Association between extremely high prognostic nutritional index and all-cause mortality in patients with coronary artery disease: secondary analysis of a prospective cohort study in China.

OBJECTIVES: Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD). DESIGN: The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study. SETTING: The study setting was Xinjiang Medical University Affiliated First Hospital in China. PARTICIPANTS: Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI <51.35, n = 7515), Q2 (51.35 ≤ PNI < 59.80, n = 5958) and Q3 (PNI ≥ 59.80, n = 1510). The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). PRIMARY OUTCOME: The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). RESULTS: In 14 983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 major adverse cardiovascular events (MACE) and 1276 major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. The incidence of adverse outcomes was significantly different among the three groups (p <0.001). There were 338 (4.5%), 77 (1.3%) and 33 (2.2%) ACM events in the three groups, respectively. A restricted cubic spline displayed a J-shaped relationship between the PNI and worse 5-year outcomes, including ACM, CM, MACE and MACCE. After adjusting for traditional cardiovascular risk factors, we found that only patients with extremely high PNI values in the Q3 subgroup or low PNI values in the Q1 subgroup had a greater risk of ACM (Q3 vs Q2, HR: 1.617, 95% CI 1.012 to 2.585, p=0.045; Q1 vs Q2, HR=1.995, 95% CI 1.532 to 2.598, p <0.001). CONCLUSION: This study revealed a J-shaped relationship between the baseline PNI and ACM in patients with CAD, with a greater risk of ACM at extremely high PNI values. TRIAL REGISTRATION NUMBER: NCT05174143.

Epidemic trends of dyslipidemia in young adults: a real-world study including more than 20,000 samples.

BACKGROUND: There is an urgent need to learn more about the epidemiological features of dyslipidemia in youth to address the high burden of cardiovascular disease. METHODS: This experiment was an observational, cross-sectional study. The samples were collected from 22,379 college students at Xinjiang Medical University. RESULT: The overall prevalence of dyslipidemia was 13.17%, which was significantly higher in men (23%) than in women (7.2%), p < 0.01. Similarly, the prevalence rate of obesity in men (11.4%) was significantly higher than that in women (3.4%). The composition of blood lipids, such as triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), began to increase gradually from the age of 22 and showed a sharp increase after the age of 30; however, a reverse trend was present in high density lipoprotein cholesterol (HDL-C). In terms of the proportion of dyslipidemia in both men and women, low HDL-C accounted for the largest proportion (74%), followed by elevated TGs (14.5%). The overall distribution of rates of dyslipidemia and excess weight showed a U-shaped trend with increasing age, with the lowest rates seen in the 20-24 age group. CONCLUSION: Our study sheds light on the epidemiological features of dyslipidemia in young adults and enriches the limited data available on dyslipidemia, providing a reference for the close monitoring and control of risk factors to reduce the occurrence and progression of atherosclerotic cardiovascular disease events.

Applications of functional near-infrared spectroscopy in non-drug therapy of traditional Chinese medicine: a review.

Non-drug therapies of traditional Chinese medicine (TCM), including acupuncture, massage, tai chi chuan, and Baduanjin, have emerged as widespread interventions for the treatment of various diseases in clinical practice. In recent years, preliminary studies on the mechanisms of non-drug therapies of TCM have been mostly based on functional near-infrared spectroscopy (fNIRS) technology. FNIRS is an innovative, non-invasive tool to monitor hemodynamic changes in the cerebral cortex. Our review included clinical research conducted over the last 10 years, establishing fNIRS as a reliable and stable neuroimaging technique. This review explores new applications of this technology in the field of neuroscience. First, we summarize the working principles of fNIRS. We then present preventive research on the use of fNIRS in healthy individuals and therapeutic research on patients undergoing non-drug therapies of TCM. Finally, we emphasize the potential for encouraging future advancements in fNIRS studies to establish a theoretical framework for research in related fields.

Genetic basis of sorghum leaf width and its potential as a surrogate for transpiration efficiency.

KEY MESSAGE: Leaf width was correlated with plant-level transpiration efficiency and associated with 19 QTL in sorghum, suggesting it could be a surrogate for transpiration efficiency in large breeding program. Enhancing plant transpiration efficiency (TE) by reducing transpiration without compromising photosynthesis and yield is a desirable selection target in crop improvement programs. While narrow individual leaf width has been correlated with greater intrinsic water use efficiency in C4 species, the extent to which this translates to greater plant TE has not been investigated. The aims of this study were to evaluate the correlation of leaf width with TE at the whole-plant scale and investigate the genetic control of leaf width in sorghum. Two lysimetry experiments using 16 genotypes varying for stomatal conductance and three field trials using a large sorghum diversity panel (n = 701 lines) were conducted. Negative associations of leaf width with plant TE were found in the lysimetry experiments, suggesting narrow leaves may result in reduced plant transpiration without trade-offs in biomass accumulation. A wide range in width of the largest leaf was found in the sorghum diversity panel with consistent ranking among sorghum races, suggesting that environmental adaptation may have a role in modifying leaf width. Nineteen QTL were identified by genome-wide association studies on leaf width adjusted for flowering time. The QTL identified showed high levels of correspondence with those in maize and rice, suggesting similarities in the genetic control of leaf width across cereals. Three a priori candidate genes for leaf width, previously found to regulate dorsoventrality, were identified based on a 1-cM threshold. This study provides useful physiological and genetic insights for potential manipulation of leaf width to improve plant adaptation to diverse environments.

Estimating Photosynthetic Attributes from High-Throughput Canopy Hyperspectral Sensing in Sorghum.

Sorghum, a genetically diverse C4 cereal, is an ideal model to study natural variation in photosynthetic capacity. Specific leaf nitrogen (SLN) and leaf mass per leaf area (LMA), as well as, maximal rates of Rubisco carboxylation (V cmax), phosphoenolpyruvate (PEP) carboxylation (V pmax), and electron transport (J max), quantified using a C4 photosynthesis model, were evaluated in two field-grown training sets (n = 169 plots including 124 genotypes) in 2019 and 2020. Partial least square regression (PLSR) was used to predict V cmax (R 2 = 0.83), V pmax (R 2 = 0.93), J max (R 2 = 0.76), SLN (R 2 = 0.82), and LMA (R 2 = 0.68) from tractor-based hyperspectral sensing. Further assessments of the capability of the PLSR models for V cmax, V pmax, J max, SLN, and LMA were conducted by extrapolating these models to two trials of genome-wide association studies adjacent to the training sets in 2019 (n = 875 plots including 650 genotypes) and 2020 (n = 912 plots with 634 genotypes). The predicted traits showed medium to high heritability and genome-wide association studies using the predicted values identified four QTL for V cmax and two QTL for J max. Candidate genes within 200 kb of the V cmax QTL were involved in nitrogen storage, which is closely associated with Rubisco, while not directly associated with Rubisco activity per se. J max QTL was enriched for candidate genes involved in electron transport. These outcomes suggest the methods here are of great promise to effectively screen large germplasm collections for enhanced photosynthetic capacity.

First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.

Chemotherapy in combination with immune checkpoint inhibitor (ICI) or bevacizumab has demonstrated a superior effect for non-squamous non-small cell lung cancer (NS-NSCLC). There are still few randomized controlled trials (RCTs) investigating the differences between ICI plus chemotherapy (ICI-chemotherapy) and bevacizumab plus chemotherapy (Bev-chemotherapy) in first-line treatment of NS-NSCLC. We identified RCTs in databases and conference abstracts presented at international conferences by Sep 1, 2021. Bayesian network meta-analysis was performed using randomized effect consistency model to estimate hazard ratio (HR) and odds ratio (OR). The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥ 3 treatment-related adverse events (TRAEs). Fifteen RCTs (17 articles) of 6561 advanced NS-NSCLC patients receiving ICI-chemotherapy, Bev-chemotherapy, or chemotherapy at first-line were eligible for analysis. NMA results showed that first-line ICI-chemotherapy prolonged OS (HR 0.79, 0.66-0.94) in patients with advanced NS-NSCLC compared with Bev-chemotherapy, while no differences were in PFS, ORR, and grade ≥ 3 TRAEs (p > 0.05). Ranking plots suggested that ICI-chemotherapy had the most probability to offer the best OS (probability 0.993), PFS (probability 0.658), and ORR (probability 0.565), and Bev-chemotherapy had the most risks of grade ≥ 3 TRAEs (probability 0.833). Therefore, our findings showed that first-line ICI-chemotherapy was associated with better OS than Bev-chemotherapy in patients with advanced NS-NSCLC, and more clinical trials are warranted to confirm these results.

Efficacy and safety of tuina for senile insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia is a common diseases of the elderly, tuina is a widely used treatment. At present, there is a lack of supportive evidence on efficacy and safety of tuina for senile insomnia. The purpose of this systematic review is to assess the effectiveness and safety of tuina therapy in the treatment of senile insomnia. METHODS: Literature on tuina for senile insomnia in the PubMed, EMBASE, Web of Science, Cochrane, China National Knowledge Infrastructure Database, Wanfang, Chinese Scientific and Journal Database, Japanese medical database, Korean Robotics Institute Summer Scholars, and Thai-Journal Citation Index Center will be conducted to search from the creation of these databases. We will search the databases from the beginning to January 2022. The primary outcome was the Pittsburgh Sleep Quality Index score, and the secondary outcomes included clinical efficacy and safety. RevMan 5.4.1 will be used for the meta-analysis. RESULTS: This study aimed to will prove the effectiveness and safety of tuina therapy for the treatment of insomnia in the elderly. CONCLUSION: This study provides up-to-date evidence of the effectiveness and safety of tuina for the treatment of senile insomnia. INPLASY REGISTRATION NUMBER: INPLASY2021110063. ETHICS AND COMMUNICATION: This systematic review will evaluate the effectiveness and safety of massage therapy for insomnia in the elderly population. As all the included data have been published, systematic reviews do not require ethical approval.

Tuina for perimenopausal insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia in perimenopausal women has a negative impact on quality of life and increases health care costs. With the increasing incidence of the disease, Tuina has been accepted by perimenopausal women. The purpose of this study is to explore the effectiveness and safety of Tuina for perimenopausal insomnia. METHODS: We will search 9 electronic databases: Chinese Biomedical Literature Database, Cochrane Library, China National Knowledge Infrastructure, EMBASE, MEDLINE, Web of Science, PubMed, Wan fang, Chinese Scientific Journal Database, and 1 clinical trials register platform: WHO International Clinical Trials Registry Platform. All relevant randomized controlled trial using Tuina for perimenopausal insomnia will be included. Two reviewers will independently screen date, and meta-analysis will be performed with RevMan (V5.3.5) software. RESULTS: This study will provide an evidence of Tuina for perimenopausal insomnia. CONCLUSION: This study will provide a reliable evidence for the evaluation of the efficacy and side effects of Tuina in the treatment of perimenopausal insomnia. PROSPERO REGISTRATION NUMBER: CRD42021259017. ETHICS AND DISSEMINATION: This systematics review will evaluate the efficacy and safety of tuina in the treatment of perimenopausal insomnia. Since all the data included were published, the systematic review did not require ethical approval.

Genetic control of leaf angle in sorghum and its effect on light interception.

Developing sorghum genotypes adapted to different light environments requires understanding of a plant's ability to capture light, determined through leaf angle specifically. This study dissected the genetic basis of leaf angle in 3 year field trials at two sites, using a sorghum diversity panel (729 accessions). A wide range of variation in leaf angle with medium heritability was observed. Leaf angle explained 36% variation in canopy light extinction coefficient, highlighting the extent to which variation in leaf angle influences light interception at the whole-canopy level. This study also found that the sorghum races of Guinea and Durra consistently having the largest and smallest leaf angle, respectively, highlighting the potential role of leaf angle in adaptation to distinct environments. The genome-wide association study detected 33 quantitative trait loci (QTLs) associated with leaf angle. Strong synteny was observed with previously detected leaf angle QTLs in maize (70%) and rice (40%) within 10 cM, among which the overlap was significantly enriched according to χ2 tests, suggesting a highly consistent genetic control in grasses. A priori leaf angle candidate genes identified in maize and rice were found to be enriched within a 1-cM window around the sorghum leaf angle QTLs. Additionally, protein domain analysis identified the WD40 protein domain as being enriched within a 1-cM window around the QTLs. These outcomes show that there is sufficient heritability and natural variation in the angle of upper leaves in sorghum which may be exploited to change light interception and optimize crop canopies for different contexts.

Efficacy and safety evaluation of acupuncture in the treatment of impaired glucose regulation: A protocol for systematic review and meta-analysis.

BACKGROUND: Impaired of glucose regulation belongs to the stage of prediabetes, which is a state of glucose metabolism between diabetes and normal blood glucose. The prevalence of prediabetes in people over 20 years old in China is significantly higher than that in diabetic patients. If no measures are taken to prevent the transition from prediabetes to diabetes, the number of diabetic patients in China will further increase. This study conducted a meta-analysis of the effectiveness of acupuncture in the treatment of impaired glucose regulation by collecting relevant literatures. METHODS: Nine electronic databases: PubMed, EMBASE, Cochrane library, Web of Science, Google Scholar, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database, Wan Fang database, and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/) will be searched for randomized clinical trails of acupuncture for impaired glucose regulation. The screening process will be developed by 2 independent reviewers, and meta-analysis will be performed with RevMan (V5.3.5) software. RESULTS: This meta-analysis further confirmed the benefits of acupuncture in the treatment of impaired of glucose regulation. CONCLUSION: This study will provide a high-quality evidence of the efficacy and safety of acupuncture on patients with impaired glucose regulation. PROSPERO REGISTRATION NUMBER: INPLASY202170058. ETHICS AND DISSEMINATION: This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of impaired of glucose regulation. Since all the data included were published, the systematic review did not require ethical approval.

Case Report: Osimertinib Followed by Osimertinib Plus Bevacizumab, Personalized Treatment Strategy for a Lung Cancer Patient With a Novel EGFR Exon 20 Insertion D770_N771insGT and Multiple Brain Metastases.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) are the standard of care for non-small cell lung cancer (NSCLC) patients with EGFR exon 19 deletion and L858R mutations. However, no EGFR TKI has been approved for NSCLC patients harboring insertion mutations in EGFR exon 20 (EGFRex20ins), a subgroup of uncommon EGFR mutations resistant to first-generation EGFR TKIs. This unmet clinical challenge is further complicated by disease progression due to brain metastases (BMs), which limits the use of EGFR TKIs with low intracranial activity. Osimertinib, a third-generation EGFR TKI with high CNS activity, has demonstrated superior efficacy as a first-line treatment for EGFR-mutant NSCLC with or without BM. The VEGF pathway is a key mediator of cancer metastasis and resistance to EGFR TKIs. Accumulating evidence has demonstrated that the addition of anti-VEGF agents to EGFR TKIs provides an alternative treatment option for the clinical management of EGFR-mutant NSCLC. We herein report an NSCLC case with a novel EGFRex20ins mutation D770_N771insGT and multiple brain metastases who briefly responded to first-line osimertinib treatment and subsequently achieved prolonged disease control with osimertinib plus bevacizumab as second-line treatment. Our case suggests that osimertinib in combination with bevacizumab may be an effective option for NSCLC patients with specific EGFRex20ins mutations and brain metastases.

Study on the mechanism of regulating the hypothalamic cortical hormone releasing hormone/corticotropin releasing hormone type I receptor pathway by vibro-annular abdominal massage under the brain-intestine interaction in the treatment of insomnia.

BACKGROUND: Insomnia is a common disease associated with different nervous system stress response and endocrine disorders. It has been reported previously that abdominal vibration and ring massage therapy can significantly improve the symptoms of insomnia patients, enhance the activity of neurons. In addition, functional MRI (resting state brain functional magnetic resonance imaging [Rs_fMRI]) of the resting state brain test has proved that the functional connection between hypothalamus and parahippocampal gyrus could be significantly enhanced after abdominal massage treatment. It has been confirmed that there is possible involvement of brain-gut interaction effect in the treatment of insomnia, but there is a lack of research to elucidate the possible mechanisms of brain-gut interaction in the treatment of insomnia. The purpose of this study is to investigate the relationship between the hypothalamus and intestinal interaction in the treatment of insomnia by abdominal massage. METHODS AND DESIGN: A single blind randomized controlled trial will be conducted. Sixty chronic insomnia volunteers and 30 healthy volunteers will be recruited for this study. Sixty insomnia volunteers will be randomly divided into a drug group and a massage group, and 30 healthy volunteers will be assigned to the healthy group. The manipulation of the treatment group will be mainly carried out through abdominal rubbing and vibration massage, once a day, 30 min/time, 5 days for a course of treatment, and a total of 4 intervention courses will be carried out. Patients in the drug group will be given orally spleen-invigorating bolus, twice a day, 1 pill in the morning and 1 pill in the evening. The course of treatment will be carried for 5 days, and a total of 4 courses of treatment will be administered.The massage group will be compared with the healthy group and the drug group by Pittsburgh Sleep Index scale (PSQI), Hyperarousal scale (HAS), Hamilton Depression scale (HAMD), Fatigue scale-14 (FS-14), and Wechsler Adult Memory scale (WAIS) scales using to observe the sleep quality. Rs-fMRI will be used to observe various BOLD signals in the brain and compare the values of Reho, fALFF, and FC. MRS technology will be used to observe the contents of GABA and 5-HT in the hypothalamus. Additionally, the contents of cortical hormone releasing hormone (CRH), adrenocorticotropic hormone (ACTH), COR, GABA, NE, PGE2, and 5-HT in the serum will be also detected. The serum of each group will be taken for 1H nuclear magnetic resonance (1HNMR) metabolomics study to analyze the various common metabolites, differential metabolites, potential metabolic biomarkers, and metabolic pathways among the 3 groups. Finally, in combination with the brain functional imaging and brain spectrum, the potential mechanism of abdominal vibration and ring massage will be discussed. DISCUSSION: The results of this study will be used to possibly elaborate the various mechanisms of brain and intestine interaction in the treatment of insomnia by employing abdomen ring rubbing.

[Research Progress of Circular RNA in Lung Cancer].

Lung cancer is the most common malignant tumor with the highest morbidity and mortality worldwide, and its imposes an insupportable burden on patients due to its poor prognosis. The diagnosis and treatment of lung cancer is under great pressure. Therefore, it is urgent to explore effective therapeutic targets and molecular markers. Circular RNA (circRNA) is a kind of covalently closed non-coding RNAs, which has attracted much attention due to its conservation, stability and tissue specificity. Many studies have found that circRNA participates in the regulation of lung cancer through various mechanisms such as sponging miRNA and plays a part vital role in the early diagnosis, treatment and prognosis evaluation. In recent years, there have been numerous studies on circRNA in lung cancer. This paper summarizes the current progress of circRNA in the diagnosis, treatment and prognosis of lung cancer.
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Pretreatment hemoglobin level as a predictor to evaluate the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.

BACKGROUND: Targeting immune checkpoints represents an immense breakthrough in cancer therapeutics. The prognostic value of hemoglobin (Hb) has been investigated in many malignancies including non-small cell lung cancer (NSCLC). However, the prognostic impact of pretreatment Hb count for immune checkpoint inhibitors (ICIs) in advanced NSCLC patients remains unclear. METHODS: A total of 310 late-stage NSCLC patients who received ICI therapies between January 2015 and March 2019 were prospectively enrolled. We used a propensity score-matched cohort analysis for this study. Patients' clinicopathological characteristics and pretreatment Hb concentration were assessed against the progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: A propensity score (PS)-matched cohort analysis was applied to adjust for potential bias and to create two comparable groups according to patients' clinicopathological characteristics. The patients with normal baseline Hb levels (⩾110 g/L) had significantly longer PFS [median: 10.0 versus 4.0 months, hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46-0.86; p = 0.001] and OS [median: 17.6 versus 10.5 months, HR (95% CI): 0.56 (0.40-0.79); p < 0.001] than those with decreased Hb count (<110 g/L) in a PS-matched cohort (n = 255). For patients with normal pretreatment Hb levels, ICI combination therapy was significantly associated with better PFS [median: 11.1 versus 8.0 months, HR (95% CI): 0.74 (0.50-1.06); p = 0.09] and OS [median: 26.0 versus 12.9 months, HR (95% CI): 0.56 (0.37-0.86); p = 0.008] than monotherapy, but there was no such trend for patients with decreased baseline Hb levels. CONCLUSION: Our findings showed that normal pretreatment Hb count served as a favorable prognostic marker in advanced NSCLC patients treated with ICIs, representing an economical biomarker with readily measuring performance among all reported ones.

Dynamics of Serum Tumor Markers Can Serve as a Prognostic Biomarker for Chinese Advanced Non-small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors.

Background: Serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cytokeratin 19 fragment (CYFRA21-1) and squamous-cell carcinoma-related antigen (SCC-Ag) are routinely used for monitoring the response to chemotherapy or targeted therapy in advanced-stage non-small cell lung cancer (NSCLC), however their role in immunotherapy remains unclear. The aim of this study was to investigate whether dynamics of these serum markers were associated with the efficacy and prognosis of Chinese late-stage NSCLC patients treated with programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors. Methods: We initiated a longitudinal prospective study on advanced NSCLC patients treated with PD-1/PD-L1 inhibitors in Chinese PLA general hospital (Beijing, China). Blood samples of baseline and after 6 weeks' treatment were collected. CT scan were used by all patients to evaluate treatment efficacy according to RECIST 1.1. Serum tumor markers levels were measured with an electrochemical luminescence for SCC-Ag and with a chemiluminescent microparticle immunoassay for serum CEA, CA125, and CYFRA21-1. At least 20% decreases of the biomarkers from baseline were considered as meaningful improvements after 6 weeks of treatment with immune checkpoint inhibitors (ICIs). Optimization-based method was used to balance baseline covariates between different groups. Associations between serum tumor biomarker improvements and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: A total of 308 Chinese patients with advanced NSCLC were enrolled in the study. After balancing baseline covariates, patients with meaningful improvements in <2 out of 4 biomarkers (CEA, CA125, CYFRA21-1, and SCC-Ag) was ended up with lower ORR (0.08 vs. 0.35, p < 0.001), shorten PFS (median: 5.4 vs. 12.5 months, p < 0.001), and OS (median: 11.7 vs. 25.6 months, p < 0.001) in the total population. Subgroup analysis of patients with adenocarcinoma revealed that patients with meaningful improvements in <2 out of 4 biomarkers had significant lower ORR (0.06 vs. 0.36, p < 0.001), shorten PFS (median: 4.1 vs. 11.9 months, p < 0.001), and OS (median: 11.9 vs. 24.2 months, p < 0.001). So as in patients with squamous cell carcinoma, meaningful improvements in at least 2 out of 4 biomarkers were linked to better ORR (0.42 vs. 0.08, p = 0.014), longer PFS (median: 13.1 vs. 5.6 months, p = 0.001), and OS (median: 25.6 vs. 10.9 months, p = 0.06). Conclusions: The dynamic change of CEA, CA125, CYFRA21-1, and SCC-Ag from baseline have prognostic value for late-stage NSCLC patients treated with PD-1/PD-L1 inhibitors. Decrease of associated biomarkers serum levels were associated with favorable clinical outcomes.

Immunotherapy beyond progression in patients with advanced non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent a great breakthrough in the treatment of advanced non-small cell lung cancer (aNSCLC). However, whether immunotherapy beyond progression (IBP) is effective for aNSCLC has yet to be established. Therefore, a retrospective clinical study was conducted to investigate the efficacy of IBP in patients with aNSCLC under real-world conditions. METHODS: A total of 125 Chinese patients with aNSCLC who experienced progressive disease (PD) after receiving monotherapy or combination therapy (combined with chemotherapy or/and antiangiogenic therapy) with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors between January 2015 and March 2019 were enrolled. Patients who were treated with ICIs for more than 6 weeks after PD were defined as IBP (n=39), while those who received ICI treatment for less than 6 weeks or discontinued it due to PD were defined as non-IBP (n=86). Patient clinical characteristics were evaluated. An optimization-based method was applied to balance the clinical baseline characteristics between the two groups. RESULTS: In total population, the IBP group had longer overall survival (median OS, 26.6 vs. 9.5 months; HR, 0.40; 95% CI: 0.23-0.69; P<0.001) and progression-free survival (median PFS, 8.9 vs. 4.1 months; HR, 0.41; 95% CI: 0.26-0.65; P<0.001), compared with the non-IBP group. Despite no significant difference in objective response rate (ORR, 15.4% vs. 11.6%, P=0.560), disease control rate (DCR) was significantly higher in the IBP group (89.7% vs. 61.6%, P<0.001). After balancing baseline covariates, the IBP group also had longer OS (median: 26.6 vs. 10.7 months; HR, 0.40; 95% CI: 0.19-0.84; P=0.015) and PFS (median: 9.7 vs. 4.3 months; HR, 0.28; 95% CI: 0.15-0.51; P<0.001), with a benefit in either of patients previously treated with ICI monotherapy or in combination therapy and with non-response to the previously ICI. CONCLUSIONS: IBP is associated with longer OS and PFS in patients with aNSCLC. Our findings may suggest new therapeutic options for patients with aNSCLC who experienced disease progression after initial immunotherapy.

Mesoporous silica induces hippocampal neurons cell autophagy through AMPK/mTOR/P70S6K signaling pathway.

Mesoporous silica is a drug carrier with strong targeting, large loading capacity, and easy modification of its surface while its toxicity draws increasing attention recently. In this study, we evaluated the impact of SBA-15 nanomaterials on hippocampal neurons. We found that SBA-15 induces oxidative damage to hippocampal neurons HT22, which further activates autophagy. Treatment with the mammalian target of rapamycin (mTOR) inhibitor AZD8055, the phosphorylation level of mTOR and P70S6K reduced and increased levels of p-AMPK meaning that the adenosine-activated protein kinase (AMPK)/mTOR/P70S6K pathway is involved in SBA-15 induced autophagy of HT22. These results suggested that mesoporous silica material SBA-15 might affect central nervous cells via oxidative stress activation of the AMPK/mTOR/P70S6K pathway, which provides a theoretical basis for safe administration of such materials in patients.

[Advances in the Influence of EGFR Mutation on the PD-L1 Expression in Non-small Cell Lung Cancer].

Researches on the inhibitors of programmed death-1 (PD-1) and programmed death-1 ligand (PD-L1) enjoy considerable breakthroughs in recent years, which has brought relative changes in the therapeutic model of non-small cell lung cancer (NSCLC) at an unexpected speed. However, it seems that PD-1/PD-L1 inhibitors are less effective in patients with epidermal growth factor receptor (EGFR) mutation than those without. Previous studies have shown that the expression rate of PD-L1 on tumor cells is correlated with the therapeutic effect of PD-1/PD-L1 inhibitors. Yet, there is no complete agreement on the effect of EGFR mutation on PD-L1 expression. In this review, relevant studies will be summarized with an expectation of making some contributions to basic researches and to the clinical treatment.

Adjusting cotton planting density under the climatic conditions of Henan Province, China.

The growth and development of cotton are closely related to climatic variables such as temperature and solar radiation. Adjusting planting density is one of the most effective measures for maximizing cotton yield under certain climatic conditions. The objectives of this study were (1) to determine the optimum planting density and the corresponding leaf area index (LAI) and yield under the climatic conditions of Henan Province, China, and (2) to learn how climatic conditions influence cotton growth, yield, and yield components. A three-year (2013-2015) field experiment was conducted in Anyang, Henan Province, using cultivar SCRC28 across six planting density treatments: 15,000, 33,000, 51,000, 69,000, 87,000, and 105,000 plants ha-1. The data showed that the yield attributes, including seed cotton yield, lint yield, dry matter accumulation, and the LAI, increased as planting density increased. Consequently, the treatment of the maximum density with 105,000 plants ha-1 was the highest-yielding over three years, with the LAIs averaged across the three years being 0.37 at the bud stage, 2.36 at the flower and boll-forming stage, and 1.37 at the boll-opening stage. Furthermore, the correlation between the cotton yield attributes and meteorological conditions indicated that light interception (LI) and the diurnal temperature range were the climatic factors that most strongly influenced cotton seed yield. Moreover, the influence of the number of growing degree days (GDD) on cotton was different at different growth stages. These observations will be useful for determining best management practices for cotton production under the climatic conditions of Henan Province, China.

How do cotton light interception and carbohydrate partitioning respond to cropping systems including monoculture, intercropping with wheat, and direct-seeding after wheat?

Different cotton (Gossypium hirsutum L.)-wheat (Triticum aestivum) planting patterns are widely applied in the Yellow River Valley of China, and crop yield mainly depends on light interception. However, little information is available on how cotton canopy light capturing and yield distribution are affected by planting patterns. Hence, field experiments were conducted in 2016 and 2017 to study the response of cotton canopy light interception, square and boll distribution, the leaf area index (LAI) and biomass accumulation to three planting patterns: a cotton monoculture (CM, planted on 15 May) system, a cotton/wheat relay intercropping (CWI, planted on 15 May) system, in which three rows of wheat rows were intercropped with one row of cotton, and a system in which cotton was directly seeded after wheat (CWD, planted on 15 June). The following results were obtained: 1) greater light capture capacity was observed for cotton plants in the CM and CWI compared with the CWD, and the light interception of the CM was 22.4% and 51.4% greater than that of the CWI and CWD, respectively, at 30 days after sowing (DAS) in 2016; 2) more bolls occurred at the first sympodial position (SP) than at other SPs for plants in the CM; 3) based on the LAI and biomass accumulation, the cotton growth rate was the greatest in CWD, followed by CM and CWI; and 4) the CM produced significantly greater yields than did the other two treatments because it yielded more bolls and greater boll weight. Information on the characteristics of cotton growth and development in response to different planting patterns would be helpful for understanding the response of cotton yields to planting patterns and would facilitate the improvement of cotton productivity.