The Association of Epicardial Adipose Tissue Volume and Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: As Assessed by Cardiac MR.

BACKGROUND: Epicardial adipose tissue (EAT) is a metabolically active visceral fat linked to cardiovascular disease. Prior studies demonstrated the predictive value of EAT volume (EATV) in atrial fibrillation (AF) among hypertrophic obstructive cardiomyopathy patients. PURPOSE: To investigate the association between EATV and AF in hypertrophic cardiomyopathy (HCM). STUDY TYPE: Retrospective. POPULATION: Two hundred and twenty-four HCM patients (including 79 patients with AF and 145 patients without AF, 154 men) and 80 healthy controls (54 men). FIELD STRENGTH/SEQUENCE: 3.0 T scanner; balanced steady-state free precession (SSFP) cine sequence, gradient echo. ASSESSMENT: EAT thickness was assessed in the 4-chamber and basal short-axis planes. EAT volume was calculated by outlining the epicardial border and visceral pericardium layer on short-axis cine images. STATISTICAL TESTS: Shapiro-Wilk test, Student's t test or the Mann-Whitney U test, chi-square test or Fisher's exact test, Multivariate linear regression analyses, Multivariable binary logistic regression analysis. Intraclass correlation coefficient. Significance was determined at P < 0.05. RESULTS: EATV and EAT volume index (EATVI) were significantly greater in HCM patients with AF than those without AF (126.6 ± 25.9 mL vs. 90.5 ± 24.5 mL, and 73.0 ± 15.9 mL/m2 vs. 51.3 ± 13.4 mL/m2). EATVI was associated with AF in multivariable linear regression analysis among HCM patients (ß = 0.62). Multivariable logistic regression analysis revealed that compared to other indicators, the area under curve (AUC) of EATVI was 0.86 (cut-off, 53.9 mL/m2, 95% CI, 0.80-0.89), provided a better performance, with the sensitivity of 96.2% and specificity of 58.6%. The combined model exhibited superior association with AF presence compared to the clinical model (AUC 0.96 vs. 0.76) and the imaging model (AUC 0.96 vs. 0.93). DATA CONCLUSION: EATVI was associated with AF. EATVI was significantly correlated with incident AF, and provided a better performance in HCM patients compared to other indicators. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Electron withdrawing group-dependent substrate inhibition of an α-ketoamide reductase from Saccharomyces cerevisiae.

Aldo-keto reductases remain enzymes of interest in biocatalysis due to their ability to reduce carbonyls to alcohols stereospecifically. Based on genomic sequence, we identified aldo-keto reductases of a S. cerevisiae strain extracted from an ancient amber sample. One of the putative enzymes, AKR 163, displays 99% identity with α-amide ketoreductases from the S288C and YJM248 S. cerevisiae strains, which have been investigated for biocatalytic applications. To further investigate AKR 163, we successfully cloned, expressed in E.coli as a glutathione-S-transferase fusion protein, and affinity purified AKR 163. Kinetic studies revealed that AKR 163 experiences strong substrate inhibition by substrates containing halogen atoms or other electron withdrawing groups adjacent to the reactive carbonyl, with Ki values ranging from 0.29 to 0.6 mM and KM values ranging from 0.38 to 0.9 mM at pH 8.0. Substrates without electron withdrawing groups do not display substrate inhibition kinetics and possess much larger KM values between 83 and 260 mM under the same conditions. The kcat values ranged from 0.5 to 2.5s-1 for substrates exhibiting substrate inhibition and 0.22 to 0.52s-1 for substrates that do not engage in substrate inhibition. Overall, the results are consistent with rate-limiting dissociation of the NADP+ cofactor after hydride transfer when electron withdrawing groups are present and activating the reduction step. This process leads to a buildup of enzyme-NADP+ complex that is susceptible to binding and inhibition by a second substrate molecule.

Full-space wavefront manipulation enabled by asymmetric photonic spin-orbit interactions.

Optical metasurfaces empower complete wavefront manipulation of electromagnetic waves and have been found in extensive applications, whereas most of them work in either transmission or reflection space. Here, we demonstrate that two independent and arbitrary phase profiles in transmission and reflection spaces could be produced by a monolayer all-dielectric metasurface based on the asymmetric photonic spin-orbit interactions, realizing full-space wavefront independent manipulation. Furthermore, the supercell-based non-local approach is employed to suppress crosstalk between adjacent nanopillars in one supercell for broadband and high-efficiency wavefront manipulation in full space. Compared with the conventional unit cell-based local approach, such a method could improve efficiency about 10%. As a proof of concept, two metadevices are designed, in which the maximum diffraction efficiencies are ∼95.53%/∼74.07% within the wavelength range of 1500-1600 nm in reflection/transmission space under circularly polarized light incidence. This configuration may offer an efficient way for 2π-space holographic imaging, augmented reality, virtual reality technologies, three-dimensional imaging, and so forth.

Broadband and high-efficiency photonic spin-Hall effect with all-metallic metasurfaces.

In this paper, all-metallic reflective metasurfaces comprising S-shape streamline structures are proposed to achieve the photonic spin-Hall effect with average cross-polarization conversion efficiency exceeding ∼84% in the range of 8-14 µm. By comparing with all-metallic nanobricks, it is demonstrated that the electric field coupling could be enhanced by constructing a similar split ring resonator between adjacent unit elements to further improve its efficiency and bandwidth. As a proof of concept, the photonic spin Hall effect and spin-to-orbit angular momentum conversion could be observed by two metadevices with the maximum diffraction efficiency of ∼95.7%. Such an all-metallic configuration may provide a platform for various high-efficiency electromagnetic components, catenary optics, and practical applications.

p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), accompanied by accumulation of α-synuclein, chronic neuroinflammation and autophagy dysfunction. Previous studies suggested that misfolded α-synuclein induces the inflammatory response and autophagy dysfunction in microglial cells. The NLRP3 inflammasome signaling pathway plays a crucial role in the neuroinflammatory process in the central nervous system. However, the relationship between autophagy deficiency and NLRP3 activation induced by α-synuclein accumulation is not well understood. METHODS: Through immunoblotting, immunocytochemistry, immunofluorescence, flow cytometry, ELISA and behavioral tests, we investigated the role of p38-TFEB-NLRP3 signaling pathways on neuroinflammation in the α-synuclein A53T PD models. RESULTS: Our results showed that increased protein levels of NLRP3, ASC, and caspase-1 in the α-synuclein A53T PD models. P38 is activated by overexpression of α-synuclein A53T mutant, which inhibited the master transcriptional activator of autophagy TFEB. And we found that NLRP3 was degraded by chaperone-mediated autophagy (CMA) in microglial cells. Furthermore, p38-TFEB pathways inhibited CMA-mediated NLRP3 degradation in Parkinson's disease. Inhibition of p38 had a protective effect on Parkinson's disease model via suppressing the activation of NLRP3 inflammasome pathway. Moreover, both p38 inhibitor SB203580 and NLRP3 inhibitor MCC950 not only prevented neurodegeneration in vivo, but also alleviated movement impairment in α-synuclein A53T-tg mice model of Parkinson's disease. CONCLUSION: Our research reveals p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in Parkinson's disease, which could be a potential therapeutic strategy for PD. p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in Parkinson's disease. In this model, p38 activates NLRP3 inflammasome via inhibiting TFEB in microglia. TFEB signaling negatively regulates NLRP3 inflammasome through increasing LAMP2A expression, which binds to NLRP3 and promotes its degradation via chaperone-mediated autophagy (CMA). NLRP3-mediated microglial activation promotes the death of dopaminergic neurons.

Chemical constituents, clinical efficacy and molecular mechanisms of the ethanol extract of Abelmoschus manihot flowers in treatment of kidney diseases.

Abelmoschus manihot, also called as "Huangkui" in Chinese, is an annual flowering herb plant in the family of Malvaceae. As a traditional Chinese medicine, the ethanol extract of the flower in Abelmoschus manihot is made as Huangkui capsule and has been used for medication of the patients with kidney diseases. Its efficacy in clinical symptoms is mainly improving renal function and reducing proteinuria among the patients with chronic kidney disease, diabetic kidney disease or IgA nephropathy. The possible mechanism of Huangkui capsule treatment in kidney diseases may include reducing inflammation and anti-oxidative stress, improving immune response, protecting renal tubular epithelial cells, ameliorating podocyte apoptosis, glomerulosclerosis and mesangial proliferation, as well as inhibiting renal fibrosis. In this review, we first described chemical constituents and pharmacokinetic characteristics in ethanol extract of the flower of Abelmoschus manihot. We then summarized the clinical and epidemiological relevancies of kidney diseases particularly in the mainland of China and discussed the possible molecular mechanisms of Huangkui capsule in the treatment of kidney diseases. Finally, we prospected further research on cellular and molecular mechanisms and application of this Chinese natural medicine in kidney diseases.

p38 MAPK-DRP1 signaling is involved in mitochondrial dysfunction and cell death in mutant A53T α-synuclein model of Parkinson's disease.

Abnormal accumulation of α-synuclein and mitochondria dynamics dysfunction are considered to be implicated in the pathogenesis of Parkinson's disease. However, the underlying mechanisms how α-synuclein abnormal accumulation causes mitochondrial dynamics dysfunction remains unclear. Here, we demonstrate that dynamin-related protein 1(DRP1) is a substrate for p38 MAPK, mutant α-synuclein overexpression in SN4741 cell caused p38 MAPK activation, p38 MAPK-mediated phosphorylation DRP1 at serine 616 to activate DRP1 and is associated with increased mitochondrial fission, which resulted in mitochondrial dysfunction and neuronal loss. Inhibition of p38 MAPK or expression of a kinase death form of p38 MAPK not only attenuates DRP1-mediated mitochondrial fission，but also restores the mitochondrial dysfunction and cell death in α-synuclein A53T model. These findings showed that inhibition of p38 MAPK-DRP1 signaling pathway may be a viable therapeutic strategy of PD on maintenance of mitochondrial homeostasis.

Cluster analysis of differences in medical economic burden among residents of different economic levels in Guangdong Province, China.

BACKGROUND: This study compares and analyzes the differences of residents' medical economic burden in different economic levels, explores the factors for improving the equity of health services in Guangdong, China. METHODS: Cluster analysis was carried out in 20 cities of Guangdong Province by taking 7 key factors on the equity of health services as indicators. Seven key factors were collected from Guangdong Statistical Yearbook 2017 and the Sixth National Population Census. R-type clustering was used to reduce the dimensionality of 7 candidate variables through similarity index. Q-type clustering was used to classify 20 cities in Guangdong Province. RESULTS: The cluster analysis divided Guangdong Province into three regions with different medical economic burden. The greater the proportion of the elderly over 65 years old, the greater the proportion of health care expenditure to per capita consumer expenditure of residents, and the heavier the medical economic burden. On average, 10.75% of the general budget expenditure of each city in Guangdong Province is spent on health care. CONCLUSIONS: The lower per capita GDP, the higher proportion of the elderly over 65 years old and the lack of medical technicians are risk factors for the heavier medical burden of the residents and the fairness of health services. While increasing the health expenditure, the government needs to further complete the reform of the medical and health system, improve the efficiency of the medical system and curb the rapid rise of absolute health expenditures of individuals, which can reduce the economic burden of residents' medical care.

Efficient generation and tight focusing of radially polarized beam from linearly polarized beam with all-dielectric metasurface.

We propose a single layer all-dielectric metasurface lens to simultaneously convert and focus an incident linear polarization into a radial beam with high efficiency and high numerical aperture (NA). It shows a better focusing property compared with the linearly polarized metasurface lens for high NA. A tight spot size (0.502λ) is achieved for the NA = 0.94. Additionally, the emergent polarization can in principle be switched flexibly between radially and azimuthally polarized beams by the adjustment of incident polarization direction. It is expected that our scheme may have potential value in microscopy, material processing, medicine, particles accelerating and trapping, and so on.

Rheological Behavior of a Novel Organic-Inorganic Hybrid: Micro/Nano-Tin Fluorophosphate Glass-Polycarbonate.

The rheological behavior of a novel, binary organic-inorganic hybrid consisting of an ultra-low Tg tin fluorophosphate glass (Pglass) and polycarbonate (PC) was investigated using oscillatory rheometry. It was found that the complex viscosity of the hybrid showed Pglass content dependence. Under low Pglass content (10-30%), the complex viscosity of the hybrid was lower than that of pure PC. While the complex viscosity was dramatically increased and higher than that of pure PC with the content of Pglass above 30%. This phenomenon was particularly remarkable at low frequencies. Besides, with the addition of Pglass the hybrid material exhibited shear-thinning behavior and the shear-thinning characteristics became more obvious with the enhancement of the Pglass content, indicating the presence of nonlinear chemical and physical interactions between the hybrid components. Differential scanning calorimetry (DSC) measurements revealed that increasing the content of Pglass caused a decrease of the glass transition temperature (Tg) of the hybrids, suggesting that Pglass was acting as a macromolecular plasticizer for the PC. The microstructure of the Pglass in the hybrid material was characterized by scanning electron microscopy (SEM). The results showed that the Pglass were dispersed as micro- and nano-bead in the continuous phase of PC and the Pglass appeared aggregation partly with the increase of the Pglass content. This contribution was anticipated to be a guideline for the processing of this promising new class of hybrid materials.

Sharp Fano resonance induced by a single layer of nanorods with perturbed periodicity.

In this paper, we report the formation of extremely sharp (Quality factor Q~ + ∞) FR in a single layer of dielectric nanorods with perturbed periodicity. The interference between the broadband Fabry-Perot (F-P) resonance and defect induced dark mode results in refractive index sensitivity (S) of 1312.75 nm/RIU and figure of merit (FOM) of 500, offering an excellent platform for biological sensing and detection.

Highly efficient wavefront manipulation in terahertz based on plasmonic gradient metasurfaces.

Polarization conversion efficiency is vitally important to highly efficient wavefront manipulation based on phase discontinuities. However, previous single-layer phase gradient metasurfaces have suffered from low polarization conversion efficiency (at most 25%). Here we present a three-layer structure to enhance polarization conversion efficiency. The average efficiency is 76% for circularly polarized incident light converted to its opposite handedness. By arraying metallic antennas with varied optical axes for circularly polarized incident light, the efficiency of anomalous refraction is apparently increased, and the focused intensity of flat lenses can be significantly enhanced in the terahertz regime. It is expected that this scheme has potential applications in detection, focusing, and imaging.

Stepwise phosphorylation and SUMOylation of PIDD1 drive PIDDosome assembly in response to DNA repair failure.

SUMOylation regulates numerous cellular stress responses, yet targets in the apoptotic machinery remain elusive. We show that a single, DNA damage-induced monoSUMOylation event controls PIDDosome (PIDD1/RAIDD/caspase-2) formation and apoptotic death in response to unresolved DNA interstrand crosslinks (ICLs). SUMO-1 conjugation occurs on conserved K879 in the PIDD1 death domain (DD); is catalyzed by PIAS1 and countered by SENP3; and is triggered by ATR phosphorylation of neighboring T788 in the PIDD1 DD, which enables PIAS1 docking. Phospho/SUMO-PIDD1 proteins are captured by nucleolar RAIDD monomers via a SUMO-interacting motif (SIM) in the RAIDD DD, thus compartmentalizing nascent PIDDosomes for caspase-2 recruitment. Denying SUMOylation or the SUMO-SIM interaction spares the onset of PIDDosome assembly but blocks its completion, thus eliminating the apoptotic response to ICL repair failure. Conversely, removal of SENP3 forces apoptosis, even in cells with tolerable ICL levels. SUMO-mediated PIDDosome control is also seen in response to DNA breaks but not supernumerary centrosomes. These results illuminate PIDDosome formation in space and time and identify a direct role for SUMOylation in the assembly of a major pro-apoptotic device.

Blue honeysuckle fermentation with Lacticaseibacillus rhamnosus L08 improves its biological activity, sensory and flavor characteristics, and storage stability.

The objective of this study was to investigate the potential of Lacticaseibacillus rhamnosus L08 (L. rhamnosus L08) to enhance the functionality, improve the taste, and explore efficient storage methods of blue honeysuckle juice (BHJ). The fermentation process resulted in an increase in the levels of polyphenols, flavonoids, and anthocyanins in blue honeysuckle juice, which was attributed to the action of ß-glucosidase on specific phenolic compounds, namely Cyanidin-3-Glucoside and Quinic acid. The increase in phenolic content resulted in an enhancement of the antioxidant capacity of BHJ. The fermentation processed, utilizing L. rhamnosus L08, not only enhanced the flavor and taste of BHJ, but also mitigated its bitter aftertaste while minimizing the loss of bioactive components during storage. In conclusion, this study demonstrated a potential avenue for enhancing the commercial value and dietary significance of this lesser-known superfruit, with fermented BHJ emerging as a promising innovation in the field of functional foods.

Conversion of broadband energy to narrowband emission through double-sided metamaterials.

In this paper, an energy harvesting/re-radiating device is proposed to realize high efficiency energy conversion in the solar thermo-photovoltaic system. Such device consists of double-sided metamaterials which are assembled by a broadband absorber working in the major solar spectrum, and a back-by-back narrowband emitter working in the infrared band. It is theoretically proved that most of solar light (from 0.28 µm to 4 µm) can be collected, and then, converted to a sharp emission at the maximal response energy level (~0.4 eV) of photovoltaic cells in thermal equilibrium state. The impact of high temperature (as large as 966 K) and the parasitic radiation on the performance is discussed and compensated by geometric optimization.

Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway.

PURPOSE: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. METHODS: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. RESULTS: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. CONCLUSIONS: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

A noncanonical IRAK4-IRAK1 pathway counters DNA damage-induced apoptosis independently of TLR/IL-1R signaling.

Interleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptors (TLRs) and IL-1R in innate immunity. Here, we found that IRAK4 and IRAK1 together inhibited DNA damage-induced cell death independently of TLR or IL-1R signaling. In human cancer cells, IRAK4 was activated downstream of ATR kinase in response to double-strand breaks (DSBs) induced by ionizing radiation (IR). Activated IRAK4 then formed a complex with and activated IRAK1. The formation of this complex required the E3 ubiquitin ligase Pellino1, acting structurally but not catalytically, and the activation of IRAK1 occurred independently of extracellular signaling, intracellular TLRs, and the TLR/IL-1R signaling adaptor MyD88. Activated IRAK1 translocated to the nucleus in a Pellino2-dependent manner. In the nucleus, IRAK1 bound to the PIDD1 subunit of the proapoptotic PIDDosome and interfered with platform assembly, thus supporting cell survival. This noncanonical IRAK signaling pathway was also activated in response to other DSB-inducing agents. The loss of IRAK4, of IRAK4 kinase activity, of either Pellino protein, or of the nuclear localization sequence in IRAK1 sensitized p53-mutant zebrafish to radiation. Thus, the findings may lead to strategies for overcoming tumor resistance to conventional cancer treatments.

Pin1 aggravates renal injury induced by ischemia and reperfusion in rats via Nrf2/HO-1 mediated endoplasmic reticulum stress.

PURPOSE: To investigate the role of peptidyl-prolyl cis/trans isomerase 1 (Pin1) on renal ischemia-reperfusion (I/R) injury and underlying mechanism. METHODS: By establishing the in vitro and in vivo models of renal I/R, the role of Pin1 was explored by using molecular assays. RESULTS: In renal I/R, endogenous Pin1 level was up-regulated in I/R-impaired kidney. Suppression of Pin1 with juglone afforded protection against I/R-mediated kidney dysfunction, and reduced I/R-induced endoplasmic reticulum (ER) stress in vivo. Consistent with the in vivo results, repression of Pin1 with juglone or gene knockdown with si-Pin1 conferred cytoprotection and restricted hypoxia/reoxygenation (H/R)-driven ER stress in HK-2 cells. Simultaneously, further study uncovered that Nrf-2/HO-1 signals was the association between Pin1 and ER stress in response to renal I/R. In addition, Nrf-2/HO-1 signal pathway was inactivated after kidney exposed to I/R, as indicated by the down-regulation of Nrf-2/HO-1 levels. Furthermore, inhibition of Pin1 remarkably rescued the inactivation ofNrf-2/HO-1. CONCLUSIONS: Pin1 modulated I/R-mediated kidney injury in ER stress manner dependent on Nrf2-HO-1 pathway in I/R injury.

Deacetylation of ZKSCAN3 by SIRT1 induces autophagy and protects SN4741 cells against MPP+-induced oxidative stress.

Mitochondrial dysfunction, oxidative stress and misfolded protein aggregation are related to autophagy-lysosomal dysregulation and contribute to the pathogenesis of Parkinson' s disease (PD). ZKSCAN3, a transcriptional repressor, plays a crucial role in autophagy and lysosomal biogenesis. However, the role and modification of ZKSCAN3 in the defection of ALP, along with the molecular mechanism involved in pathogenesis of PD, still remain unclear. In this study, we demonstrated that cellular reactive oxygen species (ROS) generated by MPP+ exposure and the resulting oxidative damage were counteracted by SIRT1-ZKSCAN3 pathway induction. Here we showed that nuclear ZKSCAN3 significantly increased in ventral midbrain of MPTP-treated mice and MPP+-treated SN4741 cells. Knockdown of ZKSCAN3 alleviated MPP+-induced ALP defect, Tyrosine Hydroxylase (TH) declination and neuronal death. NAC, a ROS scavenger, reduced the nuclear translocation of ZKSCAN3 and sequentially improved ALP function in MPP+-treated SN4741 cells. SRT2104, a SIRT1 activator, attenuated impairment of ALP in MPP+-treated SN47417 cells through decreasing nuclear accumulation of ZKSCAN3 and protected dopaminergic neurons from MPTP injury. Moreover, SRT2104 relieved impairment in locomotor activities and coordination skills upon treatment of MPTP in C57/BL6J mice through behavior tests including rotarod, pole climbing and grid. Furthermore, ZKSCAN3 was a novel substrate of SIRT1 which was deacetylated at lysine 148 residues by SIRT1. This subsequently facilitated the shuttling of ZKSCAN3 to the cytoplasm. Therefore, our study identifies a novel acetylation-dependent regulatory mechanism of nuclear translocation of ZKSCAN3. It results in autophagy-lysosomal dysfunction and then leads to DA neuronal death in MPTP/MPP+ model of PD.

Association between polymorphisms of collagen genes and susceptibility to intervertebral disc degeneration: a meta-analysis.

BACKGROUND: Collagens are important structural components of intervertebral disc. A number of studies have been performed for association between polymorphisms of collagen genes and risk of intervertebral disc degeneration (IVDD) but yielded inconsistent results. Here, we performed a meta-analysis to investigate the association of collagen IX alpha 2 (COL9A2) Trp2, collagen IX alpha 3 (COL9A3) Trp3, collagen I alpha 1 (COL1A1) Sp1 and collagen XI alpha 1 (COL11A1) C4603T polymorphisms with susceptibility to IVDD. METHOD: Eligible studies were retrieved by searching MEDLINE, EMBASE, Web of Science prior to 31 March, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for association strength. RESULTS: A total of 28 eligible studies (31 datasets comprising 5497 cases and 5335 controls) were included. COL9A2 Trp2 carriers had an increased risk of IVDD than non-carriers in overall population (OR = 1.43, 95% CI 0.99-2.06, P = 0.058), which did not reach statistical significance. However, Trp2 carriers had 2.62-fold (95% CI 1.15-6.01, P = 0.022) risk than non-carriers in Caucasians. COL9A3 Trp3 was not associated with IVDD risk (OR = 1.28, 95% CI 0.81-2.02, P = 0.299). T allele and TT genotype of COL1A1 Sp1 (+ 1245G > T) were correlated with increased risk of IVDD. Significant associations were found between COL11A1 C4603T and IVDD risk under allelic (OR = 1.33, 95% CI 1.20-1.48), dominant (OR = 1.45, 95% CI 1.26-1.67), recessive (OR = 1.55, 95% CI 1.21-1.98) and homozygote model (OR = 1.81, 95% CI 1.40-2.34). CONCLUSIONS: COL1A1 Sp1 and COL11A1 C4603T polymorphism are associated with IVDD risk while the predictive roles of collagen IX gene Trp2/3 need verification in more large-scale studies.