Targeting bone homeostasis regulation: potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis.

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/ß-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP. Therefore, this study presents a systematic review of the recent literature to provide comprehensive information on the traditional Chinese medicine flavonoids involved in the regulation of bone homeostasis. Also, the molecular mechanisms and pharmacological uses of these metabolites are summarized, and their clinical translation and development potential are discussed.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Increases in computationally predicted deleterious variants of unknown significance and sperm mtDNA copy numbers may be associated with semen quality.

BACKGROUND: Mitochondria are essential for sperm motility because they provide the energy required for the movement. Changes in sperm mtDNA, such as point mutations, large-scale deletions, or copy number variations, may interfere with ATP production and reduce sperm motility. However, it is not clear if changes in mtDNA are linked to semen quality. OBJECTIVES: To explore the association between sperm mitochondrial DNA (mtDNA) changes and semen quality. MATERIALS AND METHODS: Sixty-five oligo and/or astheno and/or terato patients (O/A/T) patients and 41 controls were recruited from couples undergoing assisted reproduction. Semen and blood samples were collected from the same individual on the day of oocyte retrieval to extract, isolate and purify mtDNA for next-generation sequencing. mtDNA copy numbers were assessed in 64 patient and 39 control sperm DNA samples using quantitative real-time PCR. The 4977 bp deletion was assessed in 20 patient and 20 control sperm DNA samples using polymerase chain reaction. RESULTS: The mtDNA of patients was more likely to carry pathogenic variants or variants of unknown significance (VUSs) (P = 0.091) with higher heteroplasmy levels (P < 0.05) than that of controls. Interestingly, 33.85% of O/A/T patients (22 out of 65) lacked unique variants in their spermatozoa. but presented an exceptionally high mtDNA copy number (P < 0.0001). Moreover, we observed a decrease in the heteroplasmy level of common mtDNA variants shared by somatic and gamete cells (P < 0.0001) and the emergence of a very large number of de novo mtDNA variants with low-level heteroplasmy in spermatozoa. DISCUSSION AND CONCLUSION: The increases in the number of computationally predicted deleterious VUS and mtDNA copies in spermatozoa may be associated with semen quality. Exposure to environmental mutation pressure that causes novel mtDNA variants with low-level heteroplasmy may occur during spermatogenesis. Furthermore, when a certain harmful threshold is reached, male germ cells may degrade mtDNA with mutations and replicate the correct mtDNA sequence to maintain the mitochondrial function in spermatozoa.

Huogu injection protects against SONFH by promoting osteogenic differentiation of BMSCs and preventing osteoblast apoptosis.

To investigate the effect and mechanism of Huogu injection (HG) on steroid-induced osteonecrosis of the femoral head (SONFH), we established a SONFH model in rabbits using horse serum and dexamethasone (DEX) and applied HG locally at the hip joint. We evaluated the therapeutic efficacy at 4 weeks using scanning electron microscopy (SEM), micro-CT, and qualitative histology including H&E, Masson's trichrome, ALP, and TUNEL staining. In vitro, we induced osteogenic differentiation of bone marrow stromal cells (BMSCs) and performed analysis on days 14 and 21 of cell differentiation. The findings, in vivo, including SEM, micro-CT, and H&E staining, showed that HG significantly maintained bone quality and trabecular number. ALP staining indicated that HG promoted the proliferation of bone cells. Moreover, the results of Masson's trichrome staining demonstrated the essential role of HG in collagen synthesis. Additionally, TUNEL staining revealed that HG reduced apoptosis. ALP and ARS staining in vitro confirmed that HG enhanced osteogenic differentiation and mineralization, consistent with the WB and qRT-PCR analysis. Furthermore, Annexin V-FITC/PI staining verified that HG inhibited osteoblast apoptosis, in agreement with the WB and qRT-PCR analyses. Furthermore, combined with the UPLC analysis, we found that naringin enhanced the osteogenic differentiation and accelerated the deposition of calcium phosphate. Salvianolic acid B protected osteoblasts derived from BMSCs against GCs-mediated apoptosis. Thus, this study not only reveals the mechanism of HG in promoting osteogenesis and anti-apoptosis of osteoblasts but also identifies the active-related components in HG, by which we provide the evidence for the application of HG in SONFH.

Exploring the mechanism of traditional Chinese medicine in regulating gut-derived 5-HT for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by an imbalance in the relationship between osteoblasts, osteocytes, and osteoclasts. This imbalance in bone metabolism results in the destruction of the bone's microstructure and an increase in bone brittleness, thereby increasing the risk of fractures. Osteoporosis has complex causes, one of which is related to the dysregulation of 5-hydroxytryptamine, a neurotransmitter closely associated with bone tissue metabolism. Dysregulation of 5-HT directly or indirectly promotes the occurrence and development of osteoporosis. This paper aims to discuss the regulation of 5-HT by Traditional Chinese Medicine and its impact on bone metabolism, as well as the underlying mechanism of action. The results of this study demonstrate that Traditional Chinese Medicine has the ability to regulate 5-HT, thereby modulating bone metabolism and improving bone loss. These findings provide valuable insights for future osteoporosis treatment.

Facile Solid-State Synthesis to In Situ Generate a Composite Coating Layer Composed of Spinel-Structural Compounds and Li3PO4 for Stable Cycling of LiCoO2 at 4.6 V.

Due to its high energy density, high-voltage LiCoO2 is the preferred cathode material for consumer electronic products. However, its commercial viability is hindered by rapid capacity decay resulting from structural degradation and surface passivation during cycling at 4.6 V. The key to achieving stable cycling of LiCoO2 at high voltages lies in constructing a highly stable interface to mitigate surface side reactions. In this study, we present a facile in situ coating strategy that is amenable to mass production through a simple wet-mixing process, followed by high-temperature calcination. By capitalizing on the facile dispersion characteristics of nano-TiO2 in ethanol and the ethanol dissolubility of LiPO2F2, we construct a uniform precoating layer on LiCoO2 with nano-TiO2 and LiPO2F2. The subsequent thermal treatment triggers an in situ reaction between the coating reagents and LiCoO2, yielding a uniform composite coating layer. This composite layer comprises spinel-structured compounds (e.g., LiCoTiO4) and Li3PO4, which exhibit excellent chemical and structural stability under high-voltage conditions. The uniform and stable coating layer effectively prevents direct contact between LiCoO2 and the electrolyte, thereby reducing side reactions and suppressing the surface passivation of LiCoO2 particles. As a result, coated LiCoO2 maintains favorable electronic and ionic conductivity even after prolonged cycling. The synergistic effects of spinel-structured compounds and Li3PO4 contribute to the superior performance of LiCoO2, demonstrating a high capacity of 202.1 mA h g-1 (3.0-4.6 V, 0.5 C, 1 C = 274 mA g-1), with a capacity retention rate of 96.7% after 100 cycles.

Targeting different phenotypes of macrophages: A potential strategy for natural products to treat inflammatory bone and joint diseases.

BACKGROUND: Macrophages, a key class of immune cells, have a dual role in inflammatory responses, switching between anti-inflammatory M2 and pro-inflammatory M1 subtypes depending on the specific environment. Greater numbers of M1 macrophages correlate with increased production of inflammatory chemicals, decreased osteogenic potential, and eventually bone and joint disorders. Therefore, reversing M1 macrophages polarization is advantageous for lowering inflammatory factors. To better treat inflammatory bone disorders in the future, it may be helpful to gain insight into the specific mechanisms and natural products that modulate macrophage polarization. OBJECTIVE: This review examines the impact of programmed cell death and different cells in the bone microenvironment on macrophage polarization, as well as the effects of natural products on the various phenotypes of macrophages, in order to suggest some possibilities for the treatment of inflammatory osteoarthritic disorders. METHODS: Using 'macrophage polarization,' 'M1 macrophage' 'M2 macrophage' 'osteoporosis,' 'osteonecrosis of femoral head,' 'osteolysis,' 'gouty arthritis,' 'collagen-induced arthritis,' 'freund's adjuvant-induced arthritis,' 'adjuvant arthritis,' and 'rheumatoid arthritis' as search terms, the relevant literature was searched using the PubMed, the Cochrane Library and Web of Science databases. RESULTS: Targeting macrophages through different signaling pathways has become a key mechanism for the treatment of inflammatory bone and joint diseases, including HIF-1α, NF-κB, AKT/mTOR, JAK1/2-STAT1, NF-κB, JNK, ERK, p-38α/ß, p38/MAPK, PI3K/AKT, AMPK, AMPK/Sirt1, STAT TLR4/NF-κB, TLR4/NLRP3, NAMPT pathway, as well as the programmed cell death autophagy, pyroptosis and ERS. CONCLUSION: As a result of a search of databases, we have summarized the available experimental and clinical evidence supporting herbal products as potential treatment agents for inflammatory osteoarthropathy. In this paper, we outline the various modulatory effects of natural substances targeting macrophages in various diseases, which may provide insight into drug options and directions for future clinical trials. In spite of this, more mechanistic studies on natural substances, as well as pharmacological, toxicological, and clinical studies are required.

Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies.

BACKGROUND: The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I (TsI), on SIONFH remain unknown. Here, we evaluated the effects of TsI on SIONFH, particularly focusing on its effects on angiogenesis, in in vivo and in vitro research. METHODS: SIONFH was induced in Sprague-Dawley rats by an intramuscular injection of methylprednisolone (40 mg/kg) in combination with an intraperitoneal injection of lipopolysaccharide (20 µg/kg). Morphological alterations of the femoral head were observed by dual-energy X-ray absorptiometry and HE staining. Western blot, qRT-PCR, and immunohistochemical/immunofluorescence staining were used to determine gene expression. RESULTS: TsI (10 mg/kg) alleviated bone loss and rescued the expression of angiogenesis-related molecules (CD31, VWF, VEGF, and VEGFR2) in the femoral heads of SIONFH rats. Notably, TsI rescued the down-regulated expression of SRY-box transcription factor 11 (SOX11) in CD31+ endothelial cells in the femoral heads of SIONFH rats. In vitro studies showed that TsI preserved the dexamethasone-harmed angiogenic property (migration and tube formation) of human umbilical vein cells (EA.hy926), suppressed dexamethasone-induced cell apoptosis, reduced pro-apoptotic proteins (cytosolic cytochrome C, Bax, and caspase 3/9) and increased anti-apoptotic protein Bcl-2, whereas silencing of SOX11 reversed these beneficial effects. CONCLUSIONS: This study demonstrates that TsI alleviates SIONFH and promotes angiogenesis by regulating SOX11 expression. Our work would provide new evidence for the application of TsI to treat SIONFH.

Novel homozygous variants in TTC12 cause male infertility with asthenoteratozoospermia owing to dynein arm complex and mitochondrial sheath defects in flagella.

Introduction: Tracing the genetic causes for male infertility due to asthenoteratozoospermia has revealed at least 40 causative genes, which provides valuable reference for the genetic testing of asthenoteratozoospermia in clinical practice. To identify deleterious variants in the human tetratricopeptide repeat domain 12 (TTC12) gene in a large cohort of infertile Chinese males with asthenoteratozoospermia. Methods: A total of 314 unrelated asthenoteratozoospermia-affected men were recruited for whole exome sequencing. The effects of the identified variants were evaluated by in silico analysis, and confirmed by in vitro experiments. Intracytoplasmic sperm injection (ICSI) was used to evaluate the efficiency of assisted reproduction technique therapy. Results and Discussion: Novel homozygous TTC12 variants (c.1467_1467delG (p.Asp490Thrfs*14), c.1139_1139delA (p.His380Profs*4), and c.1117G>A (p.Gly373Arg)) were identified in three (0.96%) of the 314 cases. Three mutants were indicated to be damaging using in silico prediction tools, and were further confirmed by in vitro functional analysis. Hematoxylin and eosin staining and ultrastructural observation of the spermatozoa revealed multiple morphological abnormalities of flagella, with the absence of outer and inner dynein arms. Notably, significant mitochondrial sheath malformations were also observed in the sperm flagella. Immunostaining assays indicated that TTC12 is present throughout the flagella, and was strongly concentrated in the mid-piece in control spermatozoa. However, spermatozoa from TTC12-mutated individuals exhibited almost no staining intensity of TTC12 and outer and inner dynein arms components. The three men accepted ICSI treatment using their ejaculated spermatozoa, and two female partners successfully delivered healthy babies. Our findings provide direct genetic evidence that homozygous variants in TTC12 cause male infertility with asthenoteratozoospermia by causing dynein arm complex defects and mitochondrial sheath malformations in the flagellar. We also demonstrated that TTC12 deficiency-mediated infertility could be overcome by ICSI technology.

Therapeutic potential of naringin in improving the survival rate of skin flap: A review.

Naringin is the main component of Drynaria. Modern pharmacological studies have shown that naringin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, and anti-osteoporosis effects. Its therapeutic effects have been observed in various clinical models, such as atherosclerosis, cardiovascular diseases, diabetes, neurodegenerative diseases, and rheumatic diseases. This review investigates the pharmacological effects of naringin and the associated mechanisms in improving flap survival. This review will also provide a reference for future rational application of naringin, especially in research to improve flap survival.

Huogu injection alleviates SONFH by regulating adipogenic differentiation of BMSCs via targeting the miR-34c-5p/MDM4 pathway.

Although the precise pathogenesis of steroid-induced osteonecrosis of femoral head (SONFH) is not yet fully understood, evidence shows miRNAs-mediated posttranscription control directs the adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and plays a pivotal role in the SONFH processes. Huogu injection formulated according to traditional Chinese medicine (TCM) theory has been used to treat SONFH by intra-articular injection. In this study, we asked whether the therapeutic effects of Huogu injection might depend on the inhibition of adipogenic differentiation of BMSCs, and if so, the pathway might be a therapeutic target to promote bone repair. Consequently, miR-34c-5p was upregulated in the dexamethasone (DEX)-treated BMSCs and might participate in the adipogenesis of BMSCs. TargetScan database and the luciferase reporter assay showed miR-34c-5p targeted on the MDM4 and negatively regulated its expression. Huogu injection in vitro inhibited the adipogenesis in the DEX-treated BMSCs by inhibiting the expression levels of PPARγ and C/EBPα, as well as reducing miR-34c-5p to prevent the degradation of MDM4. Moreover, miR-34c-5p mimic or MDM4 knockdown using shRNA neutralized the anti-adipogenesis of Huogu injection in BMSCs. In vivo, the results of X-ray imaging confirmed that Huogu injection alleviated the bone loss in rat SONFH. Consistent with results in vitro, Huogu injection reduced the lipid accumulation, removed the suppression of MDM4 by downregulating the expression of miR-34c-5p, and inhibited the expression of C/EBPα and PPARγ in bone tissues. When the lentivirus encoding miR-34c-5p was conducted by intra-articular injection, the overexpression of miR-34c-5p antagonized the therapeutic effects of Huogu injection. Our results underline the critical importance of the miR-34c-5p/MDM4 pathway in regulating the adipogenic outcome of BMSCs, suggesting the miR-34c-5p as a potentially effective therapeutic target in SONFH. These results further reinforce the potential of Huogu injection as an alternative approach in SONFH.

Altered gut microbiota and metabolites profile are associated with reduced bone metabolism in ethanol-induced osteoporosis.

OBJECTIVE: Chronic heavy drinking causes ethanol-induced osteoporosis (EIO). The present study aimed to explore the role of GM in EIO. MATERIAL AND METHODS: A rat EIO model was established by chronic ethanol intake. Taking the antibiotic application as the matched group of dysbacteriosis, an integrated 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry-based metabolomics in serum and faeces were applied to explore the association of differential metabolic phenotypes and screen out the candidate metabolites detrimental to ossification. The colon organoids were used to track the source of 5-HT and the effect of 5-HT on bone formation was examined in vitro. RESULTS: Compared with antibiotics application, ethanol-gavaged decreased the BMD in rats. We found that both ethanol and antibiotic intake affected the composition of GM, but ethanol intake increased the ratio of Firmicutes to Bacteroidetes. Elevated serotonin was proved to be positively correlated with the changes of the composition of GM and faecal metabolites and inhibited the proliferation and mineralization of osteogenesis-related cells. However, the direct secretory promotion of serotonin was absent in the colon organoids exposed to ethanol. CONCLUSION: This study demonstrated that ethanol consumption led to osteoporosis and intestinal-specific dysbacteriosis. Conjoint analysis of the genetic profiles of GM and metabolic phenotypes in serum and faeces allowed us to understand the endogenous metabolite, 5-HT, as detrimental regulators in the gut-bone axis to impair bone formation.

Bi-allelic variants in SHOC1 cause non-obstructive azoospermia with meiosis arrest in humans and mice.

Meiosis is pivotal to gametogenesis and fertility. Meiotic recombination is a mandatory process that ensures faithful chromosome segregation and generates genetic diversity in gametes. Non-obstructive azoospermia (NOA) caused by meiotic arrest is a common cause of male infertility and has many genetic origins, including chromosome abnormalities, Y chromosome microdeletion and monogenic mutations. However, the genetic causes of the majority of NOA cases remain to be elucidated. Here, we report our findings of three Shortage in chiasmata 1 (SHOC1) bi-allelic variants in three NOA patients, of which two are homozygous for the same loss-of-function variant (c.231_232del: p.L78Sfs*9), and one is heterozygous for two different missense variants (c.1978G>A: p.A660T; c.4274G>A: p.R1425H). Testicular biopsy of one patient revealed impairment of spermatocyte maturation. Both germ-cell-specific and general Shoc1-knockout mice exhibited similar male infertility phenotypes. Subsequent analysis revealed comprehensive defects in homologous pairing and synapsis along with abnormal expression of DMC1, RAD51 and RPA2 in Shoc1-defective spermatocyte spreads. These findings imply that SHOC1 may have a presynaptic function during meiotic recombination apart from its previously identified role in crossover formation. Overall, our results provide strong evidence for the clinical relevance of SHOC1 mutations in patients with NOA and contribute to a deeper mechanistic understanding of the role of SHOC1 during meiotic recombination.

[Pre-conception carrier screening for 21 inherited metabolic diseases in a Chinese population].

OBJECTIVE: To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age. METHODS: A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed. RESULTS: One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria. CONCLUSION: This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.

Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases.

It's challenging work to identify disease-causing genes from the next-generation sequencing (NGS) data of patients with Mendelian disorders. To improve this situation, researchers have developed many phenotype-driven gene prioritization methods using a patient's genotype and phenotype information, or phenotype information only as input to rank the candidate's pathogenic genes. Evaluations of these ranking methods provide practitioners with convenience for choosing an appropriate tool for their workflows, but retrospective benchmarks are underpowered to provide statistically significant results in their attempt to differentiate. In this research, the performance of ten recognized causal-gene prioritization methods was benchmarked using 305 cases from the Deciphering Developmental Disorders (DDD) project and 209 in-house cases via a relatively unbiased methodology. The evaluation results show that methods using Human Phenotype Ontology (HPO) terms and Variant Call Format (VCF) files as input achieved better overall performance than those using phenotypic data alone. Besides, LIRICAL and AMELIE, two of the best methods in our benchmark experiments, complement each other in cases with the causal genes ranked highly, suggesting a possible integrative approach to further enhance the diagnostic efficiency. Our benchmarking provides valuable reference information to the computer-assisted rapid diagnosis in Mendelian diseases and sheds some light on the potential direction of future improvement on disease-causing gene prioritization methods.

The comprehensive variant and phenotypic spectrum of TUBB8 in female infertility.

PURPOSE: TUBB8 is a gene that is frequently analysed in the genetic diagnosis of female infertility; 102 variants of this gene have been identified. However, the evaluation of its pathogenicity and the resulting phenotypes vary. Here, we aimed to identify novel TUBB8 variants as well as to summarize the reported variants and phenotypes in order for them to be included in genetic counselling analyses. METHODS: We performed whole exome sequencing to screen for candidate variants in 100 infertile female subjects and 100 controls who were able to conceive naturally. All variants were confirmed by Sanger sequencing. The effects of the variants in oocytes/arrested embryos were assessed by morphological observations, polar body biopsies, and chromosome analysis. A molecular modelling analysis was used to evaluate the possible effects of variants on protein secondary structure. RESULTS: We identified 29 TUBB8 variants, of which 20 were novel and five were maternally inherited. We identified three of a total of six recurrent variants that were specific for complete cleavage failure. Moreover, we obtained evidence that TUBB8 variants with large polar bodies had chromosome segregation errors. CONCLUSIONS: Our study expands the spectrum of TUBB8 variants, particularly for embryonic arrest. Together with the extant knowledge of TUBB8 variants, this study provides a foundation for the genetic counselling of female infertility.

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats.

Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 µg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.

A biomechanical comparison of crossed and parallel rod configurations in atlantoaxial internal fixation.

BACKGROUND: Posterior atlantoaxial fixation with screw rod forms an approximate "II" shape or "H" increasing transverse link for better stability. In order to improve stability and in consideration of difficult placement of transverse connecting rod, possibility of inadequate bone graft, some scholars have preliminarily researched biomechanics of a novel crossed rod as an approximate "X" configuration of screw rod. PURPOSE: The aim of this study was to evaluate and compare the biomechanics of the crossed and parallel rod configurations in the screw rod system for posterior atlantoaxial fixation on a cadaveric model. METHODS: Six fresh cervical specimens were used to complete the range of motion (ROM) testing by applying pure moments of ± 2.0 nm. Following intact state and under destabilization testing, screws were implanted. The specimens were then tested in the following sequence: Group BLS + PR (C2 bilateral laminar screws + parallel rod), Group BLS + CR (C2 bilateral laminar screws + crossed rod), LPRLS + PR (C2 left pedicle screw and right laminar screw + parallel rod), LPRLS + CR (C2 left pedicle screw and right laminar screw + crossed rod), BPS + PR (C2 bilateral pedicle screws + parallel rod) and BPS + CR (C2 bilateral pedicle screws + crossed rod). The ROM of the C1-2 segments was measured in flexion-extension, lateral bending and axial rotation. Six surgical constructs were compared between the groups and with intact condition, respectively. RESULTS: The six fixed modes significantly increased stability compared with both the intact and destabilization group in flexion-extension, lateral bending and axial rotation (p < .05). In extension, BPS + CR and BLS + CR showed greater stability than BLS + PR (p < .05). During flexion, the six fixation methods showed no statistical significance (p > .05). In left lateral bending, stability of the other five screw rod fixation techniques significantly increased when compared with BLS + PR (p < .05). In the right lateral bending direction, the stability of BLS + PR was worse than that of BPS + CR and BPS + PR (p < .05). In the left axial rotation, stability of BLS + CR, LPRLS + CR and BPS + CR was greater than that of BLS + PR, LPRLS + PR and BPS + PR (p < .05). In the right axial rotation, the stability of BPS + CR and BLS + CR was greater than that of BLS + PR (p < .05). CONCLUSION: The six investigated fixation methods provide sufficient biomechanical stability. The crossed rod configuration can further enhance the axial rotation stability of the screw rod system, which consists of C1 bilateral pedicle and C2 pedicle, or C2 lamina screws. The crossed rod can also improve the stability of the screw rod system made up of C1 bilateral pedicle and C2 lamina screws in lateral bending and extension. The crossed rod configuration is reliable and provides superior stability for clinical application.

[Biomechanical stability evaluation of the fixation technique for crossed rods consisting of occipital plate and C 2 bilateral lamina screws].

OBJECTIVE: To evaluate the stability of the fixation technique for the crossed rods consisting of occipital plate and C 2 bilateral lamina screws by biomechanical test. METHODS: Six fresh cervical specimens were harvested and established an atlantoaxial instability model. The models were fixed with parallel rods and crossed rods after occipital plate and C 2 bilateral laminae screws were implanted. The specimens were tested in the following sequence: atlantoaxial instability model (unstable model group), under parallel rods fixation (parallel fixation group), and under crossed rods fixation (cross fixation group). The range of motion (ROM) of the C 0-2 segments were measured in flexion-extension, left/right lateral bending, and left/right axial rotation. After the test, X-ray film was taken to observe the internal fixator position. RESULTS: The biomechanical test results showed that the ROMs in flexion-extension, left/right lateral bending, and left/right axial rotation were significantly lower in the cross fixation group and the parallel fixation group than in the unstable model group ( P<0.05). There was no significant difference between the cross fixation group and the parallel fixation group in flexion-extension and left/right lateral bending ( P>0.05). In the left/right axial rotation, the ROMs of the cross fixation group were significantly lower than those of the parallel fixation group ( P<0.05). After the test, the X-ray film showed the good internal fixator position. CONCLUSION: The axial rotational stability of occipitocervical fusion can be further improved by crossed rods fixation when the occipital plate and C 2 bilateral lamina screws are used.

Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a crucial role in varieties of biological processes. This study is aimed at investigating meniscal degeneration-specific lncRNAs and mRNAs and their related networks in knee osteoarthritis (KOA). METHODS: The dataset GSE98918, which included 24 meniscus samples and related clinical data, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the meniscus between KOA and control groups were identified. Based on the enriched differentially expressed lncRNAs and mRNAs, we constructed the coexpression network using WGCNA (weighted correlation network analysis) and identified the critical module related to KOA. For mRNAs in the key module, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out using the DAVID database. A competing endogenous RNA network (ceRNA) based on the screened mRNAs, lncRNAs, and related miRNAs was constructed to reveal presumptive biomarkers further. Finally, the hub lncRNAs and mRNAs were screened, and the diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. Hub mRNAs were validated using the dataset GSE113825. RESULTS: We screened 208 significantly differentially expressed lncRNAs and mRNAs in menisci between the KOA and non-KOA samples, which were enriched in sixteen modules using WGCNA, especially the green module. Coexpression network based on the enriched differentially expressed lncRNAs and mRNAs in the green module uncovered 5 lncRNAs and 56 mRNAs. The lncRNA-miRNA-mRNA ceRNA network revealed that lnc-HLA-DQA1-5, lnc-RP11-127H5.1.1-1, lnc-RTN2-1, IGFBP4 (insulin-like growth factor binding protein 4), and KLF2 (Kruppel-like factor 2) were significantly correlated with the meniscus degeneration of KOA. ROC curve analysis revealed that these hub lncRNAs and mRNAs showed excellent diagnostic value for KOA. CONCLUSIONS: These hub lncRNAs and mRNAs were potential prognostic biomarkers for the meniscus degeneration of KOA. Further studies are required to validate these new biomarkers and better understand the pathological process of the meniscus degeneration of KOA.