Mitochondrial dynamics modulate the allergic inflammation in a murine model of allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is a common allergic disorder, afflicting thousands of human beings. Aberrant mitochondrial dynamics are important pathological elements for various immune cell dysfunctions and allergic diseases. However, the connection between mitochondrial dynamics and AR remains poorly understood. This study aimed to determine whether mitochondrial dynamics influence the inflammatory response in AR. METHODS: In the present study, we established a murine model of AR by sensitization with ovalbumin (OVA). Then, we investigated the mitochondrial morphology in mice with AR by transmission electron microscopy and confocal fluorescence microscopy, and evaluated the role of Mdivi-1 (an inhibitor of mitochondrial fission) on allergic symptoms, inflammatory responses, allergic-related signals, and reactive oxygen species formation. RESULTS: There was a notable enhancement in mitochondrial fragmentation in the nasal mucosa of mice following OVA stimulation, whereas Mdivi-1 prevented aberrant mitochondrial morphology. Indeed, Mdivi-1 alleviated the rubbing and sneezing responses in OVA-sensitized mice. Compared with vehicle-treated ones, mice treated with Mdivi-1 exhibited a reduction in interleukin (IL)-4, IL-5, and specific IgE levels in both serum and nasal lavage fluid, and shown an amelioration in inflammatory response of nasal mucosa. Meanwhile, Mdivi-1 treatment was associated with a suppression in JAK2 and STAT6 activation and reactive oxygen species generation, which act as important signaling for allergic response. CONCLUSION: Our findings reveal mitochondrial dynamics modulate the allergic responses in AR. Mitochondrial dynamics may represent a promising target for the treatment of AR.

Identification of a novel isolated 4q35.2 microdeletion in a Chinese pediatric patient using chromosomal microarray analysis: a case report and literature review.

BACKGROUND: Isolated terminal 4q35.2 microdeletion is an extremely rare copy number variant affecting people all over the world. To date, researchers still have controversial opinions and results on its pathogenicity. Here, we aim to present a Chinese pediatric patient with terminal 4q35.2 microdeletion and use this case to clarify the underlying genotype-phenotype correlation. METHODS: A 17-year-old boy from Quanzhou, South China, was recruited as the main subject in this study. Karyotype and single-nucleotide polymorphism (SNP) based microarray analysis were carried out to detect chromosomal abnormalities and copy number variants in this family. Trio whole exome sequencing (Trio-WES) was performed to investigate the potential pathogenic variant in this family. RESULTS: During observation, we identified abnormal clinical phenotypes including upper eyelid ptosis, motor developmental delay, abnormal posturing, abnormality of coordination, attention deficit hyperactivity disorder, and involuntary movements in the patient. SNP array analysis results confirmed a case of 2.0 Mb 4q35.2 microdeletion and parental SNP array verification results indicated that the terminal 4q35.2 microdeletion was inherited from his mother. No copy number variants were detected in his father. In addition, the trio-WES results demonstrated none of pathogenic or likely pathogenic variants in the patient. CONCLUSIONS: This study brings a novel analysis of a case of 2.0 Mb terminal 4q35.2 microdeletion affecting a Chinese individual. In addition, additional clinical symptoms such as upper eyelid ptosis and involuntary movements were first reported to affect a patient with terminal 4q35.2 microdeletion, which may broaden the phenotype spectrum of the condition.

Prenatal whole exome sequencing identified two rare compound heterozygous variants in EVC2 causing Ellis-van Creveld syndrome.

BACKGROUND: Pathogenic mutations in EVC or EVC2 gene can lead to Ellis-van Creveld (EvC) syndrome, which is a rare autosomal recessive skeletal dysplasia disorder. This study aimed to determine pathogenic gene variations associated with EvC syndrome in fetuses showing ultrasound anomalies. METHODS: A 32-year-old pregnant woman from Quanzhou, China was investigated. In her pregnancy examination, the fetus exhibited multiple fetal malformations, including a narrow thorax, short limbs, postaxial polydactyly, cardiac malformations, and separation of double renal pelvis. Karyotype, chromosomal microarray analysis and whole exome sequencing were performed for prenatal genetic etiology analysis. RESULTS: Chromosome abnormalities and copy number variants were not observed in the fetus using karyotype and chromosomal microarray analysis. Using whole exome sequencing, two compound heterozygous variants NM_147127.5:c.[2484G>A(p.Trp828Ter)];[871-2_894del] in EVC2 gene were identified in the fetus as pathogenic variants inherited from parents. CONCLUSIONS: The study is the first to identify two rare compound variants in EVC2 gene in a Chinese family using whole exome sequencing. The application of whole-exome sequencing would be helpful in fetal etiological diagnosis with ultrasound anomalies.

Role of microglial metabolic reprogramming in Parkinson's disease.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Parkinson's Disease as a Risk Factor for Prostate Adenocarcinoma: A Molecular Point of View.

INTRODUCTION: Cancer and neurodegeneration are two major leading causes of morbidity and death worldwide. Neurodegeneration results in excessive neuronal cell death, and cancer emerges from increased proliferation and resistance to cell death. Although most epidemiological studies support an inverse association between the risk for the development of neurodegenerative diseases and cancer, increasing evidence points to a positive correlation between specific types of cancer, like prostate adenocarcinoma (PRAD), and neurodegenerative diseases, like Parkinson's disease (PD). METHODS: PD and PRAD differential genes were screened through the GEO database, and the differential genes were analyzed using David, String, GEPIA, Kaplan-Meier plotter, TIMER2.0, proteinatlas, cBioPortal, and CTD databases to elucidate the biological function and molecular mechanism of PD and PRAD-related genes. RESULTS: Studies have shown that the hub gene and differentially expressed genes (DEGs) in PD were differentially expressed in PRAD, including CDC20, HSPA4L, ROBO1, DMKN, IFI27L2, LUZP2, PTN, PTGDS. In PRAD, the high expression of HSPA4L, ROBO1, DMKN, IFI27L2, PTN, and PTGDS genes was associated with longer survival, while the patients with low expression of CDC20 and LUZP2 genes had longer survival. The mRNA of CDC20 and LUZP2 were highly expressed, while the mRNAs of HSPA4L, ROBO1, DMKN, IFI27L2, and PTGDS were low expressed. Gene methylation did not affect the survival of patients. The high expression of miR-142, miR-186, miR-30a, miR-497, miR-590, miR-28, and miR-576 in microRNA (miRNA) might potentially be used as biomarkers for the progression of PD and PRAD and for the early diagnosis of PD and PRAD in the populations. The genes in this study were highly associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Somatic mutation mainly focused on missense mutation. Therapeutic drugs included acetaminophen and valproic acid (VPA). CONCLUSION: Bioinformatics was used to identify potential targets and novel molecular mechanisms that may serve as clinical markers for the diagnosis and treatment of PD and PRAD.

Shikonin inhibits neuronal apoptosis via regulating endoplasmic reticulum stress in the rat model of double-level chronic cervical cord compression.

Cervical spondylotic myelopathy (CSM) is a clinically symptomatic entity arising from the spinal cord compression by degenerative diseases. Although endoplasmic reticulum (ER) stress has been commonly observed in several neurodegenerative diseases, the relationship between ER stress and CSM remains unknown. Shikonin is known to protect PC12 by inhibiting apoptosis in vitro. This study hypothesised that ER stress was vital in neuronal apoptosis in CSM. Shikonin might inhibit such responses by regulating ER stress through the protein kinase-like ER kinase-eukaryotic translation initiation factor 2 α-subunit-C/EBP homologous protein (PERK-eIF2α-CHOP) signalling pathway. Thus, the aim of this study was evaluating the neuroprotective effect of shikonin in rats with double-level chronic cervical cord compression, as well as primary rat cortical neurons with glutamate-induced neurotoxicity. The result showed that ER stress-related upregulation of PERK-eIF2α-CHOP resulted in rat neuronal apoptosis after chronic cervical cord compression; then, shikonin promoted motor recovery and inhibited neuronal apoptosis by attenuating PERK-eIF2α-CHOP and prevented Bax translocation from cytoplasm to mitochondrion induced by CHOP of neurons in rats with chronic compression. Also, it was found that shikonin could protect rat primary cortical neuron against glutamate toxicity by regulating ER stress through the PERK-eIF2α-CHOP pathway in vitro. In conclusion, shikonin might inhibit neuronal apoptosis by regulating ER stress through attenuating the activation of PERK-eIF2α-CHOP.

Recent research progress on metabolic syndrome and risk of Parkinson's disease.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Update on the application of mesenchymal stem cell-derived exosomes in the treatment of Parkinson's disease: A systematic review.

Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.

Bone marrow stromal cells attenuate oxygen and glucose deprivation followed by re­oxygenation­induced brain microvascular endothelial cell injury.

Ischemic stroke is a severe threat to the health of older individuals. Bone marrow mesenchymal stem cells (BMSCs) have been implicated in ischemic stroke. Urokinase­type plasminogen activator (uPA) and its specific receptor (uPAR) are associated with the pathological process of ischemic stroke. However, the relationship between BMSCs and uPA/uPAR in ischemic stroke remains unclear. For simulating the occurrence of an ischemic stroke in vitro, human cerebral microvascular endothelial cells (HBMECs) were subjected to oxygen and glucose deprivation followed by re­oxygenation (OGD/R) and were then cocultured with BMSCs. 3,4,5­dimethylthiazol­2,5­diphenyltetrazolium bromide and bromodeoxyuridine staining were used for measuring cell viability and proliferation. Flow cytometry was performed for assessing cell apoptosis. Endothelial cell tube formation was determined using angiogenesis assays. Alterations in the protein and gene expression in HBMECs were evaluated using western blot analysis and quantitative reverse transcription­polymerase chain reaction, respectively. OGD/R considerably inhibited the viability and proliferation of HBMECs by inducing apoptosis, which was reversed by BMSCs. Consistently, OGD/R­induced inhibition of angiogenesis was attenuated by BMSCs. In addition, BMSCs could protect HBMECs against OGD/R­induced injury by positively regulating the uPA/uPAR/stromal cell­derived factor­1α (SDF­1α)/C­X­C chemokine receptor type 4 (CXCR4) pathway, and uPA/uPAR could mediate the SDF­1α/CXCR4 pathway in OGD/R­treated HBMECs. Therefore, this study provides novel strategies to investigate the specific role of BMSCs in ameliorating OGD/R­induced vascular endothelial cell injury.

Neuroinflammation and apoptosis after surgery for a rat model of double-level cervical cord compression.

INTRODUCTION: Cervical spondylotic myelopathy (CSM) is the most prevalent type of non-traumatic spinal cord injury. The pathological process of CSM is relatively complicated. Most of the chronic cervical cord compression animal models established using hydrophilic expanding polymer are single-segment compression, which was deviated from clinical practice with double-segment or multi-segment compression. This study aims to better mimic the actual clinical compression by using a new type of hydrophilic expanding polymer to establish an animal model of double-level cervical cord compression. MATERIALS AND METHODS: Progressive cord compression was done with implantation of polyvinyl alcohol-polyacrylamide hydrogel in the spinal canal at the C3-4 and C5-6 levels. Sprague-Dawley rats (n = 32) were divided into three groups: sham (no compression, n = 12) and screw compression group (n = 8), and hydrogel compression group (n = 12). Functional deficits were characterized using motor function scores, forelimb grip strength, hindlimb pain threshold, and gait analysis, while compression was imaged with magnetic resonance imaging. The apoptosis, inflammation, and demyelination were assessed by hematoxylin and eosin staining, Luxol fast blue staining, TUNEL assay, immunofluorescence staining, and Western blot analysis. RESULTS: Motor function scores for rats with cervical cord hydrogel compression were significantly decline in motor function scores, an increase in allodynia, neurons and oligodendrocytes apoptosis related to B cell lymphoma-2 (Bcl-2)/Bcl-2 associated X (Bax)/cleaved caspase-3, and impaired axonal conduction, as well as neuroinflammation zone related to microglia or macrophages aggregation related to the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome activation, and activation of astrocytes, as well as oxidative stress were observed. CONCLUSION: We believe that this model utilizing compression on double-level cervical cord will allow researchers to investigate of translationally relevant therapeutic methods for CSM.

Vitamin D/Vitamin D Receptor Signaling Attenuates Skeletal Muscle Atrophy by Suppressing Renin-Angiotensin System.

The nutritional level of vitamin D may affect musculoskeletal health. We have reported that vitamin D is a pivotal protector against tissue injuries by suppressing local renin-angiotensin system (RAS). This study aimed to explore the role of the vitamin D receptor (VDR) in the protection against muscle atrophy and the underlying mechanism. A cross-sectional study on participants (n = 1034) in Shanghai (China) was performed to analyze the association between vitamin D level and the risk of low muscle strength as well as to detect the circulating level of angiotensin II (Ang II). In animal studies, dexamethasone (Dex) was applied to induce muscle atrophy in wild-type (WT) and VDR-null mice, and the mice with the induction of muscle atrophy were treated with calcitriol for 10 days. The skeletal muscle cell line C2C12 and the muscle satellite cells were applied in in vitro studies. The increased risk of low muscle strength was correlated to a lower level of vitamin D (adjusted odds ratio [OR] 0.58) accompanied by an elevation in serum Ang II level. Ang II impaired the myogenic differentiation of C2C12 myoblasts as illustrated by the decrease in the area of myotubes and the downregulation of myogenic factors (myosin heavy chain [MHC] and myogenic differentiation factor D [MyoD]). The phenotype of muscle atrophy induced by Dex and Ang II was aggravated by VDR ablation in mice and in muscle satellite cells, respectively, and mediated by RAS and its downstream phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FOXO1) signaling. Calcitriol treatment exhibited beneficial effects on muscle function as demonstrated by the increased weight-loaded swimming time, grip strength, and fiber area, and improved fiber type composition via regulating ubiquitin ligases and their substrates MHC and MyoD through suppressing renin/Ang II axis. Taken together, VDR protects against skeletal muscle atrophy by suppressing RAS. Vitamin D could be a potential agent for the prevention and treatment of skeletal muscle atrophy. © 2021 American Society for Bone and Mineral Research (ASBMR).

Influences of Thoracic Spinal Deformity on Exercise Performance and Pulmonary Function: A Prospective Study of 168 Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the factors associated with cardiopulmonary exercise testing (CPET) measurements in patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Patients with AIS display restrictive pulmonary dysfunction on pulmonary function testing (PFT). It remains unknown whether thoracic spinal deformity affects exercise performance. METHODS: One hundred and sixty-eight patients with AIS from January 2014 to December 2019 were included. They underwent preoperative spinal radiological assessment, PFT, and CPET. The effects of the thoracic curve magnitude, body mass index, physical activity level and history of bracing on pulmonary function and exercise performance were analyzed. The Student t test and two-tailed Pearson test were used in data analysis. RESULTS: We found significantly reduced forced expiratory volume in 1second (FEV1) in patients with a larger magnitude of the proximal thoracic curve (P < 0.001) and the main thoracic curve (P < 0.001). There was a negative correlation between forced vital capacity (FVC) and the magnitude of the main thoracic curve (P < 0.001) and thoracic hypokyphosis (P < 0.001). In CPET, exercise capacity indicators such as the work rate, peak oxygen intake, and heart rate were not affected by the thoracic curve magnitude. Patients with moderate or severe pulmonary dysfunction had decreased tidal volume (P = 0.01) and ventilatory reserve (P < 0.001), as well as increased respiratory frequency at maximal exercise (P = 0.01). Patients with a moderate or high physical activity level had better exercise capacity, which was reflected by a higher work rate (P = 0.009) and oxygen intake (P < 0.001). CONCLUSION: There was no significant correlation between radiographic parameters and exercise capacity indicators. When the thoracic curve increased, patients had restrictive ventilatory dysfunction, which led to a tachypneic breathing pattern and reduction of ventilatory reserve during exercise. A physiological change of improved peak oxygen intake was demonstrated in patients with a moderate or high physical activity level.Level of Evidence: 3.

Structural elucidation and anti-diabetic osteoporotic activity of an arabinogalactan from Phellodendron chinense Schneid.

Phellodendron chinense Schneid. was widely used as a medicinal herb for the treatment of diabetic osteoporosis in China. In this study, an arabinogalactan, named as PPCP-1, was isolated from the bark of Phellodendron chinense Schneid., and purified by DEAE-cellulose DE52 and Sephacryl S-200 HR column chromatography. The structure of PPCP-1 was characterized as a repeating unit consisting of →3)-ß-d-Galp-(1→, →3,6)-ß-d-Galp-(1→, →5)-α-l-Araf-(1→, →4)-α-d-Glcp-(1→, →3)-α-d-Glcp-(1→, →4)-α-d-Manp-(1→ with branches of →5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→ and terminal α-l-Araf. Pharmacologically, the oral administration of PPCP-1 preserved osteoporosis associated with hyperglycemia by inhibiting α-glucosidase activity, improving glucose tolerance, decreasing the accumulation of advanced glycation end products (AGEs), as well as down-regulating the expression of receptor for AGEs in tibias of streptozotocin-induced diabetic rats. Collectively, the present study suggested that the arabinogalactan PPCP-1 from Phellodendron chinense Schneid. might potentially be used as functional foods for bone health and/or developed for drug discovery for alleviating diabetic osteoporosis.

Preparation of Naringenin Solution for In Vivo Application.

The preparation of a compound (phytochemical) solution is an overlooked but critical step prior to its application in studies such as drug screening. The complete solubilization of the compound is necessary for its safe use and relatively stable results. Here, a protocol for preparing naringenin solution and its intraperitoneal administration in a high-fat diet and streptozotocin (STZ)-induced diabetic model is demonstrated as an example. A small amount of naringenin (3.52-6.69 mg) was used to test its solubilization in solvents, including ethanol, dimethylsulfoxide (DMSO), and DMSO plus Tween 80 reconstituted in physiological saline (PS), respectively. Complete solubilization of the compound is determined by observing the color of the solution, the presence of precipitates after centrifugation (2000 x g for 30 s), or allowing the solution to stand for 2 h at room temperature (RT). After obtaining a stable compound/phytochemical solution, the final concentration/amount of the compound required for in vivo studies can be prepared in a solvent-only (no PS) stock solution, and then diluted/mixed with PS as desired. The antidiabetic osteoporotic effects of naringenin in mice (intraperitoneal administration at 2 mg/mL) were assessed by measuring blood glucose, bone mass (micro-CT), and bone resorption rate (TRAP staining and ELISA). Researchers looking for detailed organic/phytochemical solution preparations will benefit from this technique.

A Neuronal Apoptosis Model induced by Spinal Cord Compression in Rat.

As a severe progressive degenerative disease, cervical spondylotic myelopathy (CSM) has a poor prognosis and is associated with physical pain, stiffness, motor or sensory dysfunction, and a high risk of spinal cord injury and acroparalysis. Thus, therapeutic strategies that promote efficient spinal cord regeneration in this chronic and progressive disease are urgently needed. Effective and reproducible animal spinal cord compression models are required to understand the complex biological mechanism underlying CSM. Most spinal cord injury models reflect acute and structural destructive conditions, whereas animal models of CSM present a chronic compression in the spinal cord. This paper presents a protocol to generate a rat spinal cord compression model, which was further evaluated by assessing the behavioral score and observing the compressed spinal cord region. The behavioral assessments showed decreased monitor motor disability, including joint movements, stepping ability, coordination, trunk stability, and limb muscle strength. Hematoxylin and eosin (H&E) staining and immunostaining revealed considerable neuronal apoptosis in the compressed region of the spinal cord.

Anti-HCV antibody titer highly predicts HCV viremia in patients with hepatitis B virus dual-infection.

BACKGROUND/AIMS: Hepatitis C Virus (HCV) infection is diagnosed by the presence of antibody to HCV and/or HCV RNA. This study aimed to evaluate the accuracy of anti-HCV titer (S/CO ratio) in predicting HCV viremia in patients with or without hepatitis B virus (HBV) dual infection. METHODS: Anti-HCV seropositive patients who were treatment-naïve consecutively enrolled. Anti-HCV antibodies were detected using a commercially chemiluminescent microparticle immunoassay. HCV RNA was detected by real-time PCR method. RESULTS: A total of 1321 including1196 mono-infected and 125 HBV dually infected patients were analyzed. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001). Of the entire cohort, the anti-HCV cut-off value of 10 provided the best accuracy, 96.8%, with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96.3%, 98.9%, 99.7% and 87.3% respectively. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001) and 9.36 (AUROC 1.00, P<0.0001) in patients with HCV mono-infection and HBV dual-infection respectively. Among the HBV dually infected patients, the accuracy of anti-HCV titer in predicting HCV viremia reached up to 100% with the cut-off value of 9. All the patients were HCV-viremic if their anti-HCV titer was greater than 9 (PPV 100%). On the other hand, all the patients were HCV non-viremic if their anti-HCV titer was less than 9 (NPV 100%). CONCLUSIONS: Anti-HCV titer strongly predicted HCV viremia. This excellent performance could be generalized to either HCV mono-infected or HBV dually infected patients.

Is physical capacity correlated with health-related quality of life in patients with adolescent idiopathic scoliosis?

BACKGROUND: There have been no report about the association between physical capacity and health-related quality of life in patients with adolescent idiopathic structural scoliosis (AIS). This study aims to investigate the correlation between dynamic cardiopulmonary capacity and quality of life in AIS patients. METHODS: This retrospective study involved 63 patients. Correlations between cardiopulmonary exercise test parameters and Scoliosis Research Society (SRS)-22 scores were evaluated using Spearman's correlation test. RESULTS: Fifty-four female patients [mean age: 14.1 (range, 10-19) years] and 9 male patients [15.9 (range, 14-19) years] with AIS (Cobb angle: 28°-86°) were included. Significant correlations were found between the peak oxygen uptake normalized by body weight and the SRS-22 scores in female patients, as reflected by the function (r=0.511, P<0.001), pain (r=0.418, P=0.002), mental health (r=0.536, P<0.001) and subtotal (r=0.618, P<0.001) scores. Significant correlations were also found between oxygen uptake at anaerobic threshold normalized by body weight and the SRS-22 scores in female patients, as reflected by the function (r=0.404, P=0.002), pain (r=0.455, P=0.001), and subtotal (r=0.501, P<0.001) scores, along with respiratory exchange ratio reflected by subtotal (r=0.464, P<0.001) score. CONCLUSIONS: The physical capacity and capacity for the exercise intensity and endurance correlated with quality of life among patients with AIS. Exercise may better the quality of life of patients with AIS.

A Mouse Model of Lumbar Spine Instability.

Intervertebral disc degeneration (IDD) is a common pathological change leading to low back pain. Appropriate animal models are desired for understanding the pathological processes and evaluating new drugs. Here, we introduced a surgically induced lumbar spine instability (LSI) mouse model that develops IDD starting from 1 week post operation. In detail, the mouse under anesthesia was operated by low back skin incision, L3-L5 spinous processes exposure, detachment of paraspinous muscles, resection of processes and ligaments, and skin closure. L4-L5 IVDs were chosen for the observation. The LSI model develops lumbar IDD by porosity and hypertrophy in endplates at an early stage, decrease in intervertebral disc volume, shrinkage in nucleus pulposus at an intermediate stage, and bone loss in lumbar vertebrae (L5) at a later stage. The LSI mouse model has the advantages of strong operability, no requirement of special equipment, reproducibility, inexpensive, and relatively short period of IDD development. However, LSI operation is still a trauma that causes inflammation within the first week post operation. Thus, this animal model is suitable for study of lumbar IDD.

Role of hepatitis D virus infection in development of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleotide/nucleoside analogues.

Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11-19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35-24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03-6.54, P < 0.001), male gender (HR/CI 2.69/1.29-5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03-1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04-19.09, P = 0.04) and BMI (HR/CI 1.11/1.03-1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.

Transcriptomic alterations underline aging of osteogenic bone marrow stromal cells.

BACKGROUND: Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo. AIM: To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss. METHODS: We collected BMSCs from mice at early to middle ages and compared their self-renewal and differentiation potential. Subsequently, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo. RESULTS: The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo. The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features. CONCLUSION: Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.