[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

miR-497 inhibits tumor growth and migration of osteosarcoma by targeting plexinA4 and CDK6.

MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level which have been reported to be involved in the pathogenesis of various cancers. In the present study, we found that miR-497 was downregulated in osteosarcoma tissues. Gain and loss of function studies were carried out to investigate the effect of miR-497 on the growth of osteosarcoma cells. The results indicated that miR-497 inhibited the growth of osteosarcoma cells. Furthermore, bioinformatics analysis predicted plexinA4 and CDK6 as targets of miR-497, which was afterward confirmed by luciferase activity assay and rescue experiments. These findings suggested that miR-497, plexinA4 and CDK6 may serve as novel potential makers for osteosarcoma diagnostics and therapy.

Theoretical investigation on the optical and EPR spectra for Cu2+ -doped ZnO-CdS nanocomposites.

The three optical absorption bands and EPR parameters of the [CuO6 ]10- center in the ZnO-CdS composite nanopowders are theoretically studied from the perturbation formulas based on the cluster approach. In the formulas, the contributions to EPR parameters arising from the ligand orbital and spin-orbit coupling interactions via covalence effect are considered. For the studied [CuO6 ]10- cluster, the Cu-O bond lengths are suggested to show a relative elongation ratio ρ (≈ 4.1%) along the z-axis due to Jahn-Teller effect. The defect models suggested in this work are different from the previous assumption that the impurity Cu2+ can replace the host Zn2+ site when it enters the lattices of the ΖnO and ΖnS nanocrystals, forming the tetrahedral [CuΧ4 ]6- clusters (Χ = O, S). The validity of the proposed model is discussed. The differences between the present calculations and the previous ones for the interstitial Cu2+ center in ZnO nanocrystals are analyzed in view of the dissimilar impurity behaviors due to the new composition CdS and distinct preparation conditions.

The emerging role of lncRNAs in the regulation of osteosarcoma stem cells.

OBJECTIVE: Osteosarcoma is a common bone sarcoma that often occurs in childhood and adolescence. In recent years, the efficacy of osteosarcoma treatments has been improved by adjuvant chemotherapies and surgical approaches. However, poor prognosis often occurs among osteosarcoma patients due to recurrence, metastasis, or drug resistance problems. Cancer stem cells (CSCs), a specific type of tumor malignant cells with stem cell-like properties, have been reported to be responsible for tumor origination, aggression, metastasis, recurrence, and drug resistance. CSCs have been identified in osteosarcomas treatment, which exhibits self-renewal, multi-potency, and enhanced drug resistance. Therefore, in the present narrative review, we intend to summarize the role of lncRNAs in regulating CSCs and their effectiveness in the treatment of osteosarcoma. MATERIALS AND METHODS: The databases PubMed (Medline), Web of Science, Embase, Scopus, and Cochrane Library, were used for the presented study. The keywords we used to complete our search are 'lncRNA', 'Stem cell', and 'osteosarcoma'. A total of over 800 relevant articles, with a time limit from 2010 to 2021, were identified according to search strategy. Duplicate records and review articles were excluded by their titles and abstracts. Finally, we found about 80 articles matching our inclusion criteria, which included about 13 relevant studies focusing on both the mechanism and effectiveness of osteosarcomas treatment among osteosarcoma patients. RESULTS: CD133, CD117, ALDH, and Stro-1 are validated as the stem cell biomarkers in osteosarcoma CSCs. Accumulating evidence has revealed that lncRNAs, containing HIF2PUT, SOX2-OT, MALAT1, THOR, B4GALT1-AS1, H19, PVT1, FER1L4, LINK-A, DANCR, and DLX6-AS1, play a potential role in regulating CSCs in osteosarcoma. The drug resistance, inhibition of the relapse, and metastasis in osteosarcoma could be avoided via regulating lncRNAs of targeting CSCs. CONCLUSIONS: Multiple lncRNAs regulate CSCs in osteosarcoma via various molecular mechanisms. This review demonstrated that the method of eliminating CSCs by targeting these lncRNAs is a safe, effective, and a well-tolerated way for osteosarcoma patients, which shows a broad research prospect in tumor diagnoses and therapies. However, this method should be further demonstrated by better animal models and more clinical experiments.

The clinical efficacy of hydroxyapatite and its composites in spinal reconstruction: a meta-analysis.

OBJECTIVE: Synthetic hydroxyapatite (HA) and its related materials have made great progress in basic research and clinical application in spinal repair and reconstruction. However, the effect of HA and its composites used in spinal fusion still remained controversial. This meta-analysis aimed at evaluating the efficacy and safety of HA compared with autologous bone. MATERIALS AND METHODS: A systematic search in PubMed, MEDLINE, China National Knowledge Internet, EMBASE, and the Cochrane Library was conducted for relevant studies from inception until May 2021. Studies investigating the application of HA and its related composites in spinal fusion were selected for analysis. RESULTS: The operation time of patients treated with artificial bone containing HA was less than that of patients with autologous bone (p = 0.02). The amount of operative blood loss in patients in the HA group was less than that in the autograft group (p = 0.007). Patients treated with autologous bone got a more significant advantage in fusion rate at 6 months (p = 0.009). Nevertheless, there was no significant difference in the fusion rate between patients in the two groups at 12 months or no less than 24 months postoperatively (p = 0.24; p = 0.87). Compared to the autograft group, the HA group significantly decreased postoperative adverse events (p = 0.03). Furthermore, there was no significant difference in the Oswestry Disability Index (p = 1.00) nor the Visual Analogue Scale score (p = 0.94) between the two groups. CONCLUSIONS: This meta-analysis suggests that the clinical application of HA and its related composite materials in spinal reconstruction is comparable to that of autologous bone, with satisfactory efficacy and safety.

Differential gene expression and functional analysis of pit cells from regenerating rat liver.

Hepatic pit cells are a population of large granular lymphocytes that substantially contribute to hepatic immunity. Studies have proven that pit cells have a role in liver regeneration, but the details of the relationship between pit cells and liver regeneration is not clear at present. We subjected rats to a two-third hepatectomy; pit cells with high purity were obtained with Percoll density centrifugation and immunomagnetic bead methods, and the changes in mRNA levels in pit cells from the regenerating liver were monitored up to 168 h using a Rat Genome 230 2.0 Array composed of 25,020 distinct rat liver cDNA clones. Of the 25,020 genes analyzed, 612 known and 358 unknown genes were identified to be associated with liver regeneration. The 612 known genes are classified into up-regulation and down-regulation patterns based on the expression levels; they primarily participate in at least 23 biological activities based on gene ontology analysis. Together with gene function enrichment analysis, cytokines and a growth factor-mediated pathway in pit cells were activated at an early phase of liver regeneration; pit cell proliferation occurred from 24-72 h after liver hepatectomy; the machinery of pit cell differentiation commenced early and came into play late; an immune/inflammatory response was enhanced late. Expression pattern analysis of functionally classified genes in pit cells can give insights into the relationship between pit cells and liver regeneration.

A case-control study of microsomal epoxide hydrolase, smoking, meat consumption, glutathione S-transferase M3, and risk of colorectal adenomas.

We estimated associations between polymorphisms in the gene encoding microsomal epoxide hydrolase (mEH) among 464 cases diagnosed with first occurrence of colorectal adenoma and 510 matched controls. In an analysis controlling only for the matching variables, we found little or no association between adenoma and mEH genotypes defined by polymorphisms at either codon 113 and 139 or mEH activity predicted by both polymorphisms. However, in subsequent analyses, high predicted mEH activity was significantly associated with adenoma among certain subgroups defined by smoking history [odds ratio (OR), 4.27; 95% confidence interval (CI), 1.68-10.81 among current smokers; interaction, P = 0.11], meat consumption (OR, 2.47; CI, 0.99-6.19 among individuals who regularly eat well-done meat; interaction, P = 0.03), and genotypes for the *A/*B polymorphism in the gene encoding glutatione S-transferase M3 (OR, 2.60; CI, 1.28-5.28 among individuals with *A*A genotype; interaction, P = 0.03). These findings are consistent with causal roles for environmental polycyclic aromatic hydrocarbons and genetically encoded variants in enzymes whose actions lead to the production of activated polycyclic aromatic hydrocarbon metabolites.

Characterization of the human ABL promoter regions.

Gel retardation and DNAase 1 footprinting experiments have been performed to characterize the promoter sequences of exon 1a and 1b of the human ABL gene. Several Sp1 motifs and CCAAT boxes are found to be protected by nuclear proteins in the 1b promoter but none of the 7 reported Sp1 sites in 1a were found to bind protein. Multiple sets of initiation sites seem to exist in the 1b promoter region which may represent individual initiation sites, distributed over a DNA region of up to 700 bp. Starting with the most distal initiation site, 1a and 1b ABL promoter sequences show a high degree of homology, suggesting that one is derived from the other. However, multiple evolutionary changes in the 1a promoter sequence indicate that type 1a ABL expression may be differently regulated than 1b.

The interaction of quinone analogues with wild-type and ubiquinone-deficient yeast mitochondria.

The interaction of the exogenous quinones, duroquinone (DQ) and the decyl analogue of ubiquinone (DB) with the mitochondrial respiratory chain was studied in both wild-type and a ubiquinone-deficient mutant of yeast. DQ can be reduced directly by NADH dehydrogenase, but cannot be reduced by succinate dehydrogenase in the absence of endogenous ubiquinone. The succinate-driven reduction of DQ can be stimulated by DB in a reaction inhibited 50% by antimycin and 70-80% by the combined use of antimycin and myxothiazol, suggesting that electron transfer occurs via the cytochrome b-c1 complex. Both DQ and DB can effectively mediate the reduction of cytochrome b by the primary dehydrogenases through center o, but their ability to mediate the reduction of cytochrome b through center i is negligible. Two reaction sites for ubiquinol seem to be present at center o: one is independent of endogenous Q6 with a high reaction rate and a high Km; the other is affected by endogenous Q6 and has a low reaction rate and a low Km. By contrast, only one ubiquinol reaction site was observed at center i, where DB appears to compete with endogenous Q6. DB can oxidize most of the pre-reduced cytochrome b, while DQ can oxidize only 50%. On the basis of these data, the possible binding patterns of DB on different Q-reaction sites and the requirement for ubiquinone in the continuous oxidation of DQH are discussed.

Rapid redox equilibrium between the mitochondrial Q pool and cytochrome b during triphasic reduction of cytochrome b by succinate.

The reliability of monitoring the redox reactions of cytochrome b using the different wavelengths employed by different authors has been reexamined. It was found that 562-575 nm is suitable in succinate: cytochrome c reductase but not in mitochondria, in which case 562-540 nm is a better pair. Direct optical measurements of the redox reaction kinetics of the mitochondrial Q pool using a commercial dual-wavelength spectrophotometer are possible when succinate is used as the electron donor. Using the correct wavelength pair, and with malonate to slow down the electron input, the reduction course of cytochrome b was still triphasic but a plateau or a turn replaced the oxidation phase previously reported by several authors. At the same time, the reduction course of the Q pool was also triphasic, and in perfect match with that of cytochrome b. Destruction of the Rieske iron-sulfur cluster by British anti-Lewisite (BAL) + O2 treatment or prereduction of the high-potential components made the reduction of both Q and b monophasic. The plot of log (Q/QH2) against log (b3+/b2+) gave a straight line with an n value of 1.7 for cytochrome b at pH 7.4. This n value rose to 2.0 at pH 6.5 and dropped to 1.4 at pH 8.5. On the other hand, the mid-point potential of cytochrome b relative to that of the Q pool remained essentially unchanged between pH 6.5 and 8.4. BAL treatment had a small effect on the midpoint potential of cytochrome b relative to that of the Q pool and had no effect on the n value. Addition of quinone homologues and analogues extended the plateau phase in the reduction of cytochrome b, but exogenous quinones did not equilibrate rapidly with cytochrome b. It was concluded that the appearance of the plateau between the two reduction phases of Q and b is caused by the rapid delivery of electrons to the high-potential components of the respiratory chain as envisaged in the Q cycle; the unexpected n value for cytochrome b suggests a concerted reduction by QH2 of two species of cytochromes b-562.

On the role of ubiquinone in the respiratory chain.

(1) The V1 (substrate-Q oxidoreductase activity) and V2 (QH2 oxidase activity) for the oxidation of substrates by submitochondrial particles have been measured by using heptylhydroxyquinoline N-oxide (HQNO) as inhibitor of V2. (2) Partial destruction of the Rieske Fe-S cluster by treatment with Bal (2,3-dimercaptopropanol) + O2 has the same effect on the QH2 oxidase activity as partial saturation of the antimycin-binding site with HQNO. (3) The extent of the rapid reduction of cytochrome b in the presence of excess antimycin is proportional to the percentage of intact Rieske Fe-S cluster. (4) The measured rate of oxidation of endogenous ubiquinol (V2) by submitochondrial particles is dependent on the substrate used to reduce ubiquinone, especially at low levels of ubiquinone. (5) Pool-function kinetics in the oxidation of substrate, found both in the presence and absence of free ubiquinone, are due both to the pool of free ubiquinone and to direct collision between Q-loaded Q-reducing and -oxidizing enzymes. At infinite Q content only the former mechanism is operative; at low Q content only the latter. (6) Duroquinone can be reduced directly by NADH dehydrogenase without mediation of ubiquinone, but duroquinol cannot be oxidized in the absence of ubiquinone. On the other hand, the reduction of cytochrome b by duroquinol does not require the presence of ubiquinone. (7) It is suggested that the need for ubiquinone for the oxidation of duroquinol is due to the requirement of ubisemiquinone for the oxidation of cytochrome b, duroquinol not being able to form a stabilized semiquinone.

The effect of ring substituents on the mechanism of interaction of exogenous quinones with the mitochondrial respiratory chain.

In uncoupled pig-heart mitochondria the rate of the reduction of duroquinone by succinate in the presence of cyanide is inhibited by about 50% by antimycin. This inhibition approaches completion when myxothiazol is also added or British anti-Lewisite-treated (BAL-treated) mitochondria are used. If mitochondria are replaced by isolated succinate:cytochrome c oxidoreductase, the inhibition by antimycin alone is complete. The reduction of a plastoquinone homologue with an isoprenoid side chain (plastoquinone-2) is strongly inhibited by antimycin with either mitochondria or succinate:cytochrome c reductase. The reduction by succinate of plastoquinone analogues with an n-alkyl side chain in the presence of mitochondria is inhibited neither by antimycin nor by myxothiazol, but is sensitive to the combined use of these two inhibitors. On the other hand, the reduction of the ubiquinone homologues Q2, Q4, Q6 and Q10 and an analogue, 2,3-dimethoxyl-5-n-decyl-6-methyl-1,4-benzoquinone, is not sensitive to any inhibitor of QH2:cytochrome c reductase tested or their combined use, either in normal or BAL-treated mitochondria or in isolated succinate:cytochrome c reductase. It is concluded that quinones with a ubiquinone ring can be reduced directly by succinate:Q reductase, whereas those with a plastoquinone ring can not. Reduction of the latter compounds requires participation of either center i or center o (Mitchell, P. (1975) FEBS Lett. 56, 1-6) or both, of QH2:cytochrome c oxidoreductase. It is proposed that a saturated side chain promotes, while an isoprenoid side chain prevents reduction of these compounds at center o.

Kinetics of flash-induced electron transfer between bacterial reaction centres, mitochondrial ubiquinol:cytochrome c oxidoreductase and cytochrome c.

Ascorbate-reduced horse heart cytochrome c reduces photo-oxidized bacterial reaction centres with a second-order rate constant of (5-8) X 10(8) M-1 X s-1 at an ionic strength of 50 mM. In the absence of cytochrome c, the cytochrome c1 in the ubiquinol:cytochrome c oxidoreductase is oxidized relatively slowly (k = 3.3 X 10(5) M-1 X s-1). Ferrocytochrome c binds specifically to ascorbate-reduced reductase, with a Kd of 0.6 microM, and only the free cytochrome c molecules are involved in the rapid reduction of photo-oxidized reaction centres. The electron transfer between ferricytochrome c and ferrocytochrome c1 of the reductase is rapid, with a second-order rate constant of 2.1 X 10(8) M-1 X s-1 at an ionic strength of 50 mM. The rate of electron transfer from the Rieske iron-sulphur cluster to cytochrome c1 is even more rapid. The cytochrome b of the ubiquinol:cytochrome c oxidoreductase can be reduced by electrons from the reaction centres through two pathways: one is sensitive to antimycin and the other to myxothiazol. The amount of cytochrome b reduced in the absence of antimycin is dependent on the redox potential of the system, but in no case tested did it exceed 25% of the amount of photo-oxidized reaction centres.

Flash-induced electron transfer through mitochondrial QH2: cytochrome c oxidoreductase in the presence of bacterial reaction centres and cytochrome c. Analysis of subsequent processes and effect of inhibitors.

In a system containing reaction centres isolated from Rhodopseudomonas sphaeroides mutant R26, and variable amounts of horse-heart cytochrome c and bovine-heart mitochondrial QH2: cytochrome c oxidoreductase in a medium containing 2 mM ascorbate and 0.1 microM phenazine methosulphate, electron transfer was induced by a single flash. Three distinct phases of electron transfer can be distinguished: the first event is the oxidation of cytochrome c, and this is followed by an equilibration between cytochrome c, cytochrome c1 and the Rieske [2Fe-2S] cluster. The actual rates of these processes depend on the concentrations of cytochrome c and the reductase. The slower third phase is the oxidation of ubiquinol, which can follow two pathways: one sensitive to antimycin and one sensitive to myxothiazole. The antimycin-sensitive pathway (t1/2 approximately equal to 10 ms) is an equilibration between the Q/QH2 couple and cytochrome b, but may also include a direct reduction of cytochrome b by the QB of the reaction centres. The myxothiazole-sensitive pathway is a coupled reduction of cytochrome b and the Rieske [2Fe-2S] cluster which rapidly equilibrates with cytochromes c1 and c. Both pathways are sensitive to 7-(n-heptadecyl)mercapto-6-hydroxy-5,8-quinoline quinone, but with different affinities. In the absence of inhibitors the initial reduction of cytochrome b (via both pathways) is followed by a net oxidation which is the resultant of a continuing reduction (together with the reduction of the Rieske [2Fe-2S] cluster) and an oxidation (via the antimycin-sensitive site) by quinone. The results are discussed in the light of linear and cyclic models proposed to explain electron transfer between cytochromes b and c. It is concluded that only the Q-cycle model fits the present experimental data.

Identification of two different Q-binding sites in QH2-cytochrome c oxidoreductase, using the Q analogue n-heptadecylmercapto-6-hydroxy-5,8-quinolinequinone.

The pK and mid-point redox potential of the Q-analogue 7-(n-heptadecyl)mercapto-6-hydroxy-5,8-quinolinequinone (HMHQQ) in aqueous medium are so low that under the experimental conditions used for studying the inhibition of electron transfer in submitochondrial particles only the oxidized, anionic form is present. The KD of the analogue, determined by comparing its inhibitory effect with that of n-heptyl-4-hydroxyquinoline N-oxide, is (0.003 + 0.24 x mg protein/ml) microM. The inhibition of succinate oxidation is pH dependent, due to a pH-dependent change in the overcapacity of the QH2-oxidizing system above the Q-reducing system. If the terminal part of the respiratory chain is reduced with ascorbate, the analogue inhibits the reduction of cytochrome b by substrate in the presence of antimycin with a similar KD value. In the absence of ascorbate the KD value is 100-times higher. The reduction of cytochrome b by substrate in particles treated with 2,3-dimercaptopropanol (BAL) + O2 is also sensitive to HMHQQ, with a KD value in between the two values given above. It is concluded that the QH2 oxidase system contains two different sites for interaction with ubiquinone. The site responsible for the inhibition of steady-state electron transfer is near the Fe-S cluster, as is shown by the sensitivity to the redox state of this cluster and by the effect of HMHQQ on the EPR signal of the reduced cluster. The second site, which is similar to the antimycin-binding site, is occupied only at higher concentrations of inhibitor. The affinity of HMHQQ for this site is not affected by the redox state of the Fe-S cluster.

Identification of human monoamine oxidase (MAO) A and B gene promoters.

The promoter of human monoamine oxidase (MAO) A and B genes have been identified. The core promoter region of MAO A is comprised of two 90 bp repeats each of which contains two Sp1 elements and lacks a TATA box. The MAO B core promoter region contains two sets of overlapping Sp1 sites which flank a CACCC element all upstream of a TATA box. The different organization of the MAO A and B promoters may underlie their different cell and tissue specific expression.

Correlations between cadmium and mineral nutrients in absorption and accumulation in various genotypes of rice under cadmium stress.

The absorption and accumulation of Cd2+, Fe3+, Zn2+, Mn2+, Cu2+ and Mg2+ in the roots and leaves of 20 rice cultivars (Oryza sativa L.) with different genotypes under cadmium (Cd) stress were investigated with pot experiments. The results showed that there existed significant differences among the rice cultivars in the contents of six mineral elements in both roots and leaves at both heading and ripening periods. The statistical analysis showed that, for their contents in roots, significant and positive correlations between Cd2+ and Fe3+, Cd2+ and Zn2+, Cd2+ and Mn2+, Cd2+ and Cu2+ existed, but no significant correlation between Cd2+ and Mg2+, at the two periods. In the leaves, Cd also showed significant and positive correlations with Fe3+, Zn2+ and Cu2+ at the both periods, but a significant and negative correlation with Mn2+ and no significant correlation with Mg2+ at heading, a significant and positive correlation with Mg2+ and no significant correlation with Mn2+ at ripening. These results suggested that there were cooperative absorption between Cd2+ and Fe3+, Mn2+, Cu2+, Mn2+ in rice plants. Genotypic differences in Cd uptake and translocation among the rice cultivars suggested that paddy field of some rice cultivars may be irrigated with partially treated sewage water.

Development of a real-time adaptive current tomograph.

Following the successful development of a multiple-drive electrical impedance tomography system OXPACT-II featuring a voltage-driven current method for in vitro studies, research work currently being undertaken at the EIT research group in Oxford is aimed at developing a real-time multiple-drive adaptive system, called the Oxford Brookes Adaptive Current Tomograph Mark-III (OXBACT-III) which will operate at several frequencies in between 10-160 kHz. The objective of this system development is to enable EIT clinical studies to be undertaken based on the adaptive current method. One of the most important issues addressed in the new system design is to achieve high data acquisition speed while maintaining sufficient system accuracy. This paper will describe the overall data acquisition system structure and relevant system performance specifications.

A high output impedance current source.

A high output impedance current source was required for electrical impedance tomography (EIT) applications capable of operating up to 200 kHz. The architecture is based on operational-amplifier power-supply current sensing and produces a predominantly capacitive output impedance, which for the design presented is approximately 1.2 pF.