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Yongsheng Sun,1 ChengJiang Liu,2 Nianping Zhang,3 Debing Yang,4 Cungen Ma,5 Xi Zhang61Department of Neurology and Psychiatry, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 2Department of General Medicine, Affiliated Anqing First People’s Hospital of Anhui Medical University, Anhui, 246000, People’s Republic of China; 3Department of Internal Medicine, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 4Department of Anatomy, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 5Neurobiology Research Center, Shanxi University of Traditional Chinese Medicine, Jinzhong, 030619, People’s Republic of China; 6Department of Neurology, Second Medical Center, General Hospital of the Chinese People’s Liberation Army, Beijing, 100000, People’s Republic of ChinaCorrespondence: Cungen Ma; Xi Zhang, Email macungen2001@163.com; zhangxiplagh@sina.comObjective: The common chronic non-communicable diseases and epidemiological characteristics of the forsaken elders over 60 in Guangling and Tianzhen were investigated and analyzed to provide reference for health resource allocation, hospital capacity establishing and health management of the forsaken elders in county-level regions.Materials and Methods: The data of 10,331 resident elderly over 60 in Guangling and Tianzhen of Datong Civil Affairs Bureau in the management system for disabled and semi-disabled elderly was collected. The gender, age, main diagnosis and coding of diseases, common chronic non-communicable diseases, and system diseases of the respondents were retrospectively analyzed.Results: The prevalence of the forsaken elders aged over 60 in Guangling and Tianzhen were different. Hypertension, arthritis, type 2 diabetes, hyperlipidemia and cerebral infarction are the top five common chronic non infectious diseases in Guangling, Tianzhen and the two counties. Among the top five common diseases in Guangling, Tianzhen and the two counties, arthritis or rheumatism, hypertension, diabetes or elevated blood sugar were found, which were different in the 60– 65, 66– 70, 71– 75 and 76– 80 groups, with the prevalence increasing with age. The top five diseases in Guangling, Tianzhen and the two counties were consistent, while the ranking changed slightly. The proportion of circulatory diseases, musculoskeletal diseases, connective tissue diseases and endocrine/nutritional and metabolic diseases in 60– 65, 66– 70 and 71– 75 groups increased with age, and was much higher than that in other groups.Conclusion: The prevalence and disease spectrum order of common chronic non-communicable diseases and systemic diseases in Guangling and Tianzhen are diverse, also in gender and age groups. As China’s county-level local administrative divisions have relatively independent administrative autonomy, medical and health resources can be better configured according to the information mined, accurately maintaining and promoting residents’ health. It is suggested to explore the disease management mechanism with county-level administrative divisions as database management units under the background of big data, so as to implement the interconnection and sharing of information among health-related departments in county-level regions.Keywords: chronic non-communicable diseases, system diseases, administrative division, disease spectrum, the forsaken elders

Yuzhao Liu,1,* Jingru Cai,2,* Yangang Wang,1 Xiangli Zhao,3 Yun Qiao,4 Chuan-Ju Liu3 1Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Orthopaedic Surgery, New York University Grossman School of Medicine, New York, NY, USA; 4Department of Traditional Chinese Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Qiao; Chuan-Ju Liu, Email qlyyqy@163.com; Chuanju.Liu@nyulangone.orgObjective: This study is aimed to determine the metabolomic effects of the hybrid medicine formula Yi-Qi-Bu-Shen (YQBS) on the neurotransmitter aspects of cognitive impairment in diabetic rats.Methods: In the current study, streptozotocin (STZ) was used to induce diabetic animal model in male Sprague Dawley (SD) rats. After successful establishment of diabetic SD rats’ model, age-matched healthy SD rats and diabetic SD rats were treated with low and high doses of YQBS, and then tested for learning memory ability and analyzed for pathological changes. In addition, neurotransmitter metabolic changes in hippocampal subdivisions of rats from different treated groups were analyzed using liquid chromatography-mass spectrometry (LC-MS) technique.Results: YQBS could significantly improve memory-cognitive impairment in diabetic rats as evidenced by the shortening of latency to target and the reduction of latency first entrance to target. Moreover, YQBS also improved the pathological alterations in the hippocampal region in the brains of diabetic rats. Metabolomic analysis showed that the expression of noradrenaline hydrochloride was down-regulated and the expressions of levodopa and 5-hydroxytryptophan were up-regulated in the hippocampal tissues of diabetic rats treated with YQBS.Conclusion: These findings demonstrate that YQBS has protective effects against diabetic cognitive dysfunction, which might act through alteration in tyrosine and tryptophan metabolism.Keywords: diabetes mellitus, cognitive dysfunction, Yi-Qi-Bu-Shen, hippocampus, metabolomics

Rei-Chi Hsueh,1 Wan-Jung Wu,1 Chih-Lin Lin,2 Chun-Jen Liu,3 Yi-Wen Huang,4,5 Jui-Ting Hu,6 Chih-Feng Wu,1 Feng-Yu Sung,1 Wen-Jie Liu,1 Ming-Whei Yu1 1Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 2Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 4Clinical Research Center, Liver Center and Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 5Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Liver Center, Cathay General Hospital Medical Center, School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, TaiwanCorrespondence: Ming-Whei Yu, Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 522 No. 17, Xuzhou Road Zhongzheng District, Taipei City, 10055, Taiwan, Email yumw@ntu.edu.twBackground: Coexistence of hepatitis B and nonalcoholic fatty liver disease is common; however, little is known about the impact of hepatic steatosis and its major genetic determinants on the natural history of HBV infection. We aimed to study the effects of hepatic steatosis and PNPLA3 variant p.I148M on the risk of hepatocellular carcinoma (HCC) and the lifetime probability of HBsAg seroclearance, which is associated with functional remission and improved long-term outcome of HBV infection.Methods: We conducted a cohort study of 2385 male, HBsAg-positive Taiwanese civil servants recruited in 1989– 1992, and followed up until 2019. Cox regression with competing-risk models was used to estimate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs).Results: Of 2385 participants, 628 experienced HBsAg seroclearance and 217 developed HCC. Hepatic steatosis, excess body-mass index, and the PNPLA3-148M variant were significantly associated with higher HBsAg seroclearance rate. However, multivariate analyses accounting for HBsAg seroclearance and various HCC risk factors showed that, while steatosis was associated with decreased HCC risk (sHR [95% CI]: 0.49 [0.36– 0.66]), carriage of the PNPLA3-148M variant allele (vs II homozygotes: 1.64 [1.20– 2.25] for MI heterozygotes; 1.83 [1.20– 2.78] for MM homozygotes) and obesity (1.51 [1.07– 2.13]) were associated with increased risk. The inverse hepatic steatosis-HCC association persisted after additional adjustment for other viral factors or using different follow-up time cut-offs to account for reverse causality. Moreover, the PNPLA3 MM genotype was positively associated with elevations of ALT and AST and liver cirrhosis, while hepatic steatosis was positively associated with ALT but inversely associated with AST and liver cirrhosis.Conclusion: Hepatic steatosis and PNPLA3-148M variant appeared to have distinct impacts on the development of HBV-related progressive liver disease and HCC. PNPLA3 p.I148M, but not a diagnosis of hepatic steatosis, can help to identify HBV carriers with high-risk fatty liver disease in the progression to HCC.Keywords: chronic hepatitis B, HBsAg seroclearance, hepatic steatosis, hepatocellular carcinoma, liver cirrhosis, PNPLA3

Chen-Jie Liu,1 Li Yao,2 Ya-Min Hu,2 Bo-Tao Zhao2 1ECG Room of Physical Examination Center of Cangzhou Central Hospital, Cangzhou, Hebei, 061001, People’s Republic of China; 2Six Cardiovascular Departments of Cangzhou Central Hospital, Cangzhou, Hebei, 061001, People’s Republic of ChinaCorrespondence: Chen-Jie LiuECG Room of Physical Examination Center of Cangzhou Central Hospital, No. 5 Guangrong Road, Canal District, Cangzhou, Hebei Province, 061001, People’s Republic of ChinaEmail liuchenjiecz@163.comBackground: Quercetin has potential value in treating cardiovascular diseases, but it is not suitable for clinical application due to its own water solubility. The limitation of quercetin can be distinctly ameliorated by delivering it with nanocarriers.Objective: To determine the effect of quercetin-loaded mesoporous silica nanoparticles (Q-MSNs) on myocardial ischemia-reperfusion injury in rats and its mechanism.Methods: Q-MSNs were synthesized, and the morphology of Q-MSNs and MSNs was characterized by transmission electron microscopy and dynamic light scattering technique, respectively. Healthy rats were enrolled and randomly divided into a sham operation control group, an ischemia-reperfusion (IR) group, an IR+Q group, an IR+Q-MSNs group, and an MSNs group (each n = 10). Rats in the sham operation group were not treated with ischemia reperfusion, but given normal perfusion meantime. Rats in the sham operation control group, IR group, and MSNs group were given normal saline for 10 days before ischemia reperfusion, and rats in the IR+Q group and IR+Q-MSNs group were given drugs by gavage for 10 days before ischemia reperfusion. Primary myocardial cells were sampled from SD neonatal rats to construct hypoxia/reoxygenation myocardial cell models. The myocardial cells were assigned to a control group, IR group, quercetin (Q) group, Q-MSNs group, and MSNs group. Except for the control group, all the other groups were treated with hypoxia/reoxygenation. Cells in the Q group were treated with quercetin (10 μM, 20 μM, 40 μM) for 24 h in advance and then treated with measures to cause hypoxia-reoxygenation injury. Cells in the Q-MSNs group were treated with the same concentration of loaded quercetin and the same method used for the Q group. The myocardial apoptosis, myocardial infarction, ventricular remodeling, hemodynamic indexes, physiological and biochemical indexes, and JAK2/STAT3 pathway expression of each group were detected, and the apoptosis, viability, oxidative stress, and JAK2/STAT3 pathway expression of primary myocardial cells in each group were also detected.Results: Quercetin significantly activated the JAK2/STAT3 pathway in vivo and in vitro, and MSNs intensified the activation. Compared with quercetin, Q-MSNs were more effective in inhibiting cell apoptosis and oxidative stress, reducing myocardial infarction size, improving ventricular remodeling and cardiac function-related biochemical indexes, and promoting the recovery of cardiac blood flow.Conclusion: Q-MSNs can significantly enhance the activation effect of quercetin on JAK2/STAT3 pathway, thus enhancing its protection on the heart of MIRI rats.Keywords: myocardial ischemia-reperfusion injury, quercetin-loaded mesoporous silica nanoparticles, JAK2/STAT3 pathway, cardiovascular diseases

Chia-Jung Liu,1 Tai-Fen Lee,2 Sheng-Yuan Ruan,1 Chong-Jen Yu,1 Jung-Yien Chien,1 Po-Ren Hsueh1,21Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 2Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanObjectives: The incidence of Pneumocystis pneumonia (PCP) has been increasing among non-HIV-infected patients. Here, we investigated the clinical characteristics, treatment outcomes, and prognostic factors of PCP in non-HIV-infected patients.Patients and methods: Information on clinical characteristics, treatment outcomes, and prognostic factors of PCP patients who were treated at a medical center in northern Taiwan from October 2015 to October 2016 were retrieved from medical records and evaluated.Results: Among the patients with PCP included in the study, 84 were non-HIV-infected and 25 were HIV-infected. Non-HIV-infected patients with PCP had a longer duration between radiographic findings and treatment (P

Jing Lin,* Chaoyue Zhao,* Cuijuan Liu, Shiyao Fu, Luying Han, Xinping Lu, Chunrong Yang College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China *These authors contributed equally to this work Introduction: The development of nanodrug carriers utilizing tumor microenvironment has become a hotspot in reversing multidrug resistance (MDR). Materials and methods: This study synthesized a redox-sensitive copolymer, Pluronic F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate (FSST), through the connection of the reduction-sensitive disulfide bond between F127 and D-α-tocopheryl polyethylene glycol 1000 succinate. This polymer could induce the elevation of reactive oxygen species (ROS) levels, ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA, and Pluronic P123, were prepared to load paclitaxel (PTX). Results: The in vitro release study demonstrated that FFSSTP/PTX accelerated the PTX release through the breakage of disulfide bond in reductive environment. In cellular experiment, FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping out PTX by interfering with the mitochondrial function and ATP synthesis. Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular levels of ROS. Conclusion: FFSSTP could become a potential carrier for the treatment of MDR tumors. Keywords: redox responsive, mixed micelles, multidrug resistance, paclitaxel, tumor microenvironment

Min Zhou, Dian Huang, Chen Liu, Zhao Liu, Min Zhang, Tong Qiao, Chang-Jian Liu Department of Vascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China Objective: To compare outcomes of hybrid (combined surgical and endovascular) procedures (HYBRID) with open surgical reconstructions (OPEN) in patients with multilevel infrainguinal artery occlusive diseases. Design: Case series study with retrospective analysis of prospectively collected nonrandomized data.Methods: Between 2008 and 2012, 64 patients underwent OPEN and 43 underwent HYBRID. Patient characteristics, technique success, clinical improvement, and procedure-related morbidity were reviewed and compared. Patency rates and limb salvages were analyzed and compared using Kaplan–Meier life tables. Cox regression analyses were used to assess the influence of various risk factors on primary patency.Results: HYBRID patients were older and presented with worse New York Heart Association function compared with OPEN patients. The increase in the ankle-brachial index and improvement of Ruthford category after procedures were equivalent between two groups, but HYBRID patients had shorter hospital length of stay (7.6±12.0 versus 15.5±17.3; P= 0.018) and less overall perioperative morbidity (12% versus 28%; P=0.042) compared with OPEN patients. No statistically significant difference in 36-month primary (47.1%±7.1% versus 50.1%±9.4%; P=0.418), assisted primary (57.0%±7.9% versus 62.4%±9.2%; P=0.517), or secondary (82.0%±6.8% versus 83.1%±7.3%; P=0.445) patency was seen between the two groups. Limb salvage rates of HYBRID vs OPEN at 3 years were similar (76.3%±9.3% versus 80.4%±8.2%; P=0.579). Critical limb ischemia was a negative predictor of long-term patency of patients in both the HYBRID and OPEN groups (P=0.012 and P

The pretension of building membrane structures may relax over its service lifetime, which may cause engineering failure under external loads. Therefore, the pretension of building membrane structures should be monitored or estimated regularly to compare the actual pretension to its design pretension and then to adopt some strengthening measures to mitigate future problems. Based on the geometrically nonlinear vibration of a rectangular orthotropic membrane structure, a nondestructive detection method for monitoring its pretension is developed in this article. This method is achieved by impacting a low-velocity pellet onto the membrane surface to generate vibration and detecting its response amplitude. Then the detected amplitude is converted into a pretension estimate via a derived formula. In addition, experiments for three kinds of conventional membrane material (Heytex H5573, Xing Yi Da, and ZZF 3010) were carried out according to the theoretical idea. The experimental results proved this method is feasible and verified the theoretical derivation is reasonable.

PURPOSE: To investigate risk factors associated with progressive visual field (VF) loss in primary angle closure glaucoma (PACG). METHODS: We retrospectively reviewed medical record of PACG patients who had ≥5 reliable VF examinations (central 24-2 thresho

Hsin-Yu Yang,1 Yu-Fan Chang,1,2 Chih-Chien Hsu,1,2 Yu-Chieh Ko,1–3 Catherine Jui-Ling Liu,1,3 Mei-Ju Chen1,3 1Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 3School of Medicine, National Yang-Ming University, Taipei, Taiwan Purpose: We evaluated macular ganglion cell asymmetry as a tool for diagnosing paracentral scotoma (PCS) in early glaucoma.Patients and methods: This prospective study compared 58 patients with early glaucoma and PCS to 58 age-matched control individuals. All glaucomatous eyes had scotoma within the central 12 degrees of fixation and confined to one hemifield. We measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with Cirrus spectral domain optical coherence tomography. Macular ganglion cell asymmetry was expressed as the absolute differences and the ratios between the inferior and superior hemispheres, inferotemporal (IT) and superotemporal (ST) areas, IT and superonasal (SN) areas, IT and inferonasal (IN) areas, and ST and IN areas. The asymmetry index was the absolute log10 of the ratio. The area under the receiver operating characteristics curve (AUROC) and partial AUROC (pAUROC, specificities ≥90%) were analyzed for each parameter.Results: All GCIPL parameters and most cpRNFL parameters were significantly lower in early glaucoma than in controls. The best discriminating parameters were inferior RNFL thickness, average RNFL thickness, and minimum GCIPL thickness. The macular ganglion cell asymmetry parameters with the largest AUROCs were the log IT/ST index, the absolute difference in IT-ST GCIPL thicknesses, and the log IT/SN index. Performance was comparable between the log IT/ST index and the cpRNFL (inferior RNFL thickness, P=0.129), GCIPL (minimum GCIPL thickness, P=0.358), and ONH parameters (vertical cup-to-disc ratio, P=0.475).Conclusion: The IT/ST asymmetry index may be useful as a new parameter for detecting structural changes in glaucoma patients with PCS.Keywords: macular ganglion cell, paracentral scotoma, glaucoma, optical coherence tomography

Background. It is unclear whether hepatitis B e antigen (HBeAg) seroconversion induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that of spontaneous HBeAg seroconversion. Methods. A total of 148 noncirrhotic NUC-induced HBeAg seroconverters were consecutively enrolled. A historical control of 407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts. Results. There were 1652.8 and 465.2 person-years of follow-up for spontaneous and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced seroconverters, spontaneous seroconverters were younger when achieving HBeAg seroconversion. We thus compared these 2 cohorts according to their age at HBeAg seroconversion. In patients achieving HBeAg seroconversion before 30 years of age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5-14.4). Using multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of both endpoints in young HBeAg seroconverters. Conclusion. NUC-induced HBeAg seroconverters may not have durable response after stopping therapy. For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in NUC-induced seroconverters than spontaneous HBeAg seroconverters. [ABSTRACT FROM AUTHOR]

Background: Percutaneous cholecystostomy is an alternative treatment for acute cholecystitis patients with high surgical risk.Methods: One hundred and sixty-six patients consecutively treated by percutaneous cholecystostomy for acute cholecystitis in a single medical center were retrospectively reviewed.Results: The cohort included 121 males and 45 females with mean age of 75.9 years. The overall inhospital mortality rate was 15.1 % (n = 25). Elevated serum creatinine level at diagnosis [odds ratio (OR) 1.497; p = 0.020], septic shock (OR 11.755; p = 0.001), and development of cholecystitis during admission (OR 7.256; p = 0.007) were predictive of inhospital mortality. Of 126 patients who recovered from calculous cholecystitis, 11 experienced recurrent cholecystitis within 2 months. Serum C-reactive protein (CRP) level >15 mg dl(-1) at diagnosis [hazard ratio (HR) 10.141; p = 0.027] and drainage duration of cholecystostomy longer than 2 weeks (HR 3.638; p = 0.039) were independent risk factors of early recurrence. The 53 patients who underwent cholecystectomy had an 18.9 % perioperative complication rate and no operation-related mortality.Conclusions: In-patients or those with septic shock or renal insufficiency have worse outcome. Prolonged drainage duration and high CRP level predict early recurrence. Removal of the drainage tube is recommended after resolution of the acute illness. [ABSTRACT FROM AUTHOR]

Background: Acute appendicitis in patients with end-stage renal disease (ESRD) poses a diagnostic challenge. Delayed surgery can contribute to higher morbidity and mortality rates. However, few studies have evaluated this disease among ESRD patients. Our study focused on the lack of data on the incidence and risk factors of acute appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis modalities.Methods: This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard model was used to identify risk factors.Results: Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p = 0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient outcomes.Conclusions: ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non-dialysis populations. A careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important to prevent delayed surgery. [ABSTRACT FROM AUTHOR]

Objective: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis.Methods: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models.Results: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models.Conclusion: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: O (6) -methylguanine-DNA methyltransferase (MGMT) is a specific DNA direct reversal repair protein which ameliorates mutagenic, carcinogenic and cytotoxic adducts from O(6) -methylguanine in DNA. The aim of this study was to investigate the potential association between six polymorphisms in the coding region of the MGMT gene and oral cancer risk in Taiwanese population. METHODS: In this hospital-based case-control study, the MGMT genotypes were determined by using DNA sequencing in 176 patients with oral squamous cell carcinoma (OSCC), 77 patients with oral premalignant lesions and 110 normal individuals. RESULTS: Although L53L and L84F polymorphisms were in complete linkage disequilibrium, no statistically significant association was found between the MGMT genotypes and haplotypes and oral cancer risk. We could also not detect any variations in the codon 65, 143, 160 and 178 within the coding region of the MGMT gene in both patients and controls. After stratification of OSCC patients by their mean age (54 years old), however, a higher overall survival rate with CT genotype than CC genotypes of the L53L polymorphisms was found in older patients (P=0.031). A borderline significance (P=0.074) between these genotypes and recurrence-free survivals has also been noted. The same results were also observed in L84F polymorphism. CONCLUSIONS: The present study did not find statistically significant association between six common MGMT polymorphisms and oral cancer risk, however, both MGMT L53L and L84F polymorphisms in old patients with CT genotype have higher overall survival rates than patients with CC genotype. Because of limited power of the present study, further study may be warranted in ethnically different populations to explore outcomes of these polymorphisms in the oral cancer risk. [ABSTRACT FROM AUTHOR]

Delays in bone healing or even the development of a nonunion could be related to the concentrations and/or functions of the bone morphogenetic proteins (BMPs). The RNA expression profile of the BMPs within fracture nonunion tissue is unknown. This preliminary descriptive study was performed to define the RNA profiles of the BMPs, their receptors, and their inhibitors within human fracture nonunion tissue and correlate them to matched healing bone. All patients had hypertrophic nonunions. Tissue samples taken from the nonunion site of 15 patients undergoing surgical treatment for an established nonunion were analyzed. The RNA expression patterns of BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8; BMP receptor Types IA, IB, and II; and the BMP inhibitors chordin, Noggin, Drm (Gremlin), and follistatin were determined in the nonunion (fibrous tissue) and healing bone (callus tissue) using quantitative real-time PCR. Comparison between the nonunion and healing bone samples revealed substantially elevated concentrations of BMP-4, Drm/Gremlin, follistatin, and Noggin in nonunion tissue when compared to healing bone. In contrast, BMP-7 concentration was higher in the healing bone. Our data suggest inhibition of BMP-7, by Drm (Gremlin), follistatin, and Noggin and upregulation of BMP-4 may play an integral role in the development of nonunions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine whether explanatory illustrations can improve older adults' comprehension of written health information. METHODS: Six short health-related texts were selected from websites and pamphlets. Young and older adults were randomly assigned to read health-related texts alone or texts accompanied by explanatory illustrations. Eye movements were recorded while reading. Word recognition, text comprehension, and comprehension of the illustrations were assessed after reading. RESULTS: Older adults performed as well as or better than young adults on the word recognition and text comprehension measures. However, older adults performed less well than young adults on the illustration comprehension measures. Analysis of readers' eye movements showed that older adults spent more time reading illustration-related phrases and fixating on the illustrations than did young adults, yet had poorer comprehension of the illustrations. CONCLUSION: Older adults might not benefit from text illustrations because illustrations can be difficult to integrate with the text. PRACTICE IMPLICATIONS: Health practitioners should not assume that illustrations will increase older adults' comprehension of health information. [ABSTRACT FROM AUTHOR]

Background: The erythrocyte sedimentation rate, the C-reactive protein serum level, and the white blood-cell count are routinely used to diagnose periprosthetic infection. In the present study, the diagnostic accuracy of the interleukin-6 serum level was compared with the accuracy of these standard tests for the evaluation of a group of patients who had had a total hip or total knee arthroplasty and were undergoing a reoperation for the treatment of an infection or another implant-related problem.Methods: A prospective, case-control study of fifty-eight patients who had had a total hip or knee replacement and were undergoing a reoperation because of an infection (seventeen patients) or another implant-related problem (forty-one patients) was conducted. The serum levels of interleukin-6 and C-reactive protein, the erythrocyte sedimentation rate, and the white blood-cell count were measured. The definitive diagnosis of an infection was determined on the basis of positive histopathological evidence of infection and growth of bacteria on culture of intraoperative specimens. Two-sample Wilcoxon rank-sum (Mann-Whitney) tests were used to determine the presence of a significant difference between patients with and without infection with regard to each laboratory value studied. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each text were also calculated.Results: The serum interleukin-6 level, erythrocyte sedimentation rate, and C-reactive protein level were significantly higher in patients who had an infection than in those who did not, both when all patients were considered together and when the total hip arthroplasty and total knee arthroplasty groups were considered separately. With the numbers available, there was no significant difference with regard to the white blood-cell count between patients with and without infection. With a normal serum interleukin-6 level defined as <10 pg/mL, the serum interleukin-6 test had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 1.0, 0.95, 0.89, 1.0, and 97%, respectively.Conclusions: An elevated serum interleukin-6 level correlated positively with the presence of periprosthetic infection in patients undergoing a reoperation at the site of a total hip or knee arthroplasty. The serum interleukin-6 level is valuable for the diagnosis of periprosthetic infection in patients who have had a total hip or total knee arthroplasty. [ABSTRACT FROM AUTHOR]

Purpose: To assess the correlations between retinal nerve fiber layer (RNFL) thickness measured with scanning laser polarimetry and visual field (VF) sensitivity in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).Design: Prospective, comparative, observational cases series.Methods: Fifty patients with POAG and 56 patients with PACG were examined using scanning laser polarimetry with variable corneal compensation (GDx VCC; Laser Diagnostic Technologies, Inc.) and Humphrey VF analyzer (Carl Zeiss Meditec, Inc.) between August 2005 and July 2006 at Taipei Veterans General Hospital. Correlations between RNFL thickness and VF sensitivity, expressed as mean sensitivity in both decibel and 1/Lambert scales, were estimated by the Spearman rank correlation coefficient (r(s)) and multivariate median regression models (pseudo R(2)). The correlations were determined globally and for 6 RNFL sectors and their corresponding VF regions.Results: The correlation between RNFL thickness and mean sensitivity (in decibels) was weaker in the PACG group (r(s) = 0.38; P = .004; pseudo R(2) = 0.17) than in the POAG group (r(s) = 0.51; P < .001; pseudo R(2) = .31), but the difference in the magnitude of correlation was not significant (P = .42). With Bonferroni correction, the structure-function correlation was significant in the superotemporal (r(s) = 0.62), superonasal (r(s) = 0.56), inferonasal (r(s) = 0.53), and inferotemporal (r(s) = 0.50) sectors in the POAG group (all P < .001), whereas it was significant only in the superotemporal (r(s) = 0.53) and inferotemporal (r(s) = 0.48) sectors in the PACG group (both P < .001). The results were similar when mean sensitivity was expressed as 1/Lambert scale.Conclusions: Both POAG and PACG eyes had moderate structure-function correlations using scanning laser polarimetry. Compared with eyes with POAG, fewer RNFL sectors have significant structure-function correlations in eyes with PACG. [ABSTRACT FROM AUTHOR]

OBJECTIVES: MicroRNAs (miRNAs) are endogenous small non-coding RNAs that negatively regular target gene expression by RNA interference. The processing of the pre-miRNA hairpin generates a miRNA duplex, which consists of a miRNA (guide strand) and a miRNA(*) (passenger strand). miR-31 is an oncogenic miRNA and is up-regulated in oral squamous cell carcinoma (OSCC). miR-31(*) shows a high level of conservation across species and, based on this, this study hypothesized that miR-31(*) is a functional miRNA. MATERIALS AND METHODS: The expression of miR-31 and miR-31* in OSCC tissues and oral cells were analyzed. Functional studies were performed on OSCC cells. RESULTS: miR-31(*) is up-regulated in OSCC tissues, but its expression is less abundant than miR-31. miR-31(*) decreases the proliferation and migration of both SAS and Fadu cells. Furthermore, miR-31(*) targets the 3'UTR of RhoA and is able to down-regulate RhoA expression. Knockdown of RhoA expression is known to decrease the proliferation and migration of OSCC cells. However, up-regulation of both miR-31 and miR-31(*) by delivery of pre-mir-31 does still enhance OSCC oncogenicity. CONCLUSION: miR-31(*) is a functional miRNA involving in regulating RhoA, and the activity of miR-31(*)'s activity seems to counteract the functions of miR-31 during OSCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the pharmacokinetics of L-carnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in healthy volunteers after single L-carnitine administration.Methods: Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC.Results: The maximum plasma concentration (Cmax) and area under the curve (AUC 0-infinity) of L-carnitine was 84.7+/-25.2 micromol x L(-1) x h and 2676.4+/-708.3 micromol x L(-1) x h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h, respectively. The Cmax of ALC (12.9+/-5.5 micromol x L(-1)) and PLC (5.08+/-3.08 micromol x L(-1)) was lower than L-carnitine (P < 0.01), so as the AUC 0-infinity (166.2+/-77.4 and 155.6+/-264.2 micromol x L(-1) x h, respectively, P < 0.01). The half-life of ALC (35.9+/-28.9h) and PLC (25.7+/-30.3 h) was also shorter than L-carnitine (P < 0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5+/-161.7, 368.3+/-134.8 and 61.3+/-37.8 micromol, respectively.Conclusion: L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC. [ABSTRACT FROM AUTHOR]

MicroRNAs are short non-coding RNAs that regulate gene expression by RNA interference. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. miR-146a has been reported to regulate Toll-like receptors and cytokine signaling, which are both crucial for inflammation and oncogenesis. This study identifies that areca nut extract, TNF[alpha] and TGF[beta] up-regulates miR-146a in OSCC cells. The increased expression of miR-146a enhanced the oncogenicity of OSCC cells. In addition, a G to C polymorphism (rs2910164), which is located in the pre-miR-146a and has been associated with functional alterations in miR-146a, was significantly more prevalent among OSCC patients having more advanced nodal involvement. Our analysis also suggested a higher miR-146a expression in OSCC tissues of patients carrying C polymorphism. The present study concluded a higher prevalence of the pre-mir-146a C-variant was associated with OSCC progression in patients with this disease. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a common malignancy. The incidence of OSCC is particularly high in some Asian countries because of the popularity of the habit of chewing areca. Hypoxia-inducible factor-1alpha (HIF-1alpha) is up-regulated in the hypoxic microenvironment to enhance tumor survival. Five polymorphisms have been identified in exon 12 of HIF-1alpha including the C1772T polymorphism causing P582S, and the G1790A polymorphism causing A588T of the HIF-1alpha protein. This study investigated the relationship between these functional polymorphisms and the risk of progression of OSCC. PCR and direct sequencing were utilized to compare the genotypic polymorphism and allelic frequency of HIF-1alpha in 96 normal controls and 305 OSCC patients. No statistically significant difference in C1772T and G1790A genotypes and allelic frequency between control and OSCC patients was found. However, multivariate analysis indicated that the A carrier of HIF-1alpha G1790A in OSCC patients was significantly higher in larger tumors than in the contrasting group with an adjusted odds ratio of 2.92. The T carrier of HIF-1alpha C1772T in buccal cancer patients was significantly higher in the non-areca-chewing group with an adjusted odds ratio of 0.111. The buccal cancer patients with C1772T or G1790A had lower recurrence frequency with an odds ratio of 0.266. These findings may suggest a correlation between the HIF-1alpha C1772T and G1790A polymorphisms and the growth of OSCC, and the decrease of OSCC recurrence frequency. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting >30% of the global population. Metabolic dysregulation, particularly insulin resistance and its subsequent manifestation as type 2 diabetes mellitus, serves as the fundamental pathogenesis of metabolic liver disease. Clinical evidence of the recent nomenclature evolution is accumulating. The interaction and impacts are bidirectional between MASLD and diabetes in terms of disease course, risk, and prognosis. Therefore, there is an urgent need to highlight the multifaceted links between MASLD and diabetes for both hepatologists and diabetologists. The surveillance strategy, risk stratification of management, and current therapeutic achievements of metabolic liver disease remain the major pillars in a clinical care setting. Therefore, the Taiwan Association for the Study of the Liver (TASL), Taiwanese Association of Diabetes Educators, and Diabetes Association of the Republic of China (Taiwan) collaboratively completed the first guidance in patients with diabetes and MASLD, which provides practical recommendations for patient care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Given the crucial role of abnormal homeostasis in tumor cells for maintaining their growth, it may be more efficient with less effort to develop anti-tumor strategies that target multiple combined mechanisms by disrupting intracellular homeostasis. Here, a copper-based nanoinducer (CGBH NNs) with multiple enzyme-like activities is designed and constructed to induce disulfidptosis-enhanced pyroptosis through disrupting multiple intracellular homeostasis for effective tumor immunotherapy. Within the tumor microenvironment (TME), CGBH NNs can disrupt intracellular glucose homeostasis and inhibit NADPH production, leading to accumulation of cystine, which further blocked the substrate and key enzyme for synthesizing glutathione. Subsequently, through cascade catalytic reactions involving enzyme activities (glutathione peroxidase-like, glucose oxidase and peroxidase-like activities), CGBH NNs can produce massive reactive oxygen species (ROS) and further disrupt intracellular redox homeostasis, resulting in the disulfidptosis-enhanced pyroptosis. The tumor cells undergoing immunogenic pyroptosis can release various cytosolic contents and inflammatory factors, eliciting robust immune responses by facilitating immune cell infiltration, and reprogramming the immunosuppressive TME. After the combination with immune checkpoint blockade therapy, CGBH NNs can effectively suppress the tumor growth and prolong the survival time of tumor-bearing mice. This work presents a novel paradigm to trigger disulfidptosis-enhanced pyroptosis by destroying intracellular homeostasis for anti-tumor immunotherapy., (© 2024 Wiley‐VCH GmbH.)

The quest for effective cancer treatment methodologies underpins numerous research endeavors. Despite the therapeutic efficacy of conventional chemotherapy against malignant tumors, tumor recurrence post-therapy remains a formidable challenge. Addressing this, we developed a dual drug delivery system, rooted in a modified metal-organic framework (MOF), specifically by substituting the metal nodes of Uio-66 with cerium to augment its anti-oxidative potential. This engineered system, pyrene-modified hyaluronic acid, functions as a linker, enabling the self-assembly and encapsulation of both the material and the therapeutic agents, and encompasses both doxorubicin and curcumin, aimed at targeting cancer cell eradication and tumorigenesis inhibition. This system demonstrated significant antioxidant capacity through free radical scavenging assays, positioning it as a potential agent in mitigating tumor recurrence. Enhanced anti-tumor activity was distinctly evidenced in human colon cancer cell lines. Additionally, in vitro drug release assessments revealed slow-release kinetics and acid-responsive traits, attributed to the incorporation of pyrenylated hyaluronic acid. Within the xenograft nude mouse model, this system contained a lower amount of doxorubicin, yet, exhibited tumor inhibition capability comparable to the free doxorubicin group. Moreover, it delivered anticancer efficiency under conditions of enhanced antioxidative capacity, underscoring its prospective utility in clinical cancer therapeutics. This dual drug delivery platform not only advances cancer treatment and prophylaxis but also extends novel insights into the therapeutic implications of simultaneous dual drug delivery systems.

Background: The effects of age at HBsAg seroclearance on clinical outcomes and survival in chronic hepatitis B (CHB) have not been adequately assessed. We evaluated the impact of age at HBsAg seroclearance on long-term outcomes, along with how coexisting factors modified risks and life expectancy in CHB patients., Methods: We used multi-state modeling approach to examine transitions through the CHB continuum in a longitudinal cohort study of male civil servants recruited in 1989-1992. Hepatic outcomes and deaths were identified by clinical evaluation and linkage with national health databases. Four sets of risk factors (CHB-related, metabolic, lifestyle, and genetic factors) were assessed., Results: Of 2551 HBsAg carriers, with follow-up until 2021 or death, 695 achieved HBsAg seroclearance, 490 developed cirrhosis (88 decompensated), 252 developed hepatocellular carcinoma (HCC), and 652 died. The cumulative rates for HCC were 1.1% and 1.5% at 10 years after HBsAg seroclearance, respectively, for patients achieving seroclearance at age 50 and 60; correspondingly, the rates for cirrhosis were 2.3% and 3.0%. Developing HBsAg seroclearance was associated with a reduced risk of cirrhosis (HR = 0.37, 95% CI 0.15-0.92) but not HCC. Patients experiencing HBsAg seroclearance lived longer years free of major liver diseases than HBsAg-persistent patients, and achieving seroclearance at age 50 (vs 60) led to a greater increase in the disease-free life expectancy. However, obesity and smoking were associated with adverse hepatic outcomes and loss of the disease-free life expectancy following HBsAg seroclearance., Conclusions: Our findings highlight the benefit of earlier HBsAg seroclearance for gains in disease-free life expectancy and the impact of obesity and smoking on loss of the life years free of major liver diseases following HBsAg seroclearance., (© 2024. Japanese Society of Gastroenterology.)

n -Type Mg 3 Sb 2 -based thermoelectric materials have recently garnered significant interest due to their superior thermoelectric efficiency. Yet, the advancement of p -type Mg 3 Sb 2 for thermoelectric applications is impeded by its lower dimensionless figure of merit ( zT ). In this study, we demonstrate the improved thermoelectric performance of p -type Mg 3 Sb 2 through the strategic optimization of Zn content and Ag doping on the Mg/Zn(2) site. Initially, samples of Mg 3-x Zn x Sb 2 ( x = 0, 0.5, 1.0, and 1.5) were synthesized via elemental reactions within a Pyrex tube, followed by densification through hot pressing. X-ray diffraction analysis confirmed that the Mg 3-x Zn x Sb 2 phases retain the same P 3 ¯ m 1 space group as the pristine Mg 3 Sb 2 phase. The strategic substitution of Zn improved the power factor via band convergence and reduced lattice thermal conductivity by introducing point defect phonon scattering. This led to a peak zT of 0.5 at 725 K, with an average zT of 0.25 across the 325-725 K range. Enhancement in carrier concentration was achieved by doping Ag onto the Zn site, culminating in a peak zT of 0.95 at 725 K and an average zT of 0.46 between 325 and 725 K for the Mg 2 Zn 0.97 Ag 0.03 Sb 2 sample. This performance surpasses that of most p -type Mg 3 Sb 2 -based materials, markedly advancing the potential for Mg 3 Sb 2 -based materials in midtemperature heat recovery thermoelectric generators.

Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins. We underscore the significance of 14-3-3 proteins in the regulation of osteoblasts, osteoclasts, chondrocytes, and bone remodeling, all key factors in the maintenance and dysfunction of bone and joint systems. Specific focus is directed toward elucidating the contribution of 14-3-3 proteins in the pathology of OA, RA, and bone malignancies, where dysregulated 14-3-3-mediated signaling cascades have been implicated in the disease processes. This review illuminates how the perturbation of 14-3-3 protein interactions can lead to the pathological manifestations observed in these disorders, including joint destruction and osteolytic activity. We highlight cutting-edge research that positions 14-3-3 proteins as potential biomarkers for disease progression and as innovative therapeutic targets, offering new avenues for disease intervention and management., (© 2024. The Author(s).)