Volume 86  ·   Issue 41  ·  2006

Chronic obstructive pulmonary disease (COPD) is the fourth cause of death in the world and the second cause of disability in the United States. The prevalence rate in China is also very high. In some areas of Guangdong, the prevalence of COPD is higher in rural areas than in urban areas. The high incidence of COPD in rural areas is mainly related to the combined effect of smoking and biofuels [1]. In the past, some people thought that COPD is an irreversible pathological process, and it is difficult to make a difference in diagnosis and treatment, and it is difficult to have effective measures to slow down the progression of the disease and functional impairment. However, some experts and pharmaceutical companies have not given up their efforts, and have been devoted to obscure basic research, and strive to find and develop new and more effective drugs that can fundamentally control the progression of the disease. Now, with the gradual deepening of the research on COPD, many new achievements have been made in the understanding of the pathogenesis and treatment, and the prospect has become brighter day by day. This paper summarizes and evaluates the basic and clinical studies of COPD from several limited angles, and provides reference opinions for future work.

Airway remodeling and persistent inflammatory response are common characteristics of various airway diseases, especially allergic asthma, which are usually regulated by a series of complex surrounding cell/tissue and cytokine/mediator interactions occurring in the airway cavity and airway walls. Although airway epithelial cells are very complex in airway anatomy, it is generally considered as a passive target and does not actively participate in the regulation of disease pathogenesis in the past. However, more and more evidence shows that airway epithelial cells are also actively involved in the regulation of disease, not only as passive targets of mucosal barrier and disease symptoms. It is generally believed that airway epithelial cells are an important source of cytokines that can regulate mucosal immunity and airway inflammation. Although this regulatory effect has been recognized at present, its regulatory mechanism and possible mediators are still unclear. Recently, it has been found that interleukin (IL) -17A may directly participate in the innate and acquired immune regulation of airway, Especially when the airway is infected by bacteria, the effect is more obvious [1].

Although mucus plays a clearing and auxiliary role in the mucosal barrier, mucus hypersecretion is a major pathophysiological characteristic of chronic bronchitis. Persistent mucus hypersecretion leads to airway obstruction, which affects the clearance of inhaled bacteria and particles in the airway of patients with chronic obstructive pulmonary disease (COPD). Although the mechanism of mucus hypersecretion is still unknown, it is still a major therapeutic target. Studies have shown that human neutrophil elastase is a stimulant related to airway mucus hypersecretion in patients with chronic bronchitis, and can stimulate human airway epithelial cells to secrete mucin (glycoprotein component of mucus) in vitro. The signaling molecules related to mucus hypersecretion induced by human neutrophil elastase include protein kinase C, especially delta isomer and myristoylated alanine-rich C kinase substrate proteins (MARCKS). These molecules mean that regulating mucus secretion in patients is a potential therapeutic target.

Chronic obstructive pulmonary disease is the fourth cause of death in the world [1] and the second cause of disability in the United States. Therefore, it is necessary to establish a more convenient and reliable method to assess the prognosis of patients in clinic.At present, there is still controversy about whether bronchiectasis, cystic fibrosis and chronic asthma with irreversible airflow obstruction should be classified as chronic obstructive pulmonary disease (COPD). Two guidelines define the category of COPD as chronic obstructive bronchitis, emphysema or both according to the existing clinical evidence [2, 3].

At present, the methods for treating chronic obstructive pulmonary disease (COPD) are very limited, and there are no effective measures that can slow down the progression and functional impairment of the disease. Therefore, many pharmaceutical companies are committed to exploring and developing new and more effective drugs that can fundamentally control the progression of the disease [1, 2].

Objective to investigate the TEM and SHV genotypes and their molecular epidemiology of β-lactamase-producing Klebsiella pneumoniae in Guangzhou. Methods the genes of blaTEM and blaSHV were amplified in 57 strains of β-lactamase-producing Klebsiella pneumoniae, and the amplified products were analyzed by denaturing high performance liquid chromatography and sequencing, respectively, to clarify the gene types. Results the genes of blaTEM and blaSHV were amplified in 57 strains of Klebsiella pneumoniae. The sequencing results showed that 32 strains of TEM-116 ESBL (54.2%); The main SHV type was SHV-12, accounting for 33.3%, followed by SHV-11 and SHV-2a, and five new SHV gene subtypes were also found. 54 strains produced both TEM and SHV β-lactamase, accounting for 94.7%; Conclusion TEM-116 and SHV-12 are the main gene subtypes of β-lactamase-producing TEM-type and SHV-type resistance plasmids of Klebsiella pneumoniae in Guangzhou, respectively. The proportion of blaTEM and blaSHV produced in Klebsiella pneumoniae is very high, which suggests that the region is about to face resistance and epidemic of new resistance mechanism of Klebsiella pneumoniae, and the molecular epidemiological surveillance of ESBL-producing Klebsiella pneumoniae must be strengthened.

Objective to investigate the effects of insulin receptor substrate-1 (IRS-1), serine (Ser307) phosphorylation and tyrosine (Tyr) phosphorylation on insulin resistance (IR) in skeletal muscle of rats with different degrees of infection. Methods SD rats were randomly divided into control group, 10% group and 30% group. The infection model was made by cecal ligation and perforation in 10% group and 30% group. The ligation length was 10% and 30% of the total length, respectively. The control group was sham operation group. The rats in the three groups were sacrificed after taking fasting blood and gastrocnemius muscle of hind legs at each time point before and after operation. Plasma fasting blood glucose (FPG), fasting blood insulin (FINS), TNF-α and IL-6 concentrations were measured, IR index (lgIRI) was calculated, and IRS-1, Tyr phosphorylation and Ser307 phosphorylation levels were measured at the same time. Results There were statistically significant differences in survival curves between the three groups (P<0.01). TNF-α and IL-6 in 10% group and 30% group were significantly higher than those in control group (P<0.01), and 30% group was higher (P<0.01). In the control group and 30% group, IRS-1 was positive and located in the cytoplasm of skeletal muscle; IRS-1Tyr phosphorylation was positive in the control group, while only scattered positive in 30% group; The phosphorylation of IRS-1Ser307 in the control group was negative, while the phosphorylation of IRS-1Ser307 in the 30% group was strongly positive. Semi-quantitative analysis showed that IRS-1 in the 30% group was similar to that in the control group at all postoperative time points (all P>0.05), the phosphorylation of IRS-1Tyr in the 30% group was significantly lower than that in the control group at all postoperative time points (all P<0.01), and the phosphorylation of IRS-1Ser307 in the 30% group was significantly higher than that in the control group at all postoperative time points (all P<0.01). There was a significant negative correlation between IRS-1 and IRS-1 Tyr phosphorylation (r = -0.957, P<0.01), and a significant positive correlation between IRS-1 Ser307 phosphorylation and IRS-1 Ser307 phosphorylation (r =0.955, P<0.01). Conclusion The content of IRS-1 in skeletal muscle cells remains unchanged under infection, but the phosphorylation of Tyr decreases, while the phosphorylation of Ser307 increases. The degree of change is closely related to the degree of insulin resistance.

Objective to observe the role of Notch-1 signal in the differentiation of bone marrow mesenchymal stem cells (MSCs) into neural cells. Methods Mouse Notch-1 shRNA was constructed by RNA interference technique and transfected into MSCs to induce their differentiation into neural cells. At the same time, untransfected MSC and transfected glyceraldehyde-3-phosphate dehydrogenase (GAPDH) shRNA were used as controls. The expressions of nestin, neuron-specific enolase (NSE), neurofilamin 200 (NF200), glial fibrillar acidic protein (GFAP) and Notch-1 protein were detected by immunocytochemical staining and Western blot. The apoptosis rate of mNotch-1 shRNA was evaluated by in situ end labeling staining. Results After 6 days of induction, the cells induced by Notch-1 shRNA formed a typical neural cell morphology, and expressed Nestin, NSE and NF200 efficiently, but did not express GFAP. However, the apoptosis rate of mNotch-1 shRNA transfection was significantly higher than that of the control group (13.3%±2.3%). Conclusion The transverse differentiation process of MSC may be similar to that of neural stem cells, and blocking Notch signaling pathway will increase the differentiation effect of MSC into neural cells.

Objective to investigate the significance of quantitative detection of differential display encoding 3 (DD3) mRNA in peripheral blood in the diagnosis and therapeutic monitoring of prostate carcinoma. Methods FQ-RT-PCR was used to quantitatively detect the contents of DD3 mRNA in peripheral blood of 35 patients with untreated prostate carcinoma, 58 patients with prostate carcinoma after endocrine therapy, 59 patients with benign prostatic hyperplasia and 10 healthy male volunteers, and the value of DD3 mRNA in diagnosis and therapeutic monitoring was evaluated. Results The contents of DD3 mRNA in peripheral blood of untreated prostate carcinoma group were significantly higher than those of posttreatment prostate carcinoma group, prostatic hyperplasia group and healthy male volunteers group, and the difference was statistically significant (P<0.01). With the increase of clinical stage, the contents of DD3 mRNA in peripheral blood of untreated prostate carcinoma patients also increased, and the difference was statistically significant (P<0.01). When the critical value was 846 copies/ml, the area under the curve of DD3 mRNA was 0.822 (95% CI: 0.725~0.919), and the sensitivity and specificity were 722 (95% CI: 0.725~0.919)

Objective to investigate the method and efficacy of microsurgical treatment of trigeminal nerve schwannoma.Methods 27 cases of trigeminal nerve schwannoma treated by microsurgical treatment of middle cranial fossa floor were retrospectively analyzed.Results 25 cases of total tumor resection and 2 cases of subtotal tumor resection were observed.Postoperative cranial nerve dysfunction was improved in 18 cases compared with preoperative,4 cases had no obvious changes, 5 cases were aggravated, and 4 cases had new cranial nerve paralysis (incomplete paralysis); Two cases had cerebrospinal fluid leakage and intracranial infection, which were cured by lumbar puncture, cerebrospinal fluid drainage and antibiotic therapy. There were no postoperative deaths in this group, and the patients were followed up for 6~48 months. Except one case who recurred 40 months after operation and underwent secondary operation, all the other patients recovered well. Conclusion This approach has light brain tissue traction, good surgical field exposure, and can be operated from multiple angles, which is helpful to improve the total tumor resection rate and reduce the morbidity rate.

Objective to investigate the surgical methods, effects, factors affecting the surgical effect and prevention of postoperative complications in the treatment of obstructive hydrocephalus.Methods the clinical data of 55 cases of obstructive hydrocephalus treated by neuroendoscopy were retrospectively analyzed.Results Among 55 patients, 54 cases had successful fistula, 1 case could not be fistulated because of vascular network in the floor of the third ventricle, 50 cases had good effect, 4 cases were ineffective, and ventriculoperitoneal shunt was performed within 3 months after fistula.Subdural effusion occurred in 8 cases, chronic subdural hematoma occurred in 1 case and external drainage was performed after 4 months, subscalp effusion occurred in 8 cases, fever occurred after operation in 15 cases, epilepsy occurred in 1 case, epidural hemorrhage occurred in 1 case. Conclusion Neuroendoscopic fistula of the floor of the third ventricle is safe and effective, with satisfactory results.

Objective to investigate the diagnosis and treatment of rare femoral neck fractures in patients with 17 α-hydroxylase deficiency. Methods the clinical data of patients were collected in detail, comprehensive physical examination and auxiliary examination were performed, and the femoral neck fractures were treated by hormone replacement therapy and surgery. The diagnosis and genetic basis of femoral neck fractures were confirmed by molecular genetic research. Results the medical history, physical examination and auxiliary examination supported the diagnosis of 17 α-hydroxylase deficiency. The displaced femoral neck fractures were restored by closed reduction and cannulated nail internal fixation under intraspinal anesthesia to restore the function of the affected limb. Molecular genetic studies showed that this patient had homozygous mutation of CYP17A1 gene, and exon 6 6436-6438 (TAC → AA) caused Y329K, 418X, resulting in the formation of truncated protein lacking enzyme active center. Conclusion Femoral neck fractures in patients with 17 α-hydroxylase deficiency can be restored by surgery. The mutation of CYP17A1 gene exon 6 TAC329AA has certain ethnic specificity in China.

The most common disease of sleep apnea is obstructive sleep apnea hypopnea syndrome (OSAHS). Its main pathophysiological changes are the frequent occurrence of hypoxia-reoxygenation process and sleep segments in patients at night, and these two processes will inevitably cause a series of neurological, endocrine hormones, thrombosis, metabolic abnormalities and inflammatory reactions, resulting in multiple organ damage in the whole body, and thus a variety of cardiovascular and cerebrovascular diseases. Even if there is no obvious cardiovascular and cerebrovascular diseases, the above pathophysiological changes will eventually lead to cardiovascular and cerebrovascular diseases. Therefore, OSAHS is closely related to the occurrence and development of cardiovascular and cerebrovascular diseases.

ventilator associated pneumonia (VAP) refers to new infectious inflammation of lung parenchyma (excluding non-invasive mechanical ventilation) that occurs within 48 hours after tracheal intubation or tracheotomy and mechanical ventilation, and within 48 hours after discontinuation of mechanical ventilation and removal of tracheal tube [1]. VAP is one of the most common types of nosocomial pneumonia, and the incidence of VAP is high in patients treated with mechanical ventilation. Compared with patients without VAP, VAP patients have longer hospital stay, higher medical cost and higher mortality.

Clinical data A 42-year-old female, weight 49 kg, was admitted to hospital on February 2, 2006 due to rheumatic heart disease, moderate to severe mitral stenosis with mild regurgitation, severe tricuspid regurgitation, atrial fibrillation, severe pulmonary hypertension, and grade Ⅲ cardiac function.

essential tremor (ET) is a chronic progressive disease, which is characterized by motor tremor of upper arm, hand, head and trunk. The prevalence of ET is about 0.3% ~4%. The pathogenesis of ET is still unknown. At present, ET is considered to be a neurogenetic disease, and it is reported that 17% ~100% of patients have a positive family history.

Although the pedicled transfer of medial gastrocnemius muscle flap is a traditional surgical procedure for repairing soft tissue defects around the knee joint, the bloated myocutaneous flap and the unsatisfactory shape of the donor site after resection affect its wide application in clinic.Inspired by the successful transplantation of medial gastrocnemius artery musculocutaneous perforator flap [1], the clinical application of perforator myocutaneous flap in repairing soft tissue defects of prepatella and pretibia with exposed bone and tendon wounds has achieved satisfactory results, which are reported as follows.

Hepatopulmonary syndrome refers to the functional changes of the lungs caused by liver insufficiency, which can lead to clinical syndromes characterized by hypoxemia [1]. Conservative treatment can be performed first, and liver transplantation should be performed in those who are ineffective [2-4]. After liver transplantation, hypoxemia can be reversed in most patients [5, 6]. There is no report of combined liver-lung transplantation in the literature. The authors treated a patient with hepatopulmonary syndrome with liver transplantation. The liver function recovered well after operation, but the respiratory function failed to recover. The tracheotomy was performed on the third day after operation, and the pulmonary infection died on the seventh day. The pathology of lung tissue biopsy performed during operation showed that the pulmonary septum was widened and fibrosis. The authors believe that the patient with hepatopulmonary syndrome with obvious hypoxemia should perform lung histopathological examination before operation, and decide to perform liver transplantation or combined liver-lung transplantation according to the examination results.

Stress urinary incontinence (SUI) is a common disease in obstetrics and gynecology department, which greatly affects women's health and quality of life, and becomes one of the important problems that trouble women. For a long time, doctors have always evaluated pelvic floor function according to patients' clinical symptoms and subjective feelings, but there is no objective and accurate evaluation standards. In this paper, 57 patients with SUI were detected and analyzed by biofeedback pelvic floor muscle training therapy instrument, so as to explore the clinical significance of surface electromyography in evaluating female pelvic floor muscle activity function.

MAPK14 is an important member of MAPK family, and its main function is to involve stress-dependent apoptosis and inflammatory response. It can be activated by stress factors such as ischemia and hypoxia, proinflammatory factors, endotoxin and ultraviolet radiation [1]. Intraventricular injection of kainic acid induces epileptic state to damage hippocampal neurons, and inhibits p38 MAPK pathway, which plays a significant protective role on hippocampal neurons [2]. Therefore, we measured the expression of p38 and p-P38 in drug-resistant temporal lobe epilepsy (DR-TLE) to explore its role.

annexin Ⅰ is the first member of calcium-dependent phospholipid binding proteins, which may be involved in signaling related to inflammation, differentiation and proliferation [1]. The characteristic distribution and expression of annexin Ⅰ are also different in different normal tissues (high expression in leukocytes, histiocytes, respiratory tract, genitourinary tract epithelium and non-keratinized squamous epithelium, but no expression in liver tissue and pancreatic exocrine glands) [2]; The expression of annexin Ⅰ was increased in breast cancer [3,4], liver cancer [5,6] and pancreatic cancer [7], while the expression of annexin Ⅰ was downregulated in esophageal squamous cell carcinoma [8,9], prostate cancer, head and neck squamous cell carcinoma and B cell non-Hodgkin lymphoma.

Pituitary thyroid stimulating hormone (TSH) adenomas account for 0.2% ~2.8% of pituitary adenomas, and the clinical manifestation is central hyperthyroidism (hyperthyroidism) [1]. The management principle of central hyperthyroidism caused by pituitary TSH adenomas is completely different from that of primary hyperthyroidism [2]. Wrong anti-thyroid therapy not only cannot control the symptoms of central hyperthyroidism, but can stimulate the rapid and invasive growth of pituitary TSH adenomas, which increases the difficulty of operation and the chance of postoperative recurrence. This paper retrospectively analyzes the data of 9 patients with pituitary TSH adenomas confirmed by pathology admitted to Peking Union Medical College Hospital from July 2001 to December 2004, and summarizes the management of central hyperthyroidism during perioperative period as follows.