Quantum Mechanics-Based Fast and Reliable Prediction of Binding Pose Structures.

Predicting the binding poses of docking with an accurate estimation of binding energies is highly important but very challenging in computational drug design. A quantum mechanics (QM) calculation-based docking approach considering multiple conformations and orientations of the ligand is introduced here to tackle the problem. This QM docking consists of three steps: generating an ensemble of binding poses with a conventional docking simulation, computing the binding energies with self-consistent charge density functional theory tightly binding with dispersion correction (DFTB-D) to selecting the 10 top binding modes, and optimizing the selected binding mode structures using the ONIOM(DFTB:PM7) technique to determine the binding poses. The ONIOM(DFTB-D:PM6) docking approach is tested on 121 ligand-receptor biocomplexes with the crystal structures obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). The result shows that the new method is highly satisfactory for the accurate prediction of the binding poses. The new docking method should be beneficial to structure-based drug design.

Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration.

Background: Autophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA. Methods: GSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs. Results: A total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils. Conclusion: CDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.

Quantitative Polymerase Chain Reaction (qPCR)-Based Rapid Diagnosis of Helicobacter pylori Infection and Antibiotic Resistance.

Helicobacter pylori is a major human pathogen that infects approximately half of the global population and is becoming a serious health threat due to its increasing antibiotic resistance. It is the causative agent of chronic active gastritis, peptic ulcer disease, and gastric cancer and has been classified as a Group I Carcinogen by the International Agency for Research on Cancer. Therefore, the rapid and accurate diagnosis of H. pylori and the determination of its antibiotic resistance are important for the efficient eradication of this bacterial pathogen. Currently, H. pylori diagnosis methods mainly include the urea breath test (UBT), the antigen test, the serum antibody test, gastroscopy, the rapid urease test (RUT), and bacterial culture. Among them, the first three detection methods are noninvasive, meaning they are easy tests to conduct. However, bacteria cannot be retrieved through these techniques; thus, drug resistance testing cannot be performed. The last three are invasive examinations, but they are costly, require high skills, and have the potential to cause damage to patients. Therefore, a noninvasive, rapid, and simultaneous method for H. pylori detection and drug resistance testing is very important for efficiently eradicating H. pylori in clinical practice. This protocol aims to present a specific procedure involving the string test in combination with quantitative polymerase chain reaction (qPCR) for the rapid detection of H. pylori infection and antibiotic resistance. Unlike bacterial cultures, this method allows for easy, rapid, noninvasive diagnosis of H. pylori infection status and drug resistance. Specifically, we used qPCR to detect rea for H. pylori infection and mutations in the 23S rRNA and gyrA genes, which encode resistance against clarithromycin and levofloxacin, respectively. Compared to routinely used culturing techniques, this protocol provides a noninvasive, low-cost, and time-saving technique to detect H. pylori infection and determine its antibiotic resistance using qPCR.

Temporal transcriptome highlights the involvement of cytokine/JAK/STAT3 signaling pathway in the osteoinduction of BMSCs.

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy offers an effective strategy for bone regeneration to solve the clinical orthopedic problems. However, the transcriptional regulation of multiple transitional stages of continuous osteogenesis from MSCs has not been fully characterized. METHODS: Bone marrow mesenchymal stem cells (BMSCs) stimulated with osteogenic induction media were utilized to construct the in vitro osteogenic differentiation model. BMSCs were harvested after induction for 0, 7, 14 and 21 days, respectively, to perform the mRNA-sequencing (mRNA-Seq). The transcription factor networks and common molecules during the osteogenesis were revealed by using the temporal transcriptome. Further verification was performed by the quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence and Western blotting. RESULTS: It showed that BMSCs could differentiate into osteogenic, and crucial regulator in the MAPK signaling pathway, the PPAR signaling pathway, the Toll-like receptor signaling and the Cytokine/JAK/STAT signaling pathway. PPI protein interaction analysis also suggested that three cytokines are involved in osteogenic differentiation as core genes, including leukemia inhibitory factor (LIF), interleukin-6 (IL6) and colony-stimulating factor 3 (CSF3). The osteogenic process was negatively affected by the inhibition of JAK/STAT3 signaling pathway. CONCLUSIONS: This work might provide new insights in the crucial features of the transcriptional regulation during the osteogenesis, as well as offer important clues about the activity and regulation of the relatively long-activated Cytokine/JAK/STAT3 signaling pathway in osteoinduction of BMSCs.

Prediction and Identification of GPCRs Targeting for Drug Repurposing in Osteosarcoma.

Background: Osteosarcoma (OS) is a malignant bone tumor common in children and adolescents. The 5-year survival rate is only 67-69% and there is an urgent need to explore novel drugs effective for the OS. G protein-coupled receptors (GPCRs) are the common drug targets and have been found to be associated with the OS, but have been seldom used in OS. Methods: The GPCRs were obtained from GPCRdb, and the GPCRs expression profile of the OS was downloaded from the UCSC Xena platform including clinical data. 10-GPCRs model signatures related to OS risk were identified by risk model analysis with R software. The predictive ability and pathological association of the signatures in OS were explored by bio-informatics analysis. The therapeutic effect of the target was investigated, followed by the investigation of the targeting drug by the colony formation experiment were. Results: We screened out 10 representative GPCRs from 50 GPCRs related to OS risk and established a 10-GPCRs prognostic model (with CCR4, HCRTR2, DRD2, HTR1A, GPR158, and GPR3 as protective factors, and HTR1E, OPN3, GRM4, and GPR144 as risk factors). We found that the low-risk group of the model was significantly associated with the higher survival probability, with the area under the curve (AUC) of the ROC greater than 0.9, conforming with the model. Moreover, both risk-score and metastasis were the independent risk factor of the OS, and the risk score was positively associated with the metastatic. Importantly, the CD8 T-cells were more aggregated in the low-risk group, in line with the predict survival rate of the model. Finally, we found that DRD2 was a novel target with approved drugs (cabergoline and bromocriptine), and preliminarily proved the therapeutic effects of the drugs on OS. These novel findings might facilitate the development of OS drugs. Conclusion: This study offers a satisfactory 10-GPCRs model signature to predict the OS prognostic, and based on the model signature, candidate targets with approved drugs were provided.

A novel nomogram for individualized preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma / 中华外科杂志

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.

Sestrin2 is involved in the Nrf2-regulated antioxidative signaling pathway in luteolin-induced prevention of the diabetic rat heart from ischemia/reperfusion injury.

Luteolin attenuates myocardial ischemia/reperfusion (I/R) injury in diabetes through activating the nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidative response. Though sestrin2, a highly conserved stress-inducible protein, is regarded as a modulator of Nrf2 and reduces I/R injury, the effect of sestrin2 on luteolin-induced prevention of the diabetic heart from I/R injury remains unclear. We hypothesized that luteolin could relieve myocardial I/R injury in diabetes by activating the sestrin2-modulated Nrf2 antioxidative response. Diabetes was induced in rats using a single dose of streptozotocin (65 mg kg-1, i.p.) for 6 weeks, and then luteolin (100 mg kg-1 d-1, i.g.), Nrf2 inhibitor brusatol, or sestrin2 blocker leucine was administered for 2 consecutive weeks. After that, the hearts were isolated and exposed to global I/R (30 min/120 min). Luteolin markedly improved cardiac function, myocardial viability and expressions of Nrf2-regulated antioxidative genes, and reduced lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R hearts. Ca2+-induced mitochondrial permeability transition and membrane potential disruption were markedly inhibited in luteolin-treated diabetic ventricular myocytes. All these effects of luteolin were significantly reversed by Nrf2 inhibitor brusatol or sestrin2 inhibitor leucine. Luteolin-induced diminished Keap1 and augmented nuclear translocation and ARE binding activity of Nrf2 were hampered by leucine in the diabetic I/R heart. In addition, luteolin-induced augmented transcription of sestrin2 was markedly blocked by brusatol in the diabetic I/R heart. These data suggest that sestrin2 and Nrf2 positively interact to promote antioxidative actions and attenuate mitochondrial damage, by which luteolin relieves diabetic myocardial I/R injury.

Genetic Algorithm Embedded with a Search Space Dimension Reduction Scheme for Efficient Peptide Structure Predictions.

The computational determination of peptide conformations is a challenging task of finding minima in a high dimensional space. By combining the sampling efficiency of the genetic algorithm (GA) and the dimensionality reduction resulted from the backbone dihedral angle correlations, named as the path matrix (PM) method, a new searching algorithm, parallel microgenetic algorithm (PMGA), is proposed. Meanwhile, PMGA employs the density functional theory based energy as the fitness function and performs local geometry optimizations to enhance the reliability of its GA encoding strategy. Tests on peptides with up to eight amino-acid residues show PMGA is quite efficient for providing high-quality conformational coverages. The computational cost of the PMGA search increases slowly with the number of amino-acid residues in a peptide, with no sign of deterioration on the searching results for the increased length of the peptide. The PMGA method should therefore be useful for determining the conformations of oligopeptide, studying the protein-ligand interactions, and designing the peptide-based drugs.

Effects of 17ß-Estradiol on growth-related genes expression in female and male spotted scat (Scatophagus argus).

Growth hormone (GH) is the most important endocrine factor to regulate somatic growth. Spotted scat (Scatophagus argus) is a famous marine aquaculture species in China with a typical sexual growth dimorphism in which females grow faster and larger than males. In this study, gh messenger RNA (gh mRNA) and GH protein expression were examined in the pituitary glands of female and male spotted scat. Based on qPCR analysis, gh mRNA was mainly expressed in the pituitary gland, and weakly in the gonads and hypothalamus. Furthermore, gh mRNA expression in the pituitary gland was significantly higher in females at stages II-IV than in males at stages III-V. In addition, gh mRNA was highly expressed in the ovary and testis during mature development stages. In this study, spotted scat GH polyclonal antibody was produced. Western blot analysis showed that the molecular weight of spotted scat GH was about 21 KDa. Immunohistochemistry (IHC) in pituitary glands showed that GH was mainly expressed in the proximal pars distal (PPD) and a few cells were distributed in the rostral pairs distal (RPD). After injecting 17ß-Estradiol (E2) in vivo, gh mRNA expression was significantly up-regulated in the pituitary gland, whereas igf1 and ghr1 mRNA levels were down-regulated in the liver, which might regulate gh mRNA expression in the pituitary gland. These results provide valuable insight into the molecular mechanisms of E2 regulating gh expression in spotted scat.

Thioredoxin-Interacting Protein (TXNIP) Regulates Parkin/PINK1-mediated Mitophagy in Dopaminergic Neurons Under High-glucose Conditions: Implications for Molecular Links Between Parkinson's Disease and Diabetes.

Patients with diabetes mellitus have a higher risk of developing Parkinson's disease (PD). However, the molecular links between PD and diabetes remain unclear. In this study, we investigated the roles of thioredoxin-interacting protein (TXNIP) in Parkin/PINK1-mediated mitophagy in dopaminergic (DA) cells under high-glucose (HG) conditions. In streptozotocin-induced diabetic mice, TXNIP was upregulated and autophagy was inhibited in the midbrain, while the loss of DA neurons was accelerated by hyperglycemia. In cultured PC12 cells under HG, TXNIP expression was upregulated and the intracellular reactive oxygen species (ROS) levels increased, leading to cell death. Autophagic flux was further blocked and PINK1 expression was decreased under HG conditions. Parkin expression in the mitochondrial fraction and carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced co-localization of COX IV (marker for mitochondria) and LAMP1 (marker for lysosomes) were also significantly decreased by HG. Overexpression of TXNIP was sufficient to decrease the expression of both PINK1 and Parkin in PC12 cells, while knockdown of the expression of TXNIP by siRNA decreased intracellular ROS and attenuated cellular injury under HG. Moreover, inhibition of TXNIP improved the CCCP-induced co-localization of COX IV and LAMP1 in PC12 cells under HG. Together, these results suggest that TXNIP regulates Parkin/PINK1-mediated mitophagy under HG conditions, and targeting TXNIP may be a promising therapeutic strategy for reducing the risk of PD under hyperglycemic conditions.

Bile salt hydrolase activity is present in nonintestinal lactic acid bacteria at an intermediate level.

It is generally considered that bile salt hydrolase (BSH) activity is hardly detected in nonintestinal lactic acid bacteria (LAB). The aim of this study was to investigate the distribution and intensity of BSH activity in LAB isolated from naturally fermented vegetables and milk. A total of 624 lactic acid bacterial strains classified into 6 genera and 50 species were isolated from 144 naturally fermented vegetable samples and 103 naturally fermented milk samples, and their BSH activity was screened by gas chromatography with electron capture detection. The BSH-positive strains were further analyzed quantitatively for their deconjugation ability against six human-conjugated bile salts by HPLC based on the disappearance of the conjugated bile salts from the reaction mixture. The results showed that 39% of the strains possessed BSH activity distributed in 24 lactic acid bacterial species. The strains of the fermented vegetable origin showed a 0.5-fold higher incidence of BSH-positive strains than those of the fermented milk origin, and the lactic acid bacilli exhibited 2.5-fold higher incidence of BSH-positive strains than the lactic acid cocci in general. The strains of the fermented vegetable origin generally had greater bile salt deconjugation ability than those of the fermented milk origin. More than 97% and 93% of the BSH-positive strains exhibited a greater substrate preference for glycoconjugated bile salts than tauroconjugated bile salts and for dihydroxy bile salts than trihydroxy bile salts, respectively. This study demonstrated that BSH activity was also present in nonintestinal LAB.

Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector.

BACKGROUND: After injury, mesenchymal progenitors in the kidney interstitium differentiate into myofibroblasts, cells that have a critical role in kidney fibrogenesis. The ability to deliver genetic material to myofibroblast progenitors could allow new therapeutic approaches to treat kidney fibrosis. Preclinical and clinical studies show that adeno-associated viruses (AAVs) efficiently and safely transduce various tissue targets in vivo; however, protocols for transduction of kidney mesenchymal cells have not been established. METHODS: We evaluated the transduction profiles of various pseudotyped AAV vectors expressing either GFP or Cre recombinase reporters in mouse kidney and human kidney organoids. RESULTS: Of the six AAVs tested, a synthetic AAV called Anc80 showed specific and high-efficiency transduction of kidney stroma and mesangial cells. We characterized the cell specificity, dose dependence, and expression kinetics and showed the efficacy of this approach by knocking out Gli2 from kidney mesenchymal cells by injection of Anc80-Cre virus into either homozygous or heterozygous Gli2-floxed mice. After unilateral ureteral obstruction, the homozygous Gli2-floxed mice had less fibrosis than the Gli2 heterozygotes had. We observed the same antifibrotic effect in ß-catenin-floxed mice injected with Anc80-Cre virus before obstructive injury, strongly supporting a central role for canonical Wnt signaling in kidney myofibroblast activation. Finally, we showed that the Anc80 synthetic virus can transduce the mesenchymal lineage in human kidney organoids. CONCLUSIONS: These studies establish a novel method for inducible knockout of floxed genes in mouse mesangium, pericytes, and perivascular fibroblasts and are the foundation for future gene therapy approaches to treat kidney fibrosis.

Absorption and subcellular distribution of cadmium in tea plant (Camellia sinensis cv. "Shuchazao").

A hydroponic experiment was performed to investigate the Cd absorption and subcellular distribution in tea plant, Camellia sinensis. Increased Cd accumulation potential was observed in the tea plant in a Cd-enriched environment, but most of the Cd was absorbed by the roots of C. sinensis. The Cd in all the root fractions was mostly distributed in the soluble fraction, followed by the cell wall fraction. By contrast, the Cd was least distributed in the organelle fraction. The adsorption of Cd onto the C. sinensis roots was described well by the Langmuir isotherm model than the Freundlich isotherm. Most of the Cd (38.6 to 59.4%) was integrated with pectates and proteins in the roots and leaves. Fourier transform infrared spectroscopy (FTIR) analysis showed that small molecular organic substances, such as amino acids, organic acids, and carbohydrates with N-H, C=O, C-N, and O-H functional groups in the roots, bonded with Cd(II). The Cd accumulation in the C. sinensis leaves occurred in the cell wall and organelle fractions. C. sinensis has great capability to transport Cd, thereby indicating pollution risk. The metal homeostasis of Fe, Mn, Ca, and Mg in C. sinensis was affected when the Cd concentration was 1.0-15.0 mg/L.

A clinical and mechanistic study of topical bingpian-induced analgesia / 中国药理学与毒理学杂志

OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of (+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millen-nia. However, the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topi-cal bingpian in humans, and elucidated the underling mechanisms in animal models of pain. METH-ODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital. Capsaicin, formalin, CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging, patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells. RESULTS (1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized, double-blind, placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice. (3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia. (4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.

Structural Information-Based Method for the Efficient and Reliable Prediction of Oligopeptide Conformations.

Predictions of structures of biomolecules are challenging due to the high dimensionalities of the potential energy surfaces (PESs) involved. Reducing the necessary PES dimensionality is helpful for improving the computational efficiency of all relevant structure prediction methods. For that purpose, a systematic analysis of the backbone dihedral angles (DAs) in the low energy conformations of amino acids, di-, tri-, and tetrapeptides is performed. The analysis reveals that the DAs can be represented by a set of discretized values. Moreover, there are rules limiting the combinations of neighboring DA states. The DA combination rules are used to formulate a path matrix scheme for locating the low energy conformations of peptides. Comparing with the full DA combinations, the PES dimensionality in the path matrix method is reduced by a factor of 2.5n, where n is the number of amino acid residues in a peptide. The path matrix method is validated by applications to find the conformations of representative tri-, tetra-, and pentapeptides and comparison with the best literature results. All the tests show that the path matrix method is very efficient and highly reliable by producing the best search results for the low energy peptide conformations.

Curative effect and safety of L-carnitine combined with alprostadil for patients with diabetic nephropathy / 药物评价研究

Objective To explore the curative effect and safety of L-carnitine combined with alprostadil for patients with diabetic nephropathy.Methods 102 patients with diabetic nephropathy were enrolled in hospital of Inner Mongolia normal university from August 2013 to December 2016,of which patients divided into two groups randomly,control group (n =50) accepted alprostadil treatment,and combined group (n =52) adopted L-camitine based on the patients in control group.The blood glucose and renal functions were detected respectively after treatment.And the curative effect was evaluated and compared between two groups;The adverse reactions were recorded and analyzed in the period of treatment.Results After treatment,the FBP,2 h BG,24 h uPro,BUN,Scr and β2-MG of patients in two groups were decreased significantly (P ＜ 0.05),and the change of combined group was higher than those control group significantly (P ＜ 0.05).After treatment,the total efficiency of combined group was higher than that patients in control group (P ＜ 0.05).The incidence of adverse reactions of control group in the period of treatment was 20.0％ (10/50),and combined group was 5.8％ (3/52),and which difference from two groups was no significance.Conclusions L-carnitine combined with alprostadil for patients with diabetic nephropathy deserved popularization in clinic,and which not only possessed remarkable curative effect,but also well controlled the blood glucose level,improved the renal function,decreased the incidence of adverse reactions certainly.

Proposal and Validation of a Basic Progression Scoring System for Patients with Skull Base Chordoma.

OBJECTIVE: To propose and further validate a basic progression scoring system for patients with skull base chordoma. METHODS: All patients (n = 170) undergoing operation for skull base chordoma were classified randomly into a training (n = 113) or validation set (n = 57). In the training set, adverse factors for progression were analyzed by univariate and multivariate analyses. Significant independent factors were included into the scoring system. Scores for each risk category were allocated 1 point and each protection category 0 point. Three prognostic groups were formed on the basis of total score. The same scoring and grouping dispositions were made in the validation set. Analyses of the differences among the 3 groups in individual sets with regard to recurrence and the comparisons between the corresponding prognostic groups of both sets were all carried out by the Kaplan-Meier method. RESULTS: In the training set, age, treatment history, preoperative Karnofsky performance scale, pathology, and features on magnetic resonance imaging were all significant independent factors and were included into the scoring system. According to the total score, 3 prognostic groups were formed, group A (0-1 points), group B (2-3 points), and group C (3-4 points), respectively. The pairwise comparisons between every 2 of 3 groups in the training set showed significance with P < 0.001, whereas in validation set, a log-rank test showed significance, P ≤ 0.001 (log-rank test). The comparisons between the corresponding prognostic groups of both sets did not show significance. CONCLUSIONS: The basic progression scoring system for patients with skull base chordoma is valid and reproducible.

A genetic algorithm encoded with the structural information of amino acids and dipeptides for efficient conformational searches of oligopeptides.

The genetic algorithm (GA) is an intelligent approach for finding minima in a highly dimensional parametric space. However, the success of GA searches for low energy conformations of biomolecules is rather limited so far. Herein an improved GA scheme is proposed for the conformational search of oligopeptides. A systematic analysis of the backbone dihedral angles of conformations of amino acids (AAs) and dipeptides is performed. The structural information is used to design a new encoding scheme to improve the efficiency of GA search. Local geometry optimizations based on the energy calculations by the density functional theory are employed to safeguard the quality and reliability of the GA structures. The GA scheme is applied to the conformational searches of Lys, Arg, Met-Gly, Lys-Gly, and Phe-Gly-Gly representative of AAs, dipeptides, and tripeptides with complicated side chains. Comparison with the best literature results shows that the new GA method is both highly efficient and reliable by providing the most complete set of the low energy conformations. Moreover, the computational cost of the GA method increases only moderately with the complexity of the molecule. The GA scheme is valuable for the study of the conformations and properties of oligopeptides. © 2016 Wiley Periodicals, Inc.

Frontolateral Approach Applied to Sellar Region Lesions: A Retrospective Study in 79 Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Various surgical approaches for the removal of sellar region lesions have previously been described. This study aimed to evaluate the reliability and safety of the frontolateral approach (FLA) to remove sellar region lesions.</p><p><b>METHODS</b>We presented a retrospective study of 79 patients with sellar region lesions who were admitted and operated by the FLA approach from August 2011 to August 2015 in Department of Neurosurgery of Beijing Tian Tan Hospital. We classified FLA into three types, compared the FLA types to the areas of lesion invasion, and analyzed operation bleeding volume, gross total resection (GTR) rate, visual outcome, and mortality.</p><p><b>RESULTS</b>Seventy-nine patients were followed up from 2.9 to 50.3 months with a mean follow-up of 20.5 months. There were 42 cases of meningiomas, 25 cases of craniopharyngiomas, and 12 cases of pituitary adenomas. The mean follow-up Karnofsky Performance Scale was 90.4. GTR was achieved in 75 patients (94.9%). Two patients (2.5%) had tumor recurrence. No patients died perioperatively or during short-term follow-up. Three patients (3.8%) with craniopharyngioma died 10, 12, and 23 months, respectively, after surgery. The operative bleeding volume of this study was no more than that of the other approaches in the sellar region (P = 0.783). In this study, 35 patients (44.3%) had visual improvement after surgery, 38 patients (48.1%) remained unchanged, and three patients' visual outcome (3.8%) worsened.</p><p><b>CONCLUSIONS</b>FLA was an effective approach in the treatment of sellar region lesions with good preservation of visual function. FLA classification enabled tailored craniotomies for each patient according to the anatomic site of tumor invasion. This study found that FLA had similar outcomes to other surgical approaches of sellar region lesions.</p>

[Chromosomal Aberrations in Myelodysplastic Syndromes].

Myelodysplastic syndromes (MDS) are a group of clonal hematopioetic disorders characterized by myelodysplasia, decreased peripheral blood cells and high-risk of transformation into acute leukemia. MDS are often accompanied by a variety of chromosomal aberrations which play a role in disease pathogenesis, and are crucial in diagnosis and prognostic evaluation of this disease. About half of the patients with MDS have chromosomal abnormalities, mainly unbalanced chromosomal aberration. Different chromosomal aberration types are associated with different clinical outcome of this disease. Though balanced chromosomal translocations are not common in MDS, it seems that the patients with them have a higher leukemia transformation rate than those with other type of chromosomal aberrations. In this review, the chromosomal aberrations in MDS and their clinical significance for diagnosis and prognosis are briefly summarized.