Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

Warming affects leaf light use efficiency and functional traits in alpine plants: evidence from a 4-year in-situ field experiment.

Introduction: Light use efficiency (LUE) is a crucial determinant of plant productivity, while leaf functional traits directly affect ecosystem functions. However, it remains unclear how climate warming affects LUE and leaf functional traits of dominant species in alpine meadows. Methods: We conducted a 4-year in-situ field warming experiment to investigate the eco-physiological characteristics for a dominant species (Elymus nutans) and a common species (Potentilla anserina) on the Tibetan Plateau. The leaf traits, photosynthesis and fluorescence characteristics were measured, along with the soil physical-chemical properties associated with the two species. Results and discussions: Experimental warming increased the leaf LUE, maximum photochemical efficiency, non-photochemical quenching, relative water content and specific leaf area for both species. However, there was a decrease in leaf and soil element content. Different species exhibit varying adaptability to warming. Increasing temperature significantly increased the photosynthetic rate, stomatal conductance, transpiration rate, total water content, and specific leaf volume of E. nutans; however, all these traits exhibited an opposite trend in P. anserina. Warming has a direct negative impact on leaf LUE and an indirectly enhances LUE through its effects on leaf traits. The impact of warming on plant photosynthetic capacity is primarily mediated by soil nutrients and leaf traits. These results indicate that the two different species employ distinct adaptive strategies in response to climate change, which are related to their species-specific variations. Such changes can confer an adaptive advantage for plant to cope with environmental change and potentially lead to alterations to ecosystem structure and functioning.

Anlotinib plus tislelizumab for recurrent metastatic pancreas ductal adenocarcinoma with germline BRCA2 mutation: A case report.

While combined immunotherapy and anti-angiogenic therapy have demonstrated efficacy in renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma, the efficacy of first-line treatment for pancreatic ductal adenocarcinoma (PDAC) with germline BRCA2 mutation remains unproven. We described a BRCA2-mutated patient with PDAC who presented with posterior cardiac metastasis 8 months after surgery. After receiving four cycles of anlotinib combined with tislelizumab, abdominal CT scans indicated a complete response. The patient sustained this response for over 14 months on the combination regimen, with no reported adverse events. In conclusion, the combination of tislelizumab and anlotinib may offer a viable therapeutic option for recurrent metastatic BRCA2-mutated PDAC.

Red blood cell-derived materials for cancer therapy: Construction, distribution, and applications.

Cancer has become an increasingly important public health issue owing to its high morbidity and mortality rates. Although traditional treatment methods are relatively effective, they have limitations such as highly toxic side effects, easy drug resistance, and high individual variability. Meanwhile, emerging therapies remain limited, and their actual anti-tumor effects need to be improved. Nanotechnology has received considerable attention for its development and application. In particular, artificial nanocarriers have emerged as a crucial approach for tumor therapy. However, certain deficiencies persist, including immunogenicity, permeability, targeting, and biocompatibility. The application of erythrocyte-derived materials will help overcome the above problems and enhance therapeutic effects. Erythrocyte-derived materials can be acquired via the application of physical and chemical techniques from natural erythrocyte membranes, or through the integration of these membranes with synthetic inner core materials using cell membrane biomimetic technology. Their natural properties such as biocompatibility and long circulation time make them an ideal choice for drug delivery or nanoparticle biocoating. Thus, red blood cell-derived materials are widely used in the field of biomedicine. However, further studies are required to evaluate their efficacy, in vivo metabolism, preparation, design, and clinical translation. Based on the latest research reports, this review summarizes the biology, synthesis, characteristics, and distribution of red blood cell-derived materials. Furthermore, we provide a reference for further research and clinical transformation by comprehensively discussing the applications and technical challenges faced by red blood cell-derived materials in the treatment of malignant tumors.

Histological transformation into SCLC: An important resistance mechanism of NSCLC upon immunotherapy.

The phenomenon of histological transformation has been widely reported in advanced non-small cell lung cancer (NSCLC) with EGFR mutations following the failure of EGFR-TKI treatment. Recent evidence suggests that similar histological changes can also occur in advanced NSCLC without driver gene mutations after developing resistance to immunotherapy. In this review, it was found that 66.7% of cases with immunotherapy-induced histological transformation were classified as lung squamous cell carcinoma (LSCC), while histological conversion into lung adenocarcinoma (LUAD) without EGFR or ALK gene mutations has rarely been reported. There have been sporadic reports on the occurrence of mutual transformation between LUAD and LSCC. The histological conversion from NSCLC into small cell lung cancer (SCLC) appears to be significantly underestimated, likely due to the infrequency of re-biopsy following the development of immunotherapy resistance. Several studies have reported a close association between the transformation and mutations at TP53 and the RB1 splice site, as well as the loss of an FBXW7 mutation. However, the exact mechanisms underlying this conversion remain unclear. Currently, there is a lack of guidelines for the management of transformed SCLC from NSCLC following immunotherapy, with chemotherapy being the most commonly employed treatment approach.

Immunotherapy-based therapy as a promising treatment for EGFR-mutant advanced non-small cell lung cancer patients after EGFR-TKI resistance.

INTRODUCTION: Traditionally, epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has been regarded as a cold tumor based on the immunosuppressive tumor immune microenvironment (TIME). However, recent studies have found that EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment could shift host immunity from immunosuppressive to immunosupportive TIME, which has renewed hopes of immunotherapy. AREAS COVERED: In this review, we highlight five main immunotherapy-based therapies for patients after EGFR-TKI failure, including safety and efficacy data from prospective and retrospective clinical studies. EXPERT OPINION: The efficacy of immunotherapy alone is extremely limited. Immunotherapy plus chemotherapy show an ORR of 29.5%-59.3% and an mPFS of about 7 months. There is still scarce evidence for immunotherapy plus antiangiogenesis therapy. A combination of immunotherapy with EGFR-TKIs exhibits higher treatment-related adverse events and lower clinical outcomes compared to EGFR-TKI alone. Importantly, immunotherapy plus antiangiogenesis and chemotherapy achieves an mPFS of 6.9-10.2 months. In general, the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug is a novel and promising method for treating advanced NSCLC after EGFR-TKI failure. Therefore, the dominant population of EGFR-TKI resistant patients were characterized by EGFR uncommon mutation, EGFR L858R mutation, PD-L1 ≥ 50%, prior antiangiogenic drugs, and negative T790 M mutation for immunotherapy-based therapy.

Aumolertinib challenge as an optional treatment in advanced non small-cell lung cancer after osimertinib failure with epidermal growth factor receptor-sensitive mutation: A case series.

Osimertinib, as the first third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been recommended universally as the priority front-line therapeutic for advanced non-small cell lung cancer (NSCLC) carrying EGFR-sensitive mutations. However, patients inevitably acquire drug resistance to osimertinib. Aumolertinib is the second third-generation EGFR-TKI and has been similarly approved as a first-line treatment agent. The present study reports the cases of 3 patients who were challenged with aumolertinib after osimertinib failure. All 3 patients achieved a partial remission. The progression-free survival periods following aumolertinib were 10.0, 11 and 9.0 months (at the time of writing the study). Although the patient in case 2 succumbed to an intracerebral hemorrhage due to hypertension, aumolertinib remained effective as a treatment in cases 1 and 3. The present case series suggests the use of aumolertinib challenge as an optional treatment for patients with metastatic NSCLC harboring EGFR-sensitive mutations after osimertinib failure. The therapeutic strategy of switching from osimertinib to aumolertinib is worth exploring further in the near future.

Environmental filtering rather than dispersal limitation dominated plant community assembly in the Zoige Plateau.

Identifying the mechanisms that underlie the assembly of plant communities is critical to the conservation of terrestrial biodiversity. However, it is seldom measured or quantified how much deterministic versus stochastic processes contribute to community assembly in alpine meadows. Here, we measured the decay in community similarity with spatial and environmental distance in the Zoige Plateau. Furthermore, we used redundancy analysis (RDA) to divide the variations in the relative abundance of plant families into four components to assess the effects of environmental and spatial. Species assemblage similarity liner declined with geographical distance (p < .001, R 2 = .6388), and it decreased significantly with increasing distance of total phosphorus (TP), alkali-hydrolyzable nitrogen (AN), available potassium (AK), nitrate nitrogen (NO3 +-N), and ammonia nitrogen (NH4 +-N). Environmental and spatial variables jointly explained a large proportion (55.2%) of the variation in the relative abundance of plant families. Environmental variables accounted for 13.1% of the total variation, whereas spatial variables accounted for 11.4%, perhaps due to the pronounced abiotic gradients in the alpine areas. Our study highlights the mechanism of plant community assembly in the alpine ecosystem, where environmental filtering plays a more important role than dispersal limitation. In addition, a reasonably controlled abundance of Compositae (the family with the highest niche breadth and large niche overlap value with Gramineae and Cyperaceae) was expected to maintain sustainable development in pastoral production. These results suggest that management measures should be developed with the goal of improving or maintaining suitable local environmental conditions.

LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma.

Currently, the mechanisms of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance have been a focus of clinical research. Despite that most of the mechanisms of acquired EGFR TKI resistance have been revealed, about 30% of non-small-cell lung cancer (NSCLC) cases have not been fully elucidated, especially for lung adenocarcinoma (LUAD). Recently, LPCAT1, an important enzyme of phospholipid metabolism, has been found to bridge the gap between the oncogene and metabolic reprogramming. In NSCLC, LPCAT1 has been shown to participate in progression and metastasis. However, little is known about the role of LPCAT1 in acquired EGFR TKI resistance. In this study, elevated LPCAT1 expressions were observed in an EGFR TKI-resistant cell line (PC-9R) relative to a corresponding EGFR TKI-sensitive cell line (PC-9). In vivo and in vitro gene functional studies showed that LPCAT1 contributed to the pathogenesis of gefitinib resistance in LUAD, where an LPCAT1-EGFR positive feedback loop formed and then regulated its downstream signaling molecules of the EGFR/PI3K/AKT signaling pathway. The results provided novel insights into the acquired resistance mechanism of EGFR TKI from the perspective of phospholipid metabolism. These findings suggest LPCAT1 may serve as a potential therapeutic target for patients with EGFR TKI-resistant NSCLC.

Long-acting granulocyte colony-stimulating factor in primary prophylaxis of early infection in patients with newly diagnosed multiple myeloma.

PURPOSE: This study sought to compare the efficacy of prophylactic long-acting and standard granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia, early infections, and treatment delay in patients with newly diagnosed multiple myeloma (MM) receiving the therapeutic regimen of bortezomib, lenalidomide, and dexamethasone (VRd). METHODS: A prospective study with 68 consecutive patients with MM was conducted in three regional hospitals. Participants were randomly treated with the VRd regimen in combination with prophylactic long-acting G-CSF (treatment group) or prophylactic standard G-CSF (control group). The primary endpoints were the incidence rates of febrile neutropenia, early infection, and treatment delays. The secondary endpoint was clinical outcomes. RESULTS: Thirty-three patients were assigned to the treatment group, and thirty-five patients were assigned to the control group. The incidence of febrile neutropenia was 6.1% and 17.1% in the treatment and control groups, respectively (p = 0.297). However, the rates of early infection and treatment delay were markedly lower in the treatment group than in the control group (6.1% vs. 25.7% and 9.1% vs. 31.4%; p < 0.05). Notably, all early infections occurred during the first four cycles of VRd therapy, and the most common type of infection was pneumonia. No significant difference in clinical efficacy was found between the two groups. All participants achieved at least partial remission. CONCLUSIONS: Prophylactic administration of domestic long-acting G-CSF markedly reduced the rates of early infection and treatment delay as compared with standard G-CSF in patients newly diagnosed with MM. Notably, all early infections occurred during the first four cycles of VRd therapy. As such, it seems appropriate to administer long-acting G-CSF with the aim of primary prophylaxis of early infection in the setting of newly diagnosed MM.

Leaf and Community Photosynthetic Carbon Assimilation of Alpine Plants Under in-situ Warming.

The Tibetan Plateau is highly sensitive to elevated temperatures and has experienced significant climate warming in the last decades. While climate warming is known to greatly impact alpine ecosystems, the gas exchange responses at the leaf and community levels to climate warming in alpine meadow ecosystems remain unclear. In this study, the alpine grass, Elymus nutans, and forb, Potentilla anserina, were grown in open-top chambers (OTCs) for 3 consecutive years to evaluate their response to warming. Gas exchange measurements were used to assess the effects of in-situ warming on leaf- and community-level photosynthetic carbon assimilation based on leaf photosynthetic physiological parameters. We introduced a means of up-scaling photosynthetic measurements from the leaf level to the community level based on six easily measurable parameters, including leaf net photosynthetic rate, fresh leaf mass per unit leaf area, fresh weight of all plant leaves in the community, the percentage of healthy leaves, the percentage of received effective light by leaves in the community, and community coverage. The community-level photosynthetic carbon assimilation and productivity all increased with warming, and the net photosynthetic rate at the leaf level was significantly higher than at the community level. Under elevated temperature, the net photosynthetic rate of E. nutans decreased, while that of P. anserina increased. These results indicated that climate warming may significantly influence plant carbon assimilation, which could alter alpine meadow community composition in the future.

Effective treatment of apatinib for chemotherapy-refractory advanced gastric carcinoma with AFP-secretion and HER2-positivity: A case report.

α-fetoprotein (AFP)-secreting gastric cancer (AFP-GC) is a relatively rare, aggressive malignancy among all GC types. However, no GC case with simultaneous expression of AFP and epidermal growth factor receptor 2 (HER2) has been reported to date. To the best of our knowledge, the present report was the first to describe the use of apatinib to treat a patient with advanced GC characterized by AFP-secretion and HER2-positivity. An 86-year-old man with advanced GC was diagnosed with AFP-secretive and HER2-positive GC with liver metastasis at The Affiliated Hospital of Jiujiang University (Jiujiang, China). The patient received first-line (i.e., S-1 plus oxaliplatin) and second-line (i.e., docetaxel) chemotherapy combined with trastuzumab for two cycles, respectively. However, the disease progressed rapidly. Subsequently, apatinib was administered as third-line therapy. After two cycles of apatinib therapy, the patient reported the disappearance of upper abdominal pain and an improvement in his appetite. Furthermore, the AFP level had sharply decreased to 620 ng/ml. Subsequently, upper abdominal computed tomography imaging revealed that the gastric lesion and liver metastatic lesion had reduced in size by 67% and 24%, respectively, suggesting partial remission. Currently, the patient has continued to receive apatinib therapy. It was speculated that AFP-secretion status could contribute to the chemoresistance of HER2-positive GC. Apatinib may be a promising anticancer agent in the case of advanced AFP-producing and HER2-positive GC.

Responses of Plant Bud Bank Characteristics to the Enclosure in Different Desertified Grasslands on the Tibetan Plateau.

Asexual reproduction is the main mode of alpine plant reproduction, and buds play an important role in plant community succession. The purpose of this study is to explore whether the desertified grassland can recover itself through the existing bud bank. The bud bank composition, distribution and size of different desertified grasslands were studied using unit volume excavation on the Tibetan Plateau. The bud bank consisted of tiller, long and short rhizome buds, and more than 40% of buds were distributed in the 0-10 cm soil layer. Enclosure changed the bud density, distribution and composition. The bud densities were 4327 and 2681 No./m2 in light and middle desertified grasslands before enclosure, while that decreased to 3833 and 2567 No./m2 after enclosure. Tiller bud density and proportion of middle desertified grassland were the highest, increased from 2765 (31.26%, before enclosure) to 5556 No./m3 (62.67%, after enclosure). There were new grasses growing out in the extreme desertified grassland after enclosure. The meristem limitation index of moderate desertified grassland was the lowest (0.37), indicating that plant renewal was limited by bud bank. Plants constantly adjust the bud bank composition, distribution, and asexual reproduction strategy, and desertified grasslands can recover naturally, relying on their bud banks through an enclosure.