The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients. In CYP3A5 non-expressers, the patients carrying the IL-3 rs181781 AA genotype showed a significantly higher TAC logC0/D than those with the AG genotype at 30 and 90 d post-operation (AA vs AG, 2.21±0.06 vs 2.01±0.03, P=0.004; and 2.17±0.06 vs 2.03±0.03, P=0.033, respectively), and than those with the GG genotype at 30 d (AA vs GG, 2.21±0.06 vs 2.04±0.03, P=0.011). At 30 d, the TAC logC0/D in the grouped AG+GG genotypes of CTLA4 rs4553808 was significantly lower than that in the AA genotype (P=0.041) in CYP3A5 expressers, but it was higher (P=0.008) in the non-expressers. We further validated the influence of CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437 on the TAC C0/D; other candidate SNPs were not associated with the differences in TAC C0/D. In conclusion, genetic polymorphisms in the immune genes IL-3 rs181781 and CTLA4 rs4553808 may influence the TAC C0/D. They may, together with CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437, contribute to the variation in TAC dose requirements. When conducting individualized therapy with tacrolimus, these genetic factors should be taken into account.

Background With the rapid development of online health communities, increasing numbers of patients and families are seeking health information on the internet. Objective This study aimed to discuss how to fully reveal the health information needs expressed by patients with hypertension in their questions in a web-based environment and how to use the internet to help patients with hypertension receive personalized health education. Methods This study randomly selected 1000 text records from the question data of patients with hypertension from 2008 to 2018 collected from Good Doctor Online and constructed a classification system through literature research and content analysis. This paper identified the background characteristics and questioning intention of each patient with hypertension based on the patient’s question and used co-occurrence network analysis and the k-means clustering method to explore the features of the health information needs of patients with hypertension. Results The classification system for the health information needs of patients with hypertension included the following nine dimensions: drugs (355 names), symptoms and signs (395 names), tests and examinations (545 names), demographic data (526 kinds), diseases (80 names), risk factors (37 names), emotions (43 kinds), lifestyles (6 kinds), and questions (49 kinds). There were several characteristics of the explored web-based health information needs of patients with hypertension. First, more than 49% of patients described features, such as drugs, symptoms and signs, tests and examinations, demographic data, and diseases. Second, patients with hypertension were most concerned about treatment (778/1000, 77.80%), followed by diagnosis (323/1000, 32.30%). Third, 65.80% (658/1000) of patients asked physicians several questions at the same time. Moreover, 28.30% (283/1000) of patients were very concerned about how to adjust the medication, and they asked other treatment-related questions at the same time, including drug side effects, whether to take the drugs, how to treat the disease, etc. Furthermore, 17.60% (176/1000) of patients consulted physicians about the causes of clinical findings, including the relationship between the clinical findings and a disease, the treatment of a disease, and medications and examinations. Fourth, by k-means clustering, the questioning intentions of patients with hypertension were classified into the following seven categories: “how to adjust medication,” “what to do,” “how to treat,” “phenomenon explanation,” “test and examination,” “disease diagnosis,” and “disease prognosis.” Conclusions In a web-based environment, the health information needs expressed by Chinese patients with hypertension to physicians are common and distinct, that is, patients with different background features ask relatively common questions to physicians. The classification system constructed in this study can provide guidance to health information service providers for the construction of web-based health resources, as well as guidance for patient education, which could help solve the problem of information asymmetry in communication between physicians and patients.

Cyberchondria is considered “the anxiety-amplifying effects of online health-related searches.” During the COVID-19 pandemic, people are likely to search health-related information online for reassurance because of fear and related physical symptoms, while cyberchondria may be triggered due to the escalation of health anxiety, different online seeking behavior preference, information overload, and insufficient e-health literacy. This study aimed to investigate the status and influencing factors of cyberchondria in residents in China during the epidemic period of COVID-19. The participants were 674 community residents of Nanyang city surveyed from February 1 to 15, 2020. We administered online measures, including the Chinese Short Form of the Cyberchondria Severity Scale (C-CSS-12), Short Health Anxiety Inventory (SHAI), eHealth Literacy Scale (eHEALS), Patient Health Questionnaire-15 (PHQ-15), and COVID-19-related online information seeking behavior questionnaire. In our study, the average C-CSS-12 total score of residents was 30.65 ± 11.53 during the virus epidemic; 25% of participants scored 22 or below, 50% scored 23 to 38, and 21.9% scored 39 to 60. The SHAI total score (β = 0.598 > 0, P < 0.001), the use of general search engines (β = 1.867 > 0, P = 0.039), and searching for information on how to diagnose COVID-19 (β = 2.280 > 0, P = 0.020) were independent risk factors for cyberchondria, while searching lasting less than 10 min each (β = −2.992 < 0, P = 0.048), the use of traditional media digital platforms (β = −1.650 < 0, P = 0.024) and professional medical communication platforms (β = −4.189 < 0, P = 0.007) were independent protective factors. Our findings showed that nearly a quarter of the participants scored 39 or higher on the C-CSS-12 in Nanyang city during the pandemic, which should be taken seriously. Health anxiety and COVID-19-related online information seeking behavior including online duration, topics and choice on different information channels were important influencing factors of cyberchondria. These findings have implications for further research and clinical practice on cyberchondria in China.

Disregulation of fatty acid oxidation, one of the major mechanisms for maintaining hepatic lipid homeostasis under fasting conditions, leads to hepatic steatosis. Although obesity and type 2 diabetes-induced endoplasmic reticulum (ER) stress contribute to hepatic steatosis, it is largely unknown how ER stress regulates fatty acid oxidation. Here we show that fasting glucagon stimulates the dephosphorylation and nuclear translocation of histone deacetylase 5 (HDAC5), where it interacts with PPARα and promotes transcriptional activity of PPARα. As a result, overexpression of HDAC5 but not PPARα binding-deficient HDAC5 in liver improves lipid homeostasis, whereas RNAi-mediated knockdown of HDAC5 deteriorates hepatic steatosis. ER stress inhibits fatty acid oxidation gene expression via calcium/calmodulin-dependent protein kinase II-mediated phosphorylation of HDAC5. Most important, hepatic overexpression of a phosphorylation-deficient mutant HDAC5 2SA promotes hepatic fatty acid oxidation gene expression and protects against hepatic steatosis in mice fed a high-fat diet. We have identified HDAC5 as a novel mediator of hepatic fatty acid oxidation by fasting and ER stress signals, and strategies to promote HDAC5 dephosphorylation could serve as new tools for the treatment of obesity-associated hepatic steatosis.

Drug-induced diabetes is widely reported in clinical conditions, and it is becoming a global issue because of its potential to increase the risk of severe cardiovascular complications. However, which drug mechanisms exert their diabetogenic effects and why the effects present significant inter-individual differences remain largely unknown. Pharmacogenomics, which is the study of how genomic variation influences drug responses, provides an explanation for individual differences in drug-induced diabetes. We highlight that pharmacogenomics can be involved in regulating the expression of genes in signaling pathways related to the pharmacokinetics or pharmacodynamics of drugs or the pathogenesis of diabetes, contributing to the differences in drug-induced glucose impairment. The pharmacogenomics studies of the major diabetogenic drugs are reviewed, including calcineurin inhibitors, antipsychotics, hormones, and antihypertensive drugs. We intend to elucidate the genetic basis of drug-induced diabetes and pave the way for the precise use of these drugs in the clinic.