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

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

The rapid and non-destructive detection of constituent content of fresh tea leaves shows an important reference value for quality identification of tea.Visible near infrared(Vis-NIR)spectroscopy has been used for qualitative and quantitative analysis of chemical components in plant samples with the advantages such as simple,rapid and non-destructive detection.In this study,residual attention convolutional neural network(RACNN)was used to predict the internal constituent content of fresh tea leaves.Firstly,the reflectance spectral data of the samples in the Vis-NIR band range and the constituent contents of gallic acid(GA),gallocatechin(GC),epigallocatechin(EGC),and epigallocatechin gallate(ECG)in fresh tea leaves were collected.Based on the preprocessing of the spectral data,the contents of the four components were predicted using a partial least squares regression(PLSR)model,and the optimal preprocessing was determined.Subsequently,the characteristic bands were extracted using the random forest(RF)algorithm.Finally,the performances of PLSR,convolutional neural network(CNN)and RACNN models were compared.The results showed that for GA,the RACNN model worked best with a validation set coefficient of determination(R2)of 0.946 and a root mean square error of the prediction set(RMSEP)of 1.173;for GC,the RACNN model works best with a validation set R2 of 0.928 and RMSEP of 6.081;for EGC,the RACNN model works best with a validation set R2 of 0.891 and a RMSEP of 15.197;for ECG,the RACNN model worked best with a validation set R2 of 0.878 and a RMSEP of 7.837.The RACNN model established by Vis-NIR spectroscopy combined with chemometrics could realize the accurate detection of the contents of components in fresh tea.

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 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 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 To investigate the efficacy and safety of stereotactic body radiotherapy(SBRT)combined with camrelizumab and apatinib in treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data were retrospectively analyzed of 85 patients with advanced HCC treated in the Fifth Affiliated Hospital of Zhengzhou University and People's Hospital of Zhengzhou from January 2019 to September 2021.They were divided into observation group(n=31,SBRT combined with camrelizumab and apatinib)and control group(n=54,treated with camrelizumab and apatinib)according to whether they received SBRT.The propensity score matching(PSM)was used to balance the influence of confounding factors.The objective remission rate(ORR)and disease control rate(DCR)were compared between the two groups.The 6-month overall survival rate,1-year overall survival rate and progression-free survival(PFS)were compared between the two groups by Kaplan-Meier method.The safety of the two groups was evaluated by Common Terminology Criteria for Adverse Events(CTCAE)version 5.0.Results Before PSM,there were significant differences in age(P=0.043),number of extrahepatic metastasis(P=0.028),and previous surgical treatment(P=0.038)between the two groups.After PSM,there was no significant difference in baseline characteristics between the two groups(P>0.05).After PSM,27 cases were included in each groups,and three months after treatment,the ORR in observation group and control group were 66.7%and 29.6%,respectively,showed difference with statistically significant(P=0.006);and the DCR in the both groups were 96.3%and 85.2%respectively,showed no statistically significant difference(P=0.175).There were statistical differences in 6-month overall survival rate(96.3%vs.80.9%,P=0.001),1-year overall survival rate(75.0%vs.61.4%,P=0.034)and median PFS(8 months vs.5 months,P=0.003)between the observation group and control group.Multi-factor Cox regression analysis showed that baseline alpha-fetoprotein(AFP)≥400 ng/ml was an independent risk factor for affecting the survival of patients with advanced HCC(HR>1,P<0.05),while the triple therapy and previous targeted drugs therapy were the protective factors for the survival of patients with advanced HCC(HR<1,P<0.05).In the observation group,4 patients had grade 3 adverse reactions,and the common adverse reactions were dyspepsia(14.8%).One case of grade 3 adverse reactions occurred in control group,and there was no statistically significant difference in the incidence of adverse reactions between the two groups(P=0.639).Conclusion SBRT combined with camrelizumab and apatinib is a safe and effective treatment for advanced HCC with significant clinical effect and controllable adverse reactions.