Goose astrovirus(GAstV)has become one of the most important pathogens endangering the goose farming industry in China.To discover the genomic information of prevalent strains in China in 2022 and reveal their biological characteristics,the whole genomes of 9 strains of GAstV-1 and 12 strains of GAstV-2 isolated from parts of China in 2022 were sequenced by the Chromo-some Walking and analyzed by bioinformatics software and websites.The analysis results of gene structure showed that the sizes of the coding genes ranged from 6 977 to 7 215 bp.The open read-ing frame 1(ORF1)of all strains contained the characteristic motifs of serine protease,nuclear lo-calization signal(NLS)and RNA-dependent RNA polymerase(RdRp).The ribosomal frameshift signals(RFS)were all in the form of stem-loop structures.However,the numbers of stem and loop nucleotides in GAstV-1 were"14+11"configuration,while those in GAstV-2 were"12+14"configuration,and the loop of GAstV-2 was in the"8+6"double-loop configuration.The results of homological analysis for ORF1b showed that the homology of the GAstV-1 isolats compared with the representative strains of avian astrovirus types 1,2,and 3(AAstV-1,AAstV-2,AAstV-3)ranged from 7％to 64％,and the homology of the GAstV-2 isolates ranged from 8％to 68％.The average genetic distances of ORF2 were 0.9,1.2,and 0.9 respectively compared with the represent-ative strains of AAstV-1,AAstV-2 and AAstV-3.While for the GAstV-2 isolates,the highest ho-mologies were 68％and 56％,the lowest homologies were 8％and 36％respectively.And the aver-age genetic distances of ORF2 were 1.0,1.2,and 0.5 respectively.B-cell-conformational epitopes screening results of ORF2 showed that,there were four common epitopes in the GAstV Group 1 i-solates,namely PRE,LALQSQSVNTFA,AAG and YQQVTSDQSI except for N-145,N-287 and N-314 in the two strains G1FJ267 and G1JS277.And there were seven common conformational epitopes in the GAstV-2 isolates,namely NQE,RAN,GPE,PRQ,TRAQ,SNS,and AVPPNTPL except for N-83,N-136,N-331 and N-351 in the strain G2FJ283-3B.The above results indicated that GAstV maybe belong to a new type of AAstV because of the difference between the clinical i-solates and the known strains of AAstV.And there was pathogenic diversity among the isolates.All the isolates of GAstV-1 and GAstV-2 belong to two different serotypes,and the possible serologi-cal subtypes among the isolates of GAstV-1 or GAstV-2 are remained to be further identified by serological tests.

Goose astrovirus(GAstV)has become one of the most important pathogens endangering the goose farming industry in China.To discover the genomic information of prevalent strains in China in 2022 and reveal their biological characteristics,the whole genomes of 9 strains of GAstV-1 and 12 strains of GAstV-2 isolated from parts of China in 2022 were sequenced by the Chromo-some Walking and analyzed by bioinformatics software and websites.The analysis results of gene structure showed that the sizes of the coding genes ranged from 6 977 to 7 215 bp.The open read-ing frame 1(ORF1)of all strains contained the characteristic motifs of serine protease,nuclear lo-calization signal(NLS)and RNA-dependent RNA polymerase(RdRp).The ribosomal frameshift signals(RFS)were all in the form of stem-loop structures.However,the numbers of stem and loop nucleotides in GAstV-1 were"14+11"configuration,while those in GAstV-2 were"12+14"configuration,and the loop of GAstV-2 was in the"8+6"double-loop configuration.The results of homological analysis for ORF1b showed that the homology of the GAstV-1 isolats compared with the representative strains of avian astrovirus types 1,2,and 3(AAstV-1,AAstV-2,AAstV-3)ranged from 7％to 64％,and the homology of the GAstV-2 isolates ranged from 8％to 68％.The average genetic distances of ORF2 were 0.9,1.2,and 0.9 respectively compared with the represent-ative strains of AAstV-1,AAstV-2 and AAstV-3.While for the GAstV-2 isolates,the highest ho-mologies were 68％and 56％,the lowest homologies were 8％and 36％respectively.And the aver-age genetic distances of ORF2 were 1.0,1.2,and 0.5 respectively.B-cell-conformational epitopes screening results of ORF2 showed that,there were four common epitopes in the GAstV Group 1 i-solates,namely PRE,LALQSQSVNTFA,AAG and YQQVTSDQSI except for N-145,N-287 and N-314 in the two strains G1FJ267 and G1JS277.And there were seven common conformational epitopes in the GAstV-2 isolates,namely NQE,RAN,GPE,PRQ,TRAQ,SNS,and AVPPNTPL except for N-83,N-136,N-331 and N-351 in the strain G2FJ283-3B.The above results indicated that GAstV maybe belong to a new type of AAstV because of the difference between the clinical i-solates and the known strains of AAstV.And there was pathogenic diversity among the isolates.All the isolates of GAstV-1 and GAstV-2 belong to two different serotypes,and the possible serologi-cal subtypes among the isolates of GAstV-1 or GAstV-2 are remained to be further identified by serological tests.

Objective To develop a platform for reporting medication near miss events and evaluate its application effectiveness,aiming to enhance medication safety of patients.Methods Based on literature review,qualitative interviews,and expert group meetings,a medication near-miss event reporting platform was constructed,including 4 modules:event content filling,event risk grading,event handling,and statistical analysis.50 nurses were conveniently selected from the pediatric ward of a tertiary grade A hospital in Henan Province as the application subjects.The reporting situation and filling duration of medication near miss events,the score of the Medication Near Miss Reporting Disorder Scale,and the incidence of medication near miss events were compared after the application of the platform(from March to August 2023)and before the application(from September 2022 to February 2023).Results The reporting rate of medication near miss events after the application of the platform was higher than that before the application of the platform,and the comparison of the distribution of event nature and occurrence links showed statistically significant differences(P＜0.05).After the application of the platform,the reporting duration of medication near miss events was shorter than that before the application of the platform,and the score of the Medication Near Miss Reporting Disorder Scale was lower than that before the application of the platform.The differences were statistically significant(P＜0.001).There was no statistically significant difference in the incidence of medication near miss events before and after the application of the platform(P=0.241).Conclusion Using this platform can help improve the reporting rate of medication near miss events,reduce the time taken to fill out reports,and minimize reporting barriers for nurses.

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

Objective To develop a platform for reporting medication near miss events and evaluate its application effectiveness,aiming to enhance medication safety of patients.Methods Based on literature review,qualitative interviews,and expert group meetings,a medication near-miss event reporting platform was constructed,including 4 modules:event content filling,event risk grading,event handling,and statistical analysis.50 nurses were conveniently selected from the pediatric ward of a tertiary grade A hospital in Henan Province as the application subjects.The reporting situation and filling duration of medication near miss events,the score of the Medication Near Miss Reporting Disorder Scale,and the incidence of medication near miss events were compared after the application of the platform(from March to August 2023)and before the application(from September 2022 to February 2023).Results The reporting rate of medication near miss events after the application of the platform was higher than that before the application of the platform,and the comparison of the distribution of event nature and occurrence links showed statistically significant differences(P＜0.05).After the application of the platform,the reporting duration of medication near miss events was shorter than that before the application of the platform,and the score of the Medication Near Miss Reporting Disorder Scale was lower than that before the application of the platform.The differences were statistically significant(P＜0.001).There was no statistically significant difference in the incidence of medication near miss events before and after the application of the platform(P=0.241).Conclusion Using this platform can help improve the reporting rate of medication near miss events,reduce the time taken to fill out reports,and minimize reporting barriers for nurses.

Objective To investigate the effect of hydrogen sulfide(H2S)on olfactory function in mice and the recovery of olfactory function after H2S poisoning test.Methods Thirty-six clean grade BALB/c mice were randomly divided into control group,0.05 mg/L H2S exposure group,and 5.00 mg/L H2S exposure group according to the random number table method,with 12 mice in each group.The recovery of olfactory function was observed after H2S exposure cycle.The behavior and foraging time of the mice were recorded.Results Before the exposure test,there was no significant difference in olfaction time among the groups(P>0.05).On the 10th,20th and 30th day of the exposure test,the foraging time of 5.00 mg/L H2S exposure group was gradually prolonged,which was significantly different from that of the control group and 0.05 mg/L H2S exposure group(P<0.05).On the 5th,10th and 15th day after exposure test,the foraging time of 5.00 mg/L H2S exposure group gradually shortened,which was significantly longer than that of the control group and 0.05 mg/L H2S exposure group(P<0.05).Conclusion The short-term toxicity test of 5.00 mg/L H2S can cause olfactory dysfunction in mice,manifested by differences in foraging time.This olfactory dysfunction can be recovered to some extent within 15 days after leaving the exposed environment.

ObjectiveTo investigate the association between serum 25-hydroxy vitamin D [25(OH)D] and the occurrence and outcome of stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) in emergency ward. MethodsThe clinical data of 256 patients with AIS from January, 2019 to December, 2021 were collected in the emergency department of Beijing Bo'ai Hospital. Blood routine, biochemical indicators and serum concentration of 25(OH)D were detected within 24 hours after enrollment; meanwhile, National Institute of Health Stroke Scale (NIHSS) and A2DS2 score were evaluated. The patients were divided into non-SAP group (n = 164) and SAP group (n = 92) according to whether pneumonia occurred during hospitalization. Multivariable logistic regression model was used to analyze the influencing factors of SAP. The predictive ability of serum 25(OH)D and A2DS2 for SAP were evaluated by receiver operating characteristic (ROC) curves. The 28-day survival of patients with SAP was followed up. Multivariable Cox proportional hazard regression model was used to investigate the association between vitamin D nutritional status and 28-day all-cause mortality. ResultsSerum 25(OH)D was significantly lower in the SAP group than that in the non-SAP group (Z = 6.896, P < 0.001). After adjusting age, sex, infarct volume, A2DS2 score and other factors, lower serum 25(OH)D level (OR = 0.934, 95%CI 0.884 to 0.986, P = 0.014) was an independent risk factor for SAP. The areas under curve (95%CI) of serum 25(OH)D, A2DS2 score and their combined model for predicting SAP were 0.774 (0.718 to 0.824), 0.832 (0.781 to 0.876) and 0.851 (0.802 to 0.893) (P < 0.001), respectively; and the optimum cut-off values were 25(OH)D < 10.2 ng/mL, A2DS2 score > 5 points, combined prediction > 0.207, and the Youden index were 0.493, 0.662 and 0.616, respectively. A2DS2 score could improve the prediction efficiency of serum 25(OH)D (Z = 2.106, P = 0.035). After adjusting age, sex, infarct volume and NIHSS score, vitamin D deficiency was an independent risk factor for all-cause mortality after 28 days of SAP (HR = 2.871, 95%CI 1.004 to 8.208, P = 0.049) . ConclusionSerum 25(OH)D is independently associated with the occurrence and outcome of SAP in patients with AIS in emergency ward, which could serve as an independent predictor for SAP.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

Postnatal heart maturation is the basis of normal cardiac function and provides critical insights into heart repair and regenerative medicine. While static snapshots of the maturing heart have provided much insight into its molecular signatures, few key events during postnatal cardiomyocyte maturation have been uncovered. Here, we report that cardiomyocytes (CMs) experience epigenetic and transcriptional decline of cardiac gene expression immediately after birth, leading to a transition state of CMs at postnatal day 7 (P7) that was essential for CM subtype specification during heart maturation. Large-scale single-cell analysis and genetic lineage tracing confirm the presence of transition state CMs at P7 bridging immature state and mature states. Silencing of key transcription factor JUN in P1-hearts significantly repressed CM transition, resulting in perturbed CM subtype proportions and reduced cardiac function in mature hearts. In addition, transplantation of P7-CMs into infarcted hearts exhibited cardiac repair potential superior to P1-CMs. Collectively, our data uncover CM state transition as a key event in postnatal heart maturation, which not only provides insights into molecular foundations of heart maturation, but also opens an avenue for manipulation of cardiomyocyte fate in disease and regenerative medicine.
Gene Expression Regulation ; Heart ; Myocytes, Cardiac/metabolism* ; Single-Cell Analysis ; Transcription Factors/metabolism*