Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

Objective To investigate the prognosis of childhood T-lymphoblastic lymphoma(T-LBL)treated with acute lymphoblastic leukemia(ALL)regimen and related influencing factors.Methods A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen(ALL-2009 or CCCG-ALL-2015 regimen)from May 2010 to May 2022.Results The 29 children with T-LBL had a 5-year overall survival(OS)rate of 84％±7％and an event-free survival(EFS)rate of 81％±8％.The children with B systemic symptoms(unexplained fever＞38° C for more than 3 days;night sweats;weight loss＞10％within 6 months)at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms(P＜0.05).The children with platelet count＞400x109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates(P＜0.05).There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen(P＞0.05).Compared with the ALL-2009 regimen,the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections(P＜0.05).Conclusions The ALL regimen is safe and effective in children with T-LBL.Children with B systemic symptoms,platelet count＞400x109/L,and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis.Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections,but it does not affect prognosis.

Purpose::The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique.Methods::A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD.Results::The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory.Conclusion::Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.

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.

This study investigated the effects of Agrimoniae Herba-Coptidis Rhizoma(XHC-HL)-medicated serum on the proliferation, migration, invasion, and apoptosis of human colorectal cancer HT29 and HCT116 cells via the autophagy mediated by lysosome-associated membrane protein type 2A(LAMP2A). Bioinformatics analysis was conducted to explore the role of LAMP2A in the development and progression of colorectal cancer. Western blot(WB) was used to detect the expression of LAMP2A protein in colorectal cancer cell lines. Lentiviral transfection was utilized to construct LAMP2A knockdown in HT29 and overexpression in HCT116 colorectal cancer cell models. Real-time fluorescence quantitative polymerase chain reaction(real-time qPCR) was performed to assess transfection efficiency. HT29 and HCT116 cells were treated with different concentrations of XHC-HL-medicated serum. The cell counting kit-8(CCK-8) assay was used to detect cell proliferation and determine the optimal concentration and duration of medicated serum intervention. HT29 cells were divided into a normal control(NC) group, an XHC-HL(medicated serum treatment) group, and an XHC-HL+shLAMP2A(medicated serum treatment+LAMP2A knockdown) group. HCT116 cells were divided into a NC group, an XHC-HL group, and an XHC-HL+LAMP2A(medicated serum treatment+LAMP2A overexpression) group. CCK-8 was used to measure cell viability. Colony formation assay was employed to assess cell proliferation ability. Scratch and Transwell migration assays were conducted to evaluate cell migration ability, and Transwell invasion assay was used to detect cell invasion ability. Flow cytometry was adopted to determine apoptosis rates. WB and real-time qPCR were employed to detect the effect of XHC-HL on the protein and mRNA expression of LAMP2A, heat shock cognate protein 70(HSC70), heat shock protein 90(HSP90), and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) in colorectal cancer cells. Differential expression analysis revealed that LAMP2A expression was significantly higher in colorectal cancer patients compared to that in normal controls. Survival analysis indicated that the key molecule of chaperone-mediated autophagy(CMA), LAMP2A, was closely associated with colorectal cancer progression. Gene set enrichment analysis showed that patients with high LAMP2A expression significantly upregulated tumor progression-related signaling pathways such as angiogenesis and immune suppression. Immune infiltration analysis found that patients with high LAMP2A expression had fewer CD8 T cell infiltrations in their tumor microenvironment. XHC-HL-medicated serum inhibited the viability of HT29 and HCT116 cells, with the optimal intervention concentration and duration being 20% and 48 hours, respectively. Compared to the NC group, XHC-HL inhibited the proliferation, migration, and invasion of HT29 and HCT116 cells, and induced apoptosis. The medicated serum treatment with LAMP2A knockdown further inhibited colorectal cancer cell proliferation, invasion, and migration, and promoted apoptosis, whereas overexpression of LAMP2A reversed the inhibitory effects of the medicated serum on proliferation, migration, and invasion, and reduced apoptosis rates. XHC-HL-medicated serum inhibited CMA by upregulating the protein and mRNA expression of LAMP2A, HSC70, and HSP90 and downregulating substrate protein GAPDH expression via the autophagy mediated by LAMP2A. In conclusion, XHC-HL-medicated serum inhibits the proliferation, migration, and invasion of colorectal cancer cells and induces apoptosis by downregulating the expression of the key CMA molecule LAMP2A and inhibiting CMA activity.
Humans ; Colorectal Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Lysosomal-Associated Membrane Protein 2/metabolism* ; Cell Proliferation/drug effects* ; Autophagy/drug effects* ; HCT116 Cells ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; HT29 Cells ; Serum/chemistry* ; Coptis chinensis

This study aims to investigate the effect and mechanism of the herb pair Agrimoniae Herba-Coptidis Rhizoma in inhibiting angiogenesis in the colorectal cancer inflammatory microenvironment by using the method of network pharmacology and the zebrafish model. The method of network pharmacology was employed to obtain the active components, potential core targets, and signaling pathways regulated by the herb pair in inhibiting angiogenesis in the inflammatory microenvironment of colorectal cancer, on the basis of which the underlying mechanism was predicted. The zebrafish model of colorectal cancer was established, and the inflammatory microenvironment was modeled. The effects of different concentrations of the herb pair on the area, number, and length of intersegmental vessels(ISVs) of the zebrafish model were observed. Western blot and real-time quantitative PCR were employed to measure the protein and mRNA levels, respectively, of vascular endothelial growth factor A(VEGFA), vascular epidermal growth factor receptor 2(VEGFR2, also known as kdrl, Flk1), and vascular epidermal growth factor receptor 3(VEGFR3, also known as Flt4). A total of 18 active components and 488 potential targets of Agrimoniae Herba-Coptidis Rhizoma were predicted, and 108 common targets were shared by the herb pair and the disease. According to the results of KEGG pathway enrichment analysis, the angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway were selected for verification. The zebrafish experiment showed that compared with the blank group, the model group showed increased area, number, and length of ISVs in the inflammatory microenvironment. Compared with the model group, the herb pair decreased the area, number, and length of ISVs in a concentration-dependent manner. Compared with the blank group, the model group showed up-regulated protein and mRNA levels of VEGFA, kdrl, and Flt4 in the inflammatory microenvironment. Compared with the model group, the herb pair down-regulated the protein and mRNA levels of VEGFA, kdrl, and Flt4 in a concentration-dependent manner. The results indicated that in the colorectal cancer inflammatory microenvironment, the herb pair Agrimoniae Herba-Coptidis Rhizoma could inhibit angiogenesis via multiple components, targets, and pathways. The anti-angiogenesis effect might be related to the down-regulation of the expression levels of angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway.
Zebrafish ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Colorectal Neoplasms/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Microenvironment/drug effects* ; Angiogenesis Inhibitors/pharmacology* ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Signal Transduction/drug effects* ; Coptis chinensis ; Inflammation/drug therapy* ; Angiogenesis

Objective To explore the prognostic value of MCF in elderly patients with cardiac amy-loidosis using CMR.Methods A retrospective analysis was conducted on 54 elderly patients with cardiac amyloidosis diagnosed in our hospital.All patients underwent CMR imaging.They were di-vided into a survival group of 25 cases and a mortality group of 29 cases based on clinical out-comes.Correlations of MCF with CMR parameters and biochemical indicators were evaluated.Cox regression analysis was performed to identify independent predictors of patient survival.Survival analysis was used to assess the value of MCF in predicting patient prognosis.Results The surviv-al group had significantly higher MCF than the mortality group[(70.63±24.72)％vs(43.59± 13.36)％,P=0.001].As MCF increasing,LVEF level was in an increasing trend,while LVMI,LVGPWT,ECV,and troponin T and NT-proBNP levels showed a decreasing trend.Multivariate Cox regression analysis revealed that MCF was an independent predictor of patient survival(HR=0.922,95％CI:0.866-0.981,P=0.011).Kaplan-Meier survival curve showed that the patients with MCF＞57％had significantly higher survival rates than those with MCF ≤57％(P＜0.01).Conclusion MCF is an effective imaging indicator for evaluating the prognosis of elderly patients with cardiac amyloidosis,which can help identify high-risk patients and guide clinical treatment.

OBJECTIVE: To investigate the effects of different manners of heat exposure on thoracic aorta injury in spontaneously hypertensive rats (SHRs) and explore the underlying mechanism. METHODS: Normal 6 to 7-week-old male SHRs were randomized into control group (cage at room temperature), intermittent heat exposure group (SHR-8 group, exposed to 32 ℃ for 8 h daily for 7 days) and SHR-24 group (with continuous exposure to 32 ℃ for 7 days). After the treatments, the pathologies of the thoracic aorta of the rats were observed with HE staining, and the expressions of Beclin1, LC3B and p62 were detected with Western blotting and immunofluorescence assay; TUNEL staining was used to observe cell apoptosis in the thoracic aorta, and the expressions of caspase-3, Bax, and Bcl-2 were detected using Western blotting. The effects of intraperitoneal injections of 3-MA (an autophagy agonist), rapamycin (an autophagy inhibitor) or compound C 30 min before intermittent heat exposure on the expressions of proteins associated with autophagy, apoptosis and the AMPK/mTOR/ULK1 pathway in the aorta were examined with immunohistochemistry. RESULTS: In SHR-8 group, the rats showed incomplete aortic intima with disordered cell distribution and significantly increased expressions of Beclin1, LC3II/LC3I and Bax, lowered expressions of p62 and Bcl-2, and increased apoptotic cells in the thoracic aorta (P < 0.05). Pretreatment with 3-MA obviously inhibited the expressions of autophagy- and apoptosis-related proteins, whereas rapamycin promoted their expressions. Compared with the control group, the rats in SHR-8 group had significantly down-regulated p-mTOR and up-regulated p-AMPK and p-ULK1 expression of in the aorta; Treatment with compound C obviously lowered the expressions of p-AMPK and p-ULK1 and those of LC3B and Beclin1 as well. CONCLUSION In SHRs, intermittent heat exposure causes significant pathologies and promotes autophagy and apoptosis in the thoracic aorta possibly by activating the AMPK/mTOR/ULK1 pathway.
Rats ; Male ; Animals ; Rats, Inbred SHR ; AMP-Activated Protein Kinases/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Aorta, Thoracic ; Beclin-1 ; Hot Temperature ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis ; Aortic Diseases ; Autophagy ; Autophagy-Related Protein-1 Homolog/metabolism*

Radiation-induced bystander effect (RIBE) refers to that irradiated cells release signaling factors and induce responses in nonirradiated cells.In other words, it is the communication between irradiated and nonirradiated cells by intracellular signals. RIBE could influence the efficacy of tumor radiotherapy, but also has potential risk to the normal tissues outside of radiation field. Studies have found that ionizing radiation can induce the alteration of miRNA expression not only in the irradiated cells but also in adjacent nonirradiated tissues, and miRNAs may play an important role in the regulation of signaling pathways between irradiated and nonirradiated bystander cells. This article reviewed the roles of miRNAs in RIBE.

Objective:Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods:A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed.Results:Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades ( P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender ( P=0.010), tumor size ( P=0.042), mitotic count ( P=0.003), and the modified NIH risk stratification ( P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions:Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.