Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

Roles and competencies in the nutritional domain for the management of the metabolic diseases and in the hospital setting: A position paper of the Italian College of Academic Nutritionists,MED-49 (ICAN-49)

Epidemiological evidence has confirmed the potential causal relationship between specific dietary factors and non-communicable diseases. However, currently nutrition was shown to be insufficiently integrated into medical education, regardless of the country. Without an adequate nutrition education, it is reasonable to assume that future physicians, as well as other health care professionals, will be not able to provide the highest quality care to patients in preventing and treating non-communicable diseases. Furthermore, the insufficient availability of physicians with specializations in nutrition has posed the basis for the development of non-medical careers in the field of nutrition. The present document was drafting by the Italian College of Academic Nutritionists, MED-49 (ICAN-49), with the aim to provide an overview on the nutritional competency standards covered by several health care professionals (Physicians Clinical Nutrition Specialists, Clinical Dietitians, Professional Clinical Nutrition Specialists, etc) for the prevention of diseases and/or support of pharmacological therapies. The aim of the ICAN 49 is to suggest a major shift in practice opportunities and roles for many nutritionists, especially for the management of the metabolic diseases, and promote a paradigm change: a clinical and educational leadership role for Physician Clinical Nutrition Specialists in the hospital setting.     

Tumor-derived extracellular vesicles containing long noncoding RNA PART1 exert oncogenic effect in hepatocellular carcinoma by polarizing macrophages into M2

AimWe explored whether tumor-derived extracellular vesicles (EVs) could deliver long noncoding RNA (lncRNA) PART1 into macrophage to orchestrate macrophage polarization in the progression of hepatocellular carcinoma (HCC).MethodThe expression patterns of PART1, microRNA (miR)-372-3p and TLR4 were detected by RT-qPCR in the HCC tissues and HCC cells. PART1 was silenced or overexpressed in HCC cells to assess its effects on the HCC cell process. EVs were isolated from PART1-overexpressed HCC cells, and co-cultured with macrophages, and gain- and loss-of-function assays were implemented in macrophages to evaluate their role in macrophage polarization. Relationship among PART1, miR-372-3p, and TLR4 was evaluated. Effect of EV-PART1 on tumorigenicity in vivo was detected by subcutaneous tumorigenicity test in nude mice.ResultPART1 and TLR4 were upregulated while miR-372-3p was downregulated in HCC tissues and cells. PART1 increased HCC cell proliferation, migration, invasion, and EMT. Mechanistically, PART1 bound to miR-372-3p to downregulate its expression, whereas TLR4 was negatively targeted by miR-372-3p in the macrophages. EVs containing PART1, TLR4 overexpression, or miR-372-3p inhibition induced M2 polarization of macrophages. Also, EVs containing PART1 promoted M2 polarization of macrophages and the occurrence of HCC by affecting miR-372-3p/TLR4 axis.ConclusionHCC cell-derived EVs might up-regulate TLR4 by inhibiting miR-372-3p via PART1 delivery to promote macrophage M2 polarization in HCC.     

NRG1/ErbB4信号通路与精神疾病关联的研究进展*

在中枢神经系统中,神经调节素1（NRG1）可激活其ErbB受体,影响神经元的发育和迁移,突触的形成、成熟以及突触可塑性。许多研究表明,NRG1与ErbB4基因为精神疾病的易感基因。最早与精神分裂症关联,随后与双向情感障碍、焦虑、抑郁的联系也被逐渐发现。该文通过对NRG1/ErbB4信号通路在中枢神经系统的作用及其与多种精神疾病相关性的研究进行综述,以期为相关精神疾病带来更多的研究思路。     

Patient-led breast cancer follow up

The audit aimed to assess patient satisfaction and GP workload following the introduction of patient-led breast cancer follow up (PLFU), comprising regular mammographic surveillance and easy access self-referral to the breast clinic if required. A questionnaire was sent to 217 patients at low risk of recurrence or death following breast cancer treatment and to 302 GPs. From 217 patients there were 130 respondents (60%) and of these 126 (97%) patients had a clear idea of how to contact the breast unit, and only 5 of 130 patients (4%) required a breast clinic appointment. All 106 respondents (100%) were satisfied with the process to contact the breast unit. Only 10 of 277 GP respondents (3.6%) referred a patient on PLFU back to the breast unit during the study period. PLFU has been well received by patients following breast cancer treatment with little increase in GP workload.     

An Opportunity for Prevention: Associations Between the Life's Essential 8 Score and Cardiovascular Incidence Using Prospective Data from UK Biobank

To investigate the association between the Life's Essential 8 (LE8) score and the incidence of four cardiovascular outcomes (ischemic heart disease, myocardial infarction, stroke, and heart failure [HF]) – separately and as a composite outcome of major adverse cardiovascular events (MACE) – in UK Biobank.250,825 participants were included in this prospective study. Smoking, non-HDL cholesterol, blood pressure, body mass index, HbA1c, physical activity, diet, and sleep were used to create a modified version of the LE8 score. Associations between the score (both as a continuous score and as quartiles) and outcomes were investigated using adjusted Cox proportional hazard models. The potential impact fractions of two scenarios were also calculated. Over a median follow-up of 10.4 years, there were 25,068 MACE. Compared to individuals in the highest quartile of the score (healthiest), those in the lowest quartile (least healthy) had 2.07 (95% CI: 1.99; 2.16) higher risk for MACE. The highest relative risk gradient of the individual outcomes was observed for HF (HR_{lowest quartile}: 2.67 [95% CI: 2.42; 2.94]). The magnitude of association was stronger in participants below 50 years, women, and ethnic minorities. A targeted intervention that increased, by 10-points, the score among individuals in the lowest quartile could have prevented 9.2% of MACE. Individuals with a lower LE8 score experienced more MACE, driven especially by incident HF. Our scenarios suggested that relevant interventions targeted towards those in the lowest quartile may have a greater impact than interventions producing small equal changes across all quartiles.     

Urban–rural environmental exposure during childhood and subsequent risk of inflammatory bowel disease: a meta-analysis

Background: The relationship between living conditions in urban and rural areas during childhood and subsequent inflammatory bowel disease (IBD) remains controversial.

Aim: To explore the association between environmental exposures early in life and the subsequent risk of IBD.

Methods: Literature searches were conducted in the following databases: PubMed, EMBASE, and Conference Proceedings Citation Index. Studies were analyzed separately using rate ratios (RRs) or odds ratios (ORs) with 95% confidence intervals.

Results: The search strategy identified 15 studies. Of these, 9 studies explored the association between urban exposure during childhood and ulcerative colitis (UC), and 12 and 4 studies explored this relationship with Crohn’s disease (CD) and IBD, respectively. A meta-analysis showed that the pooled ORs estimated for the case–control studies of UC, CD, and IBD were 1.16 (0.83, 1.61), 1.45 (1.45, 1.85), and 1.34 (1.11, 1.62), respectively. The pooled RR estimated for the cohort studies of CD and IBD was 1.48 (1.17, 1.87). The stratified analysis and meta-regression showed significant relationships between CD and living conditions in case–control studies published during 2010–2017 and in non-European countries (P < 0.05).

Conclusions: Living conditions during childhood are positively associated with the subsequent development of IBD. Urban living environment is more common among those with CD than UC.     

Predictors of Recurrent Ischemic Stroke in Obese Patients With Type 2 Diabetes Mellitus: A Population-based Study

BackgroundDiabetes and obesity are established risk factors for stroke. The current study aimed to assess risk factors of ischemic stroke recurrence in diabetic patients based on their body mass index (BMI).MethodsA total of 4005 diabetic patients who had a history of ischemic stroke were identified in a retrospective cross-sectional dataset from the Malaysian National Neurology Registry. Patients were classified based on BMI, and multivariable regression analysis was used to evaluate the association between risk factors and recurrent ischemic stroke.ResultsAmong obese patients, those with ischemic heart disease (aOR, 1.873; 95% CI, 1.131–3.103), received formal education (aOR, 2.236; 95% CI, 1.306–3.830), and received anti-diabetic medication (aOR, 1.788; 95% CI, 1.180–2.708) had a higher stroke recurrence risk, while receiving angiotensin receptors blockers (aOR, 0.261; 95% CI, 0.126–0.543) lowered the odds of recurrence. Overweight patients with hypertension (aOR, 1.011; 95% CI, 1.002–1.019) for over 10 years (aOR, 3.385; 95% CI, 1.088–10.532) and diabetes prior to the first stroke (aOR, 1.823; 95% CI, 1.020–3.259) as well as those received formal education (aOR, 2.403; 95% CI, 1.126–5.129) had higher odds of stroke recurrence, while receiving angiotensin-converting enzyme inhibitors (aOR, 0.244; 95% CI, 0.111–0.538) lowered the recurrence risk. Normal weight East Malaysians (aOR, 0.351; 95% CI, 0.164–0.750) receiving beta-blockers (aOR, 0.410; 95% CI, 0.174–0.966) had lower odds of stroke recurrence.ConclusionsIschemic heart disease, hypertension, receiving anti-hypertensive agents, and educational level were independent predictors of recurrent stroke in obese patients. Managing the modifiable risk factors can decrease the odds of stroke recurrence.