Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

Application of laparoscopic backtracking full-thickness continuous everting suture for non-AOSC choledocholithiasis.

BACKGROUND: Based on the current trend of increasing incidence of choledocholithiasis, it is of great significance to explore the closure method of the common bile duct during laparoscopic choledocholithotomy. METHODS: Backtracking full-thickness continuous everting suture was selected for primary closure of the common bile duct suture, while traditional T-tube drainage was selected for the control group. Propensity score matching (PSM) was used to reduce baseline differences between the two groups. RESULT: The intraoperative blood loss, operation time, postoperative recovery speed, postoperative bleeding, postoperative pancreatitis, recurrence rate of bile duct stones, and hospitalization time in the primary closure group were all less than those in the T-tube drainage group. CONCLUSION: Under certain conditions, backtracking full-thickness continuous everting suture could benefit patients with choledocholithiasis compared with traditional T-tube drainage.

Caregiver burden and parenting stress among left-behind elderly individuals in rural China: a cross-sectional study.

BACKGROUND: One public health problem that cannot be ignored is the mental health of left-behind elderly individuals in rural areas. However, the burden of care and parenting stress among left-behind elderly individuals has never been analyzed. The purpose of this study was to explore the level of caregiver burden and parenting stress and their relationship among left-behind elderly individuals. METHODS: A total of 261 left-behind elderly people responded to the study. The 22-item Zarit Burden Interview and the 36-item Parenting Stress Index-Short Form were used. RESULTS: We sent out 300 questionnaires in total. The effective rate was 87% (n = 261). Among the left-behind elderly individuals, most respondents were female (n = 171; 65.5%). The results showed that older age (OR:3.04; 95%CI: 1.307-7.048), an annual income of ¥5000-¥9900 (OR:3.25; 95%CI: 1.192-8.852) and higher parenting stress (OR:1.17; 95%CI: 1.103-1.242) were the risk factors related to higher caregiver burden in the left-behind elderly individuals. The influencing factor for lower caregiver burden in the left-behind elderly was gender (being male) (OR:0.08; 95%CI:0.036-0.178). Age (r = - 0.789; P < 0.001) and gender (r = 0.325; P < 0.001) were significant positively correlated with parenting stress, and annual income (r = - 0.717; P < 0.001) was negatively correlated with parenting stress. CONCLUSION: Parenting stress is a risk factor affecting caregiver burden of left-behind elderly individuals. Healthcare professionals should pay close attention to the caregiver burden and parenting stress of left-behind elderly individuals, especially those who are older, female and have lower income.

Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch-1 signaling pathway in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) has become the fourth most lethal among human cancers. Long noncoding RNAs (lncRNAs) have been reported to play a role in the progression of a variety of cancers. However, the role of lncRNA SNHG1 in PC is not clear. METHODS: Real-time Quantitative PCR Detection System (qPCR) was used to detect the expression of SNHG1 in PC cells. Then, the SNHG1 knockdown cell was constructed with si-SNHG1. AsPC-1 and PANC1 cells were used to analyze the ability of cell proliferation, invasion, and migration. MTT assay was used to analyze the proliferation ability. Transwell experiments and wound healing experiments were used to detect the capacity of invasion and migration. Finally, Western blot analysis was used to explore the mechanism of SNHG1 in PC. RESULTS: SNHG1 was significantly upregulated in PC cells. Knockdown of SNHG1 could obviously suppress cell proliferation, invasion, and migration. Furthermore, SNHG1 knockdown inhibited the activation of the Notch-1 signaling pathway and inhibited the expression of N-cadherin, Hes1, Vimentin, Notch-1. The inhabitation was reversed when Notch-1 was overexpressed in si-SNHG1 cells. CONCLUSION: The lncRNA SNHG1 promotes cell growth and metastasis in PC through activation of the Notch-1 signaling pathway in PC.

Soil bacterial community characteristics and its effect on organic carbon under different fertilization treatments.

Introduction: By implementing small-scale and efficient fertilization techniques, it is possible to enhance the activity of microorganisms, thereby improving soil carbon sequestration and ecological value in agriculture. Methods: In this study, field experiments were conducted using various types of fertilizers: organic fertilizer, microbial fungal fertilizer, composite fertilizer, and an unfertilized control (CK). Additionally, different dosages of compound fertilizers were applied, including 0.5 times compound fertilizers, constant compound fertilizers, 1.5 times compound fertilizers and CK. Using advanced technologies such as Illumina MiSeq high-throughput sequencing, PICRUSt2 prediction, Anosim analysis, redundancy analysis, canonical correlation analysis, and correlation matrix, soil organic carbon (SOC) content and components, bacterial diversity, metabolic functions, and interaction mechanisms were examined in different fields. Results and Discussion: The results showed pronounced effects of various fertilization modes on SOC and the bacterial community, particularly in the topsoil layer (0-20 cm). Organic fertilizer treatments increased the richness and diversity of bacterial communities in the soil. However, conventional doses and excessive application of compound fertilizers reduced the diversity of soil bacterial communities and SOC content. Additionally, different fertilization treatments led to an increase in easily oxidizable organic carbon (EOC) contents. Interestingly, the relationship between SOC components and soil bacteria exhibited inconsistency. EOC was positively correlated with the bacterial diversity index. Additionally, Chloroflexi exhibited a negative correlation with both SOC and its components. The influence of metabolismon primary metabolic functions on the content of SOC components in the soil was more notable. It included seven types of tertiary functional metabolic pathways significantly correlated with SOC components (p < 0.05). Purpose and Significance: These findings enhance the understanding of the relative abundance of bacterial communities, particularly those related to the carbon cycle, by adjusting agricultural fertilization patterns. This adjustment serves as a reference for enhancing carbon sinks and reducing emissions in agricultural soils.

SIN1 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition.

BACKGROUND: Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is essential for early embryonic development and is the key regulator of Akt, which plays an important role in various pathological conditions such as cancer. However, the biological function and clinical significance of SIN1 in hepatocellular carcinoma (HCC) remains unknown. METHODS: Real-time quantitative reverse-transcriptase polymerase chain reaction analysis, western blot analysis, and immunohistochemical staining were used to test the expression level of SIN1, and its correlation with clinicopathologic parameters as well as the prognosis for patients with HCC were analyzed. In addition, the biological function and molecular mechanisms of SIN1 in HCC were investigated. RESULTS: SIN1 levels were elevated predominantly in HCC tissues, and its level in solitary large HCC was significantly lower than those in nodular HCC (P = .016), but showed no significant differences between solitary large HCC and small HCC (P > .05). Levels of SIN1 were up-regulated in highly metastatic HCC cell lines (HCCLM3 and MHCC97-H), whereas their invasion and migration significantly decreased after depletion of SIN1. High expression of SIN1 was associated with tumor number (P = .012), capsular formation (P = .037), and venous invasion (P = .023) and was an independent risk factor for overall survival (P = .046). Finally, SIN1 was capable of promoting invasion and metastasis of HCC by facilitating epithelial-mesenchymal transition. CONCLUSIONS: The current findings suggest that SIN1 plays an important role in HCC invasion and metastasis by facilitating epithelial-mesenchymal transition.

Extraction and detection of morin from Sanghuangporus lonicericola by magnetic molecularly imprinted polymers coupled with HPLC analysis.

In this study, morin magnetic molecularly imprinted polymers (Morin-MMIPs) were synthesized based on magnetic nanoparticles and surface molecularly imprinted technology with superparamagnetism and extraction selectivity. The polymers allowed the separating of morin from complex matrices in the presence of an external magnetic field with no need for centrifugation or filtration. The microstructure of the polymers was characterized by scanning electron microscopy and transmission electron microscopy. Meanwhile, the functional group and magnetic properties of the polymers were characterized using Fourier transform infrared spectroscopy (FT-IR) and magnetic vibration meter (VSM). The maximum adsorption capacity of MMIPs was 3.24 mg/g, which was 2.55 times higher than that of MNIPs (1.27 mg/g). Morin was quantified by HPLC-DAD, which showed good linearity in the concentration range of 0.05-60 µg/ml with the correlation coefficient R2  = 0.9993. The limit of detection (LOD) was 0.08 µg/ml, and the spiked recoveries were 87.5-106.8%. The calculation of the adsorption isotherm and kinetic model revealed the adsorption mechanisms, and the adsorption process was consistent with the Langmuir adsorption isotherm and pseudo-secondary kinetic models. Likewise, the material has been successfully used to extract and separate morin from food samples. The method reported in this paper has the advantages of fast adsorption speed, high selectivity, and environmental friendliness. It provided a reliable method for the separation and detection of morin or other natural products.

A ratio fluorescence method based on dual emissive gold nanoclusters for detection of biomolecules and metal ions.

Gold nanoclusters have good biocompatibility and can be easily modified to improve their luminescence properties. In this study, we prepared a new type of dual-emitting gold nanoclusters (d-Au NCs) for discriminative detection of phenylalanine and Fe3+ with high selectivity and sensitivity. The fluorescence sensor which was synthesized without any further assembly or conjugation shows dual-emissions at 430 nm and 600 nm under a single excitation at 350 nm. Phenylalanine can turn on the red emission of the probe, while Fe3+ can turn on its yellow emission and turn off the red emission. By detecting a variety of amino acids and metal ions, d-Au NCs showed good selectivity to phenylalanine and Fe3+. Finally, this method was applied to determine phenylalanine and Fe3+ in lake water, human urine and milk, which has certain application prospects in the field of biology and environment.

Effects of cubic ecological restoration of mining wasteland and the preferred restoration scheme.

In view of the strong acidity and high heavy metal contents of the soil, the low vegetation cover, and strong soil erosion caused by mining activities, the reasonable determination of the cubic restoration mode is the key to determining the good or bad ecological restoration effects on mining wasteland. In this study, based on field experiments, a combined cubic ecological restoration scheme for soil improvement-vegetation reconstruction was constructed. Using analysis of variance, a regression model, and the Mantel test, the differences in soil properties and the biodiversity were analyzed under different restoration schemes, the entropy-weighted-TOPSIS method was used to optimize the best ecological restoration model. The results revealed that compared with the pre-restoration state, the restoration significantly increased the soil pH (p < 0.05) by 4.07-5.73, regulated the strong acidic environment of the soil, increased the organic matter content by 5.35-11.21 times, and improved the soil fertility. The available contents of Pb and Cd were reduced by 67.15-75.58 % and 64.15-88.68 %, respectively compared with the background values. Biodiversity improved significantly, and the available content of Cd was an important factor in the biodiversity recovery. The evaluation of the effect of the restoration scheme showed that the combination of mixed soil amendments of rice husks and chicken manure (10 kg/m2), bacterial fertilizer (1.8 kg/m2), biochar (1.3 kg/m2), lime (8.3 kg/m2), and soil conditioner (1.0 kg/m2) and tolerant plants (Pinus elliottii, Lagerstroemia indica, and Plantago asiatica) are the optimal cubic ecological restoration scheme for the study area, with a plant survival rate of > 90 %, eight families and 10 species of plants, and a coverage rate of 100 %. These research results provide a scientific basis and technical support for reasonable artificial intervention in ecological restoration of mining waste sites in Nanling, northern Guangdong.

Delayed Facial Palsy After Microvascular Decompression for Hemifacial Spasm.

OBJECTIVE: We explored the risk factors for the occurrence of delayed facial paralysis (DFP) after microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: A retrospective study was conducted of 636 patients who had undergone MVD for HFS by the same neurosurgery department of China-Japan Friendship Hospital from January 2006 to May 2016. Of the 636 patients, 50 (7.9%) had presented with DFP, which had developed from 2 to 60 days postoperatively (average, 12.9 ± 10.0005 days). All 50 patients with DFP had recovered completely within 10-300 days (average, 88.7 ± 61.389 days) after the onset of DFP. We randomly selected 100 patients from the 586 patients without DFP as the control group. Univariate and multivariate logistic analyses were used to analyze the risk factors involved in the occurrence of DFP. RESULTS: Univariate analysis showed that the disease course was the only factor associated with the development of DFP (P = 0.003). Furthermore, on multivariate logistic analysis, the course of HFS was the only risk factor associated with the development of DFP (P = 0.01). Additionally, the Spearman test revealed a positive correlation between the onset of DFP and the duration of the DFP symptoms (rs = 0.682; P < 0.001). CONCLUSION: Although DFP frequently occurred after MVD, it can recover spontaneously. The longer the course of HFS, the more frequently DFP will occur after MVD. The earlier that DFP develops, the shorter will be the time to recovery.

CircCSPP1 Functions as a ceRNA to Promote Colorectal Carcinoma Cell EMT and Liver Metastasis by Upregulating COL1A1.

The aberrant regulation of circular RNAs (circRNAs), ring structures formed by exon or intron backsplicing, has been identified as a novel characteristic of multiple cancers. However, the role of circRNAs in colorectal carcinoma remains to be elucidated. In the present study, we investigated the mRNA level and the promoting effect of circRNA CSPP1 (circCSPP1) in colorectal carcinoma liver metastasis. By bioinformatic analysis of 10 paired samples of colorectal carcinoma and adjacent mucosal tissues, we identified circCSPP1 as a significantly upregulated circRNA in colorectal carcinoma tissues, and its upregulation was correlated with a higher M stage. The gain- and loss-of-function assays revealed that circCSPP1 promotes the migration and invasion of colorectal carcinoma cells in vitro and in vivo. Mechanistically, similar miRNA response elements are shared between circCSPP1 and COL1A1. We demonstrated that circCSPP1 upregulates the mRNA levels of COL1A1, which plays a pivotal role in the process of epithelial-mesenchymal transition (EMT), by competitively binding to miR-193a-5p and preventing miR-193a-5p from decreasing the expression of COL1A1. In conclusion, this finding indicates that circCSPP1 may act as a promising therapeutic target by regulating the EMT process in colorectal carcinoma via activation of the circCSPP1/miR-193a-5p/COL1A1 axis.

A provincial lateral carbon emissions compensation plan in China based on carbon budget perspective.

Inter-provincial lateral carbon compensation (IPLCC) is considered as a market-based tool to achieve the goal of carbon emission mitigation from the national level as well as contribute to fair development rights of various provinces. However, empirical research on lateral carbon compensation is still insufficient at the provincial level. Therefore, the improved carbon budget method is proposed to construct a provincial carbon budget accounting and evaluate the level of provincial lateral carbon compensation. The findings are concluded as follows: (1) Carbon emission and absorption in China have experienced rapid growth in the period of 2005-2015. (2) There exists an obvious spatial difference in the provincial carbon budget. The amount of provincial carbon emissions is high in the east and low in the west, while the provincial carbon absorption is high in the northeast and southwest and low in the other regions. (3) 30 Provinces in China can be classified into three types, namely those that have to pay for lateral carbon compensation, those that should be refunded, and those in relative equilibrium. (4) Whether a province should pay for or be refunded from lateral carbon compensation is related to the development level of the secondary industry. (5) Inter-provincial lateral carbon compensation will play a significant role in the top-level design of total carbon emission controlling across different provinces in China. Finally, three policy implications are proposed, including constant promotion of the decoupling of provincial economic development and carbon emissions, formulation of accounting standards and methods for lateral carbon compensation, and adoption of multiple lateral carbon compensation methods.

[Composition, Characteristics, and Accumulation of Antibiotics in the Soil in Agricultural Land].

Exploring the composition and accumulation of antibiotics in agricultural land soil for soil for quality management of agricultural land and control of antibiotic pollution is of great significance. A total of 95 soil samples were collected from farmland soil in a typical agricultural and sideline production base of northern China. In this study, the concentrations of 10 antibiotics, including tetracycline antibiotics (TCs), macrolide antibiotics (MLs), and sulfonamide antibiotics (SAs), were determined in soil samples from different land use types using HPLC-MS/MS. In addition, the composition and spatial distribution of the antibiotics were compared. The relationships between the concentration distributions and the distance from livestock farms, highways, and rivers were analyzed. Moreover, the composition and accumulation of antibiotics in the soil with different planting patterns and soil properties were preliminarily discussed. The results showed that the concentrations of antibiotics in the soil were low-level, while the detection rate was high; in particular, the detection rate of the total amount of antibiotics was as high as 100%. In the study area, TCs were the dominant antibiotic types, accounting for 94% of the total. The coefficient variation (CV) was high, which reflected a significant difference in the spatial variation of these antibiotics. The spatial distribution and accumulation of antibiotics in the soil in this area were affected by the intensity of human activity. The detection rate and concentrations of the various antibiotics decreased with increasing distance between the soil sample and livestock farms, highways, and rivers. Among these, there was a significant negative correlation between the concentration of antibiotics and the distance between livestock farms and the soil samples (P<0.05). The detection rate of three types of antibiotics in soil samples from within 50 meters of a river reached 100%. The total concentration of the 10 antibiotics was the highest in orchards, followed by vegetable plots, and mixed fruit and vegetable areas. Furthermore, the sources and concentrations of antibiotics in a peach orchard and open-air vegetable field were significantly different from those in a walnut orchard, greenhouse vegetable field, and mixed field. Moreover, the soil pH, soil organic matter (SOM), cation exchange capacity (CEC), total nitrogen (TN), available phosphorus (AP), and available potassium (AK) were selected to characterize soil properties. Redundancy analysis showed that soil properties such as pH, SOM, CEC, AP, AK have a greater impact on the distribution of antibiotics. The distribution of antibiotics was most closely related to AK, and the effect of TN was relatively weak. The results of this study suggested that the composition and accumulation of soil antibiotics in the area were affected by human activities and soil properties.

Hyperspectral indirect inversion of heavy-metal copper in reclaimed soil of iron ore area.

To explore a rapid detection technology for detecting heavy metals in soil based on hyperspectral data, this paper took an iron mine in Daye Country, Hubei Province, as the research area, used a FieldSpec4 portable ground object spectrometer to obtain soil spectral reflectance and combine the measured data, and used three spectral transformation methods: first-order differential, second-order differential, and continuum removal. We studied the indirect hyperspectral inversion of heavy metals in reclaimed soils in the iron mine area by using three models: partial least squares regression, support vector machine, and back propagation (BP) neural network. The results show that spectral transformation can effectively highlight the position of spectral characteristic bands and improve the correlation between spectral curves and iron (Fe) element concentration. The partial least squares regression model based on first-order differential had the highest inversion accuracy for Fe element concentration in the study area, R2 and RMSE were 0.88 and 0.53, respectively. The correlation analysis of soil elements showed that the highest correlation coefficient between Cu and Fe was 0.81. We selected the copper (Cu) element with the largest correlation coefficient with the Fe element as an example and realized the indirect prediction of soil Cu concentration using a linear regression model and BP neural network model. Among them, the model based on BP neural network is better, R2 was 0.82, RMSE was 0.62, compared with the direct method, the model R2 increased by about 0.2, and the root mean square error decreased by about 0.1. The effect of the indirect method was better than that of the direct method. We selected the optimum statistical interpolation method for spatial analysis of Fe and Cu concentrations in the soil of the study area and further demonstrated the feasibility of the indirect inversion method of heavy metals in the soil of iron mine areas based on hyperspectral data. These results provide a theoretical basis and new ideas for the application of near-earth sensing technology in soil and for efficient detection of heavy metals in iron ore areas.

The autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer.

PURPOSE: To investigate the role of the autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer. METHODS: A total of 86 pancreatic cancer tissues and 84 paired, adjacent normal pancreatic tissues were collected from 86 patients who underwent pancreatic resection surgery in our hospital from January 2009 to August 2011. Demographic data including age, gender, family cancer history, and clinic-pathological characteristics, including tumor diameter, differential, TNM staging and lymphatic metastasis were collected. The expressions of Beclin1 and LC3 were determined using both immunohistochemistry (IHC) and RT-qPCR. RESULTS: The expression levels of both Beclin1 and LC3 mRNA and proteins were significantly up-regulated in the tumor tissues compared with the normal tissues. Higher expressions of Beclin1 and LC3 were found in the tumor tissues of patients with TNM stages III~IV, patients with lymphatic metastasis, and patients who died. Meanwhile Beclin1 and LC3 correlated with TNM stage, differential condition, and the patients' lymphatic metastasis rates. A survival analysis showed that patients with low expressions of Beclin1 and LC3 had longer survival times, and both the Beclin1 and LC3 genes were independent risk factors for 5-year mortality in pancreatic cancer patients. CONCLUSION: The Beclin1 and LC3 genes correlate with the tumor stage, metastasis conditions, and pancreatic cancer patients' mortality.