Jiunn-liang Ko - Academia.edu (original) (raw)

Papers by Jiunn-liang Ko

Reproductive Sciences, Jul 2, 2010

Hypothesis: Single-nucleotide polymorphisms (SNP) in promoter of human nonmetastatic clone 23 typ... more Hypothesis: Single-nucleotide polymorphisms (SNP) in promoter of human nonmetastatic clone 23 type 1 (nm23-H1) may affect their binding with transcription factors and affect promoter activity as well as gene transcription. Therefore, we investigated the impact of the nm23-H1 gene polymorphisms on the neoplastic lesions of uterine cervix in mid-Taiwan women (women who live in the central area of Taiwan). We expected that women with different genotypes in nm23-H1 polymorphisms, such as rs34214448, rs16949649, or rs2302254, may have different incidences of cervical neoplasia. Materials and Methods: In total, 366 blood samples were collected from 244 healthy women and 122 patients with cervical neoplasia to analyze 3 nm23-H1 gene single-nucleotide polymorphisms (rs34214448, rs16949649, and rs2302254). Results: The heterozygous genotypes, TG in rs34214448 or TC in rs16949649, were differentially distributed between patients with cervical neoplasia and normal women (Hommel adjusted P ¼ .0440 and .0435, respectively) as compared to their homozygotes. Moreover, compared to those with wild-type homozygotes and heterozygotes, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exert different distributions between patients with cervical neoplasia and normal women (P ¼ .058 and .058). Interestingly, we found the genotype distribution of rs34214448 has significant association with that of rs16949649 with high consistency. Conclusions: Mid-Taiwan women with the polymorphic heterozygotes TG in rs34214448 or TC in rs16949649 of human nonmetastatic clone 23 type 1 promoter have the tendency to develop cervical neoplasia while compared to their homozygous counterparts. However, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exhibit less tendency as compared to those with wild-type homozygotes and heterozygotes.

Reproductive Sciences, May 1, 2007

Most of cervical intraepithelial neoplasia 1 (CIN 1) will regress and 12% to 40% of high-grade CI... more Most of cervical intraepithelial neoplasia 1 (CIN 1) will regress and 12% to 40% of high-grade CIN may progress to squamous cell carcinoma (SCC) of the uterine cervix. However, the differentiation of CIN 1 and high-grade CIN is sometimes controversial among pathologists. Human telomerase reverse transcriptase (hTERT) is therefore applied to detect the differences among normal, CIN 1, high-grade CIN, and SCC tissues of uterine cervix. One hundred six cervical specimens were collected for immunohistochemical study of hTERT. These data were compared with the human papillomavirus (HPV) DNA status. Expression of hTERT in high-grade CIN increased significantly compared to that in CIN 1 ( P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). A positive relationship was found between high hTERT expression and degree of malignant transformation ( P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Most of the cases with high hTERT expression tested positive for the high-risk HPV groups. High hTERT expression was detected in 88.73% of the samples with cervical high-grade CIN or SCC. Low hTERT expression was found in 94.29% of low-grade CIN or normal tissues. Furthermore, 96.92% of the cervical tissues with high hTERT expression were high-grade CIN or SCC. A total of 80.49% of samples with low hTERT expression were low-grade CIN or normal tissues. A significantly increased hTERT expression between CIN 1 and high-grade CIN exhibits a critical progression in cervical carcinogenesis. hTERT can be offered as additional molecular information correlated with more severe dysplasia and SCC. Furthermore, this increased hTERT expression is correlated whigh-risk HPVs infection.

Journal of Agricultural and Food Chemistry, May 4, 2012

FIP-fve is a protein that is isolated from Flammulina velutipes. Its known immunomodulatory activ... more FIP-fve is a protein that is isolated from Flammulina velutipes. Its known immunomodulatory activities are elicitation of the production of type II interferon from human peripheral mononuclear cells (hPBMCs) and hemagglutination. How the target receptors mediate activation of FIP-fve-induced immunomodulatory effects remains to be elucidated. This study postulates the three-dimensional structures to determine whether the carbohydrate binding module family 34 (CBM-34) on FIPfve is conserved to site N of Thermoactinomyces vulgaris R-47 α-amylase I. Experimental site-directed mutagenesis data as well as ligand-specific binding competition assay are adopted to identify the key residues W24, T28, D34, T90, I91, and W111 of FIP-fve that participate in binding to polysaccharides that are linked to the membrane of immune cells. Treatments of hPBMCs with tunicamycin and deglycosylation enzymes that removed the carbohydrate moieties reduced the secretion of IFN-γ induction from hPBMCs. In conclusion, the experiments herein demonstrated the ligand-binding CBM-34 on FIP-fve and ligand-like glycoproteins on the surface of hPBMCs must be required to induce physiological immunomodulatory effects.

Oral Diseases, Feb 15, 2013

OBJECTIVE: DDX3 has diverse biological functions in translation control, cell growth regulation, ... more OBJECTIVE: DDX3 has diverse biological functions in translation control, cell growth regulation, and tumor progression. Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide with a poor clinical prognosis. The impact of DDX3 expression in OSCC is seldom discussed. MATERIALS AND METHODS: Tumor tissues and adjacent normal tissues were obtained from 324 patients with OSCC. In this study, we used immunohistochemical staining methods to investigate the associations between DDX3 expression and the clinicopathological characteristics of OSCC. RESULTS: Low/negative DDX3 expression in tumor cells was significantly associated OSCC patient characteristics including male gender (P < 0.001), smoking (P < 0.001), alcohol consumption (P < 0.001), betel quid chewing (P = 0.002), poor relapse-free survival (P = 0.001), and poor overall survival (OS) (P = 0.001). Patients with low/negative DDX3 expression, and particularly non-smoker OSCC patients, had significantly worse OS as defined by the log-rank test (P = 0.020 for all cases; P = 0.008 for non-smoker patients). In nonsmoker patients with OSCC, low/negative DDX3 expression in tumor cells was associated with poor prognosis (P = 0.024) and a 3.802-fold higher death risk, as determined by Cox regression. CONCLUSIONS: Low/negative DDX3 expression in tumor cells was significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in non-smoker patients with OSCC.

Reproductive Sciences, Mar 21, 2011

Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) has high affinity for matrix metalloprote... more Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) has high affinity for matrix metalloproteinase-2 (MMP-2). Few studies simultaneously investigate their implication in prognosis of patients with cervical cancer. We used reverse transcription-polymerase chain reaction and immunohistochemical method for cervical tissues and microarrays to investigate the association among TIMP-2, MMP-2, clinicopathological parameters, and prognosis of patients with cancer. Our results showed that cancer tissues exhibited less TIMP-2 expression and patients with pelvic lymph node metastasis had less TIMP-2 expression. Positive TIMP-2 constellated with negative MMP-2 indicated lower recurrence probability and better overall survival. The protective effect of TIMP-2 expression may overcome the adverse effect of MMP-2 expression in terms of disease-free interval and overall survival while neither TIMP-2 nor MMP-2 alone can be used to predict outcome. We suggest that following patients other than those with positive TIMP-2 and negative MMP-2 expression more closely and intensely may improve their prognosis.

International Journal of Gynecological Cancer, Jul 1, 2007

L-Y. Concurrent high expression of human telomerase reverse transcriptase and human nonmetastatic... more L-Y. Concurrent high expression of human telomerase reverse transcriptase and human nonmetastatic clone 23 in high-grade squamous intraepithelial neoplasia and squamous cell carcinoma of uterine cervix.

Oncotarget, Sep 12, 2017

The purposes of this study were to associate the genetic polymorphisms in carbonic anhydrase (CA)... more The purposes of this study were to associate the genetic polymorphisms in carbonic anhydrase (CA) 9 with uterine cervical cancer and identify the clinical implications. Three single-nucleotide polymorphisms (SNPs), rs2071676 (+201, G/A), rs3829078 (+1081, A/G), and rs1048638 (+1584, C/A), and an 18-base-pair deletion/insertion (376del393) in CA9 were examined. We used the Boyden chamber assay to evaluate the influence of CA9 on the migration of cervical cancers. Tissue microarrays were used to evaluate CAIX immunoreactivity and determine its clinical significance. The results revealed that the CA9 SNP rs1048638 is the only significant polymorphism that increases the risk of cervical cancer in Taiwanese women. We discovered that the CA9 SNP rs1048638 influences the expression of CA9 through the interaction between the 3′-untranslated region (UTR) of exon 11, where the SNP is located, and miR-34a, and influences the migration of cervical cancer cells. Moreover, we demonstrated that CAIX immunoreactivity is related to the occurrence of cervical cancer, and elevated CAIX immunoreactivity is associated with a more advanced stage. In conclusion, the finding that the CA9 SNP rs1048638 exerts its action through duplexes of the miR-34a and CA9 3′-UTRs and plays a vital role in cervical cancer in Taiwanese women may be applicable to translational medicine.

Reproductive Sciences, Oct 1, 2007

To correlate matrix metalloproteinase-2 (MMP-2) expression with cervical carcinogenesis, the auth... more To correlate matrix metalloproteinase-2 (MMP-2) expression with cervical carcinogenesis, the authors use reverse-transcription polymerase chain reaction to detect MMP-2 mRNA expression in 10 cervical squamous cell carcinoma (SCC), 10 high-grade cervical intraepithelial neoplasia (CIN), and 10 normal tissues. They further detect MMP-2 immunoreactivity of 24 tissue cores in each SCC, high-and low-grade CINs, and a healthy subgroup on a tissue array using integrated optical density (IOD) for number and intensity of stained cells in 345 x 345 pixels. They found the mRNA expression of MMP-2 to be higher in most SCCs (9/10 samples) and high-grade CINs (7/10 samples) but lower in normal tissues. The IOD of MMP-2 was significantly higher in high-grade CIN than in normal and low-grade CIN tissue cores (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001 for both) and significantly higher in SCC than in high-grade CIN tissue cores (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). The results show that MMP-2 upregulation confers on tumor cells the ability to degrade the subepithelial basement membrane and subsequently invade the cervix.

Journal of Microbiology Immunology and Infection, Oct 1, 2018

Background: Asthma is one of the most common allergic diseases. Our previous studies have reporte... more Background: Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-fve in acute allergic mouse model can reduce inflammation, improve the balance of the Th1/Th2 system. However, the effects of reducing airway remodeling on FIP-fve is still unknown. Objective: We hypothesized that orally administrated FIP-fve should be able to reduce airway remodeling in chronic allergic models. Methods: The chronic asthma animal model was established with 6e8 weeks female Balb/c mice. After intranasal challenges with OVA, the airway inflammation and AHR were determined by a BUXCO system. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathologic changes and Collagen deposition were assayed with H&E, Masson's trichrome and IHC stain. Results: FIP-fve significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines and increased Th1 cytokines in BALF and serum compared with the OVA sensitized mice. FIP-fve had a better effect than corticosteroid could reduce infiltrating cells in lung especially neutrophils and eosinophils. We also found that the oral FIP-fve group suppressed IL-17 and enhanced IL-22 in the serum and BALF. In addition, oral FIP-fve decreased MMP9 expression, collagen expression and airway remodeling in lung tissues.

Journal of Microbiology Immunology and Infection, Jun 1, 2017

Background/Purpose: House dust mite (HDM) is well known as one of the major indoor allergens that... more Background/Purpose: House dust mite (HDM) is well known as one of the major indoor allergens that trigger allergic inflammation, especially asthma, and accounts for 85% of all cases. So far, asthma has been thought of as a condition of imbalance between T helper (Th)1 and Th2. Fungal immunomodulatory protein-Flammulina velutipes (FIP-fve) has been seemingly demonstrated to modulate the response to Th1 cytokine production. The aim of this study was to investigate if the oral administration of FIP-fve can inhibit HDM-induced asthma inflammation in the mouse model. Methods: We divided the mice (female BALB/c, 4e6 weeks) into four groups: the prevention group, which consisted of mice sensitized by HDM (intraperitoneally on Day 1, Day 7, and Day 14, and intranasally on Day 14, Day 17, Day 21, Day 24, and Day 27) fed with FIP-fve from Day 1 to Day 14; the treatment group, which comprised mice that received treatment from Day 14 to Day 28; the positive control (PC, sensitized by HDM fed without FIP-fve) group; and the negative control group (NC, nonsensitized). Airway hyperresponsiveness induced by

Gynecologic Oncology, Mar 1, 2008

To study the expression of matrix metalloproteinase-2 (MMP-2) in cancer of uterine cervix and cor... more To study the expression of matrix metalloproteinase-2 (MMP-2) in cancer of uterine cervix and correlate its expression with clinicopathological parameters, recurrence and survival of patients. Twenty cervical cancer and 20 normal tissues from the same patients were collected to detect MMP-2 mRNA expression. From them, 16 cancer and 16 normal tissues were collected and added with another 64 cancer tissues to construct a 96-tissue core microarray for immunohistochemical study. We evaluated the relationships among MMP-2 immunoreactivity using semiquantitative H scores, obtained by multiplying proportion score of stained cells and their mean digital density, and clinicopathological variables, recurrence and survival in cervical cancer patients. We used univariate and multivariate analyses of all parameters for recurrence and survival, further including time interval for evaluation. MMP-2 mRNA expression was higher in most of cervical cancerous tissues than normal counterparts. H score of MMP-2 was significantly higher in cancerous tissue cores than normal counterparts (median H scores: 1.5 vs. 0.3, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). MMP-2 expression was significantly associated with parametrium invasion (P=0.004) and lymph node metastasis (P=0.015), but not with cancer recurrence, recurrence-free and overall survival rates of these patients. However, poor tumor cell differentiation and positive parametrium invasion significantly increased the recurrence and poor cell differentiation increased the risk of death. MMP-2 is highly expressed in cervical cancer tissues at mRNA and protein levels and associated with lymph node metastasis and parametrium invasion but not predictive of recurrence and survival in cervical cancer patients.

International Journal of Medical Sciences, 2018

This study aimed to explore the involvement of carbonic anhydrase 9 (CA9) single nucleotide polym... more This study aimed to explore the involvement of carbonic anhydrase 9 (CA9) single nucleotide polymorphisms (SNPs) in the development of invasive cancer of uterine cervix for Taiwanese women. Ninety-seven patients with cervical invasive squamous cell carcinoma and 88 with preinvasive squamous cell lesions as well as 324 control women were recruited. Two CA9 SNPs in exons, including rs2071676 (+201, G/A) in exon 1 and rs3829078 (+1081, A/G) in exon 7, rs1048638 (+1584, C/A) in 3′-untranslated region of exon 11, as well as an 18-base pair deletion/insertion (376deltion393) in exon 1 were selected and their genotypic distributions were determined by real-time polymerase chain reaction. Haplotype was then constructed with rs2071676, 376del393, rs3829078 and rs1048638 in order. The results revealed that Taiwanese women with genotypes CA or CA/AA in CA9 SNP rs1048638 displayed a more risk in developing cervical invasive cancer, assigning wild genotype CC as a reference. AA in SNP rs2071676 tended to increase the risk of developing cervical invasive cancer, using GG/GA as a reference. When women had the diplotypes, carrying at least one haplotype A1AA (one mutant allele A in rs2071676, no deletion in 376del393, no mutant allele A in rs3829078 and one mutant allele A in rs1048638), they were significantly susceptible to cervical invasive cancer. In conclusion, CA9 SNP rs1048638 and haplotype A1AA are associated with the susceptibility of cervical invasive squamous cell carcinoma for Taiwanese women.

Antiviral Research, Oct 1, 2014

Respiratory syncytial virus (RSV) causes bronchiolitis in children followed by inflammation and a... more Respiratory syncytial virus (RSV) causes bronchiolitis in children followed by inflammation and asthmalike symptoms. The development of preventive therapy for this virus continues to pose a challenge. Fungal immunomodulatory proteins (FIPs) exhibit anti-inflammatory function. FIP-fve is an immunomodulatory protein isolated from Flammulina velutipes. To determine whether FIP-fve affects the infection or consequence of immunity of RSV, we investigated viral titers of RSV and inflammatory cytokine levels in vivo and in vitro. Oral FIP-fve decreased RSV-induced airway hyperresponsiveness (AHR), airway inflammation, and IL-6 expression in bronchoalveolar lavage fluid (BALF) of BALB/c mice. RSV replication and interleukin 6 (IL-6) levels in RSV-infected HEp-2 cells were compared before and after FIP-fve treatment. FIP-fve inhibited viral titers on plaque assay and Western blot, as well as inhibited RSV-stimulated expression of IL-6 on ELISA and RT-PCR. The results of this study suggested that FIP-fve decreases RSV replication, RSV-induced inflammation and respiratory pathogenesis. FIP-fve is a widely used, natural compound from F. velutipes that may be a safe agent for viral prevention and even therapy.

Surgical Endoscopy

Objectives McKeown esophagectomy is a standard and significant component of multimodality therapy... more Objectives McKeown esophagectomy is a standard and significant component of multimodality therapy in esophageal cancer, however, experience in switching the resection and reconstruction sequence in esophageal cancer surgery is not available. Here, we have retrospectively reviewed the experience of reverse sequencing procedure at our institute. Methods We retrospectively reviewed 192 patients who had undergone minimally invasive esophagectomy (MIE) with McKeown esophagectomy between August 2008 and Dec 2015. The patient’s demographics and relevant variables were evaluated. The overall survival (OS) and disease-free survival (DFS) were analyzed. Results Among the 192 patients, 119 (61.98%) received the reverse sequence MIE (the reverse group) and 73 patients (38.02%) received the standard operation (the standard group). Both patient groups had similar demographics. There were no inter-group differences existed in blood loss, hospital stay, conversion rate, resection margin status, ope...

International Journal of Molecular Sciences, 2022

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In centra... more House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras (Der m), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component (Der m 1). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal compone...

Cell death & disease, Jan 5, 2017

Hispolon, a phenolic compound isolated from Phellinus igniarius, induces apoptosis and anti-tumor... more Hispolon, a phenolic compound isolated from Phellinus igniarius, induces apoptosis and anti-tumor effects in cancers. However, the molecular mechanism involved in hispolon-mediated tumor-suppressing activities observed in cervical cancer is poorly characterized. Here, we demonstrated that treatment with hispolon inhibited cell metastasis in two cervical cancer cell lines. In addition, the downregulation of the lysosomal protease Cathepsin S (CTSS) was critical for hispolon-mediated suppression of tumor cell metastasis in both in vitro and in vivo models. Moreover, hispolon induced autophagy, which increased LC3 conversion and acidic vesicular organelle formation. Mechanistically, hispolon inhibited the cell motility of cervical cells through the extracellular signal-regulated kinase (ERK) pathway, and blocking of the ERK pathway reversed autophagy-mediated cell motility and CTSS inhibition. Our results indicate that autophagy is essential for decreasing CTSS activity to inhibit tumo...

Oncotarget, 2017

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, Jan 29, 2017

Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-f... more Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-fve in acute allergic mouse model can reduce inflammation, improve the balance of the Th1/Th2 system. However, the effects of reducing airway remodeling on FIP-fve is still unknown. We hypothesized that orally administrated FIP-fve should be able to reduce airway remodeling in chronic allergic models. The chronic asthma animal model was established with 6-8 weeks female Balb/c mice. After intranasal challenges with OVA, the airway inflammation and AHR were determined by a BUXCO system. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathologic changes and Collagen deposition were assayed with H&E, Masson's trichrome and IHC stain. FIP-fve significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines and increased Th1 cytokines in BALF and serum compared with the OVA sensitized mice. FIP-fve had a better effect than corticosteroid could reduc...

Reproductive sciences (Thousand Oaks, Calif.), 2007

The authors investigate the effects of human nonmetastatic clone 23 type 1 (nm23-H1 ) gene and fu... more The authors investigate the effects of human nonmetastatic clone 23 type 1 (nm23-H1 ) gene and fungal immunomodulatory protein-Ganoderma tsugae (FIP-gts) on the metastatic potential of cervical cancer cells and assess whether nm23-H1 can influence the action of FIP-gts using cell migration and invasion assays and gelatin zymography. The nm23-H1 gene was stably transfected into Caski cells, which lacked nm23-H1 expression. The results show that nm23-H1 stably transfected Caski cells exhibit reduced cell migration but no change of cell invasion and matrix metalloproteinase (MMP)-2 and -9 activities. FIP-gts reduced cell migration in SiHa and nm23-H1 transfected Caski cells more significantly compared with Caski cells and reduced invasion in Caski and nm23-H1-transfected Caski cells, but it exerted no influence on MMP-2 and MMP-9 activities in them. Conclusively, the nm23-H1 gene suppresses cervical cancer cell migration but not invasion and activities of MMP-2 and MMP-9 and enhances t...

PLoS ONE, 2014

Background: A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The ... more Background: A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan. Methods: Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants. Results: The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend = 0.013) for carbon monoxide (CO), 1.10 (P-trend = 0.015) for nitrogen dioxide (NO 2), and 1.20 (P-trend , 0.0001) for particulate matter with an aerodynamic diameter !10mm (PM 10) in the child group (aged 0-18). For adults aged 19-44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO 2, and 1.13 (P-trend , 0.0001) for PM 10. For adults aged 45-64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (Ptrend = 0.0002) for NO 2, and 1.10 (P-trend = 0.001) for PM 10. For the elderly (aged$ 65), the RRs of outpatient visits in were 1.12 (P-trend = 0.003) for NO 2 and 1.10 (P-trend = 0.006) for PM 10. For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups. Conclusions: There were positive associations between CO levels and childhood inpatient visits as well as NO 2 , CO and PM 10 and outpatient visits.