[Magnetic resonance imaging features and classification of intraductal papillary neoplasm of the bile duct].

Objective: To explore the magnetic resonance imaging (MRI) features and classification of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Data from 90 patients with intraductal papillary neoplasm of the bile duct confirmed pathologically between June 2010 and January 2023 were retrospectively analyzed. The image analysis included the shape and location of the tumor, whether bile ducts had dilatation and the degree of dilation, whether there was a history of liver disease, whether there was a history of schistosomiasis, whether there was cancerous transformation, whether there were concurrent bile duct stones, whether there was hepatic lobe atrophy, whether there was hilar or abdominal lymph node enlargement, whether there was invasion of the bile duct wall, whether there was invasion of surrounding blood vessels, whether the tumor appears on T1-and T2 weighted imaging (T(1)WI and T(2)WI), whether the diffusion was limited, whether there was concurrent bleeding, enhancement rate, and whether there was abdominal fluid accumulation. Intraductal papillary neoplasms of the bile duct were divided into four types according to the morphological classification standards: type I (local bile duct dilation), type II (cystic), type III (free tumor), and type IV (dilated bile duct). The differences in the clinical and MRI features of the four groups of lesions were analyzed. Statistical analysis was performed with a t-test, an analysis of variance, and an χ(2)-test according to the different data. Results: Among the 90 cases with hepatic IPNB, there were 31 cases of type I, 15 cases of type II, 16 cases of type III, and 28 cases of type IV, 41 cases of liver left lobe, 11 cases of right and left lobe liver span, 7 cases of liver right lobes, 2 cases of liver caudate lobe, and 13 cases of hepatic hilar. There were statistically significant differences between the four groups (P < 0.05) in terms of age, clinical symptoms, direct bilirubin, γ-glutamyltransferase, whether they were cancerous, whether they were combined with bile duct stones, whether the liver lobes were atrophying, whether there was limited diffusion, intrahepatic bile duct diameter, and common bile duct diameter. However, there were no statistically significant differences among the four groups in gender, location, carbohydrate antigen 19-9, history of liver disease, history of schistosomiasis, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, total bilirubin, whether hemorrhage was associated, lesion enhancement rate, whether the hilar/retroperitoneal lymph node was enlarged, whether the bile duct wall was invaded, whether blood vessels were invaded, and whether abdominal fluid was accumulated (P > 0.05). Conclusion: MRI manifestations have certain features for different types of intraductal papillary neoplasm of the bile duct tumors; hence, MRI aids in the diagnosis and differential diagnosis of this disease.

[Fumarate hydratase deficient uterine leiomyoma: a clinicopathological and molecular analysis of 80 cases].

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.

Time resolved absolute extreme ultraviolet radiation measurement on the ENN XuanLong-50 spherical tokamak.

A plasma radiation measurement system for a wide spectral range, based on compact Absolute eXtreme UltraViolet (AXUV) silicon photodiodes, has been implemented on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak. The system consists of two 16-channel AXUV16ELG arrays and one AXUV63HS1 single-cell detector mounted on ceramic sockets. The two arrays, facing toward the EXL-50 slim central post from two locations inside a top and a side ConFlat 400 port, have 32 view chords covering the interested plasma region in a poloidal cross section at toroidal 330°. The single-cell detector, seated on a retractable feedthrough, could be arranged flexibly with the help of an ultra-high vacuum compatible gate valve. The design details together with considerations on the EXL-50 specific engineering realities and physics requirements are described. Preliminary results from the EXL-50 2020 experimental campaign are presented.

Real-time signal processing system based on FPGA for motional Stark effect diagnostic on EAST.

The plasma current density profile plays a key role in the development of a high poloidal beta scenario, which is essential for long-pulse and high-performance plasma operation on a tokamak. Based on the polarimetry technique, a Motional Stark Effect (MSE) diagnostic has been built on the Experimental Advanced Superconducting Tokamak. To be prepared for real-time (RT) feedback control of the plasma current density profile in the future, a RT signal processing system has been developed. The RT signal processing system is composed of three functional modules: analog-to-digital conversion (ADC) module, polarization information extraction module, and digital-to-analog conversion (DAC) module. The final objective of this system is to acquire the polarization information of the MSE. Based on the field-programmable gate array unit, fast Fourier transformation is adopted to process the Photoelastic Modulator (PEM) digital signal, which was converted from a PEM signal via the ADC module. By means of frequency spectrum separation, the components around double modulating frequencies are restored through inverse fast Fourier transformation. Furthermore, the two amplitudes of their corresponding components can be obtained through a digital harmonic analyzer technique. Afterward, the ratio of the two amplitudes is calculated by arc tangent so that the polarization angle is obtained. Finally, the information of this polarization angle is converted into a voltage signal by the DAC module and then output in RT. The test results based on the RT signal processing system are in good agreement with those based on the phase lock-in amplifiers. The working cycle of this system is shorter than 10 ms, which meets the requirements of the MSE diagnostic as a RT controller. The algorithm of RT signal processing and the relevant technology applied for building this system are presented in the main body of this paper in detail.

Atomic structure, tensile property, and dislocation behavior of Fe-W interfaces from molecular dynamics simulation.

Molecular dynamic simulations based on a recently constructed potential reveal that quasi-repeating patterns could appear in both Fe(110)/W(110) and W(110)/Fe(110) interfaces, and that three kinds of atomic displacements of Fe atoms because of the Fe-W interaction intrinsically bring about the interesting quasi-repeating patterns of the Fe-W interfaces. It is also found that the Fe-W interface becomes more brittle with less critical strains under tensile loading than pure Fe or W, which is fundamentally attributed to the movement of the interface dislocations as a result of the lattice mismatch between Fe and W. Interestingly, the dislocation loops could be formed in the Fe-W interface under tensile loading due to the pinning of the100edge dislocations by the edge dislocations of1/2111, whereas no dislocation loop would be generated in pure Fe or W.

Hydrogen solubility and diffusivity at Σ3 grain boundary of PdCu.

First principles calculations have been performed to comparatively reveal hydrogen solubility and diffusivity at grain boundaries of BCC and FCC PdCu phases. It is found that the temperature-dependent hydrogen solubility at BCC Σ3 (112) GB of PdCu seems much higher than that in BCC PdCu bulk, while hydrogen solubility in FCC Σ3 (111) GB of PdCu is much lower than that in its corresponding FCC bulk. Calculations also reveal that grain boundary has an important effect on hydrogen diffusion of BCC and FCC PdCu, i.e., hydrogen diffusivities of BCC Σ3 (112) and FCC Σ3 (111) grain boundaries of PdCu seem much smaller and bigger than those of its corresponding bulks, respectively. The predicted results could deepen the comprehension of hydrogen solubility and diffusion of PdCu phases.

Peripheral ProBDNF Delivered by an AAV Vector to the Muscle Triggers Depression-Like Behaviours in Mice.

Major depression is a leading cause of morbidity and disease burden in modern society. Current drug treatment is only effective in a fraction of patients as underlying mechanisms of depression are not fully understood. ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), and its receptor p75NTR are highly upregulated in patients with major depression and in animal models of depression induced by chronic stress. Here, we hypothesise that proBDNF may be a pathogenic factor triggering depression. C57BL/6 mice were injected in the bilateral gluteus maximus muscle with AAV-proBDNF or AAV-EGFP. Four weeks after the injection, AAV-proBDNF injected animals developed depression-like behaviours, which were evident for 4-8 weeks and then returned to the control level after 12 weeks. In the second experiment, mice were divided into three groups; one group was treated with sheep anti-proBDNF antibody after AAV-proBDNF injection whereas the other two groups received PBS injection after the AAV-proBDNF or AAV-EGFP delivery. The group that was injected with AAV-proBDNF showed a time-dependent increase in immobility time in the tail suspension test and forced swim test, reduced sucrose consumption and decreased grooming time after sucrose spraying. Treatment with sheep anti-proBDNF antibody alleviated the depressive-like symptoms. Peripheral AAV-proBDNF delivery also resulted in a reduction of density and length of dendritic spines in the dentate gyrus and amygdala. Thus, we conclude that peripheral proBDNF is a primary pathogenic factor triggering depression-like behavioural changes in mice likely by reducing dendritic spine plasticity.

[Clinical effects of expanded super-thin perforator flaps in the shoulder, neck, and chest in reconstruction of extensive burn scars in the face].

Objective: To explore the clinical effects and key techniques of expanded super-thin perforator flaps in the shoulder, neck, and chest in reconstruction of extensive burn scars in the face. Methods: From January 2008 to November 2018, 22 patients with extensive burn scars in the face were admitted to the Department of Plastic Surgery of Dongguan Kanghua Hospital and the Department of Plastic Surgery of Dermatology Hospital of Southern Medical University, with 3 males and 19 females, aged from 4 to 48 years. There were 16 cases of type Ⅱ and 6 cases of type Ⅲ in facial scars. Before the first stage of expansion surgery, Doppler blood flow survey meter or multi-slice CT was used to locate the perforator vessels. One to four expanders with rated capacity ranged from 100 to 600 mL were placed in the patients. We gave 20% to 30% of the rated capacity of expander intro-operation and common injection with 10% to 15% of the rated capacity of expander per week post-operation until the volume reached 1.5 to 2.5 times of the rated capacity of expander during the past 3 to 4 months. At the second stage of surgery, the perforators were located again before surgery with the same method. The size of defects after the excision of facial scars ranged from 6 cm×4 cm to 18 cm×16 cm. With perforators used as nutrient vessels, narrow pedicle flaps or random flaps ranging from 6 cm×6 cm to 22 cm×18 cm were elevated as rotating or advancing to reconstruct the defects. The donor sites were sutured directly. Some of the flaps needed stage Ⅲ operation for cutting the pedicle. The survival of flaps, post-operation complications, and follow-up were assessed. Results: All flaps of 22 patients survived. All the donor sites were closed simultaneously. One patient underwent an additional surgery for 5 cm×4 cm necrosis on distal part of flap caused by subcutaneous hematoma. Two patients with epidermis blister on the flaps were healed by themselves after dressing change. Due to rapid expansion, blood capillary proliferation appeared on the central part of the flap in 3 cases, after slowing down the expansion speed properly, which had no impact on flap transfer. No ischemia or venous congestion phenomenon were observed in the other flaps. During follow-up of 5 to 48 months, the flaps of patients showed no significant bloated appearance, with good complexion and texture, and even could reproduce facial fine-grained expressions naturally. Conclusions: For the reconstruction of extensive burn scars in the face, expanded super-thin perforator flaps can not only acquire large and thin flaps with high matching degree surface skin defect, but also reproduce facial fine-grained expressions. It is a simple and safe method which conforms to the facial aesthetic standard.

Population dynamics of Echinops gmelinii Turcz. at different successional stages of biological soil crusts in a temperate desert in China.

The effects of biological soil crusts (BSC) on vascular plant growth can be positive, neutral or negative, and little information is available on the impacts of different BSC successional stages on vascular plant population dynamics. We analysed seedling emergence, survival, plant growth and reproduction in response to different BSC successional stages (i.e. habitats: bare soil, cyanobacteria, lichen and moss crusts) in natural populations of Echinops gmelinii Turcz. in the Tengger Desert of northwest China. The winter annual E. gmelinii is a dominant pioneer herb after sand stabilisation. During the early stages of BSC succession, the studied populations of E. gmelinii were characterised by high density, plant growth and fecundity. As the BSC succession proceeded beyond moss crusts, the fecundity decreased sharply, which limited seedling recruitment. Differences in seedling survival among the successional stages were not evident, indicating that BSC have little effect on survival in arid desert regions. Moreover, E. gmelinii biomass allocation exhibited low plasticity, and only reproductive allocation was sensitive to the various habitats. Our results further suggest that the negative effects of BSC succession on population dynamics are primarily driven by increasing topsoil water-holding capacity and decreasing rain water infiltration into deeper soil. We conclude that BSC succession drives population dynamics of E. gmelinii, primarily via its effect on soil moisture. The primary cause for E. gmelinii population decline during the moss-dominated stage of BSC succession is decreased fecundity of individual plants, with declining seed mass possibly reducing the success of seedling establishment.

Association of use of rehabilitation services with development of osteoporosis among patients with rheumatoid arthritis: a nationwide population-based cohort study.

This is the first study that has found that rehabilitation services (RS) intervention, following the onset of rheumatoid arthritis (RA), may significantly reduce the risk of osteoporosis in RA patients. Those patients who received more than five sessions of RS had the greatest benefit for the prevention of osteoporosis. INTRODUCTION: People with rheumatoid arthritis have increased risk of developing osteoporosis (OP). It remains unclear whether use of rehabilitation services can reduce the risk of developing OP. We conducted a longitudinal cohort study to compare the effect of RS on the risk of OP in Taiwanese individuals with RA. METHODS: A national health insurance database was used to identify 2693 newly diagnosed RA patients, 20-70 years old, between 1998 and 2007. Among them, 808 received RS after the onset of RA (RS users) and 1885 patients did not receive RS (non-RS users). All enrollees were followed until the end of 2012 to record incident cases of OP. A Cox proportional hazards regression model was used to compute adjusted hazard ratios (aHRs) for the relationship of use of RS with OP. RESULTS: During the 15-year follow-up, 358 RS users and 1238 non-RS users developed OP, corresponding to incidence rates of 87.24 and 129.27 per 1000 person-years, respectively. Use of RS was significantly associated with a lower risk of OP (aHR 0.62; 95% confidence interval [CI] = 0.56-0.71). Those who received more than five sessions of RS had the greatest benefit (aHR 0.47; 95% CI = 0.38-0.56). CONCLUSIONS: The integration of RS into the clinical management of patients with RA may decrease their risk of developing OP.

[Advances in the p75 neurotrophic factor receptor in stomatology].

The p75 neurotrophic factor receptor is a low affinity receptor for neurotrophic factors and plays an important role in nerve growth, development and function integrity. It is closely related to dental development, oral and maxillofacial tumor, nerve repair and tissue engineering. It shows good prospect for application. In this paper, the research progress of p75 neurotrophic factor receptor in Stomatology is reviewed.

[Expression of p75 neurotrophin receptor during the mineralization of ectomesenchymal stem cells in vitro].

OBJECTIVE: To investigate the mineralized capacities of ectomesenchymal stem cells (EMSC) from facial process of Sprague Dawley(SD) rat embryo of different age in vitro and the expression of p75 neurotrophin receptor(p75NTR) in this process. METHODS: The stem cell surface antigens of EMSC from 12.5 d, 15.5 d and 18.5 d SD rat embryonic facial process were tested by flow cytometry technology. E12.5 d EMSC, E15.5 d EMSC and E18.5 d EMSC were incubated under mineralization induction and analysed by alkaline phosphatase(ALP) staining on day 7(d7) and alizarin red staining on day 21(d21). Expression changes of Runt-related transcription factor-2(RUNX2), collagen Ⅰ (Col Ⅰ) and p75NTR in each group were measured using Western blotting and real time(RT)-PCR on day 0(d0), day 7(d7), day 14(d14) and day 21(d21). RESULTS: The expression of the special substances CD29, CD146 and p75NTR in E12.5 d EMSC, E15.5 d EMSC and E18.5 d EMSC were positive, and the expression of CD45 was negative. The expression level of p75NTR in E18.5 d EMSC(84.04%) was much higher than that of E12.5 d EMSC (22.53%) and E15.5 d EMSC(81.43%). The mineralized capacities of E18.5 d EMSC was stronger than that of E12.5 d EMSC and E15.5 d EMSC. The higher expression of RUNX2, Col Ⅰ in E18.5 d EMSC(RUNX2: 1.92±0.20, Col Ⅰ: 1.85±0.66) was found compared with E12.5 d EMSC(RUNX2: 0.38±0.02, Col Ⅰ: 0.33± 0.94) and E15.5 d EMSC(RUNX2: 0.72±0.22, Col Ⅰ: 0.64±0.07) (P<0.05), and p75NTR in the E18.5 d EMSC experimental group(E12.5 d: 0.79±0.23, E15.5 d: 0.84±0.29, E18.5 d: 1.35±0.22) was significantly higher than the in control group(E12.5 d: 0.42±0.12, E15.5 d: 0.43±0.13, E18.5 d: 0.48±0.15)(P<0.05). RT-PCR further proved the results of the Western blotting. CONCLUSIONS: p75NTR participated in the mineralization differentiation of EMSC. E18.5 d EMSC had a higher expression of p75NTR and stronger mineralization capacity and was the ideal engineering seed cells.

Characterization of antibody responses against a neutralizing epitope on the glycoprotein E2 of classical swine fever virus.

The sequence TAVSPTTLR is a conserved and linear neutralizing epitope on the glycoprotein E2 of classical swine fever virus. In this study, TAVSPTTLR-directed antibodies, induced either by virions or by an epitope-focused immunogen, were characterized. The results revealed that despite the same epitope specificity, the antibodies induced by different immunogens varied significantly both in the neutralizing test and in binding inhibition assays. This suggests that the protective immunity induced by this epitope is due to more than simply the epitope specificity and that this epitope might need essential contributions from its flanking context to induce functional epitope-specific antibodies.

The hypocretin neurotransmission system in myotonic dystrophy type 1.

BACKGROUND: Patients with myotonic dystrophy type 1 (DM1) frequently have symptoms of excessive daytime sleepiness (EDS). Some patients with DM1 show sleep-onset REM, similar to that observed in narcolepsy. Narcolepsy is characterized by impaired hypocretin (Hcrt) neurotransmission. OBJECTIVE: To test for dysregulation of Hcrt neurotransmission in a prospective cohort of patients with DM1. METHODS: Hcrt levels in CSF were measured by radioimmunoassay. Sleep physiology was assessed by overnight polysomnography (PSG) and a multiple sleep latency test (MSLT). Splicing of Hcrt receptor 1 and 2 (HcrtR1 and HcrtR2) mRNA was examined in postmortem samples of temporal cortex. RESULTS: Seventeen of 38 patients with DM1 reported symptoms of EDS. Among patients with DM1 with EDS who underwent PSG/MSLT, 7 of 13 showed reduced sleep latency, sleep-onset REM, or both. However, CSF Hcrt levels in DM1 (mean 277 pg/mL, n = 38) were not different from controls (mean 277 pg/mL, n = 33). Also, splicing of HcrtR1 and HcrtR2 mRNA in patients with DM1 was similar to controls. CONCLUSIONS: Excessive daytime sleepiness and dysregulation of REM sleep occur frequently in patients with myotonic dystrophy type 1 (DM1). However, the pathophysiologic basis is distinct from narcolepsy, as patients with DM1 do not have a consistent defect of Hcrt release or receptor splicing.

Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus.

Decoy receptor 3 (DcR3/TR6) is a decoy receptor for the Fas ligand (FasL) and can inhibit FasL-induced apoptosis. It has been reported recently that DcR3 can induce T cell activation via co-stimulation of T cells, suggesting that DcR3 may be involved in the pathophysiology of autoimmune diseases. This study aims to analyse the serum DcR3 in patients with systemic lupus erythematosus (SLE) and to investigate the role of DcR3 in the pathogenesis of SLE. Significantly elevated serum DcR3 was observed in SLE patients, and the mean serum DcR3 level was significantly higher for those with active disease [SLE disease activity index (SLEDAI) >/= 10] compared with that in patients with inactive disease (SLEDAI < 10). In addition to reducing activation-induced cell death in activated T cells via neutralization of the FasL, soluble DcR3-Fc enhanced T cell proliferation and increased interleukin-2 and interferon-gamma production via co-stimulation of T cells. Moreover, enhanced T cell reactivity to DcR3-induced co-stimulation was demonstrated in lymphocytes from patients with SLE, suggesting the elevated serum DcR3 may associate with enhanced T cell activation in vivo. These findings are the first to demonstrate that serum DcR3 concentrations are increased in SLE patients, and this may imply a possible role of DcR3 in the pathogenesis of SLE via enhanced T cell hyperreactivity and reduced apoptosis in activated T cells.

Neural correlates of priming on occluded figure interpretation in human fusiform cortex.

The visual system rapidly completes a partially occluded figure. We probed the completion process by using priming in combination with neuroimaging techniques. Priming leads to more efficient visual processing and thus a reduction in neural activity in relevant brain areas. These areas were studied with high spatial resolution and temporal accuracy with focus on early perceptual processing. We recorded magnetoencephalographic responses from 10 human volunteers in a primed same-different task for test figures. The test figures were preceded by a sequence of two figures, a prime or control figure followed by an occluded figure. The prime figures were one of three possible interpretations of the occluded figures: global and local completions and mosaic interpretation. A significant priming effect was evident: in primed trials as compared with control trials, subjects responded faster and the latency was shorter in the magnetoencephalographic signal for the largest peak between 50 and 300 ms after the occluded figure onset. Tomographic and statistical parametric mapping analyses revealed stages of activation in occipitotemporal areas during occluded figure processing. Notably, we found significantly reduced activation in the right fusiform cortex between 120 and 200 ms after occluded figure onset for primed trials as compared with control trials. We also found significant spatiotemporal differences of local, global and mosaic interpretations for individual subjects but not across subjects. We conclude that modulation of activity in the right fusiform cortex may be a neural correlate of priming in the interpretation of an occluded figure, and that this area acts as a hub for different occluded figure interpretations in this early stage of perception.

Single-trial variability in early visual neuromagnetic responses: an explorative study based on the regional activation contributing to the N70m peak.

Cortical activity evoked by repeated identical sensory stimulation is extremely variable. The source of this variability is often assigned to "random ongoing background activity" which is considered to be irrelevant to the processing of the stimuli and can therefore be eliminated by ensemble averaging. In this work, we studied the single-trial variability in neuromagnetic responses elicited by circular checkerboard pattern stimuli with radii of 1.8 degrees, 3.7 degrees, and 4.5 degrees. For most of the MEG sensors over the occipital areas, the averaged signal showed a clear early (N70m) response following the stimulus onset and this response was modulated by the checkerboard size. A data-driven spatial filter was used to extract one of the many possible composite time courses of single-trial activity corresponding to the complex of N70m generators. Pattern analysis principles were then employed to analyze, classify, and handle the extracted temporal patterns. We explored whether these patterns correspond to distinct response modes, which could characterize the evoked response better than the averaged signal and over an extended range of latencies around N70m. A novel scheme for detecting and organizing the structure in single-trial recordings was utilized. This served as a basis for comparisons between runs with different checkerboard sizes and provided a causal interpretation of variability in terms of regional dynamics, including the relatively weak activation in primary visual cortex. At the level of single trial activity, the polymorphic response to a simple stimulus is generated by a coupling of polymodal areas and cooperative activity in striate and extrastriate areas. Our results suggest a state-dependent response with a wide range of characteristic time scales and indicate the ongoing activity as a marker of the responsiveness state.

Osteoblast-specific targeting of soluble colony-stimulating factor-1 increases cortical bone thickness in mice.

UNLABELLED: The soluble and membrane-bound forms of CSF-1 are synthesized by osteoblasts and stromal cells in the bone microenvironment. Transgenic mice, generated to selectively express sCSF-1 in bone, showed increased cortical thickness in the femoral diaphysis caused by new bone formation along the endosteal surface. The ability of sCSF-1 to enhance bone cell activity in vivo is potentially relevant for increasing cortical bone in a variety of disorders. INTRODUCTION: The soluble form of colony-stimulating factor-1 (sCSF-1) and the membrane-bound form of CSF-1 (mCSF-1) have been shown to support osteoclastogenesis in vitro; however, the effect of each peptide on bone remodeling in vivo is unclear. To determine the effect of sCSF-1, selectively expressed in bone, the skeletal phenotype of transgenic mice harboring the human sCSF-1 cDNA under the control of the osteocalcin promoter was assessed. METHODS: At 5 and 14 weeks, mice were analyzed for CSF-1 protein levels, weighed, and X-rayed, and femurs were removed for peripheral quantitative computed tomography, histology, and histomorphometry. RESULTS: High levels of human sCSF-1 were detected in bone extracts and, to a lesser extent, in plasma. Adult transgenic mice showed normal body weight and increased circulating monocytic cells. At 5 weeks, the femoral diaphysis was similar in CSF-1T and wt/wt littermates. However, by 14 weeks, the femoral diaphysis in CSF-1T mice showed increased cortical thickness and bone mineral density. In contrast to the diaphysis, the femoral metaphysis of CSF-1T mice showed normal cancellous bone comparable with wt/wt littermates at each time point. Histological sections demonstrated increased woven bone along the endosteal surface of the diaphysis and intracortical remodeling. Fluorochrome-labeling analysis confirmed endocortical bone formation in CSF-1T, with a 3.1-fold increase in the percentage of double-labeled surfaces and a 3.6-fold increase in the bone formation rate compared with wt/wt mice. Although remodeling resulted in a slightly porous cortex, sCSF-1 preferentially stimulated endocortical bone formation, leading to increased cortical thickness. CONCLUSIONS: These findings indicate that sCSF-1 is a key determinant of bone cell activity in the corticoendosteal envelope.