Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.

OBJECTIVE: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. METHODS: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. RESULTS: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. CONCLUSION: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Extracellular regulated kinase 5 mediates osteoporosis through modulating viability and apoptosis of osteoblasts in ovariectomized rats.

Postmenopausal osteoporosis is a common condition characterized by the increase and activation of osteoclasts. The present study aimed to investigate the effects of extracellular signal-regulated kinase (ERK) 5 (ERK-5) on postmenopausal osteoporosis by regulating the biological behaviors of osteoblasts. Sprague-Dawley (SD) rats were ovariectomized to develop an osteoporosis model. A lentivirus packaging system was employed to generate lentiviruses capable of up- or down-regulating the expression of ERK-5 in ovariectomized rats. The femoral biomechanical properties, bone mineral density (BMD), contents of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) and bone turnover markers in rats, as well as viability, cycle and apoptosis of osteoblasts and ALP activity in osteoblasts were measured in the ovariectomized rats so as to explore the functional significance of ERK-5 in postmenopausal osteoporosis. The femoral mechanical strength of ovariectomized rats was enhanced by overexpression of ERK-5. Meanwhile femoral BMD, and bone metabolism were increased, and bone turnover normalized in the ovariectomized rats when ERK-5 was overexpressed. Lentivirus-mediated ERK-5 overexpression in osteoblasts was observed to inhibit osteoblast apoptosis, and promote viability, accompanied with increased ALP activity. Taken together, ERK-5 could decelerate osteoblast apoptosis and improve postmenopausal osteoporosis by increasing osteoblast viability. Thus, our study provides further understanding on a promising therapeutic target for postmenopausal osteoporosis.

A 3-Dimensional Finite Element Analysis of Adjacent Segment Disk Degeneration Induced by Transforaminal Lumbar Interbody Fusion After Pedicle Screw Fixation.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) is an effective treatment of upper lumbar intervertebral disk herniation. However, its clinical efficacy for adjacent segment disk degeneration (ASDD) remains undefined. Therefore, the biomechanical evaluation of ASDD caused by TLIF after pedicle screw fixation (PSF) was explored via a 3-dimensional (3D) finite element analysis. METHODS: Computed tomography images of a healthy male adult volunteer were used in this study. A L3-4 3D finite element model (model) was successfully constructed using Pro/E software, which was also used to establish the L4-5 of the TLIF, PSF, and PSF + TLIF models. Under the same loading conditions, the protrusion and retraction of the adjacent intervertebral disk and the stress distribution of the annulus fibrosis, facet joint, and articular process in the TLIF, PSF, and PSF + TLIF models were all compared. RESULTS: Protrusion and retraction of the adjacent intervertebral disk were more notable in the PSF + TLIF model than in the PSF model under the same loading conditions. The stress of the annulus fibrosis of the PSF + TLIF model was stronger relative to that of the PSF model under flexion, extension, or lateral bending. The stress of the articular process of the PSF + TLIF model was also stronger than that of the PSF model under extension or lateral bending. CONCLUSIONS: This study provides evidence that TLIF may aggravate ASDD after PSF. Furthermore, the findings provided in this report represent the theoretic basis for the clinical analysis of ASDD caused by TLIF after PSF.

Predictive value of microRNA-132 and its target gene NAG-1 in evaluating therapeutic efficacy of non-steroidal anti-inflammatory drugs treatment in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common chronic rheumatic disorder, accompanied by the differential expression of various microRNAs (miRNAs) in patients suffering from the condition, some of which have the potential to serve as novel complementary AS biomarkers. During this study, AS patients were recruited in connection with our investigation into the correlation of microRNA-132 (miR-132) in peripheral blood and its target gene NAG-1 expressions in relation with the clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) treatment in patients with AS. A total of 218 AS patients who had been previously treated with oral diclofenac sodium and were placed into either the response (n = 175) or non-response groups (n = 43) following a 16-week period of therapeutic evaluation. An additional 113 healthy patients were also recruited for the purposes of the study. AS patient peripheral blood samples were obtained at the 0th, 8th, and 16th week, with the corresponding samples of the healthy patients collected at week 0. The expressions of miR-132 and NAG-1 were detected by RT-qPCR and analyzed using a ROC curve for the elucidation of the diagnostic value of peripheral blood miR-132 expressions as well as their predictive value among AS patients undergoing NSAIDs treatment. The targeting relations of miR-132 and NAG-1 were validated by microRNA.org and luciferase assay. Greater levels of peripheral blood miR-132 expression were observed among AS patients prior to treatment, in comparison to the healthy patients in the study. Prior to treatment, the area under the miR-132 ROC curve (AUC) of AS patients was 0.965, with a critical point of 2.605. The sensitivity and specificity of miR-132 were 91.7 and 97.3%, respectively, in regard to the AS diagnostic clinical efficacy. In comparison with the non-response group, the miR-132 expression of patients in the response group exhibited descended levels while the mRNA expression of NAG-1 increased. The ROC results indicated that the AUC of miR-132 was 0.876 with its sensitivity and specificity observed to be 95.3 and 80.0%, respectively. The AUC of NAG-1 was 0.912 with its sensitivity and specificity observed to be 76.6 and 79.1%, respectively. In comparison with the high miR-132 expression group and the low NAG-1 mRNA expression group, significantly improved blood biochemistry indexes, sign indexes, blood indexes, and adverse reaction rate were observed among the low miR-132 expression group and the high NAG-1 mRNA expression group. The microRNA.org and luciferase assay revealed NAG-1 to be a target of miR-132. Based on the results of this study, it was concluded that the expressions of MiR-132 and NAG-1 could serve as biological markers in the prediction of the therapeutic efficiency of NSAID treatment in AS patients.

Effects of nonsteroidal anti-inflammatory drugs on serum proinflammatory cytokines in the treatment of ankylosing spondylitis.

OBJECTIVE: This study was conducted to investigate the correlation between serum levels of proinflammatory cytokines and the clinical efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with ankylosing spondylitis (AS). METHODS: A total of 148 patients with AS were selected and received NSAID treatment. ELISA was used to assess cytokine levels, and patients were assigned into the following groups: positively effective; effective; moderately effective; and ineffective. Spearman and Pearson correlation analyses were used for correlation analysis. RESULTS: The erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) levels, and immunoglobulin A (IgA) levels of the case group after NSAID treatment were markedly lower than those before NSAID treatment. After treatment, the levels of interleukin (IL)-6, IL-17, and tumor necrosis factor (TNF)-α were markedly reduced, while IL-10 levels increased in the positively effective, effective, and moderately effective groups, and IL-12 levels decreased in the positively effective and effective groups. In addition, the levels of IL-6 and TNF-α were correlated with a greater number in the efficacy indexes and clinical parameters, followed by IL-10 levels, while the levels of IL-17 and IL-12 had relatively weaker correlations with these indexes and parameters. CONCLUSION: NSAIDs could promote the clinical efficacy of treatment for ankylosing spondylitis by regulating serum levels of proinflammatory cytokines.

Traditional Chinese medicine for neck pain and low back pain: a systematic review and meta-analysis.

BACKGROUND: Neck pain (NP) and low back pain (LBP) are common symptoms bothering people in daily life. Traditional Chinese medicine (TCM) has been used to treat various symptoms and diseases in China and has been demonstrated to be effective. The objective of the present study was to review and analyze the existing data about pain and disability in TCM treatments for NP and LBP. METHODS: Studies were identified by a comprehensive search of databases, such as MEDLINE, EMBASE, and Cochrane Library, up to September 1, 2013. A meta-analysis was performed to evaluate the efficacy and safety of TCM in managing NP and LBP. RESULTS: Seventy five randomized controlled trials (n = 11077) were included. Almost all of the studies investigated individuals experiencing chronic NP (CNP) or chronic LBP (CLBP). We found moderate evidence that acupuncture was more effective than sham-acupuncture in reducing pain immediately post-treatment for CNP (visual analogue scale (VAS) 10 cm, mean difference (MD) = -0.58 (-0.94, -0.22), 95% confidence interval, p = 0.01), CLBP (standardized mean difference = -0.47 (-0.77, -0.17), p = 0.003), and acute LBP (VAS 10 cm, MD = -0.99 (-1.24, -0.73), p< 0.001). Cupping could be more effective than waitlist in VAS (100 mm) (MD = -19.10 (-27.61, -10.58), p < 0. 001) for CNP or medications (e.g. NSAID) for CLBP (MD = -5.4 (-8.9, -0.19), p = 0.003). No serious or life-threatening adverse effects were found. CONCLUSIONS: Acupuncture, acupressure, and cupping could be efficacious in treating the pain and disability associated with CNP or CLBP in the immediate term. Gua sha, tai chi, qigong, and Chinese manipulation showed fair effects, but we were unable to draw any definite conclusions, and further research is still needed. The efficacy of tuina and moxibustion is unknown because no direct evidence was obtained. These TCM modalities are relatively safe.

MALDI-TOF-MS serum protein profiling for developing diagnostic models and identifying serum markers for discogenic low back pain.

BACKGROUND: The identification of the cause of chronic low back pain (CLBP) represents a great challenge to orthopedists due to the controversy over the diagnosis of discogenic low back pain (DLBP) and the existence of a number of cases of CLBP of unknown origin. This study aimed to develop diagnostic models to distinguish DLBP from other forms of CLBP and to identify serum biomarkers for DLBP. METHODS: Serum samples were collected from patients with DLBP, chronic lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls (N), and randomly divided into a training set (n = 30) and a blind test set (n = 30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed for protein profiling of these samples. After the discriminative ability of two most significantly differential peaks from each two groups was assessed using scatter plots, classification models were developed using differential peptide peaks to evaluate their diagnostic accuracy. The identity of peptides corresponding to three representative differential peaks was analyzed. RESULTS: The fewest statistically significant differential peaks were identified between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs. CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of two most significantly differential peaks was poor in classifying DLBP vs. CLBP but good in classifying DLBP vs. LDH. The accuracy of models for classification of DLBP vs. CLBP was not very high in the blind test (forecasting ability, 67.24%; sensitivity, 70%), although a higher accuracy was observed for classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%; sensitivities, >90%). A further investigation of three representative differential peaks led to the identification of two peaks as peptides of complement C3, and one peak as a human fibrinogen peptide. CONCLUSIONS: Our findings benefit not only the diagnosis of CLBP but also the understanding of the differences between different forms of DLBP. The ability to distinguish between different causes of CLBP and the identification of serum biomarkers may be of great value to diagnose different causes of DLBP and predict treatment efficacy.

Association between Caspase-9 promoter region polymorphisms and discogenic low back pain.

Caspase-9 (CASP-9) is an initiator caspase protease for apoptosis, and plays an important role in the development and progression of lumbar disc disease (LDD). The expression and/or activity of CASP-9 are significantly enhanced in the degenerated disc. The polymorphism in the promoter region of CASP-9 enhances the transcriptional activity of this gene, thereby modulating the susceptibility to LDD. The current study investigated the relationship between the CASP-9 -1263A/G (rs4645978) and -712C/T (rs4645981) polymorphisms and discogenic low back pain (LBP). The CASP-9 -1263A/G and -712C/T genotypes in this study were defined by polymerase chain reaction in 154 patients with discogenic LBP and 216 controls that were frequency-matched by age, gender, and occupation. The results showed that the CASP-9 -1263 GG genotype, compared with the AA and AG genotypes [odds ratio (OR) = 1.997, 95% confidence interval (95% CI) = 1.216-3.279, p = 0.006] or the AA genotype (OR = 2.760, 95% CI = 1.464-5.203, p = 0.002), is associated with a significant increased risk of discogenic LBP, but the -712 TT or TT and CT genotypes do not contribute to discogenic LBP compared with the CC genotype (OR = 0.547, 95% CI = 0.200-1.494, p = 0.234 and OR = 0.669, 95% CI = 0.439-1.021, p = 0.062, respectively). These results indicated that the CASP-9 -1263A/G polymorphism is associated with a high risk of discogenic LBP.

Clinical diagnosis for discogenic low back pain.

Discogenic lower back pain (DLBP) is the most common type of chronic lower back pain (LBP), accounting for 39% of cases, compared to 30% of cases due to disc herniation, and even lower prevalence rates for other causes, such as zygapophysial joint pain. Only a small proportion (approximately 20%) of LBP cases can be attributed with reasonable certainty to a pathologic or anatomical entity. Thus, diagnosing the cause of LBP represents the biggest challenge for doctors in this field. In this review, we summarize the process of obtaining a clinical diagnosis of DLBP and discuss the potential for serum-based diagnosis in the near future. The use of serum biomarkers to diagnose DLBP is likely to increase the ease of diagnosis as well as produce more accurate and reproducible results.