[Exploration and prospect of the whole course management model of osteoporosis].

Osteoporosis is a chronic progressive bone disease whose prevalence has increased significantly in China. Fragility fractures caused by osteoporosis pose a heavy burden on patients and their families. Therefore, early and efficient whole course management of osteoporosis is imperative. However, there are great challenges currently in the whole course management of osteoporosis, including lack of disease awareness, low rates of diagnosis and treatment, as well as poor patient compliance. As there is no consensus on the whole course management path to follow in clinical practice, this review analyzes the key points of whole course management of osteoporosis, such as the risk identification of fragility fracture, diagnosis and differential diagnosis, selection of initial treatment drugs, sequential or combined treatment and evaluation of treatment response etc. Based on the current management modes, including fracture liaison service, this review explores the whole course management path of osteoporosis which is suitable for China, including the whole course management ideas and implementation steps, establishing a platform to connect hospitals, communities, and families by application of information technology, developing an innovative system and mechanism indicates that the general practitioner will be responsible for clinical management and follow-up under instruction of clinical osteoporosis specialists, providing the community liaison service, organizing patient education activities such as bone health clubs, ultimately achieving a closed-loop communication among osteoporosis specialist, general practitioner, and patient, so that patients can benefit from it.

[Clinical analysis of preimplantation genetic diagnosis with HLA matching for beta-thalassemia].

OBJECTIVE: To investigate the efficacy and feasibility of preimplantation genetic diagnosis(PGD)with human leukocyte antigen(HLA)matching for beta-thalassemia. METHODS: A total of 43 referred beta-thalassemia couples, with at least on child in need of hematopoietic stem cell transplantation(HSCT), underwent PGD for HLA matching at the First Affiliated Hospital of Sun Yat-sen University from 2010 to 2015. PGD cycles of these couples were retrospectively analyzed, and 15 infants born from PGD-HLA were followed up. RESULTS: A total of 84 oocyte retrieval cycles were performed, providing 14±7 oocytes per cycle. Fifty nine embryos biopsied cycles were done, including 24 cleavage stage and 35 blastocyst stage biopsy cycles. In cleavage stage, 259 embryos were biopsied, 93.4%(242/259)of them with conclusive molecular diagnosis, and the percentage of unaffected embryos(normo-homozygote and heterozygote)was 71.4%(185/259). The percentage of HLA matched unaffected embryos was 9.3%(24/259). In blastocyst stage, 306 embryos were biopsied, while 93.8%(287/306)of them were conclusive, and the percentage of unaffected embryos was 70.6%(216/306). The percentage of HLA matched unaffected embryos in blastocyst stage biopsy was 14.4%(44/306), which was higher than in cleavage stage biopsy(P< 0.05). Forty three female carriers underwent 48 embryo transfer cycles including 3 fresh and 45 frozen-thawed embryo transfer cycles. Three fresh embryo transfer cycles were done after cleavage stage biopsy, resulted in a birth of healthy twins born at 36 weeks' gestation. All the embryos were frozen after blastocyst biopsied. Totally, 54 frozen-thawed embryos that were transferred in 45 frozen-thawed embryo transfer cycles included 25 embryo from cleavage stage biopsy and 29 embryo from blastocyst stage biopsy, and 42 of them were HLA matched. Clinical pregnancy rate and implantation rate per cycle in frozen-thawed embryo transfer were 38%(17/45)and 37%(20/54)respectively. A total of 15 infants were born, 2 were from a fresh embryo transfer cycle, and 13 were from frozen-thawed embryo transfer cycles. RESULTS of prenatal diagnosis from delivered cases were matched to that of PGD. Four sick children have been cured by HSCT from these HLA matched born siblings. CONCLUSION: PGD with HLA matching is an established method for conceiving a child who may donate hematopoietic stem cells to save an ill sibling.

Long PCR-RFLP of 16S-ITS-23S rRNA genes: a high-resolution molecular tool for bacterial genotyping.

AIMS: To perform a systematic evaluation of the applicability, validity and reliability of the long PCR-RFLP of 16S-ITS-23S rRNA genes for bacterial genotyping using both sequences retrieved from public genome databases and the experimental data obtained on bacterial cultures. METHODS AND RESULTS: 3301 Full-length sequences of 16S-ITS-23S rRNA genes were retrieved from 885 published bacterial genomes. Copy numbers of the whole set of 16S-ITS-23S rRNA genes per genome ranged from 1 (n = 161) to 14 (n = 4) with an average of 3.71. Their length varied greatly, from 4319 to 6568 bp with an average of 4952 bp. Computer-simulated RFLP analyses of the 16S-ITS-23S fragments flanked by the conserved primers 27F and 2241R suggested MspI, RsaI, HhaI and TaqI as the most appropriate enzymes for long PCR-RFLP analysis of the 16S-ITS-23S sequence. MspI was used to screen over 900 bacterial cultures isolated from the Huguangyan Maar Lake in southern China. An experimental sequencing of 16S rRNA genes of the isolates possessing a unique RFLP band pattern proved the broad applicability and high resolution of this approach. CONCLUSIONS: These results indicate that long PCR-RFLP of 16S-ITS-23S rRNA genes is a potentially universal and reliable bacterial genotyping tool with a high resolution. SIGNIFICANCE AND IMPACT OF THE STUDY: The methodology of long PCR-RFLP of 16S-ITS-23S rRNA genes will facilitate the exploration and tracing of cultivable microbial diversity in natural environments.

Design of Ni(OH)2/M-MMT Nanocomposite With Higher Charge Transport as a High Capacity Supercapacitor.

Nano-petal nickel hydroxide was prepared on multilayered modified montmorillonite (M-MMT) using one-step hydrothermal method for the first time. This nano-petal multilayered nanostructure dominated the ion diffusion path to be shorted and the higher charge transport ability, which caused the higher specific capacitance. The results showed that in the three-electrode system, the specific capacitance of the nanocomposite with 4% M-MMT reached 1068 F/g at 1 A/g and the capacity retention rate was 70.2% after 1,000 cycles at 10 A/g, which was much higher than that of pure Ni(OH)2 (824 F/g at 1 A/g), indicating that the Ni(OH)2/M-MMT nanocomposite would be a new type of environmentally friendly energy storage supercapacitor.

High Lithium Storage Performance of Co Ion-Doped Li4Ti5O12 Induced by Fast Charge Transport.

In this study, Co3O4-doped Li4Ti5O12 (LTO) composite was designed and synthesized by the hydrothermal reduction method and metal doping modification method. The microstructure and electrochemical performance of the Co3O4-doped Li4Ti5O12 composite were characterized by XRD, SEM, TEM, electrochemical impedance spectroscopy, and galvanostatic tests. The results showed that Li4Ti5O12 particles attached to lamellar Co3O4 constituted a heterostructure and Co ion doped into Li4Ti5O12 lattice. This Co ion-doped microstructure improved the charge transportability of Li4Ti5O12 and inhibited the gas evolution behavior of Li4Ti5O12, which enhanced the lithium storage performance. After 20 cycles, the discharge specific capacity reached stability, and the capacity retention maintained 99% after 1,000 cycles at 0.1 A/g (compared to the capacity at the 20th cycle). It had an excellent rate performance and long cycle stability, in which the capacity reached 174.6 mA h/g, 2.2 times higher than that of Li4Ti5O12 at 5 A/g.

Comparison of efficacy and safety of empagliflozin vs linagliptin added to premixed insulin in patients with uncontrolled type 2 diabetes: A randomized, open-label study.

AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase (DPP)-4 inhibitors added to insulin regimens in patients with type 2 diabetes mellitus (T2DM) can improve glycaemic control. This study compared the efficacy and safety of empagliflozin and linagliptin added to premixed insulin therapy in patients with poorly controlled T2DM. METHODS: In this 24-week, open-label, parallel-design randomized controlled trial, patients with poorly controlled T2DM despite a premixed insulin regimen were randomized to receive 5mg of linagliptin (n=53) or 25mg of empagliflozin (n=53) for 24 weeks. RESULTS: At week 24, changes in glycated haemoglobin (HbA1c) from baseline were -0.06±0.17% and -1.01±0.16% in the linagliptin and empagliflozin groups, respectively, and the mean treatment HbA1c difference was -0.88% (95% CI: -1.33, -0.43). At week 24, the empagliflozin group showed significant reductions, compared with the linagliptin group, in fasting plasma glucose (P<0.001), body weight (P<0.001), systolic blood pressure (P=0.003) and total daily insulin dose (P=0.042). Hypoglycaemia was reported to be slightly, and not significantly, higher in the empagliflozin group vs linagliptin group (30.2% vs 22.6%, respectively; P=0.51). Similar percentages of patients (1.9%) had urinary tract infections in the two groups. CONCLUSION: In Asian patients with inadequately controlled T2DM while taking premixed insulin, the addition of empagliflozin for 24 weeks provided better glycaemic control and greater reductions in body weight and systolic blood pressure than the addition of linagliptin. Clinical Trial Registration #: NCT03458715.

MiR-325-3p promotes locomotor function recovery in rats with spinal cord injury via inhibiting the expression of neutrophil elastase.

OBJECTIVE: This study aims to investigate the potential function of miR-325-3p in vascular integrity and inflammatory response following spinal cord injury (SCI). MATERIALS AND METHODS: The protein levels of ANG-1, ANG-2, and caspase-3 in HUVECs incubated with 0, 100, 200, 400, and 800 ng/ml NE for 24 h were determined. The regulatory effect of overexpressed miR-325-3p on the protein levels of ANG-1 and ANG-2 was determined by Western blot. The SCI model in SD rats was established by spinal injury at T10. Subsequently, the relative levels of miR-325-3p, ANG-1, and ANG-2 were determined in SCI rats and controls. Furthermore, SCI rats were administrated with miR-325-3p mimics or negative control and the relative levels of miR-325-3p, ANG-1, and ANG-2 were examined as well. At day 14, the protein levels of iNOS and GFAP in SCI rats and those overexpressing miR-325-3p were detected. BBB (Basso, Beattie, and Bresnahan) locomotor rating scale was applied for evaluating the locomotor function recovery at day 1, 3, 7, 14, 21, and 28 following SCI. RESULTS: NE treatment in HUVECs downregulated ANG-1 and upregulated ANG-2 and caspase-3 in a dose-dependent manner. The overexpression of miR-325-3p upregulated NE-induced decreased the level of ANG-1 and downregulated NE-induced increased level of ANG-2. After the establishment of the SCI model in rats, the miR-325-3p level gradually decreased in SCI rats relative to controls in a time-dependent manner. ANG-1 level in SCI rats decreased to the lowest on the first day following SCI, and gradually increased at day 3, 5, and 7. ANG-2 level was firstly upregulated and achieved the peak on day 3, and then decreased at day 5 and 7. Moreover, SCI rats overexpressing miR-325-3p showed a higher level of ANG-1 and lower level of ANG-2 than those of SCI rats. Overexpression of miR-325-3p downregulated the protein levels of iNOS and GFAP in SCI rats. BBB scale showed elevated locomotor function recovery in SCI rats overexpressing miR-325-3p compared with SCI rats. CONCLUSIONS: MiR-325-3p protects the integrity of the vascular wall, reduces infiltration of inflammation, and improves locomotor function recovery at post-SCI.

[Adsorptive voltammetric behavior of omeprazole and its application].

AIM: To study the electrochemical behavior of omeprazole (OPZ) and a new method for the determination of the compound was established by adsorptive stripping voltammetry. METHODS: Linear-sweep polarography and cyclic voltammetry were used. RESULTS: In a supporting electrolyte containing 0.1 mol.L-1 NH3-NH4Cl, a reduction peak of OPZ was observed by linear-sweep voltammetry at Hg electrode. The peak showed a potential of -1.04 V (vs Ag/AgCl at 100 mV.s-1) and adsorptive characteristics. The adsorbed species is most probably the neutral molecular of OPZ. The saturated adsorption of OPZ at Hg electrode is 9.55 x 10(-11) mol.cm-2 and every OPZ molecule occupies and area of 1.74 nm2. On the surface of the hanging mercury drop electrode, the adsorption of OPZ obeys Frumkin adsorption isotherm. The adsorption coefficient beta is 1.32 x 10(6), the Gibbs energy of adsorption delta G theta is -34.93 kJ.mol-1, the number of electrons transferred n is 4, the kinetics parameter alpha n alpha is 0.78, the rate constant of the surface electrode reaction ks is 0.18 s-1, the diffusion coefficient D of OPZ in solution is 1.03 x 10(-5) cm2.s-1. The detection limit of the adsorptive stripping voltammetry of OPZ is 2.0 x 10(-9) mol.L-1 under optimized condition. CONCLUSION: This indicates an irreversible process with adsorption.

Genetic diversity assessment of anoxygenic photosynthetic bacteria by distance-based grouping analysis of pufM sequences.

AIM: To assess how completely the diversity of anoxygenic phototrophic bacteria (APB) was sampled in natural environments. METHODS AND RESULTS: All nucleotide sequences of the APB marker gene pufM from cultures and environmental clones were retrieved from the GenBank database. A set of cutoff values (sequence distances 0.06, 0.15 and 0.48 for species, genus, and (sub)phylum levels, respectively) was established using a distance-based grouping program. Analysis of the environmental clones revealed that current efforts on APB isolation and sampling in natural environments are largely inadequate. Analysis of the average distance between each identified genus and an uncultured environmental pufM sequence indicated that the majority of cultured APB genera lack environmental representatives. CONCLUSIONS: The distance-based grouping method is fast and efficient for bulk functional gene sequences analysis. The results clearly show that we are at a relatively early stage in sampling the global richness of APB species. Periodical assessment will undoubtedly facilitate in-depth analysis of potential biogeographical distribution pattern of APB. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first attempt to assess the present understanding of APB diversity in natural environments. The method used is also useful for assessing the diversity of other functional genes.

Natural community structure of cyanobacteria in the South China Sea as revealed by rpoC1 gene sequence analysis.

AIMS: To examine the community structure of cyanobacterial populations of the South China Sea on the surface and at depth of 80 m. METHODS AND RESULTS: Direct PCR amplification of RNA polymerase (rpoC1) genes from environmental DNAs extracted from seawater, and cloning of the fragments and sequence analysis were used. A great diversity of Prochlorococcus and Synechococcus were detected at the investigation site. Genetically related Prochlorococcus were found in both layers while Synechococcus were found only on the surface. Prochlorococcus were clustered with the known high-light adapted II genotypes, and further divided into seven groups. Synechococcus could be divided into two groups, and the second group could be further subdivided into several clades. CONCLUSION: The dominant genotype of Prochlorococcus was high-light adapted II genotype, and Synechococcus were distributed basically on the surface. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report about the cyanobacterial community structure in the South China Sea, and an important supplement to the current understanding of the relationship between genetic and ecological diversity and environments.

Nested genetic algorithm for resolving overlapping spectra.

A nested genetic algorithm, including a genetic parameter level and a genetic implemented level, has been proposed and applied for resolving simulated overlapping spectra. Parameters of genetic algorithms (GA) were optimized by use of the genetic parameter level. The number of overlapping peaks was, moreover, detected simultaneously. Parameters of individual peaks in multiplets were computed by use of the genetic implemented level. It is obvious that the parameters of GA can be optimized and the number of overlapping peaks can be detected by itself. The optimization results are less affected than in traditional curve-fitting by the initial values of the parameters of the overlapping bands. Consequently, the nested genetic algorithm is superior to the curve-fitting technique for resolution of overlapping peaks.

Active products of porcine trypsin after autolysis.

Porcine trypsin obtained from pancreas residues subsequent to insulin removal undergoes autolysis when subjected to chromatography and gives rise to new forms of autolyzed products with intra-chain split at bonds Lys145-Ala146 and Arg105-Val106. Incubation of 1% solutions of porcine trypsin either at pH 5.0 or at pH 9.1 induces autolysis to give active products involving one or two specific cleavages of bonds Lys145-Ala146 and Arg105-Val106 or Lys131-Ser132, as well as inactive degraded products. No evidence has been obtained that on autolysis of porcine trypsin, and active fragment with molecular weight lower than that of the parent molecule was identified. The active forms of autolyzed products of porcine trypsin have almost the same specific activity as the intact enzyme when assayed against BAEE. They are of the same molecular weight as the parent molecule. These findings indicate that that active forms of autolyzed products maintain the specific three-dimensional structure essential for the catalytic activity of the trypsin molecule.