G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To understand the spectrum and changes of pathogens causing healthcare-associated infec-tion(HAI)in neonatal intensive care unit(NICU).Methods Clinical medical records of neonates with HAI in a hospital from January 2018 to December 2022 were collected,spectrum of pathogens causing HAI were and analyzed retrospectively.Results A total of 7 597 hospitalized neonates were investigated,and 240 of whom had 263 cases of HAI,with an HAI incidence of 3.16％and healthcare-associated case infection incidence of 3.46％.96 cases(36.50％)were bloodstream infection,70(26.62％)were respiratory system infection,and 57(21.67％)were in-fection without clear sites.A total of 170 pathogens were detected from specimens,78(45.88％)of which were Gram-positive bacteria,with Staphylococcus spp.accounting for the highest proportion,78(45.88％)were Gram-negative bacteria,mainly Klebsiella pneumoniae,and 14(8.24％)were fungi.The detection rate of Gram-negative bacteria showed an upward trend from 2018 to 2022(P＜0.01).Conclusion The majority of HAI in NICU is bloodstream infection.In recent years,the detection rate of Gram-negative bacteria has been increasing year by year,and it is necessary to streng-then the prevention and control of HAI in clinical practice.

Consumptive thirst is widely discussed in Huangdi Neijing and it is classified as a"strange disease"in Suwen·Strange Diseases Treatise,which reflects the intractable nature of consumptive thirst.This paper explores and analyzes consumptive thirst based on the core concept in Huangdi Neijing.First,this paper approaches the subject through the use of image thinking method from Huangdi Neijing,recognizing that consumptive thirst can lead to changes in the internal climate of the human body.Then,guided by the theories of essence and qi,yin and yang,and the five elements in Huangdi Neijing,it deconstructs and analyzes the causes of these changes and the laws of qi transformation.It points out that the changing climate of consumptive thirst is characterized by"heat symptoms".The main cause of"heat symptoms"is spleen deficiency and excessive dampness,and its qi transformation law is the heat transformation of Shaoyin.The intractable nature of consumptive thirst is mainly reflected in the uncontrolled"heat symptoms"caused by the imbalance of the five elements.Based on the understanding of the heat symptoms of consumptive thirst,this paper proposes a treatment strategy for preventing the disease by resolving dampness and regulating the spleen,harmonizing kidney qi to prevent progression,and balancing yin and yang to treat chronic and recalcitrant conditions.The aim is to provide a reference for optimizing the treatment of consumptive thirst.

Objective To establish an artificial intelligence(AI)diagnostic model for the histopathologic diagnosis of extramammary Paget's disease(EMPD)and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD.Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited,and their pathological data were collected,including EMPD,Bowen's disease(BD),squamous cell carcinoma(SCC),and epidermal hyperplasia and hypertrophy.With EMPD as the main research subject,the histopathological images of BD,SCC,and non-tumor skin diseases were included in the study.The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks,and the performance of these models was evaluated.Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD,BD,SCC and non-tumor skin diseases on the images at x20 magnification were 0.97,0.98,1.00 and 0.96,respectively,with an accuracy of 0.925±0.011,while the AUC values on the images at x40 magnification were 1.00,0.99,1.00 and 0.97,respectively,with an accuracy of 0.943±0.017.The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at x20 magnification were 0.98,0.95,0.99 and 1.00,respectively,with an accuracy of 0.912±0.034,while the AUC values on the images at x40 magnification were 0.99,0.96,1.00 and 1.00,respectively,with an accuracy of 0.971±0.012.Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD,SCC and non-tumor skin diseases at low power magnification.The FLPOs of ResNet101 was 786.6 M,and the parameter was 4.5 M;The FLPOs of DensNet121 was 289.7 M,and the parameter was 0.8M.Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD.DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

Objective:To investigate the genetic causes in a phenotypically normal couple with three pregnancies of trisomy 21 offspring.Methods:A retrospective analysis was conducted on a phenotypically normal couple who had three pregnancies with trisomy 21 syndrome offspring and were transferred to Shandong Provincial Maternal and Child Health Care Hospital in December 2023. Genetic analysis was performed using quantitative fluorescence polymerase chain reaction (QF-PCR), karyotype analysis, chromosome microarray analysis (CMA), and fluorescence in situ hybridization (FISH). Relevant articles up to December 31, 2023, were retrieved from CNKI, Wanfang Database, Yiigle, and VIP using the terms "recurrent pregnancy", "consecutive pregnancy", "two pregnancies", and "trisomy 21 syndrome (Down syndrome)" in Chinese. Additionally, the English terms "recurrence or recurrent" "trisomy 21 syndrome" and "Down syndrome" were used to retrieve articles from PubMed, Embase, and Web of Science. The genetic causes of recurrent pregnancies with trisomy 21 syndrome fetuses were analyzed and summarized. Results:(1) Case from this hospital: Results of QF-PCR, karyotype analysis, and CMA of amniotic fluid cells in this pregnancy all indicated that the fetus had trisomy 21 syndrome. FISH tests on oral mucosal cells, decidual tissue, and urine sediment cells of the pregnant woman all indicated that she was a mosaic for trisomy 21. Additionally, QF-PCR detection of short tandem repeat (STR) loci on chromosome 21 suggested that there might be gonad mosaicism in the pregnant women, and an extra chromosome 21 in the fetus was derived from gonad mosaicism 21 trisomic cells. (2) Literature review: A total of 13 case reports with detailed records of recurrent pregnancy trisomy 21 syndrome history and related test results of both partners were retrieved, making a total of 14 cases, including seven cases each with a history of 2 and 3 trisomy 21 pregnancies. Translocation trisomy 21 was detected in each pregnancy of two cases. Of the 14 cases, five cases were only detected by peripheral blood samples of the couple, and the results were normal. The other nine cases were also detected by skin fibroblasts (six cases), ovarian tissue cells (two cases), oral mucosa cells (two cases), semen (two cases), and urinary sediment cells (one case), among which six cases indicated that one of the parents was chimeric trisomy 21, and five cases were female chimerism, one case was male chimerism. Only two cases were found to have mosaic trisomy 21 in peripheral blood sample, and the chimerism ratio was lower than that of other samples detected at the same time. In five cases, the extra chromosome 21 was found to be of maternal origin through testing of STR loci on chromosome 21.Conclusions:Parental mosaicism is an important cause of recurrent pregnancies with trisomy 21 syndrome. Testing samples from skin, oral mucosa, blood, semen, and ovaries can help detect low-level mosaicism.

Objective:To evaluate cardiopulmonary exercise fitness in patients with type 2 diabetes mellitus(T2DM)and investigate its influencing factors and possible mechanism. Method:A retrospective analysis was conducted on the medical records of 169 patients with T2DM who under-went cardiopulmonary exercise testing(CPET)from January 2021 to December 2022.Cardiopulmonary fitness was evaluated by peak oxygen consumption(peak VO2)value in CPET.Patients were divided into cardiopulmo-nary fitness normal group and abnormal group according to peak VO2％value in CPET.Univariate analysis was used to compare the differences in clinical data between the two groups,and multivariate Logistic regres-sion analysis was used to screen the independent influencing factors to construct risk prediction. Result:A total of 169 cases were included,with 48 cases in the cardiopulmonary fitness normal group and 121 cases in the abnormal group.Multivariate Logistic regression analysis showed that body mass index,histo-ry of hypertension,history of heart disease,glycated hemoglobin level,insulin resistance index and physical ex-ercise were independent influencing factors for the exercise fitness in T2DM(OR=1.278,5.159,3.876,2.911,2.586,0.086,all P＜0.05). Conclusion:Cardiopulmonary fitness is commonly reduced in patients with T2DM.Body mass index,glycated hemoglobin level,insulin resistance index,history of hypertension,history of heart disease are independent risk factors for declined cardiopulmonary fitness.While regular physical exercise is a protective factor.

OBJECTIVES: To establish a simple and rapid qualitative and quantitative detection method of dexmedetomidine in blood. METHODS: Blood was separated on the Allure PFP Propyl liquid chromatography column with isocratic elution after it was precipitated by acetonitrile and filtered. Qualitative and quantitative analysis of dexmedetomidine was performed using positive ion scan mode and multi-reaction monitoring mode. RESULTS: The limit of detection of dexmedetomidine in blood was 0.2 ng/mL and the limit of quantification was 0.5 ng/mL. The linearity of the method was good in the range of 0.5-1 000 ng/mL, and the correlation coefficient was greater than 0.99. The accuracy of the method was 90.34%-112.67% and the extraction recovery was 50.05%-91.08%, with no significant matrix effect. CONCLUSIONS This method is simple, selective and suitable for the qualitative and quantitative analysis of dexmedetomidine in blood, which can provide a reference for drug-facilitated cases involving dexmedetomidine.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Dexmedetomidine/analysis* ; Reproducibility of Results ; Chromatography, Liquid/methods*

[Abstract] Objective To investigate the branching pattern of the ureteric bud and the number of the nephron induced by each ureteric bud tip, through the three-dimensional tracing of the ureteric tree, combined with the morphological analysis and measurement of the ureteric tree. Methods The kidneys were obtained from three mice at various developing time points and prepared for paraffin and epoxy sections. Then the microscopic images were digitized and aligned from these sections. Based on the computer-assisted tracing and visualization of ureteric tree, the number of branches and the nephron induced by each ureteric bud tip were obtained by counting. In addition, paraffin sections were stained with HE staining for morphological observation of nephrogenic zone and ureteric bud, while in order to reflect the density of the ureteric bud tips at nephrogenic zone, the distance between two neighboring ureteric bud tips was measured aided with the Claudin-7 immunohistochemical staining. Results The ureteric bud branching tree revealed that the initial bifid iterative branching formed the framework of renal medulla, the branching became complicated and dense in cortex and nephrogenic zone, while the distance between ureteric bud tips were also decreasing. The number of the nephron induced by each ureteric bud tip increased from one (E14. 5) to two (E17. 5), and occasionally to three. Conclusion Threedimeasional Visualization of ureteric bud branching tree reveals regional complication, suggesting molecules in different regions drive different branching patterns; While the density of the ureteric bud tips at nephrogenic zone increases corresponding to decreasing of thickness of the nephrogenic zone, and the disappearance of the ureteric bud tips after birth is also consistent with the gradual consumption of nephron progenitor cells.

OBJECTIVE: To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft. RESULTS: There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4⁺CD25⁺ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078). CONCLUSION High number of CD34⁺ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ cells tend to increase the occurrence of aGVHD, but high number of CD4⁺CD25⁺ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; CD4-Positive T-Lymphocytes ; Leukemia, Myeloid, Acute/complications* ; Graft vs Host Disease