Volume 90  ·   Issue 42  ·  2010

In recent years, dynamic blood glucose monitoring has been gradually applied to clinical research and prevention and treatment of diabetes, which has raised people's understanding of the law of blood glucose fluctuation to a new level, and at the same time helped diabetic patients to adjust and formulate reasonable hypoglycemic treatment schemes, so as to make blood glucose management more scientific [1]. However, the clinical advantages, indications, accuracy judgment of monitoring data, interpretation of monitoring results and how to guide clinical practice of this technology have not been familiar to the majority of clinicians. In December 2009, the Diabetes Branch of Chinese Medical Association formulated and released China's first<Clinical Application Guidelines for ambulatory blood glucose monitoring>, which provides a basis for the standardized application of ambulatory blood glucose monitoring [2]. Considering the current clinical application status, combined with<In order to further improve the application level of ambulatory blood glucose monitoring, special attention should be paid to the following aspects in clinical practice.

The traditional view is that diabetic complications are caused by the activation of advanced glycosylation end products (AGEs), polyol pathway, protein kinase C (PKC) and hexosamine pathway, but Brownlee [1] proved that excessive mitochondrial reactive oxygen species (ROS) production may be the common mechanism of diabetic complications. Good blood glucose control is an important measure to delay or prevent the development of chronic diabetic complications, and glycosylated hemoglobin (HbA1c) is the gold standard reflecting long-term blood glucose control. However, the diabetes control and complications test (DDCT) showed that even if the level of HbA1c is the same, the risk of complications is different. Based on this result, it is speculated that in addition to genetic susceptibility, fluctuating hyperglycemia may cause more serious damage to blood vessels than persistent hyperglycemia.

Objective To evaluate the accuracy and safety of continuous glucose monitoring system (CGMS) in subjects with normal glucose tolerance (NGT), impaired glucose regulation (IGR) and newlydiagnosed type 2 diabetes mellitus (T2DM). Methods A total of 162 subjects(53 NGT, 53 IGR and 56newly diagnosed T2DM) at 22 -72 years old were recruited. Each subject received a continuous glucose monitoring(CGM) of CGMS(R) SYSTEM GOLDTM (Medtronic Minimed, Northridge,CA) for 3 consecutive days and was instructed to self-calibrate the interstitial glucose levels with finger-stick blood glucose measurements (self-monitoring of blood glucose, SMBG)7 times daily. Means of median absolute difference (median AD) and median absolute relative difference (median RAD) were calculated to assess the difference between CGM and SMBG values. The correlation between CGM and SMBG values were analyzed with the liner regression analysis. The data were analyzed by the ISO criteria for home glucose meters and Clarke error grid analysis. Results All participants showed a good tolerance to the insertion of CGMS sensor and wearing the device. The mean duration of CGMS recording was (75.6±8.3) h. A total of 4324 glucose meter values were paired with glucose measurements from CGMS. Overall, a good relationship (r=0.943,P = 0.000) and no significant difference (P >0.05) over a wide range(2.2-22.2mmol/L) were found between CGM and SMBG values. The median AD was 0.5 (0.2-0.9) mmol/L and the median RAD 7.55% (3.33%-14.09%) with 87.16% of sensor values meeting the ISO home glucose meter criteria.The Clarke error grid analysts showed that 99. 58% of the readings from CGMS fell into the clinical acceptable zones including 87.5% values in zone A (clinical exact) and 12.1% values in zone B (benign error). Conclusion Both safe and well-tolerated, continuous glucose monitoring provides comparatively accurate blood glucose values to guide the diagnosis and treatment of diabetes.

Objective To find out the features of glycemic excursion via continuous glucose monitoring system (CGMS) during continuous subcutaneous insulin infusion (CS Ⅱ) treatment in type 2diabetics and discuss the possibility of predicting nocturnal hypoglycaemia with bedtime glucose level. Methods A total of 257 diabetes patients (156 males and 101 females, aged from 27 -88 years old)with 0. 1 -40 years diabetic history were recruited. Their HbAI c level was (10. 97 ± 2. 11)%. Glycated albumin level was (31.88 ±7.51)%. All patients were switched to CS Ⅱ therapy while a 72-hour period of CGMS was performed. Participants were divided into hypoglycemia group and non-hypoglycemia group according to the reading of hypoglycemic events from CGMS data. Results (1) From CGMS profiles, the investigators found that MBG was (9. 66 ±2. 00) mmol/L and SDBG (2.98 ± 1. 03)mmol/L. (2) A total of 243 hypoglycemia events occurred in 118 participants at early stage of CS Ⅱ treatment. (3) When bedtime blood glucose was below 5.9 mmol/L, the youden index was maximal on a receiver operating characteristic curve. The sensitive was 54. 8% and specificity 77.8%. Positive predictive value was 44. 3% and negative predictive value 84.2%. So the cut-off point of bedtime blood glucose to predict nocturnal hypoglycemia might be 5. 9 mmol/L, Conclusion(1) Hypoglycemia as detected by CGMS occurs in almost 1/2 type 2diabetics during CS Ⅱ therapy. (2) There is a higher risk of nocturnal hypoglycemia if the bedtime blood glucose concentration falls below 5.9 mmol/L.

In recent years, with the aging of society, the urbanization of population, the westernization of dietary structure and the progress of detection technology, the incidence of prostate cancer (PCa) in China has obviously increased. Taking Shanghai as an example, the incidence of prostate cancer (PCa) has increased from 0.2/100,000 people in 1950s to 7.7/100,000 people in 2000. In the next 10 years, the incidence rate of large and medium-sized cities in China will increase worryingly. Argon-helium cryoablation (TCAP) for PCa has become one of the preferred therapeutic methods in Europe, America and other western developed countries, and has entered a golden period [1]. It started late in China, but it began to attract attention [2-4]. Among them, it is very important to analyze and understand the hot spots of treatment progress, relevant evidence-based medicine basis, controversy and complications for actively carrying out TCAP and treating it safely and effectively.

Objective To investigate the mechanism of oridonin (ORI)-induced autophagy in prostate cancer PC-3 cells. Methods The PC-3 cells cultured in vitro were treated with ORI. The inhibitory ratio of oridonin In PC-3 cells was assayed by MTT. The ultrastructural cellular changes were observed under light microscope, scanning electron microscope (SEM) and transmission electron microscope (TEM). AO staining was used to observe the acidic vesicular organelles (AVOs). The level of MAP1-LC3 was detected by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR) used to detect the level of mRNA of beclin 1. Results After oridonin treatment, the proliferation of PC-3 cells was inhibited significantly in a concentration and time-dependent manner. The SEM examination revealed cellular shrinkage and the disappearance of surface microvilli after ORI treatment. And on the TEM examination, the nuclei exhibited chromatin condensation and the appearance of a large number of autophagosome with doublemembrane structure in cytoplasm. AO staining showed the existence of AVOs. Simultaneously, the expressions of autophagy-related proteins, MAP-LC3 and the mRNA level of beclin 1 were elevated by ORI.The autophagy inhibitor 3-MA reversed the elevation of beclin 1 mRNA. Conclusion The growth of PC-3 cells is inhibited. And cellular is induced by oridonin with a potential anti-tumor effect.

Objective To study the inhibition and significance of pigment epithelium-derived factor (PEDF) in the development and metastasis of prostate cancer. Methods The expression of PEDF was examined in the normal prostate tissue, benign prostatic hyperplasia, prostate cancer tissue and prostate cancer cell lines, PC-3 and Lncap by immunohistochemical SP method and Western blot In combination with clinical data, statistical analysis was performed to evaluate the relation of the expression level of PEDF in prostate cancer and the relationship between different histological grades of prostate cancer. Results In normal prostate tissue and benign prostate tissue, the expression of PEDF were elevated and it was far higher than the prostate cancer and prostate cancer cell line. The expression of PEDF and the pathological grade of prostate cancer were related to the differentiated carcinoma of prostate tissue, and the expression level of PEDF in poorly differentiated carcinoma below the highly differentiated carcinoma of prostate cancer. In metastatic prostate cancer, the expression of PEDF was lower than that of prostate cancer without metastasis (12% vs 43. 1%). Conclusion The expression of PEDF and the incidence of prostate cancer have a negative correlation. The lower grade of prostate cancer cells, the less the tissue expression of PEDF and the higher tendency of invasion and metastasis.

Objective To establish the regression model predicting the probability of the capsular penetration according to the Chinese prostate cancer samples. Methods Men enrolled in the Fudan University Shanghai Cancer Centre and undergoing radical prostatectomy between January 2006 and April 2010 were used to establish the predicting model. According to the pathology after radical prostatectomy, all cases were divided into two groups: organ confined disease group and locally advanced disease group, the difference of which were whether had the capsular penetration. The cases with regional lymph node metastasis were excluded. Serum prostate specific antigen level, Gleason grade, clinical stage were collected. Multiple Logistic regression model was established according to preoperative clinical data and postoperative pathological data to predict the incidence of capsular penetration. Receiver operating characteristic curve was used for the internal validation of the model. Results 83 Chinese men were identified in the organ confined disease group with the age of 66. 8 ± 5.8 years, and 36 in the locally advanced disease group with the age of 66. 0 ± 6. 8 years. The difference of the age between the two groups were of no statistic significance(t = 0. 650, P = 0. 517). The serum prostate specific antigen level (Wilcoxon W =4562.0, P =0. 016), Gleason score(Wilcoxon W =4586. 5, P =0. 016), and clinical stage (Wilcoxon W= 4444. 5, P= 0. 001) of the locally advanced disease group were higher than the other group. The equation of the multiple Logistic regression model was Logit P = 0. 488 × Gleason score + 0. 104 × clinical stage - 6. 187, with the freedom degree of two and the likelihood ratio χ2 test of 11. 263 (P= 0. 001) . The area under the ROC curve (AUC) for capsular penetration was 0.696 (P=0.001), with the 95% onfidence interval of 0.598-0.793. Conclusion The multiple Logistic regression model based on the Chinese. population can accurately predict the probability of capsular penetration of the prostate cancer and work on well with high internal accuracy when clinical decisions are made.

Objective To study the correlation of real-time continuous monitoring system (RT-CGMS) with venous glucose and capillary glucose values. Methods A total of 33 diabetics received RT-CGMS for 5 days. Fasting venous glucose values were measured at Days 1, 3 and 5 and capillary glucose values recorded 7 times daily. The methods of correlation coefficient, error grid analysis(EGA) and BlandAltman analysis were employed to assessed the correlation, accuracy and agreement of RT-CGMS with venous glucose and capillary glucose values respectively. The mean amplitude of glucose excursions (MAGE) was calculated during RT-CGMS testing periods. Results (1) The correlation coefficient of RT-CGMS with vein glucose and capillary glucose values were 0. 936, 0. 933 (P < 0. 01); (2) The analysis results of EGA showed that 98. 67%, 98. 64% of venous and capillary values fell in the A and B zones and 1. 33%,1.36% fell in the D zone; (3) The agreement analysis showed that RT-CGMS readings were in close agreement with venous glucose and capillary glucose results; (4) The patients at the same M AGE levels had obvious differences in HbAlC. Conclusion There is a high level of correlation, accuracy and agreement between RT-CGMS and venous glucose and capillary glucose values.

Objective To explore the perioperative features of surgical treatment in valvular patients with severe dilated left ventricle and investigate the structural changes of left ventricle and its correlation with cardiac functions. Methods A total of 126 patients with severe dilated left ventricle underwent mitral valve and/or aortic valve operation from January 2003 to December 2008, including mitral valve replacement (MVR) (n = 27), mitral valvuloplasty (MVP) (n = 13), aortic valve replacement (AVR) (n = 51),AVR + MVR (n = 25) and AVR + MVP (n = 10). There were 79 males and 47 females with a mean age of (52 ± 13)years old. The mean pathological course was (18± 12)years. The pathological changes were mainly of aortic and/or mitral incompetence. The concomitant procedures included Bentall procedure (n =6), coronary artery bypass grafting (n =3), tricuspid valvuloplasty (n =58) and left atrial folding (n =62). Results The perioperative mortality was 3. 17% (4/126). Two died of multiple organ failure (MOF) secondarily to severe low-output syndrome while another 2 died of sudden ventricular fibrillation.Forty-six (36.5%) patients suffered from ventricular arrhythmia during the earlier postoperative period and they required a venous injection of lidocacin and/or amidaron. Fourteen (1 1. 1%) patients suffered from severe low-output syndrome. Among them, 4 patients were resuscitated with an intro-aortic balloon pump for another 4-6 days. And 26 (20. 6%) cases were complicated with multiple organ failure. The echocardiographic examinations showed that left ventricular dimensions decreased significantly at Days 7-14 postoperatively and progressively at Months 6-12 postoperatively. Left ventricular end-diastolic diameter (LVEDD) was (77 ±6) mm preoperatively and (63 ± 12) mm (Days 7-14), (58 ± 10) mm (Months 6-12) postoperatively (P <0.01). The contractile function of left ventricle temporarily decreased during the early postoperative stage and improved gradually afterwards. But it was not restored to normal range even until 6-12 m post-operation. Ejection fraction was 49% ± 12% preoperatively and 42% ±9% (Days 7-14),51% ±7% (Months 6-12) postoperatively (P <0. 01). Left ventricular fraction shortness was 28% ±7% preoperatively and 25% ± 4% (Days 7-14), 29% ± 5% (Months 6-12) postoperatively (P < 0.05).Conclusion For the patients with severe dilated left ventricle, cardiovalvular operation can achieve an excellent outcome through a rigorous perioperative regiment. The prevention and treatment of postoperative ventricular arrhythmia should be emphasized. The dimension of left ventricle decreases progressively during the early postoperative period. There is a postoperative decline of cardiac functions.

Objective To analyze the peri-operative risk factors of mortality in patients with aortic dissection (AD). Methods Between January 2003 and June 2008, 361 AD patients at our hospital were enrolled. Their demographics, history, clinical characteristics and laboratory examinations were retrospectively analyzed. Twenty pre-operative variables were analyzed to identify the predictors of perioperative mortality of AD patients by the analyses of univariate and multivariate logistic regression.Results The analysis of univariate logistic regression showed that history of hypertension [odds ratio (OR)0.465, 95% confidence interval (CI) 0.229 -0.947, P = 0.035], Stanford type A (OR 2. 758,95% CI 1.054- 7.213 P = 0.039), acute course (OR 7. 897,95 % CI 1. 874-33. 275 P = 0.005), neurological symptoms (OR 0.275 ,95% CI 0.140 -0.541 ,P <0.001) and operation or not (OR 8. 206 ,95% CI 4.205 -16.012,P <0.001) had a higher mortality in AD patients. The multivariate analysis revealed that acute course (OR 8. 178 ,95% CI 1. 796-37. 242, P = 0.007), Stanford type A (OR 3. 236 ,95% CI 1.104-9.487 P = 0.032), neurological symptoms (OR 0.350 , 95% CI 0.159-0.770, P = 0.009) and operation or not (OR 9.429 ,95% CI 4. 456-19. 952 ,P <0.001) were significant independent predictors of perioperative mortality in AD patients. Conclusion History of hypertension, acute course, Stanford A and positive neurological symptoms are the independent predictors of perioperative mortality in AD patients.Operation or not is a determinant of patient outcome.

Objective To investigate the quantity and function of regulatory T cells in immunorelated pancytopenia (IRP)and explore the significance of Treg cells in the pathogenesis of IRP. Methods Sixty-six IRP patients and 24 healthy donors were enrolled. The levels of IL-2 and TGF-β were detected by ElISA. The ratios of CD4+ CD25 +/CD4+ and CD4+ CD25+ CD127low/CD4+ in bone marrow were examined with flow cytometry. The expressions of Foxp3 and galectin-10 mRNA in BMMNC were measured by semi-quantitative RT-PCR. Results The levels of IL-2 and TGF-β in bone marrow of untreated or recovered IRP patients[(5.6±1.7) 、(6.2±2.5) μg/L,(1.8±0.7)、(1.9±0.8)μg/L]were significantly lower than those of healthy controls [(7.9±3.7)、(2.5±0.9)μg/L, all P< 0.05]. The ratio of CD4 + CD25 +/CD4+ cells in bone marrow of untreated IRP patients (22.5%±9.5%) was significantly lower than that of recovered IRP patients or healthy controls (27.1% ±7.1% 、30.6%±8.6% ,both P<0.05). The ratio of CD4+ CD25 + CD127low/CD4 + cells in bone marrow of untreated IRP patients was significantly lower than that of recovered IRP patients or healthy controls (7.2%±2.7% vs 9.1%±4.7% 、10.4%±3.2% ,both P <0.05). The relative mRNA expressions of Foxp3 and galectin-10 were 0.34 ±0.25, 0.69±0.51, 0.82±0.66 and 0.66±0.11, 0.74±0.11,0.76±0.09 in three groups respectively. The expressions of two factors in untreated IRP patients were significantly lower than those in recovered IRP patients or normal controls (all P < 0.05). Conclusion The abnormalities in quantity and function of Treg cells in IRP patients might play an important role in the pathogenesis of IRP.

Objective To investigate the influences of VEGF expression through the intervention of thalidomine in malignant transformation of hepatocytes. Methods Hepatoma model was induced with 2-fluorenyl-acetamide (2-FAA, 0. 05%) in male SD rats. And thalidomide was administered intragastrically to block the progress of hepatoma. Some rats were sacrificed at a fortnightly interval. Morphological changes were observed by pathological examinations (HE staining). The VEGF expressions in rat liver tissues were detected by ELISA and immunohistochemistry respectively. Results Hepatocytes in rats fed with 2-FAA showed vacuole-like denaturations at an early stage, dysplastic nodules appeared at a middle stage and finally progressed to tubercles of cancerous nest. All were the manifestations of highly differentiated hepatocellular carcinoma (HCC). An increasing tendency of hepatic VEGF protein was found for normal liver to precancerous to cancerous tissues during the development of hepatoma. The VEGF levels in hepatoma were significantly higher than those in normal ones. Thalidomine repressed the morphologic change of hepatic cells. And the VEGF level of thalidomide group was lower than those in 2-FAA group. Conclusion Thalidomide can inhibit the hepatic VEGF expression and arrest the development of rat hepatoma.

Objective To explore the inhibitory effect and anti-cancer mechanisms of adenovirusmediated ING4 gene on the human bladder cancer T24 cells in vitro.Methods The methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of ING4 in human bladder urothelial carcinoma T24 line.The influence of Ad-ING4 transfection on cell proliferation was evaluated by MTT assay and cell apoptosis by Hochest33258 staining and flow cytometry.RT-PCR and Western blot were performed to detect the transcriptional level of such apoptosis-related genes as Bcl-2, Bax, p53, HIF-1α and caspase-3.Results Human ING4 was successfully transcribed in T24 cell.Apoptosis rate of T24 cell in Ad-ING4 group was significant higher than that in control groups(17.2% ±4.1% vs 4.7% ± 1.2% and 4.8% ± 1.2% ,P <0.05).Ad-ING4 not only up-regulated the expression of p53 and Bax (1.40 ± 0.11 vs 0.27 ± 0.04,1.50 ± 0.12 vs 0.60 ± 0.05) and down-regulated the expression of Bcl-2 and HIF-1α(0.19 ±0.02 vs 1.20 ±0.08,0.33 ±0.03 vs 0.98 ±0.06,all P <0.05), but also enhanced the caspase-3 activation and eventually led to apoptosis.Conclusion Adenovirus-mediated ING4 gene exhibits anti-tumor capacity in T24 human bladder cancer cell and induces in vitro apoptosis.It may be related to the up-regulation of P53 and Bax/Bcl-2, and the down-regulation of HIF-lα.Thus the caspase-3 activation is enhanced so as to lead to apoptosis.

Objective To investigate the effects and mechanism of verapamil preventing ischemia/reperfusion (I/R) injury by cardiac performance intracellular free [Ca2+]1 and L-type calcium current (ICa-L) in cardiomyocytes of diabetes mellitus rats. Methods Diabetic rats were streptozotocin-induced and recived verapamil(8 mg·kg-1·d-1)from 6-14 weeks old.The in vitro heart models of I/R rats were randomly divided into normal control group diabetes group, verapamil control group. the changes of heart functions were observed through a Langendorff-perfusion system. The fluorescence intensity of intracellular Ca2+ was detected with Fluo-3/AM loading by laser scanning confocal microscope. ICa-L was recorded by the whole-cell technique of patch clamp in enzymatically dissociated single rat ventricular myocytes. Results (1) In verapamil diabetes group, the values of left ventricular developed pressure [(91.3 ±4.6) mm Hg],diastolic end pressure [(1535 ±280)mm Hg], the maximum rising rates of left ventricular pressure [(5833 ±256) mm Hg/s] and coronary arterial flow [(13.7 ± 0.9) mL/min] were all significantly increased, and the maximum dropping rates of left ventricular pressure [(3504 ± 319)mm Hg/s] was obviously decreased (compared with diabetes group, P < 0.01, respectively). (2) The fluorescence intensities of intracellular free Ca2+ [(155.6 ± 10.9) nmoL/L] in verapamil diabetes group were significantly reduced compared with diabetes group (245.2 ± 17. 5 nmol/L, P < 0.01). (3) When clamp voltage was - 20mV, ICa-L was (- 6.81 ±0.76)pA/pF in verapamil diabetes group(compared with normal group (-8.17±2.07) pA/pF, P<0.05,and with diabetes group (-3.21±0.54) pA/pF, P <0.01, and with verapamil control group (-7.14 ±2.17)pA/pF, P>0.05). The current-voltage curve was changed to the lower position with -20mY of peak clamp potential in verapamil diabetes group compared with diabets group. Conclusion A poor heart function is closely correlated with a rising [Ca2 +] i and a declining ICa-L associated with I/R injury in diabetic rats hearts. Along-term verapamil therapy may significantly improve the severe cardiac impairment. The mechanism is probably attributed to the fact that verapamil can adjust ICa-L influx, normalize the balance of intercellular [Ca2 +]i, and block the Ca2+ overload trigged by the effects of Ca2+ -induced Ca2+ release in diabetic cardiomyocytes.

Hypertension is a common cardiovascular disease, which affects about 25% of adults worldwide. It is estimated that its prevalence will increase to 60% by 2025, and 1.56 billion people may suffer from hypertension [1]. Essential hypertension accounts for 95% of all hypertensive patients [2], is a major risk factor for coronary heart disease and stroke, and has become a major public health problem [3]. The etiology and pathogenesis of hypertension have not been fully elucidated. The effects of lifestyle, such as excessive salt intake, excessive alcohol consumption, weight gain and lack of exercise [4-6] and familial hyperlipidemia [7] can cause the increase of blood pressure, while genetic factors account for 30% ~50% of the influence on the change of blood pressure [8].

Fibroblast growth factor (FGF) has hormone-like effects. The human FGF family consists of 22 members, which are divided into 7 subfamilies according to germline and sequence. Most of the FGF factors have regulatory effects on cell growth and differentiation. Fibroblast growth factor 21 (FGF-21) is a newly discovered new member of FGF family, which was first discovered in the study of high-throughput screening of cytokine function to discover new drugs for diabetes mellitus. Its total length is 209 amino acids, the signal peptide is located at the N-terminal, containing 181 amino acids, and the gene is located in chromosome 19. FGF-21 mRNA is only expressed in specific tissues, such as liver and thymus [1], but it has been found that the secretion of FGF-21 is limited to liver, pancreas and adipose tissue, with hormone-like effects and weak mitogenic effects. The primary structure of human and mouse FGF-21 is 75% identical [2-3].

Bronchial asthma is a chronic airway inflammatory disease involved by various cells and cellular mediators. The incidence rate is high. Because the etiology is not completely clear, the current treatment is still unsatisfactory, which brings a high economic burden to the society. Genetic background and environmental factors are the susceptible factors of asthma. If the "asthma gene" can be clearly mapped, it will undoubtedly provide a new way for the treatment of asthma. A recent small-scale study on asthma genome (GABRIEL) found that 17q21 is related to asthma in children (asthma occurring before the age of 16), which brings a hint to researchers. Therefore, Miriam et al. designed this large-scale study on asthma genome to further explore the relationship between single nucleotide polymorphism (SNP) and asthma and plasma IgE levels, and further understand whether this association can reflect the individual risk of asthma. The results were published in the New England Journal (N Engl J Med, 2010, 363: 1211-1221) published on September 23.

The symptoms of adult asthma patients are often not well controlled when low-to-medium-dose inhaled glucocorticoids (ICS) are administered. The treatment options can increase long-acting beta agonists (LABA) or increase the dose of ICS. However, recently, the FDA and asthma experts in the United States have questioned the safety of LABA treatment and suggested to reduce the use of LABA as much as possible. Therefore, more drugs can control asthma are needed. Tiotropium bromide is a long-acting anticholinergic drug for the treatment of COPD in Taiwan, but its effect on asthma is still unclear, and it has not been approved for the treatment of asthma. Peters et al. put forward two hypotheses and conducted studies: first, increasing tiotropium bromide is better than doubling the dose of ICS; Second, increasing tiotropium bromide is not inferior to increasing LABA. The results of the study were published on the website of N Engl J Med on September 19, 2010.