Causal effects of gut microbiota on the risk of erectile dysfunction: a Mendelian randomization study.

Erectile dysfunction ranks among the prevalent sexual disorders in men. Several studies have indicated a potential link between gut microbiota and erectile dysfunction. To validate this potential association, we were to screen statistical data from genome-wide association studies of gut microbiota and erectile dysfunction. p values of less than 1 × 10-5 were set as the threshold for screening instrumental variables that were strongly associated with gut microbiota. At the same time, in order to obtain more convincing findings, we further excluded instrumental variables with possible chain imbalance, instrumental variables with the presence of palindromes, instrumental variables with F-statistics less than 10, and instrumental variables associated with risk factors for erectile dysfunction. Five methods including inverse-variance weighted method, weighted median method, weighted mode, Mendelian randomization egger method and Mendelian randomization pleiotropy residual sum and outlier test were then used to analyse the 2591 instrumental variables obtained from the screening. We identified correlations between six gut microbiota and the risk of erectile dysfunction. The genus Ruminococcaceae UCG-013 exhibited an inverse association with the risk of developing erectile dysfunction (0.79 (0.65-0.97), P = 0.0214). Conversely, the genus Tyzzerella3 (1.13 (1.02-1.26), P = 0.0225), genus Erysipelotrichaceae UCG-003 (1.18 (1.01-1.38), P = 0.0412), genus LachnospiraceaeNC2004group (1.19 (1.03-1.37), P = 0.0191), genus Oscillibacter (1.23 (1.08-1.41), P = 0.0022), and family Lachnospiraceae (1.26 (1.05-1.52), P = 0.0123) demonstrated positive associations with an increased risk of erectile dysfunction. These sensitivity analyses of the gut microbiota were consistent. This study demonstrated a possible causal relationship between gut microbiota and erectile dysfunction risk through Mendelian randomization analysis, providing new potential possibilities for the prevention and treatment of erectile dysfunction.

DLEU7-AS1 promotes renal cell cancer by silencing the miR-26a-5p/coronin-3 axis.

Long non-coding RNAs (lncRNAs) have been implicated in the progression and development of many types of cancer by interacting with RNA, DNA and proteins, including DLEU7-AS1. However, the function of DLEU7-AS1 in renal cell cancer (RCC) remains unclear. In this study, two in silico prediction algorithms were used to discover the potential target of miR-26a-5p, which was determined to be a tumor suppressor gene, possibly DLEU7-AS1, through the downregulation of coronin-3 in RCC. Thus, we hypothesized that DLEU7-AS1 promotes RCC by silencing the miR-26a-5p/coronin-3 axis. To test our hypothesis, we confirmed that DLEU7-AS1 directly targets miR-26a-5p using the pmirGLO dual-luciferase reporter assay. Next, we observed that DLEU7-AS1 expression was markedly upregulated in RCC samples and inversely correlated with clinical prognosis and miR-26a-5p levels. Knockdown of DLEU7-AS1 significantly suppressed the growth and metastasis of RCC cells in vitro and attenuated tumor growth in vivo. Interestingly, exogenous expression of coronin-3 or miR-26a-5p inhibitor treatment almost completely rescued the DLEU7-AS1 knockdown-induced inhibitory effects on cell proliferation, migration and invasion. In conclusion, our data demonstrate that DLEU7-AS1 is an oncogene in RCC capable of regulating the growth and metastasis of RCC by silencing the miR-26a-5p/coronin-3 axis, suggesting that DLEU7-AS1 can be employed as a potential therapeutic target and prognostic biomarker for RCC.

Angiographic Characteristics of Cerebral Perfusion and Hemodynamics of the Bridging Artery After Surgical Treatment of Unilateral Moyamoya Disease.

Purpose: To investigate the characteristics of cerebral perfusion and hemodynamics of bypass grafting in the treatment of moyamoya disease (MMD) using the iFlow color-coded flow map in comparison with magnetic resonance imaging-perfusion-weighted imaging (MRI-PWI) and computational fluid dynamic (CFD) analysis. Materials and Methods: Patients with MMD treated with bypass grafting who had undergone MRI PWI and digital subtraction angiography for iFlow color-coded map was retrospectively enrolled and CFD was performed for calculating the hemodynamic stresses around the bypass grafting. Results: Forty-five patients with unilateral MMD treated with bypass surgery were enrolled. The bypass surgery was successful in all patients, with no severe neurological complications during the periprocedural period. Followed up for 4-12 months (median 5.5), the neurological function was good in all patients. The cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were significantly (p < 0.05) improved in the middle cerebral artery distribution area on the surgical side before and after vascular bypass, and the difference of TTP (s) measured from the proximal bifurcation of common carotid artery to the confluence of sinus was also significant (p < 0.05). A significant (p < 0.05) positive correlation existed in the perfusion parameters between the iFlow blood perfusion and the MRI-PWI perfusion, with r-value for TTP of 0.765 (p < 0.01). The iFlow color-coded blood flow map showed warm color changes on the diseased side, similar to those on the contralateral side. In CFD analysis, the hemodynamic stresses were all improved, in and around the bypass grafting and distal vessels, which were beneficial to blood flow entering distal arterial branches. Conclusion: The iFlow color-coded flow map can be used to analyze cerebral perfusion after bypass grafting for MMD, similar to MRI-PWI, and CFD can be used to analyze the hemodynamics after bypass grafting, revealing improved hemodynamics to promote blood flow entering distal arteries.

[Analysis of food sources of Eriocheir sinensis in rice-crab integrated ecosystem based on stable isotopes in saline-alkali land of the Yellow River Delta]. / åŸºäºŽç¨³å®šåŒä½ç´ çš„é»„æ²³ä¸‰è§’æ´²ç›ç¢±åœ°ç¨»èŸ¹ç§å »ç³»ç»Ÿä¸­åŽç»’èž¯èŸ¹é£Ÿç‰©æºåˆ†æž.

To explore food composition of Chinese mitten crab (Eriocheir sinensis) in rice-crab integrated ecosystem in saline-alkali land of the Yellow River Delta, we analyzed carbon and nitrogen stable isotope ratios (δ13C and δ15N) in the crab and that in food sources, including plants (Elodea, Potamogeton crispus, Ceratophyllum demersum, Lemna minor, Oryza sativa stem and leaf, rice grain), animals (benthos, zooplankton), organic debris and artificial feed (compound feed, corn meal) in Kenli District, Dongying, Shandong Province in June to October of 2020. Substantial differences in δ13C and δ15N were found among food sources. The δ13C and δ15N values of different food sources were in a range of -30.09‰--11.24‰ and 0.03‰-12.78‰, respectively, while those of the crab muscle were in range of -24.61‰--20.08‰ and 4.74‰-9.21‰, respectively, indicating diverse food sources for the crab. During the experiment, the contribution rate of different food sources followed the order: plant (46.7%-57.1%)>animal (21.5%-24.5%)>artificial feed (10.9%-21.3%)>organic detritus (7.1%-7.9%). It suggested that the natural bait of the paddy field could meet the feeding needs of Chinese mitten crabs in saline-alkali land. Even the crabs were fed with non-animal artificial feed, the contribution rates of the main food sources were not altered.

LncRNA FAM13A-AS1 Promotes Renal Carcinoma Tumorigenesis Through Sponging miR-141-3p to Upregulate NEK6 Expression.

Long non-coding RNAs are a diverse catalog of RNAs that have been implicated in various aspects of tumorigenesis. Emerging evidence indicates that they play crucial roles in tumor growth, disease progression, and drug resistance. However, the clinical significance of lncRNAs in tumor behavior prediction and disease prognosis as well as the underlying mechanism in renal cell carcinoma (RCC) remains elusive. By analyzing the gene expression profiles of 539 RCC patients from the TCGA cohort and 40 RCC patients from an independent cohort, we identified FAM13A-AS1, a poorly studied lncRNA, upregulated in RCC patients. Knockdown experiments revealed that FAM13A-AS1 promotes cell proliferation, migration, and invasion by interacting with miR-141-3p. FAM13A-AS1 regulates the expression of NEK6 by decoying miR-141-3p. In addition, there was a strong positive correlation between the expression of FAM13A-AS1 and NEK6 in RCC patients. In summary, our results demonstrate the oncogenic role of FAM13A-AS1 in RCC and suggest that it promotes tumorigenesis by upregulating the expression of NEK6 by competitively binding to miR-141-3p.

SLC7A11 negatively associates with mismatch repair gene expression and endows glioblastoma cells sensitive to radiation under low glucose conditions.

The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.

[Origin and development of HUA Tuo's acupuncturing sensation technique].

Based on HUA Tuo's personal experience, teaching experience, works as well as ancient books of similar times, this paper discusses the origin and development of HUA Tuo's acupuncturing sensation technique, and analyzes the reasons why this technology has been lost. The formation of this technique is influenced by the descriptions of "regulating qi " "arrival of qi " and "reaching qi" in Neijing (Internal Canon of Medicine) and Nanjing, and combines with the clinical summary of conduction direction and specific position of acupuncturing sensation. Due to HUA Tuo's personal experience, the inheritance characteristics of acupuncture technology and the background of his times, this technology may have been lost, but it still affects the acupuncture concept and practice of "qi reaching affected area" in later generations.

IDH1-R132H Suppresses Glioblastoma Malignancy through FAT1-ROS-HIF-1α Signaling.

BACKGROUND: Glioblastoma (GBM) is one of the most deadly primary malignant brain tumors in adults. R132H mutation of isocitrate dehydrogenase 1 (IDH1) predicts a better prognosis of GBM. IDH1-R132H is associated with increased hypoxia-inducible factor-1α (HIF-1α) expression in GBM tumors. However, the molecular mechanism underlying IDH1-R132H-HIF-1α signaling in GBM is still unclear. AIM: We aimed to investigate the molecular pathway of IDH1-R132H-HIF-1α in the regulation of GBM. MATERIALS AND METHODS: U87 and U251 GBM cells and xenograft tumor mice were used. RESULTS: We found that overexpression of IDH1-R132H decreased cell proliferation, increased apoptosis, decreased migration and invasion, enhanced temozolomide (TMZ)-induced cytotoxicity, and reduced tumor growth in xenograft mice. Overexpression of IDH1-R132H increased the expression of HIF-1α and downregulation of HIF-1α suppressed IDH1-R132H-induced effect on GBM. Reactive oxygen species (ROS) level was increased by IDH1-R132H over expression and the use of antioxidant inhibited IDH1-R132H-induced increase of HIF-1α expression. FAT Atypical Cadherin 1 (FAT1) expression was increased by IDH1-R132H over expression. Knockdown of FAT1 blocked IDH1-R132H-induced reduction of tumor growth in xenograft mice. Down regulation of FAT1 decreased HIF-1α expression and inhibited IDH1-R132H-induced increase of ROS level. CONCLUSIONS: Our findings provide new insights into IDH1-R132H-regulated downstream signaling in GBM and highlight the importance of IDH1-R132H-FAT1-ROS-HIF-1α signaling pathway in potential therapeutic intervention of GBM.

[Discussion on the needling technique with filiform needle in acupuncture-moxibustion teaching materials in the Republic of China].

Through collecting the literature data of the needling technique with filiform needle in 20 acupuncture-moxibustion teaching materials in the Republic of China， the manipulation techniques with filiform needle were analyzed, such as the technique of needle insertion, the technique of reinforcing and reducing, and the management of acupuncture abnormal conditions, as well as manual techniques and analgesics methods. It is found that the era of the Republic of China was the transition period of traditional acupuncture techniques to the modern ones in acupuncture-moxibustion teaching materials, in which, the twirling technique was predominated in the technique of needle insertion. In that period, the insertion technique of tube needle had been introduced and simplified, the theory and method of the new-style technique of reinforcing and reducing were emerged and the types of acupuncture abnormal conditions recorded in the teaching materials were different from those at present. Additionally, the applicable manipulation had not been specified nationally. There were the highly influential teaching materials, i.e. Advanced Acupuncture and Moxibustion Teaching Materials: Science of Acupuncture and Science of Moxibustion, Chinese Acupuncture and Moxibustion Teaching Materials and New Acupuncture and Moxibustion. The acupuncture-moxibustion teaching materials in the Republic of China has been influenced by the transition of acupuncture-moxibustion education modes, the introduction of Chinese-translation version of Japanese acupuncture-moxibustion books, the academic thoughts of acupuncture masters and the manufacturing process of needle devices.

Auricular Intradermal Acupuncture as a Supplementary Motor Rehabilitation Strategy in Poststroke Patients: A Randomized Preliminary Clinical Study.

We have explored the potential of auricular intradermal acupuncture (AIA) in standard rehabilitation and acupuncture treatment for motor recovery in poststroke patients. This was a randomized, controlled preliminary clinical study in which the patients were randomly assigned to the CT group (conventional treatment, standard rehabilitation, and routine acupuncture) or AIA group (AIA combined with conventional treatment) and underwent 6 sessions in 1 week (6 days). Standard procedures and previously reported acupuncture points were used. Clinical outcomes were measured by the Fugl-Meyer motor assessment (FMA) of flexor and extensor synergy movement (FSM and ESM) of the upper and lower extremities (UE and LE) at days 0, 3, and 6. The assessment was performed by blinded assessors. The AIA group showed a significant increase in FMA-UE/FMA-LE scores on day 3 (P=0.012 and 0.001, respectively) and day 6 (P=0.041 and P < 0.001, respectively), but this was not observed in the CT group. Furthermore, unlike the CT group, the AIA group exhibited a significant increase in the FMA-LE score on day 3 (P=0.004) and the FMA-UE scores on day 6 (P=0.048). Finally, the correlation between ESM and FMA-UE/FMA-LE was higher than that between FSM and FMA-UE/FMA-LE after treatment: for ESM and UE, r = 0.759, P=0.007; for ESM and LE, r = 0.697, P=0.003; for FSM and UE, r = 0.604, P=0.049; for FSM and LE, r = 0.347, P=0.188. AIA is useful for motor rehabilitation in poststroke patients, particularly in terms of improving extensor synergy. This trial is registered with CHiCTR1800020150.

[Characteristics of clinical effectiveness of bloodletting and proposed ways of mechanism research].

According to the operative characteristics, the stimulated site and the curative effect-emerged site of bloodletting therapy, its clinical characteristics may be divided into three categories: a) local stimulation induced focus-local effect, b) local stimulation induced effect of the distal target organ (point-to-point distal effect), and c) special point stimulation induced broader effect of the whole body. Accordingly, the underlying mechanisms of clinical outcomes mainly involve the improvement of the local microcirculation and secondary changes of inflammatory substances for the first category (local focus). The point-to-point distal effect might mainly involve the innervation of nerve segments, while the broad effect of specific acupoint stimulation might involve multiple levels of the neuro-endocrine-immune system. The future research on the mechanisms of bloodletting should starts from its specific effects and the type of disease, which should not be generalized.

miR-26 suppresses renal cell cancer via down-regulating coronin-3.

Coronin-3 (coronin-1C), a homotrimer F-actin-binding protein, has been reported to be important for metastasis in several types of cancers such as lung cancer, gastric cancer, and breast cancer. Here, we present an investigation of the expression and function of coronin-3 in renal cell cancer for the first time. We also confirmed that miR-26 directly targets coronin-3 and down-regulates its expression by western blot assay and dual-luciferase reporter system. The results of MTT and colony formation assay showed that miR-26 suppressed cell proliferation. Wound healing and transwell assay revealed that miR-26 inhibited migration and invasion of renal cancer cell. Moreover, overexpression of coronin-3 could reverse the miR-26-induced inhibition in cell growth and metastasis. Thus, our study suggests that coronin-3 should serve as a potential therapeutic target in renal cell cancer and provide a candidate for miRNA therapy.

[Analysis on the origin and development of elements of reinforcing and reducing needling techniques].

Reinforcing and reducing needling manipulations are important factors affecting clinical therapeutic effect. In the present paper, the relevant elements of the reinforcing and reducing techniques of acupuncture needle including the left- and right-ward twirling, gender, needling at the left and right, front and back parts of the body, needling along or against the running course of the meridian, and their origin and development recorded in ancient Chinese medical books were collected and sorted out, followed by analysis on the understandings of Chinese ancient medical practitioners about them. Results show that the right- or left-ward twirling of needles, gender, and needling at the right or left part, the front or the back part of the body of patients are not the core components of the reinforcing and reducing techniques. Of the three stimulus parameters of needling, named amplitude, frequency and duration which are frequently researched at present, only the duration of single twirling (frequency) was highly noted in GAO Wu's book Zhenjiu Juying (A Collection of Gems in Acupuncture and Moxibustion). It is worthy of being studied in the further. Regarding the stimulation intensity of acupuncture involving the identification of reinforcing or reducing manipulations, the factors influencing the patients' feelings of needling intensity of acupuncture should be studied at the same time.

[Parameters and connotations of quantity of mild moxibustion stimulation].

The quantity of mild moxibustion stimulation is an important factor affecting clinical therapeutic effect. In the present study, we collected related literature by using key word "moxibustion stimulation quantity" from CNKI Database and make a summary about its concept. The quantity of mild moxibustion stimulation has two common characters, namely thermal intensity and cumulative stimulating quantity, and contains 6 components (parameters), including thermal energy, thermal stimulus, heated area of the skin, and stimulating duration, intensity and frequency. According to the facts mentioned above, we hold that the mild moxibustion quantity actually has 3 dimensions, i．e., the duration of stimulation, the stimulating quantity of one treatment session, and the total stimulating quantity of multiple treatment sessions. Accurately grasping and rationally using the basic term of the quantity of mild moxibustion is not only conductive to control clinical moxibustion operation, but also conforms to the basic requirements for quantitative control of intervention measures in experimental researches.

[The origin, development and mechanisms of special acupuncture needle tools for cutaneous region].

In this paper, we expound the origin and development of special acupuncture needle tools for cutaneous region, and discuss its mechanisms from modern medical theory. By consulting related acupuncture books and literature and in combination with needles used in clinical practice, we conclude that acupuncture needle tools can be divided into skin massage needle (digital pressing, spoon needle, etc.), cutaneous pricking blood needle (shear needle, three-edged needle, plum blossom needle, etc.), subcutaneous shallow puncture needle (intradermal needle, superficial needle, subcutaneous in-dwelling needle), etc. The skin-brain axis is the core of skin stimulation therapy. Mechanical pressure exerted on the skin surface induced by acupuncture stimulation or pressing, microcirculation changes and drug superposition are probably the underlying mechanisms of special skin acupuncture needle tools for treatment of various clinical disorders.

[Summary and core technique on the origin and evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle].

By analyzing the evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle recorded in ancient literature of traditional Chinese medicine, it is found that the main contents of reinforcing-reducing manipulation by lifting and thrusting the needle include manipulating speed change, manual amplitude, insertion layer, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity. Among them, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity are the unnecessary parameters, while the manipulating speed change, manual amplitude and insertion layer are the indispensable parameters. The manipulating speed change is the core of the necessary parameters for the reinforcing-reducing manipulation achieved by lifting and thrusting the needle. Combined with the manual amplitude, the manipulating speed of needle determines the volume of needling stimulation. The insertion layer is decided on the base of the clinical demand. In the core technique of reinforcing-reducing manipulation by lifting and thrusting the needle, the reinforcing is achieved by thrusting the needle forcefully and quickly and then lifting the needle body slowly and evenly back to the original layer. The reducing is achieved by lifting the needle forcefully and quickly and then thrusting the needle body slowly and evenly back to the original layer. The manipulating speed and manual amplitude of needling are the parameters to quantize acupuncture manipulation. In association with the acupuncture effects in human body, these parameters contribute to the interpretation of the dose-effect relationship of acupuncture and the improvement of clinical effects.

Proton-Conductive Cocrystals of Twin Isomers of Coordination Polymers in Situ Formed by Keggin Anions and Cu(II)-4,4'-Bis(hydroxymethyl)-2,2'-bipyridine Complex Moieties.

Cocrystals and isomers, two well-known unique concepts in supramolecular chemistry, are rarely put together until now. For the first time, we report three unprecedented and interesting cocrystals of twin isomers of coordination polymers (CPs) in situ formed by typical Keggin anions and Cu(II)-4,4'-bis(hydroxymethyl)-2,2'-bipyridine (Cu(II)-H2L) complex moieties. In cocrystals 1-3, the Cu(II)-H2L complex moieties are quadrisupported on Keggin-type anions through W(Mo)-Ot-Cu-Ot-W(Mo) (Ot is the terminal O atom) links in the crystal to form two twin ionic/neutral CPs with a fixed chemical stoichiometry. Cocrystals 1-2 contain ionic isomers as {[Cu1(H2L)(H2O)2]2[P1W12O40]} n n+/{[Cu2(HL)(H2O)2]2[P2W12O40]} n n- for 1 and {[Cu1(H2L)(H2O)2]2[P1Mo12O40]} n n+/{[Cu2(HL)(H2O)2]2[P2Mo12O40]} n n- for 2. Cocrystal 3 contains neutral isomers as {[Cu1(H2L)(H2O)2]2[Si1W12O40]} n and {[Cu2(H2L)(H2O)2]2[Si2W12O40]} n. Cooperation of conformation and hydrogen bond network isomerism of Cu(II)-H2L fragments and tetracoordinated mode isomerism of Keggin anion is perfectly embodied in twin isomers. Moreover, based on hydrogen-bonding interactions, twin isomers are alternately arranged in a 1:1 stoichiometric ratio to give a cocrystal. Complicated accumulation of three types of hydrogen-bonding assemblies in the same crystal may be the reason that they give conductivity values over 10-4 S·cm-1 at 100 °C under 98% relative humidity.

[Evolvement of Acupuncture Needle Manipulation Techniques Described in Textbooks of Acupuncture and Moxibustion of Successive Editions].

This paper summarizes the evolvement of the needle manipulation techniques described in the textbooks of Acupuncture and Moxibustion of the past successive 10 editions in Chinese, analyzes the reasons for the evolvement and its impact on clinical treatment, and proposes future developing trends. After analyzing characteristics of needle-manipulation techniques of the well-known Chinese acupuncture specialists, and those described in multi-editions of the textbooks, we found that the currently evoluted contents primarily contain the definition and types of manipulating techniques. However, the reasons for the evolvement and connotation of needle manipulating are probably due to a) undefined descriptions in the history; b) changes in the academic studies and clinical application of acupuncture and moxibustion during the textbook compilation; c) the well-known specialists' and the participated editors' academic thoughts; d) the textbook content setting needs, etc. The evolvement reflects the changed preoccupations of factors affecting clinical efficacy of acupuncture manipulations, and facilitates the implementation of standardized clinical operative procedures. The development of current acupuncture needle manipulation techniques emphasizes the quantification of manual manipulations, fits clinical needs, and pays more attention to the pressing hand during needle insertion.

Clinical and prognostic significance of high-mobility group box-1 in human gliomas.

The objective of this study was to explore the expression and the clinical and prognostic significance of high-mobility group box-1 (HMGB1) in human gliomas. The expression of HMGB1 in 15 samples of normal brain tissue and 65 samples of different-grade glioma tissue was assayed using immunohistochemistry and western blot analysis. The associations between the differences in expression and pathology grades were analyzed statistically. Uni- and multivariate analyses were performed to investigate the prognostic value of HMGB1 expression and its expression levels. The positive rates of HMGB1 expression in normal brain and glioma tissue were 20.0% (3/15) and 76.9% (50/65), respectively. The expression of HMGB1 in glioma tissue was higher than that in normal tissue (P<0.05). The positive rates of HMGB1 expression in low-grade gliomas (LGGs, grades I and II) and high-grade gliomas (HGGs, grades III and IV) were 63.0% (17/27) and 86.8% (33/38), respectively, and the positive rates in HGG were higher than those in LGG (P=0.024). Western blot analysis showed that HMGB1 was also expressed in normal brain tissue. The expression levels in HGG were significantly higher than those in LGG (P<0.001). HMGB1-positive patients had significantly shorter overall survival times compared with HMGB1-negative patients (P=0.026). Increasing levels of HMGB1 expression significantly correlated with reduced survival times when all patients with glioma were considered (P=0.045). In conclusion, HMGB1 positivity and protein expression levels are of significant clinical and prognostic value in human gliomas. Detecting HMGB1 in human gliomas may be useful for assessing the degree of malignancy, and HMGB1 would appear to be a promising target in the clinical management of patients with glioma.

The effect of multiple evolutionary selections on synonymous codon usage of genes in the Mycoplasma bovis genome.

Mycoplasma bovis is a major pathogen causing arthritis, respiratory disease and mastitis in cattle. A better understanding of its genetic features and evolution might represent evidences of surviving host environments. In this study, multiple factors influencing synonymous codon usage patterns in M. bovis (three strains' genomes) were analyzed. The overall nucleotide content of genes in the M. bovis genome is AT-rich. Although the G and C contents at the third codon position of genes in the leading strand differ from those in the lagging strand (p<0.05), the 59 synonymous codon usage patterns of genes in the leading strand are highly similar to those in the lagging strand. The over-represented codons and the under-represented codons were identified. A comparison of the synonymous codon usage pattern of M. bovis and cattle (susceptible host) indicated the independent formation of synonymous codon usage of M. bovis. Principal component analysis revealed that (i) strand-specific mutational bias fails to affect the synonymous codon usage pattern in the leading and lagging strands, (ii) mutation pressure from nucleotide content plays a role in shaping the overall codon usage, and (iii) the major trend of synonymous codon usage has a significant correlation with the gene expression level that is estimated by the codon adaptation index. The plot of the effective number of codons against the G+C content at the third codon position also reveals that mutation pressure undoubtedly contributes to the synonymous codon usage pattern of M. bovis. Additionally, the formation of the overall codon usage is determined by certain evolutionary selections for gene function classification (30S protein, 50S protein, transposase, membrane protein, and lipoprotein) and translation elongation region of genes in M. bovis. The information could be helpful in further investigations of evolutionary mechanisms of the Mycoplasma family and heterologous expression of its functionally important proteins.