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Background Endoscopic resection (ER) is a promising technique for resecting gastric gastrointestinal stromal tumors (gGISTs); however, ER is technically challenging. This study aimed to develop and validate a difficulty scoring system (DSS) to determine the difficulty for ER of a gGIST. Methods This retrospective study enrolled 555 patients with gGISTs in multi-centers from December 2010 to December 2022. Data on patients, lesions, and outcomes of ER were collected and analyzed. A difficult case was defined as an operative time ≥ 90 min, or the occurrence of severe intraoperative bleeding, or conversion to laparoscopic resection. The DSS was developed in the training cohort (TC) and validated in the internal validation cohort (IVC) and external validation cohort (EVC). Results The difficulty occurred in 97 cases (17.5%). The DSS comprised the following: tumor size ≥ 3.0 cm (3 points) or 2.0–3.0 cm (1 point); location in the upper third of the stomach (2 points); invasion depth beyond the muscularis propria (2 points); lack of experience (1 point). The area under the curve (AUC) of DSS in IVC and EVC was 0.838 and 0.864, respectively, and the negative predictive value (NPV) was 0.923 and 0.972, respectively. The proportions of difficult operation in easy (score 0–3), intermediate (score 4–5), and difficult (score 6–8) categories were 6.5%, 29.4%, and 88.2% in the TC, 7.7%, 45.8%, and 85.7% in the IVC, and 7.0%, 29.4%, and 85.7% in the EVC, respectively. Conclusions We developed and validated a preoperative DSS for ER of gGISTs based on tumor size, location, invasion depth, and endoscopists’ experience. This DSS can be used to grade the technical difficulty before surgery.

The single progesterone receptor (PR)-positive phenotype (estrogen receptor (ER)-/PR + , sPR positive) is an infrequent and independent biological entity. However, the prognosis of patients with sPR-positive and her-2-negative phenotype is still controversial, and it is not always easy to decide treatment strategies for them.Patients during 2010-2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS). The propensity score matching (PSM) method was used to balance differences of characteristics in groups. The Life-Table method was used to calculate 5-year CSS rates and the annual hazard rate of death (HRD).A total of 97,527 patients were included, and only 745 (0.76%) patients were sPR-positive phenotype. The majority of sPR-positive breast cancer were basal-like subtype. Survival analysis showed that the sPR-positive breast cancer had similar prognosis comparing to double hormonal receptor-negative (ER-/PR-, dHoR-negative) breast cancer, and had the highest HRD during the initial 1-2 years of follow-up, then maintained the HRD of almost zero during the late years of follow-up.The patients with sPR-positive and her-2-negative breast cancer, similar to dHoR-negative breast cancer, had a worse survival, and could benefit from chemotherapy significantly. However, the escalating endocrine therapy was not recommended for sPR-positive patients. The patients with sPR positive should be excluded from future clinical trials concerning endocrine therapy.

Spasticity is a typical consequence after spinal cord injury (SCI). The critical reasons are reducing the synthesis of Gamma-Aminobutyric Acid (GABA), glycine and potassium chloride co-transporter 2 (KCC2) inside the distal spinal cord. The current work aimed to test whether exercise training could increase the expression of glutamic acid decarboxylase 65/67 (GAD-65/67, the key enzymes in GABA synthesis) and KCC2 in the distal spinal cord via tropomyosin-related kinase B (TrkB) signaling. The experimental rats were randomly assigned to the following five groups: Sham, SCI/phosphate-buffered saline (PBS), SCI-treadmill training (TT)/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG. After that, the model of T10 contusion SCI was used, then TrkB-IgG was used to prevent TrkB activity at 7 days post-SCI. Body weight-supported treadmill training started on the 8th day post-SCI for four weeks. The Hmax/Mmax ratio and the rate-dependent depression of H-reflex were used to assess the excitability of spinal motoneuronal networks. Western blotting and Immunohistochemistry techniques were utilized for measuring the expression of GAD-65, GAD-67, and KCC2. The findings revealed that exercise training could reduce motoneuronal excitability and boost GAD-65, GAD-67, and KCC2 production in the distal region of the spinal cord after SCI. The effects of exercise training were decreased after the TrkB signaling was inhibited. The present exploration demonstrated that exercise training increases GAD-65, GAD-67, and KCC2 expression in the spinal cord via TrkB signaling and that this method could also improve rats with motoneuronal hyperexcitability and spasticity induced by incomplete SCI.

Chemotherapy-related thrombocytopenia (CIT) is a significant adverse event during chemotherapy, which can lead to reduced relative dose intensity, increased risk of serious bleeding and additional medical expenditure. Herein, we aimed to develop and validate a predictive nomogram model for prediction of CIT in patients with solid tumor. From Jun 1, 2018 to Sep 9, 2021, a total of 1541 patients who received 5750 cycles of chemotherapy were retrospectively enrolled. Cox regression analysis was performed to identify predictive factors to establish the nomogram model for CIT. The incidence of chemotherapy-induced thrombocytopenia was 21.03% for patient-based and 10.26% for cycles of chemotherapy. The top five solid tumors with CIT are cervix, gastric, bladder, biliary systemic, and ovarian. The incidence of chemotherapy dose delays in any cycle because of CIT was 5.39%. Multivariate analysis showed that tumor site, treatment line, AST, oxaliplatin, and capecitabine were significantly associated with CIT. Moreover, we established a nomogram model for CIT probability prediction, and the model was well calibrated (Hosme-Lemeshow P = 0.230) and the area under the receiver operating characteristic curve was 0.844 (Sensitivity was 0.625, Specificity was 0.901). We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical characteristics. The predictive model based on clinical and laboratory indices represents a promising tool in the prediction of CIT, which might complement the clinical management of thrombocytopenia.

Chinese hamster ovary (CHO) cell lines are widely used to manufacture biopharmaceuticals. However, CHO cells are not an optimal expression host due to the intrinsic plasticity of the CHO genome. Genome plasticity can lead to chromosomal rearrangements, transgene exclusion, and phenotypic drift. A poorly understood genomic element of CHO cell line instability is extrachromosomal circular DNA (eccDNA) in gene expression and regulation. EccDNA can facilitate ultra-high gene expression and are found within many eukaryotes including humans, yeast, and plants. EccDNA confers genetic heterogeneity, providing selective advantages to individual cells in response to dynamic environments. In CHO cell cultures, maintaining genetic homogeneity is critical to ensuring consistent productivity and product quality. Understanding eccDNA structure, function, and microevolutionary dynamics under various culture conditions could reveal potential engineering targets for cell line optimization. In this study, eccDNA sequences were investigated at the beginning and end of two-week fed-batch cultures in an ambr®250 bioreactor under control and lactate-stressed conditions. This work characterized structure and function of eccDNA in a CHO-K1 clone. Gene annotation identified 1551 unique eccDNA genes including cancer driver genes and genes involved in protein production. Furthermore, RNA-seq data is integrated to identify transcriptionally active eccDNA genes.

Many species of lizards are capable of tail regeneration. There has been increased interest in the study of lizard tail regeneration in recent years as it is an amenable regeneration model for amniotes. In this study, Gekko japonicus was used as a model to investigate the initiation of vascularization, innervation and myogenesis during tail regeneration. We found that angiogenesis and axon regeneration occurred almost simultaneously within 4 days post amputation. The results showed that the endothelial cells of the original vasculature proliferated and extended into the blastema as capillary vessels, which inter-connected to form a capillary network. The nerve fibers innervated the regenerated tissue from the original spinal cord and dorsal root ganglia, and the fiber bundles increased during 14 days. Regenerating muscle tissues emerged 2 weeks after amputation. PAX3 and PAX7 expression were detected during myogenesis, with PAX7 showing a continuous increase in expression from day 3 until the day 14, whereas PAX3 reached a peak level on day 10 day post amputation, and then declined quickly to level as normal control on day 14. PCNA and PAX3 double-positive satellite cells were observed in the original rostral tissues, indicating the involvement of satellite cell proliferation during tail regeneration. Taken together, these data suggest that tail regeneration in Gekko japonicus involved rapid angiogenesis from the beginning to the day 10 and followed by capillary remodeling. The innervation of regenerated tail was significant on day 4 and increased gradually during regeneration, while the regenerated muscle tissues was obvious on day 14 after amputation.

Background Volatile components are important secondary metabolites essential to fruit aroma quality, thus, in the past decades many studies have been extensively performed in clarifying fruit aroma formation. However, aroma components and biosynthesis in the fruit of Binzi (Malus pumila × Malus asiatica), an old local species with attractive aroma remain unknown. Results We investigated two Binzi cultivars, ‘Xiangbinzi’ (here named high-fragrant Binzi, ‘HFBZ’) and ‘Hulabin’ (here named low-fragrant Binzi, ‘LFBZ’) by monitoring the variation of volatiles and their precursors by Gas Chromatography–Mass Spectrometer (GC–MS), as well as their related genes by RNA-seq during post-harvest ripening. We firstly confirmed that ‘HFBZ’ and ‘LFBZ’ fruit showed respiratory climacteric by detecting respiratory rate and ethylene emission during post-harvest; found that esters were the major aroma components in ‘HFBZ’ fruit, and hexyl 2-methylbutyrate was responsible for the ‘fruity’ note and most potent aroma component, followed by ethyl acetate, ethyl butanoate, (E)-2-hexenal, and 1-hexanol. Regarding aroma synthesis, fatty acid metabolism seemed to be more important than amino acid metabolism for aroma synthesis in ‘HFBZ’ fruit. Based on RNA-seq and quantitative reverse transcription PCR (RT-qPCR), LOX2a, LOX5a, ADH1, and AAT1 genes are pointed to the LOX pathway, which may play a vital role in the aroma formation of ‘HFBZ’ fruit. Conclusion Our study firstly investigated the aroma components and related genes of Binzi fruit, and provided an insight into the fragrant nature of Malus species.

The formation of wound epithelium initiates regeneration of amputated tail in Gekko japonicus. Energy metabolism is indispensable for the growth of living creatures and typically influenced by temperature. In this study, we reveal that low temperature lowers energy metabolism level and inhibits the regeneration of amputated tails of Gekko japonicus. We further find that low temperature attenuates the activation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in regenerated tissues upon injury signals, and the inhibition of Akt hinders proliferation of the wound epithelium. Additionally, wingless/integrated (Wnt) inhibition suppresses epithelium proliferation and formation by inhibiting Akt activation. Finally, low temperature elevates the activity of adenylate-activated kinase (AMPK) pathway and in turn attenuates wound epithelium formation. Meanwhile, either mTOR downregulation or AMPK upregulation is associated with worse wound epithelium formation. Summarily, low temperature restricts wound epithelium formation by influencing energy sensory pathways including Akt/mTOR and AMPK signaling, which is also modulated by injury induced Wnt signal. Our results provide a mechanism that incorporates the injury signals with metabolic pathway to facilitate regeneration.

Immune checkpoint inhibitors (ICIs) are most commonly used for melanoma and non-small cell lung cancer (NSCLC) patients. FAT atypical cadherin 1 (FAT1), which frequently mutates in melanoma and NSCLC. In this study, we aim to investigate the association of FAT1 mutations with ICI response and outcome. We collected somatic mutation profiles and clinical information from ICI-treated 631 melanoma and 109 NSCLC samples, respectively. For validation, a pan-cancer cohort with 1661 patients in an immunotherapy setting was also used. Melanoma and NSCLC samples from the Cancer Genome Atlas were used to evaluate the potential immunologic mechanisms of FAT1 mutations. In melanoma, patients with FAT1 mutations had a significantly improved survival outcome than those wild-type patients (HR: 0.67, 95% CI: 0.46–0.97, P = 0.033). An elevated ICI response rate also appeared in FAT1-mutated patients (43.2% vs. 29.2%, P = 0.032). Associations of FAT1 mutations with improved prognosis and ICI response were confirmed in NSCLC patients. In the pan-cancer cohort, the association between FAT1 mutations and favorable ICI outcome was further validated (HR: 0.74, 95% CI: 0.58–0.96, P = 0.022). Genomic and immunologic analysis showed that a high mutational burden, increased infiltration of immune-response cells, decreased infiltration of immune-suppressive cells, interferon and cell cycle-related pathways were enriched in patients with FAT1 mutations. Our study revealed that FAT1 mutations were associated with better immunogenicity and ICI efficacy, which may be considered as a biomarker for selecting patients to receive immunotherapy.

Four heterotic QTL and a heterozygous segment for plant weight were identified by Graded Pool-Seq, QTL-seq and traditional genetic linkage analysis in heading Chinese cabbage. Heading Chinese cabbage (Brassica rapa L. spp. pekinensis) is a cross-pollinated leafy vegetable with significant heterosis. The use of heterosis is important for breeding high-yield Chinese cabbage hybrids. However, the formation and mechanism of heterosis have not been studied. We dissected the molecular mechanism of heterosis of yield-related traits in Chinese cabbage. An F

Background Baculoviruses act as effective biological control agents against the invasive pest Hyphantria cunea Drury. In this study, two Chinese Hyphantria cunea nucleopolyhedrovirus (HycuNPV) isolates, HycuNPV-BJ and HycuNPV-HB, were deep sequenced and compared with the Japanese isolate, HycuNPV-N9, to determine whole-genome level diversity and evolutionary history. Results The divergence of the phylogenetic tree and the K2P distances based on 38 core-gene concatenated alignment revealed that two Chinese HycuNPV isolates were a novel species of Alphabaculovirus that infected Hyphantria cunea in China. The gene contents indicated significant differences in the HycuNPV genomes between the Chinese and Japanese isolates. The differences included gene deletions, acquisitions and structural transversions, but the main difference was the high number of single nucleotide polymorphisms (SNPs). In total, 10,393 SNPs, corresponding to approximately 8% of the entire HycuNPV-N9 genome sequence, were detected in the aligned reads. By analyzing non-synonymous variants, we found that hotspot mutation-containing genes had mainly unknown functions and most were early expressing genes. We found that the hycu78 gene which had early and late promoter was under positive selection. Biological activity assays revealed that the infectivity of HycuNPV-HB was greater than that of HycuNPV-BJ, and the killing speed of HycuNPV-HB was faster than that of HycuNPV-BJ. A comparison of molecular genetic characteristics indicated that the virulence differences between the two isolates were affected by SNP and structural variants, especially the homologous repeat regions. Conclusions The genomes of the two Chinese HycuNPV isolates were characterized, they belonged to a novel species of Alphabaculovirus that infected Hyphantria cunea in China. We inferred that the loss or gain of genetic material in the HycuNPV-HB and HycuNPV-BJ genomes resulted in new important adaptive capabilities to the H. cunea host. These results extend the current understanding of the genetic diversity of HycuNPV and will be useful for improving the applicability of this virus as a biological control agent.

Intracerebral hemorrhage (ICH) is the most fatal subtype of stroke; there is still a lack of effective treatment. Microglia are a major component of the innate immune system, and they respond to acute brain injury by activating and forming classic M1-like (pro-inflammatory) or alternative M2-like (anti-inflammatory) phenotype. The existence of the polarization indicates that the role of microglia in disease's progression and recovery after ICH is still unclear, perhaps involving microglial secretion of anti-inflammatory or pro-inflammatory cytokines and chemokines. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is considered to be the main participant in neuroinflammation. Recent evidence has shown that NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. Furthermore, previous studies have reported that NLRP3 inflammasome is mainly present in microglia, so we speculate that its activation may be strongly associated with microglial polarization. Many scholars have investigated the role of brain injury caused by NLRP3 inflammasome after ICH, but the precise operating mechanisms remain uncertain. This review summarized the activation mechanism of NLRP3 inflammasome after ICH and the possible mechanism of NLRP3 inflammasome promoting neuroinflammation and aggravating nerve injury and discussed the relevant potential therapeutic targets.

Considering a family of rational maps Tnλ concerning renormalization transformation, we give a perfect description about the dynamical properties of Tnλ and the topological properties of the Fatou components F(Tnλ). Furthermore, we discuss the continuity of the Hausdorff dimension HD(J(Tnλ)) about real parameter λ.

Background Prostate cancer (PCa) is the second leading cause of cancer-related male deaths worldwide. The purpose of this study was to investigate the effects of homo sapiens solute carrier family 4 member 4 (SLC4A4), which encodes the electrogenic Na+/HCO3− cotransporter isoform 1 (NBCe1), in the development and progression of PCa. Methods The expression levels of SLC4A4 in PCa and normal prostate tissues were evaluated by immunohistochemistry. The SLC4A4 knockdown cell model was structured by lentiviral infection, and the knockdown efficiency was validated by RT-qPCR and Western blotting. The effects of SLC4A4 knockdown on cell proliferation, apoptosis and cycle, migration, and invasion were detected by Celigo cell counting assay and CCK-8 assay, flow cytometry analysis, wound-healing, and Transwell assay, respectively. Tumor growth in nude mice was surveyed by in vivo imaging and Ki-67 staining. Furthermore, underlying mechanism of SLC4A4 silence induced inhibition of PCa progression was explored by human phospho-kinase array. Results Our results revealed that SLC4A4 expression was up-regulated in PCa tissues and human PCa cell lines. High expression of SLC4A4 in tumor specimens was significantly correlated with disease progression. SLC4A4 knockdown inhibited cell proliferation, migration and invasion, while facilitated apoptosis, which was also confirmed in vivo. Moreover, SLC4A4 promoted PCa progression through the AKT-mediated signalling pathway. Conclusion The results of this study indicated that SLC4A4 overexpression was closely associated with the progression of PCa; SLC4A4 knockdown suppressed PCa development in vitro and in vivo. SLC4A4 acts as a tumor promotor in PCa by regulating key components of the AKT pathway and may therefore act as a potential therapeutic target for PCa treatment.

Image deblurring is a fundamental problem in imaging field which often needs to recover the important structure of images. This paper addresses the image deblurring problem by considering an image as a combination of its cartoon (the piecewise smooth part of the image) and texture (the oscillation part of the image) components. To recover both of these parts, we propose the use of coupled analysis-based sparse representations to regularize the cartoon structure and the texture part of the image. We apply anisotropic total variation with a quadratic term to enhance the edges existing in the cartoon part. Furthermore, we develop a multivariable Bregman optimization method to solve the proposed image restoration model by combining the alternating minimization method and the split Bregman iteration. The experiments show that the proposed algorithm not only performs well for image decomposition, but also outperforms the previously established methods in terms of the visual residual error, the structure similarity index and the peak signal-to-noise ratio for image deblurring.

On 7 March 2019, African swine fever in a domestic pig farm was detected in Guangxi Province of China. The phylogenetic analysis showed that its causative strain contained two tandem repeat sequence insertions in the intergenic region between the I73R and the I329L genes, and was different from previously reported strains in China and other countries.

Background As bioprocess intensification has increased over the last 30 years, yields from mammalian cell processes have increased from 10’s of milligrams to over 10’s of grams per liter. Most of these gains in productivity can be attributed to increasing cell densities within bioreactors. As such, strategies have been developed to minimize accumulation of metabolic wastes, such as lactate and ammonia. Unfortunately, neither cell growth nor biopharmaceutical production can occur without some waste metabolite accumulation. Inevitably, metabolic waste accumulation leads to decline and termination of the culture. While it is understood that the accumulation of these unwanted compounds imparts a suboptimal culture environment, little is known about the genotoxic properties of these compounds that may lead to global genome instability. In this study, we examined the effects of high and moderate extracellular ammonia on the physiology and genomic integrity of Chinese hamster ovary (CHO) cells. Results Through whole genome sequencing, we discovered 2394 variant sites within functional genes comprised of both single nucleotide polymorphisms and insertion/deletion mutations as a result of ammonia stress with high or moderate impact on functional genes. Furthermore, several of these de novo mutations were found in genes whose functions are to maintain genome stability, such as Tp53, Tnfsf11, Brca1, as well as Nfkb1. Furthermore, we characterized microsatellite content of the cultures using the CriGri-PICR Chinese hamster genome assembly and discovered an abundance of microsatellite loci that are not replicated faithfully in the ammonia-stressed cultures. Unfaithful replication of these loci is a signature of microsatellite instability. With rigorous filtering, we found 124 candidate microsatellite loci that may be suitable for further investigation to determine whether these loci may be reliable biomarkers to predict genome instability in CHO cultures. Conclusion This study advances our knowledge with regards to the effects of ammonia accumulation on CHO cell culture performance by identifying ammonia-sensitive genes linked to genome stability and lays the foundation for the development of a new diagnostic tool for assessing genome stability.

Background Extant literature reveals that medical students suffer from various mental health problems in the process of learning medicine. However, there are few studies evaluating the implementation of a mental health education course in medical curriculum. The current study aimed to test the effectiveness of an 8-week intensive mental health education course, the College Student Mental Health Education Course (CSMHEC), and to gain further insights on how the course could be improved from students’ feedback. Methods This is a quasi-experimental study with both quantitative and qualitative analyses. We recruited 374 first year medical students as our subjects with 188 (age = 17.97 ± 0.65 years, 37.2% male) for the experiment group and 186 (age = 18.02 ± 0.63 years, 40.3% male) for the control group. For quantitative analysis, Depression Anxiety Stress Scales-21 (DASS-21), Chinese College Student Academic Burnout Inventory (CCSABI) and Satisfaction With Life Scale (SWLS) were used and a 5-point Likert scale was used to indicate students’ overall satisfaction with CSMHEC. For qualitative analysis, a thematic analysis method was adopted to gain insights from the feedback of medical students. Results Medical students in the experiment group saw a significant decline in psychological distress (p d = 0.31) and academic burnout (p d = 1.46), while they experienced a significant increase in life satisfaction levels after the intervention (p d = 0.48). Compared with students in the control group, students in the experiment group had statistically significant lower levels of psychological distress (p d = 0.23) and academic burnout (p d = 0.70), but statistically significant higher levels of life satisfaction in the post-test (p d = 0.31). Most students in the experiment group were satisfied with CSMHEC and themes extracted in the thematic analysis shed light on how the course could be improved. Conclusions Implementing a mental health education course like CSMHEC in medical curriculum can be effective in helping medical students improve psychological health. More research needs to be conducted on further refinement and better design of such a course to implement in medical education.

Background Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder arising from mutations of the MEN1 tumor suppressor gene on chromosome 11q13; MEN1 is characterized by the development of neuroendocrine tumors, including those of the parathyroid, gastrointestinal endocrine tissue and anterior pituitary. Additionally, thymic neuroendocrine tumors in MEN1 are also rarely reported. Case presentation This case report observed a family that presented with MEN1 p.L105Vfs mutation, and two of the family members had been diagnosed with thymic neuroendocrine tumor combined with MEN1. To the best of our knowledge, this is the first time such a mutation in the MEN1 gene has been reported. The proband presented with thymic neuroendocrine tumor, parathyroid adenoma and rectum adenocarcinoma. The son of the proband presented with thymic neuroendocrine tumor, gastrinoma, hypophysoma and parathyroid adenoma. Genetic testing revealed the frameshift mutation p.L105Vfs, leading to the identification of one carrier in the pedigree (the patient’s younger sister). The proband then underwent parathyroidectomy at the age of 26 years (in 1980) for a parathyroid adenoma. Subsequently, the patient underwent thymectomy, radiotherapy and chemotherapy. The patient is now 64 years old, still alive and still undergoing Lanreotide therapy. Conclusion Thymic neuroendocrine MEN1 is rare, but it accounts for almost 20% of MEN1-associated mortality. Consequently, we should focus on regular clinical screening of the thymus in MEN1 patients.

BackgroundThe objective of this study was to evaluate the clinical effect and correlation between preoperative imaging parameters and the clinical effect of endoscopic transforaminal decompression for lumbar spinal stenosis.MethodsIn this prospective study, 87 patients from Shanxi Province People’s Hospital met the criteria for lumbar spinal stenosis and were recruited from June 2014 to January 2016. These patients underwent endoscopic transforaminal decompression. The clinical symptoms were evaluated by VAS, ODI, and claudication at 3 and 6 months after surgery. The overall clinical efficacy was evaluated using the MacNab score. Yellow ligament thickness and area of the dural sac were examined by MRI. Bony vertebral canal area, real spinal canal area, nerve root canal bony area, nerve root canal real area, distance between the articular joints, and vertebral canal sagittal diameter were examined by CT. The soft tissue invasion ratio of the vertebral canal and the invasion ratio of the nerve root canal were calculated. Correlations between imaging parameters and age, sex, and clinical efficacy were examined.ResultsThe MacNab scores were excellent in 47% of cases, good in 34%, generally good in 8%, and poor in 11%. VAS, ODI, and claudication were significantly improved compared with the preoperative values (P P ConclusionTreatment of lumbar spinal stenosis by endoscopic transforaminal decompression can achieve good clinical results. This operation is less effective in patients older than 71 years of age. There were positive correlations between clinical efficacy and the vertebral canal sagittal diameter, the articular joints, soft tissue invasion ratio of the vertebral canal, and invasion ratio of the nerve root canal.

Background Medical education is widely known to be a demanding process that may cause various mental health problems, such as burnout, which can lead to lowered levels of life satisfaction among medical students. Research shows that empathy is negatively correlated with burnout, but there are few studies on the relationship among empathy, burnout and life satisfaction in medical students. The objective of the present study is to explore the correlations of empathy and burnout with life satisfaction and the associated socio-demographic factors among Chinese undergraduate medical students. Methods In this cross-sectional study, 1271 undergraduate medical students (age 19.42 ± 1.34 years, 36% male) from 1st to 4th grades completed questionnaires including the Interpersonal Reactivity Index Chinese version (IRI-C), the Maslach Burnout Inventory Modified Chinese version (MBI-MC), the Satisfaction With Life Scale (SWLS) and socio-demographic characteristics. Statistical analyses included Student’s t-test, one-way ANOVA, post hoc Bonferroni tests, hierarchical linear regression analysis and general linear model-univariate full factorial model. Results Over four academic years, medical students’ empathy levels declined, but their burnout levels almost plateaued and their life satisfaction levels witnessed an initial fall before a rebound. Empathy was correlated with students’ age and grade, and burnout was associated with students’ maternal education. Significant differences in life satisfaction were detected with regard to medical students’ age, academic year, the number of children in the family, place of residence and parents’ educational levels. Conclusions Empathy explained 0.6% of the variance in life satisfaction in contrast to 13.7% of the variance explained by burnout in life satisfaction. Although empathy did not have a main effect on life satisfaction, there was an interaction effect of empathy and burnout on life satisfaction among students of high and low empathy and burnout levels. Students with high levels of empathy and low levels of burnout were most satisfied with life. Medical institutions and related authorities need to find effective measures to enhance students’ empathy levels and reduce burnout to improve their life satisfaction.

The bimetallic sulfide of CoNi2S4 nanosheet arrays have been successfully prepared via a facile one-step potentiostatic deposition on nickel foam using Co(NO3)2, NiCl2, and thiourea as the raw materials. The effect of deposition time on the morphology, structure, and electrochemical performance of the products is carefully investigated. The results show that when the potentiostatic deposition time is set as 10 min, the most uniform nanosheet arrays with the optimal supercapacitive performance are achieved on the nickel foam. The specific capacitance of material obtained under this condition is determined to be 1932 F g−1 at 2 A g−1 and 1640 F g−1 at 20 A g−1, respectively. The material retains 89.2 % of its original specific capacitance after 1000 charge–discharge cycles at a current density of 10 A g−1, demonstrating that the CoNi2S4 nanosheet arrays have an outstanding long-term cycling stability. These impressive performances can be ascribed to the unique architecture and properties of the deposited product, such as high interfacial contact area, rich redox activity, large pore size, and excellent conductivity. This work provides more supporting data to obtain high-performance supercapacitive bimetallic sulfide material by electrodeposition method.

In this study, the residual strain of a thin conductive metal wire on a polymer substrate after electrical failure is measured with SEM moire. Focused ion beam (FIB) milling is applied to fabricate micron moire gratings on the surfaces of constantan wires and the random phase shifting technique is used to process moire fringes. The virtual strain method is briefly introduced and used to calculate the real strain of specimens. In order to study the influence of a defect on the electrical failure of the constantan wire, experiments were conducted on two specimens, one with a crack, while the other one without any crack. By comparing the results, we found that the defect makes the critical beam current of electrical failure decrease. In addition, the specimens were subjected to compression after electrical failure, in agreement with the observed crack closure of the specimen. The successful results demonstrate that the moire method is effective to characterize the full-field deformation of constantan wires on the polymer membrane, and has a good potential for further application to the deformation measurement of thin films.

Few literatures have evaluated the exact role of metabolomics in the identification process of potential biomarkers for acute kidney injury among the patients receiving renal transplantation. On top of this, the success of metabolomics in biomarker translation seems to lie in the robust quantitative method. As such, a single-center retrospective observational study was conducted enrolling 42 patients underwent renal transplantation with/without acute kidney injury, as well as 24 healthy volunteers, in Shanghai Changzheng Hospital. Plasma amino acid metabolic patterns for the participants were investigated by targeted UHPLC-MS/MS metabolic profiling. The most significant changes of the explored metabolites were related to the disturbance of tryptophan metabolism and arginine metabolism. Abnormal circulating tryptophan and symmetric dimethylarginine were identified to be potential biomarkers of acute kidney injury, combination of which showed a higher area under receiver-operator curve value (AUC = 0.901), improved sensitivity (0.889) and specificity (0.831) compared with creatinine only. Overall, these results revealed that targeted metabolomics analysis would be a potent and promising strategy for identification and pre-validation of biomarkers of acute kidney injury in renal transplantation patients.

Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1β were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.

Ghrelin is a stomach-derived peptide hormone that stimulates appetite and promotes adiposity through binding to the growth hormone secretagogue receptor (GHS-R1a). Administration of ghrelin in rodents increases weight gain due to stimulating food intake and reducing fat utilization. Therefore, reducing circulating ghrelin levels holds the potential to reduce weight gain. We developed a GHS-R1a-fusion constructs of a decoy protein containing the ligand-binding domains of the ghrelin receptor. Intramuscular injection of the GHSR/Fc plasmid decreased circulating levels of acylated-ghrelin. When challenged with the high fat diet, treated mice displayed reduced weight gain compared with controls, which was associated with reduced fat accumulation in the peritoneum but not lean mass. Quantitative PCR with reverse transcription showed increased PPARγ and hormone sensitive lipase transcripts levels in adipose tissue of treated animals, illustrating a preference for increased fat utilization. Intra-peritoneal glucose tolerance and insulin tolerance tests showed improved glucose clearance and insulin sensitivity in GHSR/Fc treated animals. We suggest that in vivo expression of the GHSR-based fusion protein prevents diet-induced weight gain, altering adipose gene expression and improving glucose tolerance. These findings, while confirming the role of ghrelin in peripheral energy metabolism, suggest that a strategy involving neutralization of the circulation ghrelin by intramuscular injection of the GHSR1/Fc fusion construct may find clinical application in the treatment of obesity.

A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for the simultaneous determination of 70 pesticides in tea was developed using gas chromatography-tandem mass spectrometry. Prior to acetonitrile extraction of the target compounds from tea matrix, samples were soaked in distilled water to improve the extraction efficiency. A mixture of adsorbents containing primary–secondary amine, octadecylsilane, graphite carbon black, and multiwalled carbon nanotubes was applied for the cleanup. Additional steps of concentration and solvent exchange were performed to reduce the amount of co-extracts and to decrease the limit of detection of the method. For all pesticides, good linear calibrations with coefficients (R 2) ≥0.99 were obtained at the concentration levels of 10, or 50 to 1,000 μg ml−1. The limits of quantifications (LOQs) were 5–25 μg ml−1, respectively. The recovery rates of samples spiked with 20, 100, and 200 μg kg−1 of analytes ranged from 71 % to 105 %. In addition, the relative standard deviations were lower than 20 %. A total of 331 tea samples were analyzed using this method, and the levels of five pesticide residues in nine tea samples exceeded the strictest maximum residual limits (MRLs).

The photochromic behaviors of four Schiff bases derived from (R)-3-phenyl-2-phthalimidopropionic acid were studied to reveal the substituent effect on the photosensitivity. Upon ultraviolet light radiation, all of compounds 1–4 exhibit photochromic behavior in solution through intramolecular hydrogen atom transfer. In solid state, only compound 2 is photochromic, which may be due to the presence of meta-site methoxyl. In solution, the photochromic behavior of compound 3 is remarkable than the other compounds, which may be ascribed to the presence of para-site hydroxyl. Only compound 4 exhibits solvatochromism, which may be ascribed to the large dissociation tendency of the naphthol hydroxyl. The influences of acidity on the UV–Vis absorption spectra of the title compounds were also studied.

Excessive secretion of glucagon partially contributes to the development of diabetic hyperglycaemia. However, complete blocking of glucagon action will lead to adverse effects, since glucagon exerts certain beneficial effects via its receptor in many organs. We aimed to study the effects of a 'decoy receptor' for circulating glucagon on modulating beta cell function and glucose homeostasis in mice by over-producing the glucagon receptor (GCGR) in skeletal muscles.We generated transgenic mice in which the expression of Gcgr is driven by the muscle specific creatine kinase (Mck) promoter, and assessed the effects of glucagon on the modulation of glucose homeostasis under conditions of extremes of glucose influx or efflux.Mck/Gcgr mice showed increased circulating levels of glucagon and insulin, resulting in an unchanged ratio of glucagon-to-insulin. The levels of hepatic glucose-6-phosphatase (G6PC) and fructose-1,6-bisphosphatase (F1,6P2ase) were significantly decreased, whereas the phosphorylation level of pancreatic cAMP-response-element-binding-protein (CREB) was significantly increased in these transgenic mice. Under basal conditions, the mice displayed normal blood glucose levels and unchanged glucose tolerance and insulin sensitivity when compared with their age-matched wild-type (WT) littermates. However, following multiple low-dose streptozotocin injections, Mck/Gcgr mice exhibited a delay in the onset of hyperglycaemia compared with the WT controls. This was associated with preserved beta cell mass and beta cell secretory capacity in response to glucose challenge.We suggest that mild and chronic hyperglucagonaemia, through a strategy involving neutralising peripheral glucagon action, provides beneficial effects on beta cell function and glucose homeostasis. Mck/Gcgr mice thus represent a novel mouse model for studying the physiological effects of glucagon.

Mineral-microbe interactions are widespread in a number of environmental processes such as mineral weathering, decomposition, and transformation. Both clay minerals and silicate-weathering bacteria are widely distributed in nature, and the latter contribute to weathering, diagenesis, and mineralization of major rock-forming minerals. The purpose of this study was to observe changes in the chemical composition and structure, especially the phase transformation, of smectite after processing by a silicate-weathering bacterium. The interaction between Bacillus mucilaginosus and bentonite was studied using custom culture media. Results from Inductively Coupled Plasma-Atomic Emission Spectrometry revealed that the bacterium promoted release of Si and Al from solid bentonite to solution. Concomitantly, the K and Fe contents of the mineral increased as shown by X-ray photoelectron spectroscopy results. After interaction with the bacterium, the montmorillonite underwent a possible structure transformation to smectite, as indicated by the emergence of a new weak peak ( d = 9.08 A ° ) shown by X-ray diffraction patterns. The mineralogical changes were also demonstrated by the decrease in the specific surface area of the mineral from 33.0 to 24.0 m2/g (these lower values for SSA of bentonite are related to the particle size of the smectite examined (120–160 mesh) and the weakened absorption bands in Al–O–H and Si–O–Si vibrations by Micro Fourier-transform infrared spectroscopy. The morphology changes in the bacteria observed by environmental scanning electron microscopy and atomic force microscopy revealed an obvious growth of the flagella in the presence of bentonite.

A novel plant annexin, CkANN, was isolated from Cynanchum komarovii. Sequence analysis showed that CkANN contained four conserved exdonexin fold regions, a putative peroxidase heme binding motif and two S3 clusters. Real-time PCR analysis indicated that the CkANN mRNA was abundant in leaf, flower, root and stem and that its level is highest in leaf and flower. The transcription level of CkANN was increased significantly following stress by salicylic acid (SA), methyl jasmonate (MeJA), abscisic acid (ABA), NaCl, PEG 6000 (polyethylene glycol) and H2O2. Over-expression of CkANN in transgenic cotton caused a significant increase in tolerance to drought and led to higher levels of proline and soluble carbohydrates compared to wild-type (WT) plants. In response to drought, the transgenic plants also displayed higher total chlorophyll levels and reduced accumulation of thiobarbituric acid-reactive substances (TBARS) compared to WT plants. Furthermore, the transgenic cotton showed enhanced resistance to Fusarium oxysporum via increased total peroxidase activity and induction of the expression of some pathogenesis-related proteins. In conclusion, this study has demonstrated that C. komarovii CkANN is involved in drought tolerance and disease resistance and therefore may contribute significantly to the development of drought- or disease-resistant crops.

It is important that endogenous reference genes for real-time RT-PCR be empirically evaluated for stability in different cell types, developmental stages, and/or sample treatment. To select the most stable endogenous reference genes during planarian regeneration, three housekeeping genes, 18S rRNA, ACTB and DjEF2, were identified and established expression levels by real-time RT-PCR. The data were analyzed by GeNorm and NormFinder software. Expression levels of the Djsix-1 gene were studied in parallel with ACTB and DjEF2 both or each and 18S rRNA as reference during regeneration. The results showed that ACTB was the most stable expressed reference gene in the planarian regeneration.

Hetianhe gasfield in Bachu region of the Tarim Basin is mainly composed of three reservoir-caprock assembly, namely regional caprock of upper mudstone, middle mudstone and lower mudstone of the Carboniferous and reservoir of Bachu bioclastic limestone, glutenite and the Ordovician carbonate buried hill. Natural gas in Hetianhe gasfield sourced from the Cambrian source rock. It is thought that gases in Ma4 well block in the east of Hetianhe gasfield are mainly crude-oil cracked gases, while those in Ma3 and Ma8 well blocks in the west are the mixture gases of kerogen cracked gases and crude-oil cracked gases. Natural gas is rich in H2S and accumulated in multiply stages as the result of TSR. The accumulation history is divided into three stages, namely accumulation and breakage in the late Caledonian-early Hercynian, migration and dissipation in the late Hercynian and accumulation in Himalayan. The main accumulation of reformed gas reservoir is in Himalayan.

The genomes of seven native goat populations were screened by using microsatellites as molecular markers; the populations were Yichang white, Matou, Xiangdong black, Fuqing, Daiyun, Huanghuai and Yangtse River Delta white goats. A total of 23 microsatellite markers were used and genetic diversities and genetic distances were also determined. The results showed that only 21 loci showed polymorphism in all populations. BM0203 was a homozygotic locus in every population, but more than one allele was found among all populations. Alleles of BM6444 were homozygotic in Xiangdong Black and Yichang White goats, but more than one allele was detected in other populations. Average heterozygosity of all populations was 0.819 0, and the mean polymorphism information content (PIC) of all seven populations was 0.630 5–0.691 9. An unweighted pair group method with arithmetic mean (UPGMA) dendrogram was constructed on Nei’s standard genetic distance. Matou and Xiangdong black were grouped at first, then Fuqing, Daiyun, Yangtse River Delta white and Huanghuai goats joined them respectively. Finally, Yichang white goats clustered with all of the above.

Type I diabetes mellitus (T1D) is due to a loss of immune tolerance to islet antigen and thus, there is intense interest in developing therapies that can re-establish it. Tolerance is maintained by complex mechanisms that include inhibitory molecules and several types of regulatory T cells (Tr). A major historical question is whether gene therapy can be employed to generate Tr cells. This review shows that gene transfer of immunoregulatory molecules can prevent T1D and other autoimmune diseases. In our studies, non-viral gene transfer is enhanced by in vivo electroporation (EP). This technique can be used to perform DNA vaccination against islet cell antigens and when combined with appropriate immune ligands results in the generation of Tr cells and protection against T1D. In vivo EP can also be applied for non-immune therapy of diabetes. It can be used to deliver protein drugs such as glucagon-like peptide 1 (GLP-1), leptin or transforming growth factor beta (TGF-beta). These act in T1D or type II diabetes (T2D) by restoring glucose homeostasis, promoting islet cell survival and growth or improving wound healing and other complications. Furthermore, we show that in large animals EP can deliver peptide hormones, such as growth hormone releasing hormone (GHRH). We conclude that the non-viral gene therapy and EP represent a safe and efficacious approach with clinical potential.

Sensor deployment is an important problem in mobile wireless sensor networks. This paper presents a distributed self-spreading deployment algorithm (SOMDA) for mobile sensors based on artificial neural-networks self-organizing maps algorithm. During the deployment, the nodes compete to track the event and cooperate to form an ordered topology. After going through the algorithm, the statistical distribution of the nodes approaches that of the events in the interest area. The performance of the algorithm is evaluated by the covered percentage of region/events, the detecting ability and the energy equalization of the networks. The simulation results indicate that SOMDA outperforms uniform and random deployment with lossless coverage, enhancive detecting ability and significant energy equalization.

The role of gamma-aminobutyric acid (GABA) and A-type GABA receptors (GABA(A)Rs) in modulating islet endocrine function has been actively investigated since the identification of GABA and GABA(A)Rs in the pancreatic islets. However, the reported effects of GABA(A)R activation on insulin secretion from islet beta cells have been controversial.This study examined the hypothesis that the effect of GABA on beta cell insulin secretion is dependent on glucose concentration.Perforated patch-clamp recordings in INS-1 cells demonstrated that GABA, at concentrations ranging from 1 to 1,000 micromol/l, induced a transmembrane current (I(GABA)) which was sensitive to the GABA(A)R antagonist bicuculline. The current-voltage relationship revealed that I(GABA) reversed at -42+/-2.2 mV, independently of glucose concentration. Nevertheless, the glucose concentration critically controlled the membrane potential (V (M)), i.e., at low glucose (0 or 2.8 mmol/l) the endogenous V (M) of INS-1 cells was below the I(GABA) reversal potential and at high glucose (16.7 or 28 mmol/l), the endogenous V (M) of INS-1 cells was above the I(GABA) reversal potential. Therefore, GABA dose-dependently induced membrane depolarisation at a low glucose concentration, but hyperpolarisation at a high glucose concentration. Consistent with electrophysiological findings, insulin secretion assays demonstrated that at 2.8 mmol/l glucose, GABA increased insulin secretion in a dose-dependent fashion (p0.05, n=7). This enhancement was blocked by bicuculline (p0.05, n=4). In contrast, in the presence of 28 mmol/l glucose, GABA suppressed the secretion of insulin (p0.05, n=5).These findings indicate that activation of GABA(A)Rs in beta cells regulates insulin secretion in concert with changes in glucose levels.

Lunnan heave had experienced denudation during late Caledonian and Hercynian movements and reconstruction during Indosinian movement. Lunnan heave and its circumference areas are located on the direction of petroleum migration, and experienced three reservoir formation cycles that are divided by wave cycle: The first reservoir formation cycle is characterized by breakage, the second by alteration, and the third by enrichment. Three layers of dissolving-cave developed on the vertical in Lunnan area. Development degree of slit-cave system and their connectivity are important factors to control petroleum enrichment in the weathering crust reservoir. The area where dissolving-caves are communicated by silts and faults was a fine petroleum enrichment area, and water was often encountered in the area with isolation cave while drilling because of no oil and gas origin. The top part of the faulted-horst as a leaking area is bearing water area, and the higher part of slope nearing the top part of the faulted-horst as a high seepage area is a heavy oil area due to lack of fine cap rock, and the lower part of slope and the platform are light and condensate oil area. The area with the middle-upper Ordovician is the favorable area to explore original carbonate reservoir formed in the earlier stage. The best favorable petroleum enrichment area for carbonates is surrounding Lunnan heave along the slope down to the direction of sags. The precondition to discover petroleum in carbonates is accurately prognosticating the distribution area of silts and caves, and the key to improving the exploration success ratio is accurately recognizing silts and small faults.

There were different opinions about the origin of petroleum property variations in the Lunnan Low Uplift of the Tarim Basin. In this paper, a software PVTsim was applied to investigate the compositions of the petroleum fluid inclusions in different sets of reservoir rocks from this area. The results show that there are three phases of petroleum inclusions in the Ordovician carbonate reservoirs and two types of petroleum inclusions in the Carboniferous and Triassic sandstone reservoirs. The three phases of the petroleum inclusions from the Ordovician reservoir rocks have similar compositions with the type 1 petroleum inclusion from the carboniferous and Triassic reservoir rocks, but the type 2 petroleum inclusion from the carboniferous and Triassic reservoirs is characterized by higher content of C1 and higher GOR values. With the combination of the geological background, it was inferred that the current petroleum pools in the Lunnan Low Uplift were formed mainly by two phases of petroleum charges, one is normal oils and another light oils, and both occurred during the late Tertiary. The light oils came from eastern-south direction, and migrated and charged into the reservoirs upward and toward northern west directions. On the basis of this, it was believed that the multiphases of the petroleum charges and some composition dissipation caused by the preserved condition changes would be the main reason of the petroleum property variations in the petroleum pools in this area.