McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Penicillin G acylases (PGAs) are industrially important enzymes primarily used for the synthesis of first- and second-generation cephalosporins or penicillins. This study aims to establish a high-efficiency biosynthetic system for cefradine on the purpose of significantly enhancing its catalytic efficiency in cefradine synthesis and developing its potentials for industrial application. In this study, we identified and engineered penicillin G acylase and obtained a highly active mutant KsPGA M7(M168F/F313G) for the synthesis of cefradine. The mutant achieved a conversion rate over 95% in the scaled-up reaction. To validate its industrial applicability, we immobilized both the wild-type and mutant enzymes and applied them in continuous flow reactions, which achieved a space-time yield of 2 800 g/(L·d). This study lays a foundation for the future applications of penicillin G acylases in the industrial synthesis of cefradine.
Penicillin Amidase/biosynthesis* ; Protein Engineering/methods* ; Cephradine/metabolism* ; Escherichia coli/metabolism* ; Enzymes, Immobilized/metabolism* ; Recombinant Proteins/biosynthesis*

Vacuum compression molding (VCM) is a novel technology supporting the research and development of pharmaceutical solid dispersions. It is widely applied due to its precision and convenience in sample preparation. This technology integrates the principles of heating, melting, cooling, and vacuum compression to transform solid powders into shaped solids directly. By selecting different molds, temperatures, and pressures, researchers can prepare samples with diverse characteristics. This paper presents an overview of the equipment composition and working principles of VCM technology, demonstrating its distinct advantages in the formulation screening process of amorphous solid dispersions through comparative analysis with hot melt extrusion using case studies, and introduces its applications in the development of drug delivery systems and rheological characterization analysis, with a perspective on the future development of its functions.

The bidirectional communication between gut microbiome and host significantly affects brain function,and there is increasing evidence that the imbalance of gut microbiota is closely related to the onset of Alzheimer's disease(AD).Blood-and gut-based metabolites,such as trimethylamine oxide,short-chain fatty acids,GABA and tryptophan metabolites,are likely to be the main mediators of the"microbiota-gut-brain axis",and play an important role in maintaining intestinal flora homeostasis and intestinal mucosal integrity,regulating the host immune system and cognitive function.This paper aims to summarize the blood and intestinal metabolites in the development of AD disease,and provide a new direction for the treatment of AD in the future.

The bidirectional communication between gut microbiome and host significantly affects brain function,and there is increasing evidence that the imbalance of gut microbiota is closely related to the onset of Alzheimer's disease(AD).Blood-and gut-based metabolites,such as trimethylamine oxide,short-chain fatty acids,GABA and tryptophan metabolites,are likely to be the main mediators of the"microbiota-gut-brain axis",and play an important role in maintaining intestinal flora homeostasis and intestinal mucosal integrity,regulating the host immune system and cognitive function.This paper aims to summarize the blood and intestinal metabolites in the development of AD disease,and provide a new direction for the treatment of AD in the future.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

ObjectiveTo observe the effect of the enhanced external counterpulsation （EECP） combined with drug on social function and efficacy in patients with depressive episodes， so as to provide references for the treatment of depressive episodes. MethodsA total of 66 hospitalized patients who was in hospital at department of psychiatry of the Second Xiangya Hospital of Central South University， met the criteria of Diagnostic and Statistical Manual of Mental Disorders，fifth edition（DSM-5） diagnosis of depressive episode or bipolar disorder depressive episode from May 2019 to March 2020 were included by simple random sampling. The participants were divided into study group （n=36） and control group （n=30） according to the random number table method. Both groups received conventional drug treatment， and the study group recieved the EECP intervention at same time. The Depression symptoms and social function were assessed before and after treatment by using Hamilton Depression Scale-24 item （HAMD-24） and Sheehan Disability Scale （SDS）. Treatment efficacy of the two groups was compared. ResultsAfter the intervention， the HAMD-24 and SDS scores in both groups were lower than those before treatment， the differences were statistically significant （t=8.149， 5.791， 8.016， 3.488， P˂0.01）. And the SDS score of the study group was siginficantly lower than that of the control group （t=-3.008， P<0.05）. The total effective rate of treatment in the study group was higher than that of the control group， and the difference was statistically significant （90.63% vs. 63.33%， χ²=8.725， P˂0.05）. ConclusionEECP therapy combined with drug has better efficacy on the patients with depressive episodes， and it can improve social function effectively.

Objective:To establish a nomograph prediction model of early critical changes in children with febrile convulsion, and to provide guidance for the prevention and nursing of children with febrile convulsion.Methods:Convenient sampling method was adopted to select 384 children with febrile convulsion in Anhui Children ′s Hospital from January 2018 to April 2021 as the research objects. Based on pews, the children with febrile convulsion were divided into 334 cases of non risk group and 50 cases of risk group. Binary Logistic regression analysis were used to determine the independent risk factors affecting the early critical changes of children with febrile convulsion. A nomogram was drawn based on the independent risk factors. The discrimination and consistency of the model were verified by model ROC curve and Hosmer Lemeshow goodness of fit.The external validation of model prediction efficiency were verified by validation data. Results:Binary Logistic regression analysis showed that age, respiratory rhythm disorder, unconsciousness, breath rate, heart rate, neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), duration of first convulsion and mean body temperature after first convulsion were influence factors for early critical changes in children with febrile convulsion ( P<0.05). The C-index of the model was 0.974 (95% CI 0.954-0.993), and the C-index of the external validation of the model was 0.922 (95% CI 0.880-0.966). The results of H-L fitting test showed that the difference was not statistically significant( χ2=0.29, P>0.05). Conclusions:The early critical changes of children with febrile convulsion may be affected by respiratory rhythm disorder, confusion of consciousness, breath rate, heart rate, NLR, RDW, duration of the first convulsion, mean temperature after the first convulsion and other factors. Pediatric emergency department should collect corresponding intervention measures for children with febrile convulsion according to the establishment of prediction model to prevent their early deterioration.

Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 (