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

Objective: To establish a method for determining the content of bear bile powder in Longze Xiongdan capsules with taursodeoxycholic acid（TUDCA） and taurchenodeoxycholic acid（TCDCA） as indexes.
Methods: HPLC series evaporation photodetector was adopted on Chrom Core AQ C₁₈ column(4.6 mm×250 mm, 5 μm), with the mobile phase comprising of acetonitrile ( A ) and 5 mmol·L^-1 ammonium acetate solution (B) in a gradient elution (0-40 min, 25%A; 40-50 min, 25%A→29%A; 50-80 min, 29%A; 80-100 min, 29%A→40%A) at the flow rate of 1.0 mL·min^-1. The column temperature was 30 ℃. The ELSD was used, of which the drift tube temperature was 110 ℃ and the flow rate of carrier gas（N₂） was 2.5 L·min^-1.
Results: In the ranges of 1.069-9.57 μg and 0.740 46-7.404 64 μg, logarithms of the injected amount of TUDCA and TCDCA presented good linear relationships with logarithms of the peak area, respectively. The RSDs of precision, repeatability and stability tests were all lower than 2.0%. At three concentration levels the recoveries of TUDCA and TCDCA were 95.2%-97.7% and 91.9%-95.9%, respectively. Samples of 42 batches showed that the contents of TUDCA and TCDCA were 0.18-0.43 and 0.10-0.44 mg·granule^-1, respectively.
Conclusion: This method can be used for the quality control of bear bile powder in Longze Xiongdan capsules, thus provides a scientific basis for improving its quality standard.

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.

ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii （CRAB） nosocomial infection in an intensive care unit （ICU） and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection. MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing （MLST） were conducted and intervention measures were taken. ResultsA total of 4 cases with CRAB infection were identified， among which 1 case was determined to be community-acquired and3 cases were hospital-acquired. The isolated strains shared the same drug resistance， and were all classified into ST368 type. In the surface and hand samples （n=40）， 2 CRAB strains were detected in the air filter beside the bed of the first case， with a detection rate of 5%. After adopting comprehensive prevention and control strategies， including environmental cleaning and disinfection， hand hygiene， staff management and training， and supervision， no similar case with CRAB infection was found. ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection， and inadequate implementation of hand hygiene. Timely identification， investigation， and targeted measures remain crucial to effective control of possible nosocomial infection.

Objective To investigate the effectiveness and safety of endoscopic mucosal resection with precutting(EMR-P)for the treatment of rectal neuroendocrine neoplasm(RNEN)smaller than 1 cm in diameter.Methods Clinical data of 177 patients with RNEN smaller than 1 cm in diameter from December 2016 to December 2021 were retrospectively analyzed.According to different treatment protocols,177 patients with RNEN were divided into endoscopic mucosal resection(EMR)group(n = 46),EMR-P group(n = 40)and endoscopic submucosal dissection(ESD)group(n = 91).The en bloc resection rate,complete resection rate,operation time,postoperative hospitalization time and incidence of operative complications among the three groups were compared.Results The complete resection rate in the EMR-P group(95.0%)and ESD group(97.8%)were significantly higher than that in the EMR group(87.0%)(P<0.05);The operation time in the EMR-P group(9.86±2.23)min was longer than that in the EMR group(4.12±0.88)min,EMR-P group and EMR group were shorter than that in the ESD group(19.55±3.67)min,the difference was statistically significant(P<0.05);Postoperative hospitalization time in the EMR group was(2.45±0.29)d and EMR-P group was(2.43±0.23)d,which were shorter than that in the ESD group(3.30±0.32)d,and the difference was statistically significant(P<0.05).There were no significant difference in the rates of en bloc resection and operative complications among the three groups(P>0.05).Conclusion EMR-P for the treatment of RNEN<1 cm in diameter has the advantages,such as simple operation,short operation time and hospitalization time,high histological complete resection rate and low complication rate,which is worthy of clinical application.

African swine fever(ASF),caused by the African swine fever virus(ASFV),is a highly contagious infectious disease of pigs.This disease has been spread rapidly in China since 2018,po-sing a huge threat to China's pig farming industry.To rapid detect the ASFV,a loop-mediated iso-thermal amplification(LAMP)combined with the disposable nucleic acid visualization test strip was established for visual detection of the nucleic acid of ASFV B646L gene.The method was easy to operate without special instruments and equipment,while it effectively avoided the disadvantage of false positives caused by aerosol contamination.The method was able to detect 1.16 copies/μL of the recombinant plasmid in 50 min at 65 ℃.In addition,the method was specific with no cross-re-action with classical swine fever virus,porcine reproductive and respiratory syndrome virus,por-cine parvovirus,transmissible gastroenteritis virus.The results in this study provides a rapid,con-venient,sensitive and reliable method for early diagnosis and screening for ASFV suspected infec-tion cases.

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 Improving the limb management strategy for patients undergoing coronary intervention through radial artery puncture and observe the application effect,and to provide scientific basis for the prevention of limb complications.Methods From March 2023 to February 2024,patients who underwent coronary intervention in the Cardiovascular Department of a Tertiary A hospital in Wenzhou City were selected.They were randomly di-vided into an experimental group of 241 cases and a control group of 236 cases using a random number table method.After surgery,they were all treated with a rotary hemostatic device for compression hemostasis.The experi-mental group implement improvement strategies for surgical limb management,specifically underwent a reverse Bar-beau test upon returning to the ward after surgery to achieve non-occlusive compression,followed by decompression every hour.The compression intensity of the control group was guided by palpating the distal radial artery pulsa-tion,and the first decompression was performed 1 hour after surgery,followed by decompression at intervals of every 2 hours.The main evaluation indicators are the incidence of surgical limb complications and simplified Chinese version of General Comfort Questionnaire(GCQ)scores in 2 groups of patients,while the secondary evaluation indi-cators are the duration of compression and the number of decompression times in both groups.Results The inci-dence of postoperative complications in the experimental group was 14.11%,which was statistically significant com-pared to 44.49%in the control group(χ2=53.308,P<0.001).The GCQ score of the experimental group was(77.71±5.43)points,which was higher than(74.66±5.83)points in the control group,and the difference was statistically signif-icant(t=-3.354,P=0.001).The compression duration of(172±52)minutes and decompression frequency of 2(2,3)in the experimental group were lower than(289±60)minutes and 4(3,4)in the control group,and the differences were statistically significant(P<0.001).Conclusion The non-occlusive compression method of the radial artery based on the reverse Barbeau test can significantly reduce limb complications in patients undergoing coronary inter-vention,shorten the duration of hemostatic compression,reduce the number of depressions,and improve patient com-fort.It provides objective basis for nursing staff to evaluate the intensity of hemostatic compression and the timing of decompression.

Objective To conduct a scoping review of research on the application of mobile health(mHealth)in the management of home enteral tube feeding,so as to provide references for future research and clinical practice.Methods A literature search was performed in the PubMed,Cochrane Library,Embase,Web of Science,CINAHL,CNKI,Wanfang,and CMB databases to identify relevant studies.The search period spanned from the establishment of databases until February 18,2024.According to the scoping review framework,2 researchers independently screened the studies,extracted the data of the included studies,and collaborated on the final analysis.Results A total of 24 studies were included.9 studies were conducted with interventions based on nursing models such as discharge planning model,"Hospital to Home"nutrition management model,guided care nursing model.The management forms included application,network communication software,and website.The content elements included education,assessment,consultation,referral,self-management,electronic health archive,appointment service,peer support.The outcome indicators included patients'physical and mental health,self-management ability,caregiver competence,family burden and user assessment.Conclusion The mHealth has played a positive role in the management of home enteral tube feeding.In the future,it is recommended to establish a multidisciplinary team to conduct high-quality research and continuously improve the form and content of mHealth management.