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Summary Background/Objective Steroid-associated osteonecrosis (SAON) mostly occurs in large joints such as hip that finally results in joint collapse and replacement. An effective strategy for preventing SAON is inhibition of bone resorption and lipid formation, whereas promoting bone formation at osteonecrotic-sensitive skeletal sites. The objective of this study was to investigate whether gastrin administration could effectively prevent SAON in vivo and had a significant effect on osteogenesis, osteoclast differentiation and/or adipogenesis in vitro. Methods SAON was induced in rats by injection of both lipopolysaccharide and methylprednisolone. SAON rats were divided into three groups (untreated, low- ​and high-dose gastrin) and treated for two weeks. Lesions in SAON were identified, and efficacy of gastrin was evaluated in osteoclast activity, osteogenesis ​and adipogenesis. In vitro experiments evaluated the osteogenic and adipogenic potential of induced bone marrow stem cells, as well as osteoclast differentiation of stimulated bone marrow cells. Results Gastrin administration effectively prevented the development of SAON in vivo and significantly downregulated osteoclastogenesis, and upregulated osteogenesis in vitro. The underlying mechanism was potentially involved in the inhibited nuclear factor kappa-B (NF-κB) pathway leading to not only suppressed osteoclastogenesis but also facilitated osteoblastogenesis. Conclusion The present study demonstrated for the first time that gastrin could effectively prevent SAON in vivo and had a significant effect on osteogenesis, osteoclast differentiation and/or adipogenesis in vitro that should be an important link between gastrointestinal hormone and metabolic bone diseases. Translational potential of this article Gastrin prevents steroid-associated osteonecrosis with decreasing bone resorption and apoptosis, also enhancing bone formation. These findings provide in vivo evidence to support the use of gastrin to treat osteonecrosis.

Background/objectives For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. Methods In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. Results The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. Conclusion The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. The translational potential of this article The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.

Rationale: Langerhans cell histiocytosis (LCH) involves mainly the skin and bone and rarely the thyroid. Meanwhile, papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Both LCH and PTC could make the thyroid enlarged and hypermetabolic. The coincidence of these 2 events in a patient is rare, and this paper aimed to report such case. Patient concerns: A 40-year-old man presented with polyuria and polydipsia for 5 years. The symptoms had been relieved well by drug therapy for >4 years, until the drugs could not control the symptoms anymore and an extensively enlarged thyroid gland was noticed. Diagnoses: Thyroid ultrasound showed a nodule with microcalcification in the upper right lobe, positron emission tomography/computer tomography scan demonstrated thyroid hypermetabolism, and fine needle aspiration (FNA) revealed PTC. Right lobectomy of the thyroid and cervical lymph node biopsy verified the diagnosis “LCH of the thyroid complicated by PTC.” Interventions: The ultrasound-guided FNA biopsy was performed prior to right lobectomy of the thyroid and cervical lymph node biopsy. Postoperative histopathological examination confirmed the diagnosis, after which the patient received adjuvant chemotherapy. Outcomes: After 5 cycles of adjuvant chemotherapy, the patient had been followed up for 2 years. LCH was controlled satisfactorily and there was no significant sign of recurrence or metastasis of PTC. Lessons: LCH of the thyroid complicated by PTC is rare. Thyroid involvement should always be considered in the differential diagnosis of LCH patients. Surgery for PTC followed by chemotherapy for LCH may be the suitable treatment.

Background: The etiology of degenerative disc disease (DDD) is complex and includes genetic, gender, age, environment and traumatic factors. Obvious relatedness of DDD patients has been documented. Genetic factors account for 75% of the risk of DDD and although many genes have been associated with DDD, no specific marker genes have been found. Therefore, we will establish a biological sample library and database of DDD patients who have a family history of the disease and who require surgical treatment. To identify pathogenic DDD genes, we will screen the patient database for genes that contain polymorphisms and/or are differentially expressed. Methods/Design: This is a single-center, case-control study, which will be performed in Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, China. A total of 2,000 subjects will be prospectively collected from the wards and clinics of Shanghai First People's Hospital. These patients will consist of 1,000 DDD patients with a family history, 500 DDD patients without a family history, and 500 normal controls. Blood or intervertebral disc tissue samples will be collected. Total RNA will be sequenced to identify differentially expressed genes. Genome-wide association analysis will be performed using high-throughput microarrays and single nucleotide polymorphism microarrays and pooling (SNP-MAP). The primary outcome measure of this study will be the percentage of differentially expressed genes in DDD patients with or without a family history. The secondary outcome measures will be sequence variation in differentially expressed genes, SNP genotyping, routine liver and kidney function tests, routine blood tests, routine urine tests, and morphology of degenerated spinal discs. Discussion: This study aims to identify the pathological and physiological risk factors of DDD from the perspective of genetics by screening for genes that are differentially expressed in DDD and to correlate them with DDD, and to identify precise molecular targets for drug development and diagnostics. Trial registration: The study protocol was registered in Chinese Clinical Trial Registry (registration number: ChiCTR-COC-16009617) on October 10 th , 2016. Ethics: This study has been approved by Scientific Research Project Ethics Committee, Shanghai First People's Hospital, China (approval number: 2016KY166-2) and will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Informed consent: Written informed consent regarding study protocol and treatment procedure will be obtained prior to involvement in the clinical trial.

Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. In this study, the relationships between genetic polymorphisms of phase I metabolic enzymes including cytochrome P450 1A1 (CYP1A1), CYP2D6 and phase II metabolic enzymes such as glutathione S-transferase M1 (GSTM1) and GSTT1 and gastric carcinoma susceptibility were investigated. Genomic DNA was isolated from the peripheral blood of 129 healthy controls and 123 gastric carcinoma patients from Han ethnic group of Hunan Province located in Central South China. The genetic polymorphisms of the above mentioned enzymes were analyzed using PCR-RFLP techniques. There was no significant difference among the frequencies of CYP1A1 and/or CYP2D6 gene’s wild type, heterozygous or homozygous mutations between the gastric carcinoma group and control group. But the differences among the frequencies of GSTM1 and GSTT1 null genotype between the gastric carcinoma and control group were significant (both P < 0.05). Also there were significant differences in the frequencies of GSTM1 null in high/high–middle differentiated, middle differentiated, middle–low differentiated and low differentiated gastric tumor separately. GSTM1 null showed an increased risk in middle–low differentiated and low differentiated gastric carcinoma type, but GSTT1 null was not a risk factor for the four pathological types of gastric carcinoma mentioned above. We report here that the genotypes of CYP1A1 and CYP2D6 are not associated with gastric carcinoma risk; GSTM1 null, but not GSTT1 null inheritably increases risk of some pathological types of gastric carcinoma in Han ethnic population of Hunan Province.

To investigate the inhibitory effect of RNA interference (RNAi) on MMP-24 expression and invasiveness of ovarian cancer SKOV(3) cells.Two pairs of small interfering RNA (siRNA) specific to MMP-24 mRNA were designed and transfected into SKOV(3) cells. RT-PCR and Western blotting were used to detect the mRNA and protein expressions of MMP-24, and the cell invasiveness was assessed using an in vitro invasion test.After transfection with siRNA, the mRNA and protein expression levels of MMP-24 were obviously reduced in SKOV(3) cells, which also showed significantly decreased invasiveness in vitro.MMP-24 gene silencing by RNAi can suppress the invasiveness of ovarian cancer SKOV(3) cells in vitro, which may provide a new therapeutic approach of ovarian cancer.