The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr⁺ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat⁺Oxtr⁺ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.
Animals ; Receptors, Oxytocin/metabolism* ; Male ; Brain/growth & development* ; Mice ; Mice, Inbred C57BL ; Neurons/metabolism* ; Single-Cell Analysis ; Gene Expression Regulation, Developmental ; RNA, Messenger/metabolism* ; Animals, Newborn

ObjectiveTo investigate the change in the expression of magnesium transporter 1 （MagT1） in peripheral blood CD8⁺ T cells in patients with chronic hepatitis B virus （HBV） infection， as well as the correlation of serum Mg²⁺ and MagT1 with HBV DNA load. MethodsA total of 102 patients with HBV infection who were admitted to Tangshan Workers’ Hospital from January 2022 to December 2023 were enrolled， and a case-control study was conducted. According to the stage of disease progression， the subjects were divided into chronic hepatitis B group with 40 patients， compensated liver cirrhosis group with 32 patients， and hepatocellular carcinoma group with 30 patients， and 32 healthy volunteers matched by age and sex were enrolled as normal control group. The serum concentration of Mg²⁺ was measured； RT-qPCR was used to measure the mRNA expression level of MagT1 in CD8⁺ T cells and serum HBV DNA load； flow cytometry was used to measure the expression levels of programmed death-1 （PD-1）， T-cell immunoglobulin and mucin-domain containing-3 （Tim-3）， and natural killer cell group 2D （NKG2D） on the surface of CD8⁺ T cells. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the SNK-q test was used for comparison between two groups； the chi-square test was used for comparison of categorical data between groups； a Pearson linear correlation analysis was used to investigate the correlation between the mRNA expression level of MagT1 and other related indicators. ResultsThere were significant differences in the serum level of Mg²⁺ and the mRNA expression level of MagT1 between the normal control group， the chronic hepatitis B group， the compensated liver cirrhosis group， and the hepatocellular carcinoma group （F=29.014 and 145.578， both P<0.001）. The Pearson correlation analysis showed that the serum level of Mg²⁺ and the mRNA expression level of MagT1 were positively correlated with HBV DNA load （r=0.335 and 0.394， both P<0.05）. The hepatocellular carcinoma group had the highest levels of PD-1 and Tim-3， followed by the compensated liver cirrhosis group， the chronic hepatitis B group， and the normal control group； the normal control group had the highest level of NKG2D， followed by the chronic hepatitis B group， the compensated liver cirrhosis group， and the hepatocellular carcinoma group （all P<0.001）. The Pearson correlation analysis showed that the mRNA expression level of MagT1 was negatively correlated with PD-1 and Tim-3 （r=-0.643 and -0.640， both P<0.05） and was positively correlated with NKG2D （r=0.655， P<0.05）. ConclusionThere is a reduction in the mRNA expression level of MagT1 in peripheral blood CD8⁺ T cells in patients with HBV infection， which is positively correlated with serum HBV DNA load. The reduction in the expression of MagT1 may contribute to CD8⁺ T cell exhaustion by impairing Mg²⁺ influx， manifesting as the upregulation of PD-1 and Tim-3 and the downregulation of NKG2D.

Objective : To investigate the relationship between the risk occurrence of rectal cancer and the single nucleotide polymorphisms(SNP) of zinc finger protein 6(ZBED6), and to provide the experimental basis for early diagnosis and treatment of rectal cancer. Methods: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technology was used to genotype the ZBED6 gene in 109 randomly selected rectal cancer patients and 110 unrelated healthy controls. To evaluate the relationship between alleles, genotypes and the risk of rectal cancer, unconditional Logistic regression analysis was used toORand 95%CI. Results: The SNP rs7552670 of ZBED6 had significant correlation with the risk of rectal cancer. Compared with the population carrying the TT genotype, those carrying the TC genotype had a 2.653 fold increased risk of rectal cancer(TTvsTC:OR=2.635, 95%CI=1.501-4.690). Other SNPs had no significant correlation with the risk of rectal cancer. Conclusion There is an interaction between the polymorphisms of ZBED6(rs7552670) and rectal cancer. The population carried ZBED6 rs7552670 TC genotype had an growing risk of rectal cancer.

Objective To explore the preventive effect of multidisciplinary collaborative evidence-based nursing on dysphagia in patients with orotracheal intubation in intensive care unit(ICU)after extubation.Methods A retrospective analysis was performed on 200 patients with orotracheal intubation in ICU who were admitted to Dongguan Traditional Chinese Medicine Hospital between January and December 2023.Of them,96 patients who were admitted to our hospital between January and May 2023 received routine nursing(routine group),104 patients who were admitted to our hospital between June and December 2023 received multidisciplinary collaborative evidence-based nursing(evidence-based group).The incidence of dysphagia after extubation,water swallowing test result,swallowing function measured with M.D.Anderson dysphagia inventory(MDADI),psychological state assessed by connor-davidson resilience scale(CD-RISC),quality of life assessed by swallowing quality-of-life questionnaire(SWAL-QOL),and the incidence of dysphagia complications(aspiration,aspiration pneumonia,and malnutrition)were compared between the two groups.Results The incidence of dysphagia after extubation and the water swallowing test class in the evidence-based group were lower than those in the routine group(both P<0.05).The total score of MDADI and CD-RISC scores in the evidence-based group were significantly higher than those in the routine group(P<0.05),while the SWAL-QOL scores were lower(P<0.05).The incidence of complications in the evidence-based group was significantly lower than that in the routine group(P<0.05).Conclusion Multidisciplinary collaborative evidence-based nursing can effectively reduce the incidence of dysphagia in patients with orotracheal intubation in ICU after extubation,improve swallowing function,psychological state and quality of life,and reduce the incidence of complications.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective:To Summarize the best evidence of follow-up management of patients with acute kidney injury to provide reference for clinical nursing work.Methods:Retrieved relevant literature on follow-up management of ICU transferred acute kidney injury patients from databases such as Cochrane Library, PubMed, CNKI, Wanfang Database, Chinese Biomedical Literature, and related professional websites based on the "6S" model system.The search deadline was from database establishment to May 30, 2023.Two researchers independently conducted literature quality evaluation, evidence screening, and evidence level assessment, and summarized the evidence.Results:Eight articles were selected, including 4 guidelines, 3 systematic review, 1 expert consensuses. Finally 16 pieces of best evidence from 6 dimensions of follow-up principles and methods, follow-up time/requency, follow- up assessment content, nutritional guidance, drug guidance and life guidance.Conclusions:This study summarized the best evidence summary of the follow-up management of patients with ICU transfer out of acute kidney dormitory, providing a reference for the clinical work of ICU medical staff. Medical staff can develop scientific and effective follow-up management based on patients and clinical conditions to improve the quality of care for ICU transferred patients.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective To invesigate the feasibility of low radiation dose and low contrast dosage in triple-rule-out computed tomo-graphy angiography(TRO-CTA)on the 320-row detector CT.Methods A total of 120 patients who underwent CTA were prospec-tively selected.All patients were divided into control group(n=90)and experimental group(n=30).The control group employed standard-doses protocol of pulmonary CTA(120 kV tube voltage,45 mL contrast dosage),coronary CTA(120 kV,50-60 mL),and aortic CTA(120 kV,75 mL),while the experimental group received TRO-CTA with 100 kV and 70-80 mL.The peak time of contrast dosage at the pulmonary artery and aorta was measured by low-dose detection method in the experimental group,and the contrast examination was performed sequentially in the control group.Subjective scores and objective image quality of the pulmonary artery,coronary artery,and aorta in the experimental group and the control group were measured and compared,respectively.The effective dose(ED)between the two groups were recorded and compared.Independent samples t-test and Fisher exact probability were used to analyze the statistical differences between the above measures.Results There were no significant differences in CT values,con-trast-to-noise ratio(CNR),signal-to-noise ratio(SNR)of pulmonary artery,coronary artery and aorta between the two groups(P＞0.05).The mean subjective scores of pulmonary artery,coronary artery and aorta segments in the two groups were not less than 3 points,meeting the requirement of clinical diagnosis.There was no statistical difference in subjective scores between the two groups(P＞0.05).There was statistically significant difference in ED between the two groups(P＜0.05).The ED of pulmonary artery,coronary artery,and aorta in the experimental group were 11.49％,13.33％,and 11.46％significantly lower than those in the control group,respec-tively.Conclusion It is feasible to obtain TRO-CTA images used by the low radiation dose and low contrast dosage on the 320-row detector CT,and radiation dose and contrast dosage can be reduced reasonably without alterations of TRO-CTA images quality in clinical practice.

ObjectiveTo investigate the efficacy and mechanism of saffron floral bio-residues（SFB） in the treatment of hyperuricemia（HUA） combined with gouty arthritis（GA） in a compound compatibility setting. MethodScreening candidate control Chinese medicines for compound and SFB based on network target distance calculation and data analysis. After adaptive feeding of 80 SD rats for 7 days， 10 rats were randomly selected as the blank group， while the remaining 70 rats were intraperitoneally injected with 3% potassium oxonate and orally administered with 1% adenine for 14 consecutive days. On the 13^th day， rats were injected with 2.5% sodium urate solution into the right ankle joint cavity to induce swelling of the joint capsule on the opposite side， inducing a HUA combined with GA model. At the same time， the modeling rats were randomly divided into 7 groups， including the model group， benzbromarone group（positive drug， 0.02 g·kg^-1）， Tongfengshu tablets group（9 g·kg^-1）， Tongfengshu granules group（9 g·kg^-1）， SFB granules group（3.6 g·kg^-1）， Plantaginis Semen granules group（3.6 g·kg^-1）， and new formula group（SFB replacing Plantaginis Semen in Tongfengshu granules， 9 g·kg^-1）， with 10 rats in each group. Each treatment group was orally administered with the corresponding drugs according to body weight， while the control and model groups were given equal volume of distilled water by gavage once a day for 14 consecutive days. After 14 days of synchronous administration and modeling， changes in gait， ankle joint swelling and mechanical pain threshold in rats were observed， and serum uric acid， creatinine， urea nitrogen and xanthine oxidase（XOD） were measured. Enzyme-linked immunosorbent assay（ELSIA） was used to detect the levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β and IL-6 in rat serum， hematoxylin-eosin（HE） staining was used to observe the pathological changes in the liver， kidney and ankle joints of rats， Western blot was used to detect the expression levels of uric acid transporter 1（URAT1）， glucose transporter 9 （GLUT9）， organic anion transporter 1（OAT1）， adenosine triphosphate（ATP） binding cassette transporter G2（ABCG2）， and liver XOD proteins. ResultThrough network pharmacology analysis， Plantaginis Semen was selected as a candidate control herb， and Tongfengshu tablets was used as a compound compatibility environment to explore the efficacy of SFB in reducing blood uric acid levels and treating GA. Animal experiments showed that compared with the blank group， the gait score and joint swelling degree of the model group were significantly increased， and the mechanical pain threshold was significantly decreased（P<0.01）. Compared with the model group， the gait score， joint swelling degree and mechanical pain threshold of rats in each medication group were improved to varying degrees. Biochemical indicators showed that compared with the blank group， the serum uric acid， creatinine， urea nitrogen and XOD levels of the model group were significantly increased（P<0.01）. Compared with the model group， the serum uric acid and XOD levels of rats in each treatment group were significantly decreased（P<0.01）. ELISA results showed that compared with the blank group， the levels of serum TNF-α， IL-1β and IL-6 in the model group were significantly increased（P<0.01）. Compared with the model group， the levels of TNF-α， IL-1β and IL-6 in the benzbromarone group， Tongfengshu tablets group， Tongfengshu granules group and new formula group were significantly reduced（P<0.05，P<0.01）. Western blot results showed that compared with the blank group， the expression levels of URAT1 and GLUT9 proteins in renal tissue and OXD protein in liver tissue of the model group were significantly increased， while the expression levels of renal OAT1 and ABCG2 were significantly decreased（P<0.01）. Compared with the model group， the expression levels of renal URAT1 and GLUT9 in the SFB granules group， Tongfengshu granules group and new formula group were significantly decreased， while the expression levels of renal OAT1 and ABCG2 were significantly increased， and the expression of XOD protein in liver tissue was significantly decreased（P<0.05， P<0.01）. Pathological analysis showed that focal infiltration of neutrophils， cell necrosis and nuclear fragmentation were observed in the liver tissue of the model group， sodium urate deposition crystals and tubular dilation appeared in renal tissue， synovial hyperplasia and inflammatory cell infiltration appeared in ankle joint. Compared with the model group， the abnormal degrees of liver， kidney and ankle joint tissue of rats in each treatment group were alleviated. ConclusionThe new formula of SFB replacing Plantaginis Semen has the same effect in the treatment of HUA combined with GA. This study proposes a new strategy to investigate the efficacy of new resources of Chinese medicine in a compound compatibility environment， which can provide a new demonstration for the research and development of new resources of Chinese medicine.