Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

OBJECTIVES: To investigate the clinical features and gene mutation characteristics of combined oxidative phosphorylation deficiency type 7 (COXPD7) caused by mutations in the C12orf65 gene, and to enhance the awareness of this disease. METHODS: A child diagnosed with COXPD7 in the Department of Neurology, Children's Hospital Affiliated to Zhengzhou University in 2021 was included, along with 10 patients reported in the literature. All subjects were analyzed for their genotypes and clinical phenotypes. RESULTS: A total of 11 patients with COXPD7 were included, comprising 1 reported in this study and 10 from the literature. Among the 11 patients, 9 had homozygous mutations in the C12orf65 gene, while 2 had compound heterozygous mutations, which were identified as frameshift or nonsense mutations. The age of onset ranged from 1 day to 2 years, and clinical manifestations included optic nerve atrophy and delays in intellectual and motor development. Eight patients exhibited external ophthalmoplegia, and five patients displayed spastic paralysis. Cranial magnetic resonance imaging revealed optic nerve atrophy in all 11 patients, abnormal brainstem signals in 10 patients, and a lactate peak on brainstem magnetic resonance spectroscopy scans in 3 patients. CONCLUSIONS COXPD7 associated with the C12orf65 gene results from homozygous or compound heterozygous mutations, with primary clinical manifestations of optic nerve atrophy and delays in intellectual and motor development. Some patients may also present with spastic paralysis or external ophthalmoplegia. Cranial imaging reveals symmetrical abnormal signals in bilateral basal ganglia and brainstem, and a lactate peak is observed on brainstem magnetic resonance spectroscopy scans.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Oxidative Phosphorylation ; Infant, Newborn

OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: Renal cell carcinoma (RCC) is a malignant renal tumor that poses a significant threat to patient health. Accurate preoperative pathological grading plays a crucial role in determining the appropriate treatment for this disease. Currently, deep learning technology has become an important method for pathological grading of RCC. However, existing methods primarily rely on single-phase computed tomography (CT) imaging for analysis and prediction, which has limitations such as missing small lesions, one-sided evaluation, and local focusing issues. Therefore, this study proposes a multi-modal deep learning algorithm that integrates multi-phase enhanced CT images with clinical variable data, aiming to provide a basis for predicting the pathological grading of RCC. METHODS: First, the algorithm took four-phase enhanced CT images from the plain scan, arterial phase, venous phase, and delayed phase, along with clinical variables, as inputs. Then, an embedding encoding module was used to extract heterogeneous information from the clinical variables, and a 3-dimensional (3D) ResNet50 model was employed to capture spatial information from the multi-phase enhanced CT image data. Finally, a Fusion module deeply integrated the feature information from clinical variables and each phase's CT image features, further utilizing a cross-self-attention mechanism to achieve multi-phase feature fusion. This approach comprehensively captures the deep semantic information from the patient data, fully leveraging the complementary advantages of multi-modal and multi-phase data. To validate the effectiveness of the proposed method, a total of 1 229 RCC patients were approved by ethics review were included to train the model. RESULTS: Experimental results demonstrated superior performance compared to traditional radiomics and state-of-the-art deep learning methods, achieving an accuracy of 83.87%, a recall rate of 95.04%, and an F1-score of 82.23%. CONCLUSIONS The proposed algorithm exhibits strong stability and sensitivity, significantly enhancing the predictive performance of RCC pathological grading. It offers a novel approach for accurate RCC diagnosis and personalized treatment planning.
Humans ; Carcinoma, Renal Cell/pathology* ; Deep Learning ; Kidney Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Algorithms ; Neoplasm Grading ; Male ; Female ; Middle Aged

Methods: A total of 10 specific pathogen free (SPF) grade female DBA/2J mice were randomly divided into model group and QGA II group (n = 5 for each group), while additional 5 SPF-grade female C57BL/6J mice were assigned to control group. Mice presented spontaneous high IOP and showed elevated approximately at the age of seven months. The high IOP was maintained until week 38, when gavage was initiated. Mice in control group underwent the same intragastric treatment, while those in QGA II group were gavaged with QGA II (9.67 g/kg), once a day for four weeks. Retinal morphology was examined using hematoxylin and eosin (HE) staining, with the number of retinal ganglion cells (RGCs) counted. The expression level of Brn3a protein, a specific marker for RGCs, was detected by immunofluorescence, with the mean optical density (OD) measured for quantitative analysis. In addition, 16S rDNA sequencing was leveraged to analyze changes in the diversity of gut microbiota, including their α-diversity (Chao1, Shannon, Pielou’s evenness, and observed species index) and β-diversity. Venn diagrams and linear discriminant analysis effect size (LEfSe) analysis was employed to investigate the number of amplicon sequence variants (ASVs), the abundance of differential gut microbiota species, and the classification of species at both the phylum and genus levels within the three groups of mice. Results: HE staining revealed that compared with control group, model group showed significant reduction in the number of RGCs (P < 0.01), with intracellular vacuolar degeneration and nuclear pyknosis. After QGA II treatment, the number of RGCs was significantly increased compared with model group (P < 0.01), with notable improvements in intracellular vacuolar degeneration. Immunofluorescence analysis showed that the mean OD of Brn3a protein was significantly decreased in model group compared with control group (P < 0.01), while QGA II treatment significantly elevated its expression level (P < 0.01). Analysis of α-diversity showed that after QGA II intervention, the Chao1, Shannon, and Pielou’s evenness indices were significantly increased (P < 0.01), and the observed species index was elevated (P < 0.05). β-Diversity analysis demonstrated distinct clustering among the three groups, indicating relatively low similarity in bacterial community structures. ASV clustering identified a total of 14 061 ASVs across all groups, with 9 514 ASVs shared between model and QGA II groups. At the phylum level, the abundance of Bacteroidetes was significantly decreased in model group compared with control group (P < 0.01), while Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio were significantly increased (P < 0.01). QGA II treatment significantly reduced both Firmicutes abundance and the F/B ratio (P < 0.01). At the genus level, Lactobacillus was dominant across all groups, with its abundance significantly increased in model group (P < 0.01) and subsequently decreased following QGA II intervention (P < 0.05). Conclusion QGA II restructured the gut microbiota of DBA/2J mice with chronic high IOP, bringing changes in their diversity and abundance of components. Firmicutes, Bacteroidetes, Lactobacillus, along with their associated microorganisms, are likely critical components of the gut microbiota that contribute to the optic neuroprotective effects of QGA II on chronic high IOP mice.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

BACKGROUND:Clinical skin wound healing continues to be a significant concern,and tissue repair research has moved to the forefront with the development of biomaterials with immunomodulatory properties.Therefore,it is crucial to research wound dressings that have immunomodulatory properties. OBJECTIVE:To prepare chitosan hydrogels that have been modified by arginine with different configurations and assess their capacity to speed up wound healing in a rat animal model. METHODS:(1)In vitro trial:Chitosan modified by pure L-arginine,pure D-arginine,and L-arginine and D-arginine was synthesized by EDC/NHS system,which was then crosslinked with aldehyde-modified four-arm polyethylene glycol.Different chitosan-based hydrogels(CS-L,CS-D,and CS-DL)were finally formed via the Schiff base reaction.Three kinds of hydrogel extracts were co-cultured with fibroblasts respectively.Hydrogel cytocompatibility was assessed using the CCK-8 assay and live/dead staining.The effect of hydrogel on the migration capacity of fibroblasts was assessed by using a scratch test.Three kinds of hydrogels were incubated with rat erythrocyte suspension respectively to evaluate the hemocompatibility of the hydrogels.The hydrogel extract was co-cultured with RAW264.7 macrophages to test the hydrogels'capacity to enhance macrophage NO generation and polarize macrophage phenotype.(2)In vivo experiment:A total of 36 adult SD rats were divided into 4 groups with 9 rats in each group by the random number table method.Two full-layer skin defect wounds of 2 cm×2 cm were made on the back of each rat.Normal saline was added to the wounds of the control group,and corresponding hydrogel was added to the wounds of the CS-L,CS-D,and CS-DL groups,respectively,and then bandaged and fixed.The wound healing was observed regularly after operation.Hematoxylin-eosin staining was performed at 3,10,and 21 days after operation.The samples were collected 10 days after operation and M2 macrophage immunofluorescence staining was performed. RESULTS AND CONCLUSION:(1)In vitro experiments:Under scanning electron microscopy,the three kinds of hydrogels exhibited obvious interpenetrating network structures with pore sizes ranging from 70-200 μm.The three kinds of hydrogels have good swelling performance,degradation performance,self-healing performance,and suitable mechanical strength.The three kinds of hydrogels had good cytocompatibility and hemocompatibility and could promote the migration of fibroblasts.All three kinds of hydrogels had the ability to promote the polarization of macrophages,and CS-D hydrogels had the strongest ability to promote the polarization of macrophages.CS-L hydrogel could significantly promote the production of NO in macrophages.(2)In vivo experiment:3 and 10 days after operation,the wound healing rate in the CS-L and CS-D groups was higher than that in the control group(P<0.05).After 21 days,the wound healing rate of the three hydrogel groups was higher than that of the control group.Hematoxylin-eosin staining displayed that a large number of inflammatory cells were infiltrated in the wound tissue of rats in all groups,accompanied by neovessels and fibroblasts 3 days after operation.10 days after operation,there was still more inflammatory cell infiltration in the wound of the control group,and the inflammation of the other three groups was improved,especially the decrease of inflammatory cells in the CS-D group was more obvious.21 days after operation,the wound epithelium of each group was well repaired,and there was basically no inflammatory cell infiltration in the CS-L and CS-D groups,while there was still a small amount of inflammatory cell infiltration in the control group.Immunofluorescence staining revealed that the number of M2-type macrophages in the CS-D group was higher than that in the other three groups(P<0.05).(3)The results conclude that chitosan hydrogels modified by different configurations of arginine can promote wound healing through different mechanisms.