Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis.

BACKGROUND: We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data. METHODS: A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using "DESeq2" package in R language. Functional enrichment analysis was conducted using the "clusterProfiler" package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape. RESULTS: We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP. CONCLUSION: DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.

Temporal trends in mortality of tuberculosis attributable to high fasting plasma glucose in China from 1990 to 2019: a joinpoint regression and age-period-cohort analysis.

Background: Nowadays, high fasting plasma glucose (HFPG) has been identified as the important risk factor contributing to the increased burden of diseases. But there remains a lack of research on tuberculosis (TB) mortality specifically attributable to HFPG. Thus, this study aims to explore the long-term trends in HFPG-related TB mortality in China from 1990 to 2019. Methods: Data on HFPG-related TB mortality were obtained from the Global Burden of Disease (GBD) Study 2019. Analyzing the data using joinpoint regression and age-period-cohort methods adjusting for age, period, and cohort allowed us to assess the trends in TB mortality due to HFPG. Results: The age-standardized mortality rates (ASMRs) of TB attributable to HFPG exhibited a downward trend in China from 1990 to 2019, with an average annual percentage change (AAPC) of -7.0 (95% CI, -7.5 to -6.6). Similar trends were found for male (AAPC of -6.5 [95% CI, -7.0 to -6.0]) and female (AAPC of -8.2 [95% CI, -8.5 to -7.9]), respectively. Local drifts curve with a U-shaped pattern reflected the AAPC of TB mortality due to HFPG across age groups. The greatest decline was observed in the age group of 60-64 years. The mortality rates related to HFPG first increased and then decreased with increasing age, peaking in the 55-59 age group. Our analysis of the period and cohort effects found that the rate ratios of TB mortality due to HFPG have decreased over the past three decades, more prominently in women. It is noteworthy that while both genders have seen a decline in HFPG-attributable TB mortality and risk, men have a higher risk and slightly less significant decline than women. Conclusion: The present study shows that HFPG-related ASMRs and risk of TB in China decreased over the last 30 years, with similar trends observed in both men and women. In order to attain the recommended level set by the WHO, the effective strategies for glycemic control and management still needed to be implemented strictly to further decrease the burden of TB.

Seasonal Variation and Global Public Interest in the Internet Searches for Osteoporosis.

BACKGROUND: To ascertain the seasonal pattern and global public interest in osteoporosis by evaluating search term popularity changes of the disease over a decade. METHODS: We applied Google Trends to retrieve search popularity scores for the term "osteoporosis" between January 01, 2004, and December 31, 2019. Cosinor analyses were conducted to examine the seasonality of osteoporosis, and analysis on osteoporosis-related topics including hot topics and rising-related topics was also performed. RESULTS: The cosinor analyses demonstrated a statistically significant seasonal variation in relative search volume of the "osteoporosis" in the world (p = 0.0083), USA (p < 0.001), UK (p < 0.001), Canada (p < 0.001), Ireland (p < 0.001), Australia (p < 0.001), and New Zealand (p < 0.001), with a peak in the late winter months and trough in the summer months. The peaks in late winter and valley in summer presented an approximately 6-month difference between hemispheres. The top 11 rising topics were denosumab, FRAX, hypocalcaemia, zoledronic acid, ibandronic acid, osteomyelitis, osteopenia, osteoarthritis, bone, calcium, and bone density. CONCLUSIONS: Google search query volumes related to osteoporosis follow strong seasonal patterns with late winter peaks and summer troughs. Further studies aimed at elucidating the possible mechanisms behind seasonality in osteoporosis are needed. Moreover, Internet data including the top rising topics may alert physicians to strengthen the propaganda of osteoporosis timely, so as to further promote the development of public health interventions.

Differential proteomic analysis of tibial subchondral bone from male and female guinea pigs with spontaneous osteoarthritis.

A proteomic study on the tibial subchondral bone in guinea pigs with spontaneous osteoarthritis was performed to investigate the molecular alterations that occur in early osteoarthritis. A total of 132 healthy Hartley guinea pigs (aged 1 month; 66 female and 66 male) were randomly divided into 11 groups of six. Changes in articular cartilage and tibial subchondral bone were assessed using macroscopic examinations and micro-computed tomography. iTRAQ-integrated liquid chromatography-tandem mass spectrometry was used to identify differentially altered proteins in the tibial subchondral bone between 1- and 3-month-old guinea pigs, which were then validated using western blotting. A gradual progression of cartilage degeneration was observed in the knee joints of the subject animals from 5-11 months. With aging, the tibial subchondral trabecular bone acquired more plate-like and less anisotropic properties, with increased bone mineral density, bone volume, trabecular thickness and numbers. The proteomic study identified 138 and 113 proteins significantly differentially expressed between 3- and 1-month old guinea pigs in both the male and female animals, respectively. Western blotting confirmed the increased expression of osteoblast-associated protein S100 calcium-binding protein A8 (S100A8) and the deregulated expression of osteoclast-associated proteins coronin 1A (CORO1A) and T-cell immune regulator 1 (TCIRG1) in the 3-month old guinea pigs in comparison to the 1-month old guinea pigs. Spontaneous cartilage degeneration in the knee joints of male Hartley guinea pigs tended to be more serious compared with the females during the development of osteoarthritis. Together, the results suggest that osteoblast-associated protein S100A8 and osteoclast-associated proteins CORO1A and TCIRG1 are potentially key regulators of early osteoarthritic development in tibial subchondral bone.

Sublingual immunotherapy of atopic dermatitis in mite-sensitized patients: a multi-centre, randomized, double-blind, placebo-controlled study.

Allergen-specific immunotherapy is widely used for allergic rhinitis and asthma treatment worldwide. This study explored the efficacy and safety of sublingual immunotherapy (SLIT) with the extracts of Dermatophagoides Farinae (D. farinae Drops) on house dust mites (HDM)-induced atopic dermatitis (AD). 239 patients with HDM-induced AD were recruited and exposure to a multi-centre, randomized, double-blind, and placebo-controlled clinical trials for 36 weeks, which were randomly divided into placebo and sublingual D. farinae Drops groups (high-dose, medium-dose and low-dose), respectively. Statistical analysis was performed in three groups: Full Analysis Set, Per Protocol Set and Safety Set. 48 cases have withdrawn from the study before the end of study. As primary outcomes, significant decreases in scoring atopic dermatitis and total medication score were showed in medium-dose and high-dose D. farinae Drops groups. In the sixth visit, the skin lesion area showed a statistically significant difference between high-dose/medium-dose D. farinae Drops group and placebo group (p < .05). Most adverse events are slight, and no life-threatening adverse drug reaction happened. Our research demonstrates the beneficial effect of SLIT with high or medium dose D. farinae Drops on AD, and the treatment was well tolerated.

Intelligent Fault Diagnosis of Diesel Engines via Extreme Gradient Boosting and High-Accuracy Time-Frequency Information of Vibration Signals.

Accurate and timely misfire fault diagnosis is of vital significance for diesel engines. However, existing algorithms are prone to fall into model over-fitting and adopt low energy-concentrated features. This paper presents a novel extreme gradient boosting-based misfire fault diagnosis approach utilizing the high-accuracy time-frequency information of vibration signals. First, diesel engine misfire tests were conducted under different spindle speeds, and the corresponding vibration signals were acquired via a triaxial accelerometer. The time-domain features of signals were extracted by using a time-domain statistics method, while the high-accuracy time-frequency domain features were obtained via the high-resolution multisynchrosqueezing transform. Thereafter, considering the nonlinearity and high dimensionality of the original characteristic data sets, the locally linear embedding method was employed for feature dimensionality reduction. Eventually, to avoid model overfitting, the extreme gradient boosting algorithm was utilized for diesel engine misfire fault diagnosis. Experiments under different spindle speeds and comprehensive comparisons with other evaluation methods were conducted to demonstrate the effectiveness of the proposed extreme gradient boosting-based misfire diagnosis method. The results verify that the highest classification accuracy of the proposed extreme gradient boosting-based algorithm is up to 99.93%. Simultaneously, the classification accuracy of the presented approach is approximately 24.63% higher on average than those of algorithms that use wavelet packet-based features. Moreover, it is shown that it obtains the minimum root mean squared error and can effectively prevent the model from falling into overfitting.

Comparative biomechanical study of reversed less invasive stabilization system and proximal femoral nail antirotation for unstable intertrochanteric fractures.

OBJECTIVE: Unstable intertrochanteric fractures (ITFs) are mostly treated by proximal femoral nail antirotation (PFNA), Inter-Tan, Asian Hip, and other new internal fixation devices. But for complex unstable fractures, such as crushed lateral wall of the greater trochanter, the loss of fixation point on lateral wall slightly reduces the fixing effect. This study aimed to compare the biomechanical strengths between reversed less invasive stabilization system (LISS) and PFNA for treatment of unstable ITFs. METHODS: Forty synthetic femurs were used to simulate unstable ITFs in vitro and were fixed using the reversed LISS or PFNA. These fractures were divided into two groups depending on whether the lateral wall of the greater trochanter is intact or not (AO classification: 31-A2.3 and 31-A3.3, respectively). The load-displacement of femur, stiffness, ultimate load, and cyclic fatigue resistance were detected using an incremental load test and a dynamic fatigue test through an MTS 858 test system. RESULTS: For both 31-A2.3 and 31-A3.3, the vertical sinking displacement (VSD) of the femoral head under 500 N load was insignificantly smaller after treatment with reversed LISS than with PFNA, and when the displacement was 5 mm, the femoral head bore insignificantly greater load. The fixation with reversed LISS resulted in greater axial stiffness of the femur but smaller ultimate load. During the same cycle in the dynamic fatigue test, the VSD was insignificantly smaller with the fixation of reversed LISS. CONCLUSION: Reversed LISS and PFNA have similar biomechanical strength for unstable ITFs. This conclusion should be supported by additional large-size research on basic biomechanics and clinical application. This is the first comparative biomechanical study comparing reversed LISS and PFNA for unstable ITFs.

Neural stem cell transplantation in a double-layer collagen membrane with unequal pore sizes for spinal cord injury repair.

A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-µm-diameter pores, while the outer, compact layer has about 10-µm-diameter pores. In a rat model of incomplete spinal cord injury, a large number of neural stem cells were seeded into the loose layer, which was then adhered to the injured side, and the compact layer was placed against the lateral side. The results showed that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes promoted the differentiation of neural stem cells, attenuated the pathological lesion, and significantly improved the motor function of the rats with incomplete spinal cord injuries. These experimental findings suggest that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes is an effective therapeutic strategy to repair an injured spinal cord.

Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.

BACKGROUND: Filaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis (AD). The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies. MATERIALS AND METHODS: A group of 100 family trios (a total of 300 members with one affected AD proband and both parents) were recruited and screened for three filaggrin null mutations (3222del4, 3321delA and K4671X). The subjects' manifestations of AD and IV were assessed by two experienced dermatologists and recorded in detail. The relationship of common mutations to AD were assessed using both case-control and family-based tests of association. Filaggrin expression was measured in skin of 3 subjects with K4671X heterozygote and the normal control using quantitative real-time RT-PCR and immunohistochemistry. RESULTS: Of 100 probands for AD, 22 were carriers for common FLG mutations and only 2 of them were from 40 none-IV family trios (5.00%), consistent with that of the healthy control group (3.99%, P>0.05). Significant statistical associations were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence interval 3.35-44.98) as well as K4671X (P = 0.002, odds ratio 4.53, 95% confidence interval 1.77-11.60). The family-based approach revealed that 3321delA was over-transmitted to AD offspring from parents (T:U = 12∶1, P = 0.003) but failed to demonstrate transmission disequilibrium between K4671X and AD (T:U = 10∶8, P = 0.815). Moreover, compared to the normal control, filaggrin expression at both mRNA and protein levels in epidermis of subjects with K4671X(heter) was not reduced. CONCLUSIONS: AD patients from none-IV family trios have low probability of carrying FLG mutations. The present family samples confirmed the susceptibility of mutation 3321delA to AD in Han Chinese. K4671X was not a pathogenic mutation.

[Preliminary histological and biomechanical study about the timing of surgical repair for acute rotator cuff tears in rabbits].

OBJECTIVES: To establish the animal model of acute rotator cuff tear in rabbits, and study the effect of timing of surgical repair on healing of tendon-bone interface, formation and distribution of collagens in the supraspinatus tendon insertion and biomechanical properties of supraspinatus. METHODS: Supraspinatus tenotomy was performed in the right shoulder of 90 skeletally matured male New Zealand white rabbits to establish the animal model of acute rotator cuff tear. The rabbits were randomly divided into 3 groups : group of early repair, repaired at 1 week after tenotomy; group of late repair, repaired at 4 weeks after tenotomy; and group without repair, used as control. At 2 weeks, 4 weeks and 8 weeks after repair, healing of tendon-bone interface was observed by HE staining. Collagens were observed by Sirius Red F 3B (SR) in saturated carbazotic acid staining. The areas of type I and III collagens were measured by using imaging analysis software and the ratio of type I and III collagens were calculated. Failure loads of supraspinatus on both sides were measured. The percentage of failure loads of the surgical side was calculated and contralateral supraspinatus were uninjured. RESULTS: There was no obvious fatty infiltration and muscle atrophy in supraspinatus in all groups. At 8 weeks, the formation of a new enthesis of supraspinatus in groups of early and late repair were observed. In groups of early and late repair, the ratio of areas of type I and III collagens at 8 weeks (2.02 ± 0.77 and 2.06 ± 0.58) was larger than that at 2 weeks (1.10 ± 0.24 and 1.14 ± 0.50, t = 3.082, 3.655, P < 0.01). At 2, 4 and 8 weeks, the percentages of failure loads of the surgical side and uninjured contralateral supraspinatus in group of early repair(38% ± 11%, 66% ± 7%, 89% ± 4%) and group of late repair (41% ± 16%, 63% ± 7%, 89% ± 9%) were both higher than that in group without repair (14% ± 6%, 32% ± 4%, 56% ± 12%); the differences were all statistically significant (group of early repair: t = 3.311, 8.549, 5.719; group of late repair: t = 3.713, 8.063, 6.044; P < 0.01). The percentage of failure loads of the surgical side and uninjured contralateral supraspinatus at 8 weeks was higher than those at 4 weeks (t = 3.878 - 4.613, P < 0.01) and 2 weeks (t = 7.158 - 10.024, P < 0.01) in all groups. CONCLUSIONS: Surgical repair within 4 weeks of acute rotator cuff tear lead to formation of a new enthesis of supraspinatus, improvement of both ratio of type I collagen in the supraspinatus tendon insertion and biomechanical properties of supraspinatus.

[Biomechanical research of antegrade intramedullary fixation for the metacarpal fractures].

OBJECTIVE: To study the biomechanical characteristics of antegrade intramedullary fixation for metacarpal fractures. METHODS: From March to May 2008, both the 4th and 5th metacarpals from 25 formalin embalmed cadaver hands had three-point bending test after transverse osteotomy followed by randomly fixation with one of the following three methods: plate and screw, antegrade intramedullary K-wire, crossed K-wire. While, both the 2nd and 3rd metacarpals had torsional loading test after the same management as the 4th and 5th metacarpal had undergone. RESULTS: In the three-point bending test, both the maximum bending moment (M(max)) and bending rigidity (EI) of the antegrade intramedullary K-wire were comparable with those of the plate and screw, and were significantly larger than those of the crossed K-wire. In the torsional loading test, the antegrade intramedullary K-wire had a statistically smaller maximum torque (T(max)) than the plate and screw, and had a comparable T(max) with the crossed K-wire; while, the torsional rigidity (GJ) of the intramedullary K-wire was statistically weaker than that of both the plate and screw and the crossed wire. CONCLUSIONS: One single antegrade intramedullary K-wire can provide a satisfactory M(max) and EI for metacarpal fixation and shows relatively weak in the torsional loading test. The injured finger should be well protected to avoid torsional deformity in clinical practice.

[Carrier combination of tissue engineered bone by sodium alginate and xenograft bone and bone formation in vivo].

OBJECTIVE: To produce a new bone tissue engineered carrier through combination of xenograft bone (X) and sodium alginate (A) and to investigate the biological character of the cells in the carrier and the ability of bone-forming in vivo, so as to provide experimental evidence for a more effective carrier. METHODS: BMSCs were extracted from 2-week-old New Zealand rabbits and the BMSCs were induced by rhBMP-2 (1 x 10(-8)mol/L). The second generation of the induced BMSCs was combined with 1% (V/W) A by final concentration of 1 x 10(5)/mL. After 4-day culture, cells in gel were investigated by HE staining. The second generation of the induced BMSCs was divided into the DMEM gel group and the DMEM containing 1% A group. They were seeded into 48 well-cultivated cell clusters by final concentration of 1 x 10(5)/mL. Seven days later, the BMP-2 expressions of BMSCs in A and in commonly-cultivated cells were compared. The second generation of the induced BMSCs was mixed with 2% A DMEM at a final concentration of 1 x 10(10)/mL. Then it was compounded with the no antigen X under negative pressure. After 4 days, cells growth was observed under SEM. Twenty-four nude mice were randomly divided into 2 groups (n = 12). The compound of BMSCs-A-X (experimental group) and BMSCs-X (control group) with BMSCs whose final concentration was 1 x 10(10)/mL was implanted in muscles of nude mice. Bone formation of the compound was histologically evaluated by Image Analysis System 2 and 4 weeks after the operation, respectively. RESULTS: Cells suspended in A and grew plump. Cell division and nuclear fission were found. Under the microscope, normal proliferation, many forming processes, larger nucleus, clear nucleolus and more nuclear fission could be seen. BMP-2 expression in the DMEM gel group was 44.10% +/- 3.02% and in the DMEM containing 1% A group was 42.40% +/- 4.83%. There was no statistically significant difference between the two groups (P > 0.05). A was compounded evenly in the micropore of X and cells suspended in A 3-dimensionally with matrix secretion. At 2 weeks after the implantation, according to Image Analysis System, the compound of BMSCs-A-X was 5.26% +/- 0.24% of the total area and the cartilage-like tissue was 7.31% +/- 0.32% in the experimental group; the compound of BMSCs-X was 2.16% +/- 0.22% of the total area and the cartilage-like tissue was 2.31% +/- 0.21% in the control group. There was statistically significant difference between the two groups (P < 0.05). At 4 weeks after the operation, the compound of BMSCs-A-X was 7.26% +/- 0.26% of the total area and the cartilage-like tissue was 9.31% +/- 0.31% in the experimental group; the compound of BMSCs-X was 2.26% +/- 0.28% of the total area and the cartilage-like tissue was 3.31% +/- 0.26% in the control group. There was statistically significant difference between the two groups (P < 0.05). CONCLUSION: The new carrier compounding A and no antigen X conforms to the superstructural principle of tissue engineering, with maximum cells load. BMSCs behave well in the compound carrier with efficient bone formation in vivo.