Characteristics and influencing factors of demoralization in patients with lung cancer: A latent class analysis.

OBJECTIVE: Demoralization has garnered increasing attention in recent years as a significant psychological distress. This study aims to identify latent classes of demoralization in lung cancer patients using Latent Class Analysis (LCA) from a person-centered perspective and to explore the factors influencing the latent classes of demoralization. METHODS: A cross-sectional study using convenience sampling was conducted among 567 lung cancer patients in three tertiary hospitals in China. LCA was employed to classify heterogeneous classes of demoralization. Multinomial logistic regression analyses were performed to explore the associations between demographic and clinical characteristics, as well as physical symptoms, resilience, family function, and coping strategies, with class membership in the identified heterogeneous subgroups of lung cancer patients. RESULTS: Three latent classes of demoralization were identified: the high demoralization group (Class 1, 14.8%), the moderate demoralization-distress and helplessness group (Class 2, 37.2%), and the low demoralization group (Class 3, 48.0%). In comparison to Class 3, lung cancer patients with hypertension, higher core symptom burden, poorer resilience, dysfunctional family dynamics, and resignation coping were more likely to belong to Class 1 and Class 2. CONCLUSIONS: The demoralization patterns in lung cancer patients were varied. Targeted intervention should be developed based on the characteristics of each class, and timely attention should be paid to high-risk patients.

Risk of Hemorrhagic Stroke among Patients Treated with High-Intensity Statins versus Pitavastatin-Ezetimibe: A Population Based Study.

High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults (≥ 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.

Comparison of the Clinical Efficacy and Safety of Standard and Ultrasound-Assisted Thrombolysis for Pulmonary Embolism: A Systematic Review and Meta-Analysis.

PURPOSE: Catheter-directed therapy has been increasingly used in acute pulmonary embolism (PE). Whether ultrasound-assisted thrombolysis (USAT) is superior to standard catheter-directed thrombolysis (SCDT) remains unclear. This is a systemic review and meta-analysis of comparative trials on USAT and SCDT for PE to determine whether either modality yielded better clinical efficacy and safety. MATERIALS AND METHOD: Major databases including PubMed, Embase, Cochrane Central, and Web of Science were searched through March 16, 2023. Studies that reported outcomes of SCDT and USAT for acute PE were included. Studies reported data on therapeutic efficacy (a reduction in the right ventricle [RV]/left ventricle [LV] ratio, a reduction in the systolic pulmonary artery pressure [mm Hg], change in Miller index, length of intensive care unit [ICU] and hospital stay) and safety outcomes (in-hospital mortality, overall and major bleeding events). RESULTS: A total of 9 studies with 2610 patients were included in the meta-analysis. The analysis showed significantly greater improvement in the RV/LV ratio in the SCDT group than in the USAT group (mean difference [MD]: -0.155; 95% confidence interval [CI]: -0.249 to -0.006). No statistically significant differences were found between groups comparing change in systolic pulmonary artery pressure (MD: 0.592 mm Hg; 95% CI: -2.623 to 3.807), change in Miller index (MD: -4.1%; 95% CI: -9.5 to 1.3%), hospital stay (MD: 0.372 days; 95% CI: -0.972 to 1.717), and ICU stay (MD: -0.073.038 days; 95% CI: -1.184 to 1). No significant difference was noted in safety outcomes, including in-hospital mortality (pooled odds ratio: 0.984; 95% CI: 0.597 to 1.622), and major bleeding (pooled odds ratio: 1.162; 95% CI: 0.714 to 1.894). CONCLUSIONS: In our meta-analysis of observational and randomized studies, USAT is not superior to SCDT in patients with acute PE.INSPLAY registration number: INPLASY202240082. CLINICAL IMPACT: This study compared SCDT and USAT in patients with acute pulmonary embolism. We found no additional benefit in PA pressure change, thrombus reduction, hospital stay, mortality and major bleeding rate. Additional study using consistent treatment protocol is necessary for further investigation.

Aromatization of natural products by a specialized detoxification enzyme.

In plants, lineage-specific metabolites can be created by activities derived from the catalytic promiscuity of ancestral proteins, although examples of recruiting detoxification systems to biosynthetic pathways are scarce. The ubiquitous glyoxalase (GLX) system scavenges the cytotoxic methylglyoxal, in which GLXI isomerizes the α-hydroxy carbonyl in the methylglyoxal-glutathione adduct for subsequent hydrolysis. We show that GLXIs across kingdoms are more promiscuous than recognized previously and can act as aromatases without cofactors. In cotton, a specialized GLXI variant, SPG, has lost its GSH-binding sites and organelle-targeting signal, and evolved to aromatize cyclic sesquiterpenes bearing α-hydroxyketones to synthesize defense compounds in the cytosol. Notably, SPG is able to transform acetylated deoxynivalenol, the prevalent mycotoxin contaminating cereals and foods. We propose that detoxification enzymes are a valuable source of new catalytic functions and SPG, a standalone enzyme catalyzing complex reactions, has potential for toxin degradation, crop engineering and design of novel aromatics.

Understanding factors influencing demoralization among cancer patients based on the bio-psycho-social model: A systematic review.

OBJECTIVE: Demoralization is a prevalent psychological problem among cancer patients and reflects a sense of subjective incompetence. This systematic review aims to identify factors influencing demoralization among cancer patients. METHODS: Eleven databases were systematically searched from database inception to 31 December 2020. Google Scholar and relevant reference lists were supplementarily searched. Studies reporting demoralization measured by Demoralization Scale and its influencing factors among cancer patients were included. A qualitative synthesis was conducted owing to the heterogeneity of the study outcome. RESULTS: A total of 49 studies involving 10,712 participants were included in this review. The results showed substantial effect size variation, but the psychological factors showed the strongest magnitude of association. Among the biological factors, the number of physical symptoms (mean r values [rs]: 0.331) was associated with increased demoralization. Among the psychological factors, negative psychological factors include hopelessness (mean rs: 0.633), desire for death (mean rs: 0.620), dignity-related distress (mean rs: 0.595), depression (mean rs: 0.593), anxiety (mean rs: 0.589), psychological distress (mean rs: 0.465), and suicidal ideation (mean rs: 0.460) were related to increased demoralization; whereas positive psychological factors including hope (mean rs: -0.565), attachment security (mean rs: -0.530), and sense of coherence (mean rs: -0.453) were related to decreased demoralization. Among the social factors, social support (mean rs: -0.330) was negatively related to demoralization, and the demographic factors were still controversial. Quality of life was considered to be at the intersection of biopsychosocial factors and negatively associated with demoralization (mean rs: -0.599). CONCLUSIONS: Demoralization is a consequence of the interaction of physical, psychological, and social factors among cancer patients. Factors with a significant effect should not be overlooked when designing an intervention to reduce demoralization. It is necessary to distinguish demoralization from other negative psychological states and further explore positive psychological factors influencing demoralization among cancer patients.

1,10/1,11-Cyclization catalyzed by diverged plant sesquiterpene synthases is dependent on a single residue.

The exquisite chemodiversity of terpenoids is the product of the large diverse terpene synthase (TPS) superfamily. Here, by using structural and phylogenetic analyses and site-directed mutagenesis, we identified a residue (Cys440 in Nicotiana tabacum 5-epi-aristolochene synthase) proximal to an ion-binding motif common to all TPSs and named the preNSE/DTE residue, which determines the product specificity of sesquiterpene synthases from different plant species. In sesquiterpene synthases catalyzing 1,10-cyclization (1,10-cyclases) of farnesyl diphosphate, mutation of the residue in both specific and promiscuous 1,10-cyclases from different lineages leads to the accumulation of monocyclic germacrene A-11-ol, which is "short-circuited" from complex cyclization cascades, suggesting a key role of this residue in generating the first common intermediate of 1,10-cyclization. Altering this residue in a specific 1,11-cyclase results in alternative 1,10-cyclization products. Moreover, the preNSE/DTE residue can be harnessed to engineer highly specific sesquiterpene synthases for an improved proportion of high-value terpenoids, such as patchoulol, a main constituent of several traditional Chinese medicines that could treat SARS-CoV-2.

Appropriate Use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors for Atherosclerotic Cardiovascular Disease: Comparison of Recommendations from Different Guidelines or Consensus Around the World.

Increased low-density lipoprotein cholesterol (LDL-C) is the most crucial risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the mainstay therapy, but many patients need to add non-statin treatment to reach the recommended LDL-C goal. Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective agents in LDL-C reduction, they are much more expensive than other lipid-lowering agents. In January 2020, the Taiwan National Health Insurance (NHI) program started to reimburse PCSK9 inhibitors for select ASCVD patients with certain conditions. Major guidelines or consensus worldwide also provide specific recommendations about how to appropriately use these agents. This review summarizes the Taiwan NHI regulations of using PCSK9 inhibitors and compared them with other guidelines or consensus around the world.

Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment.

BACKGROUND: In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy. OBJECTIVES: To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors. METHODS: This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n = 85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants' next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects. RESULTS: Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants. CONCLUSION: This secondary analysis provides evidence that for participants maintained on opioid agonist therapy, clonidine minimized the behavioral impact of moderate levels of negative affect and craving.

Sex differences in daily life stress and craving in opioid-dependent patients.

BACKGROUND: Responses to stress and drug craving differ between men and women. Differences in the momentary experience of stress in relation to craving are less well-understood. OBJECTIVES: Using ecological momentary assessment (EMA), we examined sex differences in real-time in two areas: (1) causes and contexts associated with stress, and (2) the extent to which stress and drug cues are associated with craving. METHODS: Outpatients on opioid-agonist treatment (135 males, 47 females) reported stress, craving, and behavior on smartphones for 16 weeks. They initiated an entry each time they felt more stressed than usual (stress event) and made randomly prompted entries 3 times/day. In stress-event entries, they identified the causes and context (location, activity, companions), and rated stress and craving severity. RESULTS: The causes reported for stress events did not differ significantly by sex. Women reported arguing and being in a store more often during stress events, and men reported working more often during stress events, compared to base rates (assessed via random prompts). Women showed a greater increase in opioid craving as a function of stress (p < 0.0001) and had higher stress ratings in the presence of both stress and drug cues relative to men (p < 0.01). Similar effects were found for cocaine craving in men (p < 0.0001). CONCLUSION: EMA methods provide evidence based on real-time activities and moods that opioid-dependent men and women experience similar contexts and causes for stress but differ in stress- and cue-induced craving. These findings support sex-based tailoring of treatment, but because not all participants conformed to the overall pattern of sex differences, any such tailoring should also consider person-level differences.

Somatic symptoms, sleep disturbance and psychological distress among women undergoing oocyte pick-up and in vitro fertilisation-embryo transfer.

AIMS AND OBJECTIVES: This study investigated the relationship between somatic symptoms, sleep disturbance and psychological distress in women who underwent oocyte pick-up and in vitro fertilisation-embryo transfer. BACKGROUND: According to worldwide research, women receiving assisted reproductive technologies may suffer from somatic and psychological symptoms and even experience sleep disturbance. Apparently, the guilt of infecundity forces Asian women to conceal this scenario and delay the time at which they accept medical assistance and mental support. DESIGN: A longitudinal study. METHODS: The subjects in this study were infertile female patients who received oocyte pick-up and in vitro fertilisation-embryo transfer therapies in a hospital in northern Taiwan. Data were collected via a structured questionnaire, including somatic symptoms, Pittsburgh Sleep Quality Index and a five-item brief symptom rating scale. Data were analysed using the McNemar's test, Wilcoxon Sign Rank and fully entered multiple regression with spss version 20.0 software. RESULTS: The mean age of 100 participants was 34·54 (SD = 3·94) years old. They experienced abdominal distention, breast engorgement, nausea, faintness, diarrhoea, sleep disturbance and psychological distress when they received in vitro fertilisation-embryo transfer; these results were apparently higher than those receiving oocyte pick-up. In addition, sleep disturbance was the most significant factor involved in psychological distress during oocyte pick-up and in vitro fertilisation-embryo transfer therapies. The most serious indicator of the women's psychological distress during oocyte pick-up and in vitro fertilisation-embryo transfer treatment is anxiety. CONCLUSIONS: Sleep disturbance was the most significant factor involved in the psychological distress of women having problems with conception. RELEVANCE TO CLINICAL PRACTICE: Assisted reproductive technologies nurses can assess women's psychological distress by caring for their sleep disturbance without directly exploring their mood state. Moreover, these medical personnel should understand infertile female patients' psychological distress is mainly associated with their sleep disturbance. Developing various strategies to improve both sleep quality and psychological distress for infertile female patients should be recognised in future studies.

Somatic symptoms, psychological distress and sleep disturbance among infertile women with intrauterine insemination treatment.

AIMS AND OBJECTIVES: To explore sleep quality in infertile women and examine the factors that contribute to sleep disturbances during intrauterine insemination treatment. BACKGROUND: Sleep disturbance is an important factor of human health and well-being. Sleep disturbances tend to occur among infertile women during intrauterine insemination treatment. Although many studies have focused on the high percentage of somatic symptoms and psychological distress in infertile women associated with their treatment, few studies have investigated factors linked to their sleep disturbances. DESIGN: A cross-sectional study. METHODS: The study was conducted during the period of September 2010-January 2011 in a teaching hospital in Taiwan. Infertile women (n = 117) who received assisted reproduction with intrauterine insemination treatment completed a questionnaire. Demographic data, somatic symptoms, psychological distress and perceived sleep quality were collected. RESULTS: More than one-third (35%) of the infertile women reported having sleep disturbances. Their nausea symptoms and psychological distress were risk factors that contributed to sleep disturbance. CONCLUSIONS: The variables of nausea and psychological distress significantly explained 30% of the sleep disturbances in the infertile women. The evaluation of nausea symptoms and/or psychological distress among infertile women is an important area of future research; such research should aim to identify the best compromise between infertility treatment and sleep quality. RELEVANCE TO CLINICAL PRACTICE: Clinical obstetrics and gynaecology nurses should develop strategies to help infertile women reduce their nausea symptoms and psychological distress during intrauterine insemination treatment to promote healthy sleep.

Regulation of Glandular Size and Phytoalexin Biosynthesis by a Negative Feedback Loop in Cotton.

Plants have evolved diverse defense mechanisms encompassing physical and chemical barriers. Cotton pigment glands are known for containing various defense metabolites, but the precise regulation of gland size to modulate defense compound levels remains enigmatic. Here, it is discovered that the VQ domain-containing protein JAVL negatively regulates pigment gland size and the biosynthesis of defense compounds, while the MYC2-like transcription factor GoPGF has the opposite effect. Notably, GoPGF directly activates the expression of JAVL, whereas JAVL suppresses GoPGF transcription, establishing a negative feedback loop that maintains the expression homeostasis between GoPGF and JAVL. Furthermore, it is observed that JAVL negatively regulates jasmonate levels by inhibiting the expression of jasmonate biosynthetic genes and interacting with GoPGF to attenuate its activation effects, thereby maintaining homeostatic regulation of jasmonate levels. The increased expression ratio of GoPGF to JAVL leads to enlarged pigment glands and elevated jasmonates and defense compounds, enhancing insect and pathogen resistance in cotton. These findings unveil a new mechanism for regulating gland size and secondary metabolites biosynthesis, providing innovative strategies for strengthening plant defense.

Single-cell RNA sequencing reveals a hierarchical transcriptional regulatory network of terpenoid biosynthesis in cotton secretory glandular cells.

Plants can synthesize a wide range of terpenoids in response to various environmental cues. However, the specific regulatory mechanisms governing terpenoid biosynthesis at the cellular level remain largely elusive. In this study, we employed single-cell RNA sequencing to comprehensively characterize the transcriptome profile of cotton leaves and established a hierarchical transcriptional network regulating cell-specific terpenoid production. We observed substantial expression levels of genes associated with the biosynthesis of both volatile terpenes (such as ß-caryophyllene and ß-myrcene) and non-volatile gossypol-type terpenoids in secretory glandular cells. Moreover, two novel transcription factors, namely GoHSFA4a and GoNAC42, are identified to function downstream of the Gossypium PIGMENT GLAND FORMATION genes. Both transcription factors could directly regulate the expression of terpenoid biosynthetic genes in secretory glandular cells in response to developmental and environmental stimuli. For convenient retrieval of the single-cell RNA sequencing data generated in this study, we developed a user-friendly web server . Our findings not only offer valuable insights into the precise regulation of terpenoid biosynthesis genes in cotton leaves but also provide potential targets for cotton breeding endeavors.

Dirigent gene editing of gossypol enantiomers for toxicity-depleted cotton seeds.

Axial chirality of biaryls can generate varied bioactivities. Gossypol is a binaphthyl compound made by cotton plants. Of its two axially chiral isomers, (-)-gossypol is the bioactive form in mammals and has antispermatogenic activity, and its accumulation in cotton seeds poses health concerns. Here we identified two extracellular dirigent proteins (DIRs) from Gossypium hirsutum, GhDIR5 and GhDIR6, which impart the hemigossypol oxidative coupling into (-)- and (+)-gossypol, respectively. To reduce cotton seed toxicity, we disrupted GhDIR5 by genome editing, which eliminated (-)-gossypol but had no effects on other phytoalexins, including (+)-gossypol, that provide pest resistance. Reciprocal mutagenesis identified three residues responsible for enantioselectivity. The (-)-gossypol-forming DIRs emerged later than their enantiocomplementary counterparts, from tandem gene duplications that occurred shortly after the cotton genus diverged. Our study offers insight into how plants control enantiomeric ratios and how to selectively modify the chemical spectra of cotton plants and thereby improve crop quality.

Influencing factors of cancer prevention and control among urban and rural adults in Fujian, China: A cross-sectional survey.

Objective: Cancer burden can be reduced when the population's knowledge of cancer prevention and control measures is increased. However, current epidemiological research investigating cancer prevention and control knowledge in China is limited. This study aimed to examine the core knowledge levels of cancer prevention and control measures as well as its influencing factors among adults in Fujian, China. Study design: A cross-sectional study. Methods: From September to December 2021, a total of 2,440 Chinese urban and rural adults from Fujian Province, located in Southeastern China, were randomly selected for this cross-sectional study. The probability proportionate approach to sampling was used. A 38-item questionnaire that covered demographics and basic knowledge of cancer, including concepts, screening, therapy, and rehabilitation-related key points was used to measure knowledge levels of cancer prevention and control measures among 2,074 participants. The level of each participants' core knowledge of cancer prevention and control measures was defined as a rate calculated by the number of correct answers divided by the total number of questions. The binary logistic regression model was used to determine if influencing factors were associated with core knowledge awareness. Results: In total, 1,290 participants (62.2%) were in the low knowledge group and 784 (37.8%) were in the high knowledge group. The average knowledge rate of cancer prevention and control measures among all participants was 56.01%. Participants from urban areas, who held white-collar jobs, were married, had a bachelor's degree or above, had a family history of cancer, or self-rated their health level as good or average were associated with higher rates of cancer prevention and control core knowledge (overall p < 0.05). Conclusion: These findings may assist healthcare providers and/or researchers in designing effective primary preventive interventions to enhance the general population's cancer prevention and control knowledge, and subsequently decrease the cancer burden in China.

Case Report: A novel desmoplakin mutation in a taiwanese woman with familial dilated cardiomyopathy that necessitated heart transplantation.

Around one-third of patients diagnosed with idiopathic dilated cardiomyopathy (DCM) turn out to be familial cases, in only a few of which the identification of a pathogenic/likely pathogenic variant could be achieved. Cardiomyopathy caused by desmoplakin gene mutations represents a distinct form with a high prevalence of left ventricle involvement. We report a novel desmoplakin mutation carried by two individuals in a Taiwanese family, in which the proband recovered well after heart transplantation and under medical control, while her son had received an implantable cardioverter defibrillator and has been under guideline-directed medical therapy. The present study broadens the genetic spectrum of this disease entity and strengthens the notion that a detailed family history with genetic study contributes to the early detection and treatment of inherited diseases.

Real-World Analyses of the Safety Outcome among a General Population Treated with Statins: An Asian Population-Based Study.

AIM: The safety concern of statins is still a major issue for Asians. The aim of this study is to compare the risk of statin-associated adverse events among potent statins. METHODS: We included patients from the Taiwan National Health Insurance Research Database who had been treated with atorvastatin, rosuvastatin, or pitavastatin and were without diabetes at baseline. They were classified into three groups: usual-dose statin (atorvastatin 10 mg/d or rosuvastatin 5-10 mg/d), high-dose statin (atorvastatin 20-40 mg/d and rosuvastatin 20 mg/d), and pitavastatin (2-4 mg/d). The primary endpoint is a composite of safety events, including hepatitis, myopathy, and new-onset diabetes mellitus (NODM). We matched age, sex, and year of recruitment among the three groups (n=50,935 in each group) and then used the multivariate Cox proportional hazards model to evaluate the relation between the safety endpoint and different statin groups. RESULTS: After a mean follow-up of 3.08±0.83 years, the safety events occurred in 9.84% in the pitavastatin group, 10.88% in the usual-dose statin group, and 10.49% in high-dose statin group. The multivariate Cox proportional hazards model indicated that usual-dose statin and high-dose statin were associated with a higher risk of the composite safety events compared with pitavastatin (adjusted hazard ratio [aHR]: 1.12, 95% confidence interval [CI]: 1.08-1.17 for usual-dose statin and aHR: 1.06, 95% CI: 1.02-1.10 for high-dose statin). The risks of hepatitis requiring hospitalization and NODM were especially lower in pitavastatin group. CONCLUSIONS: Compared with atorvastatin and rosuvastatin, pitavastatin might be associated with a lower risk of safety events in Asians.

Barriers and facilitators to uptake of lung cancer screening: A mixed methods systematic review.

Numerous factors contribute to the low adherence to lung cancer screening (LCS) programs. A theory-informed approach to identifying the obstacles and facilitators to LCS uptake is required. This study aimed to identify, assess, and synthesize the available literature at the individual and healthcare provider (HCP) levels based on a social-ecological model and identify gaps to improve practice and policy decision-making. Systematic searches were conducted in nine electronic databases from inception to December 31, 2020. We also searched Google Scholar and manually examined the reference lists of systematic reviews to include relevant articles. Primary studies were scored for quality assessment. Among 3938 potentially relevant articles, 36 studies, including 25 quantitative and 11 qualitative studies, were identified for inclusion in the review. Fifteen common factors were extracted from 34 studies, including nine barriers and six facilitators. The barriers included individual factors (n = 5), health system factors (n = 3), and social/environmental factors (n = 1). The facilitators included only individual factors (n = 6). However, two factors, age and screening harm, remain mixed. This systematic review identified and combined barriers and facilitators to LCS uptake at the individual and HCP levels. The interaction mechanisms among these factors should be further explored, which will allow the construction of tailored LCS recommendations or interventions for the Chinese context.

A Randomized Controlled Trial Evaluating Outcome Impact of Cilostazol in Patients with Coronary Artery Disease or at a High Risk of Cardiovascular Disease.

Previous studies found that cilostazol has a favorable effect on glucose and lipid homeostasis, endothelial function, atherosclerosis, and vasculo-angiogenesis. However, it is poorly understood whether these effects can translate into better clinical outcomes. This study investigated the outcome effect of cilostazol in patients with coronary artery disease (CAD) or at a high risk of cardiovascular (CV) disease. We conducted a randomized, double-blind, placebo-controlled trial involving 266 patients who received cilostazol, 200 mg/day (n = 134) or placebo (n = 132). Pre-specified clinical endpoints including composite major adverse cardiovascular events (MACE) (CV death, non-fatal myocardial infarct, non-fatal stroke, hospitalization for heart failure, or unplanned coronary revascularization), the composite major coronary event (MCE) and major adverse CV and cerebrovascular event (MACCE), were prospectively assessed. The mean duration of follow-up was 2.9 years. Relative to placebo, cilostazol treatment had a borderline effect on risk reduction of MACE (hazard ratio [HR], 0.67; 95% confidence interval (CI), 0.34-1.33), whereas the beneficial effect in favor of cilostazol was significant in patients with diabetes mellitus or a history of percutaneous coronary intervention (p for interaction, 0.02 and 0.06, respectively). Use of cilostazol, significantly reduced the risk of MCE (HR, 0.38; 95% CI, 0.17-0.86) and MACCE (HR, 0.47; 95% CI, 0.23-0.96). A significantly lower risk of angina pectoris (HR, 0.38; 95% CI, 0.17-0.86) was also observed in the cilostazol group. After multi-variable adjustment, cilostazol treatment independently predicted a lower risk of MCE. In conclusion, these results suggest cilostazol may have beneficial effects in patients with CAD or at a high risk of CV disease.

Side Products of Recombinant Amorpha-4,11-diene Synthase and Their Effect on Microbial Artemisinin Production.

Amorpha-4,11-diene synthase (ADS) is the first committed enzyme in the biosynthesis of artemisinin. Artemisinin production by biobased fermentation is considered a reliable alternative pathway. Heterologously expressed ADS has been established to generate several minor products, including structural analogues of amorpha-4,11-diene, but their fate in fermentation is still unknown. Here, using chiral analysis, we found that ADS produces one of the analogues, amorpha-4-en-11-ol, as a pair of epimers. Labeling experiments revealed that ADS mutants yielded amorphene-type sesquiterpenes, indicating the co-occurrence of initial 1,6 and 1,10 cyclization of farnesyl diphosphate in a single enzyme. Interestingly, the immediate downstream oxidase CYP71AV1 had very low affinity to the side products of the recombinant ADS, including amorpha-4-en-7-ol, which is structurally similar to amorpha-4,11-diene. Our data uncover the complex catalytic mechanism of recombinant ADS and reveal a potential negative effect of the side products of recombinant ADS on the production of the artemisinin precursor in microbes.