Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

The gene encoding regulatory subunit 15 A of protein phosphatase 1 produces a protein that is a universally present protein phosphatase in eukaryotic cells.In this study,genomic DNAs were extracted from the blood of 89 Chinese Holstein cows and were used as templates for PCR amplification of the target fragment of the PPP1R15A gene.The product was tested and a polymor-phic site,E3-250T＞A was found.The polymorphism of this side and its correlation with milk pro-duction traits in Chinese Holstein cattle were statistically analyzed using SPSS 23.0 software.The findings revealed three genotypes at this site:AA,AT and TT.Cows possessing the AT and TT genotypes exhibited significant differences(P＜0.01)in milk fat and solid non-fat content com-pared to those with the AA genotype.While no significant differences were noted for other milk production traits,including milk yield,protein,lactose,somatic cell count,blood urea nitrogen,and corrected milk.The identification of functional SNPs in the PPP1R15A gene provides a theoretical basis for further research and identification of causal variations in the cow PPP1R15A gene.

Objective:To compare and analyze the differences in the measurement of intra-abdominal pressure in different positions of critically ill patients treated with extracorporeal membrane oxygenation (ECMO) combined with prone position integration, with a view to finding a more optimal intra-abdominal pressure monitoring strategy, which can provide a theoretical basis for clinical diagnosis and treatment.Methods:Forty critically ill patients who underwent ECMO combined with prone position integrated treatment in the department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2023 were selected by convenience sampling method using an own-control trial. The differences in intra-abdominal pressure between supine position with head elevated at 0°, 15°and 30°and prone position with head high and foot low slopes at 0°, 15°and 30°were compared and analyzed. Heart rate, respiration, mean arterial pressure and oxygen saturation were also compared in patients in different positions.Results:There were 29 males and 11 females in 40 patients with the age of (62.58 ± 17.99) years.The intra-abdominal pressure in supine position with head elevated at 30° was (12.45 ± 3.43) mmHg(1 mmHg=0.133 kPa), which was higher than that of 0° and 15° of (9.38 ± 2.52) and (10.70 ± 2.95) mmHg, and the differences were statistically significant ( t=4.56, 2.45, both P<0.05);the difference in intra-abdominal pressure between 0° and 15° was not statistically significant ( P>0.05); the intra-abdominal pressure in prone position with head-high-foot-low slope of 30° was (12.92 ± 4.19) mmHg, which was higher than that of 0°and 15°of (9.67 ± 2.80), and (11.01 ± 3.10) mmHg, and the differences were statistically significant ( t=4.08, 2.32, both P<0.05); the difference in intra-abdominal pressure between 0° and 15° was not statistically significant ( P>0.05).The differences in intra-abdominal pressure between groups of supine bed head elevation 0°, 15°, 30°and prone position with head high and foot low slopes 0°, 15°, 30°were not statistically significant (all P>0.05). The differences in heart rate, respiration, mean arterial pressure and oxygen saturation in the supine position with head elevated at 0°, 15°and 30° were not statistically significant when compared within groups (all P>0.05); the differences in heart rate, respiration, mean arterial pressure and oxygen saturation in the prone position with head elevated with feet and feet on low slopes at 0°, 15°and 30°were not statistically significant when compared within groups (all P>0.05); and the differences in supine position with head elevated at 0°, 15°, 30°and prone head-height-foot-low slope 0°, 15°, 30°of heart rate, respiration, mean arterial pressure were not statistically significant (all P>0.05); supine bed head elevation 0°, 15°, 30°and prone head-height-foot-low slope 0°, 15°, 30°of oxygen saturation between the groups, the differences were statistically significant ( Z=6.85, 6.82, 6.68, all P<0.05). Conclusions:Intra-abdominal pressure can be measured in the 15° prone position in critically ill patients treated with ECMO combined with prone position integration; the different positions have little effect on vital signs, but the prone position significantly improves oxygen saturation.

Objective To evaluate adverse events(AEs)of hematological toxicities in cyclin-dependent kinase 4/6(CDK4/6)inhibitors based on the FDA adverse event reporting system(FAERS)database,and to provide a reference for rational drug use in the clinic.Methods A total of 29 quarterly AEs were extracted from the FAERS database from January 2015 to March 2022.Reported odds ratio(ROR)and proportional reported ratio(PRR)were used for data mining of CDK4/6 inhibitor AEs.Results A total of 7 872 AEs related to CDK4/6 inhibitors were reported,and the proportion of hematological AEs of each inhibitor was palbociclib(80.31%),ribociclib(15.36%),and abemaciclib(4.33%).Neutropenia and anemia were common in hematological toxicities.Palbociclib(2 982/6 322,47.17%)and ribociclib(613/1 209,50.70%)caused more neutropenia than abemaciclib(117/341,34.31%).Hematological toxicities mainly occurred 60 days after drug initiation(1 630,61.86%).Palbociclib had the longest median onset time,and 32.9%of patients still had hematological toxicities after 90 days of treatment.The clinical features and intensity were different among CDK4/6 inhibitors.Conclusions Palbociclib,abemaciclib,and ribociclib all cause significant hematological toxicities,among which abemaciclib has fewest reports of hematological toxicities.Still,the risk of death after anemia caused by abemaciclib should be noted.Complete blood cell count should be closely monitored within the first two months after treatment to monitor the patient's neutrophils and hemoglobin.The occurrence of hematological AEs associated with CDK4/6 inhibitors should be noted in the clinic.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.
Animals ; Apoptosis ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Down-Regulation ; Endoplasmic Reticulum Stress ; Head and Neck Neoplasms ; Mice ; Mouth Neoplasms ; Oxidoreductases

Objective:To visualize the research hot spots and frontiers of non-surgical treatments for idiopathic scoliosis (IS) based on CiteSpace.Methods:The Web of Science Core Database and China National Knowledge Infrastructure from 1990 to 2020 were searched for studies of non-surgical treatments of idiopathic scoliosis. The time, distributions of nations, institutions, academic disciplines and keywords of literature were analyzed. With CiteSpace 5.7.R4 and Excel 2017, the visualized knowledge graphs and the data tables were generated.Results:A total of 822 studies including 548 articles in English and 274 articles in Chinese were retrieved, including 378 articles published during 2015—2020. The top three nations with higher number of published articles were USA (114 studies), Canada (77 studies) and China (68 studies). Studies covered 33 disciplines, including rehabilitation, engineering and orthopedics, and the betweenness centrality of rehabilitation medicine was the highest (0.59). The non-surgical treatment research was focused on adolescents (187 studies) and brace treatment (116 studies). From 1990 to 2014, the non-surgical treatment of IS mainly focused on the brace treatment (70.4%,69/98) in domestic studies. After 2014, comprehensive treatments such as exercise therapy and manual therapy gradually became the research trend in this field (61.3%,92/150). Research hotspots included different forms of brace treatment (betweenness centrality: 0.31), exercise (6 studies), manual therapy (3 studies), guide of medicine (2 studies), acupuncture therapy (2 studies) of non-surgical treatments. Among top 30 research institutions for domestic publication of Chinese literature, there were 22 tertiary hospitals, 1 secondary hospital, 5 schools, 1 comprehensive rehabilitation service organization, and 1 community health service center.Conclusion:The research content of non-surgical treatment for idiopathic scoliosis tends to be diversified, comprehensive treatment of exercise therapy, brace therapy, and manual therapy are currently the main research hotspots.

OBJECTIVE: To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease. METHODS: Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis. RESULTS: Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3). CONCLUSION The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.
Dyneins/genetics* ; Genomics ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Sperm Tail/pathology* ; Whole Exome Sequencing