The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Objective:To implement graded management based on mental state on patients with coronary heart dis-ease(CHD)in emergency intensive care unit(ICU),and analyze its clinical application value.Methods:A total of 110 CHD ICU patients admitted to Nanjing Hospital of Integrated Traditional Chinese and Western Medicine be-tween February 2020 and February 2023 were selected.They were divided into control group and observation group according to random number tablc method,with 55 cases in each group.The control group was given routine nurs-ing,and the observation group was given graded management based on psychological status.Both groups were inter-vened for a mean 2 weeks.Scores of self-rating anxiety scale(SAS)and self-rating depression scale(SDS),exer-cise of self-care agency(ESCA),Pittsburgh sleep quality index(PSQI)and the MOS 36-Item Short Form Health Survey(SF-36),cardiac function indexes before and after intervention,and incidence of adverse events were com-pared between two groups.Results:Compared with control group,there were significant decrease in scores of SAS[(60.56±3.39)points vs.(51.33±2.75)points],SDS[(62.07±2.76)points vs.(49.28±2.41)points]and PSQI[(13.41±2.32)points vs.(7.90±2.07)points],left atrial diameter[(39.06±1.05)mm vs.(36.69±1.37)mm],left ventricular end systolic diameter[(48.73±1.34)mm vs.(41.48±2.49)mm]and the incidence of ad-verse events(28.00％vs.8.00％)(P＜0.01 all);and significant increase in scores of ESCA[(142.48±4.83)points vs.(154.03±4.94)points],SF-36[(615.75±29.36)points vs.(731.56±38.43)points]and left ven-tricular ejection fraction[(50.31±3.21)％vs(63.60±3.02)％]in observation group(P＜0.001 all).Conclusion:Graded management based on mental state can significantly improve the mental state,quality of life,sleep quality,heart function and self-care ability of patients with coronary heart disease in emergency intensive care unit,and has high application value.

Objective:To analyze the diagnostic value of IgG anti-A/anti-B antibody titer in the serum of type O pregnant women after absorption of IgG anti-AB antibody for ABO hemolytic disease of fetus and newborn (ABO-HDFN).Methods:From February 2020 to September 2020,235 samples of neonatal hemolytic disease whose mother's blood type O from Beijing Blood Center were selected.The titer of IgG anti-A/anti-B antibody in mother's serum before and after absorption of IgG anti-AB antibody was detected by microcolumn gel card,and the incidence of ABO-HDFN was statistically analyzed.The titer level of IgG anti-A/anti-B antibody and the incidence of ABO-HDFN were compared before and after the absorption of IgG anti-AB antibody,and the diagnostic efficacy of the titer level of IgG anti-A/anti-B antibody in the serum of type O pregnant women after the absorption of IgG anti-A and B antibodies on the incidence of ABO-HDFN was analyzed using the receiver's work characteristic (ROC)curve.Results:Of the 235 neonatal hyperbilirubinemia samples with maternal blood type O,127 were blood type A,38 of which were diagnosed as ABO-HDFN;108 were blood type B,of which 31 were diagnosed as ABO-HDFN.Before and after absorption of IgG anti-AB antibody,there was a significant difference in the titer of IgG anti-A/anti-B antibody (P<0.05).Among the 69 confirmed cases,the incidence of ABO-HDFN increased with the increase of IgG anti-A/anti-B antibody with or without the IgG anti-AB antibody,but the anti-A/anti-B antibody titer≥1:512 before the absorption of IgG anti-AB antibody,while the anti-A/anti-B antibody titer decreased significantly,decreasing by three titers,all≤1∶512.The ROC curve shows that the titers of IgG anti-A/anti-B antibodies before and after absorption of IgG anti-AB antibodies can be used as the efficacy indicators for the diagnosis of ABO-HDFN.However,there was a significant difference in the potency of IgG anti-A/anti-B antibody titer for the diagnosis of ABO-HDFN before and after the absorption of IgG anti-AB antibody (P<0.05).The AUC values were greater than before absorption,indicating that the IgG anti-A/anti-B antibody after the absorption of IgG anti-AB antibody was better than before absorption (P<0.05).Conclusion:The higher the titer of IgG anti-A/anti-B antibody measured after absorbing IgG anti-AB antibody,the higher the incidence of ABO-HDFN. In addition,the efficacy of IgG anti-A/anti-B antibody titer to diagnose ABO-HDFN after absorption of IgG anti-AB antibody is higher than that before absorption.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.
Humans ; Sleep Initiation and Maintenance Disorders/chemically induced* ; Quality of Life ; Sleep ; Hypnotics and Sedatives/pharmacology* ; Antidepressive Agents/pharmacology*

Objective:To investigate the types, incidences, and clinical characteristics of shock in polytrauma patients at different stages after polytrauma.Methods:A retrospective study was conducted on polytrauma patients admitted to multiple trauma centers from June 2020 to December 2021. The inclusion criteria were patients >18 years old and treated due to polytrauma. Exclusion criteria included an admission time of more than 48 h after trauma, a history of malignancy, or metabolic, consumptive, and immunological diseases. The early stage was defined as the period of ≤48 h after polytrauma, and the middle stage was defined as the period between 48 h and 14 days. The patient’s medical history, clinical manifestations, laboratory tests, imaging examination, injury severity score (ISS), and Glasgow coma scale (GCS) were collected. The types, incidences, and clinical characteristics of shock in different stages after polytrauma were analyzed, according to the diagnostic criteria of each type of shock. The differences between the groups were compared by Student’s t test, χ2 test or Mann-Whitney U test. Results:The incidence of the early and middle stage shock after polytrauma were 73.1% and 36.4%, respectively, with statistically significant difference between stages ( P<0.01). There were significant differences in the incidence of hypovolemic shock (83.6% vs. 28.4%), distributed shock (13.7% vs. 80.9%) and cardiogenic shock (3.5% vs. 6.6%) between stages (all P<0.05). The incidence of obstructive shock (8.4% vs. 9.7%, P>0.05) was similar between stages. The incidence of undifferentiated shock was 1.6% and 1.2%, respectively. There were 9.5% patients with multifactorial shock in the early stage and 14.4% in the middle stage. Totally 7 combinations of multifactorial shock were found in different stages after polytrauma. In the early stage, the combination of HS and DS accounted the highest ratio (42.3%) and followed by HS and OS for 28.8%. In the middle stage, the combination of HS and DS was the most common (48.6%) and followed by DS and OS (24.3%). Conclusions:The incidence of shock in polytrauma patients is high. Different types of shock can occur simultaneously or sequentially. Therefore a comprehensive resuscitation strategy is significant to improve the success rate of treatment.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis