Role of 8-hydroxyguanine DNA glycosidase 1 deficiency in exacerbating diabetic cardiomyopathy through the regulation of insulin resistance.

Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.

PDMS-TiO2 composite films combined with LC-MS/MS for determination of phospholipids of urine in non-small cell lung cancer patients with traditional Chinese medicine syndromes.

Lung cancer is one of the most common malignant tumors in China. Most patients are already in the mid to advanced stages during the consultation and the survival rate is less than 23 % with a poor prognosis. Therefore, effective dialectical diagnosis of advanced cancer can guide individualized treatment to improve survival. Phospholipids are the building blocks of cell membranes and abnormal phospholipid metabolism is associated with plentiful diseases. Most studies of disease markers use blood as a sample. However, urine covers extensive metabolites that are produced during the body's metabolic processes. Therefore, the study of markers in urine can be used as a complement to improve the diagnosis rate of marker diseases. Moreover, urine is characterized by high water content, high polarity, and high inorganic salt, therefore the detection of phospholipids in urine is challenging. In this study, an original Polydimethylsiloxane (PDMS)-titanium dioxide (TiO2) composite film for sample pre-treatment coupled with the LC-MS/MS method for the determination of phospholipids in the urine with high selectivity and low matrix effects was prepared and developed. The extraction process was scientifically optimized by the single-factor test. After systematic validation, the established method was successfully applied to the accurate determination of phospholipid substances in the urine of lung cancer patients and healthy subjects. In conclusion, the developed method has great potential for the development of lipid enrichment analysis in urine and can be used as a beneficial tool for cancer diagnosis and Chinese medicine syndrome typing.

A Comprehensive Analysis of Microflora and Metabolites in the Development of Ulcerative Colitis into Colorectal Cancer Based on the Lung-Gut Correlation Theory.

The lungs and large intestine can co-regulate inflammation and immunity through the lung-gut axis, in which the transportation of the gut microbiota and metabolites is the most important communication channel. In our previous study, not only did the composition of the gut microbiota and metabolites related to inflammation change significantly during the transition from ulcerative colitis (UC) to colorectal cancer (CRC), but the lung tissues also showed corresponding inflammatory changes, which indicated that gastrointestinal diseases can lead to pulmonary diseases. In order to elucidate the mechanisms of this lung-gut axis, metabolites in bronchoalveolar lavage fluid (BALF) and lung tissues were detected using UHPLC-Q-TOF-MS/MS technology, while microbiome characterization was performed in BALF using 16S rDNA sequencing. The levels of pulmonary metabolites changed greatly during the development of UC to CRC. Among these changes, the concentrations of linoleic acid and 7-hydroxy-3-oxocholic acid gradually increased during the development of UC to CRC. In addition, the composition of the pulmonary microbiota also changed significantly, with an increase in the Proteobacteria and an obvious decrease in the Firmicutes. These changes were consistent with our previous studies of the gut. Collectively, the microbiota and metabolites identified above might be the key markers related to lung and gut diseases, which can be used as an indication of the transition of diseases from the gut to the lung and provide a scientific basis for clinical treatment.

Fibroblast growth factor 9 attenuates sepsis-induced fulminant hepatitis in mice.

Sepsis-induced fulminant hepatitis (FH) is a fatal syndrome that has a worse prognosis in clinical practice. Hence, seeking effective agents for sepsis-induced FH treatment is urgently needed. Fibroblast growth factors (FGFs) are vital for tissue homeostasis and damage repair in various organs including the liver. Our study aims to investigate the protective effects and potential mechanisms of FGF9 on lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced FH in mice. We found that pre-treatment with FGF9 exhibited remarkable hepaprotective effects on liver damage caused by LPS/D-Gal, as manifested by the concomitant decrease in mortality and serum aminotransferase activities, and the attenuation of hepatocellular apoptosis and hepatic histopathological abnormalities in LPS/D-Gal-intoxicated mice. We further found that FGF9 alleviated the infiltration of neutrophils into the liver, and decreased the serum levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in LPS/D-Gal-challenged mice. These effects can be explained at least in part by the inhibition of NF-κB signaling pathway. Meanwhile, FGF9 enhanced the antioxidative defense system in mice livers by upregulating the expression of NRF-2-related antioxidative enzymes, including glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H: quinone oxidoreductase 1 (NQO-1), and heme oxygenase-1 (HO-1). These data indicate that FGF9 represents a promising therapeutic drug for ameliorating sepsis-induced FH via its anti-apoptotic and anti-inflammatory capacities.

Leonurus japonicus Houtt. (Motherwort): Systematic research through chemical profiling, stability under controlled conditions and pharmacokinetic analysis on screening Q-markers for quality control.

Leonurus japonicus Houtt. (Motherwort) is the fresh or dried aerial part of Leonurus japonicus Houtt. (Labiaceae), which is widely used in clinical practice and daily life, used to treat gynecological diseases. However, the differences between different parts, single index component in Pharmacopoeias and the less stability of active ingredients affect its clinical efficacy. This study aimed to find the multi-active compounds between different parts of Motherwort to ensure its clinical efficacy, which related to stability and had pharmacokinetic behavior. Firstly, HPLC-Q-TOF-MS/MS was used to analyze the components in vitro and in vivo, as well as multivariate statistical analysis and network pharmacology analysis was conducted to find the significant different components related to activity. Secondly, the content determination methods were established to study the stability of effective components during storage in order to establish the content limit for quality control of Motherwort. Thirdly, UFLC-MS/MS was used to analyze the pharmacokinetic behavior of active components in Motherwort. The results showed that a total of 131 chemical constituents were identified in vitro and 21 prototype absorption compounds and 72 metabolites were found in vivo. Meantime, multivariate statistical analysis and network pharmacology analysis was combined to find that leonurine, stachydrine and trigonelline were activity-related substance, which could be used as active components related to pharmacodynamics in different parts. Then the stability variation trend and content limit of three alkaloids were found, which could be used for the quality control of Motherwort. Furthermore, the results showed that three alkaloids had pharmacokinetic behavior in vivo. 3 alkaloids were screened, which could be used as active components most closely related to pharmacodynamics among different parts. The stable stage, assay tolerance and pharmacokinetic characteristics were studied by the active substances, which could provide a basis for quality control and clinical medication of Motherwort.

Study on the characteristics of nitrogen dioxide adsorption and storage of coal residue in coal-fired power plants in goaf.

In order to realize the storage of the residual coal in the goaf on the flue gas of the power plant, the adsorption characteristics of nitrogen dioxide in the flue gas of the power plant were studied. The Gaussian09 was used to study the adsorption process of NO2 molecules on coal at the density functional (DFT) B3LYP/6-311G level, and the model of NO2 adsorption by coal was established. Different quantities were obtained using orbital energy changes and molecular bond length changes. According to the principle of molecular adsorption, the adsorption of NO2 by coal is considered to be physical adsorption with endothermic heat. On the basis of simulation, using self-organized experimental devices, the single-component NO2 gas and the simulated coal-fired power plant flue gas were introduced into anthracite, bituminous coal and lignite. In single-component adsorption, the adsorption of NO2 by lignite increases with time. The time to reach equilibrium is related to the properties of the coal itself. In the process of simulated flue gas adsorption, the order of the adsorption amount of coal to flue gas is CO2 > NO2 > N2 > O2. In the simulated flue gas, coal is easy to absorb NO2 and CO2, and the competition between gases reduces the frequency of contact between NO2 and the coal surface. Simulation and experimental results show that coal has obvious adsorption characteristics for NO2, and it is feasible for the residual coal in the goaf to adsorb NO2 in the flue gas of power plants.

Percutaneous versus open pedicle screw instrumentation in treatment of thoracic and lumbar spine fractures: A systematic review and meta-analysis.

BACKGROUND: To assess the safety and efficacy of percutaneous short-segment pedicle instrumentation compared with conventionally open short-segment pedicle instrumentation and provide recommendations for using these procedures to treat thoracolumbar fractures. METHODS: The Medline database, Cochrane database of Systematic Reviews, Cochrane Clinical Trial Register, and Embase were searched for articles published. The randomized controlled trials (RCTs) and non-RCTs that compared percutaneous short-segment pedicle instrumentation to open short-segment pedicle instrumentation and provided data on safety and clinical effects were included. Demographic characteristics, clinical outcomes, radiological outcomes, and adverse events were manually extracted from all of the selected studies. Methodological quality of included studies using Methodological Index for Non-Randomized Studies scale and Cochrane collaboration's tool for assessing the risk of bias by 2 reviewers independently. RESULTS: Nine studies encompassing 433 patients met the inclusion criteria. Subgroup meta-analyses were performed according to the study design. The pooled results showed there were significant differences between the 2 techniques in short- and long-term visual analog scale, intraoperative blood loss, operative time, postoperative draining loss, hospital stay, and incision size, although there were no significant differences in postoperative radiological outcomes, Oswestry Disability Index, hospitalization cost, intraoperative fluoroscopy time, and adverse events. CONCLUSION: Percutaneous short-segment pedicle instrumentation in cases with achieve satisfactory results, could replace in many cases extensive open surgery and not increased related complications. However, further high-quality RCTs are needed to assess the long-term outcome of patients between 2 techniques.

Long noncoding RNA HOXD-AS1 aggravates osteosarcoma carcinogenesis through epigenetically inhibiting p57 via EZH2.

Osteosarcoma is the most common primary malignant bone tumor and long non-coding RNAs (lncRNAs) have been proved to epigenetically regulate the oncogenesis of osteosarcoma. In this research, we investigate the role of lncRNA HOXD-AS1 on the osteosarcoma oncogenesis. Results revealed that HOXD-AS1 expression level was significantly up-regulated in osteosarcoma tissue and cells, moreover, the aberrant overexpression predicted the poor prognosis of osteosarcoma patients. Loss-of-functional experiments indicated that HOXD-AS1 silencing inhibited the osteosarcoma cells proliferation and induced G1/G0 phase arrest in vitro, and repressed tumor cell growth in vivo. Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. Rescue experiments revealed that p57 could recover the oncogenic role of HOXD-AS1 on osteosarcoma. In conclusion, our study confirmed that HOXD-AS1 could interact with EZH2, and then repress p57 expression, to aggravate osteosarcoma oncogenesis. which provide new idea for the osteosarcoma tumorigenesis.

Imaging-Assisted Diagnosis and Characteristics of Suspected Spinal Brucellosis: A Retrospective Study of 72 Cases.

BACKGROUND We clarified the imaging features of Brucella spondylitis to enhance our understanding of the disease and to minimize misdiagnosis. MATERIAL AND METHODS Imaging data (X-ray, computed tomography [CT], and magnetic resonance imaging [MRI] data) of 72 Brucella spondylitis patients treated from 2010 to 2017 were retrospectively analyzed; diagnoses was made by evaluating laboratory and pathological data. RESULTS X-ray films revealed changes in intervertebral space heights, the number of lateral osteophytes, and bone destruction, which were more severe in the following order: lumbosacral vertebrae (56 cases, 77.8%), cervical spine (6 cases, 8.3%), thoracic spine (5 cases, 6.9%), and multi-segmental mixed vertebrae (5 cases, 6.9%). CT revealed osteolytic destruction attributable to early-stage Brucella spondylitis (endplate and vertebral lamellar osteolysis), usually associated with multiple vertebral involvement, with the middle and late disease stages being characterized by osteophytes in the vertebral margins and bony bridges, endplate sclerosis, and vertebral osteosynthesis. We encountered 54 cases (75%) with endplate lamellar osteolysis, 37 (51.4%) with vertebral lamellar osteolysis, 59 (81.9%) with marginal osteophytes, 10 (13.9%) with bony bridges, 25 (34.7%) with vertebral laminar sclerosis, and 17 (23.6%) with vertebral osteosynthesis. MRI revealed early, low-intensity, differential T1WI vertebral and intervertebral signals, with occasional iso-signals, T2WI iso-signals or high-intensity signals; and T2WI-FS vertebral and intervertebral high-intensity signals, commonly from vertebral soft tissues and rarely from paravertebral abscesses. CONCLUSIONS A better understanding of the X-ray, CT, and MRI features of Brucella spondylitis could aid in diagnosis when combined with epidemiological and laboratory data, thus minimizing misdiagnosis.

Incidence and risk factors for infection in spine surgery: A prospective multicenter study of 1764 instrumented spinal procedures.

BACKGROUND: Surgical site infection (SSI) is a common complication in spinal surgery, imposing a high burden on patients and society. However, information about its characteristics and related risk factors is limited. We designed this prospective, multicenter study to address this issue. METHODS: From January 2015 through February 2016, a total of 1764 patients who had spinal trauma or degenerative spinal diseases were treated with instrumented surgeries and followed up for 1 year with complete data. Data on all patients were abstracted from electronic medical records, and SSIs were prospectively inspected and diagnosed by surgeons in our department. Any disagreement among them was settled by the leader of this study. SPSS 19.0 was used to perform the analyses. RESULTS: A total of 58 patients (3.3%, 58 of 1764) developed SSI; 1.1% had deep SSI, and 2.2% had superficial SSI. Of these, 60.6% (21 of 33) had a polymicrobial cause. Most of them (51 of 58) occurred during hospitalization. The median occurrence time was 3 days after operation (range: 1-123 days). SSI significantly prolonged hospital stays, by 9.3 days on average. The univariate analysis revealed reason for surgery as the only significant risk factor. The multivariate analysis, however, revealed 8 significant risk factors, including higher BMI, surgical site (cervical), surgical approach (posterior), surgery performed in summer, reasons for surgery (degenerative disease), autograft for fusion and fixation, and higher preoperative platelet level. CONCLUSION: Identification of these risk factors aids in stratifying preoperative risk to reduce SSI incidence. In addition, the results could be used in counseling patients and their families during the consent process.

A modified surgical procedure for congenital kyphoscoliosis: selective partial hemivertebrectomy via posterior-only approach.

OBJECTIVES: The study aims to assess the correction efficacy of selective partial hemivertebra excision via posterior-only approach for adolescent patients with congenital kyphoscoliosis. METHODS: A total of 17 cases (10 M/7 F) were enrolled to this study, all of whom were fully segmented hemivertebra. The mean grade of Risser sign was 1.82 ± 1.07. The average time of follow-up was 20.12 ± 6.88 months. Patients were all treated with selective partial hemivertebra excision and instrumentation via posterior-only approach. The maximal coronal Cobb angle, segmental curves, and segmental kyphotic curves are measured before and after operation, and at the latest follow-up. The data was analyzed to evaluate the correction efficacy. RESULTS: There were no postoperative infections and no neurological complications in all patients. The mean size of the segmental curve was 38.65 ± 5.35° before operation and 13.55 ± 1.82° after operation, with a mean correction of 25.10 ± 5.44°, which turned to 16.59 ± 2.14° at latest follow-up. The mean maximal coronal Cobb angle was 42.90 ± 7.96° before operation, 14.68 ± 2.44° after operation, and 17.50 ± 2.64° at the latest follow-up, giving a correction of 65.7%. The correction rate of segmental kyphotic curve was 72.6%, as the mean segmental kyphotic angle was 22.64 ± 6.74° before operation, 6.15 ± 2.50° after operation, and 6.9° at the latest follow-up, with a loss of 6.90 ± 2.68°. CONCLUSIONS: For the patients whose congenital kyphoscoliosis are due to hemivertebrae, selective partial hemivertebra excision and instrumentation via posterior-only approach is recommended to those ranging from 9 to 14 years old, with the Risser sign range grades 0-3 and Cobb angles <60°. This individualized treatment can balance the growth on the two sides of the spine and achieve satisfactory therapeutic effect through removing excrescent growth center.

Novel harmonic regularization approach for variable selection in Cox's proportional hazards model.

Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvex Lq (1/2 < q < 1) regularizations, to select key risk factors in the Cox's proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods.

A nutrient mixture reduces the expression of matrix metalloproteinases in an animal model of spinal cord injury by modulating matrix metalloproteinase-2 and matrix metalloproteinase-9 promoter activities.

This study aimed to determine whether a novel nutrient mixture (NM), composed of lysine, ascorbic acid, proline, green tea extracts and other micronutrients, attenuates impairments induced by spinal cord injury (SCI) and to investigate the related molecular mechanisms. A mouse model of SCI was established. Thirty-two mice were divided into four groups. The sham group received vehicle only. The SCI groups were treated orally with saline (saline group), a low dose (500 µg 3 times/day) of NM (NM-LD group) or a high dose (2,000 µg 3 times/day) of NM (NM-HD group). The levels of mouse hindlimb movement were determined every day in the first week post-surgery. The protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Wild-type and mutant MMP-2- and MMP-9-directed luciferase constructs were generated and their luciferase activities were determined. NM significantly facilitated the recovery of hindlimb movement of the mice in comparison to that in the saline group. The expression levels of MMP-2 in the NM-LD and NM-HD groups were decreased by ~50% compared with the saline group as indicated by western blotting results. The expression levels of MMP-9 in the NM-LD and NM-HD groups were decreased to ~25 and ~10%, respectively. These results suggest that NM significantly inhibits the expression of MMP-2 and MMP-9 proteins. Reverse transcription quantitative polymerase chain reaction results indicated that NM reduced the levels of MMP-2 and MMP-9 mRNA. Furthermore, the luciferase results indicated that site-directed mutagenesis comprising a -1306 C to T (C/T) base change in the MMP-2 promoter and a -1562 C/T base change in the MMP-9 promoter abolished the inhibitory effects of NM on MMP-2 and MMP-9 promoters. These results suggest that NM attenuates SCI-induced impairments in mice movement by negatively affecting the promoter activity of MMP-2 and MMP-9 genes and thus decreasing the expression of MMP-2 and MMP-9 proteins.

[Clinical application of short-segment pedicle screw in treating degenerative L4 spondylolisthesis-relation of preliminary rod bending degree to lumbar lordosis angle, slipping angle and slipping percentage].

OBJECTIVE: To investigate the short-segment pedicle screw in treating degenerative L4 spondylolisthesis and the relationship of the preliminarily bending degree of the titanium rod with the lumbar lordosis angle, the slipping angle and the slipping percentage and to evaluate the clinical coincidence and curative effects of the preliminarily-bent rod. METHODS: From September 2005 to March 2007, 31 female patients (age, 40-70 years; average, 58.3 years) were admitted for surgical treatment of their L4 degenerative spondylolisthesis (Meyerding I degree, II degree). Their lumbar lordosis angle (x1), slipping angle (x2), and slipping percentage (x3) were measured in the L(4,5) segment before operation. During the operation, the titanium rod bent beforehand according to the corresponding standards was inserted. The angle of the bent rod (Y) was measured, and then the multiple linear regression equation was established. The regression equation was applied to the surgical treatment of the 30 patients. RESULTS: According to the criteria in the JOA scoring system, the 31 patients had scores of 8.300 +/- 1.080 and 26.916 +/- 1.859 before operation and after operation, respectively. There was a significant difference between before operation and after operation (P < 0.05). The established multiple linear regression equation was as follows: Y = 0.1390 - 0.327 logx1 + 0.463x2 + 0.288x3(2). The operating time was 51.290 +/- 3.408 min in the 30 patients who underwent an insertion of the preliminarily-bent rod during the operation; however, the operating time was 102.360 +/- 5.004 min in the 31 patients who underwent an insertion of the bent rod that was made based on experience during the previous operations. There was a significant difference in the operating time between the two kinds of the rods (P < 0.05). Estimated according to 90%, 95% and 99% of the areas under the normal curve, the clinical coincidence rates in the preliminarily bending degrees of the titanium rod in the 30 patients were 80.00%, 90.00% and 96.67%, respectively. CONCLUSION: The titanium rod that has been bent into a certain angle before operation according to the established criteria can definitely diminish its strain during operation and efficiently shorten the operating time. This kind of the titanium rod has a good coincidence in clinical application and can be effectively used in clinical practice. It is worth reference during the clinical operation.

RESURRECTION OF THE GENUS ENDOLEPIS AND CLARIFICATION OF ATRIPLEX PHYLLOSTEGIA (CHENOPODIACEAE).

The genus Endolepis was first described by Torrey in 1860 with E. suckleyi (E. dioica [Nutt.] Standley) as the only species, noting that it differed from species of Atriplex by the presence of perianth parts in the female flowers. Later, Standley described two additional species: E. covillei and E. monilifera. H. M. Hall and Clements merged Endolepis with Atriplex because they thought that the presence of perianth parts in female flowers was variable in Atriplex phyllostegia. It is now clear that this observation was erroneous; A. phyllostegia never has perianth parts in its female flowers. The plants that they examined that had female flowers with perianth parts were specimens of Endolepis covillei; only those with female flowers devoid of perianth parts were specimens of Atriplex phyllostegia. These two taxa differ by several other major attributes including differences in leaf shape, leaf anatomy, fruiting-bract size and shape, fruiting-bract appendages, and flowering habit, and therefore justify taxonomic separation. Also, because the presence of perianth parts in bracteolate female flowers is a rare attribute in the tribe Atripliceae, consistently absent in Atriplex, but always present in Endolepis, the retention of the genus Endolepis, separate from Atriplex, is deemed warranted. We propose that the genus Endolepis comprise two species, E. dioica and E. covillei. The species named E. monilifera by Standley is based on a specimen of Atriplex serenana Nels.