Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.

Objective To investigate the effects of tegafur, gimeracil and oteracil potassium combined with oxaliplatin on gastric motility-related hormones, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in elderly patients with gastric cancer. Methods A total of 128 elderly patients with gastric cancer were selected as the study subjects and randomly divided into control group (n=64) and observation group (n=64). The control group was treated with tegafur, gimeracil and oteracil potassium, while the observation group received tegafur, gimeracil and oteracil potassium combined with oxaliplatin. Gastric motility-related hormones [motilin (MTL) and vasoactive intestinal peptide (VIP)], MMP-2, MMP-9, tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9)], clinical efficacy and occurrence of adverse reactions were observed in both groups. The correlations of gastric motility-related hormones with the levels of MMP-2, MMP-9 and tumor markers were analyzed. Results After treatment, MTL levels in both groups were significantly lower, while VIP levels were significantly higher compared to before treatment. Additionally, the observation group had significantly lower MTL and higher VIP levels compared to the control group (P < 0.05). After treatment, the levels of MMP-2, MMP-9, CEA, CA125 and CA19-9 were significantly reduced in both groups compared to pretreatment levels, with the observation group showing significantly lower levels than the control group (P < 0.05). The total effective rate in the observation group was 70.31%, which was significantly higher than the 53.13% in the control group (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). A negative correlation was observed between MTL and MMP-2, MMP-9, CEA, CA125 as well as CA19-9 (P < 0.05), while VIP showed a positive correlation with MMP-2, MMP-9, CEA, CA125 and CA19-9 (P < 0.05). Conclusion The combination of tegafur, gimeracil and oteracil potassium and oxaliplatin is effective and safe for the treatment of elderly patients with gastric cancer. MTL, VIP, MMP-2, MMP-9, CEA, CA125 and CA19-9 are interrelated in the development of gastric cancer in elderly patients.

Objective To investigate the protective effect of spermidine against lipopolysaccharide(LPS)-induced myocardial injury in mice and the underlying mechanism.Methods C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy.In the cell experiment,cultured rat cardiomyocytes(H9c2 cells)were pretreated with 10 or 20 μmol/L spermidine before LPS exposure for 2 h,and the changes in cell viability and levels of lactate dehydrogenase(LDH)and cardiac troponin Ⅰ(cTNI)were assessed using CCK-8 kit,LDH detection kit and ELISA,respectively.Western blotting was performed to detect the changes in the expressions of Bax,Bcl-2,cleaved caspase-3,SLC7A11 and GPX4;the changes in reactive oxygen species(ROS)and Fe2+ levels were detected using fluorescent probes,and mitochondrial membrane potential of the cells was measured using JC-1 staining.Results Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages,which were significantly alleviated by pretreatment with spermidine.In H9c2 cells,LPS exposure significantly lowered the cell viability,increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels,decreased expressions of Bcl-2,SLC7A11 and GPX4,increased ROS production and Fe2+ level(P<0.05),and lowered mitochondrial membrane potential(all P<0.05).These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure.Conclusion Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.

Objective To investigate the protective effect of spermidine against lipopolysaccharide(LPS)-induced myocardial injury in mice and the underlying mechanism.Methods C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy.In the cell experiment,cultured rat cardiomyocytes(H9c2 cells)were pretreated with 10 or 20 μmol/L spermidine before LPS exposure for 2 h,and the changes in cell viability and levels of lactate dehydrogenase(LDH)and cardiac troponin Ⅰ(cTNI)were assessed using CCK-8 kit,LDH detection kit and ELISA,respectively.Western blotting was performed to detect the changes in the expressions of Bax,Bcl-2,cleaved caspase-3,SLC7A11 and GPX4;the changes in reactive oxygen species(ROS)and Fe2+ levels were detected using fluorescent probes,and mitochondrial membrane potential of the cells was measured using JC-1 staining.Results Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages,which were significantly alleviated by pretreatment with spermidine.In H9c2 cells,LPS exposure significantly lowered the cell viability,increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels,decreased expressions of Bcl-2,SLC7A11 and GPX4,increased ROS production and Fe2+ level(P<0.05),and lowered mitochondrial membrane potential(all P<0.05).These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure.Conclusion Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.

Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.

Objective:To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.Methods:From January 2017 to March 2022,151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study,microcolumn gel card test was used for irregular antibody screening,and antibody specificity identification was further performed in some antibody-positive subjects.Results:The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91％(1 375/151 471),0.23％(355/151 471)was detected in the first trimester,0.05％(71/151 471)in the second trimester,and 0.63％(949/151 471)in the third trimester.The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester,and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester.The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11％(689/1 375),which was the highest,the suspicious positive was 18.69％(257/1 375),and the positive was 31.20％(429/1 375).The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group,however,in the third trimester,the proportion of suspicious positive and weakly positive was lower than the first trimester,while,the proportion of positive was higher than the first trimester,and the difference was statistically significant(P＜0.001).Among the irregular antibody screening positive pregnant women,the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy≤1.Among 60 pregnant women who underwent antibody identification,the distributions of the antibodies were as follows:Rh blood group system accounted for 23.33％(14/60),Lewis system 43.33％(26/60),Kidd system 3.33％(2/60),MNS system 16.67％(10/60),P1PK system 1.67％(1/60),autoantibodies 1.67％(1/60),and 4 cases was unable to identify(6.67％,4/60).Among specific antibodies,the anti-Lea was the most common(30.00％),followed by anti-E(16.67％)and anti-M(16.67％).Conclusion:The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds,understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.

Objective:To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area,and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion.Methods:The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method,and 48 122 males in the same period were taken as controls.The data were analyzed by Chi-square test.Results:There were 112 870 cases(99.64％)of RhD+in 113 283 samples.In RhD+cases,CCDee(48.39％)and CcDEe(32.88％)were the main phenotypes.The first case of D--phenotype in Chongqing area was detected.413 cases(0.36％)of RhD-were detected,with ccdee(52.78％)and Ccdee(33.41％)as the main phenotypes.Compared with RhD-group,RhD+group showed statistically significant difference in Rh phenotype distribution(P＜0.01).Among 65 161 maternal samples,the positive rate of 5 antigens of Rh blood group from high to low was D＞e＞C＞c＞E,and there was no significant difference compared with male samples(P＞0.05).There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women,as well as between pregnant/postpartum women with different ABO blood groups(P＞0.05).In pregnant and postpartum women,there was no significant difference in distribution of Rh phenotype among the normal pregnancy population,the population with adverse pregnancy history,the population using human assisted reproductive technology(ART)and the population with infertility(P＞0.05).There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors(P＞0.05).In RhD positive pregnant and postpartum women,the probability of finding compatible blood for CcDEe phenotype was 100％,the probability of finding compatible blood for CCDee,CcDee and CCDEe phenotypes was 45％-60％,the probability of finding compatible blood for ccDEE,ccDEe and CcDEE phenotypes was 5％-10％,and the probability of finding compatible blood for other phenotypes was lower than 0.5％.The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99％of patients.Conclusion:Rh phenotype detection should be carried out for pregnant and postpartum women,and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.

The advantages of 3D printing technique in medicine were described.The current status of 3D printing technique was introduced when applied to customized radiotherapy compensation film,printing tumor models and breast cancer surgical navigation molds,individualized postoperative implants and printing models for drug testing and research of new therapies.The problems of 3D printing technique in breast cancer therapy were analyzed,and the future direction of development was envisioned.[Chinese Medical Equipment Journal,2024,45(11):103-108]

Digestive tract diseases， especially digestive tract tumors， including liver cancer， pancreatic cancer， and colorectal cancer， have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world， and the incidence and mortality of tumor diseases have been increasing year by year. Therefore， the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology， more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor， immunomodulatory， cardiac boosting， pain-easing， anti-inflammatory， and swelling-relieving activities. In clinical practice， cinobufotalin is mainly used to assist the treatment of liver cancer， lung cancer， colorectal cancer， gastric cancer and other malignant tumors， which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis， regulating cell cycle， inhibiting cell proliferation and angiogenesis， modulating immune response， reversing multidrug resistance， enhancing radiochemotherapy sensitivity， inhibiting tumor inflammation， invasion， and metastasis， etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years， aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin， promote the application of cinobufotalin in tumor treatment， and facilitate the further research and development of this compound.