Elevated intramuscular adipose tissue content with a high Ishak fibrosis stage (>3) had a negative effect on liver regeneration in cirrhotic patients undergoing portal vein embolization.

This study investigated the relationship between body composition parameters and changes in future liver remnant volume (FLRV) in hepatocellular carcinoma (HCC) patients undergoing portal vein embolization (PVE) in preparation for right hepatectomy. This retrospective study enrolled 21 patients between May 2013 and October 2020. Body composition parameters, including skeletal muscle attenuation (SMA), skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR), were measured by computed tomography (CT) prior to PVE. Liver volumetry was measured before and at least 5 weeks after PVE. The mean interval between two CT volumetries was 9.1 ± 4.9 weeks, the mean value of increase in FLRV (ΔFLRV) was 236.0 ± 118.3 cm3 , the ratio of increased FLRV (ΔFLRV%) was 55.7 ± 29.4%, and the rate of increased FLRV was 31.0 ± 18.8 (cm3 /week). Subjects with high IMAC showed significantly lower (p = 0.044) ΔFLRV% than those with normal IMAC. Furthermore, ΔFLRV% was linearly reduced (p for trend = 0.043) among those with low Ishak fibrosis stage (<3) + normal IMAC (76.1 ± 36.8%), those with low Ishak fibrosis stage (<3) + high IMAC or high Ishak fibrosis stage (>3) + normal IMAC (54.0 ± 24.1%), and those with high Ishak fibrosis stage (>3) + low IMAC (28.7 ± 1.6%) (p for trend = 0.043). Our data indicated that high IMAC with a high Ishak fibrosis stage (>3) had a significant negative effect on ΔFLRV%.

Diterpene promptly executes a non-canonical autophagic cell death in doxorubicin-resistant lung cancer.

16-hydroxycleroda-3,13-dien-15,16-olide (HCD) has antitumor activity reported in numerous types of cancers. However, the efficacy of HCD treatment in non-small-cell lung cancer (NSCLC) cells and doxorubicin-resistant (Dox-R)-NSCLC cells remains to be unraveled. The underlying anti-cancer mechanism of HCD on Dox-R and Dox-sensitive (Dox-S) of A549 cells was also investigated. Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot. A further examination of its anti-cancer efficacy was performed in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation, which showed that HCD could arrest both Dox-S and Dox-R cells at G2/M phase without altering the sub-G1 cycle along with increasing of cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI3K-ClassIII/Beclin-1 signals and upregulated p62/LC3-I/II expressions to further confirm that the cell autophagy of NSCLC cells after being HCD-induced. Morphological observations of mouse lung sections illustrated that fewer cancer cells accumulated close to the trachea while less neoplastic activities were found in HCD orthotopic treated mice without liver, kidney, and spleen toxicity. Lastly, Dox, HCD, and target therapy medicines of EGFR and ALK were nicely docked with EGFR, ALK, and mTOR. Conclusively, HCD was demonstrated the chemotherapeutic potential regardless of Dox-R and Dox-S cells, suggesting natural autophagic inducer HCD provides a promising lead compound for new drug discovery and development of lung cancer therapies.

The experience of use of percutaneous transhepatic biliary drainages for early biliary complications after liver transplantation.

This study aimed to describe our experience and discuss the results, controversies, and the use of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary complications after liver transplantation (LT). Between November 2009 and August 2020, 76 consecutive patients who underwent 77 LTs (44 deceased donor LTs and 33 living donor LTs [LDLT]) were enrolled retrospectively. Endoscopic therapy as initial approach and PTBD as rescue therapy were used for patients with biliary complications. There were 31 patients (31/76, 40.8%) with biliary complications, and two of them died (2/31, 6.5%). Clinical success rate of endoscopic therapy alone was 71.0% (22/31). The remaining nine patients received salvage PTBD and their clinical results were observed according to whether their intrahepatic bile ducts (IHBDs) was dilated (group A, n = 5) or not (group B, n = 4). In group A, the technical and long-term clinical success rates of PTBD were 100% and 20%, respectively. These five patients received PTBD ranging from 75 to 732 days after their LTs, and no procedure-related complications were encountered. In group B, the technical and long-term clinical success rates of PTBD were 50% and 25%, respectively. Three group B patients (75%) underwent PTBD within 30 days after LDLT and had lethal complications. One patient had graft laceration and survived after receiving timely re-transplantation. The other two patients died of sepsis due to PTBD-related bilioportal fistula or multiple liver abscesses. Our experience showed salvage PTBD played a limited role in biliary complications without dilated IHBDs within 1 month after LT.

The potential of the three-dimensional printed titanium mesh implant for cranioplasty surgery applications: Biomechanical behaviors and surface properties.

The aim of the present study was to investigate the biomechanical behaviors of the pre-shaped titanium (PS-Ti) cranial mesh implants with different pore structures and thicknesses as well as the surface characteristics of the three-dimensional printed Ti (3DP-Ti) cranial mesh implant. The biomechanical behaviors of the PS-Ti cranial mesh implants with different pore structures (square, circular and triangular) and thicknesses (0.2, 0.6 and 1 mm) were simulated using finite element analysis. Surface properties of the 3DP-Ti cranial mesh implant were performed by means of scanning electron microscopy, X-ray diffraction and static contact angle goniometer. It was found that the stress distribution and peak Von Mises stress of the PS-Ti cranial mesh implants significantly decreased at the thickness of 1 mm. The PS-Ti mesh implant with the circular pore structure created a relatively lower Von Mises stress on the bone defect area as compared to the PS-Ti mesh implant with the triangular pore structure and square pore structure. Moreover, the spherical-like Ti particle structures were formed on the surface of the 3DP-Ti cranial mesh implant. The microstructure of the 3DP-Ti mesh implant was composed of α and rutile-TiO2 phases. For wettability evaluation, the 3DP-Ti cranial mesh implant possessed a good hydrophilicity surface. Therefore, the 3DP-Ti cranial mesh implant with the thickness of 1 mm and circular pore structure is a promising biomaterial for cranioplasty surgery applications.

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment.

Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of their antigen presentation activity. RT/IL-12 also significantly reduced accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing production of reactive oxygen species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were significantly activated toward the antitumor phenotype, as revealed by increased expression of CD107a and TNF-α. Together, our data showed that RT/IL-12 treatment could reset the intratumoral immunotolerant state and stimulate activation of antitumor cellular immunity that is capable of eliminating large established HCC tumors.

Liver-Specific Allergen Gene Transfer by Adeno-Associated Virus Suppresses Allergic Airway Inflammation in Mice.

Allergic airway inflammation driven by T helper 2 (Th2)-type immunity is characterized by airway hyperresponsiveness, eosinophilic infiltration, and elevated IgE production. Various novel strategies for managing asthma have been explored, such as DNA vaccines, T-cell peptides, and allergen-specific immunotherapy. A principal goal of most immunotherapeutic approaches is active and long-term allergen-specific tolerance. Liver-specific gene transfer using adeno-associated virus (AAV) has been shown to favorably induce tolerogenic responses to therapeutic products in various experimental models. AAV8 has strong liver tropism and induces immune tolerance in mice. The present study aimed to determine whether hepatocyte-specific allergen expression by pseudotyped AAV2/8 alleviates asthmatic symptoms in ovalbumin (OVA)-sensitized mice. Mice were intravenously injected with AAV2/8 vector carrying membrane-bound OVA transgene under transcriptional control of a hepatocyte-specific alpha 1 antitrypsin promoter (AAV2/8-OVA) and then sensitized with OVA. AAV2/8-OVA specifically transduced the OVA transgene in the liver. Airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and Th2 cytokines were significantly suppressed in both the lungs and secondary lymphoid organs of asthmatic mice infected with AAV2/8-OVA. Significant reduction of OVA-specific antibodies was detected in the bronchoalveolar lavage fluid from AAV2/8-OVA-treated mice. Moreover, AAV2/8-OVA treatment prominently promoted the expression of Foxp3, IL-10, and TGF-ß in the liver. Enhanced Foxp3 expression was also detected in the lungs of asthmatic mice after AAV2/8-OVA treatment. Taken together, these results suggest that the induction of immune tolerance by hepatic AAV gene transfer may be beneficial for modulating allergic asthma.

Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses.

RATIONALE: Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system. OBJECTIVES: Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses. METHODS: In utero injection of adjuvant-free ovalbumin (OVA) was conducted in Gestational Day 14 FVB/N mouse fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and then they were examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology. Fluorescent conjugates of OVA were used for further studies of mechanisms. MEASUREMENTS AND MAIN RESULTS: This presumed tolerogenic action turned out to be a sensitization process with the development of anaphylaxis or heightened recall, T-helper cell type 2-skewed responses to postnatal encounter with OVA. Further postnatal aerosolized OVA stress triggered allergic lungs with functional and structural alterations of airways. The unintended consequence resulted from macrophage-like fetal phagocytes that took up OVA and differentiated toward dendritic cells. These fetal dendritic cell progenitors attenuated proteolysis of endocytosed OVA for delayed presentation in postnatal life. This specialty of fetal phagocytes effectively retains the memory of antigens internalized early before full development of the immune system, leading to an event of in utero sensitization. CONCLUSIONS: Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases.

Follow-up for covered stent treatment of carotid blow-out syndrome in patients with head and neck cancer.

OBJECTIVE: Carotid blow-out syndrome (CBS) is a life-threatening complication of head and neck cancer (HNC). One of the various methods used for emergency management of CBS is covered stent placement (CSP). Our initial experience in CSP is evaluated and compared with reports in the literature. METHODS: This study analysed 17 patients with HNC who had received CSP for CBS at Kaohsiung Medical University Chung-Ho Memorial Hospital from May 2005 to December 2013. The medical records and images for these patients were retrospectively reviewed to evaluate the causes of CBS, treatment success rates and complications. RESULTS: The initial angiography success rate was 100%. Procedural or periprocedural complications were noted in two (12%) cases, both suffering from cerebral vascular accident (CVA). Short-term complications were noted in eight (47%) cases, including four rebleeding cases and four CVA cases. Medium- to long-term complications were noted in nine cases, which included two asymptomatic in-stent thrombosis cases, one symptomatic CVA case, two abscess formation cases and four rebleeding cases. Overall, eight (47%) cases of rebleeding occurred during follow-up. Three of the eight cases were fatal, accounting for 27% of the all-cause mortality. CONCLUSION: Although CSP is considered effective for achieving haemostasis in patients with HNC with CBS, the medium- to long-term outcomes are unfavourable owing to high risks of rebleeding, CVA and other complications. Therefore, CSP should be considered a temporary life-saving technique rather than a definitive treatment. ADVANCES IN KNOWLEDGE: Analysis of the relatively large series of patients with HNC in this study suggests that CSP is a useful temporary treatment for CBS.

The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma.

Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase) may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA)-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.

The surgical trends and time-frame comparison of primary surgery for stress urinary incontinence, 2006-2010 vs 1997-2005: a population-based nation-wide follow-up descriptive study.

INTRODUCTION AND HYPOTHESIS: The purpose of our study was to describe the surgical trends for female stress urinary incontinence (SUI) during 2006-2010, and a time-frame comparison with 1997-2005, based upon the National Health Insurance (NHI) claims data in Taiwan. METHODS: Women who underwent various primary surgeries for SUI during 2006-2010 were identified, with a total of 15,099 inpatients. The variables included surgical types, patient age, surgeon age and gender, specialty, and hospital accreditation levels. Chi-squared tests and SAS version 9.3.1 were used for statistical analysis. RESULTS: During the follow-up study, midurethral sling (MUS) application increased significantly from 53.09 % in 2006 to 78.74 % in 2010. It was associated concomitantly with a decrease in retropubic urethropexy (RPU) from 29.68 % to 12.99 %, and pubovaginal sling treatment (PVS) from 9.33 % to 3.46 %. MUS was most commonly used among all patients' and surgeons' age groups, and different accreditation hospital levels. MUS was more commonly used by gynecologists (71.38 %) than urologists (57.91 %); while PVS and periurethral injection were more commonly performed by urologists than gynecologists. Similar surgical trends were found during time-frame comparison, 2006-2010 vs 1997-2005. SUI surgeries increased in patients aged ≥60, surgeons aged ≥ 50, and in regional hospitals. CONCLUSION: This follow-up study depicts the increase in popularity of MUS and offers evidence of surgical trends and a paradigm shift for female SUI surgery. More older women were willing to seek healthcare and undergo surgery. The surgical skills and knowledge spread from medical centers into regional hospitals. The time-frame shift may have a profound impact on patients, as well as the healthcare providers.

Evaluation of the relationship between urodynamic examination and urinary tract infection based on urinalysis results.

OBJECTIVE: To determine risk factors for urinary tract infection (UTI) after urodynamic examination by evaluating patients' clinical characteristics and urodynamic parameters. MATERIALS AND METHODS: Two hundred and sixty-one female patients (mean age 58.7 ± 12.3 years) from May to December 2011 who had lower urinary tract symptoms or needed definite diagnosis before pelvic floor reconstruction or anti-incontinence surgery received urodynamic examination. All patients received urinalysis on the scheduled day of urodynamic examination and 3 days after urodynamic examination. Mid-stream urine samples were obtained for urinalysis before urodynamic examination. If patients had UTI based on our urinalysis criteria before urodynamic examination, the investigation was postponed until the patient had a 3-7-day course of antibiotic treatment and urinalysis showed no UTI. RESULTS: Among 261 patients, 19 and 51 patients had UTI before and after urodynamic examination, respectively. Our data suggest that urodynamic examination causes significantly increased incidence of UTI. Increased number of vaginal births, UTI before investigation, diabetes and decreased average flow rate are risk factors for UTI after urodynamic examination. CONCLUSION: When the prevalence of UTI after urodynamic examination is higher than 10%, we recommend that prophylactic antibiotics should be given for high-risk patients with parameters such as older age, diabetes and multipara (>3). Those who have UTI before urodynamic examination and who are found to have a low average flow rate of less than 7 mL/second should take prophylactic antibiotics after examination.

Surgical trends for benign ovarian tumors among hospitals of different accreditation levels: an 11-year nationwide population-based descriptive study in Taiwan.

OBJECTIVE: Using a population-based nationwide database, we describe the changing surgical trends for laparoscopy or laparotomy for benign ovarian tumors among hospitals of different accreditation levels in Taiwan (medical centers, regional hospitals, and local hospitals). MATERIALS AND METHODS: Women who had National Health Insurance and received either laparoscopy or laparotomy as the primary surgery for benign ovarian tumors in Taiwan during 1999-2009 were identified for analysis. RESULTS: In total, 135,793 women who received either laparotomic (39,779) or laparoscopic surgery (96,014) for benign ovarian pathology were identified. The increase in annual laparoscopy number from 7176 in 1999 to 11,046 in 2009 was significant according to a log-linear regression test (p < 0.0001). The decrease in laparotomies from 3845 to 3567 was not significant (p = 0.190). Service volume shifts from local hospitals to regional hospitals were noted, with a concomitant decrease in the numbers of local hospitals. Laparoscopy was used more often than laparotomy among all three hospital accreditation levels. An increasing trend for choosing laparoscopy was observed for medical centers and local hospitals (p < 0.0001), but not regional hospitals (p = 0.0745). Laparoscopy was used more often in younger patients, by younger surgeons, and by male surgeons among hospitals at all three accreditation levels. CONCLUSION: Laparoscopy was preferentially used over laparotomy at all three hospital levels. An increasing trend for choosing laparoscopy was observed for medical centers and local hospitals, but not regional hospitals. Service volume shifts from local hospitals to regional hospitals were noted. Use of laparoscopy differed according to patient age, surgeon age, and surgeon gender among different hospital levels.

Concomitant trocar-guided transvaginal mesh surgery with a midurethral sling in treating advanced pelvic organ prolapse associated with stress or occult stress urinary incontinence.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and feasibility of concomitant trocar-guided transvaginal mesh (TVM) surgery with a midurethral sling (MUS) for treating women with advanced pelvic organ prolapse (POP) and stress urinary incontinence (SUI) or occult SUI (OSUI). MATERIALS AND METHODS: Eighty-nine women with advanced POP and SUI or OSUI were retrospectively enrolled. The Total Prolift and Tension-free Vaginal Tape-Obturator Systems were used for trocar-guided TVM surgery and MUS. Patients received regular follow-up at 1 week, and 1 month, 3 months, 6 months, and 12 months postoperatively, and then annually thereafter. The endpoints were the success rate for POP, and perioperative and postoperative complications. Functional outcomes were the presence of voiding difficulty, persistent or de novo overactive bladder symptoms, postoperative SUI, and paresthesia. RESULTS: The median follow-up period was 35 months (range, 12-50 months). Within the follow-up period, 84 patients (94.4%) were objectively cured, five patients (5.6%) had vaginal apical mesh exposure, 29 individuals (32.6%) had persistent or de novo overactive bladder symptoms, six individuals (22.5%) had de novo SUI (two were found by urodynamics), and nine individuals (10.1%) had voiding difficulties (two were found by urodynamics). In addition, the vaginal hysterectomy group had greater blood loss, longer operation times, and a higher mesh erosion rate compared to the uterine suspension group. CONCLUSION: Concomitant trocar-guided TVM surgery and MUS with the use of total Prolift and Tension-free Vaginal Tape-Obturator offer good efficacy in treating women with advanced POP and SUI or OSUI. The vaginal hysterectomy group had more perioperative complications.

Alleviation of lung inflammatory responses by adeno-associated virus 2/9 vector carrying CC10 in OVA-sensitized mice.

Asthma is a chronic airway inflammatory disease characterized by eosinophilic infiltration and airway hyperresponsiveness. The over-activated Th2 and lung epithelium cells express many different cytokines, and chemokines mainly contribute to the severity of lung inflammation. Clara cell 10 kD protein (CC10) is highly expressed in airway epithelium cells and exhibits anti-inflammatory and immunomodulatory effects. Adeno-associated virus (AAV) 2/9 vector, composed of AAV2 rep and AAV9 cap genes, can efficiently and specifically target lung epithelium cells. Thus, AAV2/9 vector might carry therapeutic potential gene sequences for the treatment of asthma. This study tested whether AAV2/9 vector carrying CC10 could reduce inflammatory and asthmatic responses in OVA-induced asthmatic mouse model. The results showed that AAV2/9-CC10 vector virus significantly reduced airway hyperresponsiveness, CCL11, interleukin (IL)-4, IL-5, IL-6, IL-13, and eosinophilia in the lungs of sensitized mice. CC10 level in OVA-sensitized mice was rescued with the administration of AAV2/9-CC10 vector virus. Lung tissue remodeling, including collagen deposition and goblet cell hyperplasia, was also alleviated. However, serum levels of OVA-specific IgG1 and IgE as well as Th2 cytokine levels in OVA-stimulated splenocyte culture supernatants were at the comparable levels to the sensitized control group. The results demonstrate that AAV2/9-CC10 vector virus relieved local inflammatory and asthmatic responses in lung. Therefore, we propose that AAV2/9-CC10 vector virus guaranteed sufficient CC10 expression and had an anti-inflammatory effect in asthmatic mice. It might be applied as a novel therapeutic approach for asthma.

Pseudotyped adeno-associated virus 2/9-delivered CCL11 shRNA alleviates lung inflammation in an allergen-sensitized mouse model.

Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung epithelial cells and might carry gene sequences with therapeutic potential for asthma. This study aimed to determine whether pseudotyped AAV2/9 virus carrying the small hairpin RNA targeting CCL11 and expressed by CMV/U6 promoter could reduce eosinophilia and asthmatic responses in mite allergen-sensitized mice. Mice were sensitized by intraperitoneal and challenged by intratracheal injection with recombinant Dermatophagoides pteronyssinus group 2 allergen (rDp2). AAV2/9 viral vectors were intratracheally injected three days before the first challenge. AAV2/9 sh47 virus significantly reduced airway hyperresponsiveness, airway resistance, CCL11 levels, and eosinophilia in the lungs of sensitized mice. Th2 cytokines, including interleukins (IL)-4, IL-5, and IL-10, were also significantly reduced in the bronchoalveolar lavage fluid of AAV2/9 sh47 virus-treated mice. Th2 cytokine levels were also reduced in rDp2-stimulated mediastinal lymphocytes in treated mice. However, serum levels of rDp2-specific IgG1 and IgE, as well as Th2 cytokine levels in rDp2-stimulated splenocyte culture supernatants, were comparable to the sensitized control group. The results suggest that AAV2/9 sh47 virus relieved local instead of systemic inflammatory responses. Therefore, the CMV/U6 promoter with AAV2/9 viral vector, which is preferable to target lung epithelia cells, might be applied as a novel therapeutic approach for asthma.

Evaluation of a common variant of the gene encoding clara cell 10 kd protein (CC10) as a candidate determinant for asthma severity and steroid responsiveness among Chinese children.

OBJECTIVE: The gene (SCGB1A1) encoding Clara cell 10-kDa protein (CC10), a steroid-inducible immune modulator, is a candidate gene for asthma, but the evidence is equivocal. The potential influence of a common variant on asthma severity and serum CC10 levels during acute exacerbation and after corticosteroid treatment in Chinese case-control children and its functional relevance was investigated. METHODS: Genotyping of a non-coding variant G+38A was performed in 489 children, of whom 277 had asthma with varying severity, and 212 healthy controls. Associations were tested for asthma, asthma severity, and responsiveness to steroid treatment. The transcriptional activity of this variant was examined in a Clara-like cell line (H358) using transient transfection assays. RESULTS: Significant association was observed for the combined GA and AA genotypes of the CC10 G+38A variant and an increased risk of asthma [odds ratio (OR), 2.62, p < .001]. This association was correlated with asthma severity (moderate: OR, 2.85, p < .001; near-fatal: OR, 4.81, p < .001). Also, patients with the GA and AA genotypes showed significantly lower serum CC10 (p < .01) and provocation concentration causing a 20% fall (PC(20)) in forced expiratory volume in 1 s (FEV(1)) (p < .0001) when compared with those with the GG. After glucocorticoid treatment, the CC10 levels were significantly increased in asthmatic patients with GG (p < .0001), but not those with the GA and AA genotypes. Moreover, a lower dexamethasone-induced reporter (luciferase) activity was observed for H358 cells transiently transfected with the G38A risk allele (A) compared with wild-type allele (G). CONCLUSIONS: These findings suggest that the CC10 G+38A variant may contribute to the severity of asthma and lower level of steroid responsiveness.