Small cell lung cancer (SCLC) is characterized by rapid proliferation and high propensity for local recurrence and widespread metastasis, which yields extremely poor prognosis. Approximately 2/3 of patients present with extensive-stage disease (ES-SCLC) at initial diagnosis. For ES-SCLC, the combination platinum-based chemotherapy has been the standard regimen for the past few decades. In the era of chemotherapy, multiple studies have shown the benefit of thoracic radiotherapy (TRT) for patients who responded to chemotherapy. However, with the first-line treatment of ES-SCLC shifting into the immune era, as well as the advances in diagnostic imaging modality and radiation technology, the benefit of TRT has caused a widespread controversy. In this article, the value of TRT for ES-SCLC and the latest progress in the radioimmunotherapy combination mode for ES-SCLC were reviewed.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Objective:To determine the effect of community management based on the Roy′s adaptation model (RAM) in patients with chronic obstructive pulmonary disease (COPD).Methods:This study was a cluster randomized controlled study, with the community as the cluster unit, and selected 805 COPD patients from 8 communities in Xuzhou City who had completed community registration before June 2019. A total of 735 patients actually completed follow-up and participated in intervention evaluation. They were randomly divided into control group (362 cases) and intervention group (373 cases) by random number table method. The control group received routine follow-up, while the intervention group received RAM intervention for 6 months. The forced expiratory volume in 1 second (FEV1)/forced volume vital capacity (FVC) ratio (FEV 1/FVC) and the modified British medical research council (mMRC) were used to assess the pulmonary function. The hospital anxiety and depression scales (HADS) were used to evaluate the mental health. The Chinese version of the Short Form Coping and Adaption Processing Scale (CAP-15) was used to assess the adaptive capacity. And the St. George′s Respiratory Questionnaire (SGRQ) was used to evaluate the quality of life in COPD patients. The t test or χ 2 test was used for pre-intervention comparisons between groups, and the repetitive measure analysis of variance (ANOVA) was used for post-intervention comparisons between groups. Results:After 6 months intervention, there were no significant differences in FEV 1/FVC radio between the two groups [(0.61±0.11) vs (0.62±0.12)] ( P=0.172). The scores of mMRC [(2.04±0.33) vs (2.77±0.31) points], HAD-A [(5.28±4.28) vs (6.99±4.41) points], HAD-D [(5.82±5.12) vs (7.27±4.93) points] and SGRQ [(40.17±9.30) vs (53.69±9.77) points] were all lower in the intervention group than those in the control group (all P<0.001). The CAPS-15 score was higher in the intervention group than that in the control group [(35.87±3.62) vs (26.1±3.47)] ( P<0.001). Conclusion:RAM could be used in community management of COPD patients, which could improve their dyspnea symptoms and psychological and physiological functions, also improve their adaptability and quality of life.

Objective To study the cyclic peptides from sponge Reniochalina sp. under the guidance of mass spectrometry. Methods Mass spectrometry-guided procedural separation methods were used to track and isolate the cyclic peptides from the sponge genus Reniochalina. The structures of compounds were elucidated by the determination of physicochemical parameters and comparison of spectroscopic data. The preliminary cytotoxic activity of compounds was assessed by the Cell Counting Kit-8 (CCK-8) method. Results Three cyclic peptides were isolated from the sponge Reniochalina sp. and identified as stylopeptide 1 (1), hymenamide D (2) and axinastatin 2 (3). Compound 1 exhibited cytotoxicity against six human cancer cell lines with IC₅₀ values ranging from 6.09 to 17.26 μmol/L. Conclusion Compound 1 - 3 were isolated from Reniochalina sp. for the first time, and compound 1 was a cytotoxic cyclic heptapeptide.

Objective:To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy.Methods:ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774).Results:Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G 1-G 2 hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range: 3.5-16.4 months), the median disease progression-free survival and overall survival was 7.4 months (95% CI: 6.9-8.0 months) and 14.6 months (95% CI: 9.0-20.2 months), respectively. Conclusions:Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

OBJECTIVE To investigate the effect and mechanism of Pinggan huoxue powder on cerebral ischemia-reperfusion injury （CIRI） in rats. METHODS CIRI model was induced by suture-occluded method. SD rats were divided into sham operation group， model group， positive control group （Tongxinluo capsule 0.325 g/kg）， Pinggan huoxue powder low-dose， medium-dose and high-dose groups （3.02， 6.04， 12.08 g/kg）， with 12 rats in each group. Each group was given constant volume of water or drug intragastrically， once a day， for consecutive 14 d. Longa score was used to evaluate neurological function of rats on the 1st， 7th and 14th day of intervention. After the last administration， the percentage of cerebral infarction volume in rats was measured， and neuronal injury （neuronal density） and neuronal apoptosis were observed； the protein expressions of p53， B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3 and activated Caspase-3 （Cleaved caspase-3） in brain tissue were detected. RESULTS Compared with sham operation group， Longa score at the 1st， 7th and 14th day of intervention and the percentage of cerebral infarction volume in model group significantly increased （P＜0.05）， and the arrangement of cortical cells in ischemic side was disordered， Nissl bodies were absent and vacuolated， and a large number of cell apoptosis occurred. The neuronal density and protein expression of Bcl-2 at the lesion side were significantly decreased （P＜0.05）， while the protein expressions of p53， Bax， Caspase-3 and Cleaved Caspase-3 were significantly increased （P＜0.05 or P＜0.01）. Compared with model group， the expressions of Bcl-2 in cerebral ischemia cortex of rats in Pinggan huoxue powder high-dose group were significantly increased （P＜0.05）. Longa scores of rats in Pinggan huoxue powder medium-dose and high-dose groups on the 7th and 14th day of intervention were significantly decreased （P＜0.05）， and other indexes were also significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Pinggan huoxue powder can protect cerebral nerves and inhibit apoptosis of CIRI model rats， the mechanism of which may be related to down-regulating the protein expressions of p53， Bax and Caspase-3 and up-regulating the protein expression of Bcl-2.

Podoplanin (PDPN) is a small transmembrane mucin-like glycoprotein which is expressed on the surface of lymphatic endothelial cells, glomerular podocytes, type-Ⅰ alveolar epithelial cells and some tumor cells. PDPN plays crucial function in variety of physiological and pathological processes such as embryonic development, immunoreaction, inflammation and cancer. C-type lectin-like receptor 2 (CLEC2) is mainly expressed on the platelet which specific ligand is PDPN. The interaction between PDPN and CLEC2 has received extensive attention. In this review, we summarized recent researches on the role of in sepsis and elaborated the possible mechanisms and some potential therapies for sepsis by targeting PDPN, which may provide theoretical basis for the mechanism and treatment of sepsis.