Melatonin Increases Root Cell Wall Phosphorus Reutilization via an NO Dependent Pathway in Rice (Oryza sativa).

Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.

Prevalence of nontuberculous mycobacteria and the emergence of rare species in Henan Province, China.

Nontuberculous mycobacteria (NTM) is a large group of mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. Epidemiological investigations have found that the incidence of NTM infections is increasing in China, and it is naturally resistant to many antibiotics. Therefore, studies of NTM species in clinical isolates are useful for understanding the epidemiology of NTM infections. The present study aimed to investigate the incidence of NTM infections and types of NTM species. Of the 420 samples collected, 285 were positive for M. tuberculosis, 62 samples were negative, and the remaining 73 samples contained NTM, including 35 (8.3%) only NTM and 38 (9%) mixed (M. tuberculosis and NTM). The most prevalent NTM species were Mycobacterium intracellulare (30.1%), followed by Mycobacterium abscessus (15%) and M. triviale (12%). M. gordonae infection was detected in 9.5% of total NTM-positive cases. Moreover, this study reports the presence of Mycobacterium nonchromogenicum infection and a high prevalence of M. triviale for the first time in Henan. M. intracellulare is the most prevalent, accompanied by some emerging NTM species, including M. nonchromogenicum and a high prevalence of M. triviale in Henan Province. Monitoring NTM transmission and epidemiology could enhance mycobacteriosis management in future.

Novel automated AIMLAM for diagnosis of Mycobacterium tuberculosis.

Aim: A rapid and precise diagnostic method is crucial for timely intervention and management of tuberculosis. The present study compared the diagnostic accuracy of a novel lipoarabinomannan (LAM) antigen test, AIMLAM, for tuberculosis in urine samples. Methodology: The study subjected 106 TB suspects to smear microscopy, MGIT, GeneXpert and AIMLAM. Results: Among 106, smear microscopy identified 36 as positive (33%) (sensitivity; 70.93%, 95% CI (60.14-80.22%), while MGIT showed 38 positive (36.8%). GeneXpert detected 59 positives (sensitivity; 96.83, 95% CI (89.00-99.61%)). AIMLAM declared 61 as positive (57.5%) (sensitivity; 100.00, 95% CI (94.13-100.00%) and 45 as negative (42.5%). Conclusion: Overall, AIMLAM demonstrated better diagnostic accuracy than GeneXpert Assay, smear microscopy and MGIT liquid culture in urine samples.

This study describes a new way to detect tuberculosis, called AIMLAM. Unlike traditional methods that use sputum or blood, AIMLAM tests urine samples and bodily fluids. It is automated and uses easily accessible samples to identify a tuberculosis infection, so may be a convenient and noninvasive option for healthcare providers. The test shows promising results in terms of accuracy and sensitivity.

A novel aldo-keto reductase gene, OsAKR1, from rice confers higher tolerance to cadmium stress in rice by an in vivo reactive aldehyde detoxification.

Elevated levels of cadmium (Cd) have the ability to impede plant development. Aldo-keto reductases (AKRs) have been demonstrated in a number of plant species to improve tolerance to a variety of abiotic stresses by scavenging cytotoxic aldehydes; however, only a few AKRs have been identified to improve Cd tolerance. The OsAKR1 gene was extracted and identified from rice here. After being exposed to Cd, the expression of OsAKR1 dramatically rose in both roots and shoots, although more pronounced in roots. According to a subcellular localization experiment, the nucleus and cytoplasm are where OsAKR1 is primarily found. Mutants lacking OsAKR1 exhibited Cd sensitive phenotype than that of the wild-type (WT) Nipponbare (Nip), and osakr1 mutants exhibited reduced capacity to scavenge methylglyoxal (MG). Furthermore, osakr1 mutants exhibited considerably greater hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, and increased catalase (CAT) activity in comparison to Nip. The expression of three isomeric forms of CAT was found to be considerably elevated in osakr1 mutants during Cd stress, as demonstrated by quantitative real-time PCR analysis, when compared to Nip. These results imply that OsAKR1 controlled rice's ability to withstand Cd by scavenging harmful aldehydes and turning on the reactive oxygen species (ROS) scavenging mechanism.

Brassinosteroid decreases cadmium accumulation via regulating gibberellic acid accumulation and Cd fixation capacity of root cell wall in rice (Oryza sativa).

The precise mechanism behind the association between plants' reactions to cadmium (Cd) stress and brassinosteroid (BR) remains unclear. In the current investigation, Cd stress quickly increased the endogenous BR concentration in the rice roots. Exogenous BR also increased the hemicellulose level in the root cell wall, which in turn increased its capacity to bind Cd. Simultaneously, the transcription level of genes responsible for root Cd absorption was decreased, including Natural Resistance-Associated Macrophage Protein 1/5 (OsNRAMP1/5) and a major facilitator superfamily gene called OsCd1. Ultimately, the increased expression of Heavy Metal ATPase 3 (OsHMA3) and the decreased expression of OsHMA2, which was in charge of separating Cd into vacuoles and translocating Cd to the shoots, respectively, led to a decrease in the amount of Cd that accumulated in the rice shoots. In contrast, transgenic rice lines overexpressing OsGSK2 (a negative regulator in BR signaling) accumulated more Cd, while OsGSK2 RNA interference (RNAi) rice line accumulated less Cd. Furthermore, BR increased endogenous Gibberellic acid (GA) level, and applying GA could replicate its alleviative effect. Taken together, BR decreased Cd accumulation in rice by mediating the cell wall's fixation capacity to Cd, which might relied on the buildup of the GA.

Efficacy and prognosis comparison of first-line treatment with EGFR-TKI versus chemotherapy for non-small cell lung cancer patients harboring EGFR rare mutation / 肿瘤研究与临床

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

Molecular phylogeny and inflorescence evolution of Prunus (Rosaceae) based on RAD-seq and genome skimming analyses.

Prunus is an economically important genus widely distributed in the temperate Northern Hemisphere. Previous studies on the genus using a variety of loci yielded conflicting phylogenetic hypotheses. Here, we generated nuclear reduced representation sequencing data and plastid genomes for 36 Prunus individuals and two outgroups. Both nuclear and plastome data recovered a well-resolved phylogeny. The species were divided into three main clades corresponding to their inflorescence types, - the racemose group, the solitary-flower group and the corymbose group - with the latter two sister to one another. Prunus was inferred to have diversified initially in the Late Cretaceous around 67.32 million years ago. The diversification of the three major clades began between the Paleocene and Miocene, suggesting that paleoclimatic events were an important driving force for Prunus diversification. Ancestral state reconstructions revealed that the most recent common ancestor of Prunus had racemose inflorescences, and the solitary-flower and corymb inflorescence types were derived by reduction of flower number and suppression of the rachis, respectively. We also tested the hybrid origin hypothesis of the racemose group proposed in previous studies. Prunus has undergone extensive hybridization events, although it is difficult to identify conclusively specific instances of hybridization when using SNP data, especially deep in the phylogeny. Our study provides well-resolved nuclear and plastid phylogenies of Prunus, reveals substantial cytonuclear discord at shallow scales, and sheds new light on inflorescence evolution in this economically important lineage.

Opposite effects of positive and negative symptoms on resting-state brain networks in schizophrenia.

Schizophrenia is a severe psychotic disorder characterized by positive and negative symptoms, but their neural bases remain poorly understood. Here, we utilized a nested-spectral partition (NSP) approach to detect hierarchical modules in resting-state brain functional networks in schizophrenia patients and healthy controls, and we studied dynamic transitions of segregation and integration as well as their relationships with clinical symptoms. Schizophrenia brains showed a more stable integrating process and a more variable segregating process, thus maintaining higher segregation, especially in the limbic system. Hallucinations were associated with higher integration in attention systems, and avolition was related to a more variable segregating process in default-mode network (DMN) and control systems. In a machine-learning model, NSP-based features outperformed graph measures at predicting positive and negative symptoms. Multivariate analysis confirmed that positive and negative symptoms had opposite effects on dynamic segregation and integration of brain networks. Gene ontology analysis revealed that the effect of negative symptoms was related to autistic, aggressive and violent behavior; the effect of positive symptoms was associated with hyperammonemia and acidosis; and the interaction effect was correlated with abnormal motor function. Our findings could contribute to the development of more accurate diagnostic criteria for positive and negative symptoms in schizophrenia.

Metabolic engineering of Saccharomyces cerevisiae for glycerol utilization.

Due to its wide availability, glycerol is considered as a promising alternative feedstock for microbial fermentation. As a model eukaryote, Saccharomyces cerevisiae is commonly adopted for bioproduction of various bulk and value-added chemicals, but it does not efficiently utilize glycerol. In this review, the metabolic pathway of glycerol and its regulation in S. cerevisiae are first introduced. Then, strategies, including metabolic engineering of the endogenous pathway, introduction of exogenous pathways, adaptive evolution, and reverse metabolic engineering, are summarized for improving the glycerol utilization in S. cerevisiae. Finally, methods for further improving glycerol utilization by S. cerevisiae are proposed. This review provides insights for designing engineered S. cerevisiae for efficient utilization of glycerol.

Segregation, integration and balance in resting-state brain functional networks associated with bipolar disorder symptoms.

Bipolar disorder (BD) is a serious mental disorder involving widespread abnormal interactions between brain regions, and it is believed to be associated with imbalanced functions in the brain. However, how this brain imbalance underlies distinct BD symptoms remains poorly understood. Here, we used a nested-spectral partition (NSP) method to study the segregation, integration, and balance in resting-state brain functional networks in BD patients and healthy controls (HCs). We first confirmed that there was a high deviation in the brain functional network toward more segregation in BD patients than in HCs and that the limbic system had the largest alteration. Second, we demonstrated a network balance of segregation and integration that corresponded to lower anxiety in BD patients but was not related to other symptoms. Subsequently, based on a machine-learning approach, we identified different system-level mechanisms underlying distinct BD symptoms and found that the features related to the brain network balance could predict BD symptoms better than graph theory analyses. Finally, we studied attention-deficit/hyperactivity disorder (ADHD) symptoms in BD patients and identified specific patterns that distinctly predicted ADHD and BD scores, as well as their shared common domains. Our findings supported an association of brain imbalance with anxiety symptom in BD patients and provided a potential network signature for diagnosing BD. These results contribute to further understanding the neuropathology of BD and to screening ADHD in BD patients.

Study on mechanism of Bupi Yichang pill in alleviating experimental ulcerative colitis by restoring the homeostasis of CD4+T cell subpopulations / 天津医药

Objective To investigate the regulatory effect of Bupi Yichang pill(BPYCP)on CD4+T cell subsets of ulcerative colitis(UC)mice.Methods Forty-eight C57BL/6 mice were randomly divided into 4 groups:the control group(n=10),the model group(DSS group,n=13),the model +BPYCP group(DSS+BPYCP group,n=13)and the model+ mesalazine(5-ASA)group(DSS+5-ASA group,n=12).The mouse UC model was induced by 2.5%dextrosan sulfate(DSS)solution.The DSS+BPYCP group and the DSS+5-ASA group were given BPYCP or 5-ASA for 2 weeks,respectively,and fecal viscosity and blood in stool were observed.The colon length was measured.Colonic mass index and unit colonic mass index were calculated.Hematoxylin-eosin(HE)staining was used to observe pathological changes of colon and to score the pathological tissue damage.The level of CD4+T cell subsets in mesenteric lymph nodes was detected by flow cytometry.The expression levels of cytokines interferon-γ(INF-γ),interleukin(IL-4),IL-17A,IL-10 and IL-21 secreted by CD4+T cell subsets in colon tissue were detected by ELISA.Real-time fluorescence quantitative PCR was used to detect colon tissue CD4+T cell subset nuclear transcription factors,mRNA expression levels of T-frame protein 21(T-bet),GatA-binding protein 3(GATA-3),retinoa-associated nuclear orphan receptor γt(RORγt),B cell lymphoma-6(Bcl-6)and Foxp3 in rats.Results Compared with the DSS group,the diarrhea and hematostoecium symptoms of UC mice in the DSS+BPYCP group and the DSS+5-ASA group were significantly improved,body weight and colon length of mice were increased,and colon mass,colon mass index and unit colon mass index were decreased(P＜0.05).The mucosal epithelium was more complete than that in the DSS group,and gland arrangement was more regular.The inflammatory cell infiltration was less,and the pathological tissue damage score was significantly decreased(P＜0.01).The proportion of Th2 cells in mesenteric lymph nodes was decreased,the proportion of Th17 cells and the level of IL-17A were decreased,and the mRNA levels of T-bet,GATA-3,RORγt and Bcl-6 in colon tissue were decreased(P＜0.05).In the DSS+BPYCP group,the proportion of Th1 cells decreased,the proportion of CD4+CD25+Treg cells,CD4+CD25+Foxp3+Treg cells and the level of IL-10 increased,and the proportion of CD4+CXCR5+Tfh cells and the level of IL-21 decreased.The level of Foxp3 mRNA increased(P＜0.05).The proportion of Th1 cells and the level of IFN-γ were decreased in the DSS+5-ASA group(P＜0.05).Conclusion BPYCP may alleviate UC by remodeling the homeostasis of CD4+T cell subpopulations.

Recognition of abnormal changes in echocardiographic videos by an artificial intelligence assisted diagnosis model based on 3D CNN / 中华心血管病杂志

Objective: To investigate the diagnostic efficiency and clinical application value of an artificial intelligence-assisted diagnosis model based on a three-dimensional convolutional neural network (3D CNN) on echocardiographic videos of patients with hypertensive heart disease, chronic renal failure (CRF) and hypothyroidism with cardiac involvement. Methods: This study is a retrospective study. The patients with hypertensive heart disease, CRF and hypothyroidism with cardiac involvement, who admitted in Henan Provincial People's Hospital from April 2019 to October 2021, were enrolled. Patients were divided into hypertension group, CRF group, and hypothyroidism group. Additionally, a simple random sampling method was used to select control healthy individuals, who underwent physical examination at the same period. The echocardiographic video data of enrolled participants were analyzed. The video data in each group was divided into a training set and an independent testing set in a ratio of 5 to 1. The temporal and spatial characteristics of videos were extracted using an inflated 3D convolutional network (I3D). The artificial intelligence assisted diagnosis model was trained and tested. There was no case overlapped between the training and validation sets. A model was established according to cases or videos based on video data from 3 different views (single apical four chamber (A4C) view, single parasternal left ventricular long-axis (PLAX) view and all views). The statistical analysis of diagnostic performance was completed to calculate sensitivity, specificity and area under the ROC curve (AUC). The time required for the artificial intelligence and ultrasound physicians to process cases was compared. Results: A total of 730 subjects aged (41.9±12.7) years were enrolled, including 362 males (49.6%), and 17 703 videos were collected. There were 212 cases in the hypertensive group, 210 cases in the CRF group, 105 cases in the hypothyroidism group, and 203 cases in the normal control group. The diagnostic performance of the model predicted by cases based on single PLAX view and all views data was excellent: (1) in the hypertensive group, the sensitivity, specificity and AUC of models based on all views data were 97%, 89% and 0.93, respectively, while those of models based on a single PLAX view were 94%, 95%, and 0.94, respectively; (2) in the CRF group, the sensitivity, specificity and AUC of models based on all views data were 97%, 95% and 0.96, respectively, while those of models based on a single PLAX view were 97%, 89%, and 0.93, respectively; (3) in the hypothyroidism group, the sensitivity, specificity and AUC of models based on all views data were 64%, 100% and 0.82, respectively, while those of models based on a single PLAX view were 82%, 89%, and 0.86, respectively. The time required for the 3D CNN model to measure and analyze the echocardiographic videos of each subject was significantly shorter than that for the ultrasound physicians ((23.96±6.65)s vs. (958.25±266.17)s, P<0.001). Conclusions: The artificial intelligence assisted diagnosis model based on 3D CNN can extract the dynamic temporal and spatial characteristics of echocardiographic videos jointly, and quickly and efficiently identify hypertensive heart disease and cardiac changes caused by CRF and hypothyroidism.

Towards crucial post-modification in biosynthesis of terpenoids and steroids: C3 oxidase and acetyltransferase.

Terpenoids and steroids are two large families of natural products with diverse biological activities. C3 oxidase and acetyltransferase are the key enzymes in the post-modification of terpenoids and steroids, while their discovery is of great importance for the efficient bioproduction and wide application of these natural products. In this review, we first explain the reaction mechanism of typical enzymes. Next, we summarize the current state-of-art strategies in the discovery of C3 oxidase and acetyltransferase, and discuss rational engineering of these enzymes with novel catalytic functions. Finally, we propose how to obtain an excellent biocatalyst of C3 oxidase and acetyltransferase by exploiting the discovery strategy and the reaction mechanism.

The complete chloroplast genome sequence of Zygophyllum kansuense Y. X. Liou (Zygophyllaceae).

Zygophyllum kansuense Y. X. Liou is a localized species and endemic to China. In this study, the complete chloroplast genome of Z. kansuense was sequenced and described. The length of complete chloroplast genome was 105,383 base pairs (bp) for Z. kansuense, the genome with 33.8% GC content, containing a large single-copy (LSC) of 79,594 bp, a small single-copy (SSC) of 17,061 bp, and a pair of inverted repeats (IRs) of 4,364 bp. The genome contains 112 genes, including 75 protein-coding genes, 33 tRNA genes, and four rRNA genes. The phylogenetic analysis indicated that Z. kansuense and others of Zygophyllum clustered into one clade with a high support value.

Tension zone trapped by exogenous cline: Analysis of a narrow hybrid zone between two parapatric Oxytropis species (Fabaceae).

Hybrid zones have been widely highlighted for their interest in understanding evolutionary processes. It is generally accepted that hybrid zones can be maintained in a balance between dispersal and selection. However, the selective forces can either be endogenous (i.e., genetic incompatibilities between parental taxa) or exogenous (i.e., parental taxa are adapted to different environments). In this study, we evaluated these alternatives and determined the maintenance of a narrow hybrid zone between parapatric distributed Oxytropis diversifolia and O. leptophylla in Nei Mongol, China. For 507 individuals sampled from two populations in the hybrid zone, 12 O. diversifolia populations and five O. leptophylla populations, we measured leaf-morphological characteristics, quantified genetic structure using 11 nuclear microsatellite loci and five chloroplast DNA intergenic regions, collected micro- and macrohabitat data, and conducted geographical cline analysis. We found that the two species differed in leaf morphology, and putative hybrids showed either intermediacy or a bias to O. diversifolia. Parental taxa formed two genetically distinct clusters, while populations in the hybrid zone consisted of both parental forms and various admixed individuals, exhibiting a bimodal pattern. The hybrid zone was coupled to ecological transitions of both microhabitat (i.e., the slope) and macroclimatic conditions. However, the genetic clines were significantly narrower than the environmental cline. Our results indicate that endogenous selection can be primarily responsible for maintaining the hybrid zone, while local adaptation accounts for the position of the zone. We further suggest the probable outcome of hybridization could be introgression.

Effect of timing of immune checkpoint inhibitor monotherapy and application of hormone on the efficacy and safety of brain metastasis in advanced non-small cell lung cancer: a Meta-analysis / 肿瘤研究与临床

Objective:To evaluate the efficacy and safety of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) monotherapy for brain metastasis in advanced non-small cell lung cancer (NSCLC), and to explore the timing of immunomonotherapy and the application of hormone on the efficacy of ICI.Methods:By searching literature in CNKI, Wanfang, VIP, PubMed, CBM, Embase, Cochrane Library and Web of Science databases, the advanced NSCLC patients with brain metastasis who received ICI treatment were identified, including patients with symptomatic brain metastasis who had received hormone therapy or brain surgery or radiotherapy. Meta-analysis was performed on the collected data to evaluate the systemic objective response rate (sORR) and intracerebral tumor objective response rate (iORR), the iORR of whether ICI monotherapy was first-line therapy, and the iORR of whether hormone was used were evaluated, and the incidence of adverse reactions was evaluated.Results:Fifteen studies were finally included, with a total of 4 033 patients, including 917 patients with brain metastasis. The iORR of immunomonotherapy was 26% (95% CI 19%-34%) and the sORR was 28% (95% CI 18%-40%). The iORR of first-line immunomonotherapy was 49% (95% CI 39%-58%). The iORR of symptomatic patients with hormone therapy and asymptomatic patients without hormone therapy was 26% (95% CI 20%-33%) and 19% (95% CI 16%-22%), respectively. The overall incidence of grade 3-4 adverse reactions was 14% (95% CI 11%-17%). Conclusions:The efficacy of ICI monotherapy in the first-line treatment of PD-L1-positive NSCLC patients with brain metastasis is better than that in the subsequent line therapy, and the application of hormone does not affect the efficacy of ICI. ICI monotherapy in the treatment of advanced NSCLC patients with brain metastasis is safe.

Flexible Brain Transitions Between Hierarchical Network Segregation and Integration Associated With Cognitive Performance During a Multisource Interference Task.

Cognition involves locally segregated and globally integrated processing. This process is hierarchically organized and linked to evidence from hierarchical modules in brain networks. However, researchers have not clearly determined how flexible transitions between these hierarchical processes are associated with cognitive performance. Here, we designed a multisource interference task (MSIT) and introduced the nested-spectral partition (NSP) method to detect hierarchical modules in brain functional networks. By defining hierarchical segregation and integration across multiple levels, we showed that the MSIT requires higher network segregation in the whole brain and most functional systems but generates higher integration in the control system. Meanwhile, brain networks have more flexible transitions between segregated and integrated configurations in the task state. Crucially, higher functional flexibility in the resting state, less flexibility in the task state and more efficient switching of the brain from resting to task states were associated with better task performance. Our hierarchical modular analysis was more effective at detecting alterations in functional organization and the phenotype of cognitive performance than graph-based network measures at a single level.

Effect of short hairpin RNA lentivirus-mediated silencing of pleomorphic adenoma gene like-2 on proliferation, migration and invasion of hepatocellular carcinoma cells / 解剖学报

Objective To investigate the effect of short hairpin RNA(shRNA)-mediated pleomorphic adenoma gene like-2 (PALAG2) silencing on the malignant behavior of hepatocellular carcinoma cells and its mechanism. Methods Real-time PCR and Western blotting were used to detect the expression level of PLAGL2 in liver cancer tissues and adjacent tissues. Hepatoma cells MHCC97-L were cultured in vitro, the lentiviral vector plasmid PLAGL2-shRNA and control NC-shRNA were constructed, transfected into MHCC97-L cells, and stable transfected strains were selected with puromycin. CCK-8 and Transwell chamber assay detected the proliferation activity and the number of migration and invasion of MHCC97-L cells after silencing PLAGL2. Western blotting was used to detect the expression of p-PI3K and p-Akt proteins. The PI3K/ Akt signaling pathway activator was used to treat MHCC97-L cells to detect cell proliferation, migration and invasion. Results The expression of PLAGL2 was significantly increased in liver cancer tissue (P < 0. 05). Transfection of 9 strains of MHCC97-L cells with PLAGL2-shRNA could significantly reduce the expression level of PLAGL2, and the ability of proliferation, migration, and invasion of MHCC97-L cells was also weakened (P<0. 05), and the expression levels of p-PI3K, and p-Akt were inhibited (P<0. 05), PI3K/ Akt activator could obviously reverse the above phenomenon. Conclusion shRNA lentiviral vector pathway can effectively silence the expression of PLAGL2 gene in hepatocarcinoma cells. Silencing of PLAGL2 can significantly inhibit the malignant behavior of proliferation, migration and invasion of hepatocarcinoma cells, and its mechanism may be related to the inhibition of PI3K / Akt signaling pathway activation.

Duodenal ulcer caused by coil wiggle after digital subtraction angiography-guided embolization: A case report.

BACKGROUND: Acute gastrointestinal bleeding (GIB) is a life-threatening medical emergency with high morbidity and mortality. Transcatheter embolization with endovascular coils under digital subtraction angiography guidance is a common and effective method for the treatment of GIB with high technical success rates. Duodenal ulcers caused by coils wiggled from the branch of the gastroduodenal artery, which is a rare complication, have not previously been reported in a patient with right intrathoracic stomach. CASE SUMMARY: A 62-year-old man had undergone thoracoscopy-assisted radical resection of esophageal cancer and gastroesophageal anastomosis 3 years ago, resulting in right intrathoracic stomach. He was admitted to the hospital 15 mo ago for dizziness and suffered acute GIB during his stay. Interventional surgery was urgently performed to embolize the branch of the gastroduodenal artery with endovascular coils. After 15 mo, the patient was re-admitted with a chief complaint of melena for 2 d, esophagogastroduodenoscopy and abdominal computed tomography revealed that some endovascular coils had migrated into the duodenal bulb, leading to a deep ulcer. Bleeding was controlled after conservative treatment. Seven months later, duodenal balloon dilatation was performed to relieve the stenosis after the removal of a few coils, and the patient was safely discharged with only one coil retained in the duodenum due to difficulties in complete removal and risk of bleeding. Mild melena recurred once during the long-term follow-up. CONCLUSION: Although rare, coil wiggle after interventional therapy requires careful attention, effective precautionary measures, and more secure alternative treatment methods.