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以跨產業導入「冷藏智慧藥櫃」，運用自動販賣機的概念及智慧藥櫃功能，藥師刷讀取處方箋條碼後藥品可精準計量且自動出藥，系統會自動更新庫存量，並進行藥品追蹤、清點及補藥通知。活動成果可顯著降低調劑錯誤率、改善藥品庫存管理，但問卷調查顯示對冷藏智慧藥櫃整體的滿意度偏低，整體而言，對於冷藏智慧藥櫃的設置及設計是可以再改進。 未來新型冷藏智慧藥櫃可適用如疫苗、生物製劑，以便藥品批號追溯等為佳，其應用場景可考量於門診針劑藥局、健兒疫苗藥局、急診藥局等。 A refrigerated automatic dispensing cabinet combines the concepts of a vending machine and automatic dispensing cabinets to accurately measure and automatically dispense medicine after pharmacists scan a prescription barcode. The system can also automatically track and renew inventory and send notifications when a refill is needed. These functions drastically decrease the rate of dispensing errors and improve inventory management. However, the results of the survey used in this study indicated low satisfaction with the refrigerated automatic dispensing cabinet. Thus, the application and design of the refrigerated automatic dispensing cabinet still have room for improvement. The novel refrigerated automatic dispensing cabinet can be used in outpatient, pediatric vaccination, and emergency department pharmacies to track the batch number of medicines such as vaccines and biologic agents &nbsp

Background Hypertension increases the likelihood of cardiovascular diseases (CVDs). Cytochrome P450 1A2 (CYP1A2) single nucleotide polymorphism (SNP) is related to caffeine metabolism and the risk of CVD among coffee drinkers. CYP1A2 rs762551 influenced the risk of stroke among hypertensive patients. We examined the relationship between hypertension and coffee drinking based on CYP1A2 rs762551 SNP in Taiwanese adults. Methods We used data contained in the Taiwan Biobank database (2011–2018) and included 19,133 participants having complete information on hypertension, rs762551 polymorphism, coffee intake, etc. The risk of hypertension was determined using multiple logistic regression. Results Coffee intake was significantly associated with a lower risk of hypertension. The odds ratio (OR), 95% confidence interval (CI), and p-value were 0.877, 0.807–0.954, and 0.0032, respectively. CYP1A2 rs762551 was not significantly associated with the risk of hypertension, but it had a significant interactive association with coffee drinking (p value = 0.0303). After stratification by rs762551 genotypes, the inverse coffee drinking-hypertension association was retained, but significant results were observed only in those with the AC + CC genotype (OR 0.678, 95% CI 0.722–900, p value = 0.0001). According to the combination of coffee drinking and rs762551 genotypes (reference group: no coffee drinking and rs762551 AA), the coffee drinking-AC + CC group had a lower risk of hypertension (OR 0.888, 95% CI 0.789–0.999, p value = 0.0483). Conclusion Coffee drinking, particularly among individuals with the CYP1A2 rs762551 AC + CC genotype was associated with lower odds of hypertension.

The use of synergistic antibiotic combinations has emerged as a viable approach to contain the rapid spread of antibiotic-resistant pathogens. Here we report the discovery of a new strongly synergistic pair - microcin J25 and sulfamonomethoxine. The former is a lasso peptide that inhibits the function of RNA polymerase and the latter is a sulfonamide antibacterial agent that disrupts the folate pathway. Key to our discovery was a screening strategy that focuses on an antibiotic (microcin J25) that targets a hub (transcription) in the densely interconnected network of cellular pathways. The rationale was that disrupting such a hub likely weakens the entire network, generating weak links that potentiate the growth inhibitory effect of other antibiotics. We found that MccJ25 potentiates five other antibiotics as well. These results showcase the merit of taking a more targeted approach in the search and study of synergistic antibiotic pairs.

Breast cancer (BC) is the most diagnosed cancer worldwide. Multiple myeloma (MM) is a hematologic malignancy characterized by the overproduction of monoclonal antibodies in the bone marrow. Systemic lupus erythematosus (SLE) is distinguished by the aberrant activity of the immune system with heterogeneous clinical manifestations. The coexistence of more than one major illness in a patient can present a diagnostic challenge for clinical physicians, especially when the comorbid diseases share a similar clinical presentation. Herein, we report an unusual case of secondary synchronous diagnosis of MM and SLE after BC treatment.A 69-year-old female patient with breast cancer experienced severe skin itching and rashes on the face, anterior chest wall, back, and trunk for two days before admission. She had high levels of immunoglobulin and anti-nuclear antibodies; low levels of complements 3 and 4; positive anti-cardiolipin-IgM, anti-beta 2 glycoprotein-1 (anti-β2GP1) antibodies, and lupus anticoagulant results at serological testing.The postoperative pathology report showed ductal carcinoma in situ in the right breast. SLE was confirmed based on the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria. IgG-κ type multiple myeloma was confirmed by bone marrow biopsy, and the patient was synchronously diagnosed with SLE and MM after BC treatment.Glucocorticoids and immunosuppressive agents, including intravenous hydrocortisone (5 g every 8 hours) and oral hydroxychloroquine (Plaquenil) (200 mg twice daily) were administered to treat SLE. One capsule of thalidomide 50 mg was administered orally every night at bedtime for MM.The patient died two days later, shortly after the administration of drugs, due to multiple organ failures secondary to pneumonia and respiratory failure.This is a case of MM and SLE after BC treatment. The present challenge was the early detection and accurate diagnosis of the secondary major illnesses, as the clinical manifestations were similar and non-specific between these two diseases. Awareness and prompt recognition of the common clinical symptoms of SLE and MM should be considered by clinical physicians to avoid delayed diagnoses and facilitate early treatment for a better prognosis.

Objective: To examine the clinical factors associated with the effectiveness of stapedotomy in improving hearing sensitivity in Taiwanese patients with otosclerosis. Methods: In this retrospective study, we reviewed the medical records of 31 patients (36 ears) with otosclerosis undergoing stapedotomy performed by a single surgeon. Preoperative and postoperative hearing results were analyzed to identify factors associated with hearing outcomes after stapedotomy in the Taiwanese population with clinical otosclerosis. Results: Compared with preoperative pure tone averages (PTAs), stapedotomy significantly improved postoperative air conduction (AC) thresholds ( P < .0001), bone conduction (BC) thresholds ( P = .025), and air-bone gaps (ABGs; P < .0001). Postoperative closure of ABGs less than 10 or 20 dB was achieved in 16 (44.4%) and 33 (91.7%) of 36 surgical ears. Improvement in postoperative AC thresholds and ABGs and the size of preoperative ABGs were significantly correlated (r = .650, P < .001 and r = .745, P < .001, respectively). Gender-stratified analysis indicated a stronger correlation between improvement in postoperative AC thresholds and preoperative ABGs in male patients than in female patients (r = .893, P < .001 and r = .476, P = .014, respectively), and in postoperative and preoperative ABGs (r = .933, P < .001 and r = .626, P < .001, respectively). With the more stringent criteria for surgical success, factors including age (≤50 years), type (conductive, BC ≤25 dB), and degree (PTA ≤55 dB) of preoperative hearing loss led to more favorable outcomes. Conclusions: We reported evidence supporting a potential gender difference on hearing outcomes after stapedotomy in Taiwanese patients with otosclerosis. Age, type, and degree of preoperative hearing loss may affect the surgical success rate.

Background In July 1984, Taiwan officially began a nationwide hepatitis B virus (HBV) vaccination program where only infants born to HBsAg-positive mothers were vaccinated free of charge until June 1986. However, from July 1986, all infants were vaccinated against HBV. The impact of the July 1986 HBV vaccination program on first-time blood donors has not been exhaustively studied. We, therefore, determined the risk of HBV among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. Methods Initially, we recruited 857,310 first-time blood donors whose data were collected between 2013 and 2018 from 5 blood donation centers in Taiwan. However, we excluded donors with incomplete and outlying data (n = 12,213) and those born between July 1984 and June 1986 (n = 21,054). The final study participants comprised 9118 HBV positive and 814,925 HBV negative individuals. We divided the participants into two birth cohorts (born before and after July 1986) and assumed that those born before July 1986 were not vaccinated at birth while those born after July 1986 were vaccinated. Results The prevalence of HBV among those born before and after July 1986 was 4.53 and 0.25%, respectively. Individuals born after July 1986 had a lower risk of HBV than those born before July 1986. The adjusted odds ratio (OR), 95% confidence interval (CI) was 0.16, 0.13–0.19. Men had a higher risk of HBV than women (OR = 1.40, 95% CI = 1.34–1.47). The interaction between sex and birth date was significant (p-value = 0.0067). Stratification of participants by birth date revealed a higher risk of HBV in men compared to women in both birth cohorts. The OR, 95% CI was 1.47, 1.40–1.55 for those born before July 1986 but declined to 1.15, 1.02–1.29 for those born after July 1986. Conclusions The risk of HBV was lower among those born after than those born before the July 1986 vaccination program. In both cohorts, the risk was high in men relative to women. The seemingly protective effect among those born after July 1986 was higher in women than men.

BackgroundParticulate matter (PM) < 2.5 μm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise.MethodsWe obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5data from the Air Quality Monitoring Database (AQMD) and estimated participants’ exposure using residential addresses.ResultsDLEC1 methylation and PM2.5were positively associated: beta coefficient (β) = 0.114 × 10−3;pvalue = 0.046. The test for interaction between exercise and PM2.5on DLEC1 methylation was significant (pvalue = 0.036). After stratification by exercise habits, PM2.5and DLEC1 methylation remained significantly associated only among those who exercised regularly (β= 0.237 × 10−3;pvalue = 0.007). PM2.5quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5< 27.37 μg/m3(β= − 5.280 × 10−3;pvalue = 0.009). After combining exercise habits and PM2.5quartiles, one stratum (i.e., regular exercise and PM2.5< 27.37 μg/m3) was inversely associated with DLEC1 methylation (β= -5.160 × 10−3,pvalue = 0.007).ConclusionsWe found significant positive associations between PM2.5and DLEC1 promoter methylation. Regular exercise at PM2.5< 27.37 μg/m3seemingly regulated DLEC1 promoter methylation.

Purpose High-density lipoprotein cholesterol (HDL-C) is essential for cardiometabolic health. Coffee consumption influences the body’s ability to regulate serum lipid profile. Although there is extensive information on coffee and cholesterol, not much is known whether changes in HDL-C concentrations are affected by coffee with or without flavoring substances. Materials and Methods Using historical data collected from 1272 participants in Li-Shin (Landseed) International Hospital in Northern Taiwan, we examined the relationship between HDL-C and consumption of plain black coffee with and without additives. Data on coffee consumption between 2006 and 2019 were collected based on self-reported questionnaires while HDL-C measurements were obtained from the electronic medical records of the hospital. t-test, chi-square test and multivariate linear regression analysis were used for analysis. Results In our primary analysis, we found that coffee consumption of ≥5 cups per week was positively associated with HDL-C (β = 1.9586, p=0.0442) compared with the lowest level (

Background Polycyclic aromatic hydrocarbon (PAH)-rich substances like cigarette smoke and PM2.5 induce aryl hydrocarbon receptor (AHR)-mediated aryl hydrocarbon receptor repressor (AHRR) methylation. AHRR cg05575921 and coagulation factor II (thrombin) receptor-like 3 (F2RL3) cg03636183 methylation patterns are well-established biomarkers for smoking. Even though AHRR cg05575921 methylation has recently been associated with PM2.5, the interaction between smoking and PM2.5 on AHRR methylation is yet to be fully explored. We evaluated AHRR and F2RL3 CpG sites to identify potential significant markers in relation to PM2.5 and smoking in Taiwanese adults. Methods DNA methylation and smoking data of 948 participants aged 30–70 years were obtained from the Taiwan Biobank Database (2008–2015), while PM2.5 data were obtained from the Air Quality Monitoring Database (2006–2011). Results Smoking and PM2.5 were independently associated with hypomethylation (lower levels) of AHRR cg05575921, AHRR cg23576855, F2RL3 cg03636183, and F2LR3 cg21911711 after multiple-comparison correction (Bonferroni P β = − 0.03909, P P smoking P 2.5. After adjusting for F2RL3 cg03636183, smoking and PM2.5 remained significantly associated with cg05575921 hypomethylation: β − 0.02221, P P smoking P = 0.0120 for PM2.5. After stratification by sex, smoking and PM2.5 remained associated (P β = − 0.04274, − 0.17700, and − 0.00163 for former smoking, current smoking, and PM2.5, respectively) and women (β = − 0.01937, − 0.17255, and − 0.00105 for former smoking, current smoking, and PM2.5, respectively). After stratification by residential area, former and current smoking remained associated (P β = − 0.03918 and − 0.17536, respectively (P-trendsmoking P β = − 0.01356 and − 0.01970, respectively (P-trendarea Conclusion Smoking and PM2.5 were independently associated with hypomethylation of cg05575921, cg23576855, cg03636183, and cg21911711. The most hypomethylated CpG site was cg05575921 and its association with smoking and PM2.5 was dose-dependent.

Increased ventilation during exercise in polluted areas could trigger airway inflammation. We evaluated blood DNA methylation of the SOX2-promoter region in relation to exercise and PM2.5 in Taiwanese adults. Data of 948 participants aged 30&ndash, 70 years were retrieved from the Taiwan Biobank Database (2008&ndash, 2015) and the Air Quality Monitoring Database (2006&ndash, 2011). PM2.5 was positively associated with SOX2-promoter methylation (&beta, = 0.000216, p &lt, 0.0001). The interaction between PM2.5 and exercise on SOX2-promoter methylation was significant (p = 0.0146). After stratification by exercise habits, PM2.5 was positively associated with SOX2 methylation in only individuals who did regular exercise (&beta, = 0.0003490, 0.0001). After stratification by exercise habits and residential areas, SOX2-promoter methylation levels in those who lived in the southern area were higher for both the regular exercise (&beta, = 0.00272, p = 0.0172) and no regular exercise groups (&beta, = 0.002610 and p = 0.0162). SOX2-promoter methylation levels in those who lived in the northern area and did regular exercise were lower, &beta, = -0.00314 (p = 0.0036). In conclusion, PM2.5 was positively associated with SOX2-promoter methylation in participants who did regular exercise. Living in the southern area was positively associated with SOX2-promoter methylation regardless of exercise habits.

Additional file 1: Table S1. AHRR and F2LR3 CpG sites and their association with smoking and PM2.5. Table S2. Multiple linear regression analysis showing the association of smoking and PM2.5 with F2RL3 cg03636183 methylation in the study participants. Table S3. Multiple linear regression analysis showing the association of smoking and PM2.5 with F2RL3 cg03636183 methylation in the study participants stratified by sex. Table S4. Multiple linear regression analysis showing the association of smoking and living in PM2.5 areas with F2RL3 cg03636183 methylation in the study participants. Table S5. Multiple linear regression analysis showing the association of smoking and living in PM2.5 areas and F2RL3 cg03636183 methylation in the study participants stratified by sex.

DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008–2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30–70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β = − 0.01003, P = 0.009 and β = − 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease.

Education, sex, and the APOE-rs405509 variant are associated with Alzheimer&rsquo, s disease and cognitive performance. We investigated if the rs405509 TT, TG, and GG genotypes modulate the effect of sex and education on cognitive impairment in Taiwanese adults. Data on cognitive health (defined by Mini-Mental State Examination (MMSE) scores) and rs405509 were from Taiwan Biobank. Participants included 2105 men and 2027 women with a mean age of 64 years. Education below university level was significantly associated with lower MMSE scores. The odds ratios (ORs) were 1.82, 95% confidence interval (CI) 1.38&ndash, 2.41 for senior high school, 3.39, 95% CI 2.50&ndash, 4.59 for junior high school, and 11.94, 95% CI 9.91&ndash, 15.50 for elementary school and below (p-trend &lt, 0.05). The association between MMSE score and sex was significant only in the lowest educational group (elementary and below), with lower odds of having a low MMSE score in men compared to women (OR = 0.51, 95% CI 0.34&ndash, 0.77). After stratification by rs405509 genotypes, this association was significant only among TT genotype carriers (OR = 0.481, CI = 0.253&ndash, 0.915). In conclusion, a significant association between MMSE score and sex was observed in the lowest educational group, especially among carriers of rs405509 TT genotypes.

The effects of genetic variants on the interaction between hyperlipidemia and sex have not been investigated among gout patients in Taiwan. Using Taiwan Biobank and the National Health Insurance Research Database (NHIRD), we examined hyperlipidemia, sex, and their relationship with gout among Taiwanese adults with the human leukocyte antigen B (HLA-B) genetic variants. Hyperlipidemia was present in 1437 patients with gout. Sex and hyperlipidemia had significant associations on gout risk, with hyperlipidemia showing a relatively stronger effect. Gout was present in men, with an odds ratio (OR) of 1.945 (95% confidence interval (CI) 1.568&ndash, 2.411) compared to women, and in hyperlipidemic (OR = 4.032, 95% CI: 3.581&ndash, 4.540) compared to non-hyperlipidemic patients. The interaction of sex and hyperlipidemia was significant for rs2523608 GG (p = 0.0402) and rs4713518 AA (p = 0.0003) genotypes. After stratification, hyperlipidemia remained a risk factor in women (OR = 4.735, 95% CI: 3.375&ndash, 6.643) and men (OR = 3.640, 95% CI: 2.916&ndash, 4.544) with rs2523608 GG genotype. The odds ratio in hyperlipidemic women and men with rs4713518 AA genotype was 7.454 (95% CI 5.103&ndash, 10.888) and 3.585 (95% CI 2.854&ndash, 4.503), respectively. Our study indicates that hyperlipidemia-sex interactions exist for gout risk in Taiwanese adults with rs2523608 GG and rs4713518 AA genotypes.

Background Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter

Spearman correlation between PM2.5 concentrations (Îźg/m3) and mean methylation levels (beta values) in the northern, north-central, central, and southern areas. The methylation beta values decrease as PM2.5 levels increase. (DOCX 40 kb)

Table S1. Multiple linear regression showing beta coefficients of SOX2 methylation both in and outside the promoter region. Table S2. Multiple linear regression showing beta coefficients of SOX2 methylation in the exon. Table S3. Multiple linear regression showing beta coefficients of SOX2 methylation in the 3UTR region. Table S4. Multiple linear regression showing beta coefficients of KRAS promoter methylation. (DOCX 22 kb)

AHRR CpG sites significantly associated with PM2.5. (DOCX 20 kb)

Background DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. Methods Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008–2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30–70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. Results Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β = − 0.01003, P = 0.009 and β = − 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. Conclusion Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease. Electronic supplementary material The online version of this article (10.1186/s13148-019-0662-9) contains supplementary material, which is available to authorized users.

Background Exercise is an important cardiovascular risk reducing therapy. Objective The aim of this study was to assess the relationship between weekly exercise duration and high-density lipoprotein cholesterol (HDL-c) in Taiwanese men and women. Methods Data were retrieved from the dataset of the national adult preventive medical services which is recorded under the Health Promotion Administration (HPA). The lipid profiles of 194528 eligible participants aged 40 years and above who completed a questionnaire on recent health behavior including smoking, drinking, exercise and other factors in 2014 were determined. Weekly exercise durations of 0.0

The Bozhong Depression in Bohai Bay was previously ranked as an unfavorable exploration region due to concerns about reservoir, trapping integrity and top seal risks. In the mid 1900s, a few explorationists began to view the petroleum accumulation conditions more positively. They argued that rapid Neogene subsidence could have generated a new suite of source potential and that recent continued fault movements may have provided the needed conduits for upward hydrocarbon migration. They predicted the existence of lacustrine facies that could supply the needed lateral and top seals for the intensively faulted traps. These radical thoughts were gradually formulated into a new concept for the Neogene targets. This paradigm shift in exploration concepts has, since 1995, led to the discovery of nine (9) major oil fields with a combined in-place reserves more than double those discovered in the previous thirty (30) years. Some of these Neogene reservoirs appear to be at a dynamic balance between hydrocarbon escape and charge. It is speculated that the required driving energy for the charge may have come from earthquake activities.

BACKGROUND: This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with polycystic ovarian syndrome (PCOS) and normozoospermic semen during IVF cycles. METHODS: Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Fertilization rate (two pronuclei/COC), day 2 embryonic morphology and rate of development were assessed. RESULTS: A total of 1089 cumulus-oocyte complexes (COC) were collected in 60 cycles (mean+/-SD, 18.2 +/- 7.2). Totals of 541 and 548 COC were inseminated by IVF and ICSI respectively, with a significantly higher fertilization rate in the ICSI group (ICSI versus IVF, 72.3 +/- 15.5 versus 44.8 +/- 25.1%). No fertilization failure occurred in the group of oocytes inseminated by ICSI, whereas the COC in nine patients (15%) inseminated by IVF had complete fertilization failure. The day 2 embryonic morphology and rate of development were not different regardless of the insemination method. CONCLUSIONS: Our results suggested that another randomized controlled study, randomizing patients instead of sibling oocytes, should be undertaken to compare the pregnancy rate per started cycle and to see whether ICSI should be performed on all, or at least on a portion of, oocytes for patients with PCOS undergoing IVF cycles.

Background:Human papillomaviruses (HPV) have been considered to be the necessary and central agents of cervical carcinoma. Objective: The aim of this study was to determine the prevalence and genotypes of HPV in archival cervical carcinomas. Study design:The study included 152 paraffin-embedded, formaldehyde-fixed cervical carcinoma specimens. To improve the detection and typing of HPV in archival tissues, we conducted a comprehensive study in which, polymerase chain reaction (PCR)-based methods using E7 type-specific (TS) and L1 modified general primers (MY11/GP6+ and GP5+/GP6+) were employed. Results: Overall HPV prevalence was 98% in the cervical carcinomas. HPV 16 was detected in 66% of the tumors, HPV 18 in 22%, HPV 31 in 13%, HPV 33 in 9%, and HPV 58 in 9%. Notably, multiple HPV types were present in 44 (28.9%) of the 152 cervical carcinomas. The most common co-infections were HPV types 16/18 (12 cases), followed by HPV types 16/31 (7 cases). Additionally, HPV 18 was more frequent in adenocarcinomas and adenosquamous carcinomas (86%) than in squamous cell carcinomas (15.8%) (P = 0.0002). Conclusions: The combination of L1 general primers and E7 type-specific primers can be of use in detecting HPV DNA in archival tissues. The present study showed a high frequency of multiple HPV infections in cervical carcinomas. Hence, relevant HPV typing information in cervical carcinoma is very important for further HPV vaccine design and application. © 2003 Elsevier B.V. All rights reserved.

It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH–nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a “nanoblast” and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.

Background: To assess the characteristics of progesterone (Prog) changes in women with a subtle Prog rise in recombinant follicle-stimulating hormone (r-FSH) and GnRH antagonist cycles. Methods: We enrolled 233 patients undergoing controlled ovarian hyperstimulation with r-FSH and GnRH antagonist for IVF or ICSI. A subtle Prog rise 1 day before hCG administration was defined as a Prog value of ≧1.2 ng/ml. Results: 100 of 233 cycles (42.9%) showed a subtle Prog rise in this study. The mean serum Prog levels and area under curve (AUC) in the group with Prog ≧1.2 ng/ml was significantly higher than that in the Prog Conclusion: A subtle Prog rise may occur as early as cycle day 8 in r-FSH/GnRH antagonist cycles.

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P1.2 ng/ml or P/= 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P/= 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p0.001) on the day of hCG injection than the group with P1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.

To investigate if the combination of clomiphene citrate, hMG, and cetrorelix (CC/hMG/cetrorelix protocol) can be applied to patients who had excessive response to GnRHa long protocol.Fifty patients who coasted and failed to conceive in their first cycles stimulated with GnRHa long protocol were stimulated with CC/hMG/cetrorelix protocol. The peak serum estradiol levels, the need of coasting and prolonged coasting (/=4 days), and the incidences of OHSS were compared.The peak estradiol level was significantly lower with CC/hMG/cetrorelix protocol compared to GnRHa long protocol. With CC/hMG/cetrorelix protocol, only four patients (8%) needed coasting and no one coasted/=4 days. In contrast, in the first cycles, 11 patients (22%) needed coasting/=4 days. The incidence of moderate OHSS was significantly lower with CC/hMG/cetrorelix protocol.The CC/hMG/cetrorelix protocol is an acceptable alternative protocol for patients who had excessive response to GnRHa long protocol.

Ectopic pregnancy situated in a Caesarean section scar is a rare but potentially life-threatening event. Because of its rarity, there are no universal treatment guidelines to manage this condition. We report a case of IVF-induced triplet heterotopic pregnancy of early gestational age that included one Caesarean scar pregnancy diagnosed as early as 6 weeks gestation. Treatment with embryo aspiration under vaginal ultrasonography for selective embryo reduction was given and the concurrent intrauterine twin pregnancy was preserved successfully.

BACKGROUND: The purpose of this study was to determine if there is any additional benefit from FSH priming in addition to hCG priming on in-vitro maturation (IVM) programmes. METHODS: Sixty women with polycystic ovary syndrome (PCOS) who underwent 68 IVM cycles were randomized by computer-generated numbers to receive FSH stimulation or not. Thirty-five cycles were pretreated with 75 IU rFSH for 6 days, and 33 cycles were not. Every cycle was given hCG 10 000 IU 36 h before oocyte retrieval. Immature oocytes were matured in vitro and fertilized by ICSI, and the resulting embryos were replaced on day 2 or 3. RESULTS: A total of 1528 immature oocytes were recovered. The overall maturation and fertilization rates were 74.2 and 72.8% respectively. After embryo transfer, 23 pregnancies resulted (33.8%). The oocyte numbers and endometrial thickness were similar between FSH-primed and non-FSH-primed groups. Serum estradiol level on the day of hCG injection was significantly higher in the FSH-primed group than in the non-FSH-primed group (377.2 pmol/l versus 143.8 pmol/l, P = 0.001). The maturation rate, fertilization rate and pregnancy rate were 76.5, 75.8 and 31.4% respectively for FSH-primed group, and 71.9, 69.5 and 36.4% respectively for non-FSH-primed group (all not significant). CONCLUSIONS: IVM is a feasible treatment for women with PCOS. FSH priming has no additional beneficial effect on IVM.

BACKGROUND: The introduction of GnRH antagonists such as cetrorelix acetate has made possible the simplification of ovarian stimulation. However, the most effective protocol for their administration has not yet been clearly defined. METHODS: Forty women with male-factor infertility undergoing 40 ICSI cycles were included in the study. Clomiphene citrate at 100 mg a day was given from cycle day 3 through day 7. hMG at 150 IU was given on cycle days 4, 6 and 8, and was adjusted from day 9 according to the follicular and hormone responses. Cetrorelix acetate at 2.5 mg was administered when the leading follicle reached 14 mm. The remaining 0.5 mg was divided into two 0.25 mg injections for possible later use. Serum FSH, LH, estradiol and progesterone levels were measured daily from the day of cetrorelix acetate injection until hCG was given. RESULTS: Serum LH level was suppressed effectively for 4 days. Four patients (10%) needed one or two additional injections of 0.25 mg cetrorelix acetate. No premature LH surge was detected in any of the women treated. Sixteen women became pregnant (40%), of which 14 pregnancies (35%) were ongoing at the time of writing. CONCLUSIONS: This study demonstrates that this new protocol is feasible for couples with male-factor infertility undergoing ICSI.

Nanodiamond (ND) is surrounded by layers of graphite on its surface. This unique structure feature creates unusual fluorescence spectra, which can be used as an indicator to monitor its surface modification. Meanwhile, the impurity, nitroso (CNO) inside the ND can be photolyzed by two-photon absorption, releasing NO to facilitate the formation of a sp3 diamond structure in the core of ND and transforming it into a sp2 graphite structure. Such a conformational transition enlarges the size of ND from 8to90nm, resulting in a popcornlike structure. This transition reaction may be useful as nanoknives in biomedical application.

This letter presents direct observation of growth hormone receptor in one single cancer cell using nanodiamond-growth hormone complex as a specific probe. The interaction of surface growth hormone receptor of A549 human lung epithelial cells with growth hormone was observed using nanodiamond’s unique spectroscopic signal via confocal Raman mapping. The growth hormone molecules were covalent conjugated to 100nm diameter carboxylated nanodiamonds, which can be recognized specifically by the growth hormone receptors of A549 cell. The Raman spectroscopic signal of diamond provides direct and in vitro observation of growth hormone receptors in physiology condition in a single cell level.