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Objective: The aim of this study is to assess the use of machine learning methodologies in the diagnosis of endometriosis (EM)., Methods: This study included a total of 106 patients with EM and 203 patients with non-EM conditions (like simple cysts and simple uterine fibroids), all admitted to the Shunyi Women's and Children's Hospital of Beijing Children's Hospital between January 2017 and September 2022. All participants were free of comorbidities and their diagnoses were confirmed via postoperative pathology. Comparative analysis was conducted between the EM and non-EM groups. Baseline data were assessed, including white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mean platelet volume, hemoglobin, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, coagulation parameters, and other serologic indicators. An optimal predictive model was developed using an artificial intelligence algorithm to determine the presence of EM. The objective is to provide new insights for the clinical diagnosis and treatment of EM., Results: The random forest algorithm demonstrated superior performance when compared to decision trees, LogitBoost, artificial neural networks, naïve Bayes, support vector machines, and linear regression in machine learning methods. Combining CA125 with the NLR yielded a better prediction of EM than using CA125 alone when applying the random forest algorithm. The accuracy of predicting EM with CA125 combined with NLR was 78.16%, with a sensitivity of 86.21% and an area under the curve (AUC) of 0.85 (P < 0.05). In contrast, using CA125 alone resulted in an EM prediction accuracy of 75.8%, with a sensitivity of 79.3% and an AUC of 0.82 (P < 0.05)., Conclusion: The diagnostic value of serum CA125 combined with the NLR for EM is higher than that of serum CA125 alone. This finding indicates that NLR could serve as a new supplementary biomarker along with serum CA125 in the diagnosis of EM., (© 2024. The Author(s).)

Background: BAHD acyltransferases are among the largest metabolic protein domain families in the genomes of terrestrial plants and play important roles in plant growth and development, aroma formation, and biotic and abiotic stress responses. Little is known about the BAHDs in the tea plant, a cash crop rich in secondary metabolites., Results: In this study, 112 BAHD genes (CsBAHD01-CsBAHD112) were identified from the tea plant genome, with 85% (98/112) unevenly distributed across the 15 chromosomes. The number of BAHD gene family members has significantly expanded from wild tea plants to the assamica type to the sinensis type. Phylogenetic analysis showed that they could be classified into seven subgroups. Promoter cis-acting element analysis revealed that they contain a large number of light, phytohormones, and stress-responsive elements. Many members displayed tissue-specific expression patterns. CsBAHD05 was expressed at more than 500-fold higher levels in purple tea leaves than in green tea leaves. The genes exhibiting the most significant response to MeJA treatment and feeding by herbivorous pests were primarily concentrated in subgroups 5 and 6. The expression of 23 members of these two subgroups at different time points after feeding by tea green leafhoppers and tea geometrids was examined via qPCR, and the results revealed that the expression of CsBAHD93, CsBAHD94 and CsBAHD95 was significantly induced after the tea plants were subjected to feeding by both pricking and chewing pests. Moreover, based on the transcriptome data for tea plants being fed on by these two pests, a transcriptional regulatory network of different transcription factor genes coexpressed with these 23 members was constructed., Conclusions: Our study provides new insights into the role of BAHDs in the defense response of tea plants, and will facilitate in-depth studies of the molecular function of BAHDs in resistance to herbivorous pests., (© 2024. The Author(s).)

Background: Increasing attention has been raised on the surgical option for lung cancer patients aged ≥75 years, however, few studies have focused on whether uniportal video-assisted thoracoscopic surgery (VATS) is safe and feasible for these patients. This study aimed to evaluate short-term results of uniportal versus three-port VATS for the treatment of lung cancer patients aged ≥75 years., Methods: We retrospectively evaluated 582 lung cancer patients (≥75 years) who underwent uniportal or three-port VATS from August 2007 to August 2021 based on the Western China Lung Cancer Database. The baseline and perioperative outcomes between uniportal and three-port VATS were compared in the whole cohort (WC) and the patients undergoing lobectomy (lobectomy cohort, LC) respectively. Propensity score matching (PSM) was used to minimize confounding bias between the uniportal and three-port cohorts in WC and LC., Results: Intraoperative blood loss was significantly less in the uniportal than three-port LC (50 mL vs. 83 mL, P = 0.007) before PSM and relatively less in the uniportal than three-port LC (50 mL vs. 83 mL, P = 0.05) after PSM. Significantly more lymph nodes harvested (13 vs. 9, P = 0.007) were found in the uniportal than three-port LC after PSM. In addition, in WC and LC, there were no significant differences between uniportal and three-port cohorts in terms of operation time, the rate of conversion to thoracotomy during surgery, nodal treatments (dissection or sampling or not), the overall number of lymph node stations dissected, postoperative complications, volume and duration of postoperative thoracic drainage, hospital stay after operation and hospitalization expenses before and after PSM (P > 0.05)., Conclusions: There were no significant differences in short-term outcomes between uniportal and three-port VATS for lung cancer patients (≥75 years), except relatively less intraoperative blood loss (P < 0.05 before PSM and P = 0.05 after PSM) and significantly more lymph nodes harvested (P < 0.05 after PSM) were found in uniportal LC. It is reasonable to indicate that uniportal VATS is a safe, feasible and effective operation procedure for lung cancer patients aged ≥75 years., (© 2024. The Author(s).)

Background: Malnutrition is a common geriatric syndrome and can be targeted preoperatively to decrease the risk of postoperative delirium (POD) in older adult patients. To analyze the value of the prognostic nutritional index (PNI) to predict the incidence of POD in older adult patients with hip fractures., Methods: This was a prospective, observational, cohort study of older adult patients with hip fractures. Preoperative PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/μL) using preoperative laboratory results. Patients were divided into POD and non-POD groups using the Confusion Assessment Method (CAM). The risk factors associated with POD as well as the relationship between PNI values and the incidence of POD were analyzed using univariate and multivariate logistic regression analyses. The predictive value of PNI for POD was assessed using receiver operating characteristic curve analysis., Results: In this cohort of 369 patients who underwent hip fracture surgery, 67 patients (18.2%) were diagnosed with POD by the CAM results. Low PNI increased the risk of POD (odds ratio (OR) = 0.928, 95% confidence interval (CI): 0.864-0.997). General anesthesia (OR = 2.307, 95% CI: 1.279-4.162) and Mini-Mental State Examination (MMSE) score (OR = 0.956, 95% CI: 0.920-0.994) were also identified as risk factors for POD. Receiver operating characteristic curve analysis suggested that PNI combined with the anesthetic method and MMSE score may be used as a potential predictive indicator of POD after hip fracture surgery., Conclusion: Preoperative PNI value is related to POD in older adult patients with hip fractures., Trial Registration: This secondary analysis study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (approval No. M2022578) and registered in the Chinese Clinical Trial Registry (ChiCTR2300070569)., (© 2023. The Author(s).)

Background: Diagnosis of liver disease at earlier stages can improve outcomes and reduce the risk of progression to malignancy. Liver biopsy is the gold standard for diagnosis of liver disease, but is invasive and sample acquisition errors are common. Serum biomarkers for liver function and fibrosis, combined with patient factors, may allow for noninvasive detection of liver disease. In this pilot study, we tested and validated the performance of an algorithm that combines GP73 and LG2m serum biomarkers with age and sex (GLAS) to differentiate between patients with liver disease and healthy individuals in two independent cohorts., Methods: To develop the algorithm, prototype immunoassays were used to measure GP73 and LG2m in residual serum samples collected between 2003 and 2016 from patients with staged fibrosis and cirrhosis of viral or non-viral etiology (n = 260) and healthy subjects (n = 133). The performance of five predictive models using combinations of age, sex, GP73, and/or LG2m from the development cohort were tested. Residual samples from a separate cohort with liver disease (fibrosis, cirrhosis, or chronic liver disease; n = 395) and healthy subjects (n = 106) were used to validate the best performing model., Results: GP73 and LG2m concentrations were higher in patients with liver disease than healthy controls and higher in those with cirrhosis than fibrosis in both the development and validation cohorts. The best performing model included both GP73 and LG2m plus age and sex (GLAS algorithm), which had an AUC of 0.92 (95% CI: 0.90-0.95), a sensitivity of 88.8%, and a specificity of 75.9%. In the validation cohort, the GLAS algorithm had an estimated an AUC of 0.93 (95% CI: 0.90-0.95), a sensitivity of 91.1%, and a specificity of 80.2%. In both cohorts, the GLAS algorithm had high predictive probability for distinguishing between patients with liver disease versus healthy controls., Conclusions: GP73 and LG2m serum biomarkers, when combined with age and sex (GLAS algorithm), showed high sensitivity and specificity for detection of liver disease in two independent cohorts. The GLAS algorithm will need to be validated and refined in larger cohorts and tested in longitudinal studies for differentiating between stable versus advancing liver disease over time., (© 2023. The Author(s).)

Background: CHF (Congenital hepatic fibrosis) is a rare hereditary disease characterized by periportal fibrosis and ductal plate malformation. Little is known about the clinical presentations and outcome in CHF patients with an extraordinary complication with biliary sepsis. Our case described a 23-year-old female diagnosed as CHF combined with biliary sepsis. Her blood culture was positive for KP (Klebsiella pneumoniae), and with a high level of CA19-9 (> 1200.00 U/ml, ref: <37.00 U/ml). Meanwhile, her imaging examinations showed intrahepatic bile duct dilatation, portal hypertension, splenomegaly, and renal cysts. Liver pathology revealed periportal fibrosis and irregularly shaped proliferating bile ducts. Whole-exome sequencing identified two heterozygous missense variants c.3860T > G (p. V1287G) and c.9059T > C (p. L3020P) in PKHD1 gene. After biliary sepsis relieved, her liver function test was normal, and imaging examination results showed no significant difference with the results harvested during her biliary sepsis occurred., Conclusion: The diagnosis of CHF complicated with biliary sepsis in the patient was made. Severely biliary sepsis due to KP infection may not inevitably aggravate congential liver abnormality in young patients. Our case provides a good reference for timely treatment of CHF patients with biliary sepsis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The Corona Virus Disease 2019(COVID-19) pandemic has strained healthcare systems worldwide, necessitating the early prediction of patients requiring critical care. This study aimed to analyze the laboratory examination indicators, CT features, and prognostic risk factors in COVID-19 patients., Methods: A retrospective study was conducted on 90 COVID-19 patients at the First Affiliated Hospital of Gannan Medical University between December 17, 2022, and March 17, 2023. Clinical data, laboratory examination results, and computed tomography (CT) imaging data were collected. Logistic multivariate regression analysis was performed to identify independent risk factors, and the predictive ability of each risk factor was assessed using the area under the receiver operating characteristic (ROC) curve., Results: Multivariate logistic regression analysis revealed that comorbid diabetes (odds ratio [OR] = 526.875, 95%CI = 1.384-1960.84, P = 0.053), lymphocyte count reduction (OR = 8.773, 95%CI = 1.432-53.584, P = 0.064), elevated D-dimer level (OR = 362.426, 95%CI = 1.228-984.995, P = 0.023), and involvement of five lung lobes (OR = 0.926, 95%CI = 0.026-0.686, P = 0.025) were risk factors for progression to severe COVID-19. ROC curve analysis showed the highest predictive value for 5 lung lobes (AUC = 0.782). Oxygen saturation was positively correlated with normally aerated lung volume and the proportion of normally aerated lung volume (P < 0.05)., Conclusions: The study demonstrated that comorbid diabetes, lymphocyte count reduction, elevated D-dimer levels, and involvement of the five lung lobes are significant risk factors for severe COVID-19. In CT lung volume quantification, normal aerated lung volume and the proportion of normal aerated lung volume correlated with blood oxygen saturation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background and Aims: The scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats., Methods: Rats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20., Results: SCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1β) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats., Conclusion: In conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: PYL (Pyrabactin resistance 1-like) protein is a receptor of abscisic acid (ABA), which plays an important role in ABA signaling and influences plant growth and development and stress response. However, studies on PYL gene family in tea plants have not been reported., Results: In this study, we identified 20 PYL genes from the reference genome of tea plant ('Shuchazao'). Phylogeny analysis indicated that PYLs from tea and other plant species were clustered into seven groups. The promoter region of PYL genes contains a large number of cis-elements related to hormones and stresses. A large number of PYL genes responding to stress were found by analyzing the expression levels of abiotic stress and biotic stress transcriptome data. For example, CSS0047272.1 were up-regulated by drought stress, and CSS0027597.1 could respond to both anthracnose disease and geometrid feeding treatments. In addition, 10 PYL genes related to growth and development were verified by RT-qPCR and their tissue expression characteristics were revealed., Conclusions: Our results provided a comprehensive characteristic of the PYL gene family in tea plants and provided an important clue for further exploring its functions in the growth and development, and resistance to stress of tea plants., (© 2023. The Author(s).)

Objective: We aimed to develop a robust framework to model the complex association between clinical features and traumatic brain injury (TBI) risk in children under age two, and identify significant features to derive clinical decision rules for triage decisions., Methods: In this retrospective study, four frequently used machine learning models, i.e., support vector machine (SVM), random forest (RF), deep neural network (DNN), and XGBoost (XGB), were compared to identify significant clinical features from 24 input features associated with the TBI risk in children under age two under the permutation feature importance test (PermFIT) framework by using the publicly available data set from the Pediatric Emergency Care Applied Research Network (PECARN) study. The prediction accuracy was determined by comparing the predicted TBI status with the computed tomography (CT) scan results since CT scan is the gold standard for diagnosing TBI., Results: At a significance level of [Formula: see text], DNN, RF, XGB, and SVM identified 9, 1, 2,  and 4 significant features, respectively. In a comparison of accuracy (Accuracy), the area under the curve (AUC), and the precision-recall area under the curve (PR-AUC), the permutation feature importance test for DNN model was the most powerful framework for identifying significant features and outperformed other methods, i.e., RF, XGB, and SVM, with Accuracy, AUC, and PR-AUC as 0.915, 0.794, and 0.974, respectively., Conclusion: These results indicate that the PermFIT-DNN framework robustly identifies significant clinical features associated with TBI status and improves prediction performance. The findings could be used to inform the development of clinical decision tools designed to inform triage decisions., (© 2023. The Author(s).)

Background: Simiao pill module (SMM), a traditional Chinese medicine formula, has been widely used to treat gout and gouty arthritis. The goal of this study was to investigate the effects of SMM on epithelial-mesenchymal transition (EMT) and activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome in a mouse model of potassium oxonate (PO)-induced chronic hyperuricemic nephropathy (HN)., Methods: Mice were randomly divided into the following four groups: control, HN model (PO), febuxostat (FEB)-treated (PO + FEB), and SMM-treated (PO + SMM) groups. Following 6 weeks of treatment, blood samples were collected and mice were sacrificed to collect kidney samples to study the biochemical parameters associated with renal function and histopathological changes associated with HN, respectively. The samples were analyzed for the expression of markers of EMT (collagen type 3, α-smooth muscle actin [α-SMA], fibronectin, vimentin and E-cadherin) and activation of NLRP3 inflammasome (NLRP3, apoptosis-associated speck-like protein [ASC], caspase-1, interleukin [IL]-1β, and IL-18)., Results: Our results showed that hyperuricemia, impaired kidney function, and renal pathological characteristics induced by PO treatment were improved following treatment with SMM and FEB. Additionally, treatment with SMM and FEB decreased the expression of vimentin, collagen 3, fibronectin, and α-SMA, and increased the expression of E-cadherin. Moreover, NLRP3 inflammasome activation, as assessed by the increased expression of NLRP3, ASC, and caspase-1, and secretion of IL-1β and IL-18, was inhibited by treatment with SMM and FEB., Conclusion: These results suggest that SMM inhibited EMT and NLRP3 inflammasome activation in chronic HN mice, and the beneficial effect of SMM was compared with a standard drug, FEB., (© 2022. The Author(s).)

Background: The cyclin-dependent kinase 7 (CDK7) inhibitor THZ1 represses multiple cancer cells. However, its tumor-repressive efficiency in wild-type p53 breast cancer cells remains controversial., Methods: We conducted various assays, including CCK8, colony formation, flow cytometry, western blotting, and lactate dehydrogenase release detection, to clarify whether p53 elevation sensitizes breast cancer cells to THZ1., Results: We found that upregulating functional p53 contributes to the increased sensitivity of breast cancer cells to THZ1. Increased THZ1 sensitivity requires active p53 and an intact p53 pathway, which was confirmed by introducing exogenous wild-type p53 and the subsequent elevation of THZ1-mediated tumor suppression in breast cancer cells carrying mutant p53. We confirmed that p53 accumulates in the nucleus and mitochondria during cell death. Furthermore, we identified extensive transcriptional disruption, rather than solely CDK7 inhibition, as the mechanism underlying the nutlin-3 and THZ1-induced death of breast cancer cells. Finally, we observed the combined nutlin-3 and THZ1 treatment amplified gasdermin E cleavage., Conclusion: Enhanced sensitivity of breast cancer cells to THZ1 can be achieved by increasing effective p53 expression. Our approach may serve as a potential treatment for patients with breast cancer resistant to regular therapies. Video Abstract., (© 2022. The Author(s).)

Background: At present, intraocular injection of anti-VEGF (vascular endothelial growth factor) drugs has replaced traditional laser therapy as the first-line treatment for DME (diabetic macular edema). However, ranibizumab, a commonly used anti-VEGF drug, is expensive and requires multiple intraocular injections. It places a heavy economic burden on patients with DME. Micropulse laser is safer than conventional laser and can reduce edema. Combined treatment with anti-VEGF may reduce the number of intraocular injections. This study will compare the efficacy of micropulse laser combined with ranibizumab treatment to ranibizumab monotherapy in the treatment of DME, providing a new regimen for future DME treatment., Methods: This study is a prospective randomized double-blind controlled clinical trial (RCT) in patients with DME. After 1-year follow-up, visual acuity and macular edema regression will be compared between micropulse laser combined with ranibizumab group and ranibizumab monotherapy group to determine whether the efficacy of micropulse laser combined with ranibizumab treatment was not lower than that of ranibizumab monotherapy in the treatment of DME. Visual acuity measured by the ETDRS chart is the primary outcome measure. The secondary outcome measures are CMT (central macular thickness) measured by OCT (optical coherence tomography) and the number of injections of two groups. Changes in visual acuity and CMT of the two groups will be compared at 12-month follow-up. Before patients are recruited, we provide them with informed consent, in which we explain to them the purpose and process of the study., Discussion: Micropulse laser combined with anti-VEGF drugs in the treatment of DME can reduce the number of intravitreal anti-VEGF injections, not only relieve the pain of the patients, but also ease the economic and psychological burden of patients, bringing great benefits. However, there is no treatment consensus for the parameters and specific methods of micropulse laser treatment for DME. There is a lack of clinical research data reference of micropulse laser combined with anti-VEGF therapy in clinical practice. This study intends to provide a new direction for clinical DME treatment and also provide a realistic consideration for the application of micropulse laser in DME treatment., Trial Registration: ClinicalTrials.gov NCT03690947. Registered on 1 October 2018., (© 2022. The Author(s).)

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. P21 activated kinase 4 (PAK4) and Breast cancer anti-estrogen resistance 3 (BCAR3) have been reported to be involved in numerous aspects in tumorous progression. In this study, we propose to screen multi-targeted microRNAs. (miRNAs), which simultaneously inhibit neoplastic evolution through suppressing the transcription of target genes., Methods: MTT and Colony formation assays measured cell's viability and proliferation. Scratch wound and Transwell assays detected the ability in migration and invasion for SW116 cells. The multi-targeted microRNAs of PAK4 and BCAR3 were predicted using bioinformatics analysis and verified by conducting dual luciferase reporter assay, western blot and qRT-PCR that could detect the expression levels of miR-199a/b-3p., Results: The knockdown of PAK4 significantly impeded proliferation and colony formation of SW1116 cells when the knockdown of BCAR3 hindered migration and invasion of SW1116 cells. MiR-199a/b-3p directly targeted the 3'-UTR of PAK4 and BCAR3, further effected proliferation, colony formation, migration, and invasion of SW1116 cells. PAK4 or BCAR3 overexpression could partially reversed inhibitory effects of miR-199a/b-3p., Conclusions: These results provided a new multi-targeted cite for cancerous suppressant to improve the prognosis of CRC inpatients., (© 2022. The Author(s).)

Background: Declining ovarian function in advance-aged women and in premature ovarian insufficiency (POI) patients seriously affects quality of life, and there is currently no effective treatment to rescue ovarian function in clinic. Stem cell transplantation is a promising therapeutic strategy for ovarian aging, but its clinical application is limited due to the low efficiency and unclear mechanism. Here, a novel combination of umbilical cord-mesenchymal stem cells (UC-MSCs) and autocrosslinked hyaluronic acid (HA) gel is explored to rescue ovarian reserve and fecundity in POI and naturally aging mice., Methods: To investigate HA prolonged the survival after UC-MSCs transplantation, PCR and immunofluorescence were performed to track the cells on day 1, 3, 7 and 14 after transplantation. The effects of HA on UC-MSCs were analyzed by CCK8 assay, RNA-sequencing and 440 cytokine array. In vivo experiments were conducted to evaluate the therapeutic effects of UC-MSCs combined with HA transplantation in 4-vinylcyclohexene diepoxide (VCD)-induced POI mice and naturally aging mice model. Ovarian function was analyzed by ovarian morphology, follicle counts, estrous cycle, hormone levels and fertility ability. To investigate the mechanisms of stem cell therapy, conditioned medium was collected from UC-MSCs and fibroblast. Both in vitro ovarian culture model and 440 cytokine array were applied to assess the paracrine effect and determine the underlying mechanism. Hepatocyte growth factor (HGF) was identified as an effective factor and verified by HGF cytokine/neutralization antibody supplementation into ovarian culture system., Results: HA not only prolongs the retention of UC-MSCs in the ovary, but also boosts their secretory function, and UC-MSCs promote follicular survival by activating the PI3K-AKT pathway through a paracrine mechanism both in vitro and in vivo. More importantly, HGF is identified as the key functional cytokine secreted by MSCs., Conclusions: The results show that HA is an excellent cell scaffold to improve the treatment efficiency of UC-MSCs for ovarian aging under both physiological and pathological conditions, and the therapeutic mechanism is through activation of the PI3K-AKT pathway via HGF. These findings will facilitate the clinical application of MSCs transplantation for ovarian disorders., (© 2022. The Author(s).)

Background: In line with aging populations and increased application of anesthesia and surgery, perioperative neurocognitive disorder (PND) has received growing attention worldwide. Considerable researches into PND are being conducted; however, the quantity and quality of such researches have not been reported. Through a retrospective bibliometric analysis, this study aims to identify and characterize the top 100 cited publications on PND., Methods: We searched the Web of Science database to find the top 100 cited articles focusing on PND. We collected bibliographic information, including year of publication, country of origin, article type, published journal, citation count, and authorship. To determine changes with time, we compared older and newest articles., Results: The top 100 cited articles were published between 1955 and 2016; the number of citations ranged from 111 to 1248. The United States had the most published papers; clinical trial was the most common article type. The specialty journals of Anesthesiology and Anesthesia & Analgesia were the two most cited journals. Newest articles had a comparable number of citations to older articles, but the former had higher annual citation rates, greater funding disclosures, more focus on basic research, and more open access publications., Conclusions: This study provides a comprehensive overview of the most cited articles and highlights the increasing attention on PND. High-quality clinical trials with a greater journal impact factor receive more citations. However, there has been a growth in the number of basic science studies as an area of research with respect to the pathogenesis of PND.

Lung cancer is one of the most common malignant tumours worldwide. however, emerging immunotherapy and targeted therapies continue to show limited efficacy. In the search for new targets for lung cancer treatment, exosomes have become a major focus of research. Exosomes play an important role in the tumour microenvironment (TME) of lung cancer and affect invasion, metastasis, and treatment responses. This review describes our current understanding of the release of exosomes derived from different cells in the TME, the effects of exosomes on T/Tregs, myeloid-derived suppressor cells, tumour-associated macrophages, dendritic cells, and natural killer cells, and the role of exosomes in the endothelial-mesenchymal transition, angiogenesis, and cancer-associated fibroblasts. In particular, this review focuses on the potential clinical applications of exosomes in the lung cancer microenvironment and their prognostic and diagnostic value.

Alternative splicing (AS) increases the diversity of transcripts and proteins through the selection of different splice sites and plays an important role in the growth, development and stress tolerance of plants. With the release of the reference genome of the tea plant (Camellia sinensis) and the development of transcriptome sequencing, researchers have reported the existence of AS in tea plants. However, there is a lack of a platform, centered on different RNA-seq datasets, that provides comprehensive information on AS.To facilitate access to information on AS and reveal the molecular function of AS in tea plants, we established the first comprehensive AS database for tea plants (TeaAS, http://www.teaas.cn/index.php ). In this study, 3.96 Tb reads from 66 different RNA-seq datasets were collected to identify AS events. TeaAS supports four methods of retrieval of AS information based on gene ID, gene name, annotation (non-redundant/Kyoto encyclopedia of genes and genomes/gene ontology annotation or chromosomal location) and RNA-seq data. It integrates data pertaining to genome annotation, type of AS event, transcript sequence, and isoforms expression levels from 66 RNA-seq datasets. The AS events resulting from different environmental conditions and that occurring in varied tissue types, and the expression levels of specific transcripts can be clearly identified through this online database. Moreover, it also provides two useful tools, Basic Local Alignment Search Tool and Generic Genome Browser, for sequence alignment and visualization of gene structure.The features of the TeaAS database make it a comprehensive AS bioinformatics platform for researchers, as well as a reference for studying AS events in woody crops. It could also be helpful for revealing the novel biological functions of AS in gene regulation in tea plants.

Background: Branch angle is a pivotal component of tea plant architecture. Tea plant architecture not only affects tea quality and yield but also influences the efficiency of automatic tea plant pruning. However, the molecular mechanism controlling the branch angle, which is an important aspect of plant architecture, is poorly understood in tea plants., Results: In the present study, three CsLAZY genes were identified from tea plant genome data through sequence homology analysis. Phylogenetic tree displayed that the CsLAZY genes had high sequence similarity with LAZY genes from other plant species, especially those in woody plants. The expression patterns of the three CsLAZYs were surveyed in eight tissues. We further verified the expression levels of the key CsLAZY1 transcript in different tissues among eight tea cultivars and found that CsLAZY1 was highly expressed in stem. Subcellular localization analysis showed that the CsLAZY1 protein was localized in the plasma membrane. CsLAZY1 was transferred into Arabidopsis thaliana to investigate its potential role in regulating shoot development. Remarkably, the CsLAZY1 overexpressed plants responded more effectively than the wild-type plants to a gravity inversion treatment under light and dark conditions. The results indicate that CsLAZY1 plays an important role in regulating shoot gravitropism in tea plants., Conclusions: The results provide important evidence for understanding the functions of CsLAZY1 in regulating shoot gravitropism and influencing the stem branch angle in tea plants. This report identifies CsLAZY1 as a promising gene resource for the improvement of tea plant architecture.

Background: Alternative splicing (AS) may generate multiple mRNA splicing isoforms from a single mRNA precursor using different splicing sites, leading to enhanced diversity of transcripts and proteins. AS has been implicated in cold acclimation by affecting gene expression in various ways, yet little information is known about how AS influences cold responses in tea plant (Camellia sinensis)., Results: In this study, the AS transcriptional landscape was characterized in the tea plant genome using high-throughput RNA-seq during cold acclimation. We found that more than 41% (14,103) of genes underwent AS events. We summarize the possible existence of 11 types of AS events, including the four common types of intron retention (IR), exon skipping (ES), alternative 5' splice site (A5SS), and alternative 3' splice site (A3SS); of these, IR was the major type in all samples. The number of AS events increased rapidly during cold treatment, but decreased significantly following de-acclimation (DA). It is notable that the number of differential AS genes gradually increased during cold acclimation, and these genes were enriched in pathways relating to oxidoreductase activity and sugar metabolism during acclimation and de-acclimation. Remarkably, the AS isoforms of bHLH transcription factors showed higher expression levels than their full-length ones during cold acclimation. Interestingly, the expression pattern of some AS transcripts of raffinose and sucrose synthase genes were significantly correlated with sugar contents., Conclusion: Our findings demonstrated that changes in AS numbers and transcript expression may contribute to rapid changes in gene expression and metabolite profile during cold acclimation, suggesting that AS events play an important regulatory role in response to cold acclimation in tea plant.

Background: Aquaporins (AQPs) are integral membrane proteins from a larger family of major intrinsic proteins (MIPs) and function in a huge variety of processes such as water transport, plant growth and stress response. The availability of the whole-genome data of different cotton species allows us to study systematic evolution and function of cotton AQPs on a genome-wide level., Results: Here, a total of 53, 58, 113 and 111 AQP genes were identified in G. arboreum, G. raimondii, G. hirsutum and G. barbadense, respectively. A comprehensive analysis of cotton AQPs, involved in exon/intron structure, functional domains, phylogenetic relationships and gene duplications, divided these AQPs into five subfamilies (PIP, NIP, SIP, TIP and XIP). Comparative genome analysis among 30 species from algae to angiosperm as well as common tandem duplication events in 24 well-studied plants further revealed the evolutionary conservation of AQP family in the organism kingdom. Combining transcriptome analysis and Quantitative Real-time PCR (qRT-PCR) verification, most AQPs exhibited tissue-specific expression patterns both in G. raimondii and G. hirsutum. Meanwhile, a bias of time to peak expression of several AQPs was also detected after treating G. davidsonii and G. hirsutum with 200 mM NaCl. It is interesting that both PIP1;4 h/i/j and PIP2;2a/e showed the highly conserved tandem structure, but differentially contributed to tissue development and stress response in different cotton species., Conclusions: These results demonstrated that cotton AQPs were structural conservation while experienced the functional differentiation during the process of evolution and domestication. This study will further broaden our insights into the evolution and functional elucidation of AQP gene family in cotton.

Background: Metabolomics has the promise to transform the area of personalized medicine with the rapid development of high throughput technology for untargeted analysis of metabolites. Open access, easy to use, analytic tools that are broadly accessible to the biological community need to be developed. While technology used in metabolomics varies, most metabolomics studies have a set of features identified. Galaxy is an open access platform that enables scientists at all levels to interact with big data. Galaxy promotes reproducibility by saving histories and enabling the sharing workflows among scientists., Results: SECIMTools (SouthEast Center for Integrated Metabolomics) is a set of Python applications that are available both as standalone tools and wrapped for use in Galaxy. The suite includes a comprehensive set of quality control metrics (retention time window evaluation and various peak evaluation tools), visualization techniques (hierarchical cluster heatmap, principal component analysis, modular modularity clustering), basic statistical analysis methods (partial least squares - discriminant analysis, analysis of variance, t-test, Kruskal-Wallis non-parametric test), advanced classification methods (random forest, support vector machines), and advanced variable selection tools (least absolute shrinkage and selection operator LASSO and Elastic Net)., Conclusions: SECIMTools leverages the Galaxy platform and enables integrated workflows for metabolomics data analysis made from building blocks designed for easy use and interpretability. Standard data formats and a set of utilities allow arbitrary linkages between tools to encourage novel workflow designs. The Galaxy framework enables future data integration for metabolomics studies with other omics data.

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. Our current data do not support the association between the SNP in miR-938 and type 1 diabetes.