Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

COVID-19 ; Humans ; Kidney Transplantation ; Retrospective Studies ; SARS-CoV-2 ; Transplant Recipients

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.
Humans ; Air Pollution/adverse effects* ; Temperature ; Outpatients ; Cities ; Eczema/epidemiology* ; China/epidemiology* ; Air Pollutants/analysis*

INTRODUCTION: This study aimed to assess understanding of the potential risks associated with medical imaging among caregivers and adolescent patients in a paediatric emergency department (PED) in Singapore. METHODS: A prospective convenience sample survey was performed involving adolescents and caregivers presenting to our PED from December 2015 to May 2016. The questionnaire examined demographic data, knowledge of imaging procedures and radiation risks, and expectations regarding information provided about medical radiation. RESULTS: A total of 349 questionnaires were returned (caregivers 82.5%, adolescents 17.5%). A mean of 6.2 ± 2.4 (out of 11) questions were correctly answered. Those who had tertiary education fared better than those who did not (36.4% vs. 17.2% scoring above the mean, p = 0.001). Age, gender, history of previous imaging and imaging performed during the visit did not affect the score. Two-thirds of the participants did not associate medical radiation with any negative lifetime risk of cancers or know that different scans entailed differing amounts of radiation. Most were unaware that the radiation dose in medical imaging is adjusted to a child's size. Among patients who underwent imaging, 90.1% received explanations on the need for scans, and 26.5% were informed of the risks involved. Almost all participants wished to be informed of imaging indications and risks. More preferred to learn this from physicians (75.6%) or technicians (51.6%) rather than through educational pamphlets (34.4%) or Internet resources (22.9%). CONCLUSION Awareness regarding medical radiation needs to be improved in our patient population. A mismatch exists between caregiver expectations and the actual procedure of disclosure of the risk associated with radiation.

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Objective: To investigate the mechanism of Zuoguiwan in treating ovariectomy-induced osteoporosis rats by receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway mediated by β₂-adrenergic receptor (β₂AR). Method: Forty Sprague-Dawley female rats were randomly divided into Sham-operated group (Sham) and four ovariectomized (OVX) subgroups. Rats in Sham and OVX groups were treated with 17β-estradiol (50 μg·kg^-1·d^-1), and low and high-dose ZGW (2.3,4.6 g·kg^-1 lyophilized powder) for 3 months, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum markers of bone turnover. Micro-CT was used to evaluate and measure trabecular bone microarchitecture and bone mineral density (BMD) of the right distal femur. Western blot analysis and Real-time PCR were used to measure mRNA and protein expressions of β₂AR, OPG and RANKL. Result: After 12 weeks of treatment with Zuoguiwan, the level of serum β-cross-linked c-telopeptide of type Ι collagen (β-CTX) (P<0.01) was lower, while the level of serum bone-specific alkaline phosphatase (BALP) was higher (P<0.01) than those in the OVX group. Moreover, it could prevent the OVX-induced bone loss, and alleviate the trabecular bone microarchitecture of distal femur. Furthermore, Zuoguiwan could up-regulate the mRNA and protein expressions of OPG in tibia of the Zuoguiwan groups(P<0.01), reduce the mRNA and protein expressions of β₂AR in the hypothalamus (P<0.01), and down-regulated the mRNA and protein expressions of RANKL (P<0.05) in the tibia, compared with those in the OVX group. Conclusion: The mechanism of Zuoguiwan in alleviating BMD and trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats might be related to the regulation of RANKL/OPG Pathway mediated by β₂AR.

INTRODUCTION: Family history of psychopathology is a risk factor for mood and anxiety disorders in children, but little is known about rates of parental psychopathology among treatment-seeking youth with affective disorders in the Asia Pacific region. This study examined patterns of emotional and behavioural problems in parents of clinically-referred youth in Singapore. We hypothesised that parents would have higher rates of affective disorders compared to the Singapore national prevalence rate of 12%. MATERIALS AND METHODS: In this cross-sectional study, 47 families were recruited from affective disorders and community-based psychiatry programmes run by a tertiary child psychiatry clinic. All children had a confirmed primary clinical diagnosis of depression or an anxiety disorder. Parents completed the Mini International Neuropsychiatric Interview (MINI) to assess for lifetime mood and anxiety disorders. They also completed the Adult Self Report (ASR) and Adult Behavior Checklist (ABCL) to assess current internalising and externalising symptoms. RESULTS: Consistent with our hypothesis, 38.5% of mothers and 10.5% of fathers reported a lifetime mood and anxiety disorder. Nearly 1/3 of mothers had clinical/subclinical scores on current internalising and externalising problems. A similar pattern was found for internalising problems among fathers, with a slightly lower rate of clinical/subclinical externalising problems. CONCLUSION Our findings are consistent with previous overseas studies showing elevated rates of affective disorders among parents - particularly mothers - of children seeking outpatient psychiatric care. Routine screening in this population may help to close the current treatment gap for adults with mood and anxiety disorders.
Adult ; Anxiety Disorders ; diagnosis ; epidemiology ; psychology ; Child ; Cross-Sectional Studies ; Family Health ; statistics & numerical data ; Female ; Humans ; Male ; Mood Disorders ; diagnosis ; epidemiology ; psychology ; Parent-Child Relations ; Parenting ; psychology ; Parents ; psychology ; Psychiatric Status Rating Scales ; Psychopathology ; Singapore ; epidemiology

Dao-di herbs have been recognized as "quality models" with a firmly stable status. The formation of Dao-di herbs quality is involved from the genetic inheritance on the molecular level to the metabolic phenotype of final products, and the full material-based biosynthetic pathway remains unknown. In recent years, an increasing variety of omics technologies has provided new methods and ideas for the analysis of complex life systems and are suitable for explanation of quality formation in Dao-di herbs as well. In order to alleviate the scarcity of natural resources and offer scientific guidance of transplanting varieties, achievements of omics in the aspects of Dao-di herbs from genetics to phenotyping, the biosynthetic pathway of secondary metabolites, the interaction with human body and the new methods of quality evaluation have been summarized. It will be a fundamental work for protection and utilization of Chinese medicine resources.

Objective To explore serum long stranded noncoding RNA (lncRNA) transcript 1 (PCAT-1) expression level of patients with multiple myeloma (MM) and clinical value.Methods 72 cases of patients with MM treated in the Second People's Hospital of Zhaoqing City were selected as the study objects,and 60 cases of normal subjects undergoing physical examination in the same period were as the control group.Serum lncRNA PCAT-1 expression was detected by RT-PCR method.The relationship between lncRNA PCAT 1 expression and clinical pathological parameters,treatment effect was analyzed,and 5 years survival was analyzed by using Kaplan-Meier,and survival difference was detected by using Log-Rank method.Results Serum PCAT-1mRNA expression in MM group (2.65 ± 0.64) was significantly higher than that in the control group (1.06 ± 0.23,t=18.276,P=0.000).There were no significant differences in sex,clinical stage and pathological types of hemoglobin,plasma cells,platelets,albumin,β2-MG and CRP between PCAT 1 mRNA high expression group and low expression group (x2 =0.001 ～ 3.345,all P ＞ 0.05).Ca2+ ≥ 10 mg/dl in the PCAT-1 high expression group (57.14％) was significantly higher than that in the low expression group (27.27％,x2 =5.229,P=0.022).There was no significant difference in treatment effect between PCAT-1 mRNA high expression group and low expression group (88.64 ％ vs 75.00％,x2 =2.291,P=0.130).PFS and OS expression in PCAT-1 high expression group were lower than that in the low expression group (x2 =7.269,P =0.007;x2 =9.190,P =0.002).COX risk regression multiple factor analysis showed that age and PCAT-1mRNA expression were independent prognostic factors influencing patients (OR =3.275,P =0.025,95％CI:2.691～3.761;OR=2.136,P=0.046,95％CI:2.034～2.685).Conclusion LncRNA PCAT-1 is highly expressed in serum of patients with multiple myeloma,and correlated with the prognosis of patients.

To further evaluate the safety of ginkgo diterpene lactone meglumine injection in the clinical use in ischemic stroke patients. Clinical safety study was conducted in 82 clinical units and 6 300 cases were completed and included from June 2013 to December 2014 by using multicenter, prospective, open and uncontrolled design methods for clinical research. A total of 29 cases of adverse reactions were observed in the experiment. Adverse reaction ratio (ADR) was 0.46%, and about 86.21% (25 cases) of them was mild with transient response which could be alleviated or disappeared without intervention; about 13.79% (4 cases) was moderate, including 2 cases of headache, 1 case of dizziness and 1 case of rash; no serious adverse reactions were found. The adverse reactions occurred in this study were pre-known adverse reactions or common adverse reactions of Chinese medicine injection. The overall incidence of adverse reactions was low, and the risk was controllable.