Objective To explore the correlation between the expression level of serum fibrinogen-like protein 1(FGL1)and the indexes of metabolism and renal function in patients with diabetic nephropathy(DN)and diabetes mellitus(DM),and provide reference for clinical diagnosis and treatment.Methods From January 2017 to April 2023,30 patients with DM and treated in Jiangsu Province Hospital of Chinese Medicine were selected as the DM group,68 patients with DN were selected as the DN group,and 36 healthy subjects were selected as the control group.The DN group was further divided into the early DN(DN-E)group(n=38)and the late DN(DN-A)group(n=30)according to whether there was a large amount of proteinuria and the severity.Clinical data such as serum albumin(ALB),estimated glomerular filtration rate(eGFR)and albumin-to-creatinine ratio(ACR)were collected.Serum FGL1 level was detected by enzyme-linked immunosorbent assay(ELISA).Pearson linear correlation was used for correlation,the diagnostic value was analyzed by ROC curve.Results Compared with the control group,the levels of ACR,FGL1 in patients with DM group increased,the levels of eGFR decreased,and the differences were statistically significant(t=5.686,4.336,-4.683,all P<0.05).Compated with the DM group,the levels of ACR,FGL1 in patients with DN-E group was increased,and the level of eGFR was decreased,and the differences were statistically significant(t=5.275,3.454,-4.969,all P<0.05).Compared with the DN-E group,the levels of ACR,FGL1 in the DN-A group were increased,the levels of eGFR were decreased,and the differences were statistically significant(t=7.881,7.051,-5.596,all P<0.05).Serum FGL1 level was negatively correlated with ALB and eGFR(r=-0.638,-0.547,all P<0.05),and positively correlated with ACR(r=0.691,P<0.05).The AUC(95%CI),specificity and sensitivity of serum FGL1 level in the diagnosis of DN were 0.947(0.908～0.987),100%and 82.4%,respectively.Conclusion The level of serum FGL1 in DN and DM patients is high,and the level of serum FGL1 is closely related to the common metabolic indexes such as ALB,eGFR and ACR in the diagnosis of DN,which may have certain clinical diagnostic value.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Aim To investigate the therapeutic effects of corylifol A(CYA)on Lewis lung carcinoma(LLC)cachexia mice and its ameliorating effects on myotube atrophy induced by LLC cell-conditioned medium(LLC CM)in vitro,and to explore the mechanisms.Methods The cancer cachexia was induced by subcu-taneous inoculation of LLC cells to C57BL/6J mice.The effects of CYA(10,20 mg·kg-1·d-1,i.p.)on the cachexia symptoms and survival time of cachexia mice were observed.The effects of 2.5 or 5 μmol·L-1 CYA on myotube atrophy of C2C12 induced by LLC CM were observed.The effects of CYA on its pos-sible target the serine/threonine-protein kinase TAO1(TAOK1)and downstream signaling pathways were detected using Western blot.The influence of TAOK1 knockout on the ameliorating effects of CYA on myo-tube atrophy was observed.Results CYA could sig-nificantly prolong the survival time of tumor-bearing mice and ameliorate the muscle atrophy associated with LLC.The effects of CYA on myotube atrophy are relat-ed to its regulation of TAOK1.The effects of CYA could be reduced by knockout of TAOK1.Conclusions CYA improves the survival of LLC cachexia mice and ameliorates the related skeletal muscle atrophy.The mechanism of CYA is related to its inhibition on TAOK1 and downstream signaling pathways.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Objective To explore the correlation between the expression level of serum fibrinogen-like protein 1(FGL1)and the indexes of metabolism and renal function in patients with diabetic nephropathy(DN)and diabetes mellitus(DM),and provide reference for clinical diagnosis and treatment.Methods From January 2017 to April 2023,30 patients with DM and treated in Jiangsu Province Hospital of Chinese Medicine were selected as the DM group,68 patients with DN were selected as the DN group,and 36 healthy subjects were selected as the control group.The DN group was further divided into the early DN(DN-E)group(n=38)and the late DN(DN-A)group(n=30)according to whether there was a large amount of proteinuria and the severity.Clinical data such as serum albumin(ALB),estimated glomerular filtration rate(eGFR)and albumin-to-creatinine ratio(ACR)were collected.Serum FGL1 level was detected by enzyme-linked immunosorbent assay(ELISA).Pearson linear correlation was used for correlation,the diagnostic value was analyzed by ROC curve.Results Compared with the control group,the levels of ACR,FGL1 in patients with DM group increased,the levels of eGFR decreased,and the differences were statistically significant(t=5.686,4.336,-4.683,all P<0.05).Compated with the DM group,the levels of ACR,FGL1 in patients with DN-E group was increased,and the level of eGFR was decreased,and the differences were statistically significant(t=5.275,3.454,-4.969,all P<0.05).Compared with the DN-E group,the levels of ACR,FGL1 in the DN-A group were increased,the levels of eGFR were decreased,and the differences were statistically significant(t=7.881,7.051,-5.596,all P<0.05).Serum FGL1 level was negatively correlated with ALB and eGFR(r=-0.638,-0.547,all P<0.05),and positively correlated with ACR(r=0.691,P<0.05).The AUC(95%CI),specificity and sensitivity of serum FGL1 level in the diagnosis of DN were 0.947(0.908～0.987),100%and 82.4%,respectively.Conclusion The level of serum FGL1 in DN and DM patients is high,and the level of serum FGL1 is closely related to the common metabolic indexes such as ALB,eGFR and ACR in the diagnosis of DN,which may have certain clinical diagnostic value.

Aim To investigate the therapeutic effects of corylifol A(CYA)on Lewis lung carcinoma(LLC)cachexia mice and its ameliorating effects on myotube atrophy induced by LLC cell-conditioned medium(LLC CM)in vitro,and to explore the mechanisms.Methods The cancer cachexia was induced by subcu-taneous inoculation of LLC cells to C57BL/6J mice.The effects of CYA(10,20 mg·kg-1·d-1,i.p.)on the cachexia symptoms and survival time of cachexia mice were observed.The effects of 2.5 or 5 μmol·L-1 CYA on myotube atrophy of C2C12 induced by LLC CM were observed.The effects of CYA on its pos-sible target the serine/threonine-protein kinase TAO1(TAOK1)and downstream signaling pathways were detected using Western blot.The influence of TAOK1 knockout on the ameliorating effects of CYA on myo-tube atrophy was observed.Results CYA could sig-nificantly prolong the survival time of tumor-bearing mice and ameliorate the muscle atrophy associated with LLC.The effects of CYA on myotube atrophy are relat-ed to its regulation of TAOK1.The effects of CYA could be reduced by knockout of TAOK1.Conclusions CYA improves the survival of LLC cachexia mice and ameliorates the related skeletal muscle atrophy.The mechanism of CYA is related to its inhibition on TAOK1 and downstream signaling pathways.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Objective:To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood thera-py for the treatment of diabetic mellitus erectile dysfunction.Methods:China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,Chinese Biomedical Database(CBM),PubMed,Cochrane Library,Embase and Web of Science were searched from incep-tion until October 20th of 2024,for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of dia-betic erectile dysfunction.Literature screening,quality evaluation,and data extraction were carried out in accordance with relevant standards.The software of RevMan5.4 was used for the analysis of publication bias.And meta-analysis was conducted to assess the im-pact of this therapy on IIEF-5,total effective rate,adverse reactions.The evidence levels according to the analysis results were evalua-ted.Results:Totally 19 RCTs were included,involving 1 612 patients.The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores(MD=3.59,95％CI[2.14,5.03],P＜0.01),total effective rate(OR=4.30,95％CI[3.29,5.32],P＜0.000 01).However,there was no statistically significant difference in the inci-dence of adverse reactions(OR=0.98,95％CI[0.48,2.01],P=0.96)between the two groups.Conclusions:Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction.But considering the limited quantity of included studies,more high-quality studies still be needed to validate the therapeutic effect.

Objective:To summarize and analyze the characteristics of delayed hemolytic transfusion reaction in children,in order to provide a scientific basis for clinical prevention,and ensure the safety of children's blood transfusion.Methods:The basic situation,clinical symptoms and signs,diagnosis time and disappearance time of alloantibody of delayed hemolytic transfusion reaction in children were retrospectively analyzed.The serological test,routine blood test,biochemical detection and urine analysis results were compared pre-and post-transfusion.Results:Among 15 164 children with repeated blood transfusion,23 cases occurred delayed hemolytic transfusion reactions,with an incidence rate of 0.15％,and mainly children with thalassemia and acute leukemia.39.13％of delayed hemolytic reactions occurred in children with more than 20 times of blood transfusions.Anemia was the main clinical symptom in 86.96％of children.4.35％of children had hypotension and dyspnea.Serological test results showed that the positive rate of direct antiglobulin test was 91.30％,and that of erythrocyte homologous antibody test was 100％.Erythrocyte alloantibodies were common in Rh and Kidd blood group systems,accounting for 73.91％and 13.04％,respectively.Laboratory test results showed that hemoglobin,reticulocyte,spherocyte,total bilirubin,indirect bilirubin,lactate dehydrogenase,serum ferritin and urine color were significantly different after transfusion compared with those before transfusion(all P＜0.05).The average diagnosis time of delayed hemolytic transfusion reactions was 18.56 days,and the average disappearance time of erythrocyte alloantibodies was 118.43 days.Conclusion:The incidence of delayed hemolytic transfusion reaction is high in children with repeated blood transfusion,and the disappearance time of erythrocyte homologous antibody is long.Blood matched ABO,Rh and Kidd blood group antigens should be transfused prophylactically.Once diagnosed,erythrocyte alloantibody corresponding to antigen-negative blood should be used throughout the whole process.