Uterine myoma is associated with an increased risk of lung cancer: A nationwide population-based cohort study.

OBJECTIVE: The rate of lung cancer in female patients is increasing, with different features from male patients being displayed. Hormonal factors could play a role. The association between the development of uterine myoma (UM) and female hormones has also been reported. The relationship between female lung cancer and UM may be due to the effect of female hormones. METHODS: Data from 50 711 Taiwanese women with UM were retrieved from the National Health Insurance Research Database between 2000 and 2012. They were propensity-score matched with 50 711 women without UM (control group). A multivariate Cox proportional hazard regression model was used to compare the incidence of lung cancer between groups and to determine the hazard ratio of lung cancer in the UM group. RESULTS: The risk of lung cancer was significantly higher in women with myoma (adjusted hazard ratio: 1.62, 95% confidence ratio = 1.24-2.12). Stratified analyses demonstrated that the significantly increased risk of lung cancer was more likely to be found in certain groups, such as women who (a) are of younger age, (b) have a mid-level income, (c) have the highest urbanisation level, (d) are office workers and (e) with a longer follow-up period of myoma. Furthermore, myomectomy did not affect the risk pattern. CONCLUSION: The results from this nationwide population-based cohort study suggested that UM is associated with a higher risk of developing lung cancer. However, the exact underlying mechanism accounted for this remains unclear, and our findings still need to be verified by further comprehensive studies elsewhere.

Suicide attempts in patients with head and neck cancer in Taiwan.

OBJECTIVE: We examined the risk of suicide attempts in patients with head and neck cancer (HNC) in comparison with that in the general population and in patients of other cancers (including all other cancers rather than HNC). METHODS: The definition of suicide attempt here is that an attempt of suicide with or without completed suicide. This retrospective cohort study consisted of 66 931 cases of HNC and individual without HNC from the general population assigned to the control group. Cox's proportion hazard regression analysis was conducted to compare the subsequent suicide attempt risk between patients with HNC and the control group. RESULTS: The suicide attempt rate for HNC and control groups were 7.44 and 1.98 per 10 000 person-year, respectively. A more than three-fold higher risk of suicide attempts was observed in the HNC group than in the control group (adjusted hazard ratio [HR]: 3.72; 95% confidence intervals: 2.85, 4.88). Patients of HNC also had a significantly 1.9-fold higher risk of suicide attempt than patients with other cancers. Subsequent stratified analyses revealed a significantly elevated risk of suicide attempts across every cancer anatomic subsite and almost all categories of various demographics, but the risk was limited to male patients and patients with no comorbidity. The suicide attempt rate was the highest among patients with oropharyngeal cancer, and chemotherapy was associated with an elevated risk of suicide attempt. CONCLUSIONS: Patients with HNC are vulnerable to an increased risk of suicide attempts than the general population and patients with other cancers.

Risk of suicide attempts among colorectal cancer patients: A nationwide population-based matched cohort study.

OBJECTIVE: Patients with colorectal cancer (CRC) have been found to have a higher risk of suicide in limited-number studies. However, data on the actual incidence rate of suicide remain scarce. METHODS: Using Taiwan's National Health Insurance Research Database, we examined whether patients with CRC in Taiwan are at increased risk of suicide attempts. In this retrospective matched cohort study, data of 96 470 cases of CRC during 1 January 2000 to 31 December 2010 were collected. The control group was derived from general population by frequency matching 2 individuals without CRC for each individual with CRC by year of CRC diagnosis, age, and sex. The suicide risk in the CRC group compared with the control group was determined through Cox proportional hazard regression. We also compared the Kaplan-Meier analyses to competing risk cumulative incidence curves using the Aalen-Johansen estimator. RESULTS: A statistically significant 103% higher risk of suicide was observed in the CRC group compared with the control group (adjusted hazard ratio: 2.03; 95% confidence ratio: 1.60-2.56). Additional stratified analyses revealed a significantly elevated risk across almost all demographic groups but limited to rectum location, short follow-up time (<5 years), and without comorbidity. CONCLUSIONS: Our study suggested that patients with CRC in Taiwan have an elevated risk of suicide. Oncologists should pay attention to these patients and should consider referring them for psychological consultation to prevent suicide.

Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population-based cohort study.

The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60-2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90-1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20-54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship.

Formation mechanism and regulation analysis of trumpet leaf in Ginkgo biloba L.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.

A highly efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for etomidate and etomidate acid in urine, liver and kidney.

Etomidate (ETO) is a highly-efficient drug that can induce anesthesia with increasing doses, thus subject to strict regulation. However, an accurate and efficient method for ETO intake detection is currently lacking. Therefore, this study developed a straightforward sample preparation method using LC-MS/MS to analyze ETO and its primary metabolite, etomidate acid (ETA), in urine, liver, and kidney samples. Snap frozen pig liver and kidney samples were ground into a fine powder. Then, all the biological samples, including human urine, pig liver and kidney tissues, were deproteinized using acetonitrile and filtered for analysis. The separation was achieved in 9.01 min with gradient elution. The calibration curves ranged from 0.5 to 50 ng/mL for ETO in urine and 0.5 to 50 ng/g in liver and kidney, while the curves ranged from 1 to 100 ng/mL for ETA in urine and 1 to 100 ng/g in liver and kidney. The correlation coefficients (R2) were greater than 0.9957. The Limit of detection (LOD) and limit of quantitation (LOQ) for ETO were 0.2 and 0.5 ng/mL in urine samples and 0.2 and 0.5 ng/g in liver and kidney samples, respectively. For ETA, the LOD and LOQ were 0.5 and 1 ng/mL in urine samples and 0.5 and 1 ng/g in liver and kidney samples. This method was assessed by validation parameters, including selectivity, intra- and inter-day precision and accuracy, recovery, matrix effect, dilution integrity and stability. It was successfully applied to a practical case, revealing ETO and ETA concentrations in urine of 1.01 and 5.58 µg/mL, in liver samples of 12.30 and 1.13 µg/g, and in kidney samples of 6.95 and 4.23 µg/g. This suggests that the method is suitable for routine forensic detection of illicit ETO abuse.

Urinary tract infection increases subsequent urinary tract cancer risk: a population-based cohort study.

This study examines the possible association between urinary tract infection (UTI) and urinary tract cancer (UTC). Data from the National Health Insurance system of Taiwan were used for the analysis. The UTI cohort included 70 116 patients who were diagnosed and recruited between 1997 and 2010. Each patient was randomly frequency-matched with two people without UTI from the general population based on their age, sex, and month of UTI diagnosis. Cox's proportional hazard regression analysis was used to estimate the effects of UTI on UTC risk until the end of follow-up on December 31, 2010. Patients with UTI had a significantly higher risk of developing UTC than healthy people (adjusted hazard ratio, 4.66; 95% confidence interval, 3.55-6.10). Further analyses indicated that risks are potentially related to the level of the lesion site. This study indicated that patients with UTI had a higher risk of developing UTC.

Urinary tract stone raises subsequent risk for urinary tract cancer: a population-based cohort study.

OBJECTIVE: To evaluate the association between urinary tract stone (UTS) and urinary tract cancer (UTC) in Taiwanese patients, as the results of epidemiological studies about the relationship between UTS and the development of UTC remain inconclusive. PATIENTS/SUBJECTS AND METHODS: We conducted a population-based cohort study using data from the Taiwanese National Health Insurance system. The UTS cohort included 21 862 patients, and each patient was randomly frequency-matched for age, sex, and index year with two insured members of the general population who did not have UTS. Cox proportional hazard regression analysis was performed to estimate the effect of UTS on the risk of UTC. RESULTS: Patients with UTS were at a significantly higher risk of developing UTC compared with the comparison group (adjusted hazard ratio 4.66; 95% confidence interval 2.97-7.30). Women were at higher risk than men. Further analyses showed that the level of UTC was associated with that of UTS, and that the risk for UTC became more divergent for the two groups over time. CONCLUSIONS: Taiwanese patients with UTS, particularly women, had a higher risk for developing UTC than patients without UTS. The risk became more marked over time for this group.

Does use of tetracyclic antidepressant-mirtazapine reduce cancer risk in depression patients?

PURPOSE: We conducted a nested case-control study to evaluate the association between risk of cancer and mirtazapine use in depression patients in Taiwan. METHODS: We obtained data from the Taiwan National Health Insurance Research Database to conduct a population-based nested case-control study. The study cohort included 16 897 patients diagnosed with depression between January 1, 2000 and December 31, 2008. We identified 530 cancer patients as the study group and matched 4 non-cancer subjects with each cancer patient by incident density, age, and sex. Odds ratios and 95% confidence intervals were estimated using multivariate conditional logistic regression analysis. RESULTS: Use of mirtazapine for depression did not have significant effect on overall cancer incidence (odds ratio: 1.03, 95% confidence interval: 0.72-1.48). Further analysis of annual mirtazapine dosages and the duration of mirtazapine use revealed no significant effect on cancer risk. CONCLUSION: The findings of this population-based nested case-control study suggest that mirtazapine use may not provide a tumor suppression effect in humans such as that seen in the animal model. Future large-scale and in-depth investigations in this area are warranted.

[Progress in application of microbeam X-ray fluorescence spectroscopy in forensic science].

Microbeam X-ray fluorescence (micro-XRF) spectrometry has been raised as an analytical technique of microbeam during the recent years. With its advantages of high sensitivity, small sample requirement, high testing accuracy and non-destruction, the technique is widely utilized in forensic science. This review bases on recent researches at home and abroad, describes its applications including identification of gunshot residue, visualization of fingerprints, discrimination of drug source, production process, and other material evidences of analysis in crime scene. Thanks to the advances in technology, intelligent and portable micro-XRF equipment has appeared to be applied. It is believed that it may be more popular and frequent in administration of forensic science in the near future.

The development and transcriptome regulation of the secondary trunk of Ginkgo biloba L.

Secondary trunk Ginkgo biloba is one of the specific germplasms of G. biloba. In this study, paraffin sectioning, high-performance liquid chromatography and transcriptome sequencing technology were used to study the development of the secondary trunk of G. biloba from the morphological, physiological and molecular levels. The results showed that the secondary trunk of G. biloba originated from the latent buds in the stem cortex at the junction of the root and stem of the main trunk. The development process of secondary trunk was divided into 4 periods: the dormancy period of the secondary trunk buds, the differentiation period, the formation period of transport tissue, and the budding period. Transcriptome sequencing was performed by comparing the germination period and elongation growth period of the secondary trunk with the normal parts of the same period where no secondary trunks occurred. Differential genes involved in phytohormone signal transduction, phenylpropane biosynthesis, phenylalanine metabolism, glycolysis and other pathways can regulate not only the inhibition of early dormant buds but also the later development of the secondary trunk. Genes related to IAA synthesis are upregulated and indole-3-acetic acid content is increased, leading to the up-regulated expression of IAA intracellular vector genes. The IAA response gene (SAUR) receives and responds to IAA signals to promote the development of the secondary trunk. Through the enrichment of differential genes and functional annotations, a key regulatory pathway map for the occurrence of the secondary trunk of G. biloba was sorted out.

A population-based nested case-control study in taiwan: use of 5α-reductase inhibitors did not decrease prostate cancer risk in patients with benign prostate hyperplasia.

BACKGROUND: 5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. METHODS: We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. RESULTS: Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00-3.59; overall cancer: OR = 1.51; 95% CI: 1.00-2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17-80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. CONCLUSIONS: This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.

Estrogen decrease coronary artery disease risk in patients with cervical cancer after treatment.

BACKGROUND: The purpose of this study was to explore the possible association between coronary artery disease (CAD) risk and cervical cancer. METHODS: We used data from the National Health Insurance system of Taiwan to address the research topic. The exposure cohort contained 728 patients with cervical cancer. Each cancer patient was randomly frequency-matched with 4 participants by age, index-month, and index-year from the general population who did not have a cancer history before the index date (control group). Cox's proportion hazard regression analyses were conducted to estimate the relationship between cervical cancer and CAD risk. RESULTS: Among patients with cervical cancer, the overall risk for developing CADs was significantly lower than that of the control group [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95% CI): 0.41-0.79]. Further analyses revealed that the lower risk was observed only in patients with older age (aHR: 0.57, 95% CI: 0.40-0.82), a shorter follow-up duration (aHR: 0.47, 95% CI: 0.31-0.72), or with estrogen supplements (aHR: 0.39, 95% CI: 0.22-0.68). CONCLUSIONS: The findings from this population-based study suggest that estrogen supplements are associated with a decreased CAD risk in patients with cervical cancer.

Malignancies associated with systemic lupus erythematosus in Taiwan: a nationwide population-based cohort study.

Patients with systemic lupus erythematosus (SLE) are suggestive to have a higher cancer risk. The aim of this study is to evaluate the possible association of malignancy and SLE in Taiwan. We used the data of the National Health Insurance system of Taiwan to assess this issue. The SLE cohort contained 2,150 patients, and each patient was randomly frequency matched to 8 people without SLE on age and sex. The Cox's proportion hazard regression analysis was conducted to estimate the effects of SLE on the cancer risk. In patients with SLE, the risk of developing overall cancer was marginally significantly higher [adjusted Hazard ratio (HR) = 1.26, 95% confidence interval (95% CI) = 0.99-1.59] and was significantly higher for developing prostate cancer (adjusted HR = 3.78, 95% CI = 1.30-11.0). Our study unexpectedly found that Taiwanese patients with SLE have a higher risk to develop prostate cancer.

[Effects of levonorgestrel intrauterine system on endometrial tissue after endometrial polyps resection by hysteroscopy].

OBJECTIVE: To explore the changes of endometrial tissues after the insertion of levonorgestrel intrauterine system (LNG-IUS). METHODS: The endometrial tissues were harvested from 21 cases after endometrial polyps resection by hysteroscopy. And the patients received a 1-year follow-up. The immunohistochemical stains for estrogen receptor (ER), progesterone receptor (PR), Ki-67, bcl-2 and bax were used for semi-quantitative analyses. The changes of endometrial thickness were monitored and uterine weight was observed with a 3-year follow-up. RESULTS: The endometrial thickness and uterine weight declined continuously after the insertion of LNG-IUS. The endometrial thickness decreased from the preoperative level of (9.8 ± 1.2) mm to (3.5 ± 1.0) mm while the uterine weight dropped from the preoperative level of (98.8 ± 8.6) g to (66.6 ± 9.8) g. The expressions of ER, PR and Ki-67 were significantly lower than those of the para-polyps endometrial tissue (P < 0.05). The expressions of bcl-2 and bax were significantly higher than those of the para-polyps endometrial tissue (P < 0.05). CONCLUSION: LNG-IUS may prevent the recurrence of uterine endometrial polyps through its inhibited expressions of ER, PR and Ki-67 and induced endometrial apoptosis.

Adjuvant radiotherapy did not increase the risk of coronary heart disease in patients with non-metastatic breast cancer.

OBJECTIVE: Adjuvant radiotherapy (RT) in patients with breast cancer can adversely cause the heart to receive some radiation doses, which may lead to cardiovascular diseases. The results of previous research regarding this issue are not consistent. Therefore, we conducted a nationwide population-based study in Taiwan to evaluate whether adjuvant RT for breast cancer patients increased the risk of developing coronary heart disease (CHD). METHODS: This retrospective cohort study examined data from the National Health Insurance Research Database, Registry for Catastrophic Illness Patients, and Taiwan Cancer Registry Database. We identified 83,733 patients with breast cancer between 1 January 2000 and 31 December 2017. Individuals without breast cancer from the general population were frequency-matched by age and index year with individuals with breast cancer. Participants were followed until the occurrence of a CHD event, the end of follow-up, or patient record removal due to death or withdrawal from the NHI. A Cox proportional hazards regression analysis was conducted to compare the risk of CHD in breast cancer patients with that in patients in the comparison cohort. RESULTS: Compared to breast cancer patients without RT, those who underwent RT had a similar risk of subsequently developing CHD (adjusted hazard ratio, 0.94; 95% confidence interval, 0.87-1.02). Similar results were observed in a subgroup of patients with left-sided breast cancer. However, among patients who received adjuvant RT, those with left-sided breast cancer had a significantly higher risk of CHD than did those with right-sided breast cancer (adjusted hazard ratio, 1.17; 95% confidence interval, 1.04-1.30). Patients who received RT in 2010 or later had a significantly lower risk of CHD compared with those who received RT before 2010 (adjusted hazard ratio, 0.64; 95% confidence interval, 0.45-0.91). Higher prescribed doses of RT to the left-sided breast did not correspond to a higher risk of CHD. CONCLUSION: This large, nationwide cohort study suggests that adjuvant RT in patients with breast cancer did not increase the risk of CHD.

XGBG: A Novel Method for Identifying Ovarian Carcinoma Susceptible Genes Based on Deep Learning.

Ovarian carcinomas (OCs) represent a heterogeneous group of neoplasms consisting of several entities with pathogenesis, molecular profiles, multiple risk factors, and outcomes. OC has been regarded as the most lethal cancer among women all around the world. There are at least five main types of OCs classified by the fifth edition of the World Health Organization of tumors: high-/low-grade serous carcinoma, mucinous carcinoma, clear cell carcinoma, and endometrioid carcinoma. With the improved knowledge of genome-wide association study (GWAS) and expression quantitative trait locus (eQTL) analyses, the knowledge of genomic landscape of complex diseases has been uncovered in large measure. Moreover, pathway analyses also play an important role in exploring the underlying mechanism of complex diseases by providing curated pathway models and information about molecular dynamics and cellular processes. To investigate OCs deeper, we introduced a novel disease susceptible gene prediction method, XGBG, which could be used in identifying OC-related genes based on different omics data and deep learning methods. We first employed the graph convolutional network (GCN) to reconstruct the gene features based on both gene feature and network topological structure. Then, a boosting method is utilized to predict OC susceptible genes. As a result, our model achieved a high AUC of 0.7541 and an AUPR of 0.8051, which indicates the effectiveness of the XGPG. Based on the newly predicted OC susceptible genes, we gathered and researched related literatures to provide strong support to the results, which may help in understanding the pathogenesis and mechanisms of the disease.

Analysis of Parkinson's disease and subsequent cancer risk in Taiwan: a nationwide population-based cohort study.

BACKGROUND: Patients with Parkinson's disease (PD) are suggested to be at a lower risk for the development of certain cancers and at a higher risk for melanoma. The aim of this study is to evaluate the possible association between PD and malignancy in Taiwan. MATERIALS AND METHODS: We used the data of the National Health Insurance System of Taiwan to assess this issue. The PD cohort contained 4,957 patients, and each patient was randomly frequency matched by age and sex with 4 people from the general population without PD. Cox's proportional hazard regression analysis was conducted to estimate the effects of PD on the cancer risk. RESULTS: In patients with PD, the risk of developing overall cancer was marginally significantly lower than in subjects without PD [adjusted hazard ratio (HR) = 0.88; 95% CI = 0.78-0.99]. For individual cancers, the risks of developing colorectal and lung cancers among patients with PD were marginally significantly lower than in subjects without PD. In contrast, despite the higher HR for the development of melanoma, it did not reach statistical significance because of the relatively small sample size. CONCLUSION: Our study found that Taiwanese patients with PD have a lower risk of developing colorectal and lung cancers. The findings of this study are compatible with those of prior studies from other countries.

The association between malignancy and end-stage renal disease in Taiwan.

OBJECTIVE: Patients with end-stage renal disease are suggestive to have a higher risk for the development of some kinds of cancer. The aim of this study is to evaluate the possible association between malignancy and end-stage renal disease in Taiwan. METHODS: We used the data of the National Health Insurance system of Taiwan to assess this issue. The end-stage renal disease cohort contained 21 817 patients, and each patient was randomly frequency-matched with two people from the general population without end-stage renal disease based on their age and sex. The Cox proportional hazard regression analysis was conducted to estimate the effects of end-stage renal disease on the cancer risk. RESULTS: In patients with end-stage renal disease, the risk of developing overall cancer was significantly higher than the normal healthy subjects (adjusted hazard ratio = 1.64, 95% confidence interval = 1.54-1.74). This was also true when we analyzed males and females separately. For individual cancer, the risks for developing urinary tract cancers, liver cancer and breast cancer among patients with end-stage renal disease were significantly higher. On the contrary, lung, prostate and esophageal cancer risks were significantly lower when compared with the normal healthy subjects. CONCLUSIONS: Our study found Taiwanese patients with end-stage renal disease to have a higher risk to develop urinary tract, liver and breast cancer. We unexpectedly discovered these patients to have a lower risk to get lung, prostate and esophageal cancer.