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ABSTRACT Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Abstract Purpose To assess the safety and efficacy of the extra-facet puncture technique applied in unilateral percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures. Methods Demographics (age, gender, body mass index and underlying diseases) were recorded for analyzing. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores as well as their corresponding minimal clinically important difference (MCID) were used to evaluate clinical outcomes. The segmental kyphotic angle, the vertebral compression ratio and bone cement distribution pattern were evaluated by the plain radiographs. The facet joint violation (FJV) was defined by the postoperative computed tomography scan. Binary logistic regression analysis was performed to investigate relationships between multiple risk factors and residual back pain. Results VAS and ODI scores in both traditional puncture group and extra-facet puncture group were significantly decreased after PVP surgery (p

Objective Lumbar disc degeneration (LDD) is a common cause of low back pain and disability, and its prevalence increases with age. The aim of this study is to investigate whether endplate Hounsfield unit (HU) values have an effect on lumbar disc degeneration (LDD) after transforaminal lumbar interbody fusion (TLIF) surgery in patients with degenerative lumbar stenosis. Methods This study was a retrospective analysis of patients who underwent TLIF surgery in January 2016 to October 2019. One hundred and fifty‐seven patients who underwent TLIF surgery for degenerative lumbar stenosis were enrolled in this study. Demographic data was recorded. VAS and ODI values were compared to assess the surgical outcomes in patients with or without process of LDD after TLIF surgery. Correlation analysis was performed to investigate associations between LDD and endplate HU value. Binary logistic regression analysis was carried out to study relationships between the DDD and the multiple risk factors. Results There was a statistically significant correlation between LDD, body mass index (BMI), age, paraspinal muscle atrophy, and total endplate scores (TEPS). Also, a strong and independent association between endplate HU value and LDD was found at every lumbar disc level (p

Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by‐product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress‐mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD.

Carpesium (Family – Compositae) is a genus with 24 species of mainly perennial herbs. Several species of this genus have served as folk medicine in China and Korea for their antipyretic, anti-inflammatory, analgesic, antifungal, antibacterial, and cytotoxic activity properties. Chemical constituents are mostly sesquiterpenes, diterpenes, glycosides, and several other types of compounds. This article summarizes the literature on the isolated and identified constituents from various Carpesium species and their various biological activities.

Abstract There have been an increasing number of patients with degenerative disc diseases due to the aging population. In light of this, studies on the pathogenesis of intervertebral disc degeneration have become a hot topic, and gene knockout mice have become a valuable tool in this field of research. With the development of science and technology, constitutive gene knockout mice can be constructed using homologous recombination, zinc finger nuclease, transcription activator‐like effector nuclease technology and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system, and conditional gene knockout mice can be constructed using the Cre/LoxP system. The gene‐edited mice using these techniques have been widely used in the studies on disc degeneration. This paper reviews the development process and principles of these technologies, functions of the edited genes in disc degeneration, advantages, and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene‐edited model mice are presented. At the same time, possible technological improvements in the future are also discussed.

Purpose. There have been many studies in the operative management of pyogenic spondylodiscitis with foreign materials. However, it still remains an issue of debate on whether the allografts may be used in pyogenic spondylodiscitis. This study sought to evaluate the safety and effectiveness of PEEK cages and the cadaveric allograft in transforaminal lumbar interbody fusion (TLIF) for treating lumbar pyogenic spondylodiscitis. Methods. From January 2012 to December 2019, 56 patients underwent surgery for lumbar pyogenic spondylodiscitis. The posterior debridement of all patients and their fusion with allografts, local bone grafts, and bone chip cages were performed before posterior pedicle screw fusion. An assessment of the residual pain, the grade of neurological injury, and the resolution of infection was conducted on 39 patients. The clinical outcome was evaluated using a visual analog scale (VAS) and the Oswestry Disability Index (ODI), and neurological outcomes were appraised based on Frankel grades. The radiological outcomes were evaluated via focal lordosis, lumbar lordosis, and the state of the fusion. Results. Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. The mean preoperative focal lordosis was −1.2° (−11.4° to 5.7°), and the mean postoperative focal lordosis increased to 10.3° (4.3°–17.2°). At the final follow-up, there were five cases with subsidence of the cage, no case of recurrence, and no case with cage and screw loosening or migration. The mean preoperative VAS and ODI scores were 8.9 and 74.6%, respectively, and improvements in VAS and ODI were 6.6±2.2 and 50.4±21.3%, respectively. The Frankel grade D was found in 10 patients and grade C in 7. Following the final follow-up, only one patient improved from Frankel grade C to grade D while the others recovered completely. Conclusion. The PEEK cage and cadaveric allograft combined with local bone grafts is a safe and effective choice for intervertebral fusion and restoring sagittal alignment without increased incidence of relapse for treating lumbar pyogenic spondylodiscitis.

PurposeThe current study attempts to investigate the role of anterior cervical discectomy and fusion (ACDF) in alleviating symptoms in patients with cervical vertigo associated with cervical instability.MethodsThe patients of cervical instability with vertigo and dizziness who underwent ACDF between January 2011 and December 2019 were followed-up for more than two years. Demographic data (age, sex, follow up period and levels of instable cervical segments) were assessed; Symptoms of vertigo and dizziness before and after surgery were assessed by the 15-item version of the Vertigo Symptom Scale (VSS) and the 25-item Dizziness Handicap Inventory (DHI). The severity and frequency of other symptoms like neck and occipital pain, gastrointestinal discomfort, nausea, vomiting, tinnitus, palpitations, headache, diplopia and blurring of vision before and after surgery were also assessed.ResultsA total of 92 patients underwent ACDF for cervical instability with vertigo and dizziness between January 2011 and December 2019, of which 79 patients were included in the final analysis. The number of instable levels had no correlation with VSS and DHI scores before surgery (p > 0.05), while patients with C3/4 instability suffering a severer vertigo than other levels. Both DHI and VSS scores were significantly reduced after ACDF and this was sustained within two years after surgery (p

Aim: Drylands cover about 41% of Earth's land surface and are home to fragile biota with high levels of endemism. Two hypothetical models, i.e., cradle and museum, have been proposed to account for present‐day species diversity in an ecoregion or biome. We investigated macroevolutionary patterns to test these two different models in Nitrariaceae, a characteristic component of the Eurasian dryland ecosystem. We also used this family to explore the intercontinental disjunct distribution pattern between the deserts of Eurasia and western North America, known as the Madrean–Tethyan disjunction. Location: Drylands in the Northern Hemisphere. Taxon: Nitrariaceae (Sapindales, Angiosperms). Method: We sampled all 16 of the currently recognized extant species of Nitrariaceae and 59 species from the eight other families of Sapindales. A fossil‐calibrated phylogeny was generated using 12 fossil constraints. The ancestral range and climate niche of Nitrariaceae were reconstructed, and diversification rates were estimated. Results: The most recent common ancestor of Nitrariaceae likely inhabited arid habitats with low rainfall in the temperate zone in the Late Cretaceous, which geographically corresponds to present‐day Central Asia. The western North American Peganum mexicanum split from its Central Asian sister group at approximately 39 Ma. Net diversification rates of Nitrariaceae experienced a significant increase around 11 Ma. Within Sapindales, at least seven arid species originated markedly prior to the Miocene. Main Conclusions: The North Atlantic land bridge and global cooling climate in the Late Eocene might have driven the formation of the present‐day disjunct distribution of Nitrariaceae between arid Central Asia and western North America. Nitrariaceae originated in the Late Cretaceous and exhibited long‐term climate niche conservatism, but experienced a rapid diversification in the late Miocene of Eurasia in response to orogenetic and climatic changes. These findings suggest that Eurasian drylands serve as both evolutionary cradles and museums for the diversity of Nitrariaceae and likely for other arid‐adapted lineages. [ABSTRACT FROM AUTHOR]

The existing research on the impact of digital inclusive finance on corporate behaviour is relatively extensive, but the research on the impact of digital inclusive finance on corporate value is ignored. To fill in this gap, this study examines the impact of digital inclusive finance on firm value from the perspective of financing constraints, utilizing data on A-share listed companies in China from 2012 to 2019. We found that digital inclusive finance helps increase corporate value. And digital inclusive finance uses digital technology to alleviate financing constraints and improve the credit supply, which in turn increases firm value. Moreover, the impact of digital inclusive finance on firm value demonstrates heterogeneity. Compared with other firms, digital inclusive finance has a greater value-enhancing effect on small-scale and private firms. Our findings suggest that increasing the level of digital inclusive finance in developing countries can help enhance firm value. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a prevailing neurodegenerative disorder increasingly affecting the elderly population. The involvement of microRNAs (miRNAs) in PD has been confirmed. We sought to explore the molecular mechanism of miR‐20a‐5p in PD. Methods: Lipopolysaccharide (LPS)‐induced BV2 cell model and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine hydrochloride (MPTP‐HCl)‐induced PD mouse model were established. miR‐20a‐5p, inducible nitric oxide synthase (iNOS), interleukin (IL)‐6, tumour necrosis factor (TNF)‐α, transforming growth factor (TGF)‐β1, and IL‐10 expression in BV2 cells was examined by reverse transcription – quantitative polymerase chain reaction. Cell viability was assessed by MTT assay. The apoptotic rate and levels of Bcl‐2, Bax, cleaved caspase‐3, and signal transducer and activator of transmission (STAT)3 were examined by flow cytometry and Western blot. Bioinformatics software predicted the potential binding sites of miR‐20a‐5p and STAT3. Dual‐luciferase experiment verified the binding relationship. Iba1‐positive and tyrosine hydroxylase (TH)‐positive cell numbers in substantia nigra pars compacta were detected by immunohistochemistry. The effect of miR‐20a‐5p on motor function in MPTP‐induced PD mice was detected by Rota‐rod test, Pole test, Traction test and Beam‐crossing task. Results: miR‐20a‐5p was under‐expressed in LPS‐induced BV2 cells. Overexpression of miR‐20a‐5p increased the viability of LPS‐induced BV2 cells and reduced apoptosis rates. Moreover, overexpression of miR‐20a‐5p reduced cleaved caspase‐3, Bax, iNOS, IL‐6, and TNF‐α and increased Bcl‐2 and TGF‐β1, and IL‐10. miR‐20a‐5p targeted STAT3. STAT3 overexpression partially reversed miR‐20a‐5p overexpression‐mediated effects on LPS‐induced BV2 cell viability, apoptosis, and inflammatory responses. miR‐20a‐5p overexpression inhibited MPTP‐induced STAT3 and α‐synuclein levels, microglia activation, and inflammatory response, and reduced the loss of TH‐positive cells in mice. miR‐20a‐5p overexpression ameliorated MPTP‐induced dyskinesia in PD model mice. Conclusion: miR‐20a‐5p alleviates neuronal damage and suppresses inflammation by targeting STAT3 in PD. [ABSTRACT FROM AUTHOR]

This paper studies the joint impact of exporting and abatement on the environmental performance of Chinese manufacturers. For two common air pollutants (SO 2 and industrial dust) we document that (a) exporters are significantly less emissions-intensive relative to their nonexporting counterparts and (b) this difference cannot be explained by differential rates of abatement alone. Employing variation in trade and environmental conditions across time and space, we quantify the impact of endogenous export and abatement decisions on firm-level emissions. We find that exporting reduces emissions by at least 36% across pollutants. We explore underlying determinants of export-driven reductions in emissions intensity. [ABSTRACT FROM AUTHOR]

Abstract Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K–AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53–Nedd4–Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

Abstract Intrahepatic cholangiocarcinoma is a malignant tumor originating from intrahepatic bile ducts. Surgical therapy, radiotherapy, and chemotherapy are taken to treat this disease, but it is prone to recurrence and metastasis, with poor prognosis. Therefore, it is of great significance to explore new targets and molecular mechanisms for the development of cholangiocarcinoma cells. Clinical cholangiocarcinoma tissues from patients and four human cholangiocarcinoma cell lines were analyzed for microRNA‐373 (miR‐373) expression. For investigating whether miR‐373 directly modulated unc‐51 like autophagy activating kinase 1 (ULK1), dual‐luciferase reporter assay was performed. In addition, CCK‐8 assay, flow cytometry, western blot, and immunofluorescence were applied to evaluate the proliferation, apoptosis, and autophagy of cholangiocytic hepatocellular carcinoma cells. miR‐373 downregulation was observed in clinical tissues and cell lines of cholangiocarcinoma. Overexpression of miR‐373 reduced proliferation, enhanced apoptosis, and raised expression levels of pro‐apoptosis proteins including BCL2 associated X (Bax), Caspase‐3, and Caspase‐9. Moreover, overexpression of miR‐373 downregulated expression levels of microtubule‐associated protein 1A/1B‐light chain 3 (LC3)‐II, Beclin‐1, and promoted P62 expression on mRNA and protein levels. After miR‐373 knockdown, all indexes of apoptosis and autophagy mentioned above were reversed. Luciferase activity was decreased after cotransfection of miR‐373 mimic and wild‐type ULK1 vector. Also, miR‐373 overexpression inhibited ULK1 expression. Importantly, overexpression of miR‐373 weakened expressions of ULK1, LC3, Beclin‐1, and Bcl‐2, and enhanced expressions of P62, Bax, Caspase‐3, and Caspase‐9. miR‐373 mimic treatment and subsequent ULK1 overexpression, induced reverse regulation in expressions of these proteins, compared with overexpression of miR‐373 only. miR‐373 targeted ULK1 to initiate inhibition of autophagy and subsequent promotion of apoptosis in cholangiocarcinoma cells.