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Ting Xia,1– 3 Xiao Liang,4 Chang-Shun Liu,1– 3 Yan-Nan Hu,1– 3 Zhen-Ye Luo,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China; 4School of Pharmaceutical Sciences, Guilin Medical University, Guilin, 541199, People’s Republic of ChinaCorrespondence: Xiao-Mei Tan, Tel/Fax + 86-020-61648265, Email tanxm_smu@163.comBackground: Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear.Purpose: We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD.Methods: We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics.Results: EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group.Conclusion: EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.Keywords: Ermiao Wan, atopic dermatitis, network pharmacology, serum pharmacochemistry, skin transcriptome, EGFR/AKT signaling

Jei-Wen Chang,1– 3 Chin-Su Liu,3,4 Hsin-Lin Tsai3,5 1Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; 5Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, TaiwanCorrespondence: Hsin-Lin Tsai, Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, Taiwan, Tel +886-2-2875-2101, Fax +886-2-2875-7105, Email hltsai@vghtpe.gov.twPurpose: Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs). Early detection and treatment of VUR are important to prevent renal function impairment. Therefore, the aims of this study were to determine the epidemiology of VUR and to identify clinical factors associated with VUR in Taiwanese children with a first documented UTI.Patients and Methods: We conducted this nationwide retrospective study using the Longitudinal Health Insurance Database 2010. Children ≤ 6 years of age who were admitted and received intravenous antibiotics for a newly diagnosed UTI were included. Multivariate logistic regression analysis was used to identify independent factors associated with VUR.Results: Overall, 388 (10.2%) of the children had VUR. The median (interquartile range) age at diagnosis of VUR was 0.5 (0.3– 1.3) years. Among the children with VUR, the age at first UTI and the age at diagnosis of VUR were significant lower in the males than in the females. Age ≤ 1 year at the first UTI (odds ratio (OR), 1.3; 95% confidence interval (CI): 1.0– 1.7), renal agenesis and dysgenesis (OR, 4.1; 95% CI: 1.3– 13.1), hydronephrosis (OR, 2.2; 95% CI: 1.7– 2.9), duplex collecting system/ectopic kidney/ectopic ureter (OR, 13.0; 95% CI: 8.1– 20.8), neuropathic bladder (OR, 4.7; 95% CI: 2.0– 11.1) and spina bifida (OR, 5.9; 95% CI: 1.3– 27.8) were independent factors for VUR.Conclusion: The children with VUR were more likely to have small kidneys and progression to end-stage renal disease. VUR was common in the children with a UTI and who were ≤ 1 year of age. Clinicians should arrange ultrasound to diagnose urinary tract anomalies. Infants with urinary tract anomalies, neuropathic bladder and spina bifida should receive further voiding cystourethrography to diagnose VUR early, as this may help to prevent renal damage.Keywords: congenital anomalies of the kidney and the urinary tract, vesicoureteral reflux, urinary tract infection, risk factor

Jing-Yi Ye,1 Zhong-Yun Chen,1 Chuan-Li Huang,1 Bei Huang,2 Yu-Rong Zheng,2 Ying-Feng Zhang,1 Ban-Yi Lu,2 Lin He,2 Chang-Shun Liu3 ,* Xiao-Ying Long1,4, * 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China; 2School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China; 3School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Guangdong Engineering & Technology Research Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Shun LiuSouthern Medical University, No. 1023-1063 of Shatai South Road, Guangzhou, Guangdong 510515, People’s Republic of ChinaTel +86 13430301554Email lcshun1225@163.comXiao-Ying LongGuangdong Pharmaceutical University, No. 280 of Waihuan East Road, Guangzhou, Guangdong 510006, People’s Republic of ChinaTel +86 13798171092Fax +86 2039352174Email longxy3156@163.comObjective: A non-lipolysis nanoemulsion (NNE) was designed to reduce the first-pass metabolism of raloxifene (RAL) by intestinal UDP-glucuronosyltransferases (UGTs) for increasing the oral absorption of RAL, coupled with in vitro and in vivo studies.Methods: In vitro stability of NNE was evaluated by lipolysis and the UGT metabolism system. The oral bioavailability of NNE was studied in rats and pigs. Finally, the absorption mechanisms of NNE were investigated by in situ single-pass intestinal perfusion (SPIP) in rats, Madin-Darby canine kidney (MDCK) cells model, and lymphatic blocking model.Results: The pre-NNE consisted of isopropyl palmitate, linoleic acid, Cremophor RH40, and ethanol in a weight ratio of 3.33:1.67:3:2. Compared to lipolysis nanoemulsion of RAL (RAL-LNE), the RAL-NNE was more stable in in vitro gastrointestinal buffers, lipolysis, and UGT metabolism system (p < 0.05). The oral bioavailability was significantly improved by the NNE (203.30%) and the LNE (205.89%) relative to the suspension group in rats. However, 541.28% relative bioavailability was achieved in pigs after oral NNE intake compared to the suspension and had two-fold greater bioavailability than the LNE (p < 0.05). The RAL-NNE was mainly absorbed in the jejunum and had high permeability at the intestine of rats. The results of both SPIP and MDCK cell models demonstrated that the RAL-NNE was absorbed via endocytosis mediated by caveolin and clathrin. The other absorption route, the lymphatic transport (cycloheximide as blocking agent), was significantly improved by the NNE compared with the LNE (p < 0.05).Conclusion: A NNE was successfully developed to reduce the first-pass metabolism of RAL in the intestine and enhance its lymphatic transport, thereby improving the oral bioavailability. Altogether, NNE is a promising carrier for the oral delivery of drugs with significant first-pass metabolism.Keywords: non-lipolysis nanoemulsion, raloxifene, first-pass metabolism, stability, bioavailability, endocytosis

Chang-Shun Liu,1– 3 Li Chen,4 Yan-Nan Hu,1– 3 Jin-Lian Dai,4 Biao Ma,4 Qing-Fa Tang,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of ChinaCorrespondence: Li Chen; Xiao-Mei Tan Email zmu_cl@126.com; tanxm_smu@163.comPurpose: Ferulic acid (FA) is a natural compound which is used to treat insomnia. However, its use is limited because of its poor oral bioavailability caused by extremely rapid elimination. The current study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral delivery of FA and to enhance its hypnotic efficacy.Methods: FA-SMEDDS was prepared, and its morphology and storage stability were characterized. The formulation was also subjected to pharmacokinetic and tissue distribution studies in rats. The hypnotic efficacy of FA-SMEDDS was evaluated in p-chlorophenylalanine-induced insomnia mice.Results: FA-loaded SMEDDS exhibited a small droplet size (15.24 nm) and good stability. Oral administration of FA-SMEDDS yielded relative bioavailability of 185.96%. In the kidney, SMEDDS decreased the distribution percentage of FA from 76.1% to 59.4% and significantly reduced its metabolic conversion, indicating a reduction in renal elimination. Interestingly, FA-SMEDDS showed a higher distribution in the brain and enhanced serotonin levels in the brain, which extended the sleep time by 2-fold in insomnia mice.Conclusion: This is the first study to show that FA-loaded SMEDDS decreased renal elimination, enhanced oral bioavailability, increased brain distribution, and improved hypnotic efficacy. Thus, we have demonstrated that SMEDDS is a promising carrier which can be employed to improve the oral delivery of FA and facilitate product development for the therapy of insomnia.Keywords: insomnia, ferulic acid, oral administration, pharmacokinetics, SMEDDS

Shengbing Yang,1,* Shuogui Xu,2,* Panyu Zhou,2,* Jing Wang,3 Honglue Tan,4 Yang Liu,5 TingTing Tang,4 ChangSheng Liu1,3,5 1The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Changhai Hospital, Department of Orthopedics, the Second Military Medical University, Shanghai, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine China, Shanghai, People’s Republic of China; 5Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this workAbstract: Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with siliceous mesostructured cellular foams (SMC), using the porogen leaching method. Surface hydrophilicity, morphology, and recombinant human bone morphogenetic protein 2 adsorption/release behavior of the SMC/PHBHHx scaffolds were analyzed. Results of scanning electron microscopy indicated that the SMC was uniformly dispersed in the PHBHHx scaffolds, and SMC modification scaffolds have an interconnected porous architecture with pore sizes ranging from 200 to 400 µm. The measurements of the water contact angles suggested that the incorporation of SMC into PHBHHx improves the hydrophilicity of the composite. In vitro studies with simulated body fluid show great improvements to bioactivity and biodegradability versus pure PHBHHx scaffolds. Cell adhesion and cell proliferation on the scaffolds was also evaluated, and the new tools provide a better environment for human mesenchymal stem cell attachment, spreading, proliferation, and osteogenic differentiation on PHBHHx scaffolds. Moreover, micro-computed tomography and histological evaluation confirmed that the SMC/PHBHHx scaffolds improved the efficiency of new bone regeneration with excellent biocompatibility and biodegradability and faster and more effective osteogenesis in vivo. Keywords: stem cells, mesoporous, scaffolds, bone regeneration, rhBMP-2

Richard MH Lee,1 Fook Chang Lam,1 Tassos Georgiou,1 Bobby Paul,1 Kong Yong Then,1 Ioannis Mavrikakis,1 Venkata S Avadhanam,1 Christopher SC Liu1,21Sussex Eye Hospital, Brighton, United Kingdom; 2Tongdean Eye Clinic, Hove, United KingdomAims: To report on the suturing techniques and aspects of postoperative management in penetrating keratoplasty in the United Kingdom.Methods: A postal questionnaire was sent to 137 ophthalmic consultants identified from a Royal College of Ophthalmology database as having a special interest in anterior segment surgery. The questionnaire surveyed surgeon preferences for surgical and suturing technique for penetrating keratoplasty surgery, and the postoperative care of corneal grafts.Results: In all, 68% of questionnaires were completed and returned: 73% of respondents used a Flieringa ring or equivalent, 94% routinely used cardinal sutures, with 50.5% removing them at the end of the procedure. The most common suturing technique for routine penetrating keratoplasty was a single continuous suture (35%). In these cases, a 10/0 nylon suture was used by 89%. Sixty-six percent changed their technique in high-risk cases, 52% used a 3-1-1 knot, and 75% made a distinction between a reef and granny knot, with 76% using a reef. Thirty percent buried the knots within the donor material, and 29% within the host tissue. Twenty-five percent had no routine time for graft suture removal, but 41% removed them between 1 and 2 years post-surgery. After suture removal, 98% used steroids and 88% used topical antibiotics. Thirty-four percent stopped topical steroids before suture removal, with 38% stopping topical steroids more than 3 months prior to suture removal.Conclusion: This survey demonstrates that there is considerable variation in suturing techniques and postoperative care for penetrating keratoplasty. These significant variations in practice need to be considered when interpreting outcomes and research.Keywords: corneal graft, penetrating keratoplasty, anterior segment surgery, cornea, corneal surgery, corneal transplantation

Han Guo,1,2 Jie Wei,2 Wenhua Song,2 Shan Zhang,2 Yonggang Yan,3 Changsheng Liu,2 Tiqiao Xiao11Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, People's Republic of China; 2Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People's Republic of China; 3School of Physical Science and Technology, Sichuan University, Chengdu, People's Republic of ChinaAbstract: The purpose of this study was to synthesize a self-setting bioactive cement by incorporation of wollastonite nanofibers (WNFs) into calcium phosphate cement (CPC). The composition, morphology, setting time, compressive strength, hydrophilicity, and degradation of WNF-doped CPC (wnf-CPC) were investigated. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and inductively coupled plasma atomic emission spectroscopy were utilized. Additionally, methyl-thiazolyl-tetrazolium bromide assay, scanning electron microscopy, inductively coupled plasma atomic emission spectroscopy, and histological evaluation were used to study the cell and tissue responses to wnf-CPC, both in vitro and in vivo. The results confirmed that the addition of WNFs into CPC had no obvious effect on the setting time or the compressive strength of wnf-CPC, provided the WNF amount was not more than 10 wt%. However, the hydrophilicity and degradability of wnf-CPC were significantly improved by the addition of WNFs – this was because of the change of microstructure caused by the WNFs. The preferred dissolution of WNFs caused the formation of microporosity in wnf-CPC when soaked in tris hydrochloride solution. The microporosity enlarged the surface area of the wnf-CPC and so promoted degradation of the wnf-CPC when in contact with liquid. In addition, MG-63 cell attachment and proliferation on the wnf-CPC were superior to that on the CPC, indicating that incorporation of WNFs into CPC improved the biological properties for wnf-CPC. Following the implantation of wnf-CPC into bone defects of rabbits, histological evaluation showed that wnf-CPC enhanced the efficiency of new bone formation in comparison with CPC, indicating excellent biocompatibility and osteogenesis of wnf-CPC. In conclusion, wnf-CPC exhibited promising prospects in bone regeneration.Keywords: calcium phosphate cement, degradability, cell and tissue responses, biocompatibility

An analytic solution describing an ion-acoustic collisionless shock, self-consistently with the evolution of shock-reflected ions, is obtained. The solution extends the classic soliton solution beyond a critical Mach number, where the soliton ceases to exist because of the upstream ion reflection. The reflection transforms the soliton into a shock with a trailing wave and a foot populated by the reflected ions. The solution relates parameters of the entire shock structure, such as the maximum and minimum of the potential in the trailing wave, the height of the foot, as well as the shock Mach number, to the number of reflected ions. This relation is resolvable for any given distribution of the upstream ions. In this paper, we have resolved it for a simple "box" distribution. Two separate models of electron interaction with the shock are considered. The first model corresponds to the standard Boltzmannian electron distribution in which case the critical shock Mach number only insignificantly increases from M1.6 (no ion reflection) to M1.8 (substantial reflection). The second model corresponds to adiabatically trapped electrons. They produce a stronger increase, from M3.1 to M4.5. The shock foot that is supported by the reflected ions also accelerates them somewhat further. A self-similar foot expansion into the upstream medium is described analytically.

Objectives Previous studies on the effects of angiotensinogen (AGT) gene polymorphisms and chronic exposure to occupational noise on the risk of hypertension have mainly been cross-sectional or prevalent case-control studies, where temporality constitutes problems. The present study was to assess longitudinally both independent and joint effects of AGT gene polymorphisms and chronic exposure to occupational noise on occurrence of hypertension. Methods The authors conducted a 20-year prospective cohort study of 1301 aviation workers in Taiwan. The study population included 912 workers without hypertension at baseline. The outcome of interest was the development of hypertension during the study period. The studied determinants were three AGT genotypes (TT, TM and MM) and four exposure categories according to the levels of noise representing high (>80 dBA), medium (80-65 dBA), low exposure (64-50 dBA) and the reference level (49-40 dBA). Results In Poisson regression adjusting for confounders, AGT (TT vs MM adjusted incidence rate ratio (IRR) 1.77, 95% CI 1.24 to 2.51) and noise exposure (high and medium combined) during 3-15 years (adjusted IRR 2.35, 95% CI 1.42 to 3.88) were independent determinants of hypertension. Furthermore, the risk of hypertension increased with noise exposure (adjusted IRR 3.73, 95% CI 1.84 to 7.56) among TT homozygotes but not among those with at least one M allele (Rothman synergy index=1.05). Conclusions The results evidence further the independent effects of AGT gene polymorphisms and exposure to occupational noise. Our finding also suggests that workers carrying TT variant allele have higher risk of hypertension under chronic exposure to occupational noise. [ABSTRACT FROM AUTHOR]

Objective: To examine whether combined lifestyle behaviors have an impact on all-cause and cause-specific mortality in patients aged 30-94 years with type 2 diabetes (T2DM).Research Design and Methods: Participants included 5,686 patients >30 years old with T2DM who were enrolled in a Diabetes Care Management Program at a medical center in central Taiwan before 2007. Lifestyle behaviors consisted of smoking, alcohol drinking, physical inactivity, and carbohydrate intake. The main outcomes were all-cause and cause-specific mortality. Cox proportional hazards models were used to examine the association between combined lifestyle behaviors and mortality.Results: The mortality rate among men was 24.10 per 1,000 person-years, and that among women was 17.25 per 1,000 person-years. After adjusting for the traditional risk factors, we found that combined lifestyle behavior was independently associated with all-cause mortality and mortality due to diabetes, cardiovascular disease, and cancer. Patients with three or more points were at a 3.50-fold greater risk of all-cause mortality (95% CI 2.06-5.96) and a 4.94-fold (1.62-15.06), 4.24-fold (1.20-14.95), and 1.31-fold (0.39-4.41) greater risk of diabetes-specific, CVD-specific, and cancer-specific mortality, respectively, compared with patients with zero points. Among these associations, the combined lifestyle behavior was not significantly associated with cancer mortality.Conclusions: Combined lifestyle behavior is a strong predictor of all-cause and cause-specific mortality in patients with T2DM. [ABSTRACT FROM AUTHOR]

Richard MH Lee1, Vincent DJP Dubois1, Ioannis Mavrikakis1, Salim Okera1, Gerard Ainsworth1, Sarah Vickers1, Christopher SC Liu1,21Department of Ophthalmology, Sussex Eye Hospital, Brighton, UK; 2Tongdean Eye Clinic, Hove, UKPurpose: To report the use of opaque intraocular devices in three patients with complex neuro-ophthalmic symptoms.Methods: A case series of three patients with neuro-ophthalmic symptoms requiring occlusion of one eye when alternative methods had failed to control symptoms. Morcher (Stuttgart, Germany) opaque intraocular implants were used in all patients.Results: All three patients observed an improvement in symptoms following opaque intraocular device implantation. One patient (Case 2) required multiple devices for symptom relief.Conclusion: Opaque intraocular occlusive devices are an increasingly popular choice for clinicians in patients with intractable diplopia but we highlight their use in patients with other complex neuro-ophthalmic symptoms. We learned a number of useful lessons in these patients as summarized in this case series.Keywords: intraocular lens, opaque IOL, occlusive IOL, occlusive intraocular lens, diplopia implant

Background: Although National Cholesterol Education Program (NCEP), International Diabetes Federation (IDF), American Heart Association and National Heart, Lung and Blood Institute (AHA/NHLBI), World Health Organization (WHO), and the European Group for the Study of Insulin Resistance (EGIR) definitions of metabolic syndrome (MetS) have been commonly used by studies, little is known about agreement among these five definitions. We examined the agreement among these five definitions and explored their relationship with risk factors of cardiovascular disease in a Taiwan population.Methods: A total of 1305 subjects aged 40 years and over in Taiwan were analyzed. Biomedical markers and anthropometric indices were measured. Agreement among definitions was determined by the kappa statistic. Logistic regression models were fit to estimate the odds of a high cardiovascular risk group for five definitions of MetS.Results: The agreement among the NCEP, IDF, and AHA/NHLBI definitions was from substantial to very good, and agreement between the WHO and EGIR definitions was also substantial. All MetS definitions were significantly associated prevalence of microalbuminuria, elevated highly sensitive CRP (hs-CRP), and arterial stiffness only in women. In men, MetS by NCEP and AHA/NHLBI was associated with elevated level of hs-CRP and arterial stiffness. MetS by WHO and EGIR were significantly associated with microalbuminuria. And MetS by WHO was the only MetS definition that significantly associated with prevalence of arterial stiffness (OR: 2.75, 95% CI: 1.22-6.19).Conclusions: The associations of these five definitions with cardiovascular risk factors were similar in women, and it was evident that the five definitions performed better in women than in men, with higher ORs observed in relation to arterial stiffness, elevated hs-CRP, and higher Framingham risk scores. [ABSTRACT FROM AUTHOR]

Background: As a result of metabolic syndrome becoming an important issue during recent decades, many studies have explored the risk factors contributing to its development. However, less attention has been paid to the risk associated with sedentary behavior, especially television viewing. This study examined the association between television viewing time and the risk of having metabolic syndrome in a population of Taiwanese subjects.Methods: This community-based cross-sectional study included 2,353 subjects (1,144 men and 1,209 women) aged 40 and over from October, 2004 to September, 2005. Information about the time spent watching TV was obtained using a self-administered questionnaire. The definition of metabolic syndrome was according to the Third Report of the National Cholesterol Education Program's Adult Treatment Panel modified for Asians.Results: Compared to subjects who viewed TV < 14 hr/week, those who viewed TV > 20 hr/week had a 1.50-fold (95% confidence intervals (CI): 1.10, 2.03) risk for men and a 1.93-fold (95% CI: 1.37, 2.71) risk for women of having metabolic syndrome, after adjusting for physical activity and other covariates. Stratifying by the three categories of total activity levels, TV viewing time > 20 hr/week was found to still hold a significant risk for having metabolic syndrome in the lowest of the three categories of total activity level for men and in all three categories of total activity level for women.Conclusion: The findings suggest that TV viewing is an independent risk factor associated with metabolic syndrome in Taiwanese people. [ABSTRACT FROM AUTHOR]

Background: Bone metastases are a major cause of morbidity in metastatic castration-resistant prostate cancer. Abiraterone acetate potently disrupts intracrine androgen receptor signalling pathways implicated in the progression of the disease, including bone metastases. We assessed data for pain control and skeletal-related events prospectively collected as part of the randomised, phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy.Methods: The COU-AA-301 trial enrolled patients with metastatic castration-resistant prostate cancer in whom one or two lines of chemotherapy (one docetaxel based) had been unsuccessful and who had Eastern Cooperative Oncology Group performance statuses of 2 or less. Pain intensity and interference of pain with daily activities were assessed with the Brief Pain Inventory-Short Form questionnaire at baseline, day 15 of cycle 1, and day 1 of each treatment cycle thereafter until discontinuation. We assessed, with prospectively defined response criteria that incorporated analgesic use, clinically meaningful changes in pain intensity and interference with daily living. We measured time to first occurrence of skeletal-related events, which we defined as pathological fracture, spinal cord compression, palliative radiation to bone, or bone surgery, and regularly assessed them throughout the study. Pain palliation was assessed in patients who had clinically significant baseline pain, whereas all other analyses were done in the overall intention-to-treat population. COU-AA-301 is registered with ClinicalTrials.gov, number NCT00638690.Findings: Median follow-up was 20·2 months (IQR 18·4-22·1). In patients with clinically significant pain at baseline, abiraterone acetate and prednisone resulted in significantly more palliation (157 of 349 [45·0%] patients vs 47 of 163 [28·8%]; p=0·0005) and faster palliation (median time to palliation 5·6 months [95% CI 3·7-9·2] vs 13·7 months [5·4-not estimable]; p=0·0018) of pain intensity than did prednisone only. Palliation of pain interference (134 of 223 [60·1%] vs 38 of 100 [38·0%], p=0·0002; median time to palliation of pain interference 1·0 months [95% CI 0·9-1·9] vs 3·7 months [2·7-not estimable], p=0·0004) and median duration of palliation of pain intensity (4·2 months [95% CI 3·0-4·9] vs 2·1 months [1·4-3·7]; p=0·0056) were significantly better with abiraterone acetate and prednisone than with prednisone only. In the overall population, median time to occurrence of first skeletal-related event was significantly longer with abiraterone acetate and prednisone than with prednisone only (25·0 months [95% CI 25·0-not estimable] vs 20·3 months [16·9-not estimable]; p=0·0001).Interpretation: In patients with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone acetate and prednisone offer significant benefits compared with prednisone alone in terms of pain relief, delayed pain progression, and prevention of skeletal-related events.Funding: Janssen Research & Development and Janssen Global Services. [ABSTRACT FROM AUTHOR]

Background: The cluster of cardiovascular risk factors, referred to as metabolic syndrome (MetS), represents a substantial risk factor for cardiovascular diseases and presents a significant public health challenge. However, previous epidemiological investigations exploring the link between sleep duration and MetS lack experimental evidence to establish a causal relationship. Hence, he objective of this study is to examine the association between sleep duration and MetS by employing the Mendelian randomization (MR) approach., Methods: A cross-sectional study was conducted utilizing the Taiwan Biobank database, which comprised 33,270 predominantly Han Chinese individuals aged 30-70 years with no history of cancer and enrolled between 2008 and 2020. This study was conducted using Taiwan Biobank database. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating the SNP alleles significantly associated with sleep duration. Two-stage regression analysis was used to estimate odds ratio (OR) and 95% confidence interval (CI)., Results: In the observational epidemiologic study, after multivariate adjustment, the OR for sleep durations of < 5, 8-9 and > 9 h compared to those with a sleep duration of 7 h were 1.23 (95% CI: 1.07, 1.43), 1.15 (95% CI: 1.06, 1.24) and 1.84 (95% CI: 1.43, 2.36), respectively. In the MR analyses after multivariate adjustment, the ORs of MetS per 1 standard deviation increase in the estimated sleep duration and the probability of long and short sleep durations derived from weighted genetic risk scores were 0.64 (95% CI: 0.63, 0.66), 1.55 (95% CI: 1.51, 1.59), and 1.66 (95% CI: 1.62, 1.70), respectively., Conclusions: Observational and MR analyses demonstrated that short and long sleep durations are potential causal risk factors for MetS. Therefore, long and short sleep durations should be considered as risk factors in MetS-prevention strategies., Competing Interests: Declarations. Ethics approval and consent to participate: This present study was approved by the Ethics and Governance Council of Taiwan Biobank (approval number: TWBR10811-06) and the Ethical Review Board of China Medical University Hospital (CMUH109-REC3-187). All participants provided written informed consent. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: While many studies have reported the renal outcomes and metabolic consequences of augmentation cystoplasty (AC), few have focused on changes in renal tubular function. This study investigated the prevalence of metabolic disturbances, renal tubular function, and 24-hour urine chemistry, aiming to evaluate the association between metabolic alterations and urolithiasis after AC., Methods: We investigated serum biochemistry, blood gas, and 24-hour urinary metabolic profile of children who underwent AC between January 2000 and December 2020. The assessed outcomes included metabolic complications, tubular function, and magnesium status. Associations between 24-hour urinary metabolic parameters and urolithiasis formation were also examined., Results: A total of 25 patients with a mean follow-up period of 13.8 ± 5.7 years were enrolled. The mean age at AC was 7.5 ± 4.4 years, and 22 and 3 patients underwent AC using the ileum and colon, respectively. There were no abnormalities in serum levels of sodium, potassium, chloride, and calcium. Hypomagnesemia (magnesium <1.7 mg/dL) due to renal loss was observed in one patient (4.0%). Six (24.0%) patients had increased urinary β2-microglobulin levels and normal serum levels. The ratio of the maximum rate of tubular phosphate reabsorption to the glomerular filtration rate was low in three (12.0%) patients. Four (16.0%) patients had normal serum magnesium levels but urinary magnesium excretion <40 mg/d. Urolithiasis occurred in 11 patients (44.0%). The most common 24-hour urine metabolic abnormality was hypomagnesiuria (72.0%). No urinary metabolic parameters or daily protein intake were associated with urolithiasis., Conclusion: AC for children is safe and does not significantly impact the metabolic profile. Excretions of 24-hour urinary calcium, uric acid, magnesium, and the sodium-to-potassium ratio were not associated with urolithiasis. However, a high prevalence of 24-hour urine magnesium excretion <88 mg/1.73 m 2 was noted. Further prospective studies are needed to investigate longitudinal changes in renal tubular function and 24-hour urine metabolic profiles, particularly magnesium status., Competing Interests: Conflicts of interest: Dr. Jei-Wen Chang and Dr. Chin-Su Liu, editorial board members at the Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: ABO-incompatible liver transplantation (ABOi LT) can now be successfully performed with standard pretransplant induction therapy. For patients with chronic end-stage liver disease (ESLD), ABOi LT can achieve long-term outcomes comparable to those of blood type-compatible (ABOc) LT. Outcomes of patients with acute liver failure (ALF) who undergo urgent transplantation surgery with a limited induction period should be further investigated., Methods: Between 2004 and 2023, adult patients who underwent living donor liver transplantation (LDLT) at Taipei Veterans General Hospital were enrolled. Based on the chronicity of liver disease and the transplant type, patients were divided into 4 groups for outcome analysis: ALF patients who received ABOi LDLT, ALF patients who received ABOc LDLT, ESLD patients who received ABOi LDLT, and ESLD patients who received ABOc LDLT., Results: Four instances of diffuse intrahepatic cholangiopathy (DIC) occurred in the ABOi LDLT group (n=3, 27.3% in group 1 and n=1, 2.6% in group 3, p=0.03). In ABOi LDLT patients, rituximab was administered closer to LT in group 1 (5 [3~6] days before LDLT) than that in group 3 (15 [14~22] days before LDLT) (p<0.01). Univariate analysis revealed that ALF, small graft-to-recipient weight ratio (GRWR), low rituximab dose (<210 mg/m 2) and postoperative rebound of isoagglutinin immunoglobulin M (IgM) antibody titers were factors contributing to an increased risk of DIC. Allograft loss eventually occurred in 3 of the 4 patients with DIC. Overall, ABOi LDLT showed inferior long-term outcomes for ALF (5-year patient survival: 62.3%/73.6%/74.1%/76.7% in groups 1/2/3/4, respectively, p=0.25)., Conclusion: ABOi LDLT achieved outcomes comparable to those of ABOc LDLT among ESLD patients but not among ALF patients. DIC results in a high risk of allograft loss; however, the combination of potent immunosuppressive agents and early recognition of antibody rebound and the initiation of salvage treatment may improve long-term outcomes among these patients., Competing Interests: Conflicts of interest: Dr. Chin-Su Liu, an editorial board member at the Journal of the Chinese Medical Association, had no role in the peer review process or decision to publish this article. The authors declare no conflicts of interest related to this article's subject matter or materials., (Copyright © 2025, the Chinese Medical Association.)

The quinazoline scaffold serves as a fundamental framework, demonstrating potent anti-tumor activity. Employing the pharmacophore-based scaffold hopping principle, we successfully synthesized a series of FAK/PLK1 inhibitors incorporating the quinazoline scaffold. The synthesized compounds were characterized using 1 H NMR, 13 C NMR, and HRMS techniques. Through computer-assisted screening and antitumor activity tests, the majority of the compounds demonstrated significant inhibitory effects against various cancer cell lines. Notably, compound 3m exhibited remarkable anticancer activity by inducing G2/M phase cell cycle arrest, apoptosis, as confirmed by western blot assay, cellular fluorescence staining, and transcriptomics testing. Docking simulation was performed to determine the probable binding conformation of compound 3m within the active sites of FAK and PLK1. This compound emerged as a highly promising lead compound during our screening process, displaying high efficiency., Competing Interests: Declarations. Conflict of interest: The authors have affirmed that they do not have any financial or interpersonal conflicts that would have impacted to influence the presented and discussed work in this paper. The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan., Methods: Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE))., Results: During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease., Conclusion: Carbon-ion radiotherapy was determined to be an effective and safe treatment., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2025, the Chinese Medical Association.)

Persistent cognitive challenges in bipolar disorder (BD) may be tied to insulin resistance, which crucially affects both metabolism and brain health. Additionally, mitochondrial DNA (mtDNA) copy number has emerged as an indicator of cognitive performance and response to treatment in BD. However, it remains unclear whether and how this indicator might serve as a bridge between metabolic dysfunction and cognitive capacity. In 68 study participants with euthymic BD, insulin resistance was assessed according to fasting glucose and insulin levels. mtDNA copy number was quantified from leukocytes, and executive function was measured with the Wisconsin card-sorting test (WCST). Mediation models were applied to explore the statistical relationship between insulin resistance, mtDNA copy number, and executive function. Both linear regression and Poisson distribution approaches with robust bootstrap simulations were used for significance testing. The results indicated that insulin resistance indirectly affects executive function via mtDNA copy number. This mediation relationship was statistically significant for both preservation errors and completion of categories in the WCST, although there were no significant direct effects of insulin resistance on the executive functions. We therefore concluded that insulin resistance is associated with reduced mtDNA copy number in blood, which may negatively impact executive functions in patients with euthymic BD. Further work is warranted to determine if improving metabolic and mitochondrial health may lead to better cognitive outcomes in BD., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Single-nucleus RNA-sequencing (snRNA-seq) has revealed new levels of cellular organization and diversity within the human brain. However, full-length mRNA isoforms are not resolved in typical snRNA-seq analyses using short-read sequencing that cannot capture full-length transcripts. Here we combine standard 10x Genomics short-read snRNA-seq with targeted PacBio long-read snRNA-seq to examine isoforms of genes associated with neurological diseases at the single-cell level from prefrontal cortex samples of diseased and nondiseased human brain, assessing over 165,000 cells. Samples from 25 postmortem donors with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or Parkinson's disease (PD), along with age-matched controls, were compared. Analysis of the short-read libraries identified shared and distinct gene expression changes across the diseases. The same libraries were then assayed using enrichment probes to target 50 disease-related genes followed by long-read PacBio sequencing, enabling linkage between cell type and isoform expression. Vast mRNA isoform diversity was observed in all 50 targeted genes, even those that were not differentially expressed in the short-read data. We also developed an informatics method for detection of isoform structural differences in novel isoforms versus the reference annotation. These data expand available single-cell datasets of the human prefrontal cortical transcriptome with combined short- and long-read sequencing across AD, DLB, and PD, revealing increased mRNA isoform diversity that may contribute to disease features and could potentially represent therapeutic targets for neurodegenerative diseases., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Liu et al.)

Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells. Nuclear factor erythroid-derived 2-like 2 (Nrf2), a master transcription factor that controls antioxidant and detoxification gene expression, plays a crucial role in neuroprotection in SCA3 and other neurodegenerative diseases. The present data showed that treatment with erinacine A-enriched Hericium erinaceus mycelium ethanol extract (HEME) extended longevity and improved locomotor activity in ELAV-SCA3tr-Q78 transgenic Drosophila . Moreover, HEME treatment enhanced antioxidant potency and autophagy, which, in turn, corrected levels of mutant polyQ-expanded ataxin-3 and restrained protein aggregation in both cell and Drosophila models of SCA3. Markedly, HEME increased the activation of Nrf2. Silencing Nrf2 protein expression negated most of the promising effects of HEME on SK-N-SH-MJD78 cells, highlighting the critical role of increased Nrf2 activation in the efficacy of HEME treatment. These findings suggest that HEME has therapeutic potential in SCA3 by enhancing autophagic and Nrf2-mediated antioxidant pathways, which may also influence neurodegenerative progression in other polyQ diseases.

Ethno-Pharmacological Relevance: Huangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear., Aim of the Study: Following PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE)., Materials and Methods: To evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed., Results: In mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect., Conclusions: Our findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)