Depressive disorder and elevated risk of bell's palsy: a nationwide propensity score-weighting study.

BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.

Association between amiodarone use and risk of cataract: a population-based active-comparator study.

BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.

Increased risk of olfactory and taste dysfunction in the United States psoriasis population.

BACKGROUND: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. PURPOSE: To determine the relationship between olfactory or taste dysfunction and psoriasis. METHODS: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. RESULTS: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. CONCLUSION: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis.

Autophagy inhibition plays a protective role against 3, 4-methylenedioxymethamphetamine (MDMA)-induced loss of serotonin transporters and depressive-like behaviors in rats.

The 3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, which ultimately leads to serotonergic (5-HT) neurotoxicity and psychiatric disorders. Previous in vitro studies have consistently demonstrated that MDMA provokes autophagic activation, as well as damage of 5-HT axons and nerve fibers. So far, whether autophagy, a well-conserved cellular process that is critical for cell fate, also participates in MDMA-induced neurotoxicity in vivo remains elusive. Here, we first examined time-course of autophagy-related changes during repeated administration of MDMA (10 mg/kg s.c. twice daily for 4 consecutive days) using immunofluorescent staining for tryptophan hydroxylase and microtubule-associated protein 1 light chain 3 beta in rats. We also evaluated the protective effects of 3-methyadanine (3-MA, an autophagy inhibitor, 15 mg/kg i.p.) against MDMA-induced acute and long-term reductions in serotonin transporters (SERT) density in various brain regions using immunohistochemical staining and positron emission tomography (PET) imaging respectively. Plasma corticosterone measurements and forced swim tests were performed to evaluate the depressive performance. The staining results showed that repeated administration of MDMA increased expression of autophagosome and caused reduction in SERT densities of striatum and frontal cortex, which was ameliorated in the presence of 3-MA. PET imaging data also revealed that 3-MA could ameliorate MDMA-induced long-term decreased SERT availability in various brain regions of rats. Furthermore, immobility time of forced swim tests and plasma corticosterone levels were less in the group of MDMA co-injected with 3-MA compared with that of MDMA group. Together, these findings suggest that autophagy inhibition may confer protection against neurobiological and behavioral changes induced by MDMA.

Health Care Service Utilization After Various Vascular Access Selections.

BACKGROUND: To provide clinicians with sufficient information for selecting optimal access strategies for patients with end-stage renal disease, the utilization of health-care services of patients receiving arteriovenous fistulas (AVFs), arteriovenous grafts (AVGs), and central venous catheters (CVCs) are crucial topics that require investigation. MATERIALS AND METHODS: This study involved 1248, 431, and 323 patients with end-stage renal disease who had received an AVF, AVG, or CVC, respectively. All sampled patients were monitored over the course of a 1-y study period to evaluate their medical utilization. The utilization were further categorized into nephrology and nonnephrology services. This study also performed univariate and multivariate regressions to estimate the effects of vascular accesses. RESULTS: Regarding the utilization of health care services, significant differences were observed for mean outpatient visits (45.30 versus 49.71 versus 48.80), outpatient costs (US$19117 versus US$21015 versus US$19280), inpatient days (9.77 versus 14.41 versus 21.60), inpatient costs (US$2627 versus US$3810 versus US$5238), and total costs (US$21743 versus US$24825 versus US$24518) among patients who had received an AVF, AVG, or CVC, respectively. Furthermore, patients receiving an AVF had lower total costs for all health care services and nonnephrology services than patients undergoing AVG or CVC across the categories of men, women, adults, and elderly individuals. Multiple regressions found that patients undergoing AVF had significantly lower total costs for all health services than patients undergoing other vascular accesses after adjustments. CONCLUSIONS: This study displayed that patients who received an AVF fully used health care and nonnephrology services than patients who received an AVG or CVC.

Femto/nano-second switchable passively mode-locked fiber laser with analytic modeling by the cubic-quintic Ginzburg-Landau equation.

We report a passively mode-locked erbium-doped fiber laser with pulse widths switchable from 473 fs to 76.8 ns, where the fundamental mode-locking, noise-like pulse, nanosecond mode-locking, and dual-width mode-locking (DML) are obtained by adjusting a polarization controller. Co-existence of femto- and nano-second pulses in DML is attributed to the gain balancing. Analytic modeling of the fiber laser with the cubic-quintic Ginzburg-Landau equation is presented, in which the pulse widths are calculated as functions of dispersion, self-phase modulation (SPM), cubic saturable absorption (SA), and quintic SA. The generation of nanosecond pulses is caused by the weakened intracavity pulse-shortening strength, the reduced effective SPM, and the inclusion of quintic SA in the laser cavity.

Bladder pain syndrome/interstitial cystitis is associated with asthma: A case-control study.

OBJECTIVE: Although asthma and bladder pain syndrome/interstitial cystitis (BPS/IC) are considered to share similar pathophysiological pathways, the relationship between asthma and BPS/IC is uncertain. This case-control study aimed to investigate the relationship between prior asthma and BPS/IC using a large database in Taiwan. MATERIALS AND METHODS: This study used data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 500 female patients with BPS/IC as cases and 500 propensity score-matched females without BPS/IC as controls. We conducted logistic regressions to estimate the odds ratio (OR) and 95% confidence interval (CI) for prior asthma between cases and controls. RESULTS: Results indicated that 143 (14.30%) of the total sampled patients had received a prior diagnosis of asthma. Moreover, prior asthma was found in 86 (17.20%) cases and 57 (11.40%) controls. The OR of prior asthma for cases was 1.61 (95%CI: 1.13-2.32) compared to propensity score-matched controls. Additionally, the ORs of prior asthma for females with BPS/IC aged 18-59 and ≥60 years were 1.72 (95%CI: 1.11-2.69) and 1.40 (95%CI: 0.74-2.62), respectively, compared to controls. CONCLUSIONS: We concluded that prior asthma was significantly associated with BPS/IC in a female Taiwanese population.

Increased risk for urological cancer associated with anxiety disorder: a retrospective cohort study.

BACKGROUND: Anxiety disorders (ADs) are common with a high rate of medical comorbidities. Although the association between ADs and the overall cancer risk remains controversial, patients with ADs were found to be more likely to develop specific cancer types. Herein, we estimated the risk of developing urological cancers among patients with ADs in a 5-year follow-up period using a population-based database. METHODS: Two study cohorts were identified from the Taiwan Longitudinal Health Insurance Database 2005: patients with ADs, and comparison subjects selected by one-to-one matching for sex, age, and the year of recruitment. Follow-up was undertaken to determine whether sampled patients and comparison subjects had developed urological cancers in the subsequent 5 years. RESULTS: We found that urological cancers occurred among 0.54% of patients with ADs and 0.13% of comparison subjects. After adjusting for sociodemographic characteristics, medical comorbidities, and alcohol and tobacco use disorder, the stratified Cox proportional hazard regression suggested that patients with ADs were more likely to develop urological cancers relative to comparison subjects (adjusted hazard ratio, 3.67; 95% confidence interval, 2.85 ~ 4.72). The adjusted HR for males with ADs was 3.82 (95% CI: 2.79 ~ 5.23) in comparison to males without ADs. In addition, the adjusted HR for females with ADs was 3.47 (95% CI: 2.26 ~ 5.31) than those females without ADs. CONCLUSIONS: We concluded that during the 5-year follow-up period, there was a significantly increased risk of urological cancers among patients with ADs.

A population-based study on the associations between chronic periodontitis and the risk of cancer.

BACKGROUND: To date, the associations between chronic periodontitis (CP) and cancer lack large-scale population-based epidemiological evidence. This study aimed to investigate the subsequent risk for cancers among subjects with CP. METHODS: This study cohort included 40,140 subjects with CP and 40,140 subjects who were matched for a comparison cohort. We individually tracked each patient for a 5-year period following their index date to identify those who had received a diagnosis of cancer. RESULTS: The incidence rate of cancer during the 5-year follow-up period was 14.80 (95 % CI 14.28-15.34) per 1,000 person-years in subjects with CP. Cox proportional hazards regression revealed that the hazard ratio of cancer during the 5-year follow-up period for subjects with CP was 1.23 (95 % CI 1.20-1.27) compared to that of the comparison cohort. CONCLUSION: We observed an increased risk for the subsequent development of a number of cancers among subjects with CP.

Obstructive sleep apnea and urological comorbidities in males: a population-based study.

PURPOSE: This study aimed to investigate associations between obstructive sleep apnea (OSA) and urological comorbidities using a large population-based dataset. METHODS: This cross-sectional study used the Taiwan Longitudinal Health Insurance Database 2005. We included 1236 males with OSA in the study group and 4944 males without OSA in the comparison group. Conditional logistic regressions were performed to examine relationships between OSA and urological comorbidities. RESULTS: We found that patients with OSA had significantly greater prevalences of hypertrophy of the prostate (15.13 vs. 7.28 %), chronic prostatitis (4.37 vs. 2.16 %,), urinary incontinence (3.32 vs. 0.87 %), nocturia (2.02 vs. 0.61 %), erectile dysfunction (2.91 vs. 0.97 %), urinary calculi (12.06 vs. 6.80 %), and prostate cancer (0.97 vs. 0.40 %) than the comparison group. Additionally, the adjusted odds ratios in males with OSA for hypertrophy of prostate, chronic prostatitis, urinary incontinence, nocturia, erectile dysfunction, urinary calculi, and prostate cancer were 2.54 (95 % confidence interval (CI) 2.05~3.15), 1.95 (95 % CI 1.38~2.74), 4.13 (95 % CI 2.63~6.50), 3.54 (95 % CI 2.03~6.18), 2.95 (95 % CI 1.89~4.61), 1.89 (95 % CI 1.53~2.33), and 2.14 (95 % CI 1.03~4.43) than those without OSA, respectively. CONCLUSIONS: This study concluded that males with OSA had higher odds ratios of hypertrophy of the prostate, chronic prostatitis, urinary incontinence, nocturia, erectile dysfunction, urinary calculi, and prostate cancer than comparison group.

Proteomics analysis of EV71-infected cells reveals the involvement of host protein NEDD4L in EV71 replication.

Enterovirus 71 (EV71) is a human enterovirus that has seriously affected the Asia-Pacific area for the past two decades. EV71 infection can result in mild hand-foot-and-mouth disease and herpangina and may occasionally lead to severe neurological complications in children. However, the specific biological processes that become altered during EV71 infection remain unclear. To further explore host responses upon EV71 infection, we identified proteins differentially expressed in EV71-infected human glioblastoma SF268 cells using isobaric mass tag (iTRAQ) labeling coupled with multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Network analysis of proteins altered in cells infected with EV71 revealed that the changed biological processes are related to protein and ion transport, regulation of protein degradation, and homeostatic processes. We confirmed that the levels of NEDD4L and PSMF1 were increased and reduced, respectively, in EV71-infected cells compared to mock-infected control cells. To determine the physiological relevance of our findings, we investigated the consequences of EV71 infection in cells with NEDD4L or PSMF1 depletion. We found that the depletion of NEDD4L significantly reduced the replication of EV71, whereas PSMF1 knockdown enhanced EV71 replication. Collectively, our findings provide the first evidence of proteome-wide dysregulation by EV71 infection and suggest a novel role for the host protein NEDD4L in the replication of this virus.

Comparison of clinical outcome between laparoscopic and open right hemicolectomy: a nationwide study.

BACKGROUND: This study aimed to compare clinical outcome between laparoscopic and open right hemicolectomy. METHODS: The data were sourced from Taiwan's National Health Insurance Research Database. This study included 14,320 and 1313 patients who underwent open and laparoscopic right hemicolectomies, respectively. The study outcome included "intensive care unit (ICU) admission," "over 2 h of general anesthesia," "use of mechanical ventilation," "acute respiratory failure," "in-hospital death," and "hospitalization for pneumonia." Separate conditional logistic regressions were performed for each clinical outcome. RESULTS: The results showed that patients who underwent an open right hemicolectomy had significantly higher likelihood of ICU admission (31.4 vs. 13.4%, p<0.001), acute respiratory failure (3.6 vs. 0.8%, p<0.001), mechanical ventilation (12.8 vs. 4.1%, p<0.001), in-hospital death (3.7 vs. 0.9%, p<0.001), over 2 h of general anesthesia (4.6 vs. 1.2%, p<0.001), and hospitalization for pneumonia (5.8 vs. 3.1%, p<0.001) than patients who underwent a laparoscopic right hemicolectomy. Adjusted conditional logistic regression analyses revealed that patients who underwent an open right hemicolectomy were 2.96, 4.98, 3.41, 4.01, 3.44, and 1.78 times more likely to be admitted to the ICU, to have acute respiratory failure, the use of mechanical ventilation, in-hospital death, over 2 h of general anesthesia, and hospitalization for pneumonia, respectively, than patients who underwent a laparoscopic right hemicolectomy. CONCLUSIONS: Laparoscopic right hemicolectomy reduced risk of post-operative pulmonary complications.

Prescriptions for category D and X drugs during pregnancy in Taiwan: a population-based study.

PURPOSE: This study aimed to investigate the most prescribed medications and principle diagnoses for category D and X drugs during pregnancy using a population-based dataset in Taiwan. METHODS: The data for the present study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We selected 14 125 women who had live singleton births between 1 January 2009 and 31 December 2011. In total, 217 226 prescriptions prescribed to these pregnant women were identified. RESULTS: Of the total 217 226 prescriptions, 1.1% were category D or X drugs; in the first, second, and third trimesters of pregnancy, 1.8%, 0.7%, and 0.5% of prescriptions were category D or X drugs, respectively. Progestins (15.3%) and propylthiouracil (10.7%) were the two most frequently prescribed category D or X drugs during pregnancy. In particular, progestins (20.4%) and estrogens (15.6%) were the most frequently prescribed category D or X drug in the first trimester of pregnancy. Propylthiouracil was the most prescribed category D or X drug in the second (20.3%) and third trimesters (23.1%) of pregnancy, respectively. The most common principal diagnosis during pregnancy was "disorders of menstruation and other abnormal bleeding from the female genital tract" (22% of all principal diagnoses for prescribing category D and X drugs). CONCLUSIONS: Our study found that the physicians obviously reduced the use of category D and X drugs for women after becoming aware that they were pregnant.

Xin-yi-san contains potent human CYP1A2 inhibitors and its combined use with theophylline in treatment increases adverse risks in patients.

BACKGROUND: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index. PURPOSE: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients. METHODS: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed. RESULTS: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with Ki values of 77‒84 nM, higher than those (20‒52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017‒2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99‒2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21‒2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07‒1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14‒0.40; p < 0.001). CONCLUSION: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users.

Sleep Duration and Kidney Function - Does Weekend Sleep Matter?

Objective: Weekend sleep duration is linked to health issues, including mortality. However, how weekend sleep duration can impact chronic kidney disease (CKD) still needs to be understood. Therefore, we aimed to analyze how weekend sleep duration is associated with kidney function. Methods: This is a cross-sectional study. Data were obtained from the 2017-2018 National Health and Nutrition Examination Survey. We included 5362 study participants and categorized them into nine subgroups by sleep duration (short: ≤6 hours, normal: 6-9 hours, and long: ≥9 hours) on weekdays and weekends and analyzed for the respective association with renal function using stratified multivariable linear regression. Results: Weekend sleep duration for 9 hours or more was associated with decreasing estimated glomerular filtration rate (eGFR) levels by 2.8 to 6.4 mL/min/1.73 m2 among people with long to short weekday sleep duration compared with short weekday and weekend sleep durations (control group) after adjusting for demographic characteristics, body measurement, sleep quality, smoking, and comorbidities. The study population with short weekday sleep duration (sWK) and long weekend sleep duration (lWD) had the most significant decline in eGFR. For the study population with sWK, eGFR level significantly decreased by 1.1 mL/min/1.73 m2 as sleep duration on weekends increased by one hour. Conclusion: The underlying mediators of lWD and CKD could be the dysregulation of human behaviors, metabolism, or biological functions. Longer weekend sleep duration was linked to a decrease in eGFR levels. It warrants further study to clarify the mediators.

Trend Analysis of Palliative Care Utilization in Patients with Chronic Obstructive Pulmonary Disease During Hospitalization from 2007 to 2018 in Taiwan.

Purpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD. Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan's National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization. Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions-especially cancer-and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1-2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1-2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years. Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.

Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats.

OBJECTIVES: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. METHODS: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. KEY FINDINGS: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate. CONCLUSIONS: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.