2002年 · 第115卷第03期

Objective To evaluate the influence of necrotic tissue on progressive injury in deep partial thickness burn wounds. Methods Tissue specimens were cultured both for estimation of IL-8, EGF, bFGF, PDGF-AB and histopathological examination, from the pre-operation, post-operation, and non-operation wounds from seven patients with deep partial thickness burn. Results In seven specimens from the non-operation group, IL-8 release increased compared with those in the post-operation group (P <0.001), while the levels of EGF, bFGF, PDGF-AB release were lower than those in the post-operation group. Histopathological examination revealed that in the non-operation group,the degree of neutrophil infiltration was enhanced, the extent of tissue necrosis enlarged, and residual skin appendages disappeared. In contrast, in the post-operation group, the degree of inflammatory response was decreased, with the formation of fresh granulation tissue and epithelialization. Conclusion This study suggests that the presence of necrotic tissue could be the inhibitory factor in the wound healing process, as it might cause tissue progressive injury leading to the delay of wound healing. To promote wound healing, active tangential excision is recommended to remove necrotic tissue. Chin Med J 2002; 115(3): 323-325

Objective To detect the expression of cell cycle positive regulators cyclin D1 cyclin E, CDK2, CDK4 and negative regulators p21 cip1, p27kip1, p16ink4a and p15ink4b during wound healing in rats. Methods Open wounds of full-thickness skin, diameter 1.8 cm, on rat backs were used as the wound model. Wound tissues were harvested on postwounding days 3, 5, 7, 9, 11, 14, 21 and 30. Ki67 expression in granulation tissue was detected by immunohistochemical assay. The patterns of the expression of cyclin D1, cyclin E, CDK2, CDK4 and p21cip1, p27kip1, p16ink4a, p15ink4b were detected by Western blot. Results Cell proliferation in granulation tissue took place predominantly within the first week after injury,with the proliferation peak occurring at postwounding day 5. There were no dramatic variations in the expression of cyclinD1, CDK2 and CDK4 during wound healing. Up-regulated cyclin E was maintained from day 3 to 11 after injury, and then was down-regulated. No expression of p16ink4a and p15ink4b was found. p21cip1 was expressed only from day 7 to 14, with peak expression observed on day 9. Constitutive p27kip1 was expressed throughout wound healing with low levels in the proliferating period of day 3 to 5 and with increased levels in the post-mitotic and remodeling stage. The expression of p21cip1 and p27kip1 showed an inverse gradient to that of Ki67. Conclusion p21cip1 and p27kip1 play a supervising role in preventing the hyperproliferative tendency in tissue repair. Chin Med J 2002; 115(3): 326-330

Objective To evaluate the safety and efficacy of topical application of recombinant bovine basic fibroblast growth factor (rbFGF) on the healing of chronic cutaneous wounds. Methods Twenty-eight patients with thirty-three chronic cutaneous wounds resulting from trauma, diabetes mellitus, pressure sore and radiation injuries were enrolled in this prospective, open-label crossover trial. Prior to treatment with rbFGF, all wounds failed to heal with conventional therapies within 4 weeks. All wounds were locally treated with rbFGF at a dose of 150 AU/cm2. Healing time and the quality of wounds were used to evaluate the efficacy of the treatment. Results Healing of all chronic wounds was expedited. During the study, eighteen wounds completely healed within 2 weeks, four healed within 3 weeks, and another eight completely healed within 4 weeks. Only three wounds failed to heal within 4 weeks, but healed at 30, 40 and 42 days after treatment with rbFGF. Thus, compared with conventional therapies, the effective rate of rbFGF treatment within 4 weeks was 90.9%. Histological assessment showed more abundant capillary sprouts or tubes and that fibroblasts were differentiated in wounds treated with rbFGF. No adverse side effects related to basic fibroblast growth factor were observed. Conclusions Our results indicate that rbFGF could be used to accelerate healing in chronic wounds. It is our belief that this may be a more effective method of chronic wound management. Chin Med J 2002; 115(3): 331-335

Objective To investigate the mechanism associated with thoracolumbar burst fractures. Methods Stress distribution of the spine in the upright, flexion and extension positions was analyzed using a three-dimensional finite element model of the spinal motion segment. Results Stress concentration was noted at the pedicle and posterosuperior part of the vertebral body near the pedicle. Conclusion Stress concentration of the spine may be implicated in the biomechanical mechanism underlying thoracolumbar burst fractures. Chin Med J 2002; 115(3): 336-338

Objective To determine cell proliferation and nestin expression in the ependyma of adult rat spinal cord after injury. Methods Rat spinal cord injury models were established by aneurysm clip compression, and nestin expression and proliferation of ependymal cells at different times were shown with pathological and immunohistochemical staining. Results Ependymal cells adjacent to the injured site demonstrated a dramatic increase in nestin expression 24 hours after compression. Proliferating cell nuclear antigen was positive, and significant proliferation was observed after 7 days. Nestin expression was down regulated as time went by. Conclusion Normally quiescent mature ependymal cells appear to revert to an embryonic state in response to spinal cord injury. Chin Med J 2002; 115(3): 339-341

Objective To explore the management of cerebral ischemia caused by Takayasu's arteritis. Methods Ninety-three cases treated from June 1984 to September 1999 at the General Post & Telecom Hospital, the Sir Run Run Shaw Hospital, the First Affiliated Hospital of Zhejiang University, the Second Medical College of Beijing University, Beijing An Zhen Hospital, and the Beijing Union Medical College Hospital, including 10 men and 83 women, were reviewed. Of the 93 cases, bypasses from the ascending aorta to the axillary or subclavian artery and from graft to the carotid artery were performed in 47 cases. Subclavian to carotid bypass was performed in six cases. Percutaneous transluminal angioplasty (PTA)was used in five cases and stenting in one. Results Marked improvement was achieved in 30.3%, fair in 34.9%, improvement in 21.2%,unchanged in 4.6%, and death in 9.0%before discharge; 30.6%, 38.8%, 16.3%, 4.1%, and 2.0%respectively during a mean follow-up of 48 months, and recurrence requiring revision in 8.2%. Conclusion Patients with occlusive lesions of all four cervical arteries always have severe cerebral ischemia and their distal runoff is always unvisualised by angiography. However, we found by exploration that the internal carotid artery is patent in all but one patient. Therefore, an ascending aorta to carotid bypass is feasible in most instances, and this can and should be done when the cerebral perfusion is jeopardized at a time when the patient is in a stable or relatively stable condition. Unfortunately, the cerebral re-perfusion syndrome is still a serious and not completely solved problem. Chin Med J 2002; 115(3): 342-346

Objective To compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril. Methods AMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls(n=24),(2) high-dose (10 mg-kg-1·d-1, n=25),(3) middle-dose (1 mg· kg-1·d-1, n=23), and (4)low-dose (0.1 mg·kg-1·d-1, n=25) enalapril groups. In addition, sham-operated (n=13) and normal rats(n=10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10%formalin and pathology analysis was performed. Exclusive of the dead rats and those with Ml size <35%or> 55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n=13),(2) high-dose enalapril (n=13),(3)middle-dose enalapril (n=12),(4)low-dose enalapril (n=12),(5) sham-operated (n=8) and (6) normal (n=9) groups. Results There were no significant differences among the four AMI groups in infarction size (all P > 0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume(LW), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P < 0.001), while maximum LV pressure rising and dropping rates (± dp/dt) and their corrected values by LV systolic pressure (± dp/dt/LVSP) were all significantly reduced in the AMI control group (P <0.01 -0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LW, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P <0.001), with the reduction of LVEDP, LW and LVAW being more significant in high-dose than in low-dose enalapril groups (all P <0.05). and the ± dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P <0.01). Conclusions High, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement,only high and middle-dose enalapril were effective. Chin Med J 2002; 115(3): 347-351

Objective To investigate the dynamic changes of type I collagen, and the activity of metalloproteinases-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) after angioplasty. Methods The restenotic model of iliac arteries of domestic microswine was established with hypercholesterol feed plus two angioplasties. Angioplastied vessels were harvested at the end of 1, 2, 3 and 6 months after the second angioplasty. Immunohistochemistry, transmission electronic microscopy and image quantitative analysis techniques were employed to study neointimal proliferation, the phenotype of vascular smooth muscle cells (VSMC) and the expression of type I collagen, MMP-1 and TIMP-1. Results The peak of vascular neointimal proliferation was at 3 months after angioplasty. The expression of type I collagen gradually increased from 1 to 6 months after angioplasty. For MMP-1, expression was lower in the early stage after angioplasty but increase to normal levels of control vessels at 6 months after angioplasty. Expression of TIMP-1 rapidly increased in the early phase after angioplasty, reached peak at 3 months and maintained the high level till 6 months after angioplasty. Meanwhile, the VSMC was predominantly the synthetic phenotype at the early stage and was transformed to the contractive phenotype at the late stage after angioplasty. The ratio of TIMP-1 and MMP-1 was positively related to the area of the neointima and the expression of type I collagen respectively (P <0.01). Conclusion Type I collagen increased gradually after angioplasty, which might be determined by the ratio of TIMP-1/MMP-1 and also related to the phenotype of VSMC. Chin Med J 2002; 115(3): 352-354

Objective To assess the immediate- and long-term outcomes of stent supported coronary angioplasty in patients with severe left ventricular dysfunction. Methods Seventy-four consecutive patients with angiographic left ventricular ejection fractions ≤ 40%underwent percutaneous coronary angioplasty, including 61 (81 %) with stent back-up. Clinical follow-up(29.1 ±22.9 months) data were obtained in all clinically successful patients. Results Angiographic success was achieved in 120 (89.5%) of 134 lesions. Clinical success was obtained in 66 (89.2%) patients with 1.4%procedure related mortality, 2.7%myocardial infarction and zero need of emergent bypass surgery. NYHA class reduction ≥ 1 was seen in 29 (73%) of 40 successfully treated congestive heart failure patients at 6 months after the procedure. During long-term follow-up, 58 (87.9%) of 66 patients with clinical success were alive, including 44 (68.6%) free from cardiac events. Conclusions Patients with severe left ventricular dysfunction treated with stent supported PTCA experience a high rate of success, low procedure related mortality and satisfactory long-term survival. Chin Med J 2002; 115(3): 355-358

Objective Transesophageal echocardiography was performed during closed-chest cardiopulmonary resuscitation (CPR) in in-hospital cardiac arrest to further explore the hemodynamic mechanism of CPR. Methods CPR attempts were performed according to advanced cardiovascular life support guidelines in 6 cases of in-hospital cardiac arrest. Multi-plane transesophageal echocardiography was carried out within 15 min of initiation of CPR. Throughout CPR, the motion of the mitral, tricuspid and aortic valves, the changes in the left ventricular cavity size and the thoracic aortic diameter were observed. Trans-mitral and trans-aortic Doppler files of blood flow were also documented. Results A closure of the mitral and tricuspid valves with simultaneous opening of the aortic valve occurred exclusively during chest compression, resulting in forward blood flow in the pulmonary and systemic circulation. Peak forward aortic flow at a velocity of 58.8 ± 11 .6 cm/s was recorded during the compression phase. Whereas, a closure of the aortic valve and rapid opening of the atrioventricular valves associated with ventricular filling during relaxation of chest compression was noted in all 6 patients. Peak forward mitral flow at a velocity of 60.6 ± 20.0 cm/s was recorded during the release phase. Mitral regurgitation during the chest compression period was detected in 5 patients, reflecting a positive ventricular-to-atrial pressure gradient. A reduction in the left ventricular chamber and an increase in the thoracic aortic diameter during the compression phase was found in all patients, indicating that direct cardiac compression contributed to forward blood flow. Conclusion These observations favor the cardiac pump theory as the predominant hemodynamic mechanism of forward blood flow during CPR in human beings. Chin Med J 2002; 115(3): 359-363

Objective Because maternal epidermal growth factor (EGF) may be an adaptive response to accelerate growth and maturation in premature infants, we compared the EGF content in fresh cow's milk and cow's milk-based infant formulas with full and preterm mother's milk. Methods EGF content of 57 human colostrum from mothers delivering prematurely and at term, 4 different fresh cow's milk and 8 different cow's milk-based infant formulas was determined by radioimmunoassay(RIA). Results Human milk from mothers of premature infants had a higher EGF content compared to that from mothers of term infants (28 .2 ± 10 . 3 nmol/L vs 17.3 ± 9 . 6 nmol/L). EGF content in human milk negatively correlated with gestational age and birth weight of neonates. EGF content in fresh cow's milk (13.8-18.2 nmol/L) was similar to that in human term milk. EGF levels in non-hydrolyzed protein formulas were much lower (5.6-8.6 nmol/L), and were undetactable in hydrolyzed protein formulas. Conclusion The high EGF content in premature milk may represent a maternal compensatory mechanism to accelerate the growth and development of immature infants. Feeding infants with breast milk from their own mother should be advocated since there is lack of EGF in cow's milk-based infant formulas. Chin Med J 2002; 115(3): 451-454

Objective To establish rat C6 brain-tumor models and find a simple reliable index to judge tumor volume. Methods C6 cell suspension (10 μl) containing 10 g/L agarose and 1 x 106 cells was injected into the right caudate nucleus of the rat brain by a stereotaxic method. After implantation, rats were observed and given MRI scans. Rats were perfused with paraformaldehyde trans-aorta at the 10th, 15th, 20th and 25th day and before natural death. All brains, lungs, spinal cords and tumors were sectioned and inspected. Tumor-containing samples were prepared histologically by hematoxylin and eosin (HE) stains. Results Fifty implanted rats had 100%yield of intracerebral growth, with distant metastasis of 0%to 4%. Conclusion A rat C6 brain-tumor model was successfully established. Rat survival time is correlated with tumor volume and may be useful as an index of tumor size. Chin Med J 2002; 115(3): 455-457

Purpose To review the recent developments in the structure and function of Smad proteins. Data Sources Both Chinese- and English-language literatures were searched using MEDLINE/CD-ROM(1997-2000) and the Index of Chinese-Language Literature (1997-2000). Study Selection Data from published articles about TGF-β signal transduction in recent domestic and foreign literature were selected. Data Extraction Data were mainly extracted from 22 articles which are listed in the reference section of this review. Results Smad proteins mediate signal transduction induced by the TGF-β superfamily. Based on their structural and functional properties, Smad proteins are divided into three groups. The first group, receptor-regulated Smads (R-Smads), are phosphorylated by activated type I receptors and form heteromeric complexes with the second group of Smads, common mediator Smads (Co-Smads) . These Smad complexes translocate into the nucleus to influence gene transcription. Inhibitory Smads (I-Smads) are the third group and these antagonize the activity of R-Smads. In the nucleus, Smads can directly contact Smad-binding elements (SBE) in target gene promoters. Through interaction with different transcription factors, transcriptional co-activators or co-repressors, Smads elicit different effects in various cell types. The aberrance of Smad proteins has been noted in several human disorders such as fibrosis, hypertrophic scarring and cancer. Conclusion The structure of Smads determines their function as transcriptional factors which translocate signals from the cell surface to the nucleus where Smads regulate TGF-β superfamily-dependent gene expression. Chin Med J 2002; 115(3): 446-450