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Background: Both vestibular schwannoma (VS) and Meniere's disease (MD) patients underwent hydrops MRI to clarify the relationship between VS and endolymphatic hydrops (EH)., Methods: Eighty patients with VS or MD underwent an inner ear test battery followed by hydrops MRI, and were then divided into 3 groups. Group A comprised 58 MD patients (62 ears) with positive EH but negative VS. Group B included 18 VS patients (18 ears) with negative EH, while Group C consisted of 4 patients (4 ears) who had VS concomitant with EH. Another 14 MD patients who tested negative for EH on hydrops MRI were initially excluded from this cohort, but were later included for comparison., Results: The decreasing prevalence of EH at the cochlea, saccule and utricle in Group A was identified in 59 (95%), 42 (68%) and 40 (65%) ears, respectively, mimicking a declining sequence of abnormality rates running from audiometry (86%), cervical vestibular-evoked myogenic potential (cVEMP) test (55%) to the ocular (oVEMP) test (53%). However, such decreasing trend was not identified in Groups B and C. In Groups C and A combined, 4 (6%) of 62 EH patients had concomitant VS. Conversely, 4 (18%) of 22 VS patients in Groups C and B combined had concurrent EH., Conclusion: A very low (6%) rate of VS in EH patients indicates that VS in EH patients may be coincidental. In contrast, EH was identified in 18% prevalence of VS patients, mirroring the 22% prevalence of cochlear EH demonstrated in VS donors through histopathological studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the association between paternal metformin use and risk of congenital malformations in offspring., Design: Population based, cross national cohort study., Setting: Norway and Taiwan., Participants: 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18., Main Outcome Measures: The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach., Results: Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses., Conclusions: The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this work was supported by the Norwegian Research Council and by the National Science and Technology Council of Taiwan; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The authors had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study utilized Hydrops MRI in patients with cranial nerve (CN) VIII schwannoma to assess the concomitance with endolymphatic hydrops (EH), aiming to elucidate the mechanism of hydrops formation in these patients., Methods: Twenty-six patients diagnosed as CN VIII schwannoma including vestibular schwannoma (VS) in 24 and intracochlear schwannoma (ICS) in 2 were enrolled. Fifteen patients received radiosurgery and 11 patients opted for a wait-and-scan approach. All patients underwent an inner ear test battery, followed by Hydrops MRI. Based on Hydrops MRI, 6 patients (23%) with positive EH were assigned to Group A, while the other 20 patients showing negative EH were assigned to Group B., Results: The abnormality rates of inner ear test battery in Group A ran from the audiometry (100%), cervical vestibular-evoked myogenic potential (cVEMP) test (83%), ocular VEMP (oVEMP) test (67%) to the caloric test (33%), exhibiting a significantly declining sequence. This declining sequence is consistent with the decreasing order in the prevalence of EH from the cochlea (83%), saccule (50%) to utricle (50%). However, Group B did not show such decreasing trend, indicating that Groups A and B did not share the common mechanism. The mean tumor size prior to radiosurgery was 1.91 ± 0.89 cm, which significantly reduced to 1.53 ± 0.60 cm at a mean interval of 6 years following radiosurgery. In contrast, tumor size remained unchanged in those opted for a wait-and-scan approach., Conclusion: It is recommended to utilize Hydrops MRI for patients with CN VIII schwannoma during annual follow-up, particularly those experienced episodic vertigo and/or deteriorated hearing. The Hydrops MRI can not only monitor tumor size, but also detect the presence of EH, so as to guide treatment decision., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status., Methods: In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model., Findings: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7 years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8 years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03 -5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups., Interpretation: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes., Funding: Ministry of Education, Taiwan., Competing Interests: Declaration of interests F-YH, EC-HT, and C-YW have received a research grant, awarded to the National Taiwan University, from Novo Nordisk. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to examine the longitudinal relationships between the trajectories of distinct subtypes of various domains of social supports and risk of subjective motoric cognitive risk (MCR) syndrome., Design: Longitudinal cohort study., Setting and Participants: 2,279 participants in the Taiwan Longitudinal Study on Aging (TLSA) between 1999 and 2011., Method: A group-based multi-trajectory modeling (GBMTM) was implemented to identify distinct trajectory subtypes within various social support domains, encompassing social networks, emotional support, instrumental support, as well as working and economic status. Logistic regression models were then utilized to evaluate the associations between these trajectory subtypes and the risk of subjective MCR., Results: Among 2,279 participants, GBMTM identified four distinct trajectory subtypes: "low social support" (n = 371), "medium social support " (n = 862), "high social support" (n = 292), and "high social support with employment" (n = 754). The incidence rates of subjective MCR for these groups were 9.4%, 9.0%, 4.1%, and 0.8%, respectively. After adjusting for age, sex, education level, and comorbidities, both "low social support" (adjusted odds ratio (aOR) 4.07, 95% CI [1.60-10.34]) and "medium social support" (aOR 3.10, 95% CI [1.26-7.66]) were significantly associated with an increased risk of subjective MCR compared to the "high social support with employment" group., Conclusions and Implications: The current study demonstrates that social support significantly reduces the risk of subjective MCR, with lower support levels correlating to higher risk, necessitating further intervention studies to confirm the link between social support and risk of subjective MCR., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study was undertaken to examine the association between different patterns of antiseizure medication (ASM) use during pregnancy and adverse obstetric outcomes (preterm birth, low birth weight [LBW], and small for gestational age [SGA])., Methods: This retrospective cohort study used the Birth Certificate Application and National Health Insurance data in Taiwan (January 1, 2004 through December 31, 2018). We retrieved weekly ASM among pregnant women with epilepsy who were prepregnancy chronic users and used group-based trajectory modeling to identify distinct patterns of use. Logistic regressions were adopted to examine the association between patterns of ASM use and risk of preterm birth, LBW, and SGA. In addition, we revealed postnatal ASM utilization pattern among these prepregnancy chronic users as an exploratory study., Results: Of 2175 pregnant women with epilepsy, we identified four patterns of ASM use during pregnancy: frequent and continuous (64.87%), frequent but discontinuous (7.08%), intermittent (19.72%), and intermittent and discontinuous users (8.32%). Compared to frequent and continuous users, the adjusted odds ratios for preterm birth in frequent but discontinuous, intermittent, and intermittent and discontinuous users were .83 (95% confidence interval [CI] = .47-1.48), .71 (95% CI = .47-1.05), and .88 (95% CI = .52-1.49), respectively. Similar results were observed for LBW and SGA. In the exploratory study, we found that most of our study subjects maintained the same patterns before and after delivery., Significance: After considering duration and timing of exposure, our study did not find an association between four distinct patterns of ASM use and adverse obstetric outcomes among women with epilepsy. The findings suggested that optimal seizure control could be received for pregnant women with epilepsy after evaluating the risks and benefits., (© 2024 International League Against Epilepsy.)

Background: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations., Methods: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process., Findings: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons., Interpretation: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making., Funding: National Science and Technology Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Drug-induced liver injury (DILI) is a frequent adverse drug reaction. The current clinical diagnostic methods are inadequate for accurate and early detection of DILI due to the lack of effective diagnostic biomarkers. Hepatocyte-specific miR-122 is released from injured hepatocytes promptly and its efflux is significantly correlated with the progression of DILI. Therefore, achieving precise in situ detection of miR-122 with high sensitivity is vital for early visualization of DILI. Herein, a new nanoprobe, consisting of miR-122 aptamer, upconversion nanoparticles (UCNPs) and Prussian blue nanoparticles (PBNPs) was introduced for the early and sensitive detection of DILI in situ. As the nanoprobes reached in the liver, miR-122 aptamer-based entropy-driven strand displacement (ESDR) signal amplification reaction was triggered and luminescence resonance energy transfer (LRET) between UCNPs and PBNPs was responded to achieve the high-fidelity detection of DILI. A negative correlation was observed between the intensity of upconversion luminescence (UCL) and the concentration of miR-122. UCL imaging conducted both in vivo and ex vivo indicated that a reduction in miR-122 concentration led to an increase in UCL intensity, revealing a precise state of DILI. The detection technique demonstrated a positive correlation between signal intensity and severity, offering a more straightforward and intuitive method of visualizing DILI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to use the Social Vulnerability Index (SVI) to encapsulate the complex and multidimensional nature of social determinants and their influence on alcohol intake and mortality in middle-aged and older individuals., Design: Cohort study., Setting and Participants: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with 3945 study participants aged 50 years and older., Methods: The TLSA questionnaire defined SVI (51 items including living conditions, social support, socially oriented activities of daily living, social engagement and leisure, empowerment of life, satisfaction about life, and socioeconomic status) and alcohol intake (behavior as well as type and frequency of alcohol intake). Multivariate Cox proportional hazard models were used to estimate the association between alcohol intake and mortality, stratified by sex and SVI groups., Results: Men with high social vulnerability and high alcohol intake exhibit an elevated mortality risk [adjusted hazard ratio (aHR), 1.51; 95% CI, 1.01-2.24], whereas notably, women in similar social circumstances but with moderate alcohol intake face a quintupled mortality risk (>35 g/wk; aHR, 5.67; 95% CI, 2.37-13.61). The impact of alcohol and social vulnerability on mortality was more pronounced in men younger than 65. Among them, those with high social vulnerability and moderate (35-140 g/wk; aHR, 2.83; 95% CI, 1.50-5.36) to high (>140 g/wk; aHR, 2.24; 95% CI, 1.15-4.35) alcohol intake was associated with an increased risk of mortality., Conclusions and Implications: Various factors throughout the life course of both men and women significantly impact the risk of all-cause mortality due to alcohol intake, underscoring the importance of social vulnerability as a determinant of both alcohol intake behavior and mortality risk., Competing Interests: Disclosures All authors declare no conflict of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between inflammation and covert cerebral small vessel disease (SVD) with regards to sex difference has received limited attention in research. We aim to unravel the intricate associations between inflammation and covert SVD, while also scrutinizing potential sex-based differences in these connections., Methods: Non-stroke/dementia-free study population was from the I-Lan longitudinal Aging Study. Severity and etiology of SVD were assessed by 3T-MRI in each participant. Systemic and vascular inflammatory-status was determined by the circulatory levels of high-sensitivity C-reactive protein (hsCRP) and homocysteine, respectively. Sex-specific multivariate logistic regression to calculate odds ratios (ORs) and interaction models to scrutinize women-to-men ratios of ORs (RORs) were used to evaluate the potential impact of sex on the associations between inflammatory factors and SVD., Results: Overall, 708 participants (62.19 ± 8.51 years; 392 women) were included. Only women had significant associations between homocysteine levels and covert SVD, particularly in arteriosclerosis/lipohyalinosis SVD (ORs[95%CI]: 1.14[1.03-1.27] and 1.15[1.05-1.27] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively). Furthermore, higher circulatory levels of homocysteine were associated with a greater risk of covert SVD in women compared to men, as evidenced by the RORs [95%CI]: 1.14[1.01-1.29] and 1.14[1.02-1.28] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively. No significant associations were found between circulatory hsCRP levels and SVD in either sex., Conclusion: Circulatory homocysteine is associated with covert SVD of arteriosclerosis/lipohyalinosis solely in women. The intricacies underlying the sex-specific effects of homocysteine on SVD at the preclinical stage warrant further investigations, potentially leading to personalized/tailored managements., Trial Registration: Not applicable., (© 2024. The Author(s).)

Objectives: To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis., Methods: A total of 62 patients with early carotid atherosclerosis were randomly divided into a blank group (12 cases, 1 cases dropped-off), a sham-acupuncture group (25 cases, 5 cases dropped-off) and an acupuncture group (25 cases, 3 cases dropped-off). Patients in the acupuncture group received acupuncture treatment, including ①acupuncture：Baihui (GV20), Yintang (GV24 + ), Renying (ST9), Neiguan (PC6), Yanglingquan (GB34)；②moxibustion：Yinqiguiyuan (Zhongwan ［CV12］, Xiawan ［CV10］, Qihai ［CV6］, Guanyuan ［CV4］), Sihua (Geshu ［BL17］, Danshu ［BL19］)；③Intradermal needle：Xinshu (BL15), Danshu (BL19). Patients in the sham acupuncture group received placebo acupuncture, moxibustion, an intradermal needle, and the acupoints were the same as the acupuncture group. The above treatments were performed twice a week for 12 weeks. No intervention was given to the patients in the blank group. Diet and lifestyle education was given to the three groups. The ultrafast pulse wave velocity, including beginning-systolic pulse wave velocity (BS) and end-systolic pulse wave velocity (ES), was observed before treatment and 1, 2, 3 months after treatment in the three groups. The blood lipid level and platelet count (PLT) at each time point were observed. The safety of the treatments was also evaluated., Results: Compared with those before treatment, the BS and ES values of both sides in the acupuncture group decreased at 2 and 3 months after treatment ( P <0.05). Compared with the blank group, the bilateral ES of the acupuncture group were decreased at 2 months after treatment ( P <0.05), and the bilateral BS and ES were decreased at 3 months ( P <0.05). Compared with the sham-acupuncture group, the acupuncture group showed a decrease in left BS and left ES after 3 months of treatment ( P <0.05), and the overall decrease on the left side of the acupuncture group was better than that on the right side. There were no significant differences between three groups in the levels of blood lipid and PLT at each time point. No serious adverse safety events occurred in the three groups during the treatment., Conclusions: Acupuncture and moxibustion therapy can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective.

Purpose: The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy., Methods: This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods., Results: The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16)., Conclusions: In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy., (© 2024 John Wiley & Sons Ltd.)

Background: Sarcopenia and intrinsic capacity (IC) declines pose significant challenges to healthy aging, particularly in the rapidly growing octogenarian population. This study aimed to elucidate the relationship between sarcopenia and declines in IC across multiple cohorts of community-dwelling older adults., Methods: Data from four Taiwanese cohorts were analyzed. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria (algorithm 1: categorized as either having possible sarcopenia or not (robust); algorithm 2: categorized as robust, possible sarcopenia or sarcopenia). IC was operationalized using the World Health Organization's Integrated Care for Older People (ICOPE) framework (step 1 and step 2), encompassing six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being. Multivariable logistic regression models were adopted to assess the association between sarcopenia and IC decline., Results: Among 599 octogenarians (median age 82.2 years, 54.8% male), the prevalence of possible sarcopenia (algorithm 1) was 64.6%. When adopting algorithm 2, the prevalence of possible sarcopenia and sarcopenia was 46,2% and 32.1%, respectively. After adjusting for covariates, participants with possible sarcopenia or sarcopenia (algorithm 2) were more likely to exhibit declines in vitality (ICOPE Step 1: possible sarcopenia aOR 3.65, sarcopenia aOR 4.74; ICOPE Step 2: possible sarcopenia aOR 5.11, sarcopenia aOR 14.77) and cognition (ICOPE Step 1: possible sarcopenia aOR 2.40, sarcopenia aOR 2.12; ICOPE Step 2: possible sarcopenia aOR 2.02, sarcopenia aOR 2.51) compared to robust individuals., Conclusions: This study underscores the robust association between sarcopenia and declines in vitality and cognition among octogenarians, highlighting the importance of sarcopenia screening and management in promoting healthy longevity in this vulnerable population., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The excited-state energy transfer widely exists in mixed-material systems and devices. The modulation of an electric field on the energy transfer in photoluminescence has been demonstrated. However, to date, no studies on the electric-field modulation of the excited-state energy transfer in organic optoelectronic devices have been reported. Herein, we investigate the effect of an electric field on the energy transfer in the poly( N -vinylcarbazole) (PVK) thin films doped with iridium(iii)[bis(4,6-difluorophenyl)pyridinato-N,C 2' ]-tetrakis(1-pyrazolyl)borate (Fir6) and 5,6,11,12-tetraphenylnaphthacene (rubrene) (PVK:Fir6:rubrene) and the corresponding light-emitting diodes. Combined with the Onsager model describing electric-field enhanced exciton dissociation, we find that the electric field increases the rate of Dexter energy transfer from Fir6 to rubrene in the films and the diodes. The voltage-dependent color shift in the PVK:Fir6:rubrene light-emitting diodes can be explained by the electric-field enhanced Dexter energy transfer from Fir6 to rubrene. Our findings are important for the control of energy transfer process in organic optoelectronic devices by an electric field for desirable applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Importance: Benzodiazepine use during pregnancy has raised significant concerns due to the potential harmful effects of this drug class on neonates. Studies on the association between benzodiazepine use and the risk of miscarriage are limited., Objective: To quantify the risk of miscarriage associated with benzodiazepine use during pregnancy after controlling for unmeasured confounders and exposure time trends., Design, Setting, and Participants: This was a nationwide, population-based case-time-control study using Taiwan's National Birth Certificate Application database and the National Health Insurance database. Pregnancies resulting in miscarriage between 2004 and 2018 were included in the case group and were 1:1 matched with exposure time-trend control individuals using disease risk score, considering demographic characteristics and prepregnancy comorbidities. Data were analyzed from August 2022 to March 2023., Exposures: Discordant exposures to benzodiazepines during risk period (1-28 days before miscarriage) and 2 reference periods (31-58 days and 181-208 days before the last menstrual period) were compared for each pregnancy., Main Outcomes and Measures: Miscarriage was defined as any pregnancy loss occurring between the first prenatal care visit (usually 8 weeks) and the 19th completed week of pregnancy., Results: This study comprised a total of 3 067 122 pregnancies among 1 957 601 women, 136 134 of which (4.4%) resulted in miscarriage. The mean (SD) age of the study population was 30.61 (5.91) years. The use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage (odds ratio [OR], 1.69; 95% CI, 1.52-1.87), and consistent findings were observed across multiple sensitivity analyses considering different time windows and accounting for misclassification. In subgroup analyses, an increased risk of miscarriage was associated with each commonly used individual benzodiazepine, ranging from case-time-control ORs of 1.39 (95% CI, 1.17-1.66) for alprazolam to 2.52 (95% CI, 1.89-3.36) for fludiazepam., Conclusions and Relevance: This nationwide case-time-control study revealed an increased risk of miscarriage associated with benzodiazepine use during pregnancy after accounting for measurable confounders, and results were unlikely to be due to unmeasured confounding. These findings underscore the necessity for health care professionals to meticulously balance the risk-benefit ratio when considering the use of benzodiazepines to treat psychiatric and sleep disorders during pregnancy.

Importance: Intrinsic capacity (IC), defined by the World Health Organization's Integrated Care for Older People (ICOPE) framework, is crucial for promoting healthy aging. Understanding the associations between IC impairments and age-related biomarkers can provide insights into the underlying pathophysiological mechanisms and potential interventions., Objective: To investigate the associations between IC impairments (ICOPE step 1 and step 2, respectively) and aging-related biomarkers, including inflammatory and cardiometabolic markers, in community-dwelling middle-aged and older adults., Design, Setting, and Participants: Cross-sectional analysis of data from 755 participants (aged 50-64 years, n=212; 65-74 years, n=357; ≥75 years, n=186) enrolled in the Gan-Dau Healthy Longevity Plan, a community-based survey in Taipei City, Taiwan, from 2022., Exposures: IC impairments assessed by ICOPE Step 1 (screening) and Step 2 (in-depth assessment) across six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being., Main Outcomes and Measures: Levels of inflammatory biomarkers (albumin, white blood cell count, neutrophils, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio [NLR], lymphocyte-to-monocyte ratio [LMR], platelet-to-lymphocyte ratio [PLR]) and cardiometabolic biomarkers (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, fasting glucose, triglycerides, triglyceride-glucose [TyG] index)., Results: Of the 755 participants, the mean age was 68.5 years, and 68.2% were women. The proportion of participants with any IC impairment increased with age: 63.2% for those aged 50-64, 65.8% for those aged 65-74, and 74.7% for those aged ≥75 years based on ICOPE Step 1. For ICOPE Step 2, the proportions were 59.9%, 56.9%, and 64.0%, respectively. Impairments in locomotion and cognition were significantly higher in the oldest age group (≥75 years). Adjusted for covariates, IC impairment (ICOPE Step 2) was associated with higher levels of neutrophil count (β = 3.17, p = 0.015) and NLR (β = 0.34, p = 0.021) in those aged 50-64 years, and higher levels of monocyte count in those aged 65-74 years (β = 0.65, p = 0.001) and ≥75 years (β = 0.68, p = 0.037)., Conclusions and Relevance: In conclusion, IC impairments were associated with alterations in specific inflammatory biomarkers, suggesting potential interactions between IC, age, and inflammatory processes. Longitudinal studies are warranted to establish causal relationships and elucidate the underlying mechanisms linking IC impairments, immune dysregulation, and the aging process., Competing Interests: The authors declare no conflicts of interest.

Background: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan., Methods: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection., Results: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes., Conclusion: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects., (© 2024 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Polypharmacy and potentially inappropriate medications (PIM) are widely recognized as vital quality indicators of pharmacotherapy in older adults. As Taiwan and Japan grapple with the ongoing challenges of population aging, obtaining an accurate understanding of the prevalence of these indicators is crucial for developing effective strategies to optimize pharmacotherapy in older populations. The present study aims to comprehensively evaluate the prevalence of polypharmacy and PIMs in Taiwan and two Japanese cohorts, shedding light on the similarities and differences in prescribing practices across these populations., Methods: This study employed a cross-sectional design to investigate individuals aged ≥65 years in Taiwan, as well as two Japanese cohorts: Japan Cohort 1 (dispensing data from chain pharmacies; year 2014 and 2019) and Japan Cohort 2 (claims data; year 2017 and 2019). The prescription records of these participants were collected from the national claims database in Taiwan for the years 2014, 2017, and 2019. To identify polypharmacy and hyper-polypharmacy, the study defined the use of 5-9 and 10+ drugs, respectively. Furthermore, the study identified PIMs based on the STOPP-J criteria. Notably, the study further explored the most frequently used PIMs (by categories) in Taiwan., Results: In the year 2019, the prevalence of polypharmacy exhibited similar rates in Taiwan (35.4%) and Japan Cohort 2 (33.1%), while surpassing that of Japan Cohort 1 (25.6%). Nonetheless, the incidence of PIMs in Taiwan was the highest (66.5%), exceeding those of the two Japanese cohorts (Cohort 1: 43.7% and Cohort 2: 40.2%) in the same year. Notably, the top three categories of commonly used PIMs in Taiwan comprised non-steroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, and benzodiazepines., Conclusions: This study highlights the varying prevalence of polypharmacy and PIMs between Taiwan and Japan, but emphasizes the need for collaborative efforts towards optimizing pharmacotherapy in older adults., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

The existence of intrinsic capacity (IC) subtypes and their distinct impacts on age-related outcomes remain unexplored. This study sought to investigate IC impairment trajectories across domains and their associations with the risk of age-related outcomes, including falls, functional limitations, reduced quality of life (QoL) and mortality at 4- and 8-year follow-ups. The study sample comprised 1,782 older adults residing in the community from the Taiwan Longitudinal Study on Ageing (TLSA). Utilizing group-based multitrajectory modeling, distinct subtypes of IC decline trajectories across various domains were identified. Cox proportional hazard models and multivariable logistic regression analyses were employed to assess the associations between the identified subtypes and age-related outcomes. We identified four subtypes of IC decline: robust with mild decline (n=902), hearing loss with cognitive decline (n=197), physio-cognitive decline (PCD) with depression (n=373), and severe IC decline (n=310). Over the 4-year study period, compared to the robust with mild decline group, hearing loss with cognitive decline group exhibited a significantly higher risk of diminished QoL (OR=2.53 [1.66-3.86], p<0.01), whereas those in the PCD with depression group experienced an elevated risk of falls (OR=1.62 [1.18-2.23], p<0.01), as well as functional limitation (OR=2.61 [1.81-3.75], p<.01). Individuals in the severe IC decline group faced a substantially increased risk of all outcomes of interest. Distinct subtypes of IC decline across different domains have varying impacts on age-related outcomes, highlighting the need for a personalized approach to promote healthy ageing at the population level, while further investigation into specific pathophysiological mechanisms is warranted as well.

The development of energy storage technology is beneficial for the efficient use of energy and sustainable development. As an effectual approach for storing and transporting thermal energy, latent heat storage using phase change materials (PCMs) has attracted tremendous attention. However, low thermal conductivity, poor stability, and leakages are considerable challenges to the widespread application of solid-liquid PCMs. Composite phase change materials (CPCMs) were prepared by combining expanded graphite (EG) and sodium acetate trihydrate (CH 3 COONa·3H 2 O, SAT). EG as a supporting material plays a crucial part in both enhancing the thermal conductivity and preventing the melted PCMs from leakage. The chemical structure, micromorphology, thermal stability, thermal conductivity, phase change behavior and heat storage performance of SAT/EG CPCMs have been extensively investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal conductivity analysis, differential scanning calorimetry (DSC), and cycling stability measurement. The results of SEM indicate that EG with a loose and porous layered structure has a good molding effect and can adsorb SAT well. XRD and FTIR results show that only a simple physical combination between EG and SAT exists, and no new substances have been produced. Compared with pure SAT, thermal conductivity and supercooling tests show that the supercooling degree of the CPCMs was decreased and the thermal conductivity was increased by 205.1%. In addition, the addition of 2 wt% of disodium hydrogen phosphate dodecahydrate (Na 2 HPO 4 ·12H 2 O, DHPD) as a nucleating agent and 0.5 wt% of gelatin as a thickening agent to SAT could reduce the supercooling degree and inhibit the phase separation well. Based on SAT/EG-8% CPCMs, an oven with phase change energy storage was designed and the heat storage/release performance of the oven was investigated under different operating conditions.

This study aims to investigate the pathogenesis of chronic heart failure based on ferroptosis-mediated oxidative stress and predict the targets of Shenfu Injection in treating chronic heart failure. A rat model of chronic heart failure was established by the isoproterenol induction method. According to the random number table method, the modeled rats were assigned into three groups: a model group, a Shenfu Injection group, and a ferrostatin-1(ferroptosis inhibitor) group. In addition, a normal group was designed. After 15 days of intervention, the cardiac mass index and left ventricular mass index were determined. Echocardiography was employed to eva-luate the cardiac function. Hematoxylin-eosin staining and Masson staining were employed to reveal the pathological changes and fibrosis of the heart, and Prussian blue staining to detect the aggregation of iron ions in the myocardial tissue. Transmission electron microscopy was employed to observe the mitochondrion ultrastructure in the myocardial tissue. Colorimetry was adopted to measure the levels of iron metabolism, lipid peroxidation, and antioxidant indicators. Flow cytometry was employed to measure the content of lipid-reactive oxygen species(ROS) and the fluorescence intensity of ROS. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of ferroptosis-related factors in the myocardial tissue. The results showed that the rats in the model group had reduced cardiac function, elevated levels of total iron and Fe~(2+), lowered level of glutathione(GSH), increased malondialdehyde(MDA), decreased superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px), and rising levels of ROS and lipid-ROS. In addition, the model group showed fibrous tissue hyperplasia with inflammatory cell infiltration and myocardial fibrosis, iron ion aggregation, and characteristic mitochondrial changes specific for iron death. Moreover, the model group showcased upregulated protein and mRNA levels of p53 and COX2 and downregulated protein and mRNA levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. The intervention with Shenfu Injection significantly improved the cardiac function, recovered the iron metabolism, lipid peroxidation, and antioxidant indicators, decreased iron deposition, improved mitochondrial structure and function, and alleviated inflammatory cell infiltration and fibrosis. Furthermore, Shenfu Injection downregulated the mRNA and protein levels of p53 and COX2 and upregulated the mRNA and protein levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. Shenfu Injection can improve the cardiac function by regulating iron metabolism, inhibiting ferroptosis, and reducing oxidative stress injury.

Background: Benzodiazepines and Z-hypnotics are commonly prescribed for anxiety and insomnia during pregnancy, but the evidence regarding potential adverse neonatal outcomes is insufficient because of poor control for confounding factors in previous studies. We therefore aimed to evaluate the association between the use of benzodiazepines or Z-hypnotics during early pregnancy and adverse neonatal outcomes (stillbirth, preterm birth, and small for gestational age)., Methods: We did a nationwide, population-based cohort study in Taiwan using three data sources: Taiwan's National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database. The study cohort included all singleton pregnancies of females aged 15-50 years who gave birth between Jan 1, 2004, and Dec 31, 2018. Pregnancies without valid information were excluded. Benzodiazepine and Z-hypnotic use was defined as at least one benzodiazepine or Z-hypnotic prescription during early pregnancy (the first 20 weeks of pregnancy). The primary outcomes were stillbirth (fetal death at or after 20 weeks' gestation), preterm birth (<37 weeks' gestation), and small for gestational age (birthweight below the 10th percentile for gestational age by sex). Logistic regression models with propensity score fine stratification weighting were used to control for potential confounders and examine the association between benzodiazepines or Z-hypnotics use during early pregnancy and the risk of adverse neonatal outcomes. Odds ratios (ORs) and 95% CIs were reported. We used confounding by indication control analyses, a sibling control study, and a paternal negative control design to account for unmeasured confounders. The risk associated with exposure during late pregnancy was also assessed., Findings: Between Oct 7, 2021, and June 10, 2022, we analysed the study data. The cohort included 2 882 292 singleton pregnancies; of which, 75 655 (2·6%) of the mothers were dispensed one or more benzodiazepines or Z-hypnotics during early pregnancy. Women exposed during pregnancy were older (mean age at delivery was 31·0 years [SD 5·3] for exposed women vs 30·6 years [4·9] for unexposed women), had a higher prevalence of psychiatric disorders, and were more likely to have unhealthy lifestyle behaviours than unexposed women. Information about ethnicity was not available. Early pregnancy exposure was associated with adverse neonatal outcomes compared with non-exposure. The propensity score-weighted OR was 1·19 (95% CI 1·10-1·28) for stillbirth, 1·19 (1·16-1·23) for preterm birth, and 1·16 (1·13-1·19) for small for gestational age. After controlling for confounding by indication, there was no significant association between drug exposure and stillbirth risk; however, this attenuation was not observed for preterm birth and small for gestational age. In models with sibling controls that accounted for familial confounding and genetic factors, early exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of stillbirth and preterm birth, but it remained significantly associated with small for gestational age. The paternal negative control analyses with point estimates close to the null indicated no strong evidence of unmeasured confounding shared by the mother and the father. Substantially increased risks of stillbirth and preterm birth were observed for late pregnancy exposure., Interpretation: Benzodiazepine or Z-hypnotic use in early pregnancy is not associated with a substantial increase in the risk of stillbirth and preterm birth after accounting for unmeasured confounding factors. Clinicians should be aware of the increased risk of small for gestational age and caution should be taken when prescribing these medications during late pregnancy., Funding: National Science and Technology Council, Taiwan., Translation: For the Taiwanese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose of the Research: The success of modern health care increases life expectancy and prolongs the days of having multimorbidity and functional limitations; the so-defined "high need, high cost (HNHC)" state represents the extreme scenarios of care burden and complexity. This study aims to explore health care utilization and the risk of preventable adverse outcomes stratified by age and HNHC state., Materials and Methods: We conducted a retrospective cohort study using the National Health Insurance (NHI) database. People aged ≥40 years were included and further stratified by age (middle-aged: 40-64 and older adults: 65) and HNHC state (top 10% of spending). Health care utilization and drug consumption across different groups were obtained. The multimorbidity frailty index (mFI) was developed for further analysis. Cox regression models were used to examine the associations between HNHC and adverse clinical outcomes (preventable hospitalizations, preventable emergency department visits, and mortality)., Results: HNHC participants were older, had a higher mFI and drug consumption, and had higher health care utilization. Compared with non-HNHC participants, HNHC participants exhibited a 4.4-fold and 2.4-fold higher risk of preventable hospitalizations in middle-aged (HR=4.41; 95% CI, 4.17-4.65, p<0.01) and older adults (HR=2.44; 95% CI, 2.34-2.55, p<0.01). Similar risks were observed for preventable emergency department visits and mortality (all p<0.01)., Conclusions: The HNHC state substantially increased health care utilization, polypharmacy, and potentially preventable adverse outcomes after adjustment for frailty. Intervention studies developing integrated care models using the life-course approach are needed to improve the quality of health care systems in super-aged societies., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: The early growth response 2 gene (EGR2) mutations are associated with a group of hereditary neuropathy, including axonal neuropathy and hypomyelinating neuropathy or Charcot-Marie-Tooth disease (CMT) type 1D. We aim to perform an electrodiagnostic, nerve imaging, and histological study of EGR2-associated neuropathy., Materials and Methods: We performed a retrospective analysis of two patients with EGR2-related neurology at our hospital. The neuropathy was confirmed by the nerve conduction study. Nerve imaging and sural biopsies were performed in two patients., Results: Two unrelated boys exhibited early-onset length-dependent neuropathy. Next generation sequencing identified EGR2 gene with previously described E412K mutation in the third zine finger domain in patient 1 and a previously undescribed variant D355N mutation in the first zinc finger domain in patient 2. The magnetic resonance imaging of the lumbosacral plexus showed no abnormalities in patient 1 and thickened lumbosacral plexuses in patient 2. Electrophysiology and nerve biopsies showed a prominent axonal neuropathy, accompanied with demyelinating involvement., Conclusion: Therefore, it seemed that the EGR2 mutations could cause not only the known demyelinating type and axonal type but also mixed-type CMT. Our findings expanded the phenotypic heterogeneities of EGR2-associated neuropathy.

Non-alcoholic fatty liver disease (NAFLD) has high occurrence in the global world, which poses serious threats to human health. Salvianolic acid B (SalB), an extract of the root of Salvia miltiorrhiza, has the protective effect on metabolic homeostasis. However, the mechanism is still unknown. In this study, we used ob/ob mice, a model of NAFLD, to explore the hepatoprotective effects of SalB. The results showed that SalB significantly reduced the body weights and liver weights, and ameliorated plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), hepatic free fatty acid (FFA), total cholesterol (TC) levels, and hepatic TG and TC levels in ob/ob mice. SalB reduced the number of lipid droplets and inhibited hepatic lipogenesis by regulating peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), stearoyl-Co A desaturase 1 (SCD1), and cluster of differentiation 36 (CD36). Compared to ob/ob mice, the lower expressions of the pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and F4/80, were observed after SalB treatment. Importantly, SalB treatment inhibited the activation of NLRP3 inflammasome and reduced the severity of liver inflammation. Our findings suggested that SalB improved NAFLD pathology in ob/ob mice by reducing hepatic lipid accumulation and NLRP3 inflammasome activation, which might be the potential hepatoprotective mechanism of SalB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has had strong adverse impacts on vulnerable populations, such as frail older adults. The success of COVID-19 vaccine development, together with extensive global public health efforts, has brought hope to the control of the COVID-19 pandemic. Nevertheless, challenges in COVID-19 vaccine development and vaccination strategies among older people remain. This article reviews vaccinations in older adults, compares COVID-19 vaccine platforms, the efficacy and safety of COVID-19 vaccines in frail older people in long-term care settings, and the challenges of COVID-19 vaccine development and policy making for vaccination strategies in older adults., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Frailty has been linked to an increased risk of adverse outcomes among older men with prostate cancer (PCa), which in turn impacts survival. We evaluated the associations between frailty and risks of all-cause mortality and cancer-specific mortality in PCa patients treated with radiotherapy (RT)., Methods: We conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. Patients aged ≥65 years with newly-diagnosed PCa, and receiving RT as initial treatment between 2011 and 2015 were identified in the study. Frailty was measured using the multimorbidity frailty index (mFI), categorized as fit, mild frailty, moderate frailty, and severe frailty. Cox regression models were used to examine the association between frailty and mortality., Results: Among 4,291 men with a median age of 75 years at PCa diagnosis, 21.87% were categorized as fit, 44.72% were mild frailty, 23.02% were moderate frailty, and 10.42% were severe frailty. With the mean follow-up duration of 4.8 years, patients in the severe frailty group had a significantly higher all-cause mortality risk (HR 1.86; 95% CI, 1.48-2.32) and cancer-specific mortality risk (HR 1.44; 95% CI, 1.05-1.98) than patients in the fit group, whereas no such association was found in the mild frailty group after adjustment., Conclusions: This is the first population-based cohort study to evaluate the feasibility of mFI on mortality of PCa patients treated with RT. We found that severe frailty was associated with a higher risk of both all-cause mortality and cancer-specific mortality., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: This study aims to develop and validate an integrative intrinsic capacity (IC) scoring system, to investigate its associations with a wide spectrum of biomarkers and to explore the predictive value of the integrative IC score on 4-year mortality among community dwelling people aged 50 years and older., Methods: We included 839 adults aged ≥50 years from the Social Environment and Biomarkers of Aging Study (SEBAS) and randomly divided them into derivation and validation cohorts to develop the IC scoring system. The multivariate logistic regression model was used to weight each subdomain (locomotion, sensory, vitality, psychological, and cognition) of IC according to its association with impairments in instrumental activities of daily living (IADL) and to construct the integrative IC score. Age-related biomarkers and genetic markers were compared between IC groups by ordinal logistic regression. A Cox proportional hazard model was used to examine the association between IC and mortality, and subgroup analysis was used to assess the robustness of the results among participants aged 60 years and older., Results: A 12-score IC scoring system (AUROC = 0.83; Hosmer-Lemeshow goodness-of-fit test p = 0.17) was developed, and higher scores indicated better intrinsic capacity. High interleukin (IL)-6, high E-selectin, low serum albumin and low folate were significantly associated with low IC in the whole sample. However, high IL-6, low serum albumin, low folate, high allostatic load, and APOE ε4 genotype were significantly associated with low IC in those aged 60 years old and older. Compared to the high IC group, the low IC group was significantly associated with all-cause mortality (HR: 2.50, 95% CI: 1.22-5.11, p = 0.01 for all participants; HR 2.19, 95% CI 1.03-4.64, p = 0.04 for participants aged 60 years and older)., Conclusions: The conceptually proposed IC can be easily transformed into a scoring system considering different weights of individual subdomains, which not only predicts mortality but also suggests different pathophysiologies across the life course of aging (inflammation, nutrition, stress, and ApoE4 genotype). An intervention study is needed using the composite IC score to promote healthy aging and determine the underlying pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors L-KC and L-NP., (Copyright © 2022 Meng, Huang, Peng, Chen and Hsiao.)

Objectives: To explore how age and sex affect the impacts of self-rated health, self-reported physical activities, physical function, and depressive symptoms on long-term mortality among community-dwelling middle-aged and older adults using a nationally representative population-based cohort study., Methods: Data from 1550 study participants from the Social Environment and Biomarkers of Aging Study (SEBAS) were retrieved for analysis, and all participants were divided into four groups based on their age and gender. Middle aged participants were aged 53 to 64 years, and elderly subjects were ≥ 65 years old. Multivariate logistic regression models were applied to investigate the associations between age, sex, and self-reported disabilities of physical activities, physical function (activities of daily living (ADL) and instrumental activities of daily living (IADL) and depression., Results: Although the self-reported health status was similar across different age- and sex-stratified subgroups, older women were at the highest risk in self-reported difficulty with physical activities (aOR 2.58 [1.55-4.28]) and difficulty with IADL (aOR 3.32 [2.20-5.03]) compared to men. After adjusting for living arrangement, residence locale, education levels, occupation, socioeconomic status, self-reported health, multimorbidity, impairments in daily activities, and depressive symptoms, older men were found to display the highest risk of mortality (aHR 2.06 [95% CI 1.45-2.93])., Conclusions: Although self-reported health was similar across different age and sex stratified subgroups, women (particularly older women) are significantly more likely to have worse physical and functional health than men. After adjusting for all confounding factors, men are at substantially greater risk for mortality despite reporting better health and functional performance., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study., Design: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020., Setting and Participants: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach., Methods: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models., Results: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p&lt;0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p&lt;0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p&lt;0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p&lt;0.01) remained at higher odds for EPP and PIMs after adjustment., Conclusions: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility., Competing Interests: All authors declare no conflicts of interest.

Background: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants., Case Presentation: A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A)., Conclusions: In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT., (© 2021. The Author(s).)

Preferential removal of phosphate from aqueous was conducted by a novel biomass-based nanocomposite (EP-N + -Zr) with encapsulated hydrous zirconium oxide, and the biopolymer EP-N + -Zr features were described. EP-N + -Zr exhibited high selective sequestration toward phosphate when humic acid or other competing anions (Cl - , SO 4 2- , NO 3 - , ClO 4 - ) coexisted at relatively high levels. Such excellent performance of EP-N + -Zr was attributed to its specific two site structures; the embedded HZO nanoparticles and quaternary ammonia groups [N + (CH 2 CH 3 ) 3 Cl - ] bonded inside the biomass-Enteromorpha prolifera, which facilitated preferable capture towards phosphate through specific affinity and nonspecific preconcentration of phosphate ions on the basis of the ion exchange, respectively. The maximum adsorption capacity of phosphate (20 °C) as calculated by Langmuir model was 88.5 mg(P)/g. Regeneration tests showed that EP-N + -Zr could be recycled at least five times without noticeable capacity losses using binary NaOH-NaCl as eluent., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Chymosin is widely used in the dairy industry, and much is produced through recombinant DNA in organisms such as bacteria and tobacco. In this study, we used a new transgenic method to express caprine chymosin in corn seeds with lower cost and better storage capability. The recombinant chymosin protein was successfully expressed at an average level of 0.37 mg/g dry weight, which is 0.27% of the total soluble protein in the corn seed. Prochymosin can be activated to produce a chymosin protein with the ability to induce clotting in milk, similar to the commercial protein. The activity of the purified recombinant chymosin was as high as 178.5 U/mg. These results indicate that we have successfully established a technology for generating corn seed-derived caprine chymosin for potential use in the dairy industry., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To report the clinical and myopathological features of 16 patients with Jo-1 syndrome., Methods: Sixteen patients were recruited in this study, who were diagnosed as Jo-1 syndrome in Department of Neurology of Peking University First Hospital from January, 2011 to July, 2015. The clinical data and myopathological data were analyzed., Results: The mean onset age was 41±14 (21-68) years old. 87.5% was female. The median duration was 9.5 months (1-192 months). The main clinical manifestations were weakness in 13 cases (81.2%), arthritis in 10 cases (62.5%), interstitial lung diseases in 8 cases (50%), dermatomyositis-like skin lesions in 5 cases (31.2%), fever in 3 cases (18.8%), Raynaud's phenomenon in 2 cases (12.5%) and mechanic's hands in 2 cases (12.5%). There were 3 cases with other connective tissue diseases and 1 case with non-Hodgkin's lymphoma. Mean serum CK was 3 054±2 058(470-5 222) U/L. All patients had anti-Jo-1antibody, combined with anti- Mi-2 antibody in 1 case, anti-Ro-52 antibody in 5 cases, and anti-nuclear antibody in 5 cases. 4/5 cases showed myopathic changes for electromyography (EMG) tests. Myopathological changes included edema, fragmentation and inflammatory infiltration in perimysium in 14 cases (87.5%), muscle atrophy in 13 cases including 7 cases(43.8%) predominantly in perifascicular field. Muscle fiber necrosis appeared in 8 cases with predominantly in perifascicular area in 4 cases (25%). Muscle fiber regeneration occurred in 11 cases with predominantly in perifascicular field in 5 cases (31.2%). CD8 positive T-lymphocytes, CD20 positive B-lymphocytes and CD68 positive macrophages infiltrated in various degrees, most of which were located in perimysium. MHC-Ⅰ were expressed on muscle fiber membranes in different degrees, including 7 cases (43.8%) predominantly in the cytoplasm of perifascicular muscle fibers. C5b-9 deposited in perifascicular muscle fiber membranes in 7 cases (43.8%) and perifascicular capillaries in 2 cases (12.5%)., Conclusions: The main manifestations of this group of Jo-1 syndrome are weakness, arthritis and interstitial lung diseases, and dermatomyositis-like skin lesions, fever, Raynaud's phenomenon, and mechanic's hands can also be seen. Edema, fragmentation and inflammatory infiltration in perimysium are common. Pathological changes in perifascicular fields appear in some cases.

Background: Congenital or acquired abnormalities may result in ureteral malformation, trauma, or defect. Traditional reconstructive methods are often associated with numerous complications. Tissue engineering technology may provide an alternate avenue for ureteral reconstruction. In this study, we constructed tissue-engineered tubularized grafts (TETGs) by seeding homologous adipose-derived stem cells (ADSCs) and bladder smooth muscle cells (SMCs) into bladder submucosa matrix (BSM) for ureteral reconstruction in rabbit models., Methods: ADSCs and bladder SMCs were seeded onto 2 sides of the BSM, respectively. Then the grafts were used to construct TETGs of 4.0 cm length and 8.0 mm diameter and were transplanted into the omentum of rabbits for 2 weeks before ureteral reconstruction. The 4.0-cm segment of the ureter was replaced by the TETG. Evolutionary formation of tissue structures and degree of epithelization were evaluated with the use of histologic and immunohistochemical techniques at 2, 4, 8, and 16 weeks after implantation., Results: All of the rabbits were alive until they were killed. Histologic and immunohistochemical analyses showed consistent regeneration of mature and functional urothelium. At 16 weeks after TETG implantation, multilayered urothelium covered the entire lumen, with visible neovascularization in the center and formation of organized smooth muscle bundles., Conclusions: We successfully constructed a tissue-engineered transplanted graft by seeding ADSCs and SMCs onto the BSM for ureteral repair and reconstruction in a rabbit model., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis., Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed., Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2., Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

Objectives: To acquire a thermostable xylanase, that is suitable for xylooligosaccharide production from pretreated corncobs, the metagenomic method was used to obtain the gene from an uncultured environmental microorganism., Results: A thermostable xylanase-encoding gene (xyn10CD18) was cloned directly from the metagenomic DNA of cow dung compost. When xyn10CD18 was expressed in Bacillus megaterium MS941, extracellular xylansae activity at 106 IU/ml was achieved. The purified recombinant Xyn10CD18 was optimally active at pH 7 and 75 °C as measured over 10 min. It retained over 55% of its initial activity at 70 °C and pH 7 after 24 h. Its action on birchwood xylan for 18 h liberated xylooligosaccharides with 2°-4° of polymerization, with xylobiose and xylotetraose as the main products. When pretreated corncobs were hydrolyzed by Xyn10CD18 for 18 h, the xylooligosaccharides (DP 2-4) products increased to 80% and the xylose was just increased by 3%., Conclusion: Xyn10CD18 is a thermostable endoxylanase and is a promising candidate for biomass conversion and xylooligosaccharide production.

Background: Few studies have compared the surgical outcomes of vertebroplasty (VP) and kyphoplasty (KP) in the treatment of osteoporotic vertebral compression fractures (VCFs) with intravertebral clefts., Methods: A retrospective study was conducted to review patients with a single-level osteoporotic VCF treated by VP or KP. Intravertebral clefts were assessed by preoperative computed tomography (CT) and magnetic resonance scans. All enrolled patients were followed up for 12 months. Clinical outcomes, radiological findings and complications were evaluated., Results: A total of 53 patients were available for data analysis. Most of the fractures (75.5 %) occurred in the region of the thoracolumbar junction (T10-L2). Twenty-four patients received VP and 29 patients received KP. Patients in both group had significant pain relief after surgery (P < 0.01). Compared with VP group, there was a significant lower visual analogue scale (VAS) score in KP group at the 6- (P = 0.04) and 12-month follow-up (P = 0.02), but the decreased values of VAS score had no significant correlation with the magnitude of deformity correction. Restoration of vertebral body height and reduction in kyphotic angle were achieved in both groups, and the magnitude of correction was more significant in KP group (P < 0.01). Cement leakage rate in VP group (66.7 %) was higher than that in KP group (20.7 %), and there was a significant difference (P < 0.01)., Conclusions: Intravertebral clefts occur primarily at the thoracolumbar junction and can be detected easily by CT and magnetic resonance imaging scans. Both VP and KP are effective in the treatment of clefts, but patients in KP group tend to have a better pain relief at the medium and long-term follow-up. However, the better pain relief effect of KP cannot be attributed to the higher magnitude of deformity correction.

High levels of extracellular xylanase activity (211.79 IU/mg) produced by Paenibacillus sp. NF1 were detected when it was submerged-cultured. After three consecutive purification steps using Octyl-Sepharose, Sephadex G75, and Q-Sepharose columns, a thermostable xylanase (XynNF) was purified to homogeneity and showed a molecular mass of 37 kDa according to SDS-PAGE. The specific activity of the purified XynNF was up to 3,081.05 IU/mg with a 14.55-fold purification. The activity of XynNF was stimulated by Ca(2+), Ba(2+), DTT, and β-mercaptoethanol, but was inhibited by Fe(3+), Zn(2+), Fe(2+), Cu(2+), SDS, and EDTA. The purified XynNF displayed a greater affinity for oat spelt xylan with the maximal enzymatic activity at 60°C and pH 6.0. XynNF, which was shown to be cellulose-free, with high stability at high temperature (70°C-80°C) and low pH range (pH 4.0-7.0), is potentially valuable for various industrial applications. The end products of high efficient oat spelt xylan hydrolysis by XynNF (an endoxylanase) containing 95.8% xylooligosaccharides of 2-4 degree of polymerization (DP2-4) with the enrichment of xylobiose (61.5%) indicated that XynNF is a promising candidate for xylooligosaccharides production.

Unlabelled: The aim of this retrospective study was to evaluate the effect of shape and severity of osteoporotic vertebral fractures on the clinical and surgical outcomes of kyphoplasty. Ninety-four patients with single level vertebral fractures were enrolled. Fractures were divided into two types according to the shape of the fractured vertebrae: wedge type (n = 54) or biconcave type (n = 40). All fractures were further classified into 3 grades (grade 1-3) according to their severity. The Visual Analog Score for back pain improved significantly in the "wedge" and in the "biconcave" group: there was no significant difference between groups. Wedge type fractures had a significantly greater correction of anterior vertebral height and kyphotic angle than biconcave type fractures (p < 0.01). Biconcave type fractures had a significantly greater correction of the middle vertebral height (p < 0.01), but had a higher risk of intradiscal cement leakage (p = 0.03). Rates of cement leakage in grade 1, grade 2, and grade 3 fractures were 12.8%, 25.8%, and 50.0%, respectively : there was a gradually higher risk of cement leakage as the severity of compression increased (p < 0.01)., Conclusion: assessing the shape and severity of fractured osteoporotic vertebrae gives an idea of the potential correction of body height and kyphosis, and of the risk of cement leakage.

The optimal management approach for patients with mild forms of cervical spondylotic myelopathy (MCSM) has not been well established. The aim of the present study was to investigate the outcome of conservative treatment, identify prognostic factors and provide evidence for the timing of surgical intervention. A total of 90 patients with MCSM attending hospital between February 2007 and January 2009 were prospectively enrolled. Initially, all patients received conservative treatment and were followed up periodically. When a deterioration in myelopathy was clearly identified, surgical treatment was conducted. Clinical and radiological factors correlating with the deterioration were examined, and final clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) score. At the end of January 2012, follow-ups of >3 years were completed. Seventy-eight patients were available for data analysis. Only 21 patients (26.9%) deteriorated and underwent surgery thereafter (group A), while the remaining 57 patients (73.1%) were treated conservatively throughout (group B). Statistical analysis revealed that segmental instability and cervical spinal stenosis were adverse factors for the prognosis of conservative treatment. Although the JOA scores of the patients in group A declined initially, following surgical intervention, no significant differences were identified in JOA scores between the two groups at the time of the final follow-up (P=0.46). In summary, conservative treatment is effective in MCSM patients. Patients with segmental instability and cervical spinal stenosis have a tendency to deteriorate, but conservative treatment remains the recommendation for the first action. If the myelopathy deteriorates during conservative treatment, timely surgical intervention is effective.

Background: For muscle invasive bladder cancer, radical cystectomy is the most effective treatment now and urinary diversion is often necessary. The use of intestinal tissue for urinary diversion is frequently associated with complications. In this study, we aimed to make a tissue-engineered conduit (TEC) using bladder epithelial cells and bladder acellular matrix (BAM) for urinary diversion in rabbits., Methods: Bladder epithelial cells of rabbit were cultivated and expanded in vitro, then seeded on BAM, and cultured for 7 days. Then cell-seeded graft was used to make TEC. In the experimental group, most of bladder of the rabbit was removed while bladder trigone was retained. The proximal end of TEC was anastomosed with bladder trigone and the distal end was anastomosed with the abdominal stoma. In the control group, TEC was made using unseeded BAM. Haematoxylin and eosin staining was conducted, respectively, at 1, 2, 4, and 8 weeks postoperatively. Immunohistochemistry was performed 8 weeks postoperatively. Intravenous urography, retrograde pyelography, and cystoscopy of TEC were made at 12 weeks postoperatively., Results: All animals were alive in the experimental group. Haematoxylin and eosin staining showed epithelial coverage in TEC. Immunohistochemistry showed anti-cytokeratin AE(1)/AE(3) antibody and anti-ZO1 antibody positive, confirming there were mature and functional epithelial cells on the lumen of TEC. Retrograde pyelography and intravenous urography showed that TEC developed well and that there was no obstruction. In the control group, four rabbits were dead within 2 weeks and scar formation, atresia, and severe hydronephrosis were found., Conclusions: We successfully made TEC using BAM and bladder epithelial cells for urinary diversion in rabbits. The lumen of this new TEC covered mature epithelial cells and could prevent urinary extravasation.

Background: Infants and children who undergo surgical repair of complex congenital heart diseases are prone to developing renal dysfunction. The purpose of this study was to investigate the risk factors associated with prolonged peritoneal dialysis (PD) and the mortality of pediatric patients with acute renal failure (ARF) after open heart surgery., Methods: From June 1999 to May 2007, a total of 542 children underwent open heart surgery for congenital heart disease. Fifteen (2.8%) experienced ARF and seven (1.3%) required PD. The clinical and laboratory variables were compared between the survivor and non-survivor groups of ARF patients that needed PD., Results: The non-survivors (n=3, 43%) had a Longer cardiopulmonary bypass time (154+/-21 vs. 111+/-8 minutes, p=0.012) and longer aorta clamping time (92+/-40 vs. 66+/-15 minutes, p=0.010) than the survivors (n=4, 57%). Before the PD, the pH and base excess of the arterial blood gas analysis in the survivors was much higher than that non-survivors (7.30+/-0.04 vs. 7.16+/-0.10, p=0.039; -5.15+/-3.13 vs. -12.07+/-2.9mmol/L, p=0.031). Furthermore, the survivors had a shorter interval between the onset of ARF and the day the PD was begun (1.2+/-0.4 vs. 4.3+/-1.2 days, p=0.001), and shorter duration of PD (6.6+/-2.7 vs. 13.0+/-3.5 days, p=0.036) than non-survivors., Conclusion: Early intervention with PD is a safe and effective method for managing patients with ARF after open heart surgery. The cardiopulmonary bypass and aortic clamping duration, time of initiating PD, duration of the PD, sepsis, and relative complications may predict the prognosis of these patients.

As a hole-blocking layer, 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) is usually used in blue and white light electroluminescent devices. The ability of blocking holes of BCP layer depends on its thickness, and basically holes can tunnel through thin BCP layer. In order to know the role of BCP layer in electroluminescence (EL) of multilayer organic light-emitting diodes (OLEDs), in the present paper, the authors designed a multilayer OLED ITO/NPB/BCP/Alq3 : DCJTB/Alq3/Al and investigated the influence of thickness of BCP on the EL spectra of multilayer OLEDs at different applied voltages. The experimental data show that thin BCP layer can block holes partially and tune the energy transfer between different emissive layers, and in this way, it is easy to obtain white emission, but its EL spectra will change with the applied voltages. The EL spectra of multilayer device will remain relatively stable when BCP layer is thick enough, and the holes can hardly tunnel through when the thickness of BCP layer is more than 15 nm. Furthermore, the stability of EL spectra of the multilayer OLED at different applied voltages was discussed.

Background: Total anomalous pulmonary venous return (TAPVR) is an uncommon congenital cardiovascular anomaly with poor natural prognosis. It has been detected more frequently in recent year due to the advent of echocardiography and cardiovascular magnetic resonance imaging (MRI). The aim of this study was to evaluate the clinical manifestations and outcomes in TAPVR patients with or without pulmonary venous obstruction (PVO)., Methods: From January 1985 to December 2002, a total of 27 cases with TAPVR at our institution were reviewed. Accurding to the preseace or assence of PVO, patients were divided into PVO group and non-PVO group. Patients' sex, age at diagnosis, types of TAPVR, clinical manifestations, surgical treatment and outcomes were evaluated., Results: All of them had received 2-dimensional (2-D) and color Doppler echocardiography examination. Cardiac catheterization was performed in all but 1 patient who died at the first day of birth. In addition, 10 of 27 cases had cardiovascular MRI for further study. The number of cases in PVO group and non-PVO group were 15 (56%) and 12 (44%), respectively. There was no significant difference in sex or pulmonary venous drainage sites between both groups. Cyanosis was more prevalent in the PVO group (80% vs. 30%, p = 0.038). Four (27%) cases PVO group and 3 (25%) cases of the non-PVO group had of the non-isolated cardiac lesions. Pulmonary hypertension was present in 18 (69%) of 26 cases who had received cardiac catheterization. Among them, 10 had PVO and 5 had systemic level of pulmonary arterial pressure. Seven (30%) of 23 patients who had received operation died; in contrast, 3 of 4 patients without operation expired. The remaining 1 did not had surgery because of complex heart disease. There was no significant difference in surgical mortality between PVO and non-PVO groups (33% vs. 27%)., Conclusions: Cyanosis is an obvious clinical symptom of obstructed TAPVR. Surgical mortality made no significant difference between obstructed and non-obstructed groups. Early detection and surgical treatment for TAPVR are important. Although cardiac catheterization and angiocardiography is the golden standard for the diagnosis, 2-D and color Doppler echocardiography can also provide quick and accurate diagnostic images of TAPVR.

A total of 5 Johnson and Johnson stents were implanted in two patients with significant residual peripheral pulmonary arterial stenosis. These were a 15-year-old boy with post-open heart surgery for tetralogy of Fallot and a 3 8/12 year-old boy with D-transposition of great vessels. Immediately after balloon dilatation and implantation of the stents, the diameter of the narrowing pulmonary arteries increased significantly from 6.0 +/- 0.8 mm to 13.5 +/- 1.7 mm (P < 0.001) and the systolic pressure gradients across the stenosis of peripheral pulmonary artery dropped significantly from 33.0 +/- 16.0 mmHg to 10.2 +/- 4.4 mmHg (P < 0.01). One year later, repeated cardiac catheterization was performed on both patients. In the patient with tetralogy of Fallot, a 20 mmHg pressure gradient was found between the main and left pulmonary artery. This patient then received another stent implantation to release the residual stenosis. The boy with D-transposition of great vessels had only 9 mmHg gradient between main and right pulmonary artery. Transcatheter placement of the stent is a feasible and effective method to treat certain patients with significant pulmonary arterial stenosis if surgical correction can not be performed.

13N-ammonia and 18F-fluorodeoxyglucose positron emission tomography (PET) of the heart were performed on 30 children with a history of Kawasaki disease. The results indicated PET abnormalities in 61.1% of patients during the acute and subacute stages and in 41.2% of patients in the convalescent stage of Kawasaki disease. Two-dimensional echocardiography and coronary angiography could not predict the myocardial viability and perfusion as well as PET. Different therapies during the acute stage of the disease did not effectively prevent myocardial damage, despite the absence of coronary arterial abnormalities. The patients who received 400 mg x kg(-1) x day(-1) of intravenous immunoglobulin (IVIG) for 5 days had a significantly lower incidence of PET abnormalities than those who received a single dose of 2000 mg x kg(-1) IVIG (P < 0.05).

Transcatheter closure of an interatrial septal defect (ASD) with a CardioSEAL device was successfully performed on 12 Taiwanese children. There were five boys and seven girls, aged from 3.6-13.9 (8.3+/-3.2) years and with body weight of 15-57 (33.7+/-14.7) kgs. After one year of follow-up studies, which included physical examination, ECG, chest X-ray and echocardiography, complete closure of ASD was achieved in nine (75%) patients. Two children with a trivial residual shunt were asymptomatic and without audible cardiac murmur. A girl had a small residual left to right atrial shunt by color Doppler echocardiography, but without audible cardiac murmur. There were no immediate or intermediate complications. Transcatheter implantation of the CardioSEAL device is a safe and proper treatment for children with non-complicated small to medium secundum ASD.