EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.

Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy.

Breast cancer, a complex and varied disease, has four distinct subtypes based on estrogen receptor and human epidermal growth factor receptor 2 (HER2) levels, among which a significant subtype known as HR+/HER2-breast cancer that has spurred numerous research. The prevalence of breast cancer and breast cancer-related death are the most serious threats to women's health worldwide. Current progress in treatment strategies for HR+/HER2-breast cancer encompasses targeted therapy, endocrine therapy, genomic immunotherapy, and supplementing traditional methods like surgical resection and radiotherapy. This review article summarizes the current epidemiology of HR+/HER2-breast cancer, introduces the classification of HR+/HER2-breast cancer and the commonly used treatment methods. The mechanisms of action of various drugs, including targeted therapy drugs and endocrine hormone therapy drugs, and their potential synergistic effects are deeply discussed. In addition, clinical trials of these drugs that have been completed or are still in progress are included.

Combating antimicrobial resistance: the silent war.

Once hailed as miraculous solutions, antibiotics no longer hold that status. The excessive use of antibiotics across human healthcare, agriculture, and animal husbandry has given rise to a broad array of multidrug-resistant (MDR) pathogens, posing formidable treatment challenges. Antimicrobial resistance (AMR) has evolved into a pressing global health crisis, linked to elevated mortality rates in the modern medical era. Additionally, the absence of effective antibiotics introduces substantial risks to medical and surgical procedures. The dwindling interest of pharmaceutical industries in developing new antibiotics against MDR pathogens has aggravated the scarcity issue, resulting in an exceedingly limited pipeline of new antibiotics. Given these circumstances, the imperative to devise novel strategies to combat perilous MDR pathogens has become paramount. Contemporary research has unveiled several promising avenues for addressing this challenge. The article provides a comprehensive overview of these innovative therapeutic approaches, highlighting their mechanisms of action, benefits, and drawbacks.

Thrombolysis after cardiopulmonary resuscitation in myocardial infarction with abdominal pain as the first presentation: A case report.

RATIONALE: Thrombolysis after cardiopulmonary resuscitation in patients with acute ST-segment elevation myocardial infarction (STEMI) is controversial. This case report describes a successful thrombolysis after resuscitation in delayed-diagnosis STEMI. PATIENT CONCERNS: A 58-year-old man presented with acute abdominal pain as the first symptom of a subsequent STEMI diagnosis. When he returned to the clinic after having been assisted with abdominal pain relief, he suffered a sudden cardiac arrest. Cardiopulmonary resuscitation was performed immediately, and thrombolysis was carried out for his anterior STEMI. He was successfully resuscitated in a short period of time. DIAGNOSIS: The patient was diagnosed with acute and extensive anterior STEMI. The D-dimer level was normal, and pericardial effusion was ruled out. INTERVENTIONS: After successful resuscitation, the patient received half-dose alteplase thrombolytic therapy. After a few days, the patient was transferred to a general ward. Coronary angiography revealed unobstructed flow in the left anterior descending artery. OUTCOMES: The ST segment of the patient gradually declined after thrombolytic therapy, and the myocardial injury marker levels increased. A small amount of pleural fluid in the lungs and pulmonary infection were observed. With effective diuretic, anti-infective, and other treatments, the patient's condition gradually improved, the ventilator was removed, and vasoactive drugs were successfully discontinued. Coronary angiography revealed that the flow of the culprit artery was unobstructed, and a drug-coated balloon was implanted. No wall motion abnormalities were detected on echocardiography, and the patient recovered well. CONCLUSIONS: In patients with abdominal pain as the first presentation, a simple initial electrocardiogram may help reduce the risk of missed STEMI diagnosis. Thrombolysis after successful resuscitation is an effective treatment for these patients. However, the effects of thrombolysis after resuscitation remain unclear. The point of dispute lies in the effectiveness and safety of thrombolysis (primarily for bleeding). Prompt thrombolysis would lead to a better prognosis if spontaneous circulation can be restored within 10 minutes.

Depression and Anxiety Among Quarantined People, Community Workers, Medical Staff, and General Population in the Early Stage of COVID-19 Epidemic.

Background: We described the prevalence of anxiety and depression related to COVID-19 pandemic among different types of population and examined their potential risk factors. Methods: A cross-sectional survey was conducted to collect demographic characteristics, exposure histories, and many other concerns about COVID-19. The Zung's self-rating anxiety scale (SAS) and self-rating depression scale (SDS), followed by a four-step multiple logistic regression analysis was performed to identify factors associated with mental health outcomes. Results: Out of 3,303 participants, the quarantined people (40.9%), community workstation staffs-policemen-volunteers (CPV) (36.4%) and general public (30.7%) reported higher percentages of depression than the general medical staff (18.4%). Moreover, the quarantined people (19.1%) also showed higher prevalence of anxiety than the general public (9.1%) and the general medical staff (7.8%). The quarantined people had the highest risk of anxiety and depression, whereas the self-rated health was negatively associated with the risks of anxiety and depression. Younger age group (18 to 30 years) showed higher risks of anxiety (OR = 6.22, 95% CI = 2.89-13.38, p < 0.001) and depression (OR = 3.69, 95% CI = 2.40-5.69, p < 0.001). People who had exposure history or contact from Hubei province after December 1, 2019 (OR = 1.57, 95% CI = 1.07-2.30, p < 0.001), had family or friends engaged in front-line health care work (OR = 1.47, 95% CI = 1.02-2.14, p < 0.001), had confirmed case nearby (OR = 2.44, 95% CI = 1.43-4.18, p < 0.001) were all more likely to suffer from anxiety. Moreover, the negligence (OR = 1.85, 95% CI = 1.37-2.51, p < 0.001) or overindulgence (OR = 1.45, 95% CI = 1.03-2.04, p < 0.001) toward the epidemic information was associated with a higher risk of depression and anxiety. Conclusions: Our findings show that the CPV and quarantined people were most at-risk population. We have identified that the young people, people with exposure histories and negligence or overindulgence toward epidemic information are in grave need of attention.

Remote pharmacy service in primary care: The implementation of a cloud-based pre-prescription review system.

BACKGROUND: To reduce the occurrence of inappropriate prescription in primary care through the introduction of a cloud-based pre-prescription review system. OBJECTIVE: We aimed to describe the implementation of a cloud-based pre-prescription review system in the pharmacy practice of Chinese community health centers (CHCs), which currently have few qualified pharmacists. PRACTICE DESCRIPTION: The cloud-based pre-prescription review system featured reviews by remote clinical pharmacists and targeted the prevention of inappropriate prescription in primary care. PRACTICE INNOVATION: This study describes the implementation of remote pharmacy at 22 CHCs in Futian District, Shenzhen, China. A pre-prescription system was developed and deployed in the cloud, which is linked to CHCs, and a consortium of qualified clinical pharmacists located in tertiary hospital. All prescriptions were mandatorily reviewed before printing and payment. First, prescriptions were reviewed using cloud-based rational drug use software. Then any detected potentially inappropriate prescriptions were reviewed by the remote pharmacist. The pharmacist consortium also modified review rules to improve efficiency and accuracy. EVALUATION METHODS: The frequency and proportions of potentially inappropriate prescriptions identified by the review software and the remote pharmacist consortium were analyzed descriptively. RESULTS: During the 6-month study period (July 1, 2019-December 31, 2019), 340,117 prescription entries from general practitioners in 22 community health care centers were reviewed. Of these, 6479 (3.0%) unique potential entries were suspended for pharmacist review, of which 3230 (49.9%) needed correction from prescribers in the CHCs. The most common corrections were related to improper administration routes or drug-drug interactions or had no justified indications. CONCLUSION: Inappropriate prescription is not uncommon in CHCs. The cloud-based prescription prereview model proposed in this study can serve as an important tool for the prevention of inappropriate prescription in primary care. The pre-prescription review system also provided opportunities for pharmacists to participate in the enhancement of patient care in primary care.

Association between hyperhomocysteinemia and metabolic syndrome with early carotid artery atherosclerosis: A cross-sectional study in middle-aged Chinese population.

OBJECTIVES: Homocysteine is a modifiable, independent risk factor for cardiovascular disease. The association between hyperhomocysteinemia and metabolic syndrome with the presence of early carotid artery atherosclerosis remains unknown in middle-aged Chinese adults. METHODS: Chinese adults (n = 1607) of Han ethnicity, age 35 to 65 y, and living in their communities >2 y were surveyed. Hyperhomocysteinemia was defined as homocysteine concentrations >15 µmol/L. Carotid intima-media thickness and carotid plaque were examined by ultrasonography. All participants were classified into four groups by hyperhomocysteinemia and metabolic syndrome status. RESULTS: Participants with both hyperhomocysteinemia and metabolic syndrome had the highest levels of waist circumference and systolic blood pressure compared with the three other groups. The highest proportion of increased carotid intima-media thickness (61.3%) was in the subgroup of both hyperhomocysteinemia and metabolic syndrome. After adjustments for the covariates, the risk of increased carotid intima-media thickness was only significantly higher in the group with metabolic syndrome but without hyperhomocysteinemia (odds ratio: 1.47; 95% confidence interval, 1.13-1.93) compared with people without hyperhomocysteinemia and metabolic syndrome. Furthermore, statistically significant variances of prevalence of plaque among the four subgroups were not discovered. CONCLUSIONS: Our study demonstrated that metabolic syndrome had a strong effect on carotid intima-media thickness However, the increased homocysteine levels were not significantly associated with early carotid artery atherosclerosis in middle-aged Chinese people.

The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article.

BACKGROUND: We conducted a systematic review and meta-analysis to firstly obtain a reliable estimation of the prevalence of metabolically healthy obese (MHO) individuals in obesity, then assessed the risk of developing metabolic abnormalities (MA) among MHO individuals. At last, we evaluated the effects of traditional lifestyle interventions on metabolic level for MHO subjects. METHODS: A systematic review and meta-analysis (PRISMA) guideline were conducted, and original studies were searched up to December 31, 2016. The prevalence of MHO in obesity from each study was pooled using random effects models. The relative risks (RRs) were pooled to determine the risk of developing MA for MHO compared with metabolically healthy normal-weight (MHNW) subjects. For the meta-analysis of intervention studies, the mean difference and standardized mean differences were both estimated for each metabolic parameter within each study, and then pooled using a random-effects model. RESULTS: Overall, 40 population-based studies reported the prevalence of MHO in obesity, 12 cohort studies and 7 intervention studies were included in the meta-analysis. About 35.0% obese individuals were metabolically healthy in the obese subjects. There were dramatic differences in the prevalence among different areas. However, 0.49 (95% confidence intervals [CI]: 0.38 to 0.60) of the MHO individuals would develop one or more MA within 10 years. Compared with MHNW subjects, the MHO subjects presented higher risk of incident MA (pooled RR = 1.80, 95%CI: 1.53-2.11). Following intervention, there was certain and significant improvement of metabolic state for metabolically abnormal obesity (MAO) subjects. Only diastolic blood pressure had reduced for MHO individuals after intervention. CONCLUSIONS: Almost one-third of the obese individuals are in metabolic health. However, they are still at higher risk of advancing to unhealthy state. Therefore, it is still needed to advise MHO individuals to maintain or adopt a healthy lifestyle, so as to counterbalance the adverse effects of obesity.