Objective To investigate the influence of menstrucal cycle and anatomic site on the fractional anisotropy (FA) values of diffusion tensor imaging (DTI) in normal breast. Methods Prospectively enrolled 96 volunteers, who have identified with normal menstrucal phase and without breast diseases were found via the breast examination, ultrasound and MRI scan. The cases were divided into three groups according to menstrucal phase: menstrual period group(menstrual cramps 1 to 6 d), proliferative phase group(menstrual cramps 7 to 14 d) and secretory phase group(menstrual cramps 15 d to the next), and each group consisted of 32 subjects. All subjects were performed bilateral breast cross-sectional T1WI, T2WI, DWI and DTI scaning. On the nipple level figture, the mammary gland was divided into three regions including the anterior, central and posterior parts, and the FA values of the different phases and regions were measured. The Kruskal-Wallis H test was applied to analyse the difference of FA values in different menstrual phase and anatomic site. Results The FA values of the anterior region in menstrual phase, proliferative phase and secretary phase were 0.21 ± 0.07, 0.24 ± 0.09 and 0.17 ± 0.07, and the difference had significant difference(P=0.014).The FA values of the central region were respectively 0.15±0.08, 0.18±0.09 and 0.15±0.07, and without the statistically significant difference(P=0.090). The FA values of the posterior region were 0.21 ± 0.11, 0.24 ± 0.13 and 0.16 ± 0.11, and also showed significant difference(P=0.002). In different regions, the difference of FA values between menstrual phases and proliferative phases were also had statistically significant(P=0.018, 0.045, respectively). In the same region, the FA value was lowest in the secretary phase, and the proliferative phase was slightly higher than menstrual phase. Conclusion The FA values are affected by menstrual cycle and anatomic site.

Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 Å, and in complex with its inhibitor acarbose at a resolution of 2.9 Å. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.
Acarbose ; chemistry ; Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Glycoside Hydrolase Inhibitors ; Humans ; Hydrogen Bonding ; Intestines ; enzymology ; Kinetics ; Maltose ; chemistry ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation, Missense ; Oligosaccharides ; chemistry ; Pichia ; Protein Binding ; Recombinant Proteins ; antagonists & inhibitors ; chemistry ; genetics ; Substrate Specificity ; Surface Properties ; alpha-Glucosidases ; chemistry ; genetics

Objective To investigate the mechanism of the preventive effect of alum-borneol nanoemulsion on hypertrophic scars by observing its effect on cAMP-response element-binding protein 3-like 1(CREB3L1)and inflammatory damage in hypertrophic scar tissues of rabbit ear.Methods Thirty New Zealand big-eared white rabbits were randomly divided into blank group,model group,alum-borneol nanoemulsion low-,medium-,and high-dose groups(8.15,16.3,and 32.6 mg·mL-1),and asiaticoside group.The animal model was established by thermal injury.Topical application of appropriate drugs was given on the 14th day after successful modeling of deep Ⅱ-degree burns.Equal amounts of saline were applied externally to the blank and model groups twice daily and administered continuously until the 35th day.Histopathological changes in rabbit ear scar tissue were observed by hematoxylin-eosin(HE)staining.Masson staining was used for collagen deposition in scar tissue.Coexpression of CREB3L1/alpha-smooth muscle actin(α-SMA)in rabbit ear scar tissue was detected by immunofluorescence double-labeling assay.Enzyme-linked immunosorbent assay(ELISA)was applied for the detection of interleukin-6(IL-6)and interleukin-10(IL-10)in scar tissue.Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was applied for the detection of CREB3L1,Collagen Type I(COL-Ⅰ),Collagen Type Ⅲ(COL-Ⅲ),and α-SMA mRNA expression.Protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA was detected by protein immunoblotting analysis(Western Bolt).Results Compared with the blank group,the scar proliferation index of the model group was significantly increased(P<0.01).Pathologic changes including the thickening of the dermis,the formation of dense reticular fibers,and accompaniment of inflammatory cell infiltration were observed.Masson staining reveals thickening of the dermis,disordered arrangement and large deposits of blue-stained collagen fibers.Double-labeling immunofluorescence results showed that positive expression of CREB3L1 and α-SMA in scar tissue increased.IL-6 levels were significantly increased(P<0.01),while IL-10 levels were significantly decreased(P<0.01).The relative mRNA expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA in the scar tissue of rabbit ear was significantly increased(P<0.01).The protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA was significantly increased(P<0.01).Compared with the model group,the scar proliferation index was significantly decreased after the treatment of medium-,high-dose of alum-borneol nanoemulsion and asiaticoside(P<0.01,P<0.05,P<0.01).Pathologic changes including the thinning of the dermis,as well as varying degrees of reduction of inflammatory cells and blue-stained collagen fibers were found.Double-labeling immunofluorescence showed positive expression of CREB3L1 and α-SMA in scar tissue decreased.IL-6 levels significantly reduced(P<0.01),while IL-10 levels significantly raised(P<0.01).The alum-borneol nanoemulsion medium-,high-dose and asiaticoside groups could significantly down-regulate the mRNA expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA(all P<0.01),and reduce the protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA(P<0.05,P<0.01).Conclusion Alum-borneol nanoemulsion may prevent hyperplastic scar formation by regulating the expression of CREB3L1 and related fibrotic proteins and reducing inflammatory level,which enriches the scientific connotation of"prevention of disease from exacerbating"and"treatment of the disease before its onset"in Chinese medicine.

Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment， diet， and lifestyle， which is closely related to many diseases in modern medicine， such as hyperlipidemia， obesity， fatty liver， atherosclerosis， metabolic syndrome， and cardiovascular and cerebrovascular diseases， with a wide range of influence and far-reaching harm. According to the Huangdi Neijing， lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids， which has the function of nourishing， and it is the initial state and source of important substances in the human body such as brain， marrow， essence， and blood. Once the grease of the human body is abnormal， it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach， which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments， leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity， which accumulates in the body's meridians， blood vessels， skin pores， and organs， forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays， it was divided into four common pathogenesis types： ''inability to distinguish between the clear and turbid， turbid stagnation in the Ying blood''， ''spleen not rising clear， turbid accumulation in the vessels''， ''spleen dysfunction， lipid retention in the pores''， ''spleen failure to transportation and transformation， and grease accumulation in the liver''. According to the pathogenesis， it could be divided into four common syndromes， namely， turbid stagnation in the Ying blood， turbid accumulation in the vessels， lipid retention in the pores， and grease accumulation in the liver， and the corresponding prescriptions were given for syndrome differentiation and treatment， so as to guide clinical differentiation and treatment of the lipid turbidity disease.

With high accuracy and precision,next generation sequencing (NGS) has provided a powerful tool for clinical testing of genetic diseases.To follow a standardized experimental procedure is the prerequisite to obtain stable,reliable,and effective NGS data for the assistance of diagnosis and/or screening of genetic diseases.At a conference of genetic testing industry held in Shanghai,May 2019,physicians engaged in the diagnosis and treatment of genetic diseases,experts engaged in clinical laboratory testing of genetic diseases and experts from third-party genetic testing companies have fully discussed the standardization of NGS procedures for the testing of genetic diseases.Experts from different backgrounds have provided opinions for the operation and implementation of NGS testing procedures including sample collection,reception,preservation,library construction,sequencing and data quality control.Based on the discussion,a consensus on the standardization of the testing procedures in NGS laboratories is developed with the aim to standardize NGS testing and accelerate implementation of NGS in clinical settings across China.

【Objective】 To investigate the distribution of plasma donors with high titer neutralizing antibodies against human cytomegalovirus (HCMV) in the general plasma donor population. 【Methods】 920 plasma samples of Taibang were tested in April 2014 to investigate the distribution of anti-HCMV neutralizing antibodies. After further testing of mixed plasma, the threshold for screening plasma was determined. From October 2019 to May 2020, neutralizing anti-HCMV in 40 078 plasma samples from 11 plasma stations in Shandong province were screened by the microcytopathic method (modified high-flux neutralization test method). The proportion of neutralizing anti-HCMV enriched in high titer and the distribution in the donor population were analyzed by SPSS 26 and Minitab19 analysis software. 【Results】 Among 920 samples, 73.26%, 0.43%, and 8.69% of them had neutralization titer<1∶15, ≥1∶60 and ≥1∶30, respectively. The neutralization titer of mixed plasma was detected, and 1∶30 was determined as the high titer. The yielding rate of high titer neutralizing anti-HCMV in Shandong was 9.06% (3 633/40 078). The proportion of plasma donors with high-titer neutralizing anti-HCMV in the donation population from plasma stations was 4.95%~13.03% (9.06±2.07) %. The proportion of plasma donors with high-titer neutralizing anti-HCMV by gender was 15.67% (2 185/13 951) in women and 5.54% (1 448/26 127) in men(P<0.05). 【Conclusion】 There was a certain proportion of plasma donors wiht high titer neutralizing anti-HCMV in the population of plasma donors in Shandong, and they can constantly serve neutralizing anti-HCMV to ensure the production of anti-HCMV immunoglobulin preparations.

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
Animals ; Rats ; Chondrocytes ; NF-kappa B ; Iodoacetic Acid ; Inflammation ; MAP Kinase Signaling System ; Apoptosis