Objective:Using graph theory analysis, this study compares the topological and node attributes of the brain network to explore the differences in gray matter structural and functional network topological properties between bipolar depression (BD) patients with and without obsessive-compulsive symptoms (OCS).Methods:A total of 90 BD patients (27 males, 63 females; median age 19.0(22.0, 25.0) years) were recruited from the psychiatric outpatient and inpatient departments of the First Affiliated Hospital of Jinan University between March 2018 and December 2022. Fifty healthy controls (19 males, 31 females; median age: 23.0 (20.0, 27.0) years) were also enrolled. The BD patients were divided into two groups based on the presence of OCS: 53 with OCS (OCS group) and 37 without OCS (NOCS group). Resting-state structural and functional MRI data were collected for all participants to construct gray matter structural and functional networks. Graph therory analysis was applied to calculate network topological metrics such as small-world properties. The structural and functional network topological properties were compared among the BD-OCS, BD-nOCS, and control groups. Partial correlation analysis was conducted to examine the association between network topological metrics with significant group differences and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Support vector machines (SVM) were used with these metrics as classification feature values to improve diagnostic accuracy through pairwise group classification.Results:Structural network analysis of gray matter: compared to HC group, both OCS group and NOCS group showed increased shortest path length and standardized characteristic path length (shortest path length: 0.78 and 0.80 vs. 0.69; normalized characteristic path length: 0.48 and 0.49 vs. 0.43), and decreased global efficiency (0.21 and 0.21 vs. 0.24) compared to the HC group (permutation test, all P<0.05). Compared to NOCS and HC groups, the OCS group showed increased nodal centrality and betweenness centrality in the right rolandic operculum and left superior occipital gyrus (permutation test, all P<0.05). Functional network analysis of gray matter: compared to the NOCS group, the OCS group showed increased node efficiency and decreased betweenness centrality in the cerebellum ( t=2.15, -3.04; all P<0.05); compared to HC groups, the OCS group showed decreased betweenness centrality in the cerebellum and left inferior frontal gyrus, along with increased node centrality and nodal efficiency in the right transverse temporal gyrus ( t=-2.99, -3.61, 3.06, 3.10; all P<0.05). In the OCS group, betweenness centrality in the left inferior frontal gyrus positively correlated with Y-BOCS scale obsessive thinking score ( r=0.303, P=0.034). Nodal centrality and node efficiency of the right transverse temporal gyrus negatively correlated with Y-BOCS total score ( r=-0.301, -0.311) and Y-BOCS obsessional thinking scores ( r=-0.385, -0.380) separately(all P<0.05). SVM classification: the combined network features achieved an area under the curve of 0.80 in distinguising OCS from NOCS patients. Conclusion:BD-OCS and BD-nOCS patients both exhibit consistent changes in gray matter structural network topology, with the OCS group displaying more pronounced nodal topological abnormalities. Multi-network feature integration demostrates potential for diagnostic classfication.

This study aims to determine the therapeutic effect and then elucidate the molecular mechanism of Dietary Yangrong Decoction(DYRT)on blood deficiency syndrome based on net-work pharmacology and study its active compounds.The molecular mechanism of DYRT in the treatment of blood deficiency syndrome was predicted by network pharmacology.The blood defi-ciency of rats was established using cyclophosphamide and acetophenohydrazine jointly,which was divided into a blank control group,a model group,a Men's Yangrong Decoction group(MYRT)(positive control group),a medicinal group and food-based Yangrong Decoction group.The active components were analyzed by liquid chromatography-mass spectrometry(HPLC-MS),the periph-eral hemogram was detected by an automatic biochemical analyzer,the levels of hematopoietic regulatory factors in serum were determined by ELISA,and the relative expression of EPO in kid-ney and PI3K,AKT,GM-CSF in bone marrow were measured by RT-PCR.The results showed that DYRT had 57 active ingredients and 128 potential targets for the treatment of spleen deficien-cy syndrome.1 835 items were obtained by GO enrichment analysis,and 20 pathways were ob-tained by KEGG enrichment analysis;DYRT and MYRT were identified by HPLC-MS to contain 12 same blood active compounds.Animal experiments showed that,compared with the model group,the number of red blood cells,the number of platelets and the content of hemoglobin in the DYRT group were significantly increased,and the number of white blood cells was significantly decreased(P＜0.05).The contents of EPO,IL-3,IL-6 and GM-CSF in serum were significantly in-creased,and the content of TNF-α was significantly decreased(P＜0.05).The relative expression levels of EPO in kidney and PI3K,AKT and GM-CSF mRNA in bone marrow were significantly increased(P＜0.05).Compared with the MYRT group,the number of white blood cells in the DYRT group was significantly reduced,the content of GM-CSF in serum was significantly in-creased,and the content of EPO and GM-CSF mRNA was significantly increased(P＜0.05).In conclusion,DYRT contains the same active compounds as MYRT,which can regulate hematopoi-etic factors,thereby activating the PI3K/AKT pathway to restore hematopoietic function and im-prove the blood deficiency state of the body.

Objective:To investigate the function and mechanism of exosomes in bladder cancer cell growth and metastasis regulating by NETs.Methods:The exosomes secreted by SV-HUC-1,MGH-U3 and 253J cells were extracted.PBS and the above exo-somes incubated with PMN,recorded as PBS group,SV-HUC-1 exo group,MGH-U3 exo group,253J exo group.The generation of NETs was detected by Sytox green staining,and the expressions of NETs marker proteins CIT-H3,NE and MPO were detected by Western blot.MGH-U3 and 253J cells were divided into Control group,PMN group,MGH-U3 exo group,253J exo group MGH-U3 exo+PMN group,253J exo+PMN group.The PMN culture supernatant of MGH-U3 exo group and 253J exo group were added with 1.5 U/ml DNAse,after incubation for 30 min,the collected mixture to co-incubate with MGH-U3 and 253J cells,recorded as MGH-U3 exo+PMN+DNAse group and 253J exo+PMN+DNAse group.The proliferation ability of MGH-U3 and 253J cells were detected by CCK8,the migration and invasion of cells were detected by Transwell,and the phosphorylation levels of PI3K and AKT were detected by Western blot.Results:Compared with PBS group,the formation of NETs and the expressions of CIT-H3,NE and MPO in MGH-U3 exo group and 253J exo group increased significantly(P<0.001).There was no significant change of the above indexes in SV-HUC-1 exo group.Compared with Control group,MGH-U3 exo+PMN group and 253J exo+PMN group had significantly increased cell prolifer-ation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT increased significantly(P<0.001).Com-pared with MGH-U3 exo+PMN group,MGH-U3 exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT decreased significantly(P<0.001).Compared with 293J exo+PMN group,293J exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability,the phosphor-ylation levels of PI3K and AKT decreased significantly(P<0.001).Conclusion:The exosomes of bladder cancer cells can promote the proliferation,migration and invasion of tumor cells by inducing the generation of NETs.

This study was aimed at predicting and analyzing the structural and functional properties of the persistence-associated secretory protein PaaX in Mycobacterium tuberculosis(M.tb),identifying its interacting partners,and elucidating its biological roles.Bioinformatics analysis revealed that PaaX comprises 240 amino acids with a molecular mass of 26.54 kDa(C1158H1866N354O334S14).The protein lacks transmembrane domains but contains a signal peptide.Its secondary structure is dominated by α-helices(53.33%),fol-lowed by random coils(36.25%)and extended strands(10.42%),thereby forming a homotetrameric spatial configuration.Potential PaaX-interacting proteins,including Rv0406c,EchA4,EchA5,HsaE,FadE8,LpqP,and End,were predicted.These candidate genes and the paaX gene were cloned into bacterial two-hybrid vectors and co-transformed into Escherichia coli BTH101 cells.Colony PCR and sequencing confirmed the accuracy of the recombinant constructs.Bacterial two-hybrid assays demonstrated direct interac-tions of PaaX with EchA4,HsaE,FadE8,and LpqP.Moreover,gradient dilution experiments indicated that the strongest binding af-finity occurred between PaaX and EchA4.AlphaFold 3 modeling further validated these interactions,thus providing high-confidence predictions of binding interfaces.Our findings revealed that PaaX,a secreted α-helix-rich protein,engages in specific interactions with key metabolic enzymes(EchA4,HsaE,and FadE8)and a lipoprotein(LpqP),thus suggesting its potential involvement in lipid metabolism,stress adaptation,and host-pathogen interactions.This study provides novel insights into PaaX's contribution to M.tb per-sistence and pathogenicity,and highlights its value as a potential target for tuberculosis diagnostics and therapeutic development.

This study was aimed at predicting and analyzing the structural and functional properties of the persistence-associated secretory protein PaaX in Mycobacterium tuberculosis(M.tb),identifying its interacting partners,and elucidating its biological roles.Bioinformatics analysis revealed that PaaX comprises 240 amino acids with a molecular mass of 26.54 kDa(C1158H1866N354O334S14).The protein lacks transmembrane domains but contains a signal peptide.Its secondary structure is dominated by α-helices(53.33%),fol-lowed by random coils(36.25%)and extended strands(10.42%),thereby forming a homotetrameric spatial configuration.Potential PaaX-interacting proteins,including Rv0406c,EchA4,EchA5,HsaE,FadE8,LpqP,and End,were predicted.These candidate genes and the paaX gene were cloned into bacterial two-hybrid vectors and co-transformed into Escherichia coli BTH101 cells.Colony PCR and sequencing confirmed the accuracy of the recombinant constructs.Bacterial two-hybrid assays demonstrated direct interac-tions of PaaX with EchA4,HsaE,FadE8,and LpqP.Moreover,gradient dilution experiments indicated that the strongest binding af-finity occurred between PaaX and EchA4.AlphaFold 3 modeling further validated these interactions,thus providing high-confidence predictions of binding interfaces.Our findings revealed that PaaX,a secreted α-helix-rich protein,engages in specific interactions with key metabolic enzymes(EchA4,HsaE,and FadE8)and a lipoprotein(LpqP),thus suggesting its potential involvement in lipid metabolism,stress adaptation,and host-pathogen interactions.This study provides novel insights into PaaX's contribution to M.tb per-sistence and pathogenicity,and highlights its value as a potential target for tuberculosis diagnostics and therapeutic development.

This study aims to determine the therapeutic effect and then elucidate the molecular mechanism of Dietary Yangrong Decoction(DYRT)on blood deficiency syndrome based on net-work pharmacology and study its active compounds.The molecular mechanism of DYRT in the treatment of blood deficiency syndrome was predicted by network pharmacology.The blood defi-ciency of rats was established using cyclophosphamide and acetophenohydrazine jointly,which was divided into a blank control group,a model group,a Men's Yangrong Decoction group(MYRT)(positive control group),a medicinal group and food-based Yangrong Decoction group.The active components were analyzed by liquid chromatography-mass spectrometry(HPLC-MS),the periph-eral hemogram was detected by an automatic biochemical analyzer,the levels of hematopoietic regulatory factors in serum were determined by ELISA,and the relative expression of EPO in kid-ney and PI3K,AKT,GM-CSF in bone marrow were measured by RT-PCR.The results showed that DYRT had 57 active ingredients and 128 potential targets for the treatment of spleen deficien-cy syndrome.1 835 items were obtained by GO enrichment analysis,and 20 pathways were ob-tained by KEGG enrichment analysis;DYRT and MYRT were identified by HPLC-MS to contain 12 same blood active compounds.Animal experiments showed that,compared with the model group,the number of red blood cells,the number of platelets and the content of hemoglobin in the DYRT group were significantly increased,and the number of white blood cells was significantly decreased(P＜0.05).The contents of EPO,IL-3,IL-6 and GM-CSF in serum were significantly in-creased,and the content of TNF-α was significantly decreased(P＜0.05).The relative expression levels of EPO in kidney and PI3K,AKT and GM-CSF mRNA in bone marrow were significantly increased(P＜0.05).Compared with the MYRT group,the number of white blood cells in the DYRT group was significantly reduced,the content of GM-CSF in serum was significantly in-creased,and the content of EPO and GM-CSF mRNA was significantly increased(P＜0.05).In conclusion,DYRT contains the same active compounds as MYRT,which can regulate hematopoi-etic factors,thereby activating the PI3K/AKT pathway to restore hematopoietic function and im-prove the blood deficiency state of the body.

Objective:To investigate the function and mechanism of exosomes in bladder cancer cell growth and metastasis regulating by NETs.Methods:The exosomes secreted by SV-HUC-1,MGH-U3 and 253J cells were extracted.PBS and the above exo-somes incubated with PMN,recorded as PBS group,SV-HUC-1 exo group,MGH-U3 exo group,253J exo group.The generation of NETs was detected by Sytox green staining,and the expressions of NETs marker proteins CIT-H3,NE and MPO were detected by Western blot.MGH-U3 and 253J cells were divided into Control group,PMN group,MGH-U3 exo group,253J exo group MGH-U3 exo+PMN group,253J exo+PMN group.The PMN culture supernatant of MGH-U3 exo group and 253J exo group were added with 1.5 U/ml DNAse,after incubation for 30 min,the collected mixture to co-incubate with MGH-U3 and 253J cells,recorded as MGH-U3 exo+PMN+DNAse group and 253J exo+PMN+DNAse group.The proliferation ability of MGH-U3 and 253J cells were detected by CCK8,the migration and invasion of cells were detected by Transwell,and the phosphorylation levels of PI3K and AKT were detected by Western blot.Results:Compared with PBS group,the formation of NETs and the expressions of CIT-H3,NE and MPO in MGH-U3 exo group and 253J exo group increased significantly(P<0.001).There was no significant change of the above indexes in SV-HUC-1 exo group.Compared with Control group,MGH-U3 exo+PMN group and 253J exo+PMN group had significantly increased cell prolifer-ation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT increased significantly(P<0.001).Com-pared with MGH-U3 exo+PMN group,MGH-U3 exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT decreased significantly(P<0.001).Compared with 293J exo+PMN group,293J exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability,the phosphor-ylation levels of PI3K and AKT decreased significantly(P<0.001).Conclusion:The exosomes of bladder cancer cells can promote the proliferation,migration and invasion of tumor cells by inducing the generation of NETs.

Objective:Using graph theory analysis, this study compares the topological and node attributes of the brain network to explore the differences in gray matter structural and functional network topological properties between bipolar depression (BD) patients with and without obsessive-compulsive symptoms (OCS).Methods:A total of 90 BD patients (27 males, 63 females; median age 19.0(22.0, 25.0) years) were recruited from the psychiatric outpatient and inpatient departments of the First Affiliated Hospital of Jinan University between March 2018 and December 2022. Fifty healthy controls (19 males, 31 females; median age: 23.0 (20.0, 27.0) years) were also enrolled. The BD patients were divided into two groups based on the presence of OCS: 53 with OCS (OCS group) and 37 without OCS (NOCS group). Resting-state structural and functional MRI data were collected for all participants to construct gray matter structural and functional networks. Graph therory analysis was applied to calculate network topological metrics such as small-world properties. The structural and functional network topological properties were compared among the BD-OCS, BD-nOCS, and control groups. Partial correlation analysis was conducted to examine the association between network topological metrics with significant group differences and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Support vector machines (SVM) were used with these metrics as classification feature values to improve diagnostic accuracy through pairwise group classification.Results:Structural network analysis of gray matter: compared to HC group, both OCS group and NOCS group showed increased shortest path length and standardized characteristic path length (shortest path length: 0.78 and 0.80 vs. 0.69; normalized characteristic path length: 0.48 and 0.49 vs. 0.43), and decreased global efficiency (0.21 and 0.21 vs. 0.24) compared to the HC group (permutation test, all P<0.05). Compared to NOCS and HC groups, the OCS group showed increased nodal centrality and betweenness centrality in the right rolandic operculum and left superior occipital gyrus (permutation test, all P<0.05). Functional network analysis of gray matter: compared to the NOCS group, the OCS group showed increased node efficiency and decreased betweenness centrality in the cerebellum ( t=2.15, -3.04; all P<0.05); compared to HC groups, the OCS group showed decreased betweenness centrality in the cerebellum and left inferior frontal gyrus, along with increased node centrality and nodal efficiency in the right transverse temporal gyrus ( t=-2.99, -3.61, 3.06, 3.10; all P<0.05). In the OCS group, betweenness centrality in the left inferior frontal gyrus positively correlated with Y-BOCS scale obsessive thinking score ( r=0.303, P=0.034). Nodal centrality and node efficiency of the right transverse temporal gyrus negatively correlated with Y-BOCS total score ( r=-0.301, -0.311) and Y-BOCS obsessional thinking scores ( r=-0.385, -0.380) separately(all P<0.05). SVM classification: the combined network features achieved an area under the curve of 0.80 in distinguising OCS from NOCS patients. Conclusion:BD-OCS and BD-nOCS patients both exhibit consistent changes in gray matter structural network topology, with the OCS group displaying more pronounced nodal topological abnormalities. Multi-network feature integration demostrates potential for diagnostic classfication.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

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.