Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis （GSEA） and short time-series expression miner （STEM）. MethodSD rats were randomly divided into six groups， including a normal group， a model group， high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription， and a positive drug group. The model of diabetes with depression was established by high-fat feeding， streptozotocin （STZ） injection， and chronic mild unpredictable stress. The high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52， 10.26， and 5.13 g·kg^-1 respectively. The positive drug group was orally administered 0.18 g·kg^-1 metformin and 1.8 g·kg^-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days， the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay （ELISA）. Three hippocampus samples were randomly selected from the normal group， the model group， the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis， GSEA analysis， and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR （Real-time PCR）. The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group， the fasting blood glucose， cholesterol， and triglyceride levels in the model group were significantly increased （P<0.01）. Moreover， the immobility time in the forced swimming test was significantly increased， while the time to climb the platform was significantly prolonged， and the search distance in the target quadrant was significantly reduced in the Morris water maze test （P<0.05，P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose， cholesterol， and triglycerides in rats with diabetes with depression （P<0.05，P<0.01）， reduced the immobility time in the forced swimming test， shortened the stage time in the Morris water maze test， and increased the search distance ratio in the target area （P<0.05，P<0.01）. Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group， while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription， with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group， and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription， with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group， model group， and high dose group of Zuogui Jiangtang Jieyu prescription， two significantly different trend clustering groups were obtained. One key gene set for axonal guidance， as well as key target signal elements Sema3c， Sema7a， Robo3， Epha8， and Epha7， were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group， the mRNA expression of Robo3， Sema7a， and Epha7 in the hippocampus of the model rats was significantly reduced （P<0.05， P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3， Sema7a， and Epha7 （P<0.05， P<0.01）. Western blot results showed that compared with the results in the normal group， the Sema7a， ITGB1， and FAK protein expression in the hippocampus of the model group was significantly reduced （P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a， ITGB1， and FAK in the hippocampus （P<0.05，P<0.01）. ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.

Objective To observe the protective effect of modified Baishile Decoction on hippocampal neuronal cells cultured in vitro;To explore its mechanism of treating post-stroke depression.Methods Hippocampal neuronal cells from mammary rats were isolated and cultured in vitro,cell injury was induced by oxygen glucose deprivation combined with lipopolysaccharide.The cells were divided into normal group,model group,blank serum group(10%)and modified Baishile Decoction containing serum group(10%).Invertedmicroscope was used to observe cell morphological changes,CCK-8 method was used to detect cell survival rate,Hoechst33342 staining was used to observe apoptosis,ELISA was used to detect Glu,5-HT,TNF-α,IL-1β,and IL-6 contents in cell supernatant,the expressions of purinergic P2X7 receptor(P2X7R)and NOD-like receptor protein 3(NLRP3)were detected by immunofluorescence staining.Results Compared with the normal group,the hippocampal neurons in the model group showed significant changes in cell morphology,the cell survival rate significantly decreased(P<0.01),the cell apoptosis increased(P<0.01);Glu,TNF-α,IL-1β,IL-6 contents in cell supernatant significantly increased(P<0.05,P<0.01),5-HT content significantly decreased(P<0.01),P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly increased(P<0.01).Compared with the model group,the morphology of hippocampal neurons in modified Baishile Decoction containing serum group was significantly improved,the cell survival rate significantly increased(P<0.01),the cell apoptosis reduced(P<0.01);Glu,TNF-α and IL-1β content in cell supernatant significantly reduced(P<0.05,P<0.01),5-HT content significantly increased(P<0.01),and P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly decreased(P<0.01).Conclusion Modified Baishile Decoction may exert a protective effect on oxidative glucose deprivation combined with lipopolysaccharide induced hippocampal neuronal inflammation damage by inhibiting the P2X7R/NLRP3 signaling pathway,regulating neurotransmitter secretion,and inhibiting inflammatory factor release,thus treating post-stroke depression.

Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

OBJECTIVE: To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression. METHODS: Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (n=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting. RESULTS: The diabetic rats with depression showed significantly increased levels of blood glucose and leptin (P < 0.01) and prolonged immobility time in forced swimming test (P < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test (P < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased (P < 0.01) while hippocampal Gli-3 expression was increased significantly (P < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose (P < 0.01) and leptin level (P < 0.05) and improved their performance in behavioral tests (P < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus (P < 0.01) and reduced hippocampal expression of Gli-3 (P < 0.05) in the rat models. CONCLUSION ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.
Animals ; Rats ; Blood Glucose ; Bromodeoxyuridine ; Cell Self Renewal ; Cyclin D1 ; Dentate Gyrus ; Depression ; Diabetes Mellitus, Experimental ; Hippocampus ; Leptin ; Nestin ; Rats, Sprague-Dawley

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

OBJECTIVETo appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema.

METHODSThe clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve].

RESULTSThere was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and there was obviously negative correlation between oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.674 and -0.817, P values below 0.01). In group H, there was obviously positive correlation between EVLWI and ITBVI (r = 0.751, P < 0.01) but no obvious correlation between EVLWI and PVPI, oxygenation index and EVLWI, or oxygenation index and PVPI (with r values respectively -0.275, 0.197, and 0:062, P values above 0.05). The total area under ROC curve of PVPI value for differentiating the type of pulmonary edema was 0.987 [with 95% confidence interval (CI) 0.962-1.013, P < 0.01], and 1.9 was the cutoff value with sensitivity of 94.1% and specificity of 95.2% . The total area under ROC curve of ITBVI value for differentiating the type of pulmonary edema was 0.940 (with 95% CI 0.860-1.020, P < 0.01), and 1,077. 5 mL/m2 was the cutoff value with sensitivity of 95.2% and specificity of 88.2%.

CONCLUSIONSEVLWI, PVPI, and ITBVI have an important significance in the differential diagnosis of the type of burn-induced pulmonary edema, and they may be helpful in the early diagnosis and management of burn-induced pulmonary edema.

Blood Gas Analysis ; Blood Volume ; Burns ; complications ; Capillary Permeability ; Diagnosis, Differential ; Extravascular Lung Water ; Humans ; Lung ; blood supply ; Lung Injury ; physiopathology ; therapy ; Monitoring, Physiologic ; Pulmonary Edema ; diagnosis ; etiology ; ROC Curve ; Respiration, Artificial ; Retrospective Studies