BackgroundGraduate students frequently face life events， many of which may adversely affect their mental well-being. However， the interaction between life events and the development of depression， anxiety， and somatic symptoms remains unclear. ObjectiveTo explore the relationship between life events and the development of depressive， anxiety and somatic symptoms in graduate students， thereby informing prevention strategies for these conditions. MethodsA sample of 6 722 newly enrolled graduate students at a comprehensive university in Southwest China from September to November 2018 was selected. The assessment was conducted using the Adolescent Self-rating Life Events Checklist （ASLEC）， the 7-item Generalized Anxiety Disorder scale-7 item （GAD-7）， the Patient Health Questionnaire Depression Scale-9 item （PHQ-9）， and the Patient Health Questionnaire-15 （PHQ-15）. Network analysis was implemented by using the bootnet and qgraph packages in the R software （version 4.2.3）， with centrality indices calculated to identify core and bridge symptoms within the network. ResultsThe study encompassed a total of 6 171 graduate students， representing 91.80% of the target population. The prevalence rates of anxiety， depressive， and somatic symptoms among graduate students were 12.59% （777/6 171）， 16.63% （1 026/6 171）， and 27.66% （1 707/6 171）， respectively. Network analysis revealed that 'academic stress' was the core symptom with the highest strength and expected influence （both values=1.207）， while 'feeling down， depressed， or hopeless' was the bridge symptom with the highest bridge strength and bridge expected influence （both values=0.454）. There was no significant difference in global network strength and edge weight between women and men （P>0.05）. ConclusionAcademic stress， emerging as the core symptom， assumes a dominant position within the symptom network and exhibits strong interactions with other negative affective states. There was no gender difference in the network structure.

Objective:To explore the safety key points of total pancreaticoduodenectomy in the era of vascular resection technology and the important factors affecting rapid postoperative recovery.Methods:The clinical data of 52 patients with pancreatic cancer who underwent total pancreaticoduodenectomy in Beijing Chaoyang Hospital Affiliated to Capital Medical University from November 2014 to September 2022 were retrospectively analyzed, including 34 males and 18 females, aged (62±9). The intraoperative situation, incidence of postoperative complication, postoperative blood glucose control and postoperative survival rate were analyzed.Results:All operations of the 52 patients were successfully completed, including 48 patients underwent total pancreaticoduodenectomy combined with portal vein resection and allograft vascular grafts via artery approach. The portal vein occlusion time was (20±5) min. The incidence of postoperative complications was 28.8% (15/52), including 2 cases of abnormal gastric empty, 2 cases of diarrhea, 2 cases of chylous fistula, 4 cases of abdominal infection, 1 case of gastrointestinal fistula, 3 cases of gastrointestinal bleeding, and 1 case of pulmonary infection. Subcutaneous short-acting insulin injection was used to control blood glucose in the early stage after surgery, short-acting insulin combined with long-acting insulin was used for subcutaneous injection before sleep for diet recovery. All patients did not experience uncontrolled hyperglycemia. The median survival time of 52 patients was 13 months, and the longest follow-up time was 38 months. There were 37 patients died of tumor recurrence, 4 patients died of cardiovascular and cerebrovascular accidents, and 1 patient died of pulmonary infection in the 42 died patients.Conclusions:Total pancreaticoduodenectomy via artery approach can improve the R 0 resection rate in pancreatic cancer patients with vascular invasion, the rate of postoperative complication and mortality has no significant increase. The postoperative blood sugar control is satisfactory and the quality of life is guaranteed.

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.

Takeda G protein-coupled receptor 5(TGR5)is a bile acid receptor located on the surface of cell membrane,widely distributed in many tissues and cells in the body,and can be directly activated by most bile acids in vivo.TGR5 plays an important role in various physiological and pathophysiological processes,including cellular Ca2+transport,oxidative stress,cell proliferation,inflammatory responses,and mitochondrial metabolism,thereby maintaining mitochondrial homeostasis and vascular endothelial function,and inhibiting the progression of cardiovascular diseases such as atherosclerosis,myocardial hypertrophy,and cardiac remodeling after myocardial infarction.Currently,with the gradual clinical application of numerous bile acid and bile acid derivatives drugs,it is necessary to further investigate the role of TGR5 in the cardiovascular system,which is an important basis for clinical application of these new drugs.This review discusses the relationship between TGR5 and cardiovascular system from five perspectives:TGR5's involvement in regulating macrophages,endothelial function,vascular smooth muscle cells,cardiomyocytes,and mitochondrial metabolism.It summarizes the recent research progress,aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.

Objective To construct a mouse model of alcoholic liver fibrosis and explore the effect of supplementing exogenous thyroid hormone T3 on oxidative stress in liver.Methods Eighty mice were randomly divided into 6 groups,normal control group,alcoholic liver fibrosis(ALF)model group,and low concentration T3 intervention group(25 μg/kg),medium concentration T3 intervention group(50 μg/kg),high concentration T3 intervention group(100 μg/kg)and T3 control group(the concentration of T3 is 100 μg/kg).A model of mice alcoholic liver fibrosis was established by using alcoholic liquid feed combined with 31.5％ethanol gavage.From the sixth week,mice in the T3 intervention and T3 control group were injected with corresponding concentrations of T3 intraperitoneally for three weeks.Mice in the control and T3 control groups were fed with control liquid feed.The degree of mice liver injury and fibrosis was evaluated through the sirius red staining,Western blotting,and serum biochemical testing.The activity of superoxide dismutase(SOD),the content of glutathione(GSH)and malondialdehyde(MDA)in liver tissue were detected by ELISA,and the protein expressions of microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ)and p62 were detected by immunohistochemistry and Western blotting.Results The liver structure and function in the ALF group were severely damaged,autophagy was inhibited,and the oxidative stress response was significantly enhanced compared with the control group.Compared with the ALF group,the recovery of liver functional and structure and autophagy were showed in the T3 intervention group,and SOD activity and GSH content in the liver increased in the low and medium concentrations of T3 intervention groups,while MDA content significantly decreased.In the high concentration T3 intervention group,it showed the same increase in SOD activity,a significant decrease in MDA content,while the content of GSH was lower than that in the control group,which was not different with the ALF group.Conclusion Appropriate supplementation of T3 could affect the occurrence and development of alcoholic liver fibrosis by restoring the liver autophagy to inhibit the oxidative stress response.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.
Real-Time Polymerase Chain Reaction/methods* ; Paeonia/genetics* ; Actins/genetics* ; Reproducibility of Results ; Transcriptome ; Glyceraldehyde-3-Phosphate Dehydrogenases/genetics* ; Reference Standards ; Gene Expression Profiling/methods*

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

OBJECTIVE: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01). CONCLUSION EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.
Mice ; Humans ; Animals ; NADP/metabolism* ; Toll-Like Receptor 4 ; HMGB1 Protein/metabolism* ; Receptor for Advanced Glycation End Products/metabolism* ; Blood-Brain Barrier/metabolism* ; Neuroinflammatory Diseases ; Electroacupuncture ; Alzheimer Disease/therapy* ; Hippocampus/metabolism* ; Amyloid beta-Peptides/metabolism*

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.
Mice ; Animals ; Sterol Regulatory Element Binding Protein 1 ; Colitis-Associated Neoplasms ; PPAR alpha/genetics* ; Colonic Neoplasms/genetics* ; Colon ; Azoxymethane ; RNA, Messenger ; Dextran Sulfate ; Colitis/drug therapy* ; Mice, Inbred C57BL ; Disease Models, Animal