PancanQTLv2.0: a comprehensive resource for expression quantitative trait loci across human cancers.

Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in cancer. We further integrated the latest GWAS Catalog and identified a total of 84 592 135 linkage associations between eQTLs and the existing GWAS loci, which represents a remarkable ∼50-fold increase compared to the previous version. Additionally, PancanQTLv2.0 uncovered 659516 associations between eQTLs and drug response and identified 146948 associations between eQTLs and immune cell abundance, providing potentially clinical utility of eQTLs in cancer therapy. PancanQTLv2.0 expanded the resources available for investigating gene expression regulation in human cancers, leading to advancements in cancer research and precision oncology.

Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae.

As one of the most successful pathogenic organisms, Vibrio cholerae (V. cholerae) has evolved sophisticated regulatory mechanisms to overcome host stress. During long-term colonization by V. cholerae in adult mice, many spontaneous nonmotile mutants (approximately 10% at the fifth day post-infection) were identified. These mutations occurred primarily in conserved regions of the flagellar regulator genes flrA, flrC, and rpoN, as shown by Sanger and next-generation sequencing, and significantly increased fitness during colonization in adult mice. Intriguingly, instead of key genes in DNA repair systems (mutS, nfo, xthA, uvrA) or ROS and RNS scavenging systems (katG, prxA, hmpA), which were generally thought to be associated with bacterial mutagenesis, we found that deletion of the cyclin gene dps significantly increased the mutation rate (up to 53% at the fifth day post-infection) in V. cholerae. We further determined that the dpsD65A and dpsF46E point mutants showed a similar mutagenesis profile as the Δdps mutant during long-term colonization in mice, which strongly indicated that the antioxidative function of Dps directly contributes to the development of V. cholerae nonmotile mutants. Methionine metabolism pathway may be one of the mechanism for ΔflrA, ΔflrC and ΔrpoN mutant increased colonization in adult mice. Our results revealed a new phenotype in which increased fitness of V. cholerae in the host gut via spontaneous production nonmotile mutants regulated by cyclin Dps, which may represent a novel adaptation strategy for directed evolution of pathogens in the host.

The velvet family proteins mediate low resistance to isoprothiolane in Magnaporthe oryzae.

Isoprothiolane (IPT) resistance has emerged in Magnaporthe oryzae, due to the long-term usage of IPT to control rice blast in China, yet the mechanisms of the resistance remain largely unknown. Through IPT adaptation on PDA medium, we obtained a variety of IPT-resistant mutants. Based on their EC50 values to IPT, the resistant mutants were mainly divided into three distinct categories, i.e., low resistance (LR, 6.5 ≤ EC50 < 13.0 µg/mL), moderate resistance 1 (MR-1, 13.0 ≤ EC50 < 25.0 µg/mL), and moderate resistance 2 (MR-2, 25.0 ≤ EC50 < 35.0 µg/mL). Molecular analysis of MoIRR (Magnaporthe oryzae isoprothiolane resistance related) gene demonstrated that it was associated only with the moderate resistance in MR-2 mutants, indicating that other mechanisms were associated with resistance in LR and MR-1 mutants. In this study, we mainly focused on the characterization of low resistance to IPT in M. oryzae. Mycelial growth and conidial germination were significantly reduced, indicating fitness penalties in LR mutants. Based on the differences of whole genome sequences between parental isolate and LR mutants, we identified a conserved MoVelB gene, encoding the velvet family transcription factor, and genetic transformation of wild type isolate verified that MoVelB gene was associated with the low resistance. Based on molecular analysis, we further demonstrated that the velvet family proteins VelB and VeA were indispensable for IPT toxicity and the deformation of the VelB-VeA-LaeA complex played a vital role for the low IPT-resistance in M. oryzae, most likely through the down-regulation of the secondary metabolism-related genes or CYP450 genes to reduce the toxicity of IPT.

Non-volatile metabolites mediate plant interactions with insect herbivores.

Non-volatile metabolites constitute the bulk of plant biomass. From the perspective of plant-insect interactions, these structurally diverse compounds include nutritious core metabolites and defensive specialized metabolites. In this review, we synthesize the current literature on multiple scales of plant-insect interactions mediated by non-volatile metabolites. At the molecular level, functional genetics studies have revealed a large collection of receptors targeting plant non-volatile metabolites in model insect species and agricultural pests. By contrast, examples of plant receptors of insect-derived molecules remain sparse. For insect herbivores, plant non-volatile metabolites function beyond the dichotomy of core metabolites, classed as nutrients, and specialized metabolites, classed as defensive compounds. Insect feeding tends to elicit evolutionarily conserved changes in plant specialized metabolism, whereas its effect on plant core metabolism varies widely based the interacting species. Finally, several recent studies have demonstrated that non-volatile metabolites can mediate tripartite communication on the community scale, facilitated by physical connections established through direct root-to-root communication, parasitic plants, arbuscular mycorrhizae and the rhizosphere microbiome. Recent advances in both plant and insect molecular biology will facilitate further research on the role of non-volatile metabolites in mediating plant-insect interactions.

Hsa_circ_0005397 promotes hepatocellular carcinoma progression through EIF4A3.

PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.

Immunological signatures and predictive biomarkers for first-generation somatostatin receptor ligand resistance in Acromegaly.

PURPOSE: Predicting resistance to first-generation Somatostatin Receptor Ligands (fg-SRL) in Acromegaly patients remains an ongong challenge. Tumor-associated immune components participate in various pathological processes, including drug-resistance. We aimed to identify the immune components involved in resistance of fg-SRL, and to investigate biomarkers that can be targeted to treat those drug-resistant Acromegaly. METHODS: We conducted a retrospective study involving 35 Acromegaly patients with somatotropinomas treated postoperatively with fg-SRL. Gathering clinicopathological data, SSTR2 expression, and immunological profiles, we utilized univariate, binary logistic regression, and ROC analyses to assess their predictive roles in fg-SRL resistance. Spearman correlation analysis further examined interactions among interested characteristics. RESULTS: 19 patients (54.29%) exhibited resistance to postoperative fg-SRL. GH level at diagnosis, preoperative tumor volume, T2WI-MRI intensity, granularity, PD-L1, SSTR2, and CD8 + T cell infiltration showed association with clinical outcomes of fg-SRL. Notably, T2WI-MRI hyperintensity, PD-L1-IRS > 7, CD8 + T cell infiltration < 14.8/HPF, and SSTR2-IRS < 5.4 emerged as reliable predictors for fg-SRL resistance. Correlation analysis highlighted a negative relationship between PD-L1 expression and CD8 + T cell infiltration, while showcasing a positive correlation with preoperative tumor volume of somatotropinomas. Additionally, 5 patients with fg-SRL resistance underwent re-operation were involved. Following fg-SRL treatment, significant increases in PD-L1 and SSTR5 expression were observed, while SSTR2 expression decreased in somatotropinoma. CONCLUSION: PD-L1 expression and CD8 + T cell infiltration, either independently or combined with SSTR2 expression and T2WI-MRI intensity, could form a predictive model guiding clinical decisions on fg-SRL employment. Furthermore, targeting PD-L1 through immunotherapy and embracing second-generations of SRL with higher affinity to SSTR5 represent promising strategies to tackle fg-SRL resistance in somatotropinomas.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

CCLA: an accurate method and web server for cancer cell line authentication using gene expression profiles.

Cancer cell lines (CCLs) as important model systems play critical roles in cancer research. The misidentification and contamination of CCLs are serious problems, leading to unreliable results and waste of resources. Current methods for CCL authentication are mainly based on the CCL-specific genetic polymorphism, whereas no method is available for CCL authentication using gene expression profiles. Here, we developed a novel method and homonymic web server (CCLA, Cancer Cell Line Authentication, http://bioinfo.life.hust.edu.cn/web/CCLA/) to authenticate 1291 human CCLs of 28 tissues using gene expression profiles. CCLA showed an excellent speed advantage and high accuracy for CCL authentication, a top 1 accuracy of 96.58 or 92.15% (top 3 accuracy of 100 or 95.11%) for microarray or RNA-Seq validation data (719 samples, 461 CCLs), respectively. To the best of our knowledge, CCLA is the first approach to authenticate CCLs using gene expression data. Users can freely and conveniently authenticate CCLs using gene expression profiles or NCBI GEO accession on CCLA website.

ImmuCellAI-mouse: a tool for comprehensive prediction of mouse immune cell abundance and immune microenvironment depiction.

MOTIVATION: Immune cells are important components of the immune system and are crucial for disease initiation, progression, prognosis and survival. Although several computational methods have been designed for predicting the abundance of immune cells, very few tools are applicable to mouse. Given that, mouse is the most widely used animal model in biomedical research, there is an urgent need to develop a precise algorithm for predicting mouse immune cells. RESULTS: We developed a tool named Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse), for estimating the abundance of 36 immune cell (sub)types from gene expression data in a hierarchical strategy of three layers. Reference expression profiles and robust marker gene sets of immune cell types were curated. The abundance of cells in three layers was predicted separately by calculating the ssGSEA enrichment score of the expression deviation profile per cell type. Benchmark results showed high accuracy of ImmuCellAI-mouse in predicting most immune cell types, with correlation coefficients between predicted value and real cell proportion of most cell types being larger than 0.8. We applied ImmuCellAI-mouse to a mouse breast tumor dataset and revealed the dynamic change of immune cell infiltration during treatment, which is consistent with the findings of the original study but with more details. We also constructed an online server for ImmuCellAI-mouse, on which users can upload expression matrices for analysis. ImmuCellAI-mouse will be a useful tool for studying the immune microenvironment, cancer immunology and immunotherapy in mouse models, providing an indispensable supplement for human disease studies. AVAILABILITY AND IMPLEMENTATION: Software is available at http://bioinfo.life.hust.edu.cn/ImmuCellAI-mouse/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

CBS-derived H2S facilitates host colonization of Vibrio cholerae by promoting the iron-dependent catalase activity of KatB.

Sensing and resisting oxidative stress is critical for Vibrio cholerae to survive in either the aquatic environment or the gastrointestinal tract. Previous studies mainly focused on the mechanisms of oxidative stress response regulation that rely on enzymatic antioxidant systems, while functions of non-enzymatic antioxidants are rarely discussed in V. cholerae. For the first time, we investigated the role of hydrogen sulfide (H2S), the simplest thiol compound, in protecting V. cholerae against oxidative stress. We found that degradation of L-cysteine by putative cystathionine ß-synthase (CBS) is the major source of endogenous H2S in V. cholerae. Our results indicate that intracellular H2S level has a positive correlation with cbs expression, while the enhanced H2S production can render V. cholerae cells less susceptible to H2O2 in vitro. Using proteome analysis and real-time qPCR assay, we found that cbs expression could stimulate the expression of several enzymatic antioxidants, including reactive oxygen species (ROS) detoxifying enzymes SodB, KatG and AhpC, the DNA protective protein DPS and the protein redox regulator Trx1. Assays of ROS detoxification capacities revealed that CBS-derived H2S could promote catalase activity at the post-translational level, especially for KatB, which serves as an important way that endogenous H2S participates in H2O2 detoxification. The enhancement of catalase activity by H2S is achieved through facilitating the uptake of iron. Adult mice experiments showed that cbs mutant has colonization defect, while either complementation of cbs or exogenous supplement of N-Acetyl-L-Cysteine restores its fitness in the host environment. Herein, we proposed that V. cholerae regulates CBS-dependent H2S production for better survival and proliferation under ROS stress.

Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs): increased M2 macrophage infiltration and PD-L1 expression in PIT1-lineage subset.

PURPOSE: Tumor immune microenvironment in pituitary neuroendocrine tumors (PitNETs) and application of current immunotherapy for refractory PitNETs remains debated. We aim to evaluate the immune landscape in different lineages of PitNETs and determine the potential role of pituitary transcription factors in reshaping the tumor immune microenvironment (TIME), thus promoting the application of current immunotherapy for aggressive and metastatic PitNETs. METHODS: Immunocyte infiltration and expression patterns of immune checkpoint molecules in different lineages of PitNETs were estimated via in silico analysis and validated using an IHC validation cohort. The correlation between varying immune components with clinicopathological features was assessed in PIT1-lineage PitNETs. RESULTS: Transcriptome profiles from 210 PitNETs/ 8 normal pituitaries (NPs) and immunohistochemical validations of 77 PitNETs/6 NPs revealed a significant increase in M2-macrophage infiltration in PIT1-lineage PitNETs, compared with the TPIT-lineage, SF1-lineage subsets and NPs. While CD68 + macrophage, CD4 + T cells, and CD8 + T cells were not different among them. Increased M2-macrophage infiltration was associated with tumor volume (p < 0.0001, r = 0.57) in PIT1-lineage PitNETs. Meanwhile, differentially expressed immune checkpoint molecules (PD-L1, PD1, and CTLA-4) were screened and validated in IHC cohorts. The results showed that PD-L1 was highly expressed in PIT1-lineage subsets, and PD-L1 overexpression showed a positive correlation with tumor volume (p = 0.04, r = 0.29) and cavernous sinus invasion (p < 0.0001) in PIT1-lineage PitNETs. CONCLUSION: PIT1-lineage PitNETs exhibit a distinct immune profile with enrichment of M2 macrophage infiltration and PD-L1 expression, which may contribute to its clinical aggressiveness. Application of current immune checkpoint inhibitors and M2-targeted immunotherapy might be more beneficial to treat aggressive and metastatic PIT-lineage PitNETs.

Efficacy and safety of Bifidobacterium quadruple viable tablets combined with mosapride citrate in the treatment of constipation in China: a systematic review and meta-analysis.

AIM: To analyze the efficacy and safety of Bifidobacterium quadruple viable tablets combined with mosapride citrate for the treatment of constipation. METHODS: A systematic review was performed on studies published until July 2022 in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang. The efficacy rate, adverse reaction rate, recurrence rate, and clinical symptoms were included in the measured outcomes. RESULTS: The efficacy of Bifidobacterium quadruple viable tablets combined with mosapride citrate in the treatment of constipation was higher than that of mosapride citrate alone (OR = 4.75, 95% CI (3.27, 6.90), Z = 8.19, P < 0.001; I2 = 0.0%, P = 0.645). There was no significant difference in the incidence of adverse reactions between the two groups (OR = 0.97, 95% CI (0.61,1.57), Z = 0.11, P = 0.911; I2 = 0.0%, P = 0.958). The recurrence rate of constipation in patients receiving the combination treatment was lower than that of patients treated with mosapride citrate alone (OR = 0.48, 95%CI (0.31, 0.73), Z = 3.38, P = 0.001; I2 = 29.8%, P = 0.200). CONCLUSIONS: Bifidobacterium quadruple viable tablets combined with mosapride citrate demonstrated efficacy and safety in treating constipation. Probiotics have the potential to positively influence gut health and microbial profiles in patients with functional constipation.

Intestinal crosstalk between bile acids and microbiota in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a relatively common functional gastrointestinal disease with a disturbance of intestinal bacteria. Bile acids, gut microbiota, and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Recent studies suggested that the bile acid-gut microbiota axis played a key role in the development of IBS patients. In order to investigate the role of bile acids in the pathogenesis of IBS and present potentially relevant clinical implications, we conducted a literature search on intestinal interactions between bile acid and gut microbiota. The intestinal crosstalk between bile acids and gut microbiota shapes the compositional and functional alterations in IBS, manifesting as gut microbial dysbiosis, disturbed bile acid pathway, and alteration of the microbial metabolites. Collaboratively, bile acid conducts the pathogenesis of IBS through the alterations of the farnesoid-X receptor and G protein-coupled receptor. Diagnostic markers and treatments targeting the bile acids and its receptor showed promising potential in the management of IBS. Bile acids and gut microbiota play a key role in the development of IBS and make attractive biomarkers for treatments. Individualized therapy aiming at bile acids and its receptor may provide significant diagnostic and requires further investigation.

[Developments in Research on the Relationship Between Matrix Metalloproteinases and Osteoarthritis].

Matrix metalloproteinases (MMPs) acquired their names because they depend on metal ions such as Ca 2+ and Zn 2+ as their cofactors. Members of this family of proteins share a similar structure consisting of five functionally distinct structural domains. MMPs, including MMP-1, MMP-3, MMP-9, and MMP-13, are key substances that promote cartilage matrix degradation and play an important role in the occurrence and progression of osteoarthritis (OA). MMPs boost the development of OA through the degradation of extracellular matrix proteins of chondrocytes, the promotion of inflammation, and other mechanisms, and are hence attracting extensive and increasing attention from the medical community. OA is a common degenerative disease that occurs in the joints and is associated with aging, metabolism, infections, genetics, exercise, and other predisposing factors. The pathological changes it causes can lead to a series of clinical symptoms such as joint pain, morning stiffness, and restricted joint movement, severely affecting patients' quality of life. The pathogenic mechanism of this highly prevalent disease is still unclear. At present, there is no effective treatment available for disease improvement. In the future, selective inhibition of MMPs, the key enzymes, may become an effective therapeutic approach. Focusing on the pathogenic effects of MMPs in OA, we herein reviewed the latest findings on the role of MMPs in the occurrence and progression of OA.

[Differential diagnosis of autism spectrum disorder and global developmental delay based on machine learning and Children Neuropsychological and Behavioral Scale]. / åŸºäºŽæœºå™¨å­¦ä¹ å’Œå„¿ç«¥ç¥žç»å¿ƒç†è¡Œä¸ºæ£€æŸ¥é‡è¡¨é‰´åˆ«å­¤ç‹¬ç—‡è°±ç³»éšœç¢å’Œå ¨é¢å‘è‚²è¿Ÿç¼“å„¿ç«¥çš„ç ”ç©¶.

OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS: Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.

CAR-T Cell Therapy: Challenges and Optimization.

Immunotherapy has emerged as a potent and effective treatment for multiple cancer types. For example, the engineering of T cells through the expression of chimeric antigen receptor (CAR) against tumors has shown remarkable potential. This review outlines clinical applications of CAR-T cell therapy in hematological malignancies and solid tumors, with a focus on the main challenges related to the safety and efficacy of the current CAR-T cell therapy and the promising strategies to maximize antitumor efficacy while minimizing adverse events. Finally, we present the future outlook of CAR-T cell therapy for the treatment against malignancies. We believe that potential problems can be overcome by strategies to further facilitate effective clinical translation and improve the efficacy, especially through the combination of different approaches.

Distribution of lipid levels and prevalence of hyperlipidemia: data from the NHANES 2007-2018.

BACKGROUND: Lipid-lowering therapy is important, and the distribution of lipid levels and the incidence of hyperlipidemia may vary in different subgroups of the population. We aimed to explore the distribution of lipid levels and the prevalence of hyperlipidemia in subpopulations with subgroup factors, including age, sex, race, and smoking status. METHODS: Our study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, ultimately enrolling and analyzing 15,499 participants. A cross-sectional analysis was performed to assess the distribution of lipids and prevalence of hyperlipidemia in subpopulations, and multifactorial logistic regression analyses were performed for the prevalence of hyperlipidemia, adjusted for age, sex, race and smoking status. RESULTS: Blacks had significantly lower mean serum total cholesterol and triglycerides and higher serum high-density lipoprotein cholesterol (HDL-C) than whites (P < 0.001). In contrast, Mexican Americans had markedly higher mean serum triglycerides and lower serum HDL-C than whites (P < 0.001). Furthermore, the prevalence of hypercholesterolemia and hypertriglyceridemia was lower in blacks than in whites (P = 0.003 and P < 0.001, respectively), while the prevalence of hypertriglyceridemia was significantly higher in Mexican Americans than in whites (P = 0.002). In addition, total cholesterol and triglyceride levels were significantly higher in women aged 65 years or older and markedly higher than in men in the same age group (P < 0.001). In addition, overall mean total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels were higher in smokers than in nonsmokers (P = 0.01, P < 0.001, and P = 0.005, respectively). CONCLUSION: Based on NHANES data, the mean lipid levels and prevalence of hyperlipidemia differed by sex, age, race, and smoking status.

Red blood cell transfusions post diagnosis of necrotizing enterocolitis and the deterioration of necrotizing enterocolitis in full-term and near-term infants: a propensity score adjustment retrospective cohort study.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of serious gastrointestinal inflammatory diseases in newborn infants, with a high morbidity and mortality. Red blood cell transfusion (RBCT) plays a controversial and doubtful role in the treatment of NEC. In present study, we aim to analyze the association between RBCT and the deterioration of NEC. METHODS: This was a retrospective cohort study of near-term and full-term infants with a confirmed diagnosis of Bell's stage II NEC between Jan 1, 2010 and Jan 31, 2020. The maternal and infant baseline characteristics, treatment information and laboratory test for each case were collected. The eligible subjects were divided into two groups based on receiving RBCT post NEC diagnosis or not. The propensity score was used to eliminate potential bias and baseline differences. A multivariate logistic regression model was used to adjust the propensity score and calculate the odds ratio (OR) and 95% confidential interval (CI) of RBCT for the deterioration of NEC. RESULTS: A total of 242 infants were included in this study, 60 infants had a history of RBCT post NEC diagnosis, and 40 infants deteriorated from Bell's stage II to stage III. By adjusting the propensity score, RBCT post NEC diagnosis was associated with an increased risk for NEC deteriorating from stage II to III (adjusted OR 6.06, 95%CI 2.94-12.50, P = 0.000). CONCLUSIONS: NEC infants who required RBCT post NEC diagnosis were more likely to deteriorate from stage II to III in full-term and near-term infants.

Prevalence and risk factors for myopia and high myopia: A cross-sectional study among Han and Uyghur students in Xinjiang, China.

PURPOSE: This study aimed to investigate the prevalence and risk factors for myopia and high myopia among Han and Uyghur students in Xinjiang, China. METHODS: This cross-sectional study with a multistage, stratified cluster sampling method was completed in Xinjiang, China. Visual acuity and noncycloplegic refraction were measured. The crude and sex- and age-adjusted prevalence of myopia and high myopia in Han and Uyghur students were compared. Multivariate logistic regression analyses were applied to identify risk factors associated with myopia and high myopia. RESULTS: In total, 84,033 participants were included in the final analysis, comprising 64,110 Han and 19,923 Uyghur participants. The overall age- and sex-adjusted prevalence of myopia and high myopia were 47.70% (95% CI: 47.67-47.74) and 2.55% (95% CI: 2.54-2.56), respectively. Compared to the Uyghur population, the Han population had a higher prevalence of myopia (63.59% vs. 21.34%, p < 0.0001) and high myopia (4.68% vs. 0.6%, p < 0.0001). Han ethnicity, age, female sex, higher education level and living in urban areas were found to be positively associated with myopia and high myopia. Living in northern Xinjiang was found to be positively associated with myopia but negatively associated with high myopia. CONCLUSIONS: Our study investigated the prevalence of myopia and high myopia among Han and Uyghur students aged 4-23 years in Xinjiang, China. The Han population had a higher prevalence of myopia and high myopia than the Uyghur population. However, the prevalence of myopia among the Uyghur population showed a more remarkable increasing trend than that among the Han population in Xinjiang.

Identification, Genetic Diversity, and Chemical Control of Xanthomonas arboricola pv. pruni in China.

Peach bacterial spot caused by Xanthomonas arboricola pv. pruni has become widespread in most peach-producing areas of China and has caused devastating losses to the peach industry. However, little is known about the population biology and epidemiology of X. arboricola pv. pruni in China, thus no effective management strategy is available. Altogether, 321 symptomatic samples of peach bacterial spot from 12 provinces in China were collected from which 612 bacterial isolates were obtained. Based on 16S rDNA sequence comparison in GenBank, the obtained isolates were identified as Pantoea spp. (514) and Xanthomonas spp. (98). The pathogenicity test demonstrated that the causal agent of the peach bacterial spot was the Xanthomonas spp. instead of the Pantoea spp. Based on morphological observation, physiological and biochemical characterization, and molecular identification, the Xanthomonas spp. were further identified to be X. arboricola pv. pruni. Then, 41 X. arboricola pv. pruni isolates representing different populations were selected and analyzed with repetitive element sequence based-PCR and intersimple sequence repeat markers to understand the genetic diversity and population structure along with four X. arboricola pv. pruni isolates from plum and three isolates of X. arboricola pv. juglandis as comparison. A total of 98 polymorphic alleles were identified, with a mean value of percentage of polymorphic loci of 14. Genetic diversity and phylogenetic analysis revealed the profound heterogeneity between X. arboricola pv. juglandis and X. arboricola pv. pruni, moderate genetic differentiation within X. arboricola pv. pruni, and obvious host specificity but weak geographical differentiation in X. arboricola population. Finally, the efficiency of bactericides on X. arboricola pv. pruni was evaluated in vitro and in vivo. The parallel repeated field trials in two orchards demonstrated that 80% Mancozeb (1:800) and 47% Kocide (1:800, 1:1,500, and 1:2,000) had excellent control efficacies for X. arboricola pv. pruni, especially as the control efficacy of Kocide could even reach 90%. This study conducted a systematic investigation for the occurrence, population variance, and chemical control of X. arboricola pv. pruni. It improved the understanding of the pathogen populations of peach bacterial spot in China and provided solid theoretical and practical guidance for X. arboricola pv. pruni control.