Volume 87  ·   Issue 31  ·  2007

Obstructive sleep apnea syndrome (OSAS) and obstructive sleep apnea hypopnea syndrome (OSAHS) are the most common disorders of sleep breathing disorders in clinic. They are characterized by complete or incomplete obstruction of upper airway repeatedly during sleep, and can cause a series of pathophysiological changes such as intermittent hypoxemia, hypercapnia, sleep structure disorder, etc. The main clinical symptoms include snoring, apnea or waking up during sleep, headache in the morning, drowsiness during the day, fatigue, memory loss, etc., which can cause serious damage to human health. OSAHS can seriously affect human life span.

Since childhood obstructive sleep apnea (OSA) was first reported in 1976, it has gradually been recognized and valued, and is regarded as another disease different from adult OSA (Table 1). In this paper, we will focus on the latest advances and existing controversies in this field combined with our own research results.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is mutually related to various diseases such as cardiovascular disease, obesity and other metabolic diseases. The prevalence of OSAHS is more than 3%, and even as high as 25% in middle-aged men over 40 years old. The biggest harm of OSAHS lies in car accidents and accidental injuries, and many public accidents such as the Three Mile Island nuclear power plant incident and the Exxon oil tanker spill incident are related to sleep diseases.

obstructive sleep apnea hypopnea syndrome (OSAHS) was first diagnosed in 1964 by Kulho and Doll, who used tracheotomy to improve daytime drowsiness and pulmonary hypertension.

Objective to investigate the changes of respiratory center responsiveness in chronic obstructive pulmonary disease (COPD) patients with sleep apnea (overlapping syndrome) by noninvasive ventilation therapy. Methods 10 patients with sleep apnea hypopnea syndrome (SAHS) diagnosed by sleep respiratory monitoring with multi-channel physiological recorder were selected. Among them, 5 patients with COPD had a mean FEV1/FVC of 59%±6%, and 5 patients with SAHS with CO2 retention had a normal FEV1/FVC. The age, body mass index (BMI) and sleep apnea hypopnea index (AHI) of the two groups were matched. △ VE/ △ SaO2) and high CO2 reactivity ( △ VE/ △ Results the hypoxia responsiveness of the respiratory center of patients with overlapping syndrome (OS) and obstructive sleep apnea (OSA) before treatment was (-0.023 ± 0.049) L·min-1·%-1 and (-0.16 ± 0.06) L·min-1·%-1, respectively, which were lower than the laboratory normal (-0.35 ± 0.21) L·min-1·%-1. The high CO2 responsiveness of patients with OS and OSA was (0.54 ± 0.16) L·min-1·mmHg-1 and (1.3 ± 0.62) L·min-1·mmHg-1, respectively. The former was significantly lower than the laboratory normal (1.26 ± 0.54) L·min-1·mmHg-1, and the latter was still within the normal range. Hypoxia [(-0.16±0.06) L·min-1·%-1 vs (-0.36±0.14) L·min-1·%-1] and high CO2 reactivity [(1.3±0.62) L·min-mmHg-1 vs (1.78±0.93) L·min-1·mm Hg-1] in OSA patients were significantly increased, reaching normal levels. Hypoxia reactivity in OS patients was increased [(-0.023±0.049) L·min-1·%-1 vs (-0.09±0.007) L·min-1·%-1], but it was still significantly lower than normal levels; There was no significant change in the responsiveness of high CO2 [(0.54±0.16) L·min-1·mmHg-1vs (0.51±0.23) L·min-1·mmHg-1]. Conclusion the responsiveness of respiratory center to hypoxia and high CO2 stimulation in patients with overlapping syndrome decreased, and it was difficult to recover to normal level in a short time after the sleep respiratory disturbance was removed by positive pressure ventilation, which was different from the changes in patients with simple SAHS, and this abnormal change may be influenced by genetic factors.

Objective to investigate the role of endothelial dysfunction in the pathogenesis of obstructive sleep apnea syndrome complicated with hypertension by observing the concentration of endothelin-1 (ET-1), nitric oxide (NO), nitric oxide synthase (NOS) activity and the expression of endothelial nitric oxide synthase (eNOS) mRNA in human umbilical vein endothelial cells under different intermittent hypoxia (IH) patterns. Methods ECV304 cell line, a passageable cell line of human umbilical vein endothelial cells, was exposed to different hypoxia/reoxygenation conditions. After the exposure, the concentration of ET-1 (enzyme immunoassay, EIA), nitric oxide (nitrate reductase), NOS activity (chemical colorimetry) and eNOS mRNA expression (RTPCR) were measured. Results Compared with the intermittent normal oxygen group and the blank control group, ET-1 concentration increased (F =28.453, P =0.000), NO concentration decreased (F =65.252, P =0.000), NOS activity (F =5.969, P =0.008) and eNOS mRNA expression decreased (F =16.630, P =0.000 The concentration of ET-1 increased with the prolongation of reoxygenation time (F =213.254, P =0.000), while the concentration of NO (F =15.747, P =0.000), the activity of NOS (F =2.933, P =0.048) and the expression of eNOS mRNA decreased (F =5.954, P =0.002) in the intermittent hypoxia group with different frequencies. However, the concentration of ET-1 decreased and the indexes of NO system increased when the reoxygenation time was too long. Conclusion Both hypoxia and reoxygenation process in intermittent hypoxia can lead to endothelial dysfunction, imbalance of NO and ET-1 release, and thus promote the occurrence and development of cardiovascular diseases related to obstructive sleep apnea.

Objective to investigate the relationship between severe obstructive sleep apnea syndrome (OSAS) and sinus node dysfunction (SD). Methods to analyze the electrocardiogram changes of 70 patients with severe OSAS and 36 patients with simple snoring diagnosed in sleep laboratory of our hospital from March 2005 to June 2006. The atropine test was performed in patients with the lowest heart rate<40 beats/min or the highest sinus heart rate<90 beats/min or the longest R-R interval>2.0 s under ultramicroelectrocardiogram (UMECG) to observe and compare their sinus node function and analyze the risk factors of SD. The data were processed by SPSS13.0 software package. Results SD accounted for 22.9% of patients with severe OSAS; The decrease of minimum pulse oxygen saturation during sleep is a major risk factor for SD (P =0.003, OR<0.001, 95% CI0.000~0.016). Conclusion the incidence of SD in patients with severe OSAS is higher than that in patients with snoring.

Objective to investigate the damage mechanism of vascular endothelial cells in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods the subjects were divided into normal control group (n =20), mild OSAHS group (n =21), moderate OSAHS group (n =24) and severe OSAHS group (n =20). After waking up (about 6:30), peripheral venous blood was collected from all subjects, and mononuclear cells (MNCs) were isolated. The isolated MNCs were co-cultured with human umbilical vein endothelial cells ECV304 for 48 h. After culture, the supernatant and endothelial cells were collected. TNF-α, IL-6 in the supernatant were detected by ELISA, and the apoptosis rate and Fas protein expression of endothelial cells were detected by flow cytometry. Results the tumor necrosis factor α (TNF-α) produced by MNC cells in normal control group, mild, moderate and severe OSAHS patients were (0.80±0.10) μ g/L, (1.20±0.30) μ g/L, (1.40±0.50) μ g/L and (2.10±0.60), respectively The production of interleukin-6 (IL-6) was (23.50±6.50) μ g/L, (49.60±2.80) μ g/L, (46.90±10.80) μ g/L and (64.80±9.90) μ g/L, respectively, compared with multiple groups (F =182.83, P<0.01). The production of TNF-α and IL-6 by MNC cells was higher than that of normal control group (all P<0.01); The MNC production of TNF-α and IL-6 in patients with severe OSAHS was higher than that in patients with mild and moderate OSAHS (both P<0.01), and the difference between mild and moderate OSAHS was not statistically significant. The apoptosis rates of endothelial cells were 8.3%±3.2%, 9.2%±3.0%, 19.3%±6.3% and 19.6%±3.8% in normal control group, mild, moderate and severe OSAHS patients, respectively (F =39.36,P<0.01); Patients with moderate and severe OSAHS were higher than those in normal controls (P<0.01); There was no significant difference between patients with mild OSAHS and normal control group, and between patients with moderate and severe OSAHS. There was no significant difference in the expression of Fas protein in endothelial cells between the groups. The apoptosis rate of endothelial cells was positively correlated with AHI in patients with OSAHS (r =0.589 13, P =0.0106), and negatively correlated with nocturnal minimum oxygen saturation (r = -0.507 37, P<0.01). Conclusion Mononuclear cells may play an important role in the process of vascular endothelial cell injury in patients with OSAHS, and this role is closely correlated with the severity of the disease and nocturnal hypoxia.

Objective to investigate the relationship between the disease characteristics of OSAHS and the risk of cardiovascular damage by using Framingham risk score, and to explore the predictive indexes. Methods Framingham risk score was performed in 120 patients with OSAHS, and according to whether the score was less than 10, the clinical indexes (gender, age, BMI, NC, course of disease, ESS), polysomnography (PSG) indexes (AHI, ODI, LSaO2, TS90) and serological indexes (hs-CRP) were compared between the two groups, and the correlation analysis and multiple regression analysis were performed to investigate the influence of each index on Framingham risk score. Results Besides the traditional risk factors of cardiovascular disease, the neck circumference of the patients in the non-low risk group was larger [(40.48±2.80) cmvs (39.15±4.31) cm,t =2.309,P<0.05), the course of snoring was longer [(12.77±7.89) years vs (9.36±5.98) years, t =2.595, P<0.05)], and the severity of the disease was more severe [AHI (47.61±25.63) vs (34.01 LSaO273.85%±11.10%vs 77.91%±9.77%, t = -2.129, P<0.05; TS90 23.46%±24.46% vs 14.48%±18.85%, t =2.023, P<0.05; ODI49.62±23.75vs 39.01±24.87, t =2.990, P<0.05]. Correlation analysis found that Fragmingham risk score and PSG There was a positive correlation between AHI (r =0.284, P =0.002) and ODI (r =0.224, P =0.014), and a negative correlation with LSaO2 (r = -0.212, P =0.020), among which AHI had the greatest effect on FRS (t =2.910, P =0.004). However, there was no significant difference in the distribution of serum hs-CRP levels between the two groups (P =0.567). Conclusion Cardiovascular damage in OSAHS patients is related to recurrent nocturnal hypoxia, and AHI is an important predictive index of PSG.

Objective to observe the effect of 10 mg or 20 mg atorvastatin + long-acting antihypertensive drugs on carotid intima-media thickness (IMT). Methods 151 patients with mild hypertension were randomly divided into 3 groups, 50 cases were treated with 10 mg atorvastatin + amlodipine + benazepril, 61 cases were treated with 20 mg atorvastatin + amlodipine + benazepril, and 45 cases were treated with amlodipine + benazepril in the control group; The changes of IMT, vasodilation function, low density lipoprotein cholesterol (LDL-C) and other indexes were observed before treatment, at the 3rd, 6th, 9th and 12th months. Results the results of comparison between the 10 mg or 20 mg atorvastatin group and the control group were as follows: (1) Carotid IMT decreased (P<0.01); (2) Improvement of vasodilation function (P<0.01); (3) LDL-C decreased by 30% in 10 mg atorvastatin group and 40.48% in 20 mg group (P<0.01). Conclusion 10 or 20 mg atorvastatin can delay the development of atherosclerosis in patients with hypertension; Improve vascular endothelial function; Achieve enhanced lipid-lowering effect.

Objective to analyze the pathological characteristics of clustered sudden death of unknown causes in Yunnan Province, and to provide evidence for its etiology exploration and intervention. Methods 29 autopsy cases with complete clinical and pathological data since the sudden death surveillance was carried out in Yunnan Province, accounting for 10.2% of the deaths in the same period, aged 8 to 69 years (mean 32 years), 16 males and 13 females. The cardiac specimens were checked, the histopathological changes of main organs were observed, and the cardiac conduction system was examined in 5 cases. The pathological diagnosis of myocarditis was according to the Dallas standard and the consensus of the World Heart Federation, and the pathological diagnosis of standard Keshan disease was according to the relevant national health industry standards. Results The main pathological changes of the heart were: There were 11 cases of lymphocytic myocarditis, 3 cases of neutrophilic myocarditis, 4 cases of arrhythmogenic right ventricular cardiomyopathy, 2 cases of left ventricular hypertrophy complicated with abnormal outflow tract muscle bundle, 2 cases of ischemic heart disease, 2 cases of allergic bronchitis and chronic bronchitis complicated with emphysema, 5 cases of main organs without obvious fatal pathological morphological changes. Among 29 cases, there were no pathological morphological changes of Keshan's disease and dilated cardiomyopathy. The myocarditis was focal, 5 cases of cardiac conduction tissue examination showed acute hemorrhage of His bundle or left bundle branch initial segment in 2 cases, and inflammation spread to atrioventricular node in 1 case. The pathological changes of 4 family cluster cases were different, 3 cases of first sudden death were myocarditis and 1 case of chronic infection, 3 cases of second sudden death were related to acute myocardial ischemia, and 1 case was arrhythmogenic right ventricular cardiomyopathy. Most cases were accompanied by pulmonary edema, Conclusion the basic pathological changes of unexplained cluster sudden death in Yunnan are different, most of them are myocardial inflammation, cardiac dysplasia and other fatal cardiopulmonary diseases. There is no pathological evidence of Keshan's disease. Basic heart diseases such as arrhythmic right ventricular cardiomyopathy should be paid attention to. The cluster of sudden death may be a comprehensive manifestation of many factors.

Objective to investigate the single nucleotide polymorphism (SNP) loci of hepatic lipase promoter 250G/A, 514C/T, 710T/C and 763A/G genes in patients with cerebral infarction in Shanghai, and their haplotype and linkage disequilibrium relationships. Methods Polymerase chain reaction-restriction fragment length polymorphism technique was used to analyze the polymorphism of hepatic lipase gene in 133 patients with cerebral infarction and 112 healthy controls. Results Compared with healthy controls, the genotype and allele frequency distribution of-250G/A and-514C/T in cerebral infarction group were statistically significant (all P<0.05); Compared with the healthy control group, there was no significant difference in the distribution of-710T/C, -763A/G genotypes and allele frequencies in the cerebral infarction group (all P>0.05). Meanwhile, the paired linkage disequilibrium test showed that there were strong linkage disequilibrium between-250G/A and-514C/T, -710T/C, -763A/G, between-514C/T and-710T/C, -763A/G, and between-710T/C and-763A/G. In addition, when the alleles-250G and-514C, -710C, -763G and-514C and-710C, -763G were paired, the occurrence rates in the cerebral infarction group were significantly lower than those in the control group; When the alleles-250A and-514T, -710T, -710C, -763G, -514T and-710C, -763G, and-710T and-763G were paired, the occurrence rate in the cerebral infarction group was significantly higher than that in the control group.Conclusion There is a significant haplotype and linkage disequilibrium relationship between the four SNP loci of liver lipase gene in Shanghai patients with cerebral infarction, and haplotypes GC, GG and CC may reduce the incidence of cerebral infarction, while haplotypes AT, AC, AG, TC and TG may increase the incidence of cerebral infarction.

Objective to investigate the effects of calmodulin gene (CALM1 gene) and growth hormone receptor gene (GHR gene) in the pathogenesis of adolescent idiopathic scoliosis (AIS), and whether there are interactive effects and gene-gene interaction effects between candidate gene polymorphism and AIS risk factors.Methods A case-control study was performed. The AIS case group was selected according to the inclusion criteria strictly, and the corresponding sex-age matched control samples were collected. After obtaining informed consent, peripheral venous blood was collected to extract DNA, and the suspected SNP loci of candidate gene were selected, and the gene sequencing was performed. According to the risk factors of AIS, the clinical questionnaire was designed, and the relationship between gene and clinical phenotype was studied by combining clinical data with laboratory results. Results AIS patients had higher postoperative corrected height and earlier development peak time. The distribution frequency of CALM1 gene-16C>T locus CC genotype and GHR gene-I526L locus homozygous genotype was higher in AIS case group than in control group. The frequency of SNP03G-05A and SNP03G-05C haplotype of GHR gene was significantly different between AIS case group and control group, The homozygous genotype of GHR gene I526L (referred to as PP) and the homozygous genotype of melatonin receptor gene 1B (referred to as GG) (referred to as PPGG) were distributed significantly more frequently in the AIS cases than in the control group.The postoperative corrected height of patients with homozygous GHR gene I526L (referred to as PP) in the AIS case group was higher than that of heterozygous patients, and their developmental peak time was earlier than that of heterozygous patients. Conclusion The CC genotype at-16C>T locus in the promoter region of CALM1 gene and the homozygous genotype at I526L locus of GHR gene may be related to the susceptibility of AIS.

Objective to investigate the effect of disinfection and sterilization treatment on the biomechanics of continuous carbon fiber reinforced polyolefin composites, and to provide experimental basis for selecting suitable disinfection and sterilization methods in clinical use.Methods 80 continuous carbon fiber reinforced polyolefin composite rods were divided into 8 groups, 10 rods in each group, one group was directly tested without any treatment as a blank control, and the other 7 groups were disinfected and sterilized by high pressure steam, 2% glutaraldehyde soaking, ethylene oxide soaking, 75% alcohol soaking, cobalt-60 (a) 11kGy, cobalt-60 (B) 25kGy and cobalt-60 (C) 18kGy respectively; The bending and compression mechanics tests were carried out respectively, the maximum load, ultimate strength and elastic modulus were measured, and the differences between the groups were compared to understand the biomechanical changes of the composites after disinfection and sterilization. Results Compared with the blank control group, the biomechanics of carbon fiber-reinforced polyolefin composite rods were decreased by high-pressure steam and cobalt-60 γ-ray irradiation (11, 18, 25 kGy) treatment, and the differences were statistically significant; After ethylene oxide sterilization, 2% glutaraldehyde immersion (12 h) and 75% alcohol immersion (12 h), the biomechanics of the composites also showed a decreasing trend, but the difference was not statistically significant. Conclusion When carbon fiber reinforced polyolefin composite products are used as sterile packaging, high pressure steam and cobalt-60 γ-ray irradiation should be avoided as sterilization treatment methods; Ethylene oxide sterilization, 2% glutaraldehyde immersion (12h) and 75% alcohol immersion (12h) can all be used as sterilization methods for composite materials. Considering the operability of mass production as bacteria packaging, it is suggested that ethylene oxide sterilization may be more suitable; In order to prevent the influence of γ-ray on the mechanical properties of the composites, further improvement is needed.

Objective to investigate the feasibility of using tissue engineering technique to construct tissues with certain morphology and testosterone secretion function in vitro and in vitro.Methods Male Wister rats were aseptically excised from bilateral testes to prepare castrated and transplanted rats.The testes were deenveloped, sheared, digested with collagenase, and co-cultured with differential adherence or direct mixed co-culture.Testicular mesenchymal cells (Leydig cells) and co-cultured testicular somatic cells were obtained by differential adherence or direct mixed co-culture.The two types of cells were compounded with degradable biomaterial polyhydroxyacetic acid (PGA) fibers and cultured in vitro.The tissue formation process in vitro was observed by light and electron microscope.The testosterone secretion level in the culture medium was measured regularly.The cell-material complex was cultured in vitro for 7 days and transplanted into the sheath cavity or omentum of the ovariectomized rats (n =6). The samples were collected at different time points. The formation process of androgen secretion tissue and blood testosterone level in the transplanted rats were detected by gross observation, histological staining and immunocytochemistry methods.Results Both types of cells had good affinity with PGA, Cell-material complexes with certain testosterone secretion function can be formed in vitro.After 2 months in vivo transplantation, both cell-material complexes can form androgen secretion tissues with certain morphology in omentum and testicular sheath, and the regenerated tissues have good vascularization.The results of blood testosterone detection and statistical analysis showed that after 6 weeks of transplantation, the blood testosterone level of Leydig cell group alone was (0.60±0.04) μ g/L, and the blood testosterone level of co-cultured cell group was (0.85±0.03) μ g/L, both of which were significantly higher than those of simple castrated rats (0.56±0.05) μ g/L (P<0.01). Compared with the two groups, the blood testosterone level of co-cultured cell transplantation group was significantly higher than that of Leydig cell transplantation group alone (P<0.01). Conclusion It is feasible to use co-cultured testicular somatic cells as seed cells to construct androgen secretion tissues in vivo and in vitro, and co-cultured testicular somatic cells are good seed cells for androgen secretion tissues.

Objective to investigate the effect of the induction time of transforming growth factor β 1 (TGF-β 1) on the chondrogenic differentiation of bone marrow stromal cells (BMSC) in vitro and the construction of tissue engineered cartilage. Methods the second-generation porcine BMSC were inoculated on cylindrical scaffolds made of polyhydroxyacetic acid (PGA) at a density of 5.0×107/ml. On the fifth day, the cartilage induction solution containing TGF-β 1 (10 μ g/L), IGF-Ⅰ (50 μ g/L) and dexamethasone (40 μ g/L) was started to be cultured. According to the different induction time of TGF-β 1, it was divided into 5 groups: A (2 weeks induction), B (4 weeks induction), C (6 weeks induction), D (8 weeks induction) and E (10 weeks induction). After 10 weeks in vitro culture, the samples were gross observation, histological and histochemical detection, quantitative analysis of polymeric proteoglycan (GAG) and biomechanical determination, and the expression of type Ⅱ collagen was analyzed by Western blot and immunohistochemistry. The results of immunohistochemical staining and Western blot showed that the content of type Ⅱ collagen gradually increased with the induction time, and this situation gradually stabilized after 6 weeks of induction, and there was no statistically significant difference between 6 weeks of induction and 10 weeks of induction. The elastic modulus and compressive strength of the group after 6 weeks of induction were significantly higher than those of groups A and B. Conclusion BMSC was used as seed cells to construct tissue engineered cartilage, and the induction duration was related to the quality of cartilage formed. The cartilage tissue with good tissue structure, chemical composition and mechanical properties could be formed after 6 weeks of induction.

Since the development of medicine, the human gene map shows us not the final answer of medicine, but only the beginning of the development of medicine in a deeper direction, that is, the development of systematic medicine. In biology, we have the cognition of genomics and proteomics; In medical understanding, there are "human body is an open system", "human disease and health process conforms to the basic characteristics of open complex system" [1], etc.; Some ideological debates, such as "system theory and reduction theory [2]", "structure and function", etc.; In practice, the establishment of database and evidence-based model have become new medical methods and models, which indicate to us that systematic medicine will become the trend of medical development.

In order to promote the talent team and discipline construction of acute and critical care in China, the editorial committee of Chinese medical journal of Chinese medical association, the magazine of general medicine clinical and education, and the Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine jointly organized the first acute and critical care forum for young and middle-aged physicians, which was held in Qiandao Lake, Zhejiang Province on April 26-30, 2007. More than 100 academic papers were received at the conference, and more than 150 representatives from all over the country attended the forum. Experts from all over the country gave 9 special reports on the progress of basic and clinical research in the field of acute and critical care and 16 conferences.