[Climate change affects plant aboveground biomass by regulating the growth periods in alpine grasslands of the Tibetan Plateau, China]. / 气候变化通过调控青藏高原高寒草原植物生育期影响地上生物量积累.

Climate change significantly affects plant biomass and phenological occurrence time in alpine grasslands of Tibetan Plateau. The changes in phenological periods are closely related to the length of vegetative and reproductive growth periods, which may further affect aboveground biomass accumulation. In this study, based on fixed-point observations of plant biomass and phenology as well as the corresponding climatic data from 1997 to 2020 in the alpine grasslands of Tibetan Plateau, we used statistical methods such as ordinary linear regression and piecewise structural equation model to explore the characteristics of interannual climate change in the study area, the variation trends of plant biomass and phenological periods, and the correlations between biomass and phenological and climatic factors. The results showed that mean annual temperature and annual precipitation in the study area increased significantly from 1997 to 2020, suggesting a clear "warm-wet" trend. Aboveground biomass and relative biomass of Stipa sareptana var. krylovii (the dominant species) decreased significantly. However, absolute and relative biomass of subdominant species (Kobresia humilis) increased significantly, indicating that the dominance of K. humilis increased. The warm-wet climates enhanced aboveground biomass accumulation of K. humilis by extending the period of reproductive growth. Mean annual temperature and annual precipitation decreased aboveground biomass of S. sareptana by shortening the length of vegetative growth period. In a word, the warmer and wetter climate significantly affected aboveground biomass accumulation by regulating the changes in the phenological period, and the interspecific difference in their response resulted in a larger change in community composition. This study area may show a trend from alpine grassland to alpine meadow, and thus further works are urgently needed.

The new morphologic classification of the hand motor cortex with magnetic resonance imaging in glioma patients.

Purpose: The hand motor cortex (HMC) is a reliable anatomical landmark for identifying the precentral gyrus. The current study aimed to investigate the morphology of HMC on axial MRI of glioma patients, propose a new morphological classification of HMC and analyze the effect of tumors on the morphology of HMC. Methods: A retrospective study of 276 adult right-handed glioma patients was conducted. The morphology of HMC was assessed using T2 axial images. Subsequently, the distribution of morphological subtypes was compared between the bilateral hemispheres and the tumor-affected and healthy hemispheres. Finally, the influence of tumor pathology on the morphology of HMC was investigated. Results: A new morphological classification of HMC with four subtypes (Ω, ε, Ω-ε and ε-Ω) was proposed. No significant difference was identified in the distribution of morphological subtypes between the bilateral hemispheres (p = 0.0901, Chi-square test), or between the tumor-affected and healthy hemispheres (p = 0.3507, Chi-square test), and the morphology of HMC between the bilateral hemispheres were consistent (p < 0.0001, Kappa test). In addition, a significant difference was identified in the distribution of morphological subtypes between astrocytic and oligodendroglial tumors (p = 0.0135, Chi-square test). Conclusion: In the current study, we proposed a new morphological classification of HMC, and found that tumor could affect the morphology of HMC in glioma patients. The results can help our clinical practice, enabling us to further understand the spatial structure of the cerebral hemispheres.

Consistency between self-reported disease diagnosis and clinical assessment and under-reporting for chronic conditions: data from a community-based study in Xi'an, China.

Aims: The current study aims to investigate the consistency between the surveyees' self-reported disease diagnosis and clinical assessment of eight major chronic conditions using community-based survey data collected in Xi'an, China in 2017. With a focus on under-reporting patients, we aim to explore its magnitude and associated factors, to provide an important basis for disease surveillance, health assessment and resource allocation, and public health decision-making and services. Methods: Questionnaires were administered to collect self-reported chronic condition prevalence among the study participants, while physical examinations and laboratory tests were conducted for clinical assessment. For each of the eight chronic conditions, the sensitivity, specificity, under-reporting, over-reporting, and agreement were calculated. Log-binomial regression analysis was employed to identify potential factors that may influence the consistency of chronic condition reporting. Results: A total of 2,272 participants were included in the analysis. Four out of the eight chronic conditions displayed under-reporting exceeding 50%. The highest under-reporting was observed for goiter [85.93, 95% confidence interval (CI): 85.25-86.62%], hyperuricemia (83.94, 95% CI: 83.22-84.66%), and thyroid nodules (72.89, 95% CI: 72.02-73.76%). Log-binomial regression analysis indicated that senior age and high BMI were potential factors associated with the under-reporting of chronic condition status in the study population. Conclusion: The self-reported disease diagnosis by respondents and clinical assessment data exhibit significant inconsistency for all eight chronic conditions. Large proportions of patients with multiple chronic conditions were under-reported in Xi'an, China. Combining relevant potential factors, targeted health screenings for high-risk populations might be an effective method for identifying under-reporting patients.

Prioritization of risk genes for Alzheimer's disease: an analysis framework using spatial and temporal gene expression data in the human brain based on support vector machine.

Background: Alzheimer's disease (AD) is a complex disorder, and its risk is influenced by multiple genetic and environmental factors. In this study, an AD risk gene prediction framework based on spatial and temporal features of gene expression data (STGE) was proposed. Methods: We proposed an AD risk gene prediction framework based on spatial and temporal features of gene expression data. The gene expression data of providers of different tissues and ages were used as model features. Human genes were classified as AD risk or non-risk sets based on information extracted from relevant databases. Support vector machine (SVM) models were constructed to capture the expression patterns of genes believed to contribute to the risk of AD. Results: The recursive feature elimination (RFE) method was utilized for feature selection. Data for 64 tissue-age features were obtained before feature selection, and this number was reduced to 19 after RFE was performed. The SVM models were built and evaluated using 19 selected and full features. The area under curve (AUC) values for the SVM model based on 19 selected features (0.740 [0.690-0.790]) and full feature sets (0.730 [0.678-0.769]) were very similar. Fifteen genes predicted to be risk genes for AD with a probability greater than 90% were obtained. Conclusion: The newly proposed framework performed comparably to previous prediction methods based on protein-protein interaction (PPI) network properties. A list of 15 candidate genes for AD risk was also generated to provide data support for further studies on the genetic etiology of AD.

Identification of PROK2 gene polymorphisms as predictors of methamphetamine use disorder risk and indicators of craving scale in the Chinese Han population.

Background: Methamphetamine use disorder (MUD) has become a global problem due to the highly addictive nature of methamphetamine. Earlier research have demonstrated that PROK2 functions as a compensatory and protective response against neurotoxic stress by stimulating astrocyte reactivity. The aim of our study was to evaluate the correlation between the PROK2 gene and both MUD risk susceptibility and craving scale in the Chinese Han population. Methods: A total of 5,282 participants (1,796 MUD patients and 3,486 controls) were recruited. Seven tag SNPs of the PROK2 gene were chosen and genotyped in the samples. Genetic association analyses were performed to capture the significant SNPs. To investigate the relationship between PROK2 levels and craving scores with the associated-SNP genotypes, we conducted a linear model. Results: SNP rs75433452 was significantly linked with MUD risk (p-value = 1.54 × 10-8), with the A allele being positively correlated with an increased risk of MUD. Moreover, the average serum level of PROK2 decreased when more copies of the A allele were presented in both MUD patients (p-value = 4.57 × 10-6) and controls (p-value = 1.13 × 10-5). Furthermore, the genotypes of SNP rs75433452 were strongly correlated with the craving scores in MUD patients (p-value = 4.05 × 10-4). Conclusion: Our study identified a significant association signal of the PROK2 gene with MUD risk susceptibility and methamphetamine craving scores in the Chinese Han population, providing potential valuable insights into the underlying mechanisms of METH dependence.

Establishment of a potent weighted risk model for determining the progression of diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a severe complication of diabetes. Currently, no effective measures are available to reduce the risk of DKD progression. This study aimed to establish a weighted risk model to determine DKD progression and provide effective treatment strategies. METHODS: This was a hospital-based, cross-sectional study. A total of 1104 patients with DKD were included in this study. The random forest method was used to develop weighted risk models to assess DKD progression. Receiver operating characteristic curves were used to validate the models and calculate the optimal cutoff values for important risk factors. RESULTS: We developed potent weighted risk models to evaluate DKD progression. The top six risk factors for DKD progression to chronic kidney disease were hemoglobin, hemoglobin A1c (HbA1c), serum uric acid (SUA), plasma fibrinogen, serum albumin, and neutrophil percentage. The top six risk factors for determining DKD progression to dialysis were hemoglobin, HbA1c, neutrophil percentage, serum albumin, duration of diabetes, and plasma fibrinogen level. Furthermore, the optimal cutoff values of hemoglobin and HbA1c for determining DKD progression were 112 g/L and 7.2%, respectively. CONCLUSION: We developed potent weighted risk models for DKD progression that can be employed to formulate precise therapeutic strategies. Monitoring and controlling combined risk factors and prioritizing interventions for key risk factors may help reduce the risk of DKD progression.

Validation of a Disease-Free Survival Prediction Model Using UBE2C and Clinical Indicators in Breast Cancer Patients.

Objective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients. Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression. Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714-0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786-0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581-0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use. Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.

Clinicopathological and prognostic significance of SOX9 expression in gastric cancer patients: A meta-analysis.

BACKGROUND: SOX9 is a potential prognostic marker in gastric cancer (GC) patients. This meta-analysis aimed to highlight the clinicopathological and prognostic implications of SOX9 expression in GC patients. METHODS: A systematic literature search was conducted to identify relevant studies by the electronic literature databases (PubMed, Web of Science, EMBASE and Chinese databases). Review Manager version 5.4 was employed to evaluate the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS: Seventeen studies with a total of 2893 GC patients were enrolled in this meta-analysis. The analysis with ten articles clarified that higher expression of SOX9 was observed in GC cancers than that of normal gastric samples (OR = 16.26; 95% CI: 8.16 to 32.42; P < .00001). Consequently, the results also showed that SOX9 expression was closely associated with age (OR = 1.34; 95% CI: 1.04-1.72; P = .03), tumor size (OR = 0.67; 95% CI: 0.49-0.91; P = .01), histological differentiation (OR = 0.62; 95% CI: 0.36-1.06; P = .002), tumor stage (OR = 0.48; 95% CI: 0.20-1.12; P = .04), lymph node metastasis (OR = 0.36; 95% CI: 0.19-0.67; P = .0010) and advanced TNM stage (OR = 0.46; 95% CI: 0.30-0.70; P = .0003), but not significantly related to gender, distant metastasis and vascular invasion. Furthermore, high SOX9 expression could significantly indicate poorer overall survival (OS) (HR = 1.40; 95% CI: 1.14-1.72; P = .001). CONCLUSION: SOX9 overexpression might be related to poor prognosis and could serve as a potential predictive marker of poor clinicopathological prognosis factor in GC patients.

Comparison of Augmented Reality-assisted and Instructor-assisted Cardiopulmonary Resuscitation: A Simulated Randomized Controlled Pilot Trial.

Background: A trained lay rescuer is the most important determinant of survival from sudden cardiac arrest. Augmented Reality (AR) device may represent a powerful instrument for CPR assistance and self-training especially during the COVID-19 pandemic. Methods: A prospective, parallel, 1:1 pilot randomized clinical trial was designed. An AR CPR app was developed and 28 participants were randomly allocated into AR-assisted group and instructor-assisted group. Acceptability, usability, and mean per minute/per cycle chest compression depth, rate and accuracy were measured. Results: The mean scores for acceptability and usability were all rated good in each group. Comparing real-time AR-assisted CPR to instructor-assisted CPR, the mean difference of compression depth was 0.18 (95% CI: -0.18-0.53) cm and rate was -1.58 (95% CI: -6.11-2.95) min-1. Comparing AR self-training to instructor training, the AR group was not significantly different between two groups regarding both compression depth, rate and accuracy (p > .05). Conclusion: We found that the AR CPR app was an acceptable and usable tool both in real-time-assisted CPR and self-training CPR.

Correction to: A novel role of glutathione S-transferase A3 in inhibiting hepatic stellate cell activation and rat hepatic fibrosis.

An amendment to this paper has been published and can be accessed via the original article.

Baicalein, as a Prooxidant, Triggers Mitochondrial Apoptosis in MCF-7 Human Breast Cancer Cells Through Mobilization of Intracellular Copper and Reactive Oxygen Species Generation.

BACKGROUND: Baicalein, a natural flavonoid derived from traditional Chinese herb Scutellaria baicalensis Georg (known as Huang Qin in Chinese), has been reported to exhibit notable antitumor activity in various cancer cells, including breast cancer. However, the detailed mechanisms underlying its induced apoptosis as a prooxidant in breast cancer cells are still unknown. MATERIALS AND METHODS: In this study, we investigated the effect of endogenous copper on cytotoxic activity of baicalin against human breast cancer MCF-7 cells in vitro. RESULTS: Baicalein could remarkably reduce the cell viability in both dose- and time-dependent manners in MCF-7 cells but with lower cytotoxic effects on normal breast epithelial cells, MCF-10A. Such cell death could be prevented by pretreatment with Cu (I)-specific chelator neocuproine (Neo) and reactive oxygen species (ROS) scavengers. Meanwhile, baicalein could induce MCF-7 cell morphological changes, promote apoptotic cell death and increase the apoptotic cell number. Moreover, DCHF-DA staining, flow cytometry and Western blotting analyses proved that baicalein triggered the mitochondrial-dependent apoptotic pathway, as indicated by enhancement the level of intracellular ROS, disruption of mitochondrial membrane potential (ΔΨm), downregulation of anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, release of cytochrome C and activation of caspase-9 and caspase-3 in MCF-7 cells. The pretreatment with Neo remarkably weakened these effects of baicalein. Furthermore, we confirmed that the prooxidant action of baicalein involved the direct production of hydroxyl radicals through redox recycling of copper ions. CONCLUSION: These findings suggested that baicalein, acting as a prooxidant, could trigger apoptosis in MCF-7 cells occurs via the ROS-mediated intrinsic mitochondria-dependent pathway.

A novel role of glutathione S-transferase A3 in inhibiting hepatic stellate cell activation and rat hepatic fibrosis.

BACKGROUND AND AIMS: Glutathione S-transferase A3 (GSTA3) is known as an antioxidative protease, however, the crucial role of GSTA3 in liver fibrosis remains unclear. As a recently we developed water-soluble pyridone agent with antifibrotic features, fluorofenidone (AKF-PD) can attenuate liver fibrosis, present studies were designed to explore the role of GSTA3 in liver fibrosis and its modulation by AKF-PD in vivo and in vitro. METHODS: Rats liver fibrosis models were induced by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). The two activated hepatic stellate cells (HSCs) lines, rat CFSC-2G and human LX2 were treated with AKF-PD respectively. The lipid peroxidation byproduct malondialdehyde (MDA) in rat serum was determined by ELISA. The accumulation of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescein fluorescence analysis. The expression of α-smooth muscle actin (α-SMA), fibronectin (FN), and phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 beta (GSK-3ß) were detected by western blotting (WB). RESULTS: GSTA3 was substantially reduced in the experimental fibrotic livers and transdifferentiated HSCs. AKF-PD alleviated rat hepatic fibrosis and potently inhibited HSCs activation correlated with restoring GSTA3. Moreover, GSTA3 overexpression prevented HSCs activation and fibrogenesis, while GSTA3 knockdown enhanced HSCs activation and fibrogenesis resulted from increasing accumulation of ROS and subsequent amplified MAPK signaling and GSK-3ß phosphorylation. CONCLUSIONS: We demonstrated firstly that GSTA3 inhibited HSCs activation and liver fibrosis through suppression of the MAPK and GSK-3ß signaling pathways. GSTA3 may represent a promising target for potential therapeutic intervention in liver fibrotic diseases.

Ultrasound-Guided Pectoral Nerve Block I and Serratus-Intercostal Plane Block Alleviate Postoperative Pain in Patients Undergoing Modified Radical Mastectomy.

BACKGROUND: Simultaneous application of pectoral nerve block and serratus-intercostal plane block (SPB) is one of the most desirable multimodal analgesic strategies, with wide implementation of the enhanced recovery after surgery pathway for modified radical mastectomy (MRM). OBJECTIVES: The aim of the present study was to investigate the efficacy and safety of ultrasound-guided pectoral nerve block I (PECS I) and SPB for postoperative analgesia following MRM. STUDY DESIGN: A randomized, prospective study. SETTING: An academic medical center. METHODS: A total of 61 women undergoing MRM were randomly divided into 2 groups. The control group (group C, n = 32) received general anesthesia only, whereas the PECS I + SPB treated group (group PS, n = 29) received a combination of pectoral nerve block and SPB in addition to general anesthesia. RESULTS: Pain scores on a visual analog scale, opioid consumption, the duration at the postanesthesia care unit, and the incidence of adverse events were lower in group PS, compared with that of the group C. Moreover, PECS I together with SPB contributed to better sleep quality and higher patient satisfaction of pain relief. LIMITATIONS: This study was limited by its sample size. CONCLUSIONS: These results suggest that the combination of PECS I and SPB provide superior perioperative pain relief in breast cancer surgery. KEY WORDS: Pectoral nerve block, serratus-intercostal plane block, postoperative analgesia, modified radical mastectomy.

Fluorofenidone affects hepatic stellate cell activation in hepatic fibrosis by targeting the TGF-ß1/Smad and MAPK signaling pathways.

The aim of the present research was to study the therapeutic impacts of fluorofenidone (AKF-PD) on pig serum (PS)-induced liver fibrosis in rats and the complex molecular mechanisms of its effects on hepatic stellate cells (HSCs). Wistar rats were randomly divided into normal control, PS and PS/AKF-PD treatment groups. The activated human HSC LX-2 cell line was also treated with AKF-PD. The expression of collagen I and III, and α-smooth muscle actin (α-SMA) was determined by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting and/or RT-qPCR analyses were used to determine the expression of transforming growth factor (TGF)-ß1, α-SMA, collagen I, mothers against decapentaplegic homolog (Smad)-3, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). AKF-PD attenuated the degree of hepatic fibrosis and liver injury in vivo, which was associated with the downregulation of collagen I and III, and α-SMA at the mRNA and protein levels. In vitro, AKF-PD treatment significantly reduced the TGF-ß1-induced activation of HSCs, as determined by the reduction in collagen I and α-SMA protein expression. The TGF-ß1-induced upregulation of the phosphorylation of Smad 3, ERK1/2, p38 and JNK was attenuated by AKF-PD treatment. These findings suggested that AKF-PD attenuated the progression of hepatic fibrosis by suppressing HSCs activation via the TGF-ß1/Smad and MAPK signaling pathways, and therefore that AKF-PD may be suitable for use as a novel therapeutic agent against liver fibrosis.

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer.

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma (ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1, CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.