A combination of ultrasound and contrast-enhanced ultrasound improves diagnostic accuracy for the differentiation of cervical tuberculous lymphadenitis from primary lymphoma.

OBJECTIVES: To present a method combining ultrasound (US) and contrast-enhanced ultrasound (CEUS) features for differential diagnosis of cervical tuberculous lymphadenitis (CTL) and primary lymphoma. METHODS: A total of 155 patients with CTL (n = 49) and lymphoma (n = 106) who underwent US and CEUS were retrospectively included. The features extracted from US and CEUS and the significant clinical data were created three models using the least absolute shrinkage and selection operator and logistic regression analysis. The diagnostic performance of the models was assessed using the area under the curve (AUC). RESULTS: The combined model outperformed US model and CEUS model in distinguish CTL from lymphoma achieved favorable performances in training set and validation set with AUCs of 0.958 and 0.946 as well as high accuracies (91.7% and 87.2%), sensitivities (95.9% and 84.4%) and specificities (82.4% and 93.3%). Delong's test showed that among the three models, combined model was significantly different from the other two models in training set (p = 0.011 and 0.029, respectively) and validation set (p = 0.018 and 0.001, respectively). CONCLUSIONS: A combination of US and CEUS achieved good diagnostic performance in differentiating lymphoma and CTL, which might aid in clinical decision-making.

Ultrasonographic Findings and Prognosis of Metastases to the Thyroid Gland.

Metastases to the thyroid gland (MTT) are uncommon in clinical practice. The ultrasound (US) features are easily confused with primary thyroid malignancy, Hashimoto's thyroiditis, and other thyroid diseases. Therefore, this study aimed to assess the role of US and analysis of prognosis of MTT. A total of 45 patients with MTT in the database between July 2009 and February 2022 at the Fujian Cancer Hospital were reviewed. US examinations were performed only on 20 patients, who were finally included in our study. Among the 20 patients, nine were male, and eleven were female. According to US characteristics, metastases to the thyroid gland were divided into nodular and diffuse types (17 and 3 cases, respectively). Three lesions (17.6%) had circumscribed margins, and 14 (82.4%) were uncircumscribed. Three lesions (17.6%) were regular in shape, and 14 (82.4%) were irregular. Nine metastases (52.9%) were a taller-than-wide shape, and eight (47.1%) were not a taller-than-wide shape. Ten lesions (58.8%) had rich vascularity, and seven (41.2%) had absence/not rich vascularity. The mean overall survival (OS) from the time of MTT diagnosis was 22 months (95% confidence interval: 5.95-38.05). The 1-, 3-, and 5-year OS after metastasis was 68.1%, 25.5%, and 17%, respectively. The prognosis of MTT was poor, which is closely related to the characteristics of the primary tumor and metastatic disease. The US findings and US-guided core needle biopsy may be useful in diagnosing MTT in patients with a history of the malignant tumors.

Logistic regression analyses of factors affecting the euploidy of blastocysts undergoing in vitro fertilization and preimplantation genetic testing.

Embryo chromosomal abnormalities are considered as the main cause of low pregnancy rate for in vitro fertilization (IVF). Recently, a new metric of success in assisted reproductive technology, that is, the ability to achieve at least 1 euploid blastocyst for transfer, has been brought into focus among clinicians. Our study aimed to investigate the effects of different factors on the euploidy of blastocysts undergoing IVF and preimplantation genetic testing (PGT). This retrospective observational study included 493 cycles underwent IVF/intracytroplasmatic sperm injection intended to obtain trophectoderm biopsy for PGT from June 2016 to December 2019 at a single academic fertility center. Logistic regression was adopted to analyze the clinical characteristics and embryonic data related to the ability to achieve at least 1 euploid blastocyst for transfer. The study took 1471 blastocysts from 493 cycles as samples for PGT. Among them, 149 cycles (30.22%) had no euploid blastocyst and 344 cycles (69.78%) had at least 1 euploid blastocyst. A multivariate logistic analysis suggested that maternal age >36, abnormal parental karyotype, nonfirst cycles and blastocysts number per cycle <3 were the risk factors for no euploid blastocyst. The parental karyotype, maternal age, number of cycles, and number of blastocysts per cycle were the dominant factors affecting the ability to achieve at least 1 euploid blastocyst for transfer and therefore could be regarded as potential predictors for genetic counseling.

The Diagnostic Value of Ultrasound-Based Deep Learning in Differentiating Parotid Gland Tumors.

Objectives: Evidence suggests that about 80% of all salivary gland tumors involve the parotid glands, with approximately 20% of parotid gland tumors (PGTs) being malignant. Discriminating benign and malignant parotid gland lesions preoperatively is vital for selecting the appropriate treatment strategy. This study explored the diagnostic performance of deep learning system for discriminating benign and malignant PGTs in ultrasonography images and compared it with radiologists. Methods. A total of 251 consecutive patients with surgical resection and proven parotid gland malignant or benign tumors who underwent preoperative ultrasound examinations were enrolled in this study between January 2014 and November 2020. Next, we compared the diagnostic accuracy of deep learning methods (ViT-B\16, EfficientNetB3, DenseNet121, and ResNet50) and radiologists in parotid gland tumor. In addition, the area under the curve (AUC), specificity, sensitivity, positive predictive value, and negative predictive value were calculated. Results: Among the 251 patients, 176/251 were the training set, whereas 75/251 were the validation set. Results showed that 74/251 patients had malignant tumor. Deep learning models achieved good performance in differentiating benign from malignant tumors, with the diagnostic accuracy and AUCs of ViT-B\16, EfficientNetB3, DenseNet121, and ResNet50 model being 81% and 0.81, 80% and 0.82, 77% and 0.81, and 79% and 0.80, respectively. On the other hand, the diagnostic accuracy and AUCs of radiologists were 77%-81% and 0.68-0.75, respectively. It was evident that the diagnostic accuracy of deep learning methods was higher than that of inexperienced radiologists, but there was no significant difference between deep learning methods and experienced radiologists. Conclusions: This study shows that the deep learning system can be used for diagnosing parotid tumors. The findings also suggest that the deep learning system may improve the diagnosis performance of inexperienced radiologists.

A Combination of Contrast-Enhanced Ultrasound and Thyroglobulin Level in Fine-Needle Aspirates Improves Diagnostic Accuracy for Metastatic Lymph Nodes of Papillary Thyroid Carcinoma.

OBJECTIVE: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with thyroglobulin (Tg) levels in fine-needle aspirates (FNA) washout fluid (FNA-Tg) in diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC) patients. METHODS: Data from 190 LNs in 167 patients suspected of metastasis from the US between November 2018 and September 2020 were included. All subjects underwent FNA, CEUS, and FNA-Tg examinations. The final outcomes were confirmed by histopathological or cytological examination or follow-up imaging. Data were analyzed using the Wilcoxon rank-sum or chi-squared test. The diagnostic efficacy of FNA, CEUS, and FNA-Tg in diagnosing LNs was compared. RESULTS: A cutoff value of 6.15 ng/ml (AUC 0.925, 95% confidence interval (CI) 0.885-0.966) successfully identified metastatic LNs. FNA missed 58 LN metastases, of these, 94.8% (55/58) were correctly diagnosed using the combination of CEUS and FNA-Tg. FNA-Tg showed higher sensitivity (90.2%), NPV (86.1%) and accuracy (88.9%) than either FNA (48.2, 57.4 and 69.5%, respectively) or CEUS (82.1, 67.7 and 70.5%, respectively) alone. The combination of CEUS, FNA and FNA-Tg resulted in maximal sensitivity (100%) and NPV (100%) but reduced specificity (51.3%) and overall diagnostic accuracy (80.0%). After adding FNA-Tg to discordant samples between CEUS and FNA, 81.9% of LNs (77/94) were correctly diagnosed. CONCLUSIONS: The combination of FNA, FNA-Tg and CEUS was found to be a promising imaging tool in detecting metastatic LNs in PTC patients.

Testicular STAC3 regulates Leydig cell steroidogenesis through potentiating mitochondrial membrane potential and StAR processing.

SH3 and cysteine-rich protein 3 (STAC3), a small adapter protein originally identified as a core component of excitation-contraction coupling machinery, regulates the voltage-induced Ca2+ release in skeletal muscle. However, the possibility of additional, as yet unknown, non-muscle effects of STAC3 cannot be ruled out. Herein, we provide the evidence for the expression and functional involvement of STAC3 in spermatogenesis. STAC3 expression was localized in the testicular interstitium of rodent and human testes. By using the cytotoxic drug ethylene dimethane sulfonate (EDS), STAC3 expression was observed to be decreased sharply in rat testis after selective withdrawal of Leydig cells (LCs), and reappeared immediately after LCs repopulation, indicating that testicular expression of STAC3 mainly stems from LCs. From a functional standpoint, in vivo lentiviral vector-mediated suppression of STAC3 resulted in a significant decrease in testosterone production, and thereafter caused impairment of male fertility by inducing oligozoospermia and asthenospermia. The indispensible involvement of STAC3 in testicular steroidogenesis was validated using the in vivo knockdown model with isolated primary LCs as well as in vitro experiments with primary LCs. By generating the TM3Stac3-/- cells, we further revealed that STAC3 depletion attenuated mitochondrial membrane potential and StAR processing in db-cAMP-stimulated LCs. Thus, the inhibitory effect of STAC3 deficiency on testicular steroidogenesis may be ascribed to a disturbed mitochondrial homeostasis. Collectively, the present results strongly suggest that STAC3 may function as a novel regulator linking mitochondrial homeostasis and testicular steroidogenesis in LCs. Our data underscore an unexpected reproductive facet of this muscle-derived factor.

Comprehensive analysis of inhibitor of differentiation/DNA-binding gene family in lung cancer using bioinformatics methods.

The inhibitor of differentiation/DNA-binding (ID) is a member of the helix-loop-helix (HLH) transcription factor family, and plays a role in tumorigenesis, invasiveness and angiogenesis. The aims were to investigate the expression patterns and prognostic values of individual ID family members in lung cancer, and the potential functional roles. The expression levels of ID family were assessed using the Oncomine online database and GEPIA database. Furthermore, the prognostic value of ID family members was evaluated using the Kaplan-Meier plotter database. The genetic mutations of ID family members were investigated using the cBioPortal database. Moreover, enrichment analysis was performed using STRING database and Funrich software. It was found that all the ID family members were significantly down-regulated in lung cancer. Prognostic results indicated that low mRNA expression levels of ID1 or increased mRNA expression levels of ID2/3/4 were associated with improved overall survival, first progression and post progression survival. Additionally, genetic mutations of ID family members were identified in lung cancer, and it was suggested that amplification and deep deletion were the main mutation types. Furthermore, functional enrichment analysis results suggested that ID1/2/4 were significantly enriched in 'regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism' for biological process, 'transcription factor activity' for molecular function and 'HLH domain' for protein domain. However, it was found that ID3 was not enriched in the above functions. The aberrant expression of ID family members may affect the occurrence and prognosis of lung cancer, and may be related to cell metabolism and transcriptional regulation.

Genetic and preimplantation diagnosis of cystic kidney disease with ventriculomegaly.

Ventriculomegaly with cystic kidney disease (VMCKD) is a rare and severe disorder characterized by cerebral ventriculomegaly, greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels and kidney disease similar to Finnish congenital nephrosis. Recessive mutations in the CRB2 (NM_173689) gene have been shown to cause the syndrome. Here, we described a nonconsanguineous Chinese family with two fetuses affected with VMCKD. A novel compound heterozygous mutation was identified in the CRB2 gene with co-segregation. One mutation [c.1960G>C (p.A654P)] was inherited from the father, while another mutation [c.3078_c.3093delGGCGCGGCCCCGGCCC (p.L1026Lfs*110)] was inherited from the mother. Preimplantation genetic testing for monogenic disease (PGT-M) was performed for the carrier couple with full informed consent and successfully blocked the inheritance of the disease. Our study has important implications on molecular diagnosis and genetic counseling for VMCKD and extends the mutation spectrum in CRB2 gene.

Bioinformatics identification of microRNAs involved in polycystic ovary syndrome based on microarray data.

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age. MicroRNAs (miRNAs or miRs) serve important roles in the physiological and pathological process of PCOS. To identify PCOS­associated miRNAs, the dataset GSE84376 was extracted from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE­miRNAs) were obtained from Gene­Cloud Biotechnology Information and potential target genes were predicted using TargetScan, DIANA­microT­CDS, miRDB and miRTarBase tools. Gene Ontology enrichment analysis was performed using Metascape and a protein­protein interaction network was constructed using Cytoscape. Transcription factors were obtained from FunRich. DE­miRNAs were verified by reverse transcription­quantitative PCR. At the screening phase, there were seven DE­miRNAs in the PCOS group not present in the control group. In total, 935 target genes were identified, which are involved in the development and maturation of oocytes. Mitogen­activated protein kinase 1, phosphatase and tensin homolog, cAMP responsive element binding protein 1, signal transducer and activator of transcription 3, interferon Î³, Fms­related tyrosine kinase 1, transcription factor p65, insulin receptor substrate 1, DnaJ homolog superfamily C member 10 and casein kinase 2 α 1 were identified as the top 10 hub genes in the protein­protein interaction network. Specificity protein 1 was the most enriched transcription factor. At the validation phase, the levels of Homo sapiens (hsa)­miR­3188 and hsa­miR­3135b were significantly higher in the PCOS group than in the control group. In addition, the expression level of hsa­miR­3135b was significantly correlated with the number of oocytes retrieved, the fertilization rate and the cleavage rate (P<0.05). The present bioinformatics study on miRNAs may offer a novel understanding of the mechanism of PCOS, and may serve to identify novel miRNA therapeutic targets.

Identification and potential value of candidate microRNAs in granulosa cells of polycystic ovary syndrome.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a major cause of anovulatory infertility. Some studies showed that miRNAs were used as diagnostic/prognostic biomarkers for various diseases. OBJECTIVE: To identify candidate miRNAs in Granulosa Cells (GCs) of PCOS and evaluate their potential values for PCOS diagnosis. METHODS: We screened differentially expressed miRNAs in GCs between PCOS and controls by the microarray data from the GEO database. GCs were collected from 21 controls and 24 PCOS. The candidate miRNAs were verified by qRT-PCR. The correlation was investigated between candidate miRNAs and clinical characteristics in participants. Diagnostic value of candidate miRNAs was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Seven miRNAs were differentially expressed in PCOS compared with controls. Furthermore, the validation results demonstrated that hsa-miR-3188 and hsa-miR-3135b showed higher levels in GCs with PCOS patients (p< 0.05). In addition, the expressions of hsa-miR-3188 and hsa-miR-3135b were negative correlated with FSH and hsa-miR-3188 was positive correlated with BMI (p< 0.05). ROC analysis indicated that hsa-miR-3188 and hsa-miR-3135b could differentiate PCOS from controls, and the hsa-miR-3188/3135b improved the predictive accuracy for PCOS. CONCLUSIONS: The expressions of hsa-miR-3188 and hsa-miR-3135b in human GCs were significantly associated with PCOS. Moreover, the hsa-miR-3188/3135b has certain diagnostic value for distinguishing PCOS.

Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study.

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) can potentially develop symptom flares after exposure to minor bladder irritants such as subclinical bacterial infection. To reproduce this symptom onset, we intravesically instilled a sub-noxious dose of uropathogenic E. coli component lipopolysaccharide (LPS) in young URO-OVA/OT-I mice, a transgenic autoimmune cystitis model that spontaneously develops bladder inflammation at ≥10 weeks of age. Female URO-OVA/OT-I mice (6-weeks old) were treated intravesically with phosphate-buffered saline (PBS) or PBS containing a sub-noxious dose (1 µg) of LPS. Mice were evaluated for bladder inflammation, pelvic pain, and voiding dysfunction at days 1, 7, and 14 post-treatment. Mice treated with LPS but not PBS developed early bladder inflammation with increased macrophage infiltration. Accordingly, the inflamed bladders expressed increased levels of mRNA for proinflammatory cytokines (IL-1ß and IL-6) and pain mediator (substance P precursor). In addition, LPS-treated mice exhibited pelvic pain and voiding dysfunction such as increased urinary frequency and reduced bladder capacity. These functional changes sustained up to day 14 tested. Our results indicate that a single sub-noxious dose of intravesical LPS triggers early bladder inflammation and symptom onset in URO-OVA/OT-I mice, providing a useful model for IC/BPS symptom flare study.

Expression of miR-590 in lung cancer and its correlation with prognosis.

The study aim was to evaluate the association of the expression of serum microribonucleic acid-590 (miR-590) with the risk of lung squamous cell carcinoma (LUSC), clinicopathological staging and prognosis. A total of 237 patients with LUSC and 100 healthy volunteers (control group) were included in the study. Total RNA was extracted from the peripheral blood serum of the subjects, and the expression level of miR-590 was detected by reverse transcription real-time quantitative polymerase chain reaction. The baseline clinicopathological information of LUSC patients was evaluated, and the patients were followed up with the median follow-up of 47 months. Compared with that in the control group, the expression level of serum miR-590 in LUSC patients was significantly decreased [0.532 (0.367- 0.821) vs. 1.63 (0.893-1.347), P<0.001]. The receiver operating characteristic (ROC) curve showed that the value of predicting LUSC risk using miR-590 was high, the area under curve (AUC) was 0.883, and 95% confidence interval (CI) was 0.829-0.934. In addition, the expression level of serum miR-590 was correlated with pathological staging (P=0.022), lymph node metastasis (P=0.012), distant metastasis (P<0.001) and tumor, node and metastasis (TNM) staging (P=0.044). The overall survival (OS) of patients in the serum miR-590 low expression group was significantly lower than that of the serum miR-590 high expression group (P=0.012), and the low expression of miR-590 was an independent risk factor for the prognosis of patients [hazard ratio (HR)=2.152, 95% CI=1.285-3.233, P=0.004]. The results suggested that the expression level of miR-590 can be used as a biomarker for the risk of disease, disease staging and prognosis of LUSC patients.

Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study.

Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1ß, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC/BPS research.

Comparison of mammography and ultrasound in detecting residual disease following bioptic lumpectomy in breast cancer patients.

Surgical biopsy is a method for diagnosing breast cancer. The aim of this study was to prospectively evaluate the relative accuracies of mammography (MMG) and ultrasound (US) in predicting residual disease following bioptic lumpectomy. Each prediction method was compared with the gold standard of surgical pathology. The results of MMG and US from 312 consecutive breast cancer patients diagnosed by surgical excision were analyzed. All the patients underwent re-excision mastectomy or lumpectomy and the imaging results were compared with the histopathological findings. The accuracy and sensitivity of each modality were investigated. A total of 312 patients with 312 primary breast cancers were investigated. Residual disease was identified in 118 patients. Of the 118 cases with residual disease, MMG and US were able to detect 77 (65.3%) and 32 (27.1%), respectively (chi-square P<0.001). MMG was also more sensitive compared with US in estimating residual ductal carcinoma in situ (DCIS) (94.2 vs. 33.3%, respectively; P<0.001). MMG was more accurate compared with US in detecting residual disease following bioptic lumpectomy and the diagnostic accuracy of MMG was associated with the presence of residual DCIS.

Menopausal Symptoms and Sleep Quality During Menopausal Transition and Postmenopause.

BACKGROUND: Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms and sleep quality in menopausal transition (MT) and postmenopause (PM) women in Taiyuan, Shanxi. METHODS: A community-based survey of women's menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40-59 years was divided into four groups: early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0. RESULTS: The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep. CONCLUSIONS: Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high.

Analysis of Polygala tenuifolia Transcriptome and Description of Secondary Metabolite Biosynthetic Pathways by Illumina Sequencing.

Radix polygalae, the dried roots of Polygala tenuifolia and P. sibirica, is one of the most well-known traditional Chinese medicinal plants. Radix polygalae contains various saponins, xanthones, and oligosaccharide esters and these compounds are responsible for several pharmacological properties. To provide basic breeding information, enhance molecular biological analysis, and determine secondary metabolite biosynthetic pathways of P. tenuifolia, we applied Illumina sequencing technology and de novo assembly. We also applied this technique to gain an overview of P. tenuifolia transcriptome from samples with different years. Using Illumina sequencing, approximately 67.2% of unique sequences were annotated by basic local alignment search tool similarity searches against public sequence databases. We classified the annotated unigenes by using Nr, Nt, GO, COG, and KEGG databases compared with NCBI. We also obtained many candidates CYP450s and UGTs by the analysis of genes in the secondary metabolite biosynthetic pathways, including putative terpenoid backbone and phenylpropanoid biosynthesis pathway. With this transcriptome sequencing, future genetic and genomics studies related to the molecular mechanisms associated with the chemical composition of P. tenuifolia may be improved. Genes involved in the enrichment of secondary metabolite biosynthesis-related pathways could enhance the potential applications of P. tenuifolia in pharmaceutical industries.

Effect of cervus and cucumis peptides on osteoblast activity and fracture healing in osteoporotic bone.

Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.