Safety and effectiveness of neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection in patients with stage I–IIIA small-cell lung cancer: a retrospective single-arm clinical trial

BackgroundImmunotherapy, chemotherapy and surgery all have significant roles in the management of small-cell lung cancer (SCLC). Neoadjuvant immunotherapy combined with chemotherapy followed by surgery has shown encouraging efficacy for resectable SCLC with a good tolerability and considerable survival benefit. However, there are still few data on whether surgery for stage I–IIIA SCLC can be performed after immunotherapy with chemotherapy. Therefore, we investigated the safety and effectiveness of neoadjuvant immunotherapy combined with chemotherapy followed by surgery in patients with stage I–IIIA SCLC in the hope of adding new ideas to the treatment of SCLC.MethodsThe study group comprised 19 patients with stage I–IIIA SCLC who received neoadjuvant immunotherapy and chemotherapy between 2019 and 2021. Patients received 2–4 cycles of immunotherapy combined with platinum-containing dual-drug chemotherapy (platinum + paclitaxel) before surgery. Imaging evaluation was performed every two cycles until surgery. Tumor response to neoadjuvant therapy, neoadjuvant treatment related adverse events, perioperative and postoperative complications, surgical resection rate, and degree of tumor regression were evaluated. We obtained follow-up data from the patients’ regular examination or treatment in hospital. If we can’t complete it, contacting patients by telephone or WeChat would be adopted by us. The follow-up was not terminated until 3 months after surgery.ResultsThe objective response rate (ORR) was 84.2% (16/19), and no patients had progressive disease (PD). Of the 10 patients who underwent surgery, and approximately 9 (90.0%) had R0 resection. There were no perioperative deaths, and 1 case of pyothorax. The rate of pathological complete remission (pCR) and major pathological response (MPR) was 30.0% (3/10), and 40.0% (4/10) respectively. Grade 3–4 adverse reactions comprised 1 case of anemia and 1 case of constipation.ConclusionsNeoadjuvant immunotherapy combined with chemotherapy followed by surgical resection for patients with stage I–IIIA SCLC is effective and safe with a high ORR and MPR rate, as well as a high R0 resection rate and a tolerable toxicity profile. Whether this regimen gives a survival benefit should be confirmed by further follow-up and larger, randomized controlled trials are required to confirm our findings.     

IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer

Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit β (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL-20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete the IL-20RB ligand IL-19, and IL-19 stimulated IL-20RB–expressing tumor cells to activate downstream JAK1/STAT3 signaling, leading to enhanced proliferation of tumor cells in bone. Importantly, blocking IL-20RB with a neutralizing antibody significantly suppressed bone metastasis of lung cancer. Overall, our data revealed a direct protumor role of osteoclastic niche in bone metastasis and supported IL-20RB–targeting approaches for metastasis treatment.     

Effect of thymoquinone on sepsis-induced cardiac damage via anti-inflammatory and anti-apoptotic mechanisms

ObjectiveSepsis is a systemic and deleterious host reaction to severe infection. Cardiac dysfunction is an established serious outcome of multiorgan failure associated with this condition. Therefore, it is important to develop drugs targeting sepsis-induced cardiac damage and inflammation. Thymoquinone (TQ) has anti-inflammatory, anti-oxidant, anti-fibrotic, anti-tumor, and anti-apoptotic effects. This study examined the effects of thymoquinone on sepsis-induced cardiac damage.MethodsMale BALB/c mice were randomly segregated into four groups: control, TQ, cecal ligation and puncture (CLP), and CLP + TQ groups. CLP was performed after gavaging the mice with TQ for 2 weeks. After 48 hours, we estimated the histopathological changes in the cardiac tissue and the serum levels of cardiac troponin-T. We evaluated the expression of factors associated with inflammation, apoptosis, oxidative stress, and the PI3K/AKT pathway.ResultsTQ significantly reduced intestinal histological alterations and inhibited the upregulation of interleukin-6, tumor necrosis factor-α, Bax, NOX4, p-PI3K, and p-AKT. TQ also increased Bcl-2, HO-1, and NRF2 expression.ConclusionThese results suggest that TQ effectively modulates pro-inflammatory, apoptotic, oxidative stress, and PI3K/AKT pathways, making it indispensable in the treatment of sepsis-induced cardiac damage.     

胆石清片联合熊去氧胆酸片预防肝内胆管结石术后复发25例

目的观察胆石清片联合熊去氧胆酸片预防肝内胆管结石术后复发的效果。方法回顾分析2010年3月至2012年10月行肝内胆管结石手术患者45例的临床资料,术后对照组未口服药物,治疗组口服胆石清片联合熊去氧胆酸片,观察两组患者肝功能变化和结石复发情况。结果术后肝功能均正常,患者随访时间6月-2年,治疗组结石复发率为16．00％,对照组结石复发率为25．00％,治疗组显著优于对照组（P〈0．01）。结论肝内胆管结石术后服用胆石清片和熊去氧胆酸片预防术后结石复发安全、有效,但长期疗效尚需深入研究。     

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.     

胰岛素和亚硒酸钠最佳配比组方研究

目的 确定普通胰岛素与亚硒酸钠降血糖作用的最佳组方配比.方法 采用小剂量链脲佐菌素腹腔注射联合高糖高脂饲养的大鼠模型,以血糖降低百分率为考察指标,根据权重配方法设不同配比组方6组,分析结果得出最佳理论配比,并进一步做确证性试验考察二者的相互关系.结果 胰岛素与亚硒酸钠对血糖的控制为协同作用,二者比例为1 U:5μg时可显著降低血糖.结论 胰岛素和亚硒酸钠的最佳配比为1 U:5μg.     

仙灵骨葆联合钙剂治疗高龄患者老年性骨质疏松症的临床研究

目的：观察仙灵骨葆胶囊联合钙尔奇D和骨化三醇对高龄患者老年性骨质疏松症的治疗效果.方法：选择60例高龄老年性骨质疏松症患者随机分为两组,治疗组（仙灵骨葆＋钙尔奇D＋骨化三醇）30例,对照组（钙尔奇D＋骨化三醇）30例.观察两组患者治疗前后和两组间的VAS评分、SF-36评分、BMD、血Ca、血P、ALP、TRACP的差异.结果：两组治疗后VAS评分较治疗前均明显降低（P＜0.01）,治疗组降低较对照组更明显（P＜0.01）.两组治疗后SF-36评分较治疗前均明显提高（P＜0.01）,治疗组升高较对照组更明显（P＜0.01）.治疗组治疗后BMD明显升高,对照组BMD变化不大,两组比较有显著差异（P＜0.05）.治疗前后两组血Ca和血P均变化不大,组间比较无差异（P＞0.05）.治疗组治疗后ALP明显升高,对照组ALP变化不大,两组比较有显著差异（P＜0.05）.两组治疗后TRACP较治疗前均有所降低,治疗组降低明显,组间比较有显著差异（P＜0.01）,两组所有患者无严重不良反应发生.结论：仙灵骨葆胶囊联合钙尔奇D和骨化三醇治疗高龄患者老年性骨质疏松症效果确切,且安全性良好.     

LOX与VEGF蛋白在人喉鳞癌中的表达及其相关性研究

目的检测赖氨酰氧化酶（LOX）、血管内皮生长因子（VEGF）蛋白在人喉鳞癌中的表达,探讨其对喉鳞癌转移及预后的影响及意义。方法采用免疫组织化学方法检测14例有淋巴结转移的喉鳞癌及24例未见淋巴结转移的原位癌组织中LOX及VEGF的表达情况,并分析其表达的相关性。结果①LOX、VEGF在喉鳞癌组织中表达显著高于癌旁正常组织（P均〈0．05）。②VEGF在淋巴结转移组与无转移组表达阳性率分别为100％和71％,具有显著性差异（P〈0．05）;LOX在淋巴结转移组与无转移组表达无显著性差异（P〉0．05）。③LOX、VEGF的表达与患者的年龄、性别、临床分型及临床分期等临床病理因素无关。④LOX与VEGF在人喉鳞癌组织中表达呈正相关。结论LOX与VEGF存在正相关性,可作为喉癌治疗的一个新靶点。VEGF的高表达可能是造成LOX表达变化的重要影响因素之一。