Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

Based on the theory of consolidating the root and cultivating the primary, the paper collates and reviews the theoretical evidences and the characteristics of Xin'an medical masters in treatment of bi syndrome with acupuncture and moxibustion so as to provide the ideas for further research. Xin'an medical masters thoroughly acquainted with the theory of consolidating the root and cultivating the primary in treatment of bi syndrome with acupuncture and moxibustion, emphasizing the regulation of qi and blood, yin and yang, the nutrient qi and the defensive qi; and replenishing the middle jiao (spleen and stomach) and the lower jiao (kidney). The acupoint selection was distinctive, in which, the acupoints were selected and stimulated in terms of the etiology and the pathogenesis of diseases, as well as the properties of special points. The remarkable therapeutic effect on bi syndrome was ensured through specially selecting he-sea points, ashi points and "yin-yang opposite" points; effectively using the penetrating needling technique and moxibustion method and combining acupuncture with herbal medication.
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Moxibustion ; Spleen

Objective:To investigate the prevalence and independent risk factors of non-alcoholic fatty liver disease (NAFLD) and advanced chronic liver disease among the type 2 diabetes mellitus (T2DM) population in the Shenyang community, so as to provide evidence for the prevention and control of T2DM combined with NAFLD.Methods:This cross-sectional study was conducted in July 2021. 644 T2DM cases from 13 communities in Heping District, Shenyang City were selected. All the surveyed subjects underwent physical examination (measurements of height, body mass index, neck circumference, waist circumference, abdominal circumference, hip circumference, and blood pressure), infection screening (excluding hepatitis B and C, AIDS, and syphilis), random fingertip blood glucose, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). The study subjects were divided into the non-advanced chronic liver disease group and the advanced chronic liver disease group according to whether the LSM value was greater than 10 kPa. Cirrhotic portal hypertension development was indicated in patients with LSM ≥ 15 kPa. The comparison of multiple mean values among the sample groups was performed by analysis of variance when the normal distribution was met.Results:In the T2DM community population, there were 401 cases (62.27%) combined with NAFLD, 63 cases (9.78%) combined with advanced chronic liver disease, and 14 cases (2.17%) combined with portal hypertension. There were 581 cases in the non-advanced chronic liver disease group and 63 cases (9.78%) in the advanced chronic liver disease group (LSM ≥10 kPa), including 49 cases (7.61%) with 10 kPa≤LSM<15 kPa, 11 cases (1.71%) with 15 kPa ≤LSM<25 kPa, and 3 cases (0.47%) with LSM ≥ 25 kPa. Age, body mass, body mass index, neck circumference, waist circumference, hip circumference, waist-to-height ratio, systolic blood pressure, and CAP were all statistically different between the non-advanced chronic liver disease group and the advanced chronic liver disease group ( F=-1.983,-2.598,-4.091,-2.062,-3.909, -4.581,-4.295,-2.474, and -5.191, respectively; P<0.05). There was a statistically significant difference in terms of whether or not there was combined cerebrovascular disease (2=4.632, P=0.031); however, there were no statistically significant differences in terms of lifestyle, diabetes complications, and other complications ( P>0.05). Conclusion:Patients with T2DM have a higher prevalence of NAFLD (62.27%) than those with advanced chronic liver disease (9.78%). 2.17% of T2DM cases in the community may not have had early diagnosis and early intervention, and they might have been combined with cirrhotic portal hypertension. So, the management of these patients should be strengthened.

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Prostaglandin E
Angiotensin II ; Animals ; Humans ; Hypertension/chemically induced* ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle

Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; prevention & control ; Disease Outbreaks ; Emergencies ; Hospitals, General ; Humans ; Internet ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control

Objective To investigate the active ingredients of Jingfang Baidu San for the prevention and treatment of COVID-19 by using network pharmacology and molecular docking, and to provide references for clinical applications. Methods The chemical constituents and action targets of all medicinal materials in Jingfang Baidu San were retrieved from TCMSP. Uniprot database was used to search the corresponding genes of targets. Cytoscape software was used to construct the network of medicinal materials-compounds-targets for visualization. The target proteins of COVID-19 were searched by disease databases. The intersection of both was considered to be analyzed to establish the protein-protein interaction (PPI) network by STRING database. GO function enrichment analysis and KEGG pathway enrichment analysis were performed through Metascape database to predict its mechanism. The effective strength of core constituents on preventing COVID-19 was calculated by molecular docking method. Results A total of 159 effective ingredients and 277 potential targets were obtained in Jingfang Baidu San within the given screening conditions [oral bioavailability (OB) ≥30%; drug-like (DL) ≥ 0.18], including 55 core targets with the intersection of 273 targets of COVID-19. According to the results of GO and KEGG enrichment analysis performed on the core targets, 1376 GO items and 136 KEGG pathways were obtained, involving infectious diseases, cancer, cell progress, immune system, signaling pathways etc. The results of molecular docking indicated strong binding capacity between the core ingredients and SARS-CoV-2 3CL hydrolase or angiotensin-converting enzyme II (ACE2). The hydrogen binding and hydrophobic effect were the main forms of the interaction. Conclusion The active ingredients in Jingfang Baidu San can inhibit the binding between SARS-CoV-2 protein and ACE2, thus regulating multiple targets and signal pathways, which plays a role in the prevention and the treatment of COVID-19.

Objective: Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia. Methods: An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population. Results: The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia. Conclusion Our present results suggest SHC3 as a susceptibility gene for schizophrenia.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

In commonly used oral solid preparations, poor mouthfeel results in poor patient compliance with the drug, which in turn reduces the market competitiveness of the drug. The problem of taste masking of pharmaceutical preparations has always been one of the important problems faced by pharmaceutics. With the increasing demand for the taste of drugs, the methods of masking bad taste of drugs have gradually increased in recent years. By summarizing the relevant literature covering the bad taste of drugs, the commonly used taste masking techniques include the addition of taste masking agents, inclusion techniques, microsphere/microcapsule technology, solid dispersion technology, ion exchange technology and the like. However, in addition to the above taste masking techniques, in the manufacturing process of the solid preparation, the granulation technique also can achieve the shielding of the bad taste of the medicine, and the granulation technique is simple, and can well achieve the effect of masking the bad taste of the medicine. This paper systematically introduces the research progress of granulation technology in drug taste masking, in order to provide reference for the selection of drug taste masking technology. With the increasing demand for drug taste, drug masking technology has been paid more and more attention by the majority of preparation workers, however, there are still some problems, such as imperfect taste evaluation system and low specificity of methods. This series of problems need to be further studied and solved by relevant pharmaceutical researchers.