Identification of two distinct head and neck squamous cell carcinoma subtypes based on fatty acid metabolism-related signatures: Implications for immunotherapy and chemotherapy.

The dysregulation of lipid metabolism is a critical factor in the initiation and progression of tumors. In this investigation, we aim to characterize the molecular subtypes of head and neck squamous cell carcinoma (HNSCC) based on their association with fatty acid metabolism and develop a prognostic risk model. The transcriptomic and clinical data about HNSCC were obtained from public databases. Clustering analysis was conducted on fatty acid metabolism genes (FAMG) associated with prognosis, utilizing the non-negative matrix factorization algorithm. The immune infiltration, response to immune therapy, and drug sensitivity between molecular subtypes were evaluated. Differential expression genes were identified between subtypes, and a prognostic model was constructed using Cox regression analyses. A nomogram for HNSCC was constructed and evaluated. Thirty FAMGs have been found to exhibit differential expression in HNSCC, out of which three are associated with HNSCC prognosis. By performing clustering analysis on these 3 genes, 2 distinct molecular subtypes of HNSCC were identified that exhibit significant heterogeneity in prognosis, immune landscape, and treatment response. Using a set of 7778 genes that displayed differential expression between the 2 molecular subtypes, a prognostic risk model for HNSCC was constructed comprising 11 genes. This model has the ability to stratify HNSCC patients into high-risk and low-risk groups, which exhibit significant differences in prognosis, immune infiltration, and immune therapy response. Moreover, our data suggest that this risk model is negatively correlated with B cells and most T cells, but positively correlated with macrophages, mast cells, and dendritic cells. Ultimately, we constructed a nomogram incorporating both the risk signature and radiotherapy, which has demonstrated exceptional performance in predicting prognosis for HNSCC patients. A molecular classification system and prognostic risk models were developed for HNSCC based on FAMGs. This study revealed the potential involvement of FAMGs in modulating tumor immune microenvironment and response to treatment.

ANXA3 interference inactivates ERK/ELK1 pathway to mitigate inflammation and apoptosis in sepsis-associated acute lung injury.

Acute lung injury (ALI) is a prevailing and deadly complication of sepsis coupled with increasing incidence and fatality rate. Annexin A3 (ANXA3) has been unraveled to be upregulated during sepsis. This study purposed to assess the role and the mechanism of ANXA3 in sepsis-induced ALI. After the construction of mouse model of sepsis, the pathological changes of mice lung tissues were estimated by H&E staining. ANXA3 expression in mice lung tissues and serum was examined. The degree of pulmonary edema and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were analyzed. In lipopolysaccharide (LPS)-induced mouse ALI model in vitro, CCK-8 assay measured cell viability and flow cytometry analysis detected cell apoptosis. Besides, ELISA assay detected the release of inflammatory cytokines. Western blot analyzed the expression of proteins associated with inflammation, apoptosis and extracellular-signal-regulated kinase (ERK)/ETS-like gene 1 (ELK1) signaling. Results revealed that ANXA3 was overexpressed in the lung tissues and serum of septic mice. Following the knockdown of ANXA3, sepsis-induced lung injury was alleviated, manifested as reduced lung edema, decreased inflammatory cell infiltration and inhibited cell apoptosis. Additionally, ANXA3 silence blocked ERK/ELK1 signaling both in sepsis mouse models and in vitro model of ALI induced by lipopolysaccharide (LPS). Moreover, the inhibitory effects of ANXA3 silencing on ERK/ELK1 signaling activation, the viability damage, inflammation and apoptosis in LPS-induced mouse ALI model in vitro were partially reversed by ERK activator. Collectively, depletion of ANXA3 exerted suppressive effects on the inflammation and apoptosis in sepsis-induced ALI through blocking ERK/ELK1 signaling.

The predictive value of uterine artery Doppler in the success rate of pregnancy from the first frozen embryo transfer during the implantation window.

BACKGROUND: Worldwide, frozen embryo transfer (FET) has become a new strategy for the treatment of infertility. The success of FET is closely related to endometrial receptivity. Does uterine artery Doppler during the implantation window predict pregnancy outcome from the first FET? METHODS: A total of 115 retrospectively collected cycles were included in the study, with 64 cycles of clinical pregnancy and 51 cycles of nonclinical pregnancy; There were 99 nonabsent end-diastolic flow (NAEDF) cycles and 16 absent end-diastolic flow (AEDF) cycles. The differences in uterine artery Doppler findings between different pregnancy outcomes were investigated. The clinical pregnancy rate and spontaneous abortion rate in the NAEDF and AEDF groups were compared. The predictive value of uterine artery Doppler during the implantation window in the success rate of pregnancy from the first FET was also investigated. RESULTS: Between the clinical pregnancy group and the nonclinical pregnancy group, there were no significant differences in the mean resistance index (mRI) (Z = -1.065, p = 0.287), mean pulsatility index (mPI) (Z = -0.340, p = 0.734), and mean peak systolic/end-diastolic velocity(mS/D) (Z = -0.953, p = 0.341); there were significant differences in the mean peak systolic velocity (mPSV) (Z = -1.982, p = 0.048) and mean end-diastolic velocity (mEDV) (Z = -2.767, p = 0.006). Between the NAEDF and AEDF groups, there was no significant difference in the clinical pregnancy rate (χ2 = 0.003, p = 0.959), and there was a significant difference in the spontaneous abortion rate (χ2 = 3.465, p = 0.019). Compared with uterine artery Doppler alone, its combination with artificial abortion history, waist-to-hip ratio, LH (Luteinizing hormone) of P (Progesterone) administration day, mPSV and mEDV had a higher predictive value regarding clinical pregnancy from the first FET [ROC-AUC 0.782, 95% CI (0.680-0.883) vs. 0.692, 95% CI (0.587-0.797)]. CONCLUSIONS: Uterine artery Doppler, particularly mPSV and mEDV during the implantation window, was useful for predicting clinical pregnancy, and AEDF was related to spontaneous abortion in the first trimester. Uterine artery Doppler combined with artificial abortion history, waist-to-hip ratio, LH of P administration day, mPSV and mEDV have a higher predictive value than uterine artery Doppler alone regarding the pregnancy from the first FET.

UHPLC-MS/MS-based untargeted lipidomics analysis of septic patients.

BACKGROUND: Lipids take part in many pathophysiological processes of sepsis, thus, the variation of lipid composition may have clue on the severity and pathogen to sepsis. The objective of our study is to expand the profile of lipid compositions and screen potential biomarkers in intensive care unit (ICU) patients with sepsis. METHODS: Patients admitted to the ICU clearly diagnosed with celiac sepsis were included in this prospective study. Age-matched healthy participants from the Physical Examination Center were used as the control group. Blood samples were obtained from patients within the first 12 h of admission. We analysed different components of the lipid metabolism between the sepsis patients and controls and described characteristic features during sepsis. RESULTS: Thirty patients with celiac sepsis and 30 sex- and age-matched healthy controls were enrolled in this study. The lipid metabolic signature was obviously different between the sepsis patients and healthy controls and was mostly downregulated in sepsis patients. We identified 65 lipid species. Sixty-four lipid molecules were found to be significantly downregulated in sepsis patients, and only the level of one phosphatidylethanolamine (PE) molecule, PE (34:2) was higher in the sepsis patients with sepsis group comparing with the control group. The analysis of metabolic pathway illustrated the different lipid molecules were closely related to Phosphatidylcholine (PC), Lysophosphatidylcholine (LPC), and PE. CONCLUSION: Sepsis contributes to impaired expression of most lipids, which mainly result in the disorder of glycerolipid metabolic pathway, including Phosphatidylcholine (PC), Lysophosphatidylcholine (LPC), and PE.

Exploration of the interchromosomal effects in preimplantation genetic testing for structural rearrangements based on next-generation sequencing.

BACKGROUND: To investigate the interchromosomal effect (ICE) in chromosome translocation carriers. METHODS: Data on preimplantation genetic testing aneuploidy and structural rearrangements (translocation) were retrospectively collected and classified into a reciprocal translocation group, a Robertsonian translocation group and a control group. According to the carrier's gender and age, all cases underwent further subgroup difference analysis of de novo abnormal embryo rates and the number of chromosomes involved in de novo abnormal embryos. RESULTS: Among the 283 couples who participated in this study, 1076 blastocysts from 352 cycles were collected, and 246 de novo abnormal embryos were included. There was a significant difference in the rate of de novo abnormal embryos among the three groups (p < .05) but no significant difference in the number of de novo abnormal chromosomes in the abnormal embryos (p > .05). Gender and age (classified by 35 years old) had no effect on the de novo abnormal embryo ratios among the translocation carriers (p > .05). However, the de novo abnormal ratio increased with age. The embryo constitution reflected no significant difference between the translocation groups (p > .05). CONCLUSION: The ICE was detected for the translocation carriers. The de novo abnormal embryo ratio increased with age. Gender had no effect on the de novo abnormal embryo ratio. Translocation status played a more important role than age and gender.

Screening for deafness-associated mitochondrial 12S rRNA mutations by using a multiplex allele-specific PCR method.

Mitochondrial 12S rRNA A1555G and C1494T mutations are the major contributors to hearing loss. As patients with these mutations are sensitive to aminoglycosides, mutational screening for 12S rRNA is therefore recommended before the use of aminoglycosides. Most recently, we developed a novel multiplex allele-specific PCR (MAS-PCR) that can be used for detecting A1555G and C1494T mutations. In the present study, we employed this MAS-PCR to screen the 12S rRNA mutations in 500 deaf patients and 300 controls from 5 community hospitals. After PCR and electrophoresis, two patients with A1555G and one patient with C1494T were identified, this was consistent with Sanger sequence results. We further traced the origin of three Chinese pedigrees. Clinical evaluation revealed variable phenotypes of hearing loss including severity, age at onset and audiometric configuration in these patients. Sequence analysis of the mitochondrial genomes from matrilineal relatives suggested the presence of three evolutionarily conserved mutations: tRNACys T5802C, tRNALys A8343G and tRNAThr G15930A, which may result the failure in tRNAs metabolism and lead to mitochondrial dysfunction that was responsible for deafness. However, the lack of any functional variants in GJB2, GJB3, GJB6 and TRMU suggested that nuclear genes may not play active roles in deafness expression. Hence, aminoglycosides and mitochondrial genetic background may contribute to the clinical expression of A1555G/C1494T-induced deafness. Our data indicated that the MAS-PCR was a fast, convenience method for screening the 12S rRNA mutations, which was useful for early detection and prevention of mitochondrial deafness.