ObjectiveBased on spatial metabolomics technology combined with pharmacological indexes， to analyze the mechanism of Fritillariae Cirrhosae Bulbus（FCB） powder in improving bleomycin-induced pulmonary fibrosis in rats. MethodSixty SD rats were randomly divided into five groups， including the blank group， the model group， and high， medium， low dosage groups of FCB. Except for the blank group， rats in all other groups were injected with bleomycin by tracheal injection to establish a pulmonary fibrosis model. Postoperatively， the high， medium and low dosage groups of FCB were administered aqueous solutions of FCB powder at doses of 0.36， 0.18， 0.09 g·kg^-1， respectively， continuously for 28 d. The blank and model groups were given an equal volume of distilled water by gavage. After the last administration， lung tissues and blood samples were collected， the pathological conditions of rat lung tissues were comprehensively evaluated by hematoxylin-eosin（HE） and Masson staining， and aerodynamic assisted desorption electrospray ionization mass spectrometry imaging（AFADESI-MSI） was used for MSI of rat lung tissues from different experimental groups. Spatial metabolomics analysis was conducted on the fibrotic areas of lung tissues in the model group and the high dosage group of FCB based on HE staining images. Differential metabolites between groups were screened by orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） values>1， t-test P<0.05， and fold change analysis. Metabolic pathway analysis of the identified differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. Protein expression levels of nuclear transcription factor-κB p65（NF-κB p65） and heme oxygenase-1（HO-1） in rat lung tissues were detected by Western blot. Biochemical assessments of superoxide dismutase（SOD）， malondialdehyde（MDA） and glutathione（GSH） levels in rat lung tissues were conducted. Serum levels of interleukin（IL）-1β， IL-6， nuclear factor erythroid 2 related factor 2（Nrf2）， and tumor necrosis factor-α（TNF-α） were measured by enzyme linked immunosorbent assay（ELISA）， and some of the screened signaling pathways with strong correlation were verified. ResultThe results of MSI experiment showed that after 28 d of the administration of FCB powder to rats with pulmonary fibrosis， the content of L-arginine in the fibrotic regions of lung tissues was significantly different from that of rats in the model group， and the content of phosphatidylcholine was lower than that in the fibrotic region of lung tissues of rats in the model group. Western blot results confirmed that， in comparison to the model group， oral administration of FCB powder for 28 d could inhibit the elevated expression of NF-κB p65 protein in the lung tissues of rats with pulmonary fibrosis. Furthermore， high dose of FCB powder was able to significantly inhibit the expression of HO-1 after oral administration （P<0.05）. The cytokine detection results indicated that the concentrations of IL-1β， IL-6 and TNF-α in the serum of rats from the high， medium， low dosage groups of FCB were reduced by comparing with the model group， and the high dose of Chuanbeimu powder administered by gavage could significantly inhibit the trend of decreased SOD， GSH， Nrf2 contents and increased MDA content induced by bleomycin. ConclusionOral administration of FCB powder has the potential to partially ameliorate bleomycin-induced pulmonary fibrosis in rats， and its mechanism may be related to the regulation of pathways associated with inflammation（NF-κB p65） and oxidative stress（Nrf2/HO-1）.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.
Animals ; Rats ; PC12 Cells ; Ferroptosis/genetics* ; Reactive Oxygen Species ; Transcription Factors ; Glutathione

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.
Biomarkers, Tumor ; Carcinoembryonic Antigen ; Humans ; Inflammation/classification* ; Lymphocytes ; Neutrophils ; Nomograms ; Preoperative Period ; Prognosis ; Rectal Neoplasms/surgery* ; Retrospective Studies

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective: To explore the clinical application and efficacy of lateral upper arm free flap (LUAFF) for one-stage repairing of soft tissue defect after oral cancer surgery. Methods: This article was a retrospective analysis of clinical data of 46 patients receiving treatment of one-stage repairing of soft tissue defect with LUAFF after oral cancer surgery in Hunan Cancer Hospital, from June 2019 to June 2021. Among these cases, 40 were males, and 6 were females. The patients' ages were from 23 to 64 years old. The clinical data of patients were reviewed and outcomes were evaluated. SPSS 23.0 software was used for statistical analysis. Results: In the LUAFF of 46 patients, flap area ranged from 5.0 cm×3.5 cm to 15.0 cm×7.0 cm; the mean pedicle length was 8.15±1.42 cm; the mean artery diameter was 1.20±0.41 mm (range, 1.5 to 2.5 mm); the mean diameter of the largest veins was 2.15±0.52 mm; and the median number of perforators was 2.6 (range, 1 to 4). All donor sites were closed primarily. Two cases had arterial anastomosis thrombosis, but their flaps were successfully saved with urgent re-anastomosis of the vessels. The overall flap survival rate was 93.5%(43/46), with flap necroses after operation in three cases. No patient received tracheotomy. The average hospital stay time of patients after operation was 9.4 days. The follow-up time was 6-24 months, elbow and wrist movements on the operative side were normal, and the upper limb muscle strength was not affected. Conclusions: LUAFF is a suitable choice for the repairs of small-moderate tissue defects in oral cancer surgery, with consistent perforators in the flap, simple harvest method, concealed donor-site scar, and high survival rate.
Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Retrospective Studies ; Free Tissue Flaps ; Mouth Neoplasms ; Postoperative Period ; Cicatrix

Objective:To summarize the clinical features and treatment of pneumocystis jirovecii pneumonia(PCP) in children with non-human immunodeficiency virus(HIV) infection.Methods:A retrospective study was performed on seven cases of severe PCP children with non-HIV infection who were admitted to PICU of The University of Hong Kong-Shenzhen Hospital and PICU of Xianyang Rainbow Hospital from May 1, 2015 to May 1, 2021.The risk factors, clinical manifestations, laboratory results, pulmonary radiological features, treatment and outcomes were observed.Results:Seven children with PCP, including four males and three females, aged from 13 months to 85 months[(42.4±26.8) months], were all associated with underlying diseases, and most of which was hematological malignancies.Six children had a history of using TMP-SMX for PCP prevention, but four of them stopped by themselves and infected PCP in 2 to 4 weeks.All children had hypoxic respiratory failure, whose OI was 30.6±3.4, and presented with fever, dry cough, progressive dyspnea but no lung rales in the early stage.LDH[(745.7±317.0) U/L] and β-D-glucan[(513.8±225.0) pg/mL] increased in all patients.Chest CT showed diffused interstitial changes in bilateral lung fields associated with multiple exudative lesions.Among the anti-Pneumocystis Jirovecii treatment regimens, all cases began the treatment in the first three days during the admission, five cases were treated with intravenous TMP-SMX, and two cases were treated with oral TMP-SMX + caspofungin, with a course of 21 days.All children were also treated with glucocorticoid at the same time.Three days after the treatment of PCP, two children were worsened and one of them died, while another one started to recover on the 6th day of the regimen.The remaining five cases began to show clinical improvement after 3~7 days of PCP treatment.Finally six children were cured and one was died.Conclusion:PCP infection of children without HIV has high risk of destruction in immune system.TMP-SMX can prevent PCP effectively.In the severe PCP cases, early commencement of intravenous TMP-SMX can reduce the mortality rate.In the absence of intravenous TMP-SMX, oral TMP-SMX can be used with caspofungin.

Objective: To explore the classification and reconstruction strategy of defects in lateral face region after operation of malignant tumors. Methods: Eighteen cases with the reconstruction of complicated defects after resection of tumors in the region of lateral face from January 2015 to January 2018 in Hunan Cancer Hospital were retrospectively reviewed. There were 14 males and 4 females, aged from 32 to 68 years. According to the presence or absence of bony scaffold, complicated defects were divided into two main categories: soft tissue perforating defects and soft tissue defects combined with bony scaffold defects. All soft tissue perforating defects in 5 cases were repaired with free anterolateral femoral flaps. Among 13 cases with soft tissue plus bony scaffold defects, 3 were repaired with free fibular flaps, 6 with free fibular flaps combined with free anterolateral femoral flaps, and 4 with chimeric deep circumflex iliac artery perforator flaps combined with anterolateral femoral flaps. Results: All flaps survived well. Two patients complicated with fistula in floor of mouth, but the wound healed after dressing change. Transoral feeding was resumed within 2 weeks after surgery in all patients. One year follow-up evaluation showed that 14 cases had symmetrical face and 10 cases had mouth opening more than 3 transverse fingers. After 36-50 months of follow-up, 6 patients died, with an overall 3-year survival rate of 66.7%. Conclusion: The classification of defects with or without bony stent loss is conducive to the overall repair design, the recovery of facial contour stent, the effective fill of dead space and the maintain of residual occlusal relationship. Good reconstruction results require a multi flap combination of osteocutaneous and soft tissue flaps.
Facial Neoplasms ; Female ; Free Tissue Flaps ; Humans ; Male ; Perforator Flap ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Thigh/surgery*

The human brain undergoes rapid development during childhood, with significant improvement in a wide spectrum of cognitive and affective functions. Mapping domain- and age-specific brain activity patterns has important implications for characterizing the development of children’s cognitive and affective functions. The current mainstay of brain templates is primarily derived from structural magnetic resonance imaging (MRI), and thus is not ideal for mapping children’s cognitive and affective brain development. By integrating task-dependent functional MRI data from a large sample of 250 children (aged 7 to 12) across multiple domains and the latest easy-to-use and transparent preprocessing workflow, we here created a set of age-specific brain functional activity maps across four domains: attention, executive function, emotion, and risky decision-making. Moreover, we developed a toolbox named Developmental Brain Functional Activity maps across multiple domains that enables researchers to visualize and download domain- and age-specific brain activity maps for various needs. This toolbox and maps have been released on the Neuroimaging Informatics Tools and Resources Clearinghouse website (http://www.nitrc.org/projects/dbfa). Our study provides domain- and age-specific brain activity maps for future developmental neuroimaging studies in both healthy and clinical populations.