Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

Klf4 methylated by Prmt1 restrains the commitment of primitive endoderm.

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, Prmt1 depletion promotes PrE gene expression in mouse embryonic stem cells (ESCs). Single-cell RNA sequencing and flow cytometry assays demonstrated that Prmt1 depletion in mESCs contributes to an emerging cluster, where PrE genes are upregulated significantly. Furthermore, the efficiency of extraembryonic endoderm stem cell induction increased in Prmt1-depleted ESCs. Second, the pluripotency factor Klf4 methylated at Arg396 by Prmt1 is required for recruitment of the repressive mSin3a/HDAC complex to silence PrE genes. Most importantly, an embryonic chimeric assay showed that Prmt1 inhibition and mutated Klf4 at Arg 396 induce the integration of mouse ESCs into the PrE lineage. Therefore, we reveal a regulatory mechanism for cell fate decisions centered on Prmt1-mediated Klf4 methylation.

Downregulation of Protease Cathepsin D and Upregulation of Pathologic α-Synuclein Mediate Paucity of DNAJC6-Induced Degeneration of Dopaminergic Neurons.

A homozygous mutation of the DNAJC6 gene causes autosomal recessive familial type 19 of Parkinson's disease (PARK19). To test the hypothesis that PARK19 DNAJC6 mutations induce the neurodegeneration of dopaminergic cells by reducing the protein expression of functional DNAJC6 and causing DNAJC6 paucity, an in vitro PARK19 model was constructed by using shRNA-mediated gene silencing of endogenous DANJC6 in differentiated human SH-SY5Y dopaminergic neurons. shRNA targeting DNAJC6 induced the neurodegeneration of dopaminergic cells. DNAJC6 paucity reduced the level of cytosolic clathrin heavy chain and the number of lysosomes in dopaminergic neurons. A DNAJC6 paucity-induced reduction in the lysosomal number downregulated the protein level of lysosomal protease cathepsin D and impaired macroautophagy, resulting in the upregulation of pathologic α-synuclein or phospho-α-synucleinSer129 in the endoplasmic reticulum (ER) and mitochondria. The expression of α-synuclein shRNA or cathepsin D blocked the DNAJC6 deficiency-evoked degeneration of dopaminergic cells. An increase in ER α-synuclein or phospho-α-synucleinSer129 caused by DNAJC6 paucity activated ER stress, the unfolded protein response and ER stress-triggered apoptotic signaling. The lack of DNAJC6-induced upregulation of mitochondrial α-synuclein depolarized the mitochondrial membrane potential and elevated the mitochondrial level of superoxide. The DNAJC6 paucity-evoked ER stress-related apoptotic cascade, mitochondrial malfunction and oxidative stress induced the degeneration of dopaminergic neurons via activating mitochondrial pro-apoptotic signaling. In contrast with the neuroprotective function of WT DNAJC6, the PARK19 DNAJC6 mutants (Q789X or R927G) failed to attenuate the tunicamycin- or rotenone-induced upregulation of pathologic α-synuclein and stimulation of apoptotic signaling. Our data suggest that PARK19 mutation-induced DNAJC6 paucity causes the degeneration of dopaminergic neurons via downregulating protease cathepsin D and upregulating neurotoxic α-synuclein. Our results also indicate that PARK19 mutation (Q789X or R927G) impairs the DNAJC6-mediated neuroprotective function.

Bruceine D may affect the phenylpropanoid biosynthesis by acting on ADTs thus inhibiting Bidens pilosa L. seed germination.

Bruceine D is a natural quassinoid, which was successfully isolated in our research group from the residue of Brucea javanica (L.) seeds. Our previous research showed that Bruceine D prevented Bidens pilosa L. seed germination by suppressing the activity of key enzymes and the expression levels of key genes involved in the phenylpropanoid biosynthesis pathway. In this study, integrated analyses of non-targeted metabolomic and transcriptomic were performed. A total of 356 different accumulated metabolites (DAMs) were identified, and KEGG pathway analyses revealed that most of these DAMs were involved in phenylpropanoid biosynthesis. The decreased expression of ADTs and content of L-phenylalanine implicates that Bruceine D may suppress the downstream phenylpropanoid biosynthesis pathway by disrupting primary metabolism, that is, the phenylalanine biosynthesis pathway, thus inhibiting the final products, resulting in the interruption of B. pilosa seed germination. These results suggest that Bruceine D may inhibit the B. pilosa seed germination by suppressing phenylpropanoid biosynthesis through acting on ADTs.

Determining programmed cell death ligand 1 expression in circulating tumor cells of patients with clear cell renal cell carcinoma and its correlation with response to programmed cell death protein 1 inhibitors.

OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.

[Research Progress on the Application of Artificial Intelligence in Rehabilitation Medicine in China].

The development of science and technology and the increasing demand of rehabilitation have driven the integration between artificial intelligence and rehabilitation medicine.In this study,statistical methods,document visualization tools,and other analysis methods were used in the Citespace software to analyze China's research status of artificial intelligence in the field of rehabilitation medicine with the key words of co-occurrence,emergence,and clustering.The relevant research hot spots were then classified and expounded.The results demonstrated that the current hot spots of artificial intelligence related to rehabilitation medicine included robots,brain-computer interfaces,human-computer interaction,and motor imagery.According to the clustering of key words and literature analysis,the five themes of artificial intelligence in rehabilitation medicine were determined as robot,brain-computer interface,intelligent rehabilitation training system,human-computer interaction,and assisted diagnosis and remote rehabilitation.Robotics and human-computer interaction would still be the research hot spots in the long future,and brain-computer interfaces,motor imagery,and remote rehabilitation would be new ones.This study analyzed the current hot spots,predicted the development trends,discussed the limitations,and proposed suggestions,aiming to provide reference for other scholars focusing on the application of artificial intelligence in rehabilitation medicine.

Psychometric testing of the support and control in birth scale.

BACKGROUND: The Support and Control in Birth (SCIB) scale primarily measures the perceived support and control of expectant mothers during childbirth, thereby obtaining an understanding of their birth experiences. The advantages of this scale are its good reliability and validity and that it consolidates birth support and control. However, a Chinese version of the scale has yet to be developed. Therefore, this study sought to evaluate the validity and reliability of a Chinese version of the Support and Control in Birth Scale (C-SCIB). METHODS: A total of 228 postpartum women participated in this study. The C-SCIB scale was developed through a translation and back translation, followed by an evaluation of its content validity by a group of experts. Cronbach's α internal consistency and test-retest reliability were used to test the reliability of the scale. In addition, criterion-related validity (predictive validity and concurrent validity) and construct validity were used to test the validity of the scale. RESULTS: The C-SCIB scale showed good results in terms of the item-level and scale-level content validity indices. The Cronbach's α internal consistency was 0.81, and its test-retest reliability was 0.96. The confirmatory factor analysis results showed the overall goodness-of-fit was parsimony fit indices. The predictive validity analysis showed a significant positive correlation between the C-SCIB scale and the Questionnaire Measuring Attitudes About Labor and Delivery (r = 0.31, p < 0.01). Furthermore, the concurrent validity analysis showed a significant and moderate correlation between the C-SCIB and the Bryanton Adaptation of the Nursing Support in Labor Questionnaire (r = 0.49, p < 0.01) as well as the Labor Agentry Scale (r = 0.51, p < 0.01). CONCLUSION: The C-SCIB scale was proven to have good reliability and validity, and thus can be used to measure the degree of support and the locus of control perceived by expectant women during labor.

Characterization of an Ecdysteroid-Regulated 16 kDa Protein Gene in Chinese Oak Silkworm, Antheraea pernyi (Lepidoptera: Saturniidae).

A large number of ecdysteroid-regulated 16 kDa proteins (ESR16s) of insects have been isolated and annotated in GenBank; however, knowledge on insect ESR16s remain limited. In the present study, we characterized an ecdysteroid-regulated 16 kDa protein gene isolated in Chinese oak silkworm, Antheraea pernyi Guérin-Méneville ('ApESR16' in the following), an important silk-producing and edible insect. The obtained cDNA sequence of ApESR16 is 1,049 bp, harboring an open reading frame of 441 bp that encodes a polypeptide of 146 amino acids. CD-search revealed that ApESR16 contains the putative cholesterol/lipid binding sites on conserved domain Npc2_like (Niemann-Pick type C-2) belonging to the MD-2-related lipid-recognition superfamily. Sequence comparison revealed that ApESR16 exhibits 51-57% identity to ESR16s of lepidopteran insects, 36-41% identity to ESR16 or NPC2a of nonlepidopteran insects, and 28-32% identity to NPC2a of vertebrates, indicating a high sequence divergence during the evolution of animals. Phylogenetic analysis found that the used sequences were divided into two groups corresponding to vertebrates and invertebrates, and the used insect sequences were also well clustered according to their families. The A. pernyi ESR16 mRNA is expressed during all four developmental stages and in all tested tissues. Injection of 20-hydroxyecdysone (20-E) into A. pernyi diapausing pupae triggering diapause termination induced upregulation of ESR16 mRNA compared to the diapausing pupae, with the highest expression level at day 2 in the ovaries but day 12 in the fat body. Our results suggested that ApESR16 might be a diapause-related gene and plays a vital role in the pupal diapause of A. pernyi.

Toxicity and biochemical effects of itol A on the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

Itol A, a novel isoryanodane diterpene derived from Itoa orientalis Hemsl., has potent activities against insect pests. This study was conducted to determine the contact toxicity and biochemical effects of itol A on the Nilaparvata lugens. After macropterous females of N. lugens were exposed to itol A from 0.5 to 24 h, the mortality and poisoning symptoms were measured. Effects of itol A on the major enzymes activity and oxidative stress level were assessed in dose-response (with LD10-LD70 at 24 h) and time-course (with LD50 at 0.5-24 h) experiments for the potential toxicity mechanisms. Based on the results, the mortality of N. lugens showed significant dose- and time-dependent effects, with the 24-h LD50 value was 0.58 µg/insect. The symptoms of excitation, convulsion and paralysis were also observed. However, acetylcholinesterases (AChE) activity was not altered after itol A treatment compared to control. Na+/K+-ATPases, Ca2+-ATPases, Ca2+/Mg2+-ATPases, glutathione S-transferases (GSTs), cytochrome P450 monooxygenases (P450s), superoxide dismutases (SOD) and catalases (CAT) activities were significantly reduced in dose-response and time-course experiments. While acid phosphatases (ACP) and glutathione peroxidases (GPX) activities were significantly increased. We further revealed that itol A exposure resulted in the decrease of GSH/GSSG (reduced to oxidized glutathione) ratio and the increase of hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in both experiments. The results indicated that the inhibition of Na+/K+-ATPases, Ca2+-ATPases, Ca2+/Mg2+-ATPases, GSTs, P450s, SOD and CAT activities and the induction of oxidative stress was one of the potential biochemical mechanisms of itol A against N. lugens.

Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell growth.

The deregulation of epigenetics was involved in early and subsequent carcinogenic events. Reversing cancer epigenetics to restore a normal epigenetic condition could be a rational approach for cancer treatment and specialized prevention. In the present study, we found that the expression levels of two epigenetic markers, histone H3K27 trimethylation (H3K27me3), was low but histone H3S10 phosphorylation (pH3Ser10) was high in human bladder cancer tissues, which showed opposite expression patterns in their normal counterparts. Thus, we investigated whether a natural product, emodin, has the ability to reverse these two epigenetic modifications and inhibit bladder cancer cell growth. Emodin significantly inhibited the cell growth of four bladder cancer cell lines in a dose- and time-dependent manner. Emodin treatment did not induce specific cell cycle arrest, but it altered epigenetic modifications. Emodin treatment resulted in the suppression of pH3Ser10 and increased H3K27me3, contributing to gene silencing in bladder cancer cells. Microarray analysis demonstrated that oncogenic genes including fatty acid binding protein 4 (FABP4) and fibroblast growth factor binding protein 1 (HBP17), RGS4, tissue inhibitor of metalloproteinase 3 (TIMP3), WNT5b, URB, and collagen, type VIII, alpha 1 (COL8A1) responsible for proliferation, survival, inflammation, and carcinogenesis were significantly repressed by emodin. The ChIP assays also showed that emodin increased H3K27me3 but decreased pH3Ser10 modifications on the promoters of repressed genes, which indicate that emodin reverses the cancer epigenetics towards normal epigenetic situations. In conclusion, our work demonstrates the significant anti-neoplastic activity of emodin on bladder cancer cells and elucidates the novel mechanisms of emodin-mediated epigenetic modulation of target genes. Our study warrants further investigation of emodin as an effective therapeutic or preventive agent for bladder cancer.

Evaluation of drug interactions of Saposhnikoviae Radix and its major components with astragaloside IV and paeoniflorin using in vitro and in vivo experiments.

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.

Simultaneous multi-mycotoxin determination in nutmeg by ultrasound-assisted solid-liquid extraction and immunoaffinity column clean-up coupled with liquid chromatography and on-line post-column photochemical derivatization-fluorescence detection.

A simple and sensitive analytical method based on ultrasound-assisted solid-liquid extraction and immunoaffinity column clean-up coupled with high performance liquid chromatography and on-line post-column photochemical derivatization-fluorescence detection (USLE-IAC-HPLC-PCD-FLD) has been developed for simultaneous multi-mycotoxin determination of aflatoxins B1, B2, G1, G2 (AFB1, AFB2, AFG1, AFG2) and ochratoxin A (OTA) in 13 edible and medicinal nutmeg samples marketed in China. AFs and OTA were extracted from nutmeg samples by ultrasonication using a methanol : water (80 : 20, v/v) solution, followed by an IAC clean-up step. Different USL extraction conditions, pre-processing ways for nutmeg sample and clean-up columns for mycotoxins, as well as HPLC-PCD-FLD parameters (mobile phase, column temperature, elution procedure, excitation and emission wavelengths) were optimized. This method, which was appraised for analyzing nutmeg samples, showed satisfactory results with reference to limits of detection (LODs) (from 0.02 to 0.25 µg kg(-1)), limits of quantification (LOQs) (from 0.06 to 0.8 µg kg(-1)), linear ranges (up to 30 ng mL(-1) for AFB1, AFG1 and OTA and 9 ng mL(-1) for AFB2 and AFG2), intra- and inter-day variability (all <2%) and average recoveries (from 79.6 to 90.8% for AFs and from 93.6 to 97.3% for OTA, respectively). The results of the application of developed method in nutmeg samples have elucidated that four samples were detected with contamination of AFs and one with OTA. AFB1 was the most frequently found mycotoxin in 30.8% of nutmeg samples at contamination levels of 0.73-16.31 µg kg(-1). At least two different mycotoxins were co-occurred in three samples, and three AFs were simultaneously detected in one sample.

Albumin prevents reactive oxygen species-induced mitochondrial damage, autophagy, and apoptosis during serum starvation.

Aberrant levels of reactive oxygen species (ROS) rapidly generated from NADPH oxidase (NOX) activation can be cytotoxic due to activating pro-apoptotic signals. However, ROS also induce pro-survival autophagy through the engulfment of damaged mitochondria. This study is aimed at investigating the cytoprotective role of albumin against NOX/ROS-induced autophagy and apoptosis under serum starvation. Serum starvation induced apoptosis following a myeloid cell leukemia sequence 1 (Mcl-1)/Bax imbalance, loss of the mitochondrial transmembrane potential, and caspase activation accompanied by pro-survival autophagy following canonical inhibition of mammalian target of rapamycin complex 1 (mTORC1). Aberrant ROS generation, initially occurring through NOX, facilitated mitochondrial damage, autophagy, and apoptosis. Autophagy additionally regulated the accumulation of ROS-generating mitochondria. NOX/ROS permitted p38 mitogen-activated protein kinase (p38 MAPK)-regulated mitochondrial apoptosis, accompanied by non-canonical induction of autophagy. In addition, activation of glycogen synthase kinase (GSK)-3ß by NOX/ROS-inactivated Akt facilitated a decrease in Mcl-1, followed by mitochondrial apoptosis as well as autophagy. Restoring albumin conferred an anti-oxidative effect against serum starvation-deregulated NOX, p38 MAPK, and Akt/GSK-3ß/Mcl-1/caspase-3 signaling. Albumin also prevented autophagy by sustaining mTORC1. These results indicate an anti-oxidative role for albumin via preventing NOX/ROS-mediated mitochondrial signaling to stimulate apoptosis as well as autophagy. Autophagy, initially induced by canonical inhibition of mTORC1 and enhanced by non-canonical mitochondrial damage, acts physically as a pro-survival mechanism.

Influence of impurities on the specific optical rotation of cefozopran.

The impurities of cefozopran hydrochloride are analyzed using high-performance liquid chromatography (HPLC) with UV absorbance and optical rotation (OR) detection. The results show that the impurities can affect the specific optical rotation of the cefozopran product. Due to the different composition of impurities, the Chinese cefozopran hydrochloride product has a specific optical rotation different from the Japanese product. The relationship between impurity limits and specific optical rotation of cefozopran hydrochloride is revealed. The results provide a scientific rationale for setting the limit of specific optical rotation of cefozopran hydrochloride.

Cyperus rotundus L. drives arable soil infertile by changing the structure of soil bacteria in the rhizosphere, using a maize field as an example.

Rhizosphere microorganisms can greatly affect plant growth, especially the plant growth-promoting rhizobacteria (PGPR), which can improve plant root development and growth because they contain various biological functions including nitrogen fixation, phosphate solubilization, and phytosiderophore production. This study demonstrates that Cyperus rotundus L. is capable of developing and forming complex underground reproductive systems at arbitrary burial depths and cutting modes due to its extremely strong multiplication and regeneration ability. With the densities of C. rotundus increasing, the abundance of PGPR, soil enzymes invertase and urease, the nutrient contents of the field soil, and maize quality were impacted. Notably, more abundance of PGPR-most notably, the nitrogen-fixing microorganisms (NFMs) such as Azospirillum, Burkholderia, Mycobacterium, and Rhizobium-enriches in the rhizosphere of C. rotundus than in that of maize. In addition, the activities of soil enzymes invertase (S_SC) and urease (S_SU) were significantly higher in its rhizosphere than in maize, further proving that more NFMs enrich the C. rotundus rhizosphere. The nutrient contents of the field soil of TN, SOM, and SOC were reduced, indicating that the presence of C. rotundus made the soil infertile. Hence, these pieces of evidence indicate that C. rotundus may drive the field soil infertile as reflected by reduced soil nutrients via altering rhizosphere bacteria community structure.

Nonsyndromic supernumerary teeth in patients in National Taiwan University Children's hospital.

Background/purpose: A literature review reveals limited data for supernumerary teeth in Taiwan. This study aimed to analyze the characteristics of nonsyndromic supernumerary teeth in patients in the National Taiwan University Children's Hospital. Materials and methods: This retrospective study analyzed the nonsyndromic supernumerary teeth in 1280 patients (710 boys and 570 girls) based on examination of mainly panoramic radiographs and related radiographs. Chi-square test was used for trend analysis. Results: The incidence of nonsyndromic supernumerary teeth was 11.25% (179 supernumerary teeth in 144 of the 1280 patients). There was a male predominance (4.33: 1, P < 0.0001) for our 144 patients. Most supernumerary teeth were single (63.69%), conical-shaped (78.77%), and unerupted (77.09%). Supernumerary teeth also tended to be located in the premaxilla (93.85%), fully developed (51.40%), invertedly oriented (45.25%), sagittally located in a palatal/lingual position (67.60%), and adjacent to the root and root apex of permanent teeth (70.39%). The supernumerary teeth with a normal orientation (64.52%) had a high potential to erupt into the oral cavity, but the majority of the supernumerary teeth with a transverse orientation (97.22%) or an inverted orientation (100%) were unerupted. Conclusion: The nonsyndromic supernumerary teeth occur most commonly in male patients with a male to female ratio of 4.33: 1. The incidence of nonsyndromic supernumerary teeth in our 1280 patients is 11.25%, and the most frequent location of supernumerary teeth is the anterior maxillary region. More than three quarters of supernumerary teeth are conical-shaped or unerupted. Inverted supernumerary teeth are all embedded in the jawbones.

Case report: MOG-IgG-associated encephalitis with Epstein-Barr virus infection and Alzheimer's pathologic change in cerebrospinal fluid.

Immunoglobulin G antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) associated disease is a rare, demyelinated disease in the central nerve system (CNS) predominately involving optic nerve, spinal cord, and brain leading to optic neuritis (ON), transverse myelitis (TM), encephalitis. The phenotype of MOG-IgG-associated encephalitis is similar to acute disseminated encephalomyelitis (ADEM) presenting with seizures, abnormal behavioral and psychological symptoms, and cognitive impairment. A few brain biopsies show multiple sclerosis (MS) pattern histopathology with T cells, macrophages, and complement activation. To date, how MOG-IgG is produced is unknown. Herein, we report a case of a 32-year-old male with MOG-IgG-associated encephalitis presenting MOG-IgG in cerebrospinal fluid (CSF) but seronegative, as well as Epstein-Barr virus (EBV) infection and Alzheimer's pathologic change in CSF (Aß42 = 317 pg/ml, T-Tau = 538 pg/ml, p-Tau =10.09 pg/ml). With a combination treatment of administering intravenous immunoglobulin (0.4 mg/kg/d, 5 days) with a low dose of methylprednisolone (80 mg/d, 5 days) and rituximab (100 mg/week, 3 weeks), the patient recovered significantly after 3 months follow-up. This case provides us with new thoughts into the production of MOG-IgG and the possible pathologic mechanism of MOG-IgG-associated disease (MOG-AD) and simultaneously further confirms the interaction between EBV and changes of CSF biomarkers of Alzheimer's disease (AD).

Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors.

BACKGROUND: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. METHODS: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. RESULTS: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). CONCLUSIONS: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.

Detection of circulating tumor cells as therapeutic markers in patients with penile squamous cell carcinoma: A preliminary study.

BACKGROUND: This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS: CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS: CTCs were found in all PSCC blood samples but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION: Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for noninvasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.

[The effect of culture supernatant from MSCs on the proliferation and expression of COX-2, MMP-2 in rat synovial cell line].

OBJECTIVE: To investigate the effect of culture supernatant form mesenchymal stem cells (MSCs) on the proliferation of rat fibroblast-like synovial cell line RSC-364 and the expression of COX-2, MMP-2. METHODS: After isolation and identification of MSCs, the effect of MSCs supernatant liquid (MSCs-SL) on the proliferation of RSC-364 and the expression of COX-2, MMP-2 were detected by MTT assay and RT-PCR. RESULTS: MSCs-SL enhanced the proliferation of synoviocyte and elevated the expression of COX-2 and MMP-2 in synoviocytes (P < 0.05). CONCLUSION: MSCs may influence the proliferation of synoviocytes by secreting soluble cytokines and altered the expression level of some enzymes in synoviocytes.