ß-Cell miRNA-503-5p Induced by Hypomethylation and Inflammation Promotes Insulin Resistance and ß-Cell Decompensation.

Chronic inflammation promotes pancreatic ß-cell decompensation to insulin resistance because of local accumulation of supraphysiologic interleukin 1ß (IL-1ß) levels. However, the underlying molecular mechanisms remain elusive. We show that miR-503-5p is exclusively upregulated in islets from humans with type 2 diabetes and diabetic rodents because of its promoter hypomethylation and increased local IL-1ß levels. ß-Cell-specific miR-503 transgenic mice display mild or severe diabetes in a time- and expression-dependent manner. By contrast, deletion of the miR-503 cluster protects mice from high-fat diet-induced insulin resistance and glucose intolerance. Mechanistically, miR-503-5p represses c-Jun N-terminal kinase-interacting protein 2 (JIP2) translation to activate mitogen-activated protein kinase signaling cascades, thus inhibiting glucose-stimulated insulin secretion (GSIS) and compensatory ß-cell proliferation. In addition, ß-cell miR-503-5p is packaged in nanovesicles to dampen insulin signaling transduction in liver and adipose tissues by targeting insulin receptors. Notably, specifically blocking the miR-503 cluster in ß-cells effectively remits aging-associated diabetes through recovery of GSIS capacity and insulin sensitivity. Our findings demonstrate that ß-cell miR-503-5p is required for the development of insulin resistance and ß-cell decompensation, providing a potential therapeutic target against diabetes. ARTICLE HIGHLIGHTS: Promoter hypomethylation during natural aging permits miR-503-5p overexpression in islets under inflammation conditions, conserving from rodents to humans. Impaired ß-cells release nanovesicular miR-503-5p to accumulate in liver and adipose tissue, leading to their insulin resistance via the miR-503-5p/insulin receptor/phosphorylated AKT axis. Accumulated miR-503-5p in ß-cells impairs glucose-stimulated insulin secretion via the JIP2-coordinated mitogen-activated protein kinase signaling cascades. Specific blockage of ß-cell miR-503-5p improves ß-cell function and glucose tolerance in aging mice.

Excessive proliferation and apoptosis of parathyroid cells contribute to primary hyperparathyroidism in rabbit model.

To explore the molecular pathogenesis of primary hyperparathyroidism (PHPT), we investigated the proliferation and apoptosis of parathyroid cells in a rabbit model of diet-induced PHPT. A total of 120 adult Chinese rabbits were randomly divided into normal diet (Ca:P, 1:0.7) group (control group) or a high-phosphate diet (Ca:P, 1:7) group (experimental group). The thyroid and parathyroid complexes were harvested for 1-month interval from month 1 to month 6. The expression of proliferation markers, including proliferating cell nuclear antigen (PCNA) and cyclin-D1, and B cell lymphoma-2 (Bcl-2), were evaluated by immunohistochemistry in thyroid and parathyroid tissues. Apoptosis was quantified by DNA-fragment terminal labeling. Our results demonstrated that parathyroid cells in the experimental group started proliferating from the end of the 2nd month, the expression of PCNA, Bcl-2, and cyclin-D1 were significantly higher in the PHPT group than those of the control group (p<0.05). Furthermore, the apoptosis index (AI) was positively correlated with the glandular cell count and expression of PCNA in the 6th month in the PHPT group. Overall, our results suggested that excessive proliferation and apoptosis of parathyroid cells may contribute to the pathogenesis of PHPT through PCNA-related, Bcl-2-related, and cyclin-D1-related pathways.

Rab31, a receptor of advanced glycation end products (RAGE) interacting protein, inhibits AGE induced pancreatic ß-cell apoptosis through the pAKT/BCL2 pathway.

Receptor of advanced glycation end products (RAGE) mediates diverse signal transduction following ligand stimulation and plays an important role in diabetes complications and aging associated disease. We have previously verified that advanced glycation end products (AGE) bind to RAGE to cause pancreatic ß-cell apoptosis through the mitochondrial pathway. However, the direct interacting protein(s) of RAGE in ß cells has never been appreciated. In the present study, we utilized GST pull-down assay combined with mass spectrometry to identify the interacting proteins of the RAGE intracellular domain (C-terminal 43 amino acid of RAGE). Overall four RAGE interacting proteins, including Rab31, were identified with scores over 160. Rab31 was detected in three ß-cell lines and confirmed to have interacted with RAGE via co-immunoprecipitation and immunostaining assays. This interaction was further enhanced by glycation-serum (GS) stimulation due to membrane distribution of Rab31 following treatment with GS. We further confirmed that Rab31 promoted RAGE endocytosis and inhibited GS-induced ß-cell apoptosis through the pAKT/BCL2 pathway. These findings reveal a new RAGE interaction protein Rab31 that prevents AGE/RAGE-induced pancreatic ß-cell apoptosis. Rab31 is therefore a promising therapeutic target for preserving functional ß cells under diabetes conditions.

High-resolution 3T magnetic resonance imaging and histological analysis of capsuloligamentous complex of the first metatarsophalangeal joint.

BACKGROUND: There are discrepancies in the understanding of the structure of the capsuloligamentous complex of the first metatarsophalangeal joint (MTPJ); this study aims to investigate the differences with previous anatomical reports of high-resolution 3T magnetic resonance imaging (MRI) and histological analysis in illustrating the structure of the capsuloligamentous complex of the first MTPJ. METHODS: Nine fresh frozen cadaveric feet specimens (from two women and three men; aged 32 to 58 years) were used in this study. All specimens underwent MR examination with T1-weighted imaging and T2-weighted spectral attenuated inversion recovery in three planes. Subsequently, all cadaveric feet specimens were sliced into 2-mm-thick sections. The MRI features of the capsuloligamentous complex of the first MTPJ were analyzed in these specimens. Hematoxylin-eosin and Masson's trichrome staining methods were used to explore the histologic features of the capsuloligamentous complex of the first MTPJ. RESULTS: Different from most previous studies, our results showed that the plantar plate could be divided into four portions including the central portion of the plantar plate, the intersesamoid, the sesamoid phalangeal and the metatarsosesamoid ligaments. The normal central portion of the plantar plate could be clearly visualized in the sagittal and coronal plane MR images. The intersesamoid ligament is a continuation of the central portion of the plantar plate on the sagittal plane on the gross specimen, the MR imaging, and the histological examination. On the coronal plane of the gross specimen and MR imaging, the sesamoid phalangeal ligaments and the central portion of the plantar plate can be seen as separate ligaments, but they appeared interwoven with the same continuous collagenous fibers on the histological analysis. CONCLUSION: High-resolution 3T MRI allows accurate demonstration of the different anatomical details of the capsuloligamentous complex of the first MTPJ from previous anatomical reports. The histological analysis provides further understanding of the structures of the capsuloligamentous complex of the first MTPJ from previous studies.

Traumatic injury of the triangular fibrocartilage complex (TFCC)-a refinement to the Palmer classification by using high-resolution 3-T MRI.

OBJECTIVE: The aim of this study was to investigate the MR features of the traumatic injury of the triangular fibrocartilage complex (TFCC) by using high-resolution 3-T magnetic resonance imaging (MRI) and to refine the Palmer classification system. MATERIALS AND METHODS: From November 2015 to May 2019, sixty-seven patients met the including and excluding criteria and were enrolled into this retrospective study. All subjects had high-resolution 3-T MRI scan of the wrist and eleven had indirect MR arthrography of the wrist. All the MRI were read by two experienced musculoskeletal radiologists. Diagnostic sensitivity, specificity, and accuracy of MRI were calculated by using the arthroscopy and surgery as the standard of reference. A P value less than 0.05 was considered statistically significant. The interobserver agreement was assessed by kappa analysis. RESULTS: There were 49 cases of TFCC injuries proven by the arthroscopy or surgery. The TFCC injuries in the other 18 patients were proved by the combination of clinical follow-up examination and follow-up MRI. Among the arthroscopy- or surgery-confirmed cases, there were 32 patients with original Palmer injuries (IA = 10, IB = 19, ID = 3), 5 with capsular detachment, 4 with bucket-handle tear of the TFCC that have rarely been reported, and 8 with complex injuries that involved the listed classifications above. The sensitivities and specificities of MRI for diagnosing IA, IB, ID, complex injuries, and bucket-handle tear were 67-100% and 90-100%, and overall good to perfect interobserver agreements (kappa, 0.64-1.00). The diagnostic performance for the capsular detachment was lower (kappa, 0.38). CONCLUSION: With high-resolution 3-T MRI, more detailed injury patterns were found including capsular injuries, the horizontal tear of the articular disk, and the bucket-handle tear. It is necessary to refine the classic Palmer classification of TFCC injuries.

Sports Injury-Related Fingers and Thumb Deformity Due to Tendon or Ligament Rupture.

BACKGROUND: Hand injuries are very common in sports, such as skiing and ball sports. One of the major reasons causing hand and finger deformity is due to ligament and tendon injury. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) can demonstrate the complex anatomy of the fingers and thumb, especially the tendons and ligaments, and provide the accurate diagnosis of clinically important fingers and thumbs deformity due to ligamentous and tendinous injuries during sport activities. METHODS: Sixteen fresh un-embalmed cadaveric hands were harvested from eight cadavers. A total of 20 healthy volunteers' hands and 44 patients with fingers or thumb deformity due to sports-related injuries were included in this study. All subjects had MR examination with T1-weighted images and proton density-weighted imaging with fat suppression (PD FS) in axial, coronal, and sagittal plane, respectively. Subsequently, all 16 cadaveric hands were sliced into 2-mm thick slab with a band saw (six in coronal plane, six in sagittal plane, and four in axial plane). The correlation of anatomic sections and the MRI characteristics of tendons of fingers and the ulnar collateral ligament (UCL) at the metacarpal phalangeal joint (MCPJ) of thumb between 20 healthy volunteers and 44 patients (confirmed by surgery) were analyzed. RESULTS: The normal ligaments and tendons in 16 cadaveric hands and 20 volunteers' hands showed uniform low-signal intensity on all the sequences of the MRI. Among 44 patients with tendinous and ligamentous injuries in the fingers or thumb, 12 cases with UCL injury at MCPJ of the thumb (Stener lesion = 8 and non-Stener lesion = 4), 6 cases with the central slip injury, 12 cases with terminal tendon injury, and 14 cases with flexor digitorum profundus injury. The ligaments and tendons disruption manifested as increased signal intensity and poor definition, discontinuity, and heterogeneous signal intensity of the involved ligaments and tendons. CONCLUSIONS: Sports injury-related fingers and thumb deformity are relatively common. MRI is an accurate method for evaluation of the anatomy and pathologic conditions of the fingers and thumb. It is a useful tool for accurate diagnosis of the sports-related ligaments and tendons injuries in hand.

High-resolution 3-T MRI of the triangular fibrocartilage complex in the wrist: injury pattern and MR features.

OBJECTIVES: To investigate if using high-resolution 3-T MRI can identify additional injuries of the triangular fibrocartilage complex (TFCC) beyond the Palmer classification. MATERIALS AND METHODS: Eighty-six patients with surgically proven TFCC injury were included in this study. All patients underwent high-resolution 3-T MRI of the injured wrist. The MR imaging features of TFCC were analyzed according to the Palmer classification. RESULTS: According to the Palmer classification, 69 patients could be classified as having Palmer injuries (52 had traumatic tears and 17 had degenerative tears). There were 17 patients whose injuries could not be classified according to the Palmer classification: 13 had volar or dorsal capsular TFC detachment and 4 had a horizontal tear of the articular disk. CONCLUSION: Using high-resolution 3-T MRI, we have not only found all the TFCC injuries described in the Palmer classification, additional injury types were found in this study, including horizontal tear of the TFC and capsular TFC detachment. We propose the modified Palmer classification and add the injury types that were not included in the original Palmer classification.

Accuracy of Multi-Slice Spiral Computed Tomography for Preoperative Tumor Node Metastasis (TNM) Staging of Colorectal Carcinoma.

BACKGROUND With the advances in imaging technologies, multi-slice spiral computed tomography (MSCT) has demonstrated superiority in the diagnosis and staging of colorectal carcinoma. In the current study, preoperative TNM staging of colorectal carcinoma by using MSCT was conducted and compared with the corresponding postoperative pathological examination findings, in order to evaluate the accuracy of preoperative MSCT for TNM staging. MATERIAL AND METHODS Combinations of biphasic or triphasic enhanced-phase MSCT scans were obtained for 76 patients with colorectal carcinoma, and the TNM stage was determined based on imaging reconstruction from various angles and perspectives to display the size, location, and affected range of tumors. The preoperative TNM stage was compared with the postoperative pathological stage, and the consistency between the 2 methods was tested by the k test using SPSS 17.0 software. RESULTS Among the different combinations of enhanced-phase MSCT scanning, triphasic MSCT imaging, comprising the arterial, portal venous, and delayed phases, showed the highest accuracy rates, at 81.6% (62/76), 82.89% (63/76), and 96.1% (73/76) for T, N, and M staging, respectively, with k values of 0.72, 0.65, and 0.56, respectively, indicating consistency with the postoperative pathological staging. CONCLUSIONS Combined MSCT scanning comprising the arterial phase, portal venous phase, and delayed phase showed satisfying consistency with the postoperative pathological analysis results for TNM staging of colorectal carcinoma. Thus, MSCT is an important clinical value for improving the accuracy of TNM staging and for planning the appropriate colorectal cancer treatment.

High-resolution 3T Magnetic Resonance Imaging of the Triangular Fibrocartilage Complex in Chinese Wrists: Correlation with Cross-sectional Anatomy.

BACKGROUND: The injury of the triangular fibrocartilage complex (TFCC) is a common cause of ulnar-sided wrist pain. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) could demonstrate the detailed complex anatomy of TFCC in Chinese. METHODS: Fourteen Chinese cadaveric wrists (from four men and three women; age range at death from 30 to 60 years; mean age at 46 years) and forty healthy Chinese wrists (from 20 healthy volunteers, male/female: 10/10; age range from 21 to 53 years with a mean age of 32 years) in Beijing Jishuitan Hospital from March 2014 to March 2016 were included in this study. All cadavers and volunteers had magnetic resonance (MR) examination of the wrist with coronal T1-weighted and proton density-weighted imaging with fat suppression in three planes, respectively. MR arthrography (MRAr) was performed on one of the cadaveric wrists. Subsequently, all 14 cadaveric wrists were sliced into 2 mm thick slab with band saw (six in coronal plane, four in sagittal plane, and four in axial plane). The MRI features of normal TFCC were analyzed in these specimens and forty healthy wrists. RESULTS: Triangular fibrocartilage, the ulnar collateral ligament, and the meniscal homolog could be best observed on images in coronal plane. The palmar and dorsal radioulnar ligaments were best evaluated in transverse plane. The ulnotriquetral and ulnolunate ligaments were best visualized in sagittal plane. The latter two structures and the volar and dorsal capsules were better demonstrated on MRAr. CONCLUSION: High-resolution 3T MRI is capable to show the detailed complex anatomy of the TFCC and can provide valuable information for the clinical diagnosis in Chinese.

Functional connectivity of motor cortical network in patients with brachial plexus avulsion injury after contralateral cervical nerve transfer: a resting-state fMRI study.

INTRODUCTION: The purpose of this study is to assess the functional connectivity of the motor cortical network in patients with brachial plexus avulsion injury (BPAI) after contralateral C7 nerve transfer, using resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: Twelve patients with total brachial plexus root avulsion underwent RS-fMRI after contralateral C7 nerve transfer. Seventeen healthy volunteers were also included in this fMRI study as controls. The hand motor seed regions were defined as region of interests in the bilateral hemispheres. The seed-based functional connectivity was calculated in all the subjects. Differences in functional connectivity of the motor cortical network between patients and healthy controls were compared. RESULTS: The inter-hemispheric functional connectivity of the M1 areas was increased in patients with BPAI compared with the controls. The inter-hemispheric functional connectivity between the supplementary motor areas was reduced bilaterally. CONCLUSIONS: The resting-state inter-hemispheric functional connectivity of the bilateral M1 areas is altered in patients after contralateral C7 nerve transfer, suggesting a functional reorganization of cerebral cortex.

[MRI of the thumb collateral ligament at the metacarpophalangeal joint: anatomy and injuries].

OBJECTIVE: To explore the anatomy and injuries features of the thumb collateral ligamentat the metacarpophalangeal (MCP) joints. METHODS: The study was reviewed and approved by an institutional review board of hospital. Clinical imaging data of 7 healthy volunteers who without injuries and 20 patients with thumb collateral ligament injuries were retrospectively analyzed. All subjects underwent magnetic resonance examination, then comparative analysis of the normal anatomy and the thumb collateral ligament injury at MCP joints of MRI features in healthy volunteers and patients with injury. Imaging findings were compared with the surgical results and confirmed by followed up in patients. RESULTS: Seven volunteers without ligament injures showed homogeneous low-signal-intensity on T1-weighted and proton fat saturation sequence (PD-FS) images. The average thickness of the ulnarcollateral ligament is about 2.0 to 2.3 mm, however, the normal radial collateral ligament is thinner, the average thickness is about 1.4-1.5 mm. There were 20 patients with thumb collateral ligament injuresat MCP joints, including 12 cases of ulnar collateral ligament injury and 8 cases of radial collateral ligament injury, which demonstrated poor definition, discontinuity and heterogeneously increased signal intensity in proton fat saturation sequence (PD-FS) of the involved collateral ligament. There was edema in the soft tissues surrounding the injured sites. CONCLUSION: MRI is an accurate method for evaluation of the anatomy and pathologic conditions of the thumb collateral ligamentsat MCP joints, and it is a useful tool for early diagnosis and treatment of the thumb collateral ligaments injuries.

A correlation of computed tomography perfusion and histopathology in tumor edges of hepatocellular carcinoma.

BACKGROUND: The peripheral morphologic characteristics of hepatocellular carcinoma (HCC) reflect tumor growth patterns. Computed tomography (CT) perfusion is a new method to analyze hemodynamic changes in tissues. We assessed the relationship between CT perfusion and histopathologic findings in the periphery of HCC lesions. METHODS: Non-contrast CT, enhanced dual-phase CT, and CT perfusion were performed on 77 subjects (47 patients and 30 controls). Based on the imaging findings of enhanced dual-phase CT, the tumor edges were classified into three types: type I (sharp); type II (blurry); and type III (mixed). The CT perfusion parameters included hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. The tissue sections from resected specimens were subjected to routine hematoxylin and eosin staining and immunohistochemical staining for CD34. The correlations between microvessel density (MVD) and the CT perfusion parameters were analyzed using Pearson's product-moment correlation coefficient. Changes in the perfusion parameters in tumor edges of different tumor types were evaluated. RESULTS: Type I (sharp): the pathologic findings showed fibrous connective tissue capsules in the tumor edges, and an MVD ≤30/mm2. Type II (blurry): the histology showed that the edges were clear with no capsules and an MVD>30/mm2. Type III (mixed): the pathology was similar to that of types I and II, and an MVD>30/mm2. Hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion were significantly increased in the tumor edges of HCC patients compared to those of the controls (P<0.05). The correlation between CT perfusion parameters and MVD was higher in blurry tumor edges of type II than in those of types I or III. CONCLUSION: CT perfusion imaging of tumor edges may be helpful in revealing histopathological features, and indirectly reflect angiogenic changes of HCCs.

Investigation on the optical scan condition for imaging of multi-slice spiral CT liver perfusion in rats.

BACKGROUND: Multi-slice CT liver perfusion has been widely used in experimental studies of hemodynamic changes in liver lesions, and is usually performed as an adjunct to a conventional CT examination because of its high temporal and spatial resolution, simple protocol, good reproducibility, and ability to measure hemodynamic changes of liver tissues at the capillary level. Experimental rat models, especially those of induced liver cancer, are often used in studies of hemodynamic changes in liver cancer. Carcinogenesis in rats has a similar pathological progression and characteristics resembling those in human liver cancer; as a result, rat models are often used as ideal animal models in the study of human liver cancer. However, liver perfusion imaging in rats is difficult to perform, because rats' livers are so small that different concentrations, flow rates, and dose of contrast agents during the CT perfusion scanning can influence the quality of liver perfusion images in rats. The purpose of this study, therefore, was to investigate the optimal scan protocol for the imaging of hepatic perfusion using a deconvolution mathematical method in rats by comparing the results of rats in different injection conditions of the contrast agent, including concentration, rate and time. METHODS: Plain CT scan conditions in eighty 2-month-old male Wistar rats were 5.0 mm slice thickness, 5.0 mm interval, 1.0 pitch, 120 kV tube voltage, 60 mA tube current, 512 × 512 matrix, and FOV 9.6 cm. Perfusion scanning was carried out with different concentrations of diatrizoate (19%, 38%, 57%, and 76%), different injection rates (0.3 and 0.5 ml/s), and different injection times (1, 2-3, 4-5, and 6 seconds). The above conditions were randomly matched and adjusted to determine the best perfusion scan protocol. Three-phase contrast-enhanced scanning was performed after CT perfusion. Histological examination of the liver tissues with hematoxylin and eosin stains was done after CT scanning. RESULTS: When the concentration of the contrast agent was 19% or 38%, no pseudo-color map was created. The viscosity increased when the concentration of the contrast agent was 76%; so it is difficult to inject the contrast agent at such a high concentration. Also no pseudo-color map was generated when the injection time was short (1, 2-3, and 4-5 seconds) or the injection rate was low (0.3 ml/s). The best perfusion images and perfusion parameters were obtained during 50 seconds scanning. Each rat was given an injection of 57% diatrizoate at 0.5 ml/s via the tail vein using a high-pressure syringe for 6 seconds. The perfusion parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT) of the contrast agent, capillary permeability-surface area product (PS), hepatic arterial index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). All these parameters reflected the perfusion status of liver parenchyma in normal rats. Three phases of enhancement were modified according to the time-density curves (TDCs) of the perfusion imaging: hepatic arterial phase (7 seconds), hepatic portal venous phase (15 seconds), and a delayed phase (23-31 seconds). On examination by microscopy, the liver tissues were pathologically normal. CONCLUSIONS: The appropriate protocol with multi-slice spiral CT liver perfusion reflected normal liver hemodynamics in rats. This study laid a solid foundation for further investigation of the physiological characteristics of liver cancer in a rat model, and was an important supplement to and reference for conventional contrast-enhanced CT scans.

Assessment of hemodynamics in a rat model of liver cirrhosis with precancerous lesions using multislice spiral CT perfusion imaging.

RATIONALE AND OBJECTIVES: To develop an optimal scanning protocol for multislice spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. MATERIALS AND METHODS: Male Wistar rats were randomly divided into the control group (n = 80) and the precancerous liver cirrhosis group (n = 40). The control group received saline injection and the liver cirrhosis group received 50 mg/kg DEN i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting the diatrizoate concentration, the flow rate, and the delivery time. The hemodynamics of both groups was further compared using optimized multislice spiral CTP imaging. RESULTS: High-quality CTP images were obtained with following parameters: 150 kV; 150 mAs; 5 mm thickness, 5 mm interval; pitch, 1; matrix, 512 × 512; and FOV, 9.6 cm. Compared to the control group, the liver cirrhosis group had a significantly increased value of the hepatic arterial fraction and the hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal perfusion and mean transit time (P < 0.05). CONCLUSION: Multislice spiral CTP imaging can be used to evaluate the hemodynamic changes in the rat model of liver cirrhosis with precancerous lesions.

[Skeletal disease in primary hyperparathyroidism: X-ray, CT and MR imaging founding].

OBJECTIVE: To analyze the X-ray, CT and MR imaging findings in skeletal disease with primary hyperparathyroidism (PHPT), so as to discuss the clinic feature and differential diagnosis. METHODS: Thirty patients with PHPT were confirmed by surgery and pathological examination. In 15 patients the lesion were found in femur. There were 15 tibia, 12 fibula, and 14 iliac lesions. In three patients lesions were found in vertebrae. Three patients had lesions in humeri. In five patients lesions were found in rib. Twelve patients had lesions in phalanges. Thirty patients were studied preoperatively with radiographs, CT and MR imaging. The imaging findings were compared with the pathologic diagnosis and confirmed by double blind method. RESULTS: Radiographs of the bone in 30 patients showed generalised osteopaenia. There were 20 (66.7%) cases with bone resorption, which include 12 (40.0%) cases with subperiosteal resorption, 11 (36.7%) cases with cortical bone resorption, and 10 (33.3%) cases with subchondral resorption. There were 19 (63.3%) cases with osteitis fibrosa cystica/brown tumor. There were 5 (16.7%) patients sustained a pathological fracture. CONCLUSION: X-ray, CT and MR imaging founding reflect the imaging and pathology features in skeletal disease of PHPT. The iliac lesions could been found in common, and usually eroding sacroiliac joint. Skeletal disease of PHPT should be differentiated from osteolytic metastatic tumor of bone, osteodysplasia fibrosa, giant cell tumor of bone and aneurysmal bone cysts.

[Magnetic resonance imaging evaluation of early rheumatoid arthritis of hand and wrist].

OBJECTIVE: To explore the value of Magnetic resonance imaging (MRI) in the early rheumatoid arthritis (RA). METHODS: 56 patients (24 men and 32 women) fulfilling the 2010 ACR/EULAR for RA, 34 with early RA, and 22 with established RA, (disease duration < 12 months, and >12 months, respectively) were enrolled in the study. MRI of the dominant hand and wrist was performed by using short time inversion recovery (STIR), plain and contrast-enhanced T1-weighted sequences. Evaluation of bone marrow edema, bone erosions and synovitis was performed with the OMERACT RA MRI scoring system. RESULTS: Edema, erosions, and synovitis were present in early RA and established RA, and the prevalence was 88.2% (30/34), 91.1% (31/34), 100% (34/34) and 90.9% (20/22) , 95.4% (21/22), 100% (22/22) , respectively. But no significant difference was found in two group (P > 0.05). Significant differences in edema and erosions were found between earlier RA and established RA (P < 0.05). No significant difference was found in synovitis (P > 0.05). CONCLUSIONS: Bone marrow edema, bone erosions and synovitis are important sign of early RA. But bone edema and erosions in MRI may play an important role in the diagnosis of early RA.

Early changes of hepatic hemodynamics measured by functional CT perfusion in a rabbit model of liver tumor.

BACKGROUND: Early detection and treatment of hepatocellular carcinoma is crucial to improving the patients' survival. The hemodynamic changes caused by tumors can be serially measured using CT perfusion. In this study, we used a CT perfusion technique to demonstrate the changes of hepatic hemodynamics in early tumor growth, as a proof-of-concept study for human early hepatocellular carcinoma. METHODS: VX2 tumors were implanted in the liver of ten New Zealand rabbits. CT perfusion scans were made 1 week (early) and 2 weeks (late) after tumor implantation. Ten normal rabbits served as controls. CT perfusion parameters were obtained at the tumor rim, normal tissue surrounding the tumor, and control liver; the parameters were hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial index, hepatic arterial perfusion and hepatic portal perfusion. Microvessel density and vascular endothelial growth factor were correlated. RESULTS: At the tumor rim, compared to the controls, hepatic blood flow, hepatic blood volume, permeability of capillary vessel surface, hepatic arterial index, and hepatic arterial perfusion increased, while mean transit time and hepatic portal perfusion decreased on both early and late scans (P<0.05). Hepatic arterial index increased (135%, P<0.05), combined with a sharp increase in hepatic arterial perfusion (182%, P<0.05) and a marked decrease in hepatic portal perfusion (-76%, P<0.05) at 2 weeks rather than at 1 week (P<0.05). Microvessel density and vascular endothelial growth factor showed significant linear correlations with hepatic blood flow, permeability of capillary vessel surface and hepatic arterial index, but not with hepatic blood volume or mean transit time. CONCLUSION: The CT perfusion technique demonstrated early changes of hepatic hemodynamics in this tumor model as proof-of-concept for early hepatocellular carcinoma detection in humans.

[Relationship between proliferation and apoptosis of parathyroid cell in rabbits with primary hyperparathyroidism].

OBJECTIVE: To evaluate the effect of proliferation and apoptosis of parathyroid cell in rabbits with primary hyperparathyroidism (PHPT). METHODS: A total of 80 adult Chinese rabbits were randomly divided into two groups (n = 40 each). The control group was fed with a normal diet (Ca: P, 1:0.7) while the experimental group a high phosphate diet (Ca: P,1:7) for 3-, 4-, 5-, or 6-month intervals to establish the animal model of PHPT. The parathyroid was totally removed for pathological examination after all rabbits were sacrificed. The thyroparathyroid complex was removed en bloc, fixed in neutral formalin and prepared for histological examination. The number of parathyroid cell in PHPT was calculated. Proliferation was determined by immunohistochemistry of proliferation cell nuclear antigen (PCNA) while apoptosis assessed by in situ dUTP biotin nick-end labeling (TUNEL). RESULTS: The number of parathyroid cell was 1.61 times in PHPT than that in the normal control (673 +/- 151, 418 +/- 25, t = - 12.112, P < 0.01). Apoptotic index (AI) increased significantly more in PHPT than that in normal control (200.2 per thousand +/- 125.6 per thousand, 11.0 per thousand +/- 3.0 per thousand, t = -10.193, P < 0.01). The rate of PCNA positive-cell increased significantly more in PHPT than that in control (50.5 per thousand +/- 11.6 per thousand, 26.7 per thousand +/- 2.8 per thousand, t = -13.120, P < 0.05). So did Bcl-2 (460 per thousand +/- 190 per thousand, 67 per thousand +/- 4 per thousand, t = -14. 120, P < 0.05). There was a positive correlation between AI and PCNA (r = 0.861, P < 0.05). It was the same as between AI and Bcl-2 (r = 0.871, P < 0.05). The value of bone mineral density decreased significantly more in PHPT than that in normal control (152 +/- 34, 189 +/- 12, t = 9.236, P < 0.05). CONCLUSION: PHPT may be mainly induced by an excessive proliferation of parathyroid cells and an acceleration of apoptotic process.

[The study of an animal model in rabbits with the early primary hyperparathyroidism].

OBJECTIVE: to study the biochemistry of blood and feature of pathology of an animal model in rabbits with the early primary hyperparathyroidism(PHPT). METHODS: 60 rabbits were divided into six groups of 10 each and fed a control diet (Ca:P, 1:0.7) or a high-phosphate diet (Ca:P, 1:7) for 1-, 2- or 3-month intervals. Compared with the control animals, serum PTH levels, serum calcium levels and serum phosphorus levels were determined. The parathyroid and kidneys of all animals were performed by the histologic examination. RESULTS: compared with the control animals, serum parathyroid hormone (PTH) levels were elevated at 1-, 2-, 3-month intervals in experimental group (t = -7.665, t = -16.033, t = 12.877 respective, P < 0.05), whereas serum calcium levels were decreased at all three time intervals (t = 6.184, t = 9.329, t = 13.842, respective, P < 0.05), but serum phosphorus levels did not change (t = 0.611, t = 1.041, t = 1.941, respective, P > 0.05). Parathyroid histopathologic studies demonstrated no change at 1 month whereas six of ten experimental animals showed mild hyperplasia at 2 months and nine of ten showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2- and 3-month in the experimental groups. CONCLUSION: the high-phosphate diet successfully induced an animal model in rabbits with the early primary hyperparathyroidism, which has a better stability and reproducibility.

Solitary pulmonary nodules: comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density.

BACKGROUND: The solitary pulmonary nodule (SPN) is one of the most common findings on chest radiographs. The objectives of clinical practice are to differentiate malignant nodules from benign nodules in the least invasive way and to make a specific diagnosis. This study was aimed to evaluate the correlation between perfusion imaging features and microvessel density (MVD) and vascular endothelial growth factors (VEGF) in SPNs using multi-slice computed tomography (MSCT); and to provide the theoretical basis for SPN blood flow pattern and blood flow quantitative features. Also, the study called for the discussion of the method's clinical application value in the differential diagnosis of benign and malignant SPNs. METHODS: Sixty-eight patients with SPN underwent multi-location dynamic contrast enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 ml/s) MSCT. Precontrast and postcontrast attenuations on every scan was studied. Perfusion, peak height, and the ratio of the peak height of the SPN to that of the aorta were analyzed. Perfusion was calculated using the maximum gradient of the time-density curves (TDC) and the peak height of the aorta. The quantitative parameters (perfusion, peak height, ratio of peak height of the SPN to that of the aorta) of the blood flow pattern were compared with MVD and the VEGF expression of immunohistochemistry. RESULTS: The perfusion peak heights of malignant ((96.15 +/- 11.55) HU) and inflammatory ((101.15 +/- 8.41) HU) SPNs were significantly higher than those of benign ((47.24 +/- 9.15) HU) SPNs (P < 0.05, P < 0.05). Ratios of SPN-to-aorta of malignant and inflammatory SPNs were significantly higher than those of benign SPNs (P < 0.05, P < 0.05). No significant differences were found between the peak height and SPN-to-aorta ratio of malignant SPNs and inflammatory SPNs (P > 0.05, P > 0.05). The precontrast densities of inflammatory SPNs were lower than those of malignant SPNs (P < 0.05). Perfusion values of malignant and inflammatory SPNs were significantly higher than those of the benign SPNs (P < 0.05, P < 0.05). The VEGF positive expressions appeared in 32 patients with malignant SPNs and 2 patients with benign SPNs, and the average value of the MVD was higher in patients with malignant SPNs (36.88 +/- 6.76) than in patients with either benign (4.51 +/- 0.60) or inflammatory (26.11 +/- 5.43) SPNs (P < 0.05, P < 0.05). There were statistically significant correlations between the CT perfusion feature and the MVD. The highest correlation was between the peak height of SPN and the MVD (r = 0.657, P < 0.05). CONCLUSIONS: Tumor microvessel density and VEGF expression facilitate the exploration of the pathophysiological basis of CT perfusion in SPNs. Multi-slice CT perfusion has shown strong positive correlations with angiogenesis in SPNs.