Exploring the pharmacological mechanism of Glycyrrhiza uralensis against KOA through integrating network pharmacology and experimental assessment.

Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC-Q-TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM-induced osteoarthritic mice was assessed by histomorphology, µCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM-induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC-Q-TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL-17, NF-κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti-inflammatory-related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM-induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis.

Ursolic acid alleviates steroid-induced avascular necrosis of the femoral head in mouse by inhibiting apoptosis and rescuing osteogenic differentiation.

Steroid-induced avascular necrosis of femoral head (SANFH) is a common disorder worldwide with high disability. Overdose of glucocorticoid (GC) is the most common non-traumatic cause of SANFH. Up until now, there are limited therapeutic strategies for curing SANFH, and the mechanisms underlying SANFH progression remain unclear. Nevertheless, Osteogenic dysfunction is considered to be one of the crucial pathobiological mechanisms in the development of SANFH, which involves mouse bone marrow mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation disorder. Ursolic acid (UA), an important component of the Chinese medicine formula Yougui Yin, has a wide range of pharmacological properties such as anti-tumor, anti-inflammatory and bone remodeling. Due to the positive effect of Yougui Yin on bone remodeling, the purpose of this study was to investigate the effects of UA on dexamethasone (DEX)-induced SANFH in vitro and vivo. In vitro, we demonstrated that UA can promote mouse BMSCs proliferation and resist DEX-induced apoptosis by CCK8, Western blotting, TUNEL and so on. In addition, vitro experiments such as ALP and Alizarin red staining assay showed that UA had a beneficial effect on the osteogenic differentiation of mouse BMSCs. In vivo, the results of H&E staining, immunohistochemistry staining, Elisa and micro-CT analysis showed that UA had a bone repair-promoting effect in SANFH model. Moreover, the results of Western blot and TUNEL experiments showed that UA could delay the disease progression of SANFH in mice by inhibiting apoptosis. Overall, our study suggests that UA is a potential compound for the treatment of SANFH.

Age-Related Insulin-Like Growth Factor Binding Protein-4 Overexpression Inhibits Osteogenic Differentiation of Rat Mesenchymal Stem Cells.

BACKGROUND/AIMS: Insulin-like growth factor binding proteins (IGFBP) play important roles in bone metabolism. IGFBP4 is involved in senescent-associated phenomena in mesenchymal stem cells (MSCs). The goal of the present study was to determine whether age-related IGFBP4 overexpression is associated with the impaired osteogenic differentiation potential of aged bone marrow derived MSCs. METHODS: MSCs were isolated from Sprague-Dawley rats aged 3-26 months. The bone morphogenetic protein (BMP)-2-induced osteogenic differentiation of rat MSCs was assessed by analyzing the expression levels of osteoblast marker genes [runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteocalcin (OC)], ALP activity and calcification. RESULTS: Our study showed that IGFBP4 mRNA and protein expression increased with age in parallel with impaired osteogenic differentiation of MSCs cultured in BMP2-containing osteogenic medium, as evidenced by the downregulation of osteoblast marker genes, and decreased ALP activity and calcium deposits. IGFBP4 overexpression impaired BMP2-induced osteogenic differentiation potential of young MSCs, whereas IGFBP4 knockdown restored the osteogenic potency of aged MSCs. Moreover, IGFBP4 knockdown stimulated the activation of Erk and Smad by increasing phosphorylation. CONCLUSION: Collectively, our results demonstrate that IGFBP4 overexpression plays a role in the impairment of MSC differentiation potential via the Erk and Smad pathways, suggesting potential targets to improve MSC function for cell therapy applications.

Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway.

Chondrosarcomas (CS) is the second most frequent tumors of cartilage origin. A small compound extracted from Thunder God Vine (Tripterygium wilfordii Hook. F.) called celastrol can directly bound CIP2A protein and effectively inhibit cell proliferation and induce apoptosis in several cancer cells. However, little knowledge is concern about the important role of CIP2A in CS patients and the therapeutic value of celastrol on CS. Our results showed that CIP2A and c-MYC were verified to be oncoproteins by detecting their mRNA and protein expression in 10 human CS tissues by qRT-PCR and Western blots. After treatment of celastrol, the proliferation, migration and invasion were significantly inhibited; whereas the apoptosis was largely induced in human CS cell lines. In addition, celastrol inhibited the expression of CIP2A, c-MYC, and suppressed apoptotic proteins BAX and caspase-8 in human CS cells, on the other hand, it induced the expression of antiapoptotic protein Bcl-2. Finally, knockdown of CIP2A also inhibited the migration and invasion and induced apoptosis of human CS cells. To sum up, we found that celastrol had effects on inhibiting proliferation, migration, invasion and inducing apoptosis through suppression CIP2A/c-MYC signaling pathway in vitro, which may provide a new therapeutic regimen for CS.

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA.

Osteosarcoma has become one of the most common primary malignant bone tumors in childhood and adult. Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. Herein, we showed that miR-375 was frequently downregulated in osteosarcoma tissue and cell lines compared to normal human colon tissues. Overexpression of miR-375 resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-375 overexpression markedly suppressed cell proliferation in vitro. And inhibition of miR-375 promotes osteosarcoma growth. Mechanistic studies showed that PIK3CA was a potential target of miR-375 and it mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. Taken together, our results demonstrate that miR-375 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in osteosarcoma.

Association of single nucleotide polymorphisms of nucleotide excision repair genes with laryngeal cancer risk and interaction with cigarette smoking and alcohol drinking.

We investigated the potential association of 12 single nucleotide polymorphisms (SNPs) of nucleotide excision repair (NER) genes with risk of laryngeal cancer. A ratio of 1:1 matched case-control study was conducted. Conditional regression analysis indicated that subjects with ERCC1 rs11615 CC and C allele had an increased risk of laryngeal cancer compared with the TT genotype. Individuals with the ERCC5 rs17655 GG and G allele had a moderately increased risk of laryngeal cancer when compared with the CC genotype. By stratified analysis, ERCC1 rs11615 CC genotype and C allele were significantly associated with greatly increased risk of laryngeal cancer in ever smokers. ERCC1 rs11615 and ERCC5 rs17655 polymorphisms were associated with a moderately increased risk of this cancer in ever drinkers. In summary, we suggest that genetic variations in ERCC1 rs11615 and ERCC5 rs17655 are associated with laryngeal cancer risk in a Chinese population, especially in ever smokers and drinkers. Our finding could be helpful in identifying people at high risk for the disease for early intervention.

Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions.

Introduction: Despite the protection and management of skin has been paid more and more attention, effective countermeasures are still lacking for patients suffering from UV or chemotherapy with damaged skin. Recently, gene therapy by small interfering RNA (siRNA) has emerged as a new therapeutic strategy for skin lesions. However, siRNA therapy has not been applied to skin therapy due to lack of effective delivery vector. Methods: Here, we develop a synthetic biology strategy that integrates the exosomes with artificial genetic circuits to reprogram the adipose mesenchymal stem cell to express and assemble siRNAs into exosomes and facilitate in vivo delivery siRNAs for therapy of mouse models of skin lesions. Results: Particularly, siRNA enriched exosomes (si-ADMSC-EXOs) could be directly taken up by the skin cells to inhibit the expression of skin injury related genes. When mice with skin lesions were smeared with si-ADMSC-EXOs, the repair of lesioned skin became faster and the expression of inflammatory cytokines were decreased. Discussion: Overall, this study establishes a feasible therapeutic strategy for skin injury, which may offer an alternative to conventional biological therapies requiring two or more independent compounds.

Laryngocele: Report of two rare cases and review of the literature.

Laryngocele is a rare clinical condition characterized by an abnormal dilation of the laryngeal saccule. The present study focused on two separate cases of diagnosed patients. The first patient suffered from internal laryngocele and complained of hoarseness for almost 1 year. Plasma was used to treat the internal laryngocele and the outcomes were satisfying. The patient did not undergo any tracheostomy due to previous endoscopic surgery. The second patient included in the present study was diagnosed with mixed laryngocele and complained of swelling on the left side of the upper aspect of the neck with considerable pain for >1 month. The patient was prepped for excision by an external transcervical technique under general anesthesia. None of the two patients had any recurrence or other changes during follow-up. The purpose of reporting these two cases of laryngocele was to increase awareness of this condition. Surgery is still the first-line treatment for diagnosed cases, but with the advent of new microscopic techniques, the use of plasma in an inter-pharynx setting has become more common. The results observed after using plasma to treat one internal laryngocele may be relevant to better understanding the application of this method and confirm that it may be a new suitable approach to treat this condition.

Systemic immune-inflammation index is associated with decreased bone mass density and osteoporosis in postmenopausal women but not in premenopausal women.

Purpose: This study aims to investigate the associations of the systemic immune-inflammation index (SII) with bone mineral density (BMD) and osteoporosis in adult females from a nationally representative sample. Methods: A cross-sectional study was performed among 4092 females aged ≥20 years from the National Health and Nutrition Examination Survey 2007-2010. Linear and logistic regressions were applied to explore the relationships of SII with BMD and the risk of osteoporosis, respectively. Results: Linear regression analyses found that a doubling of SII levels was significantly correlated with a 1.39% (95% CI: 0.57%, 2.20%) decrease in total femur BMD, a 1.16% (95% CI: 0.31%, 2.00%) decrease in femur neck BMD, a 1.73% (95% CI: 0.78%, 2.66%) decrease in trochanter BMD, and a 1.35% (95% CI: 0.50%, 2.20%) decrease in intertrochanteric BMD among postmenopausal women, after adjusting for covariates. Logistic regression analyses showed that compared with postmenopausal women in the lowest SII quartile, those in the highest quartile had higher risks of osteoporosis in the total femur (odds ratio (OR) = 1.70, 95% CI: 1.04, 2.76), trochanter (OR = 1.86, 95% CI: 1.07, 3.38), intertrochanter (OR = 2.01, 95% CI: 1.05, 4.04) as well as overall osteoporosis (OR = 1.57, 95% CI: 1.04, 2.37). In contrast, there was no significant association between SII and BMD in premenopausal women. Conclusions: SII levels were negatively associated with BMD levels in postmenopausal women but not in premenopausal women. Elevated SII levels could be a potential risk factor for osteoporosis in postmenopausal women.

A case report of solitary fibrous tumor of the thyroid gland and literature review.

RATIONALE: A solitary fibrous tumor (SFT) is an uncommon soft tissue tumor that was first discovered in the pleura. Although SFTs have been documented in other extra-pleural sites, an SFT in the thyroid gland is highly unusual. An SFT of the thyroid gland can be difficult to diagnose, and there is little information about their Underlying biological behavior. PATIENT CONCERNS: We present a case of a 63-year-old man with a progressively growing left-neck mass detected 1 month ago, which was pathologically confirmed to be a benign SFT of the thyroid gland. DIAGNOSIS: Postoperative pathological examination of the tumor revealed an SFT. Immunopathological examination was consistent with the diagnosis of an SFT. INTERVENTIONS: The patient underwent surgical resection of the SFT. OUTCOMES: The patient was recurrence-free during 1.5 years of follow-up. LESSONS: Surgical excision is beneficial in SFTs that show no histological signs of malignancy, such as pleomorphism, enhanced mitotic activity, necrosis, bleeding, or capsular invasion. However, because the biologic activity remains unknown, meticulous long-term monitoring is required.

Infrared Raman spectroscopy enables noninvasive biochemical assessment of skin tissue and the thermal stability.

Raman-active modes of human skin and pork belly have been studied systematically by a near-infrared Raman spectrometer with an exciting laser of 1064 nm. The main components and quantitative determination of pork belly are extracted by fitting the Raman spectra with the normalized Raman spectra of biochemical reagents such as collagen, elastin, triolein, fibronectin, fibrin, and hyaluronic acid. It demonstrates that the main components and quantity are various at different locations of pork belly, while the main components of human skin are similar to those of pig skin. In a further step, the evolution of the heating time-dependent Raman modes of isolated pig skin has been investigated for the mechanism of burnt skin. One can find that the spatial structure and main components of skin have an excellent thermal stability in the temperature range from -120 to 200 ∘C, which is confirmed by the temperature dependent Raman spectra of isolated pig skin, microporous acellular dermal matrix (MADM) as well as their corresponding biochemical reagents (collagen, elastin, triolein, etc.). These results help understand the mechanism of the living skin burnt by fire or hot water, and supplies an alternative technology for surgeons to diagnose the depth of a burn injury in time.

The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma.

OBJECTIVE: MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. METHODS: 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. RESULTS: Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p < 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p < 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. CONCLUSIONS: The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Aucubin Alleviates Intervertebral Disc Degeneration by Repressing NF-κB-NLRP3 Inflammasome Activation in Endplate Chondrocytes.

Background: Intervertebral disc degeneration (IDD) is a prevalent degenerative disease and often recognized as the primary cause of lower back pain (LBP). Aucubin (Au) is a natural compound with anti-inflammatory properties in various diseases. The present study aimed to confirm the therapeutic effect of Au on IDD and explore its potential mechanism in vivo and in vitro. Methods: The process of IDD was simulated using the lumbar spine instability (LSI) model. In vivo, the therapeutic effect of Au on LSI-induced mice was evaluated by micro-CT and histomorphometry. Additionally, immunohistochemistry was applied to detect the cartilage metabolism and inflammasome activation in endplate. In vitro, the cytotoxicity of Au on ATDC5 cells was detected by Cell Counting Kit-8 (CCK-8), and the biological effects of Au were evaluated by Quantitative Real-time PCR (qRT-PCR) and Western blotting. Results: Micro-CT analysis showed that Au administration significantly alleviated LSI-induced disc volume narrowing and endplate cartilage degeneration, which was further supported by Alcian Blue Hematoxylin/Orange G (ABH/OG) staining. Immunohistochemistry results verified that Au could increase the expression of Col2α1 and Aggrecan, reduce the expression of Mmp-13, and attenuate the degradation of the endplate extracellular matrix (ECM). Mechanistically, we found that Au treatment, both in vivo and in vitro, significantly inhibited NF-κB-NLRP3 inflammasome activation in chondrocytes as determined by the decreased expression of p-P65, NLRP3, and Caspase-1. Discussion: Taken together, our findings have demonstrated for the first time that Au treatment ameliorated the degeneration of cartilage endplates in IDD may by inhibiting NF-κB-NLRP3 inflammasome activation in chondrocytes and provided a potential candidate for the treatment of IDD.

A comparison of anterior and posterior instrumentation for restoring and retaining sagittal balance in patients with idiopathic adolescent scoliosis.

STUDY DESIGN: Retrospective, comparative study. OBJECTIVE: To compare the effects of anterior rod-screw instrumentation and posterior pedicle screw instrumentation on sagittal balance in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Lenke type 5 AIS is treated by anterior or posterior spinal fusion surgery. Most studies comparing anterior and posterior fusion surgery have focused on assessing improvement in coronal balance. Studies comparing the effects of anterior and posterior surgery on sagittal balance are lacking. METHODS: The records of 49 patients diagnosed with Lenke type 5 AIS were examined. A total of 21 patients underwent anterior surgery between 2000 and 2003, while 26 underwent posterior surgery between 2004 and 2006. Preoperative, postoperative, and follow-up thoracic kyphosis (T5-T12 and T2-T12), lumbar lordosis, thoracolumbar junction kyphosis, and spinal vertical axis measurements were made by examining radiographs. Quality of life was assessed using the Scoliosis Research Society-22 questionnaire. All patients were followed up for at least 2 years. RESULTS: There were no significant between group differences in coronal alignment, thoracic kyphosis, or T11-L2 alignment after surgery. Sagittal alignment improvement was significantly more pronounced in the anterior surgery group compared with the posterior surgery group. The fusion segment was also significantly shorter in the anterior surgery compared with the posterior surgery group. Quality of life scores were significantly higher in the anterior surgery group compared with the posterior surgery group. CONCLUSION: Anterior solid rod-screw instrumentation results in shorter fusion segments, and better sagittal alignment and quality of life than posterior pedicle screw instrumentation in patients with Lenke type 5 AIS.

LIMS2 is Downregulated in Osteosarcoma and Inhibits Cell Growth and Migration.

Methods: GEO, GEPIA, and UALCAN databases were used to assess LIMS2 expression in OS. UALCAN and CCLE databases were applied to assess the methylation levels of LIMS2 in OS tissues and cells, which was verified in OS cells using the methylation specific PCR. The effects of LIMS2 on regulating OS cell growth, migration and invasion were determined by CCK-8, Edu staining, and transwell chambers, respectively. The role of LIMS2 in the activation of MAPK signaling was assessed using western blotting assay in OS cells. Results: LIMS2 expression was declined in OS tissues and cells, while its methylation level was increased. The low expression of LIMS2 was associated with shorter overall survival and disease-free survival. Overexpression of LIMS2 inhibited cell growth, migration, and invasion and decreased the levels of p-ERK/ERK, p-P38/P38, and p-JNK/JNK. Conclusion: LIMS2 expression was decreased in OS, which was associated with hypermethylation level and poor prognosis. LIMS2 overexpression inhibited OS cell growth and migration, which may be caused by the suppression of MAPK signaling.

A case report of multiple extramedullary plasmacytoma of the head and neck.

RATIONALE: Multiple extramedullary plasmacytoma (EMP) of the head and neck is rare and a definitive first-line treatment has not been established. EMP successively as a benign mass occurring in multiple areas of the head and neck is rare. This report describes an atypical case with EMP occurring in multiple areas of the head and neck. PATIENT CONCERNS: A 35-year-old woman was admitted due to complaints of sore throat discomfort accompanied by hoarseness. The patient had undergone surgical excision of the thyroid gland and parotid gland excision several years ago. Postoperative pathological examination both indicated EMP. This time, the woman suffered EMP in head and neck who was treated with a simple surgery. DIAGNOSIS: Postoperative pathological examination of the tumor indicated EMP, and histopathological findings revealed the tumor to be a plasmacytoma. Immunopathological examination were consistent with the diagnosis of EMP. INTERVENTIONS: The patient underwent surgical resection without radiotherapy. OUTCOMES: Histopathological and immunopathological examination findings revealed the tumor to be EMP. The patient was recurrence-free and did not progress to multiple myeloma (MM) during 19 months follow-up. LESSONS: Increasing the awareness of EMP of head and neck is warranted. Our case confirmed that surgical excision is beneficial in the treatment of small, localized EMP.

Determination of lowest instrumented vertebra by the location of apical vertebra in Lenke type 1 adolescent idiopathic scoliosis.

We postulated that the lowest instrumented vertebra (LIV) can be determined based on the apical vertebra. Seventy-two Lenke type 1 patients (average age: 13.6 years) receiving posterior spinal fusion were randomised into two groups. In group A, the apical vertebra was used to determine the LIV and in group B the neutral vertebra was used. All patients had Cobb angles <90° and average follow-up was over three years. Posteroanterior and lateral standing radiographs were used to assess flexibility, Cobb angle and distance from the C7 line to the central sacral vertical line. Both methods produced statistically significant changes in Cobb angle, sagittal T5-T12 and plumb line deviation, and there were no significant differences between the two methods. More cases of imbalance occurred in group B (five) than group A (two). We conclude that the apical vertebra can be used to determine the LIV in patients with Lenke type 1 adolescent idiopathic scoliosis.

The effect of differing spinal fusion instrumentation on the occurrence of postoperative crankshaft phenomenon in adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective. OBJECTIVE: To compare the occurrence of the crankshaft phenomenon in patients with adolescent idiopathic scoliosis (AIS) who underwent hybrid, consecutive pedicle screw or interval pedicle screw instrumentation for posterior spinal fusion. SUMMARY OF BACKGROUND DATA: Scoliosis may progress after posterior spinal fusion in skeletally immature patients with AIS. The crankshaft phenomenon occurs when the anterior column continues to grow in the face of posterior fusion causing characteristic twisting of the fused segment. The optimal surgical method for preventing the occurrence of this complication has not been determined. METHODS: Sixty seven patients with AIS who underwent posterior fusion over a 6-year period were divided into groups according to fixation method: hybrid instrumentation, interval pedicle screw placement, or consecutive pedicle screw placement. Preoperative, postoperative, and follow-up radiographic measures, including Cobb angle, apical vertebral rotation (AVR), apical vertebral transposition (AVT), rib vertebral angle difference (RVAD) and trunk shift (TS) were assessed. The occurrence of the crankshaft phenomenon was determined. RESULTS: The mean follow-up duration was 36 months. There were no between-the-group differences in demographics or preoperative or immediate postoperative measures. At the last follow-up, significant differences among the groups were apparent for Cobb angle, AVR, AVT, RVAD, and TS (all P<0.05). Cobb angle, AVR, AVT, RVAD, and TS significantly increased between the postsurgery and the last follow-up in the hybrid instrumentation group (all P<0.0167). Only TS increased significantly in the 2 other groups. There were 7 cases of crankshaft phenomenon occurrence in the hybrid instrumentation group (33%), but none in the other 2 groups. CONCLUSIONS: These findings suggest that in skeletally immature patients with AIS, hybrid instrumentation cannot effectively prevent occurrence of the crankshaft phenomenon, whereas interval and consecutive pedicle screw instrumentation may be more (and equally) efficacious in this regard.

Beneficial effects of baicalein on a model of allergic rhinitis.

Allergic rhinitis (AR) is a common disease that causes severe inflammation and even disabilities. Previous studies have reported baicalein to have an anti-inflammatory effect. However, the pharmacological action of baicalein on anaphylaxis has not been clarified yet. This study assessed the in vivo protective effect of baicalein post-treatment in an ameliorating ovalbumin (OVA)-sensitized AR rat model. Baicalein attenuated histological alterations, aberrant tissue repair and inflammation after OVA-induced AR. Baicalein reduced the frequency of nasal/ear rubs and sneezes in rats, and inhibited generation of several inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in both blood and nasal lavage of rats. Infiltrations of eosinophils, lymphocyte, and neutrophils were decreased in baicalein-administered rats. Furthermore, baicalein inhibited the expression of STAT3 phosphorylation in the nasal mucosa. In summary, baicalein attenuated OVA-induced AR and inflammation, which suggests it as a promising therapeutic agent for the alleviation of AR-associated inflammation and pathology.

Angiogenesis and bone regeneration by mesenchymal stem cell transplantation with danshen in a rabbit model of avascular necrotic femoral head.

The present study aimed to explore the potential of combined treatment with mesenchymal stem cells (MSCs) and danshen for angiogenesis and bone regeneration in a rabbit model of avascular necrosis of femoral head (ANFH). A rabbit model of ANFH was established using the Shwartzman reaction with methylprednisolone and Escherichia coli endotoxin injection. Magnetic resonance imaging (MRI) and histopathological examination were used to evaluate the rabbit model of ANFH. The rabbits were randomly divided into the danshen group, the MSCs group, the danshen combined with MSCs group and the model group (treated with physiological saline). The expression level of monocyte chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1 (SDF-1) were determined by reverse transcription polymerase chain reaction (RT-PCR). The expression level of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were detected by immunofluorescence and the mRNA expression of BMP-2 and VEGF were detected by RT-PCR. Typical osteonecrosis occurred in the rabbit model of ANFH, which indicated that the model was successfully established. MCP-1 and SDF-1 were significantly increased in the model group compared with the normal group (P<0.05). Following the administration of MSCs and Salvia miltiorrhiza (danshen), MSCs labeled with 5-bromo-2-deoxyuridine were observed to be gathered in the necrotic area. The increased migration of MSCs to the necrotic area may be due to the upregulated expression of the chemokines MCP-1 and SDF-1. ANFH treated with danshen combined with MSCs may promote revascularization by increasing the expression of VEGF and BMP-2 in the femoral head, promoting re-ossification and revascularization. Danshen combined with the transplantation of MSCs may be regarded as a novel therapy for the treatment of ANFH in a clinical setting.