[Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease].

Objective: To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation. Methods: A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University. Results: ① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1ß, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions: Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis.

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cows' energy needs for milk production. The increased lipolysis in cows presents significant health risks with unclear mechanisms. The objectives of our study were to compare the longitudinal profiles of metabolites and lipids of serum from high and low-lipolysis cows. Forty multiparous Holstein dairy cows were enrolled in the retrospective study. Serum samples were collected on d 7 before expected calving, as well as on d 5, d 7, d 14, and d 21 postpartum. Dairy cows were grouped according to mean serum nonesterified fatty acids on d 5 and 7 after parturition as low (<0.600 mmol/L; n = 8; LFM) and high (>0.750 mmol/L; n = 8; HFM), indicating fat mobilization during early lactation. Lactational performance and serum metabolic parameters related to glucose and lipid metabolism, liver functions, oxidative status, and inflammatory responses were determined. Serum samples were subjected to LC-MS-based metabolomics and lipidomics. Despite differences in postpartum BW change, there were no observed variations in milk yield and composition between 2 groups. Serum BHBA, glucose, leptin, aspartate aminotransferase, IL-6, and TNF-α were greater in cows with HFM than in LFM. Serum adiponectin, revised quantitative insulin sensitivity check index and albumin were lower in cows with HFM than LFM. Intensified fat mobilization in the HFM cows came along with reduced estimated insulin sensitivity, impaired liver functions, and increased oxidative stress and inflammatory responses. Differences in metabolic patterns were observed across the transition period when comparing serum blood matrices (e.g., in different amino acids, acylcarnitines, and sphingolipids). The serum metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum metabolic status parameters suggest that cows adopt varied metabolic adaptation strategies to cope with energy deficits postpartum. Our investigation found a comprehensive remodeling of the serum metabolic profiles in transition dairy cattle, highlighting the significance of alterations in sphingolipid species, as they play a crucial role in insulin resistance and metabolic disorders.

[Research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair].

How to promote high-quality wound healing is a common problem for plastic surgery and burn physicians. In recent years, numerous animal studies have demonstrated that mesenchymal stem cell-derived exosomes promote wound repair through multiple mechanisms and are promising cell-free therapeutic agents with broad prospect of application. How to enhance the therapeutic efficacy of exosomes, optimize their drug delivery strategy, and improve their biological properties are the challenges to be overcome in order to move from basic research to clinical application of exosome therapy for wound repair. This article focuses on methods to improve the wound repair potential of mesenchymal stem cell-derived exosomes, and reviews the recent research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair from three aspects, including pretreatment of parental mesenchymal stem cells, hydrogel bio-scaffold loaded with exosomes, and engineered exosomes, to provide a reference for further clinical studies.

A case of linezolid-induced SIADH in elderly and a review of the literature.

INTRODUCTION: Linezolid is a synthetic oxazolidinone antimicrobial drug with a broad spectrum and a unique mechanism of inhibiting resistant pathogenic strains, and it was approved by the Food and Drug Administration (FDA) in April 2000. Several different systemic side effects were reported after the use of this medication. In this article, we report a case in which a syndrome of inappropriate antidiuretic hormone (SIADH) was developed after linezolid treatment was started. CASE PRESENTATION: We present the case of a 79-year-old woman who developed severe hyponatremia during linezolid treatment (0.6 g i.v. q12 h) after undergoing hemiarthroplasty for left femoral neck fracture. The patient's baseline serum sodium upon admission (138 mmol/L) decreased to 118 mmol/L, urine sodium was 102 mmol/L, plasma osmolality was 248 mOsm/kg and urine osmolarity was 310 mOsm/kg at day 4, thus a diagnosis of SIADH was made. The patient was not taking any other medication known to cause SIADH, and she did not present a comorbidity that could explain her condition. Her serum sodium increased to 135 and 137 mmol/L, respectively, 11 and 12 days after cessation of linezolid, strongly suggesting that SIADH was the cause in this case. CONCLUSIONS: This is the fourth case of linezolid-induced SIADH. A thorough workup was essential for the diagnosis to correctly differentiate between SIADH and other causes of hyponatremia, which helped us properly conducting follow-up treatments. SIADH is a rare but serious side effect of linezolid, and practicing physicians should be aware of this complication. It is necessary to periodically monitor the serum sodium.

A piercing story: ingestion of a grill wire brush bristle.

BACKGROUND: This paper reports the dangers of an ingested metal wire bristle from a barbeque brush, which resulted in oesophageal perforation. CASE REPORT: A 49-year-old gentleman presented to the emergency department with foreign body sensation and odynophagia after having consumed barbequed lamb for lunch. Computed tomography of the neck demonstrated a thin linear opacity near the thoracic inlet. The object could not be visualised on emergent rigid oesophagoscopy. Subsequent neck exploration enabled localisation of a retropharyngeal abscess and a thin wire bristle from a barbeque brush. CONCLUSION: Always consider the utensils employed in food preparation as a differential in ingested foreign bodies. Thin wire objects have a high propensity to migrate and result in complications, hence urgent intervention is vital.

Characterization of sedimentary phosphorus in Lake Erie and on-site quantification of internal phosphorus loading.

Lake Erie harmful algal blooms and hypoxia are two major environmental problems, and have severe impacts on human health, aquatic ecosystems, and the economy. However, little is known about internal loading of phosphorus (P) from sediments, which pose a challenge for assessing the efficacy of current conservation measures on the improvement of lake water quality. A modified Hedley's extraction procedure was employed to analyze representative sediment samples collected from the Lake Erie basin for assessing sedimentary P stock, potential availability for release into lake water, and internal P loading. Inorganic and organic P in the sediments were characterized by sequential extractions in H2O, 0.5 M NaHCO3, 0.1 M NaOH, and 1.0 M HCl, respectively. In the 0 - 10 cm sediment, total P stock was 172, 191, and 170 metric tons km-2 in the western, central, and eastern basins, respectively. Sedimentary P seems unlikely to contribute to internal P loading in the western basin, while in the eastern basin it can potentially contribute to an internal loading of 359 metric tons P yr-1. In the central basin, 41% of organic P, 15% of non-HCl extractable inorganic P, and 9.7% of residual P in the 0 - 10 cm sediment is potentially available for release into lake water; in the 10 - 20 cm sediment, organic P extracted by NaHCO3 and NaOH is also partially available. The central basin potentially contributes to internal P loading at a total amount of 10,599 metric tons yr-1. Internal P loading may not contribute to HABs in the western basin, but it can cause and maintain hypoxia in the central basin and delay the recovery of lake water quality for a lengthy time period in response to external P reduction measures.

[The influence of Indian medicine on traditional Chinese medicine from Dunhuang medical literature].

Through the Silk Road, Chinese medicine has different degrees of absorption on different levels of indic medicine. On the whole, Chinese medicine's absorption of indic medicine is "based on me" , "the way of my own, using the instrument." Taking the four levels of "rational, legal, prescription, and medicine" as the entrance, and analyzing the acceptance attitude of traditional Chinese medicine to Indian medicine with the Dunhuang medical literature as the center.Overall the analysis result on Chinese medicine's absorption of Indic medicine is "Based on our principles, utilising their means" , or can be understood as "fitting the foreign ideas into an already mature infrastructure" .

Long non-coding RNA TUG1 regulates the progression and metastasis of osteosarcoma cells via miR-140-5p/PFN2 axis.

OBJECTIVE: Osteosarcoma (OS) is a frequently occurred tumor. Recently, increasing reports disclosed that long non-coding RNA taurine upregulated gene 1 (TUG1) was associated with OS development. Nevertheless, the precise regulatory pattern was not completely understood. Hence, we aimed to investigate the biological role of TUG1 in OS tumorigenesis. PATIENTS AND METHODS: The levels of TUG1, microRNA-140-5p (miR-140-5p), and Profilin 2 (PFN2) were measured via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the protein level of PNF2 was assessed using Western blot. In addition, MTT assay was employed to detect the ability of cell proliferation in MG63 and U2OS cells. Cell migration and invasion were estimated adopting transwell assay. Moreover, the Dual-Luciferase reporter assay was performed to verify the interrelation between miR-140-5p and TUG1 or PFN2. RESULTS: TUG1 and PFN2 levels were evidently upregulated in OS tissues and cell lines. The knockdown of either TUG1 or PFN2 could restrain cell proliferation, migration, and invasion in OS cells. In addition, miR-140-5p was a target of TUG1 to regulate PFN2. The functions of PFN2 knockdown in cell behaviors were rescued after co-transfection with either miR-140-5p inhibitor or overexpression vector of TUG1. Importantly, TUG1 silencing could impede tumor progression in vivo. CONCLUSIONS: TUG1 modulated cell proliferation, migration, and invasion via miR-140-5p/PFN2 axis in OS progression, which might trigger the development of therapeutic strategies for the treatment of OS.

Direct observation of magnetic contrast obtained by photoemission electron microscopy with deep ultra-violet laser excitation.

Magnetic circular dichroism (MCD) and magnetic linear dichroism (MLD) have been investigated in a photoemission electron microscopy (PEEM) system excited by a deep ultra-violet (DUV) laser (with λ = 177.3 nm and hυ = 7.0 eV) for the first time. High resolution PEEM magnetic images (down to 43.2 nm) were directly obtained on a (001)-oriented magnetic FePt film surface with a circularly-polarized light under normal incidence. Furthermore, a stepped Cr seeding layer was applied to induce the formation of large-area epitaxial FePt films with (001) and (111) two orientations, where MLD with large asymmetry was observed in the transition area of two phases. It demonstrates that DUV laser can be a powerful source for high resolution magnetic imaging in the laboratory in absence of synchrotron facilities.

MicroRNA-132 reverses cisplatin resistance and metastasis in ovarian cancer by the targeted regulation on Bmi-1.

OBJECTIVE: To explore the role of micro ribonucleic acid-132 (miR-132) in cisplatin (DDP) resistance and metastasis of ovarian cancer and its related mechanisms. MATERIALS AND METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the expression levels of miR-132 and B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) in maternal SKOV3 cells and cisplatin-resistant SKOV3/DDP cells. SKOV3/DDP cells were transfected with miR-132 mimic and miR-132 mimic negative control (NC). QRT-PCR and Western blotting were used to detect the expression changes in Bmi-1, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to detect the sensitivity of cells to DDP after transfection with miR-132 mimic. The effect of transfection on the apoptosis was detected via flow cytometry, and that on cell invasion and migration abilities were examined using wound healing assay and transwell assay. Bmi-1 wild-type (wt) and mutant-type (mut) luciferase reporter plasmids were co-transfected with miRNA-132 mimic or miRNA-132 NC, and luciferase activity was analyzed by dual-luciferase reporter system. RESULTS: QRT-PCR and Western blotting results manifested that the miR-132 expression level in SKOV3/DDP cells was significantly lower than that in SKOV3 cells, while the expression level of Bmi-1 in SKOV3/DDP cells was significantly higher than that in SKOV3 cells. The overexpression of miR-132 could reduce the expression level of Bmi-1 in SKOV3/DDP cells, increase the sensitivity of SKOV3/DDP cells to DDP, and inhibit cell invasion and metastasis. Data detected by the luciferase activity revealed that miR-132 could bind to the three prime untranslated region (3'-UTR) of the Bmi-1 gene and negatively regulate the protein expression. CONCLUSIONS: MiR-132 may regulate ovarian cancer's sensitivity to DDP and inhibit its invasion and metastasis by targeted regulation on Bmi-1.

[Detection of epidermal growth factor receptor mutations using bronchial washing fluid in lung cancer patients with negative results by rapid on-site evaluation].

Objective: To evaluate the clinical application of bronchial washing fluid (BWF) in the detection of epidermal growth factor receptor (EGFR) gene mutation in lung cancer patients during diagnostic bronchoscopic procedure. Methods: Patients with suspected lung cancer lesions but failed to be identified as malignancy by rapid on-site cytologic evaluation (ROSE) were enrolled. Performed blocker PCR for EGFR mutation detection using the supernatant and cell pellet of BWF samples and compared the detective results to the EGFR mutation status detected using histologic tumor samples. Results: A total of 85 BWF and paired histological samples were collected at Fudan University Affiliated Zhongshan Hospital from October 2016 to June 2017. There were 46 male and 39 female, with a mean age of 61 years (range 30-87 years). Thirty-one patients had benign diseases and 54 patients had primary lung cancer. Among these 54 lung cancer patients, the diagnoses were made basing on bronchoscopic biopsy samples in 31 patients. The detection rate of EGFR gene mutation in BWF samples was 100.0% concordant with that using histological samples.Another 23 cases whose bronchoscopic biopsy failed to establish malignant diagnoses were further identified by other sampling methods including surgical resection, lung biopsy, etc. A total of 15 patients were identified as EGFR mutated type by pathologic detection or clinically effect assessment, and BWF could detect 11 of them, accounting for 11/15 of all cases. Overall, BWF had achieved an overall accuracy of 95.3% (81/85) comparing to paired tumor histologic samples. Conclusions: BWF is an effective complementary specimen to bronchoscopic biopsy samples in EGFR gene mutation detection in patients with suspected lung cancer lesion and negative biopsy results evaluated by ROSE during bronchoscopy.

[Effect of robot navigation assisted core decompression combined with bone graft treatment of early stage osteonecrosis of the femoral head].

Objective: To evaluate the effects of orthopedic robot navigation system used in core decompression combined with bone graft surgery for osteonecrosis of the femoral head (ONFH). Methods: A retrospective analysis was performed on 9 patients (16 hips) underwent core decompression surgery combined with bone graft treatment for early ONFH in ARCO Ⅱat Department of Osteoarthropathy, Yantaishan Hospital from June 2016 to February 2018.There were 7 males and 2 females, aged 44.6 years (range: 28-60 years). All surgery procedures were completed by the same doctor under the navigation of orthopedic surgery robot using the specific designed tools. The preoperative and postoperative Harris Hip Score and visual analogue score were compared and the time of intraoperative X-ray fluoroscopy was recorded. Results: The mean follow-up period was (12.7±3.5)months (range: 6-18 months). Four cases of treatment failure were observed in 16 hips at the last follow-up and the hip survival rate was 12/16.In stage ARCO Ⅱa, Ⅱb and Ⅱc, the survival rate was 1/1, 2/2, and 9/13.The Harris Hip Score (88.3±1.9 vs.70.0±3.8, t=16.81, P=0.000) and visual analogue score (3.7±0.7 vs. 0.9±0.6, t=13.49, P=0.000) were improved significantly at the last follow-up compared with preoperative value. The total times of intraoperative X-ray fluoroscopy were 15.9±2.5, including 5.8±1.2 before the insertion of the guiding wire and 10.1±1.7 after the insertion of the guiding wire. Conclusions: The domestic orthopedic surgery robot can be applied successfully in the core decompression combined with bone graft surgery for ONFH . It is less invasive with less fluoroscopy time and better bone graft effects.

Enhanced heat stable antifungal factor production by Lysobacter enzymogenes OH11 with cheap feedstocks: medium optimization and quantitative determination.

Heat stable antifungal factor (HSAF) is considered to be a potential biological pesticide due to its broad antifungal activity and novel mode of action. However, few studies have reported on HSAF production during fermentation. Thus, this work was executed to optimize the medium composition to maximize HSAF production by Lysobacter enzymogenes OH11, with soybean flour, glucose and CaCl2 identified as suitable nutrients with concentrations of 8·00, 7·89 and 0·72 g l-1 respectively. Simultaneously, the quantitative analysis of HSAF production was established by eliminating the emulsification problem, and the highest HSAF production was determined to be 356·34 ± 13·86 mg l-1 using the optimized medium, 12-fold higher than when using the 10% TSB medium (29·34 ± 2·57 mg l-1 ). Furthermore, the cost of this medium was assessed and nearly 31-fold lower than that of 10% TSB. This study suggests that the optimized medium is not only effective but also economical for HSAF production. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: Heat stable antifungal factor (HSAF) exhibits a potent and broad antifungal activity with a novel mode of action. Increased production and reduced cost of raw materials are particularly important for the future production of HSAF, however, no report was involved in these studies. This study aimed to improve the production of HSAF with cheap raw materials through the medium optimization, which would lay the foundation for the application of HSAF in biological control.

Cytosolic proteome profiling of monocytes for male osteoporosis.

In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes. INTRODUCTION: Osteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males. Peripheral blood monocytes (PBMs) play important roles in bone metabolism by acting as precursors of osteoclasts and producing cytokines important for osteoclast development. The first cytosolic sub-proteome profiling analysis was performed in male PBMs to identify differentially expressed proteins (DEPs) that are associated with BMDs and risk of osteoporosis. METHODS: Here, we conducted a comparative proteomics analysis in PBMs from Caucasian male subjects with discordant hip BMD (29 low BMD vs. 30 high BMD). To decrease the proteome complexity and expand the coverage range of the cellular proteome, we separated the PBM proteome into several subcellular compartments and focused on the cytosolic fractions, which are involved in a wide range of fundamental biochemical processes. RESULTS: Of the total of 3796 detected cytosolic proteins, we identified 16 significant (P < 0.05) and an additional 22 suggestive (P < 0.1) DEPs between samples with low vs. high hip BMDs. Some of the genes for DEPs, including ALDOA, MYH14, and Rap1B, showed an association with BMD in multiple omics studies (proteomic, transcriptomic, and genomic). Further bioinformatics analysis revealed the enrichment of DEPs in functional terms for monocyte proliferation, differentiation, and migration. CONCLUSIONS: The combination strategy of subcellular separation and proteome profiling allows an in-depth and refined investigation into the composition and functions of cytosolic proteome, which may shed light on the monocyte-mediated pathogenic mechanisms of osteoporosis.

The impact of small doses of LPS on NASH in high sucrose and high fat diet induced rats.

OBJECTIVE: We investigated the impact of small doses of lipolysaccharide (LPS) on the development of NASH in the context of a high sucrose and high fat diet in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into groups fed a synthetic diet (n=8), a regular diet (n=8), a synthetic diet + LPS (n=8) or saline (n=8) and a regular diet + LPS (n=8) or saline (n=8). The LPS (or saline) was administered from the 6th week on (0.5 mg/kg) by subcutaneous injection every two days under the same conditions with free access to water and food. At the end of the 9th week the animals were euthanized and the liver tissue dissected for analysis. Hematoxylin and eosin (HE) and Von Gieson's (VG) staining was performed on parafin embedded sections to observe the pathological changes of the liver, the degree of fibrosis, and infiltrative lymphocytes were counted in the liver tissue. RESULTS: We quantitatively measured the levels of LPS in the plasma of rats, ALT activity, and TNF-alpha. We found that the synthetic diet + LPS group showed severe steatosis, and was associated with bridging necrosis and mild fibrosis when compared to the group fed a Synthetic diet + saline. In addition, the amount of infiltrative lymphocytes and the level of plasma ALT and TNF-alpha in the synthetic diet + LPS group were significantly increased. The difference observed were statistically significant (p < 0.05). CONCLUSIONS: Small doses of LPS promote the development of NASH induced by a high sucrose and high fat.

Integrated bioinformatics analyses identify dysregulated miRNAs in lung cancer.

BACKGROUND: Lung cancer is the most common cause of cancer-related death worldwide. MicroRNAs (miRNAs) play important roles in various biological processes, including cell development, proliferation, differentiation and apoptosis. MATERIALS AND METHODS: In the current study, using miRNA expression profiles from the Gene Expression Omnibus (GEO) database, we used three independent tests: Wilcox test, t-test and Fisher's exact test to investigate miRNA's involvement in lung carcinogenesis. RESULTS: Ten differentially expressed miRNAs were identified. Among them, miR-675 drew specific attention. Ingenuity pathway analysis of its target genes revealed its impact on cell death and cell cycle. It is possible that miR-675 contributes to the pathogenesis of lung cancer through its down regulation of the tumor suppressor gene RB1. CONCLUSIONS: Our results suggest miR-675 may serve as a potential therapeutic target of lung cancer.