Prediction of acute toxicity to Daphnia magna and interspecific correlation: a global QSAR model and a Daphnia-minnow QTTR model.

Acute toxicity is an important basis for the assessment of hazardous chemicals, but currently there is a huge data gap in chemical toxicity information. The in silico Quantitative Structure Activity Relationship (QSAR) models can use the existing experimental data information to predict the missing chemical toxicity information data and thus reduce animal testing. In the present study, a global QSAR model for the prediction of acute Daphnia magna toxicity has been developed based on the five principles proposed by the Organization for Economic Co-operation and Development (OECD). Moreover, a Daphnia-minnow (referring specifically to the fathead minnow) Quantitative Toxicity-Toxicity Relationship (QTTR) prediction model has been developed based on the present study and our previous work on fathead minnow (Pimephales promelas). Both the QSAR and QTTR prediction models have good goodness-of-fit, robustness, and predictive ability. Finally, the acute toxicity mode of action (MOA) for fathead minnow and Daphnia magna was compared by toxicity ratio based on interspecies toxicity data. By comparison, Daphnia magna was found more sensitive to anilines and phosphorothioates than fathead minnow. The present models can fill the acute toxicity data gap and contribute to the chemicals risk assessment and priority setting.

Occupational heat-related illness emergency department visits and inpatient hospitalizations in the southeast region, 2007-2011.

BACKGROUND: Heat-related illness (HRI) is an occupational health risk for many outdoor, and some indoor, workers. METHODS: Emergency department (ED) and inpatient hospitalization (IH) data for 2007-2011 from nine southeast states were analyzed to identify occupational HRI numbers and rates, demographic characteristics, and co-morbid conditions. RESULTS: There were 8,315 occupational HRI ED visits (6.5/100,000 workers) and 1,051 IHs (0.61/100,000) in the southeast over the study period. Out-of-state residents comprised 8% of ED visits and 12% of IHs. Rates for both, ED visits and IHs were significantly elevated in males and blacks. Younger workers had elevated rates for ED visits, while older workers had higher IH rates. CONCLUSIONS: This is the first study to evaluate occupational HRI ED visits and IHs in the southeast region and indicates the need for enhanced heat-stress prevention policies in the southeast. Findings from this study can be used to direct state health department tracking and evaluation of occupational HRI.

Antioxidant content and cytological examination of aqueous fluid from patients with age-related cataracts at different stages.

We investigated the antioxidant content and conducted a cytological examination of the aqueous fluid and lenses of patients with age-related cataracts at different stages. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in the aqueous fluid and lenses were determined by the xanthine oxidase method, the colorimetric method, and the improved reduced glutathione (GSH) depletion method, respectively. SOD, CAT, and GSH-PX content in the aqueous fluid and lenses decreased significantly with increasing lenticular nucleus hardness grading. However, the number of white blood cells, neutrophils, monocytes, lymphocytes, and eosinophils did not vary significantly with varying lenticular nucleus hardness. Antioxidant content examination is an important quantitative indicator for clinical diagnosis and treatment of age-related cataracts. Antioxidant content in the aqueous fluid and lenses decreased significantly with increasing lenticular nucleus hardness grading. Lenses at hardness level V had the lowest content of antioxidants.

High-level semi-synthetic production of the potent antimalarial artemisinin.

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Hyaluronan tetrasaccharide in the cerebrospinal fluid is associated with self-repair of rats after chronic spinal cord compression.

The objective of this study was to explore changes in hyaluronan levels in the cerebrospinal fluid (CSF) in a spinal cord compression model, to investigate whether hyaluronan tetrasaccharide was involved in this process, and to test the effects of hyaluronan tetrasaccharide on neuron and oligodendrocyte repair. We developed a chronic spinal cord compression model with various sizes of polymer sheets (1.5×0.7×0.3 mm(3); 5×1.5×0.7 mm(3)) that were implanted microsurgically underneath the C(5-6) laminae. The rats were divided into three groups: a sham group, a mildly compressed (MC) group, and a widely compressed (WC) group. Locomotor functional evaluations revealed that the behavioral function of the MC and WC groups dropped to their lowest level from the fourth to fifth week and gradually recovered thereafter. The hyaluronan levels in the CSF gradually increased after spinal cord compression. Furthermore, hyaluronan tetrasaccharide was involved in the hyaluronan change. In addition, we found that nuclear factor kappa B (NF-κB) and cellular inhibitor-of-apoptosis protein 2 (c-IAP(2)) were co-expressed in neurons and oligodendrocytes, and caspase-3 expression gradually decreased in the compression model. The brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) expression was upregulated in astrocytes at the fourth week post-compression. Hyaluronan tetrasaccharide (HA(4)) induced NF-κB and c-IAP(2) to suppress the H(2)O(2)-induced apoptosis in primary neuronal cultures and increased BDNF and VEGF expression in astrocytic cultures in vitro. These findings suggest that HA(4) in the CSF may associate with behavioral recovery by increasing the levels of NF-κB, c-IAP(2), and neurotrophic factors after chronic spinal cord compression.

Antiinflammatory activity of Phyllanthus emblica, Plumbago zeylanica and Cyperus rotundus in acute models of inflammation.

Experimental studies conducted earlier have proved that Phyllanthus emblica (Pe), Plumbago zeylanica (Pz) and Cyperus rotundus (Cr), plants from the medohara group of Ayurveda possess antiatherosclerotic activity. As inflammation is also one of the pathophysiological factors, it was of interest to evaluate whether these drugs exhibit any antiinflammatory activity. Two models of acute inflammation, namely carrageenan induced rat paw edema and acetic acid induced peritonitis in mice were used. In the model of carrageenan induced paw edema Pe, Pz and Cr showed a trend to reduce the edema while the combination of Pe + Pz (PI: 20.64%) showed results comparable to aspirin (23.74%). Whereas in a model of acetic acid induced peritonitis, all the plant drugs i.e. Pe, Pz, Cr and a combination of Pe + Pz showed a significant decrease in the protein content of the peritoneal exudates compared with the disease control group (p < 0.05), however, only Pe + Pz exhibited activity comparable to aspirin.

In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells expressing BMP-7.

BACKGROUND: Adipose-derived adult stem (ADAS) cells are multipotent cells capable of differentiating into osteoblasts, adipocytes and chondrocytes. The aim of this study was to determine whether BMP-7-expressing ADAS cells would elicit bone formation invitro and in vivo. METHODS: ADAS cells were harvested from Lewis rats and transduced with adenovirus carrying the recombinant human bone morphogenetic protein-7 (Ad-BMP-7) gene. Untransduced cells and cells transduced with adenovirus carrying the enhanced green fluorescence protein (Ad-EGFP) gene served as controls. BMP-7 expression was assessed by RT-PCR, immunofluorescence on day 1, and Western blot on days 4, 8 and 12. Alkaline phosphatase (ALP) activity was assayed on days 2, 4, 6, 8, 10 and 12. Osteocalcin production and bone nodule formation were detected by immunohistochemistry and von Kossa stain on day 12. A total of 1 x 10(6) cells mixed with type I collagen were implanted into the subcutaneous pocket in Lewis rat and subjected to histologic analysis 1, 2 and 4 weeks post-implantation. RESULTS: The Ad-BMP-7-transduced ADAS cells expressed BMP-7 at both mRNA and protein levels. ALP activity was detected in Ad-BMP-7-transduced cells from day 2 to day 12, peaking on day 8. Osteocalcin production and matrix mineralization further confirmed that these cells differentiated into osteoblasts and induced bone formation in vitro. Histologic examination revealed that implantation of BMP-7-expressing ADAS cells could induce new bone formation in vivo. DISCUSSION: ADAS cells would be a promising source of adult autologous stem cells for BMP gene therapy and tissue engineering.

Relationship between osteopenia and lumbar intervertebral disc degeneration in ovariectomized rats.

Ovariectomy (OVX) can cause bone loss in rats, but little is known about how it also induces lumbar intervertebral disc degeneration (LVD). This study investigated how estrogen deficiency affected intervertebral discs in OVX rats. Thirty 3-month-old female Sprague-Dawley rats were divided randomly into three equal groups. The baseline control group (BL) was killed at the beginning of the experiment. An ovariectomy was performed in 10 rats (OVX group) and another group of 10 rats was subjected to a sham surgery (Sham group). The OVX rats were untreated after the surgery to allow for the development of moderate osteopenia. Bone mineral density (BMD) measurement and bone histomorphometric analysis were applied to the segments of lumbar spines in all rats killed 6 months after surgery. The pathological changes of intervertebral discs were observed and the degree of LVD was scored by a histological scoring system. The BMD of the spines (L3-L5) in the OVX group decreased significantly compared with the Sham group. The bone volume indices in the OVX group were significantly lower, but the bone turnover rate parameters were significantly higher than those in the Sham group (P < 0.01). The histological scores for LVD in the OVX group were significantly higher than those in the Sham group (P < 0.01). There was a significant negative correlation between the BMD and Grade II discs in the OVX rats (P = 0.042). In conclusion, LVD occurs in the OVX rats and the degeneration of cartilage end plates may be a pathogenic factor in disc degeneration.

Cbfa1/osf2 transduced bone marrow stromal cells facilitate bone formation in vitro and in vivo.

It has been well established that core binding factor a-1/osteoblast-specific factor-2 (cbfa1/osf2) is a key regulator of osteoblast differentiation and function, however, it is not known whether it can induce bone formation in vitro and in vivo. To investigate the effect of cbfa1/osf2 on bone formation, we used a recombinant adenoviral vector carrying the mouse cbfa1/osf2 gene to transduce primary cultured bone marrow stromal cells (MSCs) of BALB/c mice. We found that Ad-cbfa1/osf2-transduced MSCs produced cbfa1/osf2 protein and differentiated into osteoblast-like cells. The transduced MSCs had increased alkaline phosphatase activity, increased expression of osteocalcin, osteopontin and bone sialoprotein, and increased matrix mineralization in vitro. To observe the induction of bone formation in vivo, MSCs transduced with Ad-cbfa1/osf2 were transplanted into a 5 mm diameter critical-sized skull defect in BALB/c mice, with type I collagen as scaffolding material. Healing of the defect in treatment and control groups was examined grossly and histologically at four weeks. Skull defects transplanted with Ad-cbfa1/osf2-transduced MSCs had an average of 85% osseous closure at four weeks. Control groups in which the defects were not treated (group 1), treated with collagen only (group 2), or treated with collagen and nontransduced MSCs (group 3) showed little or no osseous healing. These studies indicate that cbfa1/osf2 can induce osteoblast differentiation and bone formation both in vitro and in vivo, suggesting that MSCs transduced with the cbfa1/osf2 gene may be useful in treating bone defects.

[Effect of sequential application of calcitonin and parathyroid hormone on bone remodeling process, an experimental research].

OBJECTIVE: To investigate the effect of sequential application of calcitonin and parathyroid hormone (PTH) on bone remodeling process. METHODS: Twelve female rats were divided equally into 2 groups: experimental group and control group. 1 U/100 g of calcitonin was injected intramuscularly to 6 rats for two days, and rrPTH in dosage of 30 micrograms was injected intramuscularly in the fourth and fifth days. At the sixth day their lumbar vertebral bodies were resected. Undecalcified and decalcified bone sections were made to be observed by optical microscopy and electronic microscopy. Bone histomorphological parameters were measured. Normal saline and solvent of the same volume were injected intramuscularly to the controls. RESULTS: The OS/BS (%), O. Th (micron), N.Ob.S (cell/mm), and Vos/TV (%) were 19.9% +/- 6.2%, 3.4 microns +/- 0.4 micron, 37.6 cells/mm +/- 4.6 cells/mm, and 1.8% +/- 0.6% respectively in the experimental group, significantly higher than those in the control group (P < 0.05). After the PTH administration, more and plumper osteoblasts were observed. They were rich in rough endoplasmic reticulum, mitochondria, and Golgi apparatus. CONCLUSION: Sequential application of calcitonin and parathyroid hormone obviously promotes the bone formation process. Both sites of bone remodeling formation and sites of bone modeling formation, especially the latter, increase.

[The preliminary result of osteoid callus allograft for bone healing].

OBJECTIVE: To investigate the feasibility of osteoid callus allograft as a kind of bone healing promoting materials. METHODS: The osteoid callus was obtained at one week after bilateral femoral fracture of a SD rat, then was kept at -196 C for 2 weeks. The bone defect model which bone repair was in intra-membranous osteogenesis was made at bilateral tibial shaft in 5 rats, and filled with the osteoid callus in the left defect area, the right side was filled with allogenous cancellous as control group. The specimen were processed with undecalcified technique and the sections were staining with light blue and sofranin T. RESULTS: After 2 weeks, there were cartilage and bone formation in the defect area of osteoid callus graft group(3/4), medullary cavity formation in bone tissue with cartilage arround it, fibrous tissues between new bone and host bone. While there were no cartilage or bone formation in the control group. CONCLUSION: The allograft osteoid callus is not absorbed by immunological rejection, but changed into bone tissue through endochondral osteogenesis. It is inspiring to develop osteoid callus allograft as a kind of material for bone healing.

[Radiographic studies of cervical spine motion range in normal Chinese subjects with computer-assisted image analysis: full flexion and extension].

OBJECTIVES: To study the degenerative regularity of normal Chinese cervical spine by observing the motion range of full cervical flexion and extension, and to provide evidences for further investigation of cervical segmental instability. METHODS: 764 X-ray plain films of full cervical flexion and extension in 382 normal Chinese subjects (214 were male and 168 female) were investigated using self-designed cervical X-ray image analysis system. The subjects within the same sex group were divided into three groups according to the age: group A (20 years to 39 years), group B (40 years to 59 years) and group C (60 years to 76 years). During the full cervical flexion and extension motion, total intervertebral motion range (from C(2) - C(3) to C(6) - C(7)) and intervertebral motion range at each level were major parameters. RESULTS: The range of total intervertebral motion showed much greater mobility in group A than in group B and group C (P < 0.01) but no statistically significant difference between group B and group C (P > 0.05). The range of intervertebral motion was maximal at C(5) - C(6) in group A. The place of maximal motion shifted to the C(4) - C(5) in both group B and group C. C(2) - C(3) showed minimal mobility in all three groups. There was no statistically significant difference (P > 0.05) between male and female. CONCLUSIONS: The motion range and degenerative regularity of normal Chinese cervical spine were similar in either sex. The range of total intervertebral motion (from C(2) - C(3) to C(6) - C(7)) had a tendency to decrease rapidly and then became steady with age. For the range of intervertebral motion, the place of maximal motion shifted to the higher level with age from C(5) - C(6) in group A to C(4) - C(5) in group B and group C.

[A color analysis of the Han dynasty's Yangling Tombs colored pottery figurine by spectroscopy].

Many colored pottery figurines have been discovered from Yangling Tombs in which Han Jingdi, Qi LIU, the fourth emperor of Xi Han dynasty was buried together with his Wang empress. They were of important academic and aesthetic value. The analysis of the colored pottery figurines from Yangling Tombs of Han Dynasty was realized by X-ray diffraction, emission spectrum, infrared spectrum, X-ray fluorescence and fiber optics reflectance spectroscopy(FORS). Consequent results showed that the colored components were respectively mercuric(II) sulphide(HgS), ferric(III) oxide(Fe2O3), and Carbon(C), among which mercuric(II) sulphide was an artificial pigment.

[Influence of solid thoracolumbar kyphosis on lumbar spine and surgical treatment].

OBJECTIVE: To investigate the influence of solid thoracolumbar kyphosis on the lumbar spine and surgical treatment. METHODS: 14 had solid kyphosis of the thoracolumbar spine. Cobb angle of kyphosis of the thoracolumbar spine and lordosis between L(2)/S(1), L(2)/L(5), L(2)/L(3), L(3)/L(4), L(4)/L(5), L(5)/S(1) pre- and post-osteotomy was measured respectively, and the amount of vertebrae slipped over 3mm was recorded. The results were compared with those of the normal group respectively. RESULTS: The Cobb angles of lordosis between L(2)/S(1), L(2)/L(5), L(2)/L(3), L(3)/L(4), L(4)/L(5), L(5)/S(1) in the deformity group were increased significantly compared with those that of the normal group respectively; obvious changes in percentage occurred in the segment between L(2)/L(3) and L(3)/L(4). Over lordosis of the lumbar spine was greatly corrected postosteotomy of the thoracolumbar spine, it was still significantly different compared with that of the normal group. In 9 patients with retrolisthesis of 20 vertebrae, 70% occurred in L(2) and L(3) vertebrae. The amount of retrolisthesis of vertebrae decreased to 3 in two patients. No retrolisthesis of vertebra was seen in the normal group. Single-stage procedures combined with anterior releasing and posterior osteotomy through facet joints for kyphosis of the thoracolumbar spine showed a correction. rate of 85.7%, but single-stage osteotomy through the posterior vertebra showed a correction rate of 60.7%. Seven of 8 patients who had had seriously back pain complained of no pain or slight backache after operation. 40% of the patients showed functional improvement in the sphincter of the urinary bladder and anus. 50% of the patients had improvement in muscle strength. CONCLUSIONS: Kyphosis of the thoracolumbar spine may result in over lordosis of the lumbar spine and retrolisthesis of vertebrae, which are obvious in the upper lumbar spine. These changes may lead to back pain. Correction of kyphosis of the thoracolumbar spine may obviously decrease over lordosis of the lumbar spine and inclination of vertebral slip, and may further decrease the overload to the posterior column of the spine and relieve back pain. Osteotomy combined with anterior and posterior procedures is effective and safe in the correction of kyphosis of the thoracolumbar spine.

A codon 891 exon 15 RET proto-oncogene mutation in familial medullary thyroid carcinoma: a detection strategy.

A ser891ala RET proto-oncogene mutation has been previously discovered in a single kindred with familial medullary thyroid carcinoma (FMTC). An additional two probands with this mutation and with medullary thyroid carcinoma (MTC) without any other manifestations of MEN 2 have been identified. In one of thse families, two other individuals also had the mutant sequence and FMTC. Analysis of both cases showed cosegregation of the mutation and MTC. To facilitate detection of this mutation, a primer was engineered which creates a Hha I recognition site in the presence of the mutant sequence. As a result, this codon 891 exon 15 mutation can be identified with a restriction enzyme digestion.

[An epidemiological survey and treatment of blindness in Zhangqiu city of Shandong province].

OBJECTIVE: An epidemiological survey of blindness was carried out in Zhangqiu city of Shandong province. METHODS: According to stratified random sampling rule, 11,884 persons were chosen as the sample (the sampling fraction is 1.27%) in the city. The WHO grading system for blindness was followed in the survey. RESULTS: The prevalence of blindness was found to be 0.31%, resulting chiefly from cataract (45.95%), glaucoma (24.32%) and vitreous retinal disease (13.51%). 1 016 cases of blindness caused by cataract were operated for restoration of vision, that were accounted for 73.89% of all cataract blindness estimated from the result of the survey. The rate of intraocular lens implantation in the restorative operations was 84.15% (855/1,016). After operation, the corrected vision in 64.47% of the blindness was >or= 1.0, in 21.26% between 0.6 - 0.9, in 10.24% between 0.3 - 0.5, and in 4.03% between 0.05 - 0.2. CONCLUSION: The epidemiological results show that the main cause of blindness is cataract. So it is the key objective for surgical restoration of vision in the prevention of the blindness in later days.

[Bone tissue engineering seeded with bone marrow stromal cells].

OBJECTIVE: To assess the ability of bone graft substitutes to support the growth of cells in vitro and new bone formation in vivo. METHODS: The methods of tissue engineering were employed, the bone marrow derived stromal cells were seeded onto blocks of hydroxypatite (HA), cultured for two weeks, and implanted intermuscularly into the rabbit back muscle, scanning electron microscopy and undecalcified bone tissue sections were used to evaluate the the growth of cells in vitro and new bone formation in vivo. RESULTS: The stromal cells were attached to and grew upon the surface of the periphery HA pores, especially in the pores adjacent to the bottom of culture flasks. No cell growth was found on the surface of the central pores. At four weeks after implantation, new bone formation was observed in most HA blocks, almost all of the new bones were lamellar bone and deposited directly on the surface of the HA pore. Active osteoblast and osteoid were found on the surface of the newly formed bone, invasion of bone marrow was observed in some newly formed bone. CONCLUSION: Bone marrow stromal cells are potentially the source of seeded cells for use in bone tissue engineering, and the HA may be considered as a suitable scaffold for these cells. The findings may be useful for detailed researches on seeded cells, scaffold and implanting fashion of bone tissue engineering.

[Construction of porous hydroxyapatite (HA) block loaded with cultured chondrocytes].

OBJECTIVE: To construct a kind of bone healing enhancing implant with cultured chondrocytes bound to hydroxyapatite (HA). METHODS: Chondrocytes were obtained from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x 3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was taken to show whether the cells grew outside and inside the pore of HA block. The cells cultured on tiny glass sheet for 2 days were used to prove where the cells come from by in situ hybridization technique with alpha1 (II) cDNA probe. RESULTS: Scanning electron micrographs showed that the pores of the HA surface and inside of the blocks are filled with cultured cells, especially the longer cultured block. The cells were chondrocytes confirmed by in situ hybridization. CONCLUSION: The porous HA can be used as cell cultured substrate and chondrocyte can adhere and proliferate inside the porous HA block.

[Motor-evoked potential in investigating neurologic function during spinal cord ischemia and reperfusion injury].

OBJECTIVE: To investigate the method monitoring the neurologic function of spinal cord ischemia and reperfusion injury. METHODS: Motor-evoked potentials (MEP)were monitored at different time points during ischemia and reperfusion of the lumbar spinal cord of the rat. RESULTS: MEP latency increased 15 minutes after ischemia (P < 0.01) and MEP amplitude decreased 25 minutes after ischemia (P < 0.01). MEP disappeared 40 minutes after ischemia and reappeared 5 minutes after reperfusion, but the latency was still longer and the amplitude was lower than the normal value (P < 0.01). The amplitude returned to normal 2 hours after reperfusion (P > 0.05) in contrast to the latency. 24 hours after reperfusion, the amplitude decreased again, and motor function of rat hind limbs was more decreased than that at early time of reperfusion (P < 0.05). CONCLUSION: MEP is a sensitive index for spinal cord ischemia and reperfusion injury.

[The experimental research of transforming growth factor-beta 1 expression during fracture healing].

OBJECTIVE: To observe the effect of TGF-beta 1 in the regulation of fracture healing. METHOD: The expression of transforming growth factor-beta 1 (TGF-beta 1) in different period of fracture healing was investigated by immunohistochemistry. RESULTS: It was found that the expression of TGF-beta 1 changed in different period. The cells in the cambial layer of the periostlum showed low or negative signal in the immediate injury response period. The osteoblasts differentiated from the periosteum cells stained strongly in the intramembranous ossification period, and the differentiated chondrocytes stained most strongly in the chondrogenesis period. The hypertrophic chondrocytes showed negative signal and the osteoblasts stained strongly in the endochondral ossification period. These results suggested that the expression of TGF-beta 1 was closely related to the proliferation and differentiation state of repair cells. CONCLUSION: TGF-beta 1 is intimately involved in the control of fracture healing.