Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Xinyang tablet alleviated cardiac dysfunction in a cardiac pressure overload model by regulating the receptor-interacting serum/three-protein kinase 3/FUN14 domain containing 1-mediated mitochondrial unfolded protein response and mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.

Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.

[Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats].

OBJECTIVE: To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD. METHODS: A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3ß (GSK-3ß) in the hippocampus was detected. RESULTS: There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3ßwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3ß was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05). CONCLUSION: Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3ß and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Epstein-Barr virus: To be a trigger of autoimmune glial fibrillary acidic protein astrocytopathy?

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune disease of central nervous system (CNS). It is unclear whether Epstein-Barr virus (EBV) is related to autoimmune GFAP astrocytopathy. OBJECTIVE: To describe the clinical, laboratory, and imaging characteristics of patients with autoimmune GFAP astrocytopathy. METHODS: The clinical, laboratory, and imaging findings of patients are presented. The levels of GFAP in CSF were detected by ELISA. T and B cell subsets in CSF were detected by flow cytometry. GFAP-IgG in serum and cerebrospinal fluid (CSF) were tested by cell-based assay (CBA) and tissue-based assay (TBA). RESULTS: All three patients had fever, cognitive dysfunction, limb weakness, and positive GFAP-IgG with EBV infection in CSF. Enteric glia cells may involve in this disease. Typical imaging findings include the gadolinium enhancement of linear perivascular radial perpendicular to the ventricle, meningeal enhancement (especially in midbrain interpeduncal fossa), longitudinally extensive lesions involving spindle cords, and more T2/Flair-hyperintense lesions in the periventricular white matter at late stage. The patients had poor response to antiviral treatment and strong response to steroid pulse therapy. CONCLUSION: EBV could induce CNS autoimmune response in autoimmune GFAP astrocytopathy. The detection of GFAP-IgG and EBV may facilitate the early diagnosis in these patients.

Baicalin induces ferroptosis in osteosarcomas through a novel Nrf2/xCT/GPX4 regulatory axis.

BACKGROUND: Osteosarcomas (OS) is a kind of malignant bone tumor which occurs primarily in children and adolescents, and the clinical therapeutics remain disappointing. As a new programmed cell death, ferroptosis is characterized by iron dependent and intracellular oxidative accumulation, which provides a potential alternative intervene for the OS treatment. Baicalin, a major bioactive flavone derived from traditional Chinese medicine Scutellaria baicalensis, has been proved to have anti-tumor properties in OS. Whether ferroptosis participated in the baicalin mediated anti-OS activity is an interesting project. PURPOSE: To explore the pro-ferroptosis effect and mechanisms of baicalin in OS. METHODS/STUDY DESIGN: Pro-ferroptosis effect of baicalin on cell death, cell proliferation, iron accumulation, lipid peroxidation production was determined in MG63 and 143B cells. The levels of glutathione (GSH), oxidized (GSSG) glutathione and malondialdehyde (MDA) were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Glutathione peroxidase 4 (GPX4) and xCT were detected by western blot in baicalin-mediated ferroptosis regulation. In vivo, a xenograft mice model was adopted to explore the anticancer effect of baicalin. RESULTS: In the present study, it was found that baicalin significantly suppress tumor cell growth in vitro and in vivo. By promoting the Fe accumulation, ROS formation, MDA production and suppressing the ratio of GSH/GSSG, baicalin was found to trigger ferroptosis in OS and ferroptosis inhibitor ferrostatin-1 (Fer-1) successfully reversed these suppressive effects, indicating that ferroptosis participated in the baicalin mediated anti-OS activity. Mechanistically, baicalin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced its stability via inducing ubiquitin degradation, which suppressed the Nrf2 downstream targets GPX4 and xCT expression, and led to stimulating ferroptosis. CONCLUSIONS: Our findings for the first time indicated that baicalin exerted anti-OS activity through a novel Nrf2/xCT/GPX4-dependent ferroptosis regulatory axis, which hopefully provides a promising candidate for OS treatment.

Characterization of Pore Size Distribution and Water Transport of UHPC Using Low-Field NMR and MIP.

Water transport is vital for the durability of ultra-high performance concrete (UHPC) in engineering, but its absorption behavior requires further comprehension. This study investigates the impact of silica fume (SF) and metakaolin (MK) on water absorption in UHPC matrix with a high volume of limestone powder (LS) under two curing temperatures, and the variation in water transport with pore size obtained by low field nuclear magnetic resonance (LF-NMR). Relations between cumulative water absorption with other properties were discussed, and the pore size distribution (PSD) measured by Mercury intrusion porosimetry (MIP) was compared with that determined by LF-NMR. Results showed that MK outperformed SF in reducing water absorption in UHPC matrix, containing 30% LS under steam curing due to the synergistic effect between MK and LS. The incorporation of LS greatly affected the water absorption process of UHPC matrix. In samples without LS, capillary and gel pores absorbed water rapidly within the first 6 h and slowly from 6 h to 48 h simultaneously. However, in samples with 30% LS, gel pore water decreased during water absorption process due to the coarsening of gel pores. MK was able to suppress gel pore deterioration caused by the addition of a large amount of LS. Compared with PSD measured by MIP, NMR performed better in detecting micropores (<10 nm).

[Three-dimensional assessment and study on temporomandibular joint and the maxillary characteristics of skeletal Class â ¢ mandibular deviation patients].

PURPOSE: To study the temporomandibular joint morphology and position and the maxillary characteristics of skeletal Class Ⅲ mandibular deviation patients with vertical disproportion in bilateral gonions. METHODS: Overall 79 adult patients with skeletal Class Ⅲ malocclusions were selected. Craniofacial spiral CT scanning was performed, and three-dimensional reconstruction of the temporomandibular joint(TMJ) was carried out by using ProPlan CMF3.0 three-dimensional analysis software. The patients were divided into two groups according to the deviation degree of the mentum: symmetric group (the S group: n=24) and deviation group (n=55). The deviation group was divided into two subgroups according to whether there was vertical disproportion in bilateral gonions, i.e., ASV group: there were vertical differences in bilateral gonions(n=27), and ASNV group: there was no vertical difference in bilateral gonions (n=28). Seven condylar morphological and position indicators and nine maxilla-related indicators were measured. SPSS 22.0 software package was used for statistical analysis. RESULTS: In deviation group, the condylar length on the deviated side was shorter than the opposite side, the difference value between the two sides was greater than the symmetric group, and there were asymmetry and different degrees of disproportion in the three-dimensional direction in the maxilla. In ASV group, the angle of the condylar axis to the horizontal plane on the deviated side was smaller and the anteroposterior diameter of the condyle was smaller. In ASV group, the mediolateral dimension of condyle on the deviated side were smaller. From variance analysis and multiple comparisons, the difference of condylar length on both sides in ASV group and ASNV group was greater than that in the symmetric group. There were asymmetries in the maxillae in ASV group and ASNV group, and the maxillary width on the deviated side was greater than that on non-deviated side. Transverse maxillary disproportion was more likely to occur in the ASNV group. The vertical maxillary disproportion on both sides in ASV group was larger than that in ASNV group and S group, and the deviated side was smaller than the opposite side. CONCLUSIONS: The TMJ morphology and position of skeletal Class Ⅲ mandibular deviation patients with vertical disproportion in bilateral gonions and the maxillary asymmetry in the three-dimensional direction require attention in the diagnosis and conceptual design of surgical-orthodontic treatment.

[Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis]. / CD4+NKG2D+ Tç»†èƒžåœ¨å¹¼å¹´ç‰¹å‘æ€§å ³èŠ‚ç‚Žç–¾ç— æ´»åŠ¨ä¸­çš„ä½œç”¨.

OBJECTIVES: To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA. METHODS: Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA. RESULTS: The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64. CONCLUSIONS: The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated-RAGE/autophagy/EndMT pathway.

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

Nonlinear Inverse Analysis for Predicting the Tensile Properties of Strain-Softening and Strain-Hardening UHPFRC.

The tensile stress-strain response is considered to be the most important and fundamental mechanical property of ultra-high-performance fiber-reinforced concrete (UHPFRC). Nevertheless, it is still a challenging matter for researchers to determine the tensile properties of UHPFRC. As a simpler alternative to the direct tensile test, bending tests are widely performed to characterize the tensile behavior of UHPFRC, but require further consideration and a sophisticated inverse analysis procedure. In order to efficiently predict the tensile properties of UHPFRC, a nonlinear inverse method based on notched three-point bending tests (3PBT) was proposed in this paper. A total of fifteen UHPFRC beams were fabricated and tested to evaluate the sensitivity of the predicted tensile behavior to variations in fiber volume fraction. A segmented stress-strain model was used, which is capable of describing the various tensile properties of UHPFRC, including strain softening and strain hardening. A more approximate formulation was adopted to simulate the load-deflection response of UHPFRC beam specimens. The closed-form analytical solutions were validated by tensile test results and existing methods in literature. Finally, parametric studies were also conducted to investigate the robustness of the proposed method. The load-deflection responses obtained from notched 3PBT could be easily converted into tensile properties with this inverse method.

Has breeding altered the light environment, photosynthetic apparatus, and photosynthetic capacity of wheat leaves?

Whether photosynthesis has improved with increasing yield in major crops remains controversial. Research in this area has often neglected to account for differences in light intensity experienced by cultivars released in different years. Light intensity is expected to be positively associated with photosynthetic capacity and the resistance of the photosynthetic apparatus to high light but negatively associated with light-utilization efficiency under low light. Here, we analyzed the light environment, photosynthetic activity, and protein components of leaves of 26 winter wheat cultivars released during the past 60 years in China. Over time, light levels on flag leaves significantly decreased due to architectural changes, but photosynthetic rates under high or low light and the resistance of the photosynthetic apparatus to high light remained steady, contrary to expectations. We propose that the difference between the actual and expected trends is due to breeding. Specifically, breeding has optimized photosynthetic performance under high light rather than low light. Moreover, breeding selectivity altered the stoichiometry of several proteins related to dynamic photosynthesis, canopy light distribution, and photoprotection. These results indicate that breeding has significantly altered the photosynthetic mechanism in wheat and its response to the light environment. These changes likely have helped increase wheat yields.

Diagnostic Value of Imaging Combined With Tumor Markers in Early Detection of Lung Cancer.

Objective: The objective of this research is to explore the diagnostic value of imaging plus tumor markers in the early detection of lung cancer. Methods: Sixty patients with lung cancer treated in our hospital from January 2018 to January 2019 were selected as group A. They were matched with 60 patients with benign lung disease as group B and 60 healthy subjects examined in our hospital as group C. The carcino-embryonic antigen (CEA), CYFRA21-1, and neuron-specific enolase (NSE) were assessed, and the diagnostic value of tumor markers plus imaging in lung cancer diagnosis was explored. Results: The CEA, CYFRA21-1, and NSE in group A were evidently superior to those in groups B and C, and those in group B were superior to those in group C (all P < 0.001). CEA had the highest sensitivity (56.7%), and NSE had the highest specificity (93.3%). The tumor markers plus imaging had the highest sensitivity for different types of lung cancer, and the sensitivity to early lung cancer (90%) was superior to other diagnostic methods (P < 0.05). Conclusion: The tumor markers plus imaging is of great significance in early lung cancer diagnosis and provides a reference for judging the pathological classification.

Cyclic Behavior of Reinforced High Strain-Hardening UHPC under Axial Tension.

The cyclic tensile behavior of steel-reinforced high strain-hardening ultrahigh-performance concrete (HSHUHPC) was investigated in this paper. In the experimental program, 12 HSHUHPC specimens concentrically placed in a single steel reinforcement under cyclic uniaxial tension were tested, accompanied by acoustic emission (AE) source locating technology, and 4 identical specimens under monotonic uniaxial tension were tested as references. The experimental variables mainly include the loading pattern, the diameter of the embedded steel rebar, and the level of target strain at each cycle. The tensile responses of the steel-reinforced HSHUHPC specimens were evaluated using multiple performance measures, including the failure pattern, load-strain response, residual strain, stiffness degradation, and the tension-stiffening behavior. The test results showed that the enhanced bond strength due to the inclusion of steel fibers transformed the failure pattern of the steel-reinforced HSHUHPC into a single, localized macro-crack in conjunction with a sprinkling of narrow and closely spaced micro-cracks, which intensified the strain concentration in the embedded steel rebar. Besides, it was observed that the larger the diameter of the embedded steel rebar, the smaller the maximum accumulative tensile strain under cyclic tension, which indicated that the larger the diameter of the embedded steel rebar, the greater the contribution to the tensile stiffness of steel-reinforced HSHUHPC specimens in the elastic-plastic stage. In addition, it was found that a larger embedded steel rebar appeared to reduce the tension-stiffening effect (peak tensile strength) of the HSHUHPC. Moreover, the residual strain and the stiffness of the steel-reinforced HSHUHPC were reduced by increasing the number of cycles and finally tended toward stability. Nevertheless, different target strain rates in each cycle resulted in different eventual cumulative tensile strain rates; hence the rules about failure pattern, residual strain, and loading stiffness were divergent. Finally, the relationship between the accumulative tensile strain and the loading stiffness degradation ratio under cyclic tension was proposed and the tension-stiffening effect was analyzed.

CircRNA_0000429 Regulates Development of NSCLC by Acting as a Sponge of miR-1197 to Control MADD.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) is the most common type of lung cancer. Circular RNA_0000429 (circ_0000429) is an identified circular RNA (circRNA) that is correlated with cancer progression. However, the role of circ_0000429 in NSCLC remains unknown. In the present study, we aimed to investigate the function of circ_0000429 in NSCLC and the underlying mechanism. METHODS: The expression patterns of circ_0000429 were determined using qRT-PCR in NSCLC samples and cell lines. The subcellular distribution of circ_0000429 in NSCLC cells was analyzed by fluorescence in situ hybridization (FISH). Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNA-mRNA interactions. RESULTS: Our results showed that circ_0000429 expressions were significantly upregulated in NSCLC tissues and cell lines. Knockdown of circ_0000429 significantly inhibited the cell proliferation, migration, and invasion of NSCLC cells in vitro. Furthermore, we demonstrated that circ_0000429 acted as a sponge to absorb microRNA-1197 (miR-1197) and promoted MADD expression. CONCLUSION: Collectively, our results demonstrated that circ_0000429 exhibited a carcinogenic role by sponging miR-1197 and regulating CMADD expression in NSCLC. These findings provided evidence for understanding the role of circ_0000429 in NSCLC tumorigenesis.

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology.

Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.

Minimally invasive maxillary sinus augmentation with simultaneous implantation on an elderly patient: A case report.

BACKGROUND: In this case study, a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient. We analyzed the cone-beam computed tomography (CBCT) findings to evaluate bone regeneration. CASE SUMMARY: A 65-year-old female with no contraindications for dental implants and loss of maxillary bilateral molars is described. Examination by CBCT showed the available vertical bone height in the bilateral posterior maxilla was 0.5-6.8 mm in the left and 2.8-6.5 mm in the right. The patient underwent a transalveolar approach using platelet-rich fibrin and bone substitute with simulataneous placement of an implant 10 mm in length. Six months post-surgery, the implant showed excellent osseointegration with the bone graft. Thereafter, full-ceramic crowns were fitted. Follow-up at 2 years demonstrated satisfactory prognosis. CONCLUSION: Platelet-rich fibrin and bone substitute can be used to augment the maxillary sinus with a vertical bone height less than 4 mm.

Spontaneous cerebellar hemorrhage with severe brainstem dysfunction through minimally invasive puncture treatment by locating the simple bedside.

This study aims to evaluate the feasibility and effectiveness of minimally invasive puncture treatment by positioning the simple bedside for spontaneous cerebellar hemorrhage.From January 2017 to March 2018, the investigators applied simple bedside positioning to perform the intracranial hematoma minimally invasive surgery for 21 patients with cerebellar hemorrhage.For these 21 patients, the bleeding amount and Glasgow Coma Scale (GCS) score before the operation were 18.5 ±â€Š5.0 cc and 9.5 ±â€Š3.3, respectively; 24 hours after the operation, the GCS score was 11.0 ±â€Š4.6. Five patients died within 7 days of the operation and the head computed tomography (CT) was re-examined. It was found that the average bleeding amount was 3.4 ±â€Š0.9 cc, the operation success rate was 76.2%, and the accurate puncture rate was 100%. Six months later, the Modified Rankin Scale (MRS) score was 2.5 ±â€Š2.0. The postoperative recovery was good. The situation shows that patients with favorable outcomes (MRS score 0-2) accounted for 38.1% (8/21), and the fatality rate was 33.3% (7/21).The efficacy of the intracranial hematoma minimally invasive surgery by positioning the simple bedside for spontaneous cerebellar hemorrhage with severe brainstem dysfunction is good.

VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with pegylated interferon.

AIM: To evaluate the predictive value of vitamin D and its metabolic pathway gene polymorphisms in response to pegylated interferon (Peg-IFN) in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS: One hundred and nineteen HBeAg-positive CHB patients who received Peg-IFN monotherapy for 48 weeks and then were followed-up for another 48 weeks were prospectively enrolled; baseline 25-hydroxy vitamin D (25-(OH)D) and hepatitis B virus serologic marker levels were detected, nine critical single nucleotide polymorphisms within vitamin D metabolism were genotyped. RESULTS: Forty-five (37.8%), 44 (37.0%), 35 (29.4%), and 11 (9.2%) of the patients achieved virological response (VR), HBeAg loss, combined response (CR), and hepatitis B surface antigen (HBsAg) level < 200 IU/mL at the end of treatment (EOT; week 48), respectively; 42 (35.3%) and six (5.0%) people achieved HBeAg and HBsAg loss at the end of follow-up (EOF; week 96). Baseline HBeAg level was independent predictor of VR (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.294-0.751; P = 0.002), HBeAg loss (OR, 0.395; 95% CI, 0.243-0.643; P < 0.001), CR (OR, 0.392; 95% CI, 0.215-0.714; P = 0.002) at EOT and HBeAg loss at EOF (OR, 0.334; 95% CI, 0.203-0.559; P < 0.001); baseline HBsAg level itself was independent predictor of both HBsAg < 200 IU/mL at EOT (OR, 0.257; 95% CI, 0.103-0.642; P = 0.004) and HBsAg loss at EOF (OR, 0.232; 95% CI, 0.077-0.702; P = 0.010). Age was also independent predictors of HBsAg loss at EOF (OR, 0.775; 95% CI, 0.634-0.948; P = 0.013). Concerning genetic variation of VDR rs7975232/ ApaI, A allele was the genetic independent predictor of VR at EOT (OR, 1.824; 95% CI, 1.024-3.248; P = 0.041) and HBsAg loss at EOF (OR, 3.566; 95% CI, 1.057-12.029; P = 0.040). CONCLUSIONS: Genetic variation of VDR rs7975232/ ApaI is a pretreatment predictor of sustained HBsAg loss in HBeAg-positive CHB patients with Peg-IFN monotherapy.

[Thrombopoietin Prevents CoCl2-inducing Apoptosis of HUVEC through the PI3K/AKT Pathway].

OBJECTIVE: To investigate the effect of thrombopoietin (TPO) on chemical hypoxia-induced apoptosis of human umbilical vein endothelial cells (HUVEC), and to explore its potential mechanism. METHODS: The experiment was divided into 4 groups. The untreated HUVECs were used as normal control group. HUVECs treated with CoCl2 was CoCl2 group, and TPO was added into the culture medium 48 h before CoCl2 treatment as TPO + CoCl2 group. The cells was treated with TPO alone as TPO group. The cell viability and apoptosis of each groups were tested by Cell Counter Kit 8 (CCK-8) assay and flow cytometry. The expression of Caspase-3 and mitochondrial membrane potential (MMP) were then determined by flow cytometry with Caspase-3-PE and JC-1. The effect of TPO in PI3K/AKT pathway was detected by using Western blot. RESULTS: CoCl2 significantly inhibited the growth of HUVECs. The cell viability of HUVECs decreased gradually with enhancement of CoCl2 at a gradient of chemical concentrations (r= -0.997). CoCl2 dramatically increased apoptosis of HUVECs, whereas pre-treatment with TPO rescued cell apoptosis induced by CoCl2 (P<0.001). Further investigation found that TPO decreased the expression of Caspase-3 and inhibited the reduction of MMP induced by CoCl2 (P<0.05). TPO could increased the activation of PI3K/AKT pathway in HUVECs. CONCLUSION: TPO has a protective effect against CoCl2-induced apoptosis of HUVECs through activating the PI3K/AKT pathway, thus decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.