Secular trends of incidence and hospitalization cost of hip fracture in Tangshan, China.

We investigated the secular trends of the incidence and hospitalization cost of hip fracture in Tangshan, China. The incidence of hip fracture and the hospitalization cost were both increasing during the observation period. INTRODUCTION: The present study aimed to determine sex-, age-, and fracture type-specific incidence and annual changes in hip fractures in Tangshan, China, between 2007 and 2018. METHODS: We analyzed annual hip fracture incidence using urban hospital data during 2007-2018 and calculated incidence rate/100,000 person years in each age group and sex. We assessed annual changes in incidence among people aged >60 years using linear-by-linear association tests and evaluated hospitalization costs with the Kruskal-Wallis test. RESULTS: During the study period, we observed an increasing proportion of hip fractures in people >60 years old from 14.2 to 22.79%. Crude hip fracture incidence increased markedly from 140.87 to 306.56/100,000 in women (p < 0.01) and from 124.83 to 167.19/100,000 in men (p < 0.01) in the age group >60 years. Type-specific analysis indicated significantly increased trends in incidence of cervical and trochanteric fractures among women and cervical fracture among men (p < 0.01). In people aged 36-60 years, the trend of hip fracture increased significantly in both sexes. The total and cervical-to-trochanteric ratio in men increased, with significant upward trends (p < 0.01). The proportion of cervical fracture was higher than that for trochanteric fracture in women, with stable levels from 2007 to 2018. Hospitalization costs for cervical and trochanteric fractures increased by 51.91% and 53.20%, respectively, during 2011-2018. CONCLUSION: Tangshan will have an increasing burden on health care resources attributable to a considerable rise in hip fracture incidence and the older population. Further investigation of risk factors and subsequent implementation of effective measures to prevent hip fracture are needed.

Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis.

OBJECTIVE: Abnormal remodeling of subchondral bone (SB) induced by estrogen deficiency has been shown to be involved in osteoarthritis (OA). Raloxifene (RAL) is commonly used to treat postmenopausal osteoporosis (OP). However, little is known about its effects on OA combined with estrogen deficiency. This study was performed to evaluate the efficacy of RAL on patella baja-induced patellofemoral joint OA (PFJOA) in an ovariectomized rat model. DESIGN: Patellar ligament shortening (PLS) and ovariectomy (OVX) were performed simultaneously in 3-month-old female Sprague-Dawley rats, which were treated with RAL (10 mg/kg/day) or vehicle at 72 h postoperatively for 10 weeks. PFJOA was assessed by immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), micro-computed tomography (µCT), histomorphology and behavioral analyses. RESULTS: X-ray examinations showed that patella baja was successfully established by PLS. Histomorphological analysis revealed that PFJOA was significantly exacerbated by OVX and markedly alleviated by RAL. Moreover, RAL improved cartilage metabolism by decreasing MMP-13, ADAMTS-4, and caspase-3 and increasing Col-II and aggrecan at both the protein and mRNA levels. Furthermore, RAL markedly improved bone mass and SB microarchitecture and reduced osteoclast numbers and the serum osteocalcin and CTX-I levels. Although RAL showed a trend toward reducing pain sensitivity based on mechanical allodynia testing, this result was not statistically significant. CONCLUSION: These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP.

Parathyroid hormone (1-34) promotes fracture healing in ovariectomized rats with type 2 diabetes mellitus.

Ovariectomized (OVX) rats with type 2 diabetes mellitus (T2DM) with femur fracture received vehicle, insulin, or insulin plus parathyroid hormone (PTH) treatment for 2 and 3 weeks. Radiography, histomorphometry, histology, and immunohistochemistry in callus were evaluated. INTRODUCTION: Reports about effects of PTH plus insulin on callus formation of osteoporotic fracture with T2DM were limited. This study was designed to investigate the effects of the combination of PTH and insulin on fracture healing in OVX rats with T2DM. METHODS: Two-month-old female rats were randomly divided into five groups: normal fracture (F), OVX fracture (OF), T2DM + OVX fracture (DOF), insulin-treated (2-4 u/daylight, 4-6 u/night, DOFI), and treated with insulin and PTH (50 µg/kg/day, 5 days/week, DOFIP). A closed mid-shaft fracture was established in the right femurs of all rats after 6 weeks of OVX. Rats were euthanized at 2 and 3 weeks post-fracture according to the time schedule, respectively. RESULTS: The administration of insulin alone or insulin combined with PTH significantly increased mineralized bone volume fraction (BV/TV) and connectivity density (Conn.D) compared with those of the DOF group at 3 weeks post-fracture and also increased cartilaginous callus area ratio in the DOFI and DOFIP groups at 2 weeks and bony callus area ratio in the DOFIP groups at both the 2 and 3 weeks post-fracture. CONCLUSIONS: OVX rats with T2DM exhibited a marked delay in the fracture healing process; insulin treatment ameliorated these effects, and the healing process was enhanced following treatment with a combination of insulin and PTH.

Parathyroid hormone(1-34) exhibits more comprehensive effects than celecoxib in cartilage metabolism and maintaining subchondral bone micro-architecture in meniscectomized guinea pigs.

OBJECTIVE: To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). METHOD: Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1-34) (24 µg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. CONCLUSIONS: Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture.

Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats.

UNLABELLED: We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae. INTRODUCTION: The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats. METHODS: We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression. RESULTS: At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats. CONCLUSIONS: Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.

Parathyroid hormone (1-34) prevents cartilage degradation and preserves subchondral bone micro-architecture in guinea pigs with spontaneous osteoarthritis.

OBJECTIVE: To assess whether parathyroid hormone (PTH) (1-34) could improve the micro-structure of subchondral bone, and retard cartilage degradation in a naturally occurring Osteoarthritis (OA) model. DESIGN: Forty-eight 1-month-old guinea pigs were divided into two groups: 32 were treated by normal saline (NS) and sacrificed at 1, 3, 6 and 9 months of age; the other 16 received PTH (1-34) from 3 months, and were sacrificed at 6 and 9 months. Masson staining and the Osteoarthritis Research Society International (OARSI) grade scores were used to assess cartilage degradation. Immunohistochemistry analyses of type-II collagen, matrix metalloproteinases-13 (MMP-13) and sclerostin (SOST) in the cartilage, osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) and PTH receptor (PTH1R) in the cartilage and subchondral bone were performed. Subchondral bone micro-architecture was assessed by micro-computed tomography (micro-CT). RESULTS: Histological analyses revealed OA occurred at 3 months of age and was more severe with increasing age, and PTH (1-34) reduced the OARSI scores at 6 and 9 months of age. Micro-CT analysis indicated that PTH (1-34) treatment increased the bone volume ratio and bone mineral density (BMD), while retarding the subchondral trabecular bone micro-architectural changes from rod-like to plate-like. Immunohistochemical staining demonstrated that PTH (1-34) treatment increased type-II collagen expression and decreased SOST and MMP-13 expression in the cartilage, while elevating the PTH1R, OPG/RANKL expression ratio in the cartilage and subchondral trabecular bone when compared with the control groups. CONCLUSIONS: PTH (1-34) can prevent cartilage damage progression and retard the deterioration of subchondral trabecular bone in guinea pigs.

Apoptosis of human gastric cancer cells line SGC 7901 induced by garlic-derived compound S-allylmercaptocysteine (SAMC).

BACKGROUND: Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic (Allium sativum) have anticancer activity. Hepatocellular carcinoma is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced Hepatocellular carcinoma leading to an urgent need to seek for novel therapeutic options. AIM: To investigate the effect of cell growth, cell apoptosis of Garlic-Derived Compound S-Allylmercaptocysteine (SAMC) on Human Gastric Cancer Cells Line SGC 7901 cells. MATERIALS AND METHODS: The SGC 7901 cells were cultured with different concentration's SAMC. Cell viability was detected by AO/EB staining. JNK and P38 pathway were assayed by PCR (polymerase chain reaction). RESULTS: The best concentration of SAMC (300 µM) for induction SGC 7901 apoptosis was confirmed through cell viability. The PCR assay demonstrated that JNK and P38 pathway play important role in apoptosis of SGC 7901 cells. CONCLUSIONS: This study indicated that SAMC can inhibit cell proliferation and induct apoptosis of SGC 7901 cells via JNK and P38 pathway.

PDE3A is hypermethylated in cisplatin resistant non-small cell lung cancer cells and is a modulator of chemotherapy response.

OBJECTIVE: In this study, we aimed to investigate the mechanism of PDE3A downregulation in chemoresistant non-small cell lung cancer (NSCLC) cells, its functional role in chemotherapy response and association with survival outcomes. MATERIALS AND METHODS: The raw data of GDS5247 was downloaded from GEO datasets and reanalyzed. The expression of PDE3A in patients with NSCLC and its DNA methylation status were analyzed in NSCLC cohort in TCGA database. Cisplatin resistant A549/Cis cells and the parental A549 cells were used as the in vitro cell model. The association between PDE3A expression and overall survival (OS) and progression-free survival (PFS) in NSCLC patients with adenocarcinoma or squamous cell carcinoma, as well as the median OS and PFS, were assessed by Kaplan-Meier curves using Kaplan-Meier plotter. RESULTS: PDE3A was significantly downregulated in chemoresistant NSCLC cells. Heat map of PDE3A expression and methylation in NSCLC patient cohort in TCGA database indicated a negative association between PDE3A expression and DNA methylation in lung adenocarcinoma. A549/Cis cells treated with 5-AZA-dC, a demethylation reagent, had significantly restored PDE3A expression. High PDE3A expression was associated with favorable OS (HR: 0.53, 95% CI: 0.41-0.68, p<0.0001) and PFS (HR: 0.54, 95% CI: 0.39-0.75, p<0.001) in patients with adenocarcinoma. However, in patients with squamous cell carcinoma, high PDE3A expression was associated with unfavorable OS (HR: 1.56, 95% CI: 1.08-2.24, p=0.017) and PFS (HR: 1.83, 95% CI: 1.02-3.29, p=0.04). CONCLUSIONS: PDE3A is downregulated in chemoresistant NSCLC cells due to DNA hypermethylation. Enforced PDE3A expression can sensitize A549/Cis cells to cisplatin. High PDE3A expression is associated with better OS and PFS in patients with adenocarcinoma, but not in patients with squamous cell carcinoma.

Downregulation of miR-361-5p associates with aggressive clinicopathological features and unfavorable prognosis in non-small cell lung cancer.

OBJECTIVE: To assess the impact of miR-361-5p expression levels on non-small-cell lung cancer (NSCLC) survival. PATIENTS AND METHODS: A total of 183 patients with NSCLC who underwent surgery between October 2007 and April 2010 were included in this study. Expression levels of miR-361-5p were detected by using qRT-PCR. The association of miR-361-5p expression with clinicopathologic characteristics of NSCLC patients was analyzed. Kaplan-Meier Plotter was performed to identify the prognostic roles of miR-361-5p in NSCLC patients. Finally, multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Results indicated that miR-361-5p was lowly expressed in NSCLC compared with adjacent non-malignant tissues (p < 0.01). And low miR-361-5p expression in NSCLC was significantly correlated with TNM stage (p = 0.000), lymph node metastasis (p = 0.001) and lymphatic invasion (p = 0.032). Kaplan-Meier analysis with the log-rank test indicated that low miR-361-5p expression had a significant impact on overall survival (p < 0.001). Furthermore, Multivariate analyses indicated that miR-361-5p represented an independent predictor for overall survival of NSCLC (p = 0.007). CONCLUSIONS: Our work revealed that miR-361-5p played critical roles in NSCLC progression and could represent a novel prognostic marker in NSCLC patients.

Overexpression of long-noncoding RNA ZFAS1 decreases survival in human NSCLC patients.

OBJECTIVE: The purpose of the current study was to characterize the expression of long-noncoding-RNA ZFAS1 (ZFAS1) and assess the clinical significance of ZFAS1 in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 173 patients with NSCLC were addressed in the present retrospective study. Expression levels of ZFAS1 were detected by quantitative real-time PCR. We further analyzed the correlation between ZFAS1 and clinicopathologic features of NSCLC with X2-test. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Univariate and multivariate analyses were performed to analyze the prognostic significance of ZFAS1 expression. RESULTS: ZFAS1 was upregulated in NSCLC tissues (p < 0.01) and higher expression levels of ZFAS1 were found in more advanced tumor tissues (All p < 0.05). ZFAS1 expression levels were significantly associated with tumor differentiation grade (p = 0.028), lymph node metastasis (p = 0.001) and TMN stage (p = 0.001). Furthermore, we found that patients with higher ZFAS1 expression level are associated with a poorer overall survival. Univariate and multivariate analyses indicated that high ZFAS1 expression was an independent prognostic factor for poor survival of NSCLC patients. CONCLUSIONS: Our results illustrated the potential role of ZFAS1 as a prognostic marker for NSCLC patients.