Chronic urticaria （CU） is a common skin disease worldwide， and its incidence is increasing year by year in various regions. Clinical manifestations such as severe itching can affect normal work， sleep， and daily life and increase the negative psychological burden caused by stress， anxiety， and depression. Mast cell activation and degranulation induced by immunoglobulin（Ig）E hypersensitivity is one of the core pathogenic mechanisms of CU， and there is no cure. Antihistamines such as cetirizine and loratadine are preferred for the clinical treatment of CU. Although they can effectively improve clinical manifestations such as itchiness， long-term application can increase the risk of adverse reactions and drug resistance. The phosphatidylinositol kinase/serine-threonine protein kinase B（PI3K/Akt） signaling pathway， as a classical signaling pathway regulated by phosphatidylinositol and tyrosine kinase receptor （RTK）， is a key target regulating the production and release of cytokines in macrophages and affecting the migration of leukocytes and the activation of mast cells and inflammation， and it can be involved in a variety of metabolic processes， such as mast cell activation and degranulation induced by IgE hypersensitivity and abnormal activation of the complement system so that the PI3K/Akt molecular pathway could be an important target for the future eradication of CU. However， the mechanism and potential role of the PI3K/Akt signaling pathway in the treatment of CU are less reported in China. Now， this paper reviewed the molecular mechanism of PI3K/Akt signaling pathway regulation in the treatment of CU and provided corroborative evidence and therapeutic strategy choices for the treatment of CU with traditional Chinese medicine （TCM） from the perspectives of molecular regulation and network pharmacology analysis.

Purpose/Significance To improve the performance of named entity recognition(NER)model of Chinese electronic medi-cal records(EMR)for better organization and mining of medical information.Method/Process The ERNIE-BiGRU-Attention-CRF NER model of Chinese EMR is constructed.Firstly,the ERNIE1.0 pre-training model is used to generate word vectors with semantic features,and then BiGRU is utilized to capture the global semantic features and grammatical structural features,which are fed into the Attention mechanism to further enhance the capture of the semantic features,and finally,the CRF decoding layer is connected to output the label sequences with the maximum global probability.Result/Conclusion Comparison experiments and ablation experiments are car-ried out on the publicly available medical text dataset CCKS2017,and examples analysis is conducted using the generated model.The model proposed in this paper achieves better recognition results.

Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

Objective To investigate carboxyl terminus of Hsc70-interacting protein(CHIP)and FAT a-typical cadherin 4(FAT4)expression in colorectal cancer(CRC)tissue and their clinical significance.Methods A total of 92 CRC patients treated in a hospital from May 2018 to May 2020 were selected as the study objects.The expressions of CHIP and FAT4 in CRC tissues and adjacent tissues were detected by im-munohistochemistry.Spearman rank correlation analysis showed the correlation between CHIP and FAT4 ex-pression in CRC tissues.Kaplan-Meier curve was used to analyze the relationship between CHIP and FAT4 expression and survival prognosis of CRC patients.Cox proportional risk model was used to analyze the prog-nostic factors of CRC patients.Results Compared with adjacent tissue,the positive rate of CHIP in CRC tis-sue was higher[65.22％(60/92)vs.10.87％(8/92)]and the positive rate of FAT4 was lower[28.26％(26/92)vs.89.13％(82/92)].The difference was statistically significant(X2=63.075,70.300,P＜0.001).There was a negative correlation between CHIP and FAT4 expression in CRC(r=-0.781,P＜0.001).The positive rates of CHIP and FAT4 were higher in CRC tissues with TNM stage Ⅰ to Ⅱ,high school differenti-ation and no lymph node metastasis,and the positive rates of CHIP and FAT4 were lower in CRC tissues with TNM stage Ⅲ,low differentiation and lymph node metastasis,and the difference was statistically significant(P＜0.05).The 3-year survival rates of CHIP positive and CHIP negative patients were 48.33％(29/60)and 78.13％(25/32),respectively,and the difference was statistically significant(Log-rank X2=6.709,P=0.010).The 3-year survival rates of FAT4-positive and FAT4-negative patients were 81.25％(13/16)and 53.95％(41/76),respectively,with statistical significance(Log-rank X2=5.124,P=0.032).TNM stage Ⅲ,low differentiation,lymph node metastasis and positive CHIP were risk factors for the prognosis of CRC pa-tients,while positive FAT4 was protective factor.Conclusion CHIP expression is increased and FAT4 ex-pression is decreased in CRC tissues.Both expressions are associated with poor clinicopathological features of CRC,which is helpful to evaluate the survival prognosis of CRC patients.

Ischemic stroke(IS)is a severe cerebrovascular disease that seriously endangers human health.Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine.In recent years,trimethylamine N-oxide(TMAO)as a gut microbiota metabolite has received widespread attention in cardiovascular diseases.Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis,atrial fibrillation,hypertension,and type 2 diabetes.TMAO exacerbates neurological damage in IS patients,increases the risk of IS recurrence,and is an independent predictor of post-stroke cognitive impairment(PSCI)in patients.Current research suggests that the mechanisms of TMAO action include endothelial dysfunction,promoting of foam cell formation,influence on cholesterol metabolism,and enhancement of platelet reactivity.Lowering plasma TMAO levels through the rational use of traditional Chinese medicine,dietary management,vitamins,and probiotics can prevent and treat IS.

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*

Objective To measure and analyze biological characteristics and aging phenotype of SHJH^hr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development. MethodsWith ICR mice of the same age as control group, the body mass growth data of SHJH^hr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJH^hr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJH^hr mice were measured. The venous blood of 8-week-old SHJH^hr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJH^hr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed. ResultsCompared with ICR mice, the female and male body mass of SHJH^hr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJH^hr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions. ConclusionSHJH^hr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging.

Objective:To explore the value of spectral CT in the preoperative evaluation of solid lung adenocarcinoma with different pathological grades based on the 2011 and 2020 version of the pathological grading system.Methods:A total of 76 cases of solid lung adenocarcinoma confirmed by surgery in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, from January 2019 to September 2021 were analyzed retrospectively. All cases were divided into groups according to the grading system for invasive adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) in 2011 and 2020 (G low group included G1 and G2 adenocarcinoma, G high group included G3 adenocarcinoma). The tumors with stage Ⅰ and Ⅱ were non-advanced and the tumors with stage Ⅲ and Ⅳ were advanced. The clinical manifestations (gender, age, smoking history and stage), routine CT parameters (tumor size, morphological characteristics, plain CT value and enhancement degree) and spectral parameters [iodine concentration, effective atomic number, enhanced monochromatic CT attenuation values of 40-200 keV (CT 40 keV-CT 200 keV), and the slope of spectral curve (k value)] were compared between G low group and G high group using independent sample t-test or Mann-Whitney U test. And the efficacy of each parameter for indicating G high adenocarcinoma was analyzed using receiver operating characteristic curve analysis and area under the curve (AUC), and the Z test was used to compare the AUC. Results:Seventy-six cases were included (59 cases of G low group and 17 cases of G high group in 2011 version; 46 cases of G low group and 30 cases of G high group in 2020 version). Among the 76 cases, 62 cases were non-advanced stage (50 cases of G low group and 12 cases of G high group in 2011 version; 37 cases of G low group and 25 cases of G high group in 2020 version) and 14 cases were advanced stage (9 cases of G low group and 5 cases in G high group in both 2011 and 2020 version). Among the non-advanced adenocarcinomas, the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase of G high group in 2011 grading system were significantly lower than those of G low group ( P<0.05), while other parameters were similar between G low and G high group in 2011 grading system ( P>0.05); and the CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase of G high group in 2020 grading system were significantly lower than those of G low group ( P<0.05). Among the advanced adenocarcinomas, all of the clinical and CT parameters were similar between G low and G high group in both 2020 and 2011 grading systems ( P>0.05). For the non-advanced adenocarcinomas, there was medium to good efficacy of the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase for diagnosing 2011 grading system G high adenocarcinoma (AUC=0.700-0.853), with CT 50 keV in venous phase as the best; while the diagnosis efficacy of CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase was poor for 2020 grading system G high adenocarcinoma (AUC=0.652-0.688), with CT 60 keV in venous phase as the best. After combining smoking history and CT 60 keV in venous phase, the diagnosis efficacy for 2020 grading system G high adenocarcinoma was slightly improved (AUC=0.772), but the difference had no significance ( Z=0.93, P=0.176). Conclusion:The spectral parameters are useful for distinguishing the pathological grades of solid lung adenocarcinoma. And the detecting efficacy for G high adenocarcinoma of IASLC 2011 version is slightly better than that of 2020 version.

Objective:To investigate whether hepatitis B virus X protein (HBx) mediates the podocyte injury through reactive oxygen species (ROS) /nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway.Methods:HBx-overexpressing lentivirus was transfected into renal podocytes of mouse to mimic the pathogenesis of hepatitis B virus-associated glomerulonephritis. Podocytes were divided into the following five groups: blank control group (no special treatment), negative control group (transfected with control lentivirus), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+NLRP3 siRNA group (transfected with HBx overexpression lentivirus and NLRP3 siRNA), and HBx overexpression+ROS inhibitor group (transfected with HBx overexpression lentivirus and adding ROS inhibitor). The morphological changes of podocytes were observed with electron microscope. The generation of ROS was detected by dichlorodihydrofluorescein diacetate assay (DCFH-DA). Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to detect caspase-1 activity, and the levels of lactate dehydrogenase, interleukin (IL)-1β and IL-18. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression levels of mRNA and protein of pyroptosis-related protein, such as NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β and IL-18. TUNEL staining and flow cytometer were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression levels of desmin and nephrin.Results:After successful infection of podocytes with HBx-overexpressing lentivirus, pyroptosis-related morphological changes in the cells were observed under electron microscope. The level of ROS in the HBx overexpression group was significantly higher compared to the negative control group ( P<0.05). Hoechst 33342 staining revealed condensed nuclei in the HBx overexpression group. TUNEL staining and flow cytometer demonstrated that podocytes underwent increased pyroptosis in the HBx overexpression group. The mRNA and protein expression levels of pyroptosis-related proteins such as NLRP3, ASC, caspase-1, IL-1β and IL-18 were up-regulated upon HBx overexpression (all P<0.05). Caspase-1 enzyme activity, lactate dehydrogenase and desmin expression levels were enhanced after HBx overexpression (all P<0.05). However, NLRP3 knockdown or addition of ROS inhibitors attenuated the pyroptosis and increased expression levels of pyroptosis-related proteins caused by HBx overexpression (all P<0.05). Conclusion:ROS/NLRP3 pathway plays an important role in HBx-induced podocyte pyroptosis.

Non-IgE-mediated food allergy most often presents with gastrointestinal symptoms such as diarrhoea, mucus stools, bloody stools, reflux and vomiting a few hours to days after exposure to the allergenic food.The pathogenesis may be related to the activation of intestinal T lymphocytes to secrete pro-inflammatory cytokines such as TNF-α and IL-4 by food allergens, leading to migration of neutrophils and eosinophils into the intestinal lumen, causing an intestinal inflammatory response and increased intestinal permeability.There is no rapid and specific diagnostic method.The diagnosis is mainly based on clinical manifestations combined with food avoidance and oral food challenge.In recent years, fecal biomarkers have been widely used as specific indicators for determining intestinal inflammation as an aid to diagnosis and condition assessment of intestinal infections and inflammatory bowel diseases, but their application in gastrointestinal allergic diseases is rarely reported.In this paper, we will focus on the significance of fecal calprotectin, fecal eosinophil-derived neurotoxin in non-IgE-mediated food allergy.