Three hundred twelve patients who underwent VATS between Jan. 2007 and Dec. 2016 were reviewed. Of those, 119 underwent L4 LND (L4D+), whereas the other 193 patients did not (L4D-). The inclusion criteria were as follows: patients diagnosed with primary left-sided NSCLC who underwent VATS lobectomy combined with LND; patients subjected to R0 resection and tumor pathological stage T1-4N0-2M0. The primary endpoint was overall survival (OS). OS was calculated from the operation date to the date of death. The chi-square test was used for categorical variables, and a t test was used for continuous variables. Results: A total of 119 patients underwent L4 LND, and the procedure was more likely to be performed on upper lobe tumors (P=0.019). Patient distributions with respect to age, gender, smoking history, clinical stage, adjuvant therapy, tumor differentiation and tumor size were well balanced between two groups. More lymph nodes (LNs) were dissected in the L4D+ group than in the L4D- group (P<0.001). The rate of metastasis to L4 lymph nodes was 9.2%, which was comparable between patients with upper and lower lobe tumors (8.9% vs. 10.0%, P=1.000). The L4D+ group exhibited a significantly better OS than the L4D- group (median OS: undefined vs. 130 months, HR 0.47; 95% CI: 0.31-0.72; P=0.002). Multivariate analysis showed that L4 LND was an independent factor for OS. However, OS did not significantly differ between the two groups of cT1aN0 and cT1bN0 patients (OS: HR 0.44; 95% CI: 0.18-1.06; P=0.12). Conclusions: L4 LND is recommended for patients with left-sided NSCLC as an essential component of radical resection. The role of L4 LND in cT1a-bN0 disease warrants further study.

[Study on mechanism of Phytolaccae Radix and its split components based on network pharmacology].

This paper aimed to explore the mechanism of the split components of Phytolaccae Radix by means of network pharmaco-logy. Based on the theoretical hypothesis of the nature and taste of traditional Chinese medicine, the chemical components of the separated components of Phytolaccae Radix were selected by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Traditional Chinese Medicines IntegratedDatabase(TCMID) databases in combination with related literatures. Relevant target analysis was carried out based on PubChem and SwissTargetPrediction databases. Targets corresponding to disease were excavated based on GeneCards for each split component, corresponding potential targets were obtained through mapping the target set of target compounds to disease targets. GO biological process analysis and KEGG pathway enrichment analysis were performed on the mapped targets with the help of DAVID database. Based on Cytoscape software and the corresponding efficacy, the network diagram of "medicinal material-split components-compound-target-pathway" was constructed to explore the mechanism of different efficacy of the separated components of Cytoscape. And the target purgation and diuretic mapping was used as the target of the traditional efficacy of smoothening secretion for the first time. The study explored esculentoside component, fatty oil component and phenolic acid component, a total of 30 target compounds and 301 corresponding targets, involving 44 potential targets for "anti-inflammatory", 50 potential targets for "immunoregulation", 52 potential targets for "smoothening secretion", 28 potential targets for "antibacterial activity", 28 potential targets for "antiviral effect", and 29 potential targets for "antitumor effect". Topological analysis revealed 14 key gene targets such as MAPK8, MAPK14, EGFR and PTGS2. A total of 684 GO entries and 235 KEGG pathways were obtained through bioinformatics enrichment analysis, mainly involving TNF signaling pathway, NF-kappaB signaling pathway and MAPK signaling pathway. This study revealed the multi-component, multi-target, and multi-channel action mechanism of the split components of Phytolaccae Radix, which provided certain basis for the next step to clarify the split components of Phytolaccae Radix through the method of system biology, and injected new content and significance into the study of properties and flavors theory.

Crystallographic and SAR analyses reveal the high requirements needed to selectively and potently inhibit SIRT2 deacetylase and decanoylase.

A high-quality X-ray crystal structure reveals the mechanism of compound 1a inhibiting SIRT2 deacetylase and decanoylase. Structure-activity relationship (SAR) analysis of the synthesized derivatives of 1a reveals the high requirements needed for selective inhibitors to bind with the induced hydrophobic pocket and potently inhibit sirtuin 2 deacetylase.

18F-FP-CIT PET imaging and SPM analysis of dopamine transporters in Parkinson's disease in various Hoehn & Yahr stages.

To investigate the usefulness of 18F-FP-CIT PET for assessing the severity of Parkinson's disease (PD) at various clinical stages, 41 patients with PD were divided into early (Hoehn&Yahr I-II, n = 23) and advanced (Hoehn & Yahr III-IV, n = 18) subgroups. 18F-FP-CIT PET was performed in these patients and 12 normal subjects. 18F-FP-CIT uptake in striatal subregions and its correlation with UPDRS were first evaluated by ROI analysis, and between-group differences were also analyzed by Statistical Parametric Mapping (SPM). Our results showed that striatal 18F-FP-CIT binding were significantly reduced to 70.9% (caudate), 46.8% (anterior putamen) and 24.0% (posterior putamen) in early PD compared with that of the control, and to 52.0%, 34.5% and 16.5% correspondingly in advanced PD, respectively. There was significant negative correlation between total motor UPDRS score of all parkinsonian patients and 18F-FP-CIT uptake in caudate nucleus (r = -0.53, p < 0.001), anterior putamen (r = -0.53, p < 0.001) and posterior putamen (r = -0.61, p < 0.001). SPM comparison of 18F-FP-CIT uptake between early or advanced PD and the control group showed significant decline in striatum, predominantly localized on the contralateral side and in the dorsal-posterior putamen. These results indicate that 18F-FP-CIT PET can serve as a suitable biomarker to represent the severity of PD in early and advanced stages.