Clinimetric properties of the "FIND-NEEDS" to screen geriatric conditions.

INTRODUCTION: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. METHODS: First-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). RESULTS: The mean age of the 114 outpatients was 78.3±7.6 years, and 79(69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r=0.494; p<0.001), and the binary score showed excellent correlation (r=0.944; p<0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). DISCUSSION/CONCLUSION: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.

Structural Analysis and Novel Mechanism of Enteromorpha prolifera Sulfated Polysaccharide in Preventing Type 2 Diabetes Mellitus.

A water-soluble polysaccharide (EP) was purified from edible algae Enteromorpha prolifera. Gel permeation chromatography (GPC), ion chromatography (IC), and fourier transform infrared (FT-IR) were performed to characterize its structure. EP was defined as a low molecular weight (6625 Da) composed of rhamnose, glucose, glucuronic acid, xylose, galactose, arabinose, and mannose. Moreover, it was a sulfated polysaccharide with a degree of substitution (DS) of 1.48. Then, the high-fat diet/streptozotocin (HFD/STZ) induced diabetic mouse model was established to support evidence for a novel hypoglycemic mechanism. Results showed that blood glucose (47.32%), liver index (7.65%), epididymal fat index (16.86%), serum total cholesterol (26.78%) and triglyceride (37.61%) in the high-dose EP (HEP) group were significantly lower than those in the HFD group. Noticeably, the content of liver glycogen in the HEP group was significantly higher (62.62%) than that in the HFD group, indicating the promotion of glycogen synthesis. These beneficial effects were attributed to significantly increased protein kinase B (AKT) phosphorylation and its downstream signaling response. Further studies showed that diabetic mice exhibited excessive O-GlcNAcylation level and high expression of O-linked ß-D-N-acetylglucosamine transferase (OGT), which were decreased by 62.21 and 30.43% in the HEP group. This result suggested that EP had a similar effect to OGT inhibitors, which restored AKT phosphorylation and prevented pathoglycemia. This work reveals a novel hypoglycemic mechanism of EP, providing a theoretical basis for further studies on its pharmacological properties in improvement of T2DM.

Efficacy of Laser in Hair Removal: A Network Meta-analysis.

BACKGROUND: Laser hair removal is an increasingly prevalent trend of cosmetic procedures. The purpose of this study was to assess the effectiveness of hair reduction among several types of laser interventions. METHODS: The selected studies searched in PubMed and EMBASE were assessed for quality of evidence, and extracted data on absolute hair count and hair reduction rate. Qualitative data were synthesized using standardized mean difference (SMD) in frequentist network meta-analysis because various measurement units were used among selected studies. Inconsistency and small study effects were examined by design-by-treatment interaction model and comparison-adjusted funnel plot. RESULTS: A total of 13 randomized controlled trials (RCTs) (n = 652) were contributed to network meta-analysis. Pooled results revealed that diode laser showed significantly lower absolute hair count within three-month (SMD = -13.21, 95% confidence interval [CI]: -22.25 to -4.17) and around six months follow-up (SMD = -11.01, 95% CI: -18.24 to -3.77) as compared with those in control group, but no significant difference among laser interventions. All side effects observed were transient without leaving any permanent scars. CONCLUSION: Eliminating unwanted hair with lasers or intense pulsed light is safe and effective; however, which type of intervention is more beneficial in the long-term process should be studied with a longer follow-up time.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Real-World Data on Comparison of Lipid-Lowering Effects between Alirocumab and Evolocumab in Patients with Hypercholesterolemia.

Background: Even though the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, have been approved to reduce plasma low-density lipoprotein cholesterol (LDL-C) and the risk of atherosclerotic cardiovascular disease in high-risk patients, real-world data showing comparisons of the lipid-lowering effects between alirocumab and evolocumab are scarce because of the low prescription rates of PCSK9 inhibitors in clinical practice. Methods: Between Feb 2018 and Sep 2021, 22 patients who received alirocumab and 22 patients who received evolocumab at a tertiary medical center were enrolled. The patients' baseline characteristics, prescribed medications, plasma LDL-C levels, and percentages of reduction in LDL-C were compared between alirocumab users and evolocumab users. Results: The alirocumab users more frequently received ezetimibe treatment (72.7% vs. 40.9%, p = 0.03) and had higher baseline LDL-C (165.6 ± 63.2 mg/dL vs. 130.8 ± 56.3 mg/dL, p = 0.04) compared with the evolocumab users. At 6 months of follow-up, the plasma LDL-C levels in the alirocumab users were similar to those in the evolocumab users (79.3 ± 64.0 mg/dL vs. 63.5 ± 44.1 mg/dL, p = 0.48). Additionally, the percentages of LDL-C reduction following treatment were similar between the alirocumab users and evolocumab users (-47.0% ± 45.0% vs. -49.8 ± 24.9%, p = 0.66). Conclusions: The LDL-C lowering effects of alirocumab are similar to those of evolocumab in clinical practice.

Beyond GHz optical frequency up-converted modulation of LEDs with integrated acousto-optic transducer.

Traditional visible light communication (VLC) via light-emitting diodes (LEDs) employs the on-off keying (OOK) modulation scheme. Even though optical frequency modulation has many advantages, it is hardly used for LED VLC because a high carrier frequency cannot be applied to the LED cavity due to the resistance-capacitance limit. Here, by monolithically integrating an LED with an integrated digital transducer, we experimentally demonstrate the intermixing of gigahertz surface acoustic waves and electrical data signals in the LED cavity at room temperature. An optical transmitter was realized by in situ frequency up-conversion of the data signals from an LED, which has the advantages of improving transmission performance by up-shifting the data spectrum away from low-frequency noise. Our proposed integrated acousto-optic transducer opens a new developing scheme on the frequency up-mixed data encoding of an LED beyond its inherent modulation bandwidth for future VLC.

Negative pressure wound therapy for burn patients: A meta-analysis and systematic review.

Negative pressure wound therapy (NPWT), which has been applied in various medical specialties to accelerate wound healing, has been the object of a few investigations. We explored the effectiveness of NPWT and the possibility of its inclusion in burn management guidelines. Randomised controlled trials comparing NPWT with non-NPWT treatments for burn wounds were extracted from PubMed. For the risk of bias analysis, all included studies were evaluated according to the Cochrane risk of bias tool and the approaches outlined in the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) Handbook. Outcomes such as graft take rate in the first week, infection rate, and overall complication rate were analysed. Six studies that included a total of 701 patients met our inclusion criteria. Qualitative analysis revealed that the NPWT group had a significantly better overall graft rate in the first week (P = 0.001) and a significantly lower infection rate (P = 0.04). No significant difference in the overall complication rate was found. Our results indicate that NPWT is a safe method for stimulating healing and lowering the infection rate of burn wounds. NPWT can be part of general burn management, and its incorporation into burn treatment guidelines is recommended.

The use of micro-needle arrays to deliver cells for cellular therapies.

Cell therapy is used to treat various diseases and to repair injuries. Cell delivery is a crucial process that delivers cells to target sites. Cells must be precisely delivered to a target site and the cells that are delivered must be localized to the target site to repair damaged tissue. For stem cell therapy, the most convenient method of cell delivery involves directly injecting cells into damaged tissue. Other strategies use carriers to transplant stem cells into damaged tissue. These are termed, stem cell delivery systems (SCDSs). Micro-needle arrays are minimally invasive transdermal delivery systems. The devices can pass through the stratum corneum barrier and deliver macromolecules into the skin. They can also access the microcirculation system in the skin. This study fabricates PMMA micro-needle using a two-stage micro-molding method. Cells are seeded on the micro-needle arrays and then transferred into the target tissue. Collagen hydrogel is used as a model biomimetic tissue. Cells are efficiently delivered to regions of interest, collagen hydrogel, by using this system. The delivery rate is about 83.2%. This demonstrates that micro-needle arrays allow very efficient delivery of cells.

The Role of Leisure Activities in the Relationship Between Marital Transition in Later Midlife and Psychological Well-Being Trajectories.

This study examined the levels and rates of changes in psychological well-being for middle-aged adults of different statuses or marital transitions. The moderating effects of different leisure activities were also tested. Longitudinal data on 1,270 persons aged 50 to 65 years at baseline from the Taiwan longitudinal study on aging were analyzed. Adults who were stably unmarried or unpartnered reported worse mental health at baseline, but their psychological well-being improved over time. The trajectory of depressive symptoms fluctuated markedly in adults who became widowed during our observation period. Engagement in physical, cognitive, or social activities was significantly associated with participants' psychological well-being. Participation in religious activities was significantly associated with life satisfaction and decreased depressive symptoms for those undergoing bereavement. Findings from this study suggest that social and physical activities, among the four selected leisure activities, have the greatest association between decreasing depressive symptoms and increasing life satisfaction, respectively. Religious activities, in particular, may improve psychological well-being in bereaved middle-aged and older adults.

[Investigation and genetic identification on Babesia infection in rodents in some areas of Fujian Province].

Objective: To explore the status of Babesia infection in rodents and the genetic characteristics of Babesia spp. in Fujian Province. Methods: Rodents were captured by the night trapping method in Shaowu, Qingliu, Shunchang, Yong'an, Changle and Youxi during 2014-2015. The rodent species was identified, and information on the time and place of capture, species and sex of rodents was recorded. Blood samples was collected, in which the fragment of 18S rRNA gene of Babesia spp. was amplified by PCR. The PCR products were sequenced and the phylogenetic tree was constructed for homology analysis. Data on positive rate were analyzed with Chi-square or Fisher exact test. Results: Two hundred and nine rats were captured, comprising of 71 domestic and 138 wild rats. The overall positive rate was 9.6%(20/209). The positive rate in domestic rats was 2.8%(2/71), including one Rattus norvebicus and one Rattus flavipectus. The positive rate in wild rats was 13.0%(18/138), including 13 Bandicota indica, one Rattus losea, 2 Rattus confucianus and 2 Rattus fulvescens. The positive rate was significantly higher in wild rats than in domestic rats (P < 0.05). The Youxi region had the highest positive rate(14.9%,13/87), followed by Yong'an(13.6%, 3/22), and no positive rat was found in Qingliu. The positive rate in the male rats was 7.9%(9/114), and that in the females was 11.6%(11/95). The positive rate was highest in adult rats (10.4%,18/173), followed by young ones (6.3%,2/32). No positive rat was found in old rats. There was no significant difference in positive rate among different regions, between male and female rats, or among different ages (P > 0.05). The sequences of PCR products had a 100% homology. The BLAST results revealed the species to be Babesia microti. The phylogenetic tree showed that the sample sequence was the most homologous with Babesia microti from Zhejiang Province(GenBank Accession No: JQ609305). Conclusion: There occurs Babesia microti infection in rats in part areas of Fujian Province. The positive rate was higher in wild rats than in domestic rats.

Suicide Reporting on Front Pages of Major Newspapers in Taiwan Violating Reporting Recommendations Between 2001 and 2012.

Media reporting can lead to the acceptance of incorrect ideas and information by the general public, which in turn can impact behavior. A number of studies have found that suicide reporting in the media can lead to an increase in the suicide rate or copycat suicides. Therefore, the aims of this study are to (a) investigate front-page reporting of suicide in four major newspapers in Taiwan; (b) investigate violation of recommendations for reporting suicide by the four major newspapers in Taiwan; and (c) investigate the impact of important events and government policy on front-page reporting of suicide (i.e., the effect of the Apple Daily newspaper entering the market, and the start of media monitoring). We carried out content analysis of reports of suicide on the front pages of the four newspapers with the highest rates of readership in Taiwan (China Times, Liberty Times, Apple Daily, and United Daily News) between 2001 and 2012. We used the chi-squared test, chi-squared test for trend, and analysis of variance to analyze trends in violation of reporting recommendations and potential associated factors. We found that (a) suicide was most commonly reported as a front-page headline and as a whole-page spread by the four major newspapers in Taiwan, with many reports including photographs; (b) reporting of suicide by the four major newspapers in Taiwan frequently violated World Health Organization (WHO) recommendations for suicide reporting in the media; (c) following the entry of the Apple Daily newspaper into the Taiwanese market, reporting approaches to suicide by the other three major newspapers changed to more sensational photos and texts; and (d) monitoring of suicide reporting by the Taiwan Suicide Prevention Center appears to have been only partially effective. In summary, reporting of suicide by the four major newspapers in Taiwan could be further improved. Effective regulation of suicide reporting by newspapers could reduce the impact of this reporting on readers. In addition, regular assessment of observance of the WHO recommendations for suicide reporting by newspapers is an important part of suicide prevention.

Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance.

Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment.

Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer.

Mitochondria are key organelles in mammary cells in responsible for a number of cellular functions including cell survival and energy metabolism. Moreover, mitochondria are one of the major targets under doxorubicin treatment. In this study, low-abundant mitochondrial proteins were enriched for proteomic analysis with the state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assistant laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the mitochondrial protein profiling changes in response to the development of doxorubicin resistance in human uterine cancer cells. The mitochondrial proteomic results demonstrate more than fifteen hundred protein features were resolved from the equal amount pooled of three purified mitochondrial proteins and 101 differentially expressed spots were identified. In which, 39 out of these 101 identified proteins belong to mitochondrial proteins. Mitochondrial proteins such as acetyl-CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) have not been reported with the roles on the formation of doxorubicin resistance in our knowledge. Further studies have used RNA interference and cell viability analysis to evidence the essential roles of ACAT1 and MDH2 on their potency in the formation of doxorubicin resistance through increased cell viability and decreased cell apoptosis during doxorubicin treatment. To sum up, our current mitochondrial proteomic approaches allowed us to identify numerous proteins, including ACAT1 and MDH2, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for the treatment of doxorubicin-resistant uterine cancer.

10 m/25 Gbps LiFi transmission system based on a two-stage injection-locked 680 nm VCSEL transmitter.

A 10 m/25 Gbps light-based WiFi (LiFi) transmission system based on a two-stage injection-locked 680 nm vertical-cavity surface-emitting laser (VCSEL) transmitter is proposed. A LiFi transmission system with a data rate of 25 Gbps is experimentally demonstrated over a 10 m free-space link. To the best of our knowledge, it is the first time a two-stage injection-locked 680 nm VCSEL transmitter in a 10 m/25 Gbps LiFi transmission system has been employed. Impressive bit error rate performance and a clear eye diagram are achieved in the proposed systems. Such a 10 m/25 Gbps LiFi transmission system provides the advantage of a communication link for higher data rates that could accelerate the deployment of visible laser light communication.

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery.

CONTEXT: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on. OBJECTIVE: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers. METHODS: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates. RESULTS AND DISCUSSION: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ∼12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX. CONCLUSION: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.

Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance.

Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2µM cells and MES-SA/DxR-8µM cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.

[Lead compound optimization strategy (2)--structure optimization strategy for reducing toxicity risks in drug design].

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.

Sex-based differences in ischemic cardiovascular and bleeding outcomes following implantation of drug-eluting stent in patients at high bleeding risk.

BACKGROUND: Patients with high bleeding risk (HBR) may exhibit uncertain adherence to dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation. The current population-based cohort study aimed to investigate the sex-based differences in adverse outcomes among the HBR population by analyzing the National Health Insurance Research Database in Taiwan. METHODS: Patients who had HBR features defined by the Academic Research Consortium (ARC) and received DES implantation between January 1, 2007, and December 31, 2017, were enrolled. Propensity score matching was adopted to select 3,981 pairs with similar clinical cardiovascular risks but different sexes. A competing risk model was performed to evaluate the risk of adverse ischemic events (cardiac death, nonfatal myocardial infarction, and ischemic stroke) and any bleeding events in both sexes. Noncardiac death was considered a competing risk. RESULTS: Within a 5-year follow-up, the incidence rates (per 1,000 person-year (95% confidence interval (CI)) of composite ischemic events and any bleeding events in males were respectively 44.09 (40.25-48.30) and 42.55 (38.79-46.68), while those in females were respectively 40.18 (36.51-44.23) and 42.35 (38.57-46.51). After adjustment for clinical variables, male patients had a marginally increased risk in the composite ischemic events (adjusted subdistribution hazard ratio (SHR) = 1.15 (1.00-1.31), p = 0.045) and a similar risk of any bleeding events (adjusted SHR = 1.00 (0.88-1.15), p = 0.946) compared with female patients. CONCLUSIONS: Of the HBR population, males had an increased risk of ischemic outcomes but a similar risk of bleeding compared with females following DES implantation.