Objective To investigate the effect of MALAT1 expressions on cell proliferation and apoptosis in astrocytes by regulating mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK1,2)pathway.Methods The MALAT1 gene was knocked down and over-expressed in C8-D1A cells by lentiviral and plasmid vectors,respectively.The expressions of MALAT1,cell proliferation-related markers(Ki67,MCM2,PCNA)and apoptosis-related proteins(Caspase-3,Bax,Bcl-2)were detected by quantitative real-time polymerase chain reaction(qPCR).CCK-8 assay and flow cytometry were used for cell proliferation and apoptosis in C8-D1A cells.Immunofluorescence was adopted to detect the protein expressions of Caspase-3 and Ki67.Western blotting was used to detect the protein expressions of Caspase-3,Bax,Bcl-2,ERK1/2,p-ERK1/2,p38MAPK and p-p38MAPK.Results Compared with the control group,over-expressed MALAT1 inhibited cell proliferation and induced cell apoptosis in C8-D1A cells while the knockdown of MALAT1 significantly enhanced cell proliferation and anti-apoptotic ability in C8-D1A cells.The proportion of C8-D1A cells in G0/G1-phase and G2/M-phase was higher than in the control group as evidenced by flow cytometry,but was lower in S-phase.Meanwhile,data showed that Caspase-3 was increased while p-ERK1/2 was decreased in terms of protein levels.The mRNA expressions of Ki67 and PCNA were decreased.After knockdown of MALAT1,the proportion of C8-D1A cells in S-phase was higher,but was lower in G2/M-phase.The protein expressions of Caspase-3 and Bax decreased while those of p-ERK1/2 and p-p38MAPK increased.The mRNA expressions of Ki67,MCM2 and PCNA were increased.The differences were all statistically significant(P＜0.05).Conclusion MALAT1 promotes astrocyte apoptosis and inhibits proliferation by regulating the MAPK/ERK1,2 signaling pathway.

Cultivating salt-alkali tolerant rice varieties is one of the important ways to meet the increasing food demand of growing global population. In this study, twenty-one rice germplasms with different salt-alkali tolerance were treated with six salt-alkali concentrations at germination and seedling stages. The germination potential, germination rate, shoot length, root length, root number, fresh weight of shoot and seedlings were measured. The average value of salt damage rate was used to evaluate the salt-alkali tolerance. As the salt-alkali concentration increases, the inhibition on seed germination and growth became more obvious. Upon treatment with 1% NaCl plus 0.25% NaHCO₃, the salt damage rate of germination rate has the largest variation, ranging from 0% to 89.80%. The salt damage rate of each trait shows a similar trend at all concentrations. Four germplasm resources with strong salt-alkali tolerance (Dajiugu, Nippobare, Mowanggu and 02428) and 7 sensitive germplasms were screened. The salt-tolerant gene sequence of 4 salt-alkali tolerant varieties and 3 sensitive germplasms were analyzed. OSHAL3 and OsRR22 were identical among the 7 germplasms, but SKC1 and DST showed clear variations between the salt-alkali tolerant and sensitive germplasms. Besides the salt-alkali tolerant germplasm resources, this study can also serve as a reference for mining of genes involved in salt-alkali tolerance and breeding of salt-alkali tolerant rice varieties.
Alkalies ; Germination ; Oryza/genetics* ; Plant Breeding ; Seedlings/genetics*

Objective:To assess the efficacy and security of 2 940 nm Er∶YAG laser combined with electronic injection of collagen in treatment of striae gravidarum.Methods:The symmetrical spots on both sides of abdomen of 21 subjects with striae gravidarum were divided into treatment and control groups by simple randomization method in the Department of Burn and Plastic Surgery, 903 Hospital from November 2017 to May 2019. The treatment group were treated with 2 940 nm Er∶YAG laser combined with electronic injection of collagen every 2 months for 3 sessions, and control group were received 2 940 nm Er∶YAG laser combined with electronic injection of physiological saline. The total effective rate, satisfaction, striae width, histopathology, and the adverse reaction were evaluated at 6 months after treatment.Results:A total of 19 subjects completed the whole trail. The clinical effective rate of the treatment group was 89.47% and the control group was 68.42%. In the treatment group, 11 cases were satisfied with and 6 cases were very satisfied with treatment outcome. In the treatment group, 8 cases were satisfied with and 3 cases were very satisfied with treatment outcome. The difference of total effective rate and satisfaction was statistically significant ( χ2 was 3.91 and 5.54, P was 0.045 and 0.019). The maximum width decreased by (1.53±0.97) mm on treatment side, and (1.37±1.01) mm on control side. The difference of striae width was statistically significant. No adverse effect was observed on both sides. Conclusions:The combination of the 2 940 nm Er∶YAG laser with electronic injection of collagen for treatment of striae gravidarum is a safe and effective approach for improving of striae gravidarum.

Objective:To investigate the prognostic value of texture analysis of MRI diffusion weighted imaging (DWI) for neonatal hypoglycemic encephalopathy (HE).Methods:The clinical data and MRI data of 119 patients with neonatal HE admitted to Children′s Hospital of Nanjing Medical University from July 2013 to September 2020 were retrospectively analyzed. The children were followed up to 7—8 months and scored by Bayley scales of infant and toddler development. According to the overall development index, the children were divided into three groups: normal group (≥85, group A, n=42), mild developmental retardation group (70－84, group B, n=46) and developmental retardation group (≤69, group C, n= 31). The whole brain region (except sulcus and cisterna) was delineated as region of interest (ROI) by LIFEx 3.4 software in MRI apparent diffusion coefficient images. A total of 37 parameters were calculated automatically by the software, The clinical data, including gender, gestational age, age at MRI scan, birth weight, mode of delivery, history of asphyxia at birth, maternal preeclampsia or diabetes, minimum blood glucose, duration of hypoglycemia, neonatal behavioral neurological assessment (NBNA), presence or absence of polycythemia); the texture parameters, including histogram, volume, gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), neighborhood gray tone difference matrix (NGTDM), gray level size zone matrix (GLSZM), in the three groups were analyzed; and the diagnostic efficacy of clinical parameters and texture parameters was analyzed. Multivariate Logistic regression was used to analyze statistically significant clinical parameters and texture parameters, and receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficacy of these parameter for neonatal HE. Results:There were no significant differences in gender, gestational age, age at MRI scan, delivery mode and blood glucose minimum among the three groups ( P>0.05). There were significant differences in birth weight [(3 150±130)g, (3 020±220)g, (2 880±140)g, F=-0.31, P=0.015], history of suffocation (10 cases, 18 cases, 20 cases, P=0.001), history of maternal diabetes or preeclampsia (14 cases, 29 cases, 21 cases, P=0.002), blood glucose duration [(5.0±0.2)d, (8.0±0.4)d, (14.0±1.7)d, F=-3.09, P=0.030] and NBNA scores (32.0±3.2, 28.0±2.6, 22.0±1.9, F=-4.21, P=0.010) among three groups. There were significant differences in kurtosis and entropy of histogram (2.57±1.12, 3.66±0.98, 4.23±0.37, F=3.54, P=0.010;5.89±1.09, 7.67±2.12, 8.92±1.62, F=-4.42, P=0.020); energy, contrast and dissimilarity of GLCM (0.48±0.01, 0.36±0.02, 0.23±0.01, F=-3.12, P=0.001;2 419±21, 3 354±31, 4 313±26, F=-4.16, P=0.020;126±14, 153±23, 344±43, F=-3.50, P<0.001); long run emphasis of GLRLM (0.78±0.15, 1.12±0.12, 1.76±0.31, F=-4.13, P=0.006), run length non-uniformity and run percentage (71.7±13.9, 96.6±10.7, 104.1±13.5, F=-0.98, P=0.001;0.91±0.05, 0.84±0.21, 0.72±0.17, F=2.97, P=0.010); coarseness and busyness of NGTDM [0.09±0.01, 0.13±0.03, 0.26±0.07, F=-1.95, P=0.003;0.16(0.04, 4.14), 0.32(0.05, 9.84), 0.45(0.15, 10.14), H=-3.24, P=0.030], short-zone emphasis and short-zone high gray length emphasis of GLSZM (4.74±0.45, 3.44±1.03, 1.88±0.67, F=-3.14, P=0.040; 278 963±239, 164 607±544, 111 653±618, F=-3.84, P=0.001) among three groups. Multivariate Logistic regression showed that duration of hypoglycemia, NBNA score, energy, kurtosis, run percentage and short zone effect were independent risk factors for poor prognosis of neonatal HE ( OR=7.43, 4.09, 1.10, 2.11, 1.36, 1.68, P=0.002, 0.027, 0.001, 0.006, 0.007, 0.010, respectively). ROC curve showed that for combined hypoglycemic duration, NBNA and texture parameters, the area under the curve (AUC) was the highest (AUC=0.94, P<0.001). Conclusion:Texture analysis of the MRI diffusion weighted imaging can predict the prognosis of neonatal hypoglycemic encephalopathy at an early stage, which has better prediction efficiency when combined with clinical features.

Metabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.
Chromatin ; DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Histones/metabolism* ; Humans ; Neoplasms/therapy*

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective To explore the clinical effect of microendoscopic discectomy through posterior approach in old patients with multilevel lumber spinal stenosis and analyze the influence factors that related to clinical effect .Methods 64 old patients with multilevel lumber spinal stenosis were selected and divided into microendoscopic group and open group based on different operation method ,each group contained 32 patients .Comparison was made between two groups in respects of operation time ,amount of bleed-ing ,hospital time post-operation and Nakai scores .Analyzed the influence factors that related to clinical effect .Results The opera-tion time ,amount of bleeding ,hospital time post-operation in microendoscopic group were lower than open group ,the differences had statistical significance .Based on the Nakei score ,the curative effect in microendoscopic group was slightly lower than open group ,but the differences had no statistical significance .The JOA score pre-operation ,walking distances and complication were rela-tive factors that could influence the clinical effect of microendoscopic discectomy through posterior approach method .Conclusion Microendoscopic discectomy through posterior approach in old patients with multilevel lumber spinal stenosis had quicker postoper-ative recovery than conventional operation ,and the JOA score pre-operation ,walking distances and complication were relative fac-tors that could influence the clinical effect of microendoscopic discectomy through posterior approach method .

ObjectiveTo investigate the proliferation of rat's osteoblasts promoted by mechanical strain via the protein kinases C ξ(PKCξ) protein path-way.MethodsOsteoblasts were retrieved from SD rats' skulls in the sterilized environment.BioDynamic testing instrument was used to exert 2％ and 0％ mechanical strain on rats' osteoblasts for 180 min on the each group(2％ mechanical strain was experimental group and 0％ mechanical strain was control group); and the same method was applied on the rats' osteoblasts which pretreated with the classical PKC ξ inhibitor with 2％ mechanical strain (inhibitor group).The cell cycles of rats' osteoblasts were measured by flow cytometry; and Western blotting and immunofluorescence were used to detect expression of protein PKC ξ and phosphorylationed PKC ξ in the rats' osteoblasts.ResultsThe mechanical strain obviously increased the ratio of S period in the cell cycles.Compared to the control group and inhibitor group,a significant increase of the expression of protein PKC ξ and phosphorylationed PKC ξ in the osteoblasts was detected in the mechanical strain experimental group.ConclusionPKCξ can respond to the stimulus of the mechanical strain,which promotes the proliferation of osteoblasts through PKCξ pathway.And it plays an important role in the process of signal conduction.

Objective To detect the expression of Cytokeratin 19 (CK19) mRNA in the peripheral blood of cervical carcinoma patients and evaluate its clinical significance.Methods The expression of CK19 mRNA was evaluated by fluorescent quantitative reverse transcription polymerase chain reaction ( FQRT-PCR ) in the peripheral blood of 138 patients with cervical carcinoma and 36 patients with benign gynecological tumors.In 138 patients,possible correlations between clinical pathological factors were analyzed.Results The positive expression rates of CK19 mRNA was 69.6％ in 138 cervical carcinomas in comparison with 13.9％ in benign gynecological tumors,and 57.9％ in patients with FIGO Stage Ⅰ A to Ⅱ A cervical carcinoma in comparison with 80.6％ in patients with FIGO Stage Ⅱb to Ⅳ cervical carcinoma.The expression of CK19 mRNA in patients with FIGO Stage Ⅰ A to Ⅱ A cervical carcinoma were significantly correlated with stage,differentiation and lymph vascular space involvement,but was not associated with prognostic factors including age,bully tumor size,pathological types,deep stromal invasion and lymph node metastasis.In multivariate survival analysis,lymph vascular space involvement was an independent risk factor of CK19mRNA expression in patients with cervical carcinoma.Conclusions Fluorescent quantitative RTPCR can be used to detect the expression of CK19 in the peripheral blood of cervical carcinoma patients,and it is a sensitive and specific technique.CK19 mRNA in peripheral blood may be a potential biomarker for detecting micrometastasis in cervical carcinoma.The results suggest a possible use of this approach for evaluating prognosis.

Multislice Cr angiography represents one of the most exciting technological revolutions in cardiac imaging and it has been increasingly used in the diagnosis of coronary artery disease.Rapid improvements in multislice CT scanners over the last decade have allowed this technique to become a potentially effective alternative to invasive coronary angiography in patients with suspected coronary artery disease.High diagnostic value has been achieved with multisfice CT angiography with use of 64-and more slice CT scanners.In addition,multislice CT angiography shows accurate detection and analysis of coronary calcium,characterization of coronary plaques,as well as prediction of the disease progression and major cardiac events.Thus,patients can benefit from multislice CT angiography that provides a rapid and accurate diagnosis while avoiding unnecessary invasive coronary angiography procedures.The aim of this article is present an overview of the clinical applications of multislice CT angiography in coronary artery disease with a focus on the diagnostic accuracy of coronary artery disease;prognostic value of coronary artery disease with regard to the prediction of major cardiac events; detection and quantification of coronary calcium and characterization of coronary plaques.Limitations of multislice Cr angiography in coronary artery disease are also briefly discussed,and future directions are highlighted.