Objective To analyze the clinical characteristics and explore the potential mechanisms under-lying acute wheezing associated with respiratory syncytial virus(RSV)and human rhinovirus(HRV)infections in infants.Methods A retrospective analysis was conducted on 560 infants who consecutively presented to the emer-gency department of Qingdao University Affiliated Women and Children's Hospital between January 2022 and December 2024 with acute exacerbation of wheezing caused by RSV and/or HRV infection;these infants constituted the infection group.A control group of 120 healthy infants who underwent routine physical examinations at the same hospital during the same period was also included.Multiplex PCR amplification sequencing technology was employed to detect respiratory pathogens via nucleic acid analysis.The infection group was further classified into the RSV-only group(n=248),the HRV-only group(n=186),and the co-infection group(HRV+RSV,n=126).One-way analysis of variance(ANOVA)was used to compare body mass index(BMI),peripheral blood white blood cell(WBC)count,neutrophil count,lymphocyte count,C-reactive protein(CRP)levels,and concentrations of interleukin(IL)-1β,IL-6,Toll-like receptor 4(TLR4),NOD-like receptor protein 3(NLRP3)inflamma-some,and matrix metalloproteinase-9(MMP-9)across the groups.Additionally,comparisons were made regarding gender distribution,severity of wheezing,history of wheezing,history of eczema,parental allergic history,oxygen supplementation requirements,and presence of concurrent pulmonary infection among the infected infants.Based on wheezing severity,the infection group was further divided into a severe wheezing group and a mild wheezing group.Clinical characteristics and biological indicators were analyzed and compared between these two groups to identify potential independent risk factors.Pearson correlation analysis was performed to evaluate the association between peripheral blood levels of IL-6,NLRP3,and MMP-9 and the severity of acute wheezing exacerbation in children.Results A one-way ANOVA indicated statistically significant differences in WBC count,neutrophil count,CRP,IL-1β,IL-6,TLR4,NLRP3,and MMP-9 levels across the study groups(all P<0.001).Both the RSV and co-infection groups demonstrated significantly higher rates of severe wheezing,oxygen requirement,and prolonged wheezing duration compared to the HRV group(all P<0.05).Among these,the co-infection group exhibited the highest oxygen requirement rate,although the duration of wheezing was shorter than that observed in the RSV group(P<0.05).The incidence of concurrent pulmonary infection was significantly greater in the RSV group compared to the HRV group(P<0.05).Additionally,the proportion of infants with a prior history of wheez-ing was significantly higher in the RSV group than in both the HRV and co-infection groups(P<0.05).Both the RSV and co-infection groups showed a significantly higher prevalence of eczema history among infants compared to the HRV group(P<0.05).Moreover,the co-infection group had a significantly higher proportion of parental allergic history compared with both the RSV and HRV groups(P<0.05).Clinical data analysis stratified by wheezing severity revealed that RSV was the most commonly detected virus among the enrolled infants,particularly in those presenting with severe wheezing(χ2=3.940,P=0.002).The severe wheezing group exhibited significantly higher rates of prior wheezing,history of eczema,parental allergy,need for oxygen supplementation,and concurrent pulmonary infections compared to the mild wheezing group(P<0.001).Furthermore,the duration of wheezing was significantly prolonged in the severe group relative to the mild group(t=2.058,P=0.040).Levels of IL-6,NLRP3,and MMP-9 were also significantly elevated in the severe wheezing group(P<0.05).Multivariate logistic regression analysis revealed that RSV infection,along with elevated levels of IL-6,NLRP3,and MMP-9,were independent risk factors associated with severe wheezing(OR=3.217,1.023,1.022,and 1.056,respectively;all P<0.05).In children with RSV/HRV infection,the severity of acute wheezing demonstrated a positive correlation with NLRP3 and MMP-9 levels(P<0.05).The Pearson correlation coefficient between NLRP3 and MMP-9 was r=0.238(P<0.001),indicating a weak yet statistically significant positive relationship.Conclusions RSV may provoke more severe respiratory inflammatory responses and clinical manifestations compared to HRV.Individuals with a genetic predisposition to allergies or a pre-existing history of respiratory conditions may experience height-ened severity of wheezing following viral infection.The NLRP3 inflammasome may further intensify airway inflam-mation and remodeling through the promotion of MMP-9 release.These mechanisms may collectively contribute to the pathogenesis of acute wheezing episodes and subsequently influence the progression of respiratory diseases.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

Objective To analyze the clinical characteristics and explore the potential mechanisms under-lying acute wheezing associated with respiratory syncytial virus(RSV)and human rhinovirus(HRV)infections in infants.Methods A retrospective analysis was conducted on 560 infants who consecutively presented to the emer-gency department of Qingdao University Affiliated Women and Children's Hospital between January 2022 and December 2024 with acute exacerbation of wheezing caused by RSV and/or HRV infection;these infants constituted the infection group.A control group of 120 healthy infants who underwent routine physical examinations at the same hospital during the same period was also included.Multiplex PCR amplification sequencing technology was employed to detect respiratory pathogens via nucleic acid analysis.The infection group was further classified into the RSV-only group(n=248),the HRV-only group(n=186),and the co-infection group(HRV+RSV,n=126).One-way analysis of variance(ANOVA)was used to compare body mass index(BMI),peripheral blood white blood cell(WBC)count,neutrophil count,lymphocyte count,C-reactive protein(CRP)levels,and concentrations of interleukin(IL)-1β,IL-6,Toll-like receptor 4(TLR4),NOD-like receptor protein 3(NLRP3)inflamma-some,and matrix metalloproteinase-9(MMP-9)across the groups.Additionally,comparisons were made regarding gender distribution,severity of wheezing,history of wheezing,history of eczema,parental allergic history,oxygen supplementation requirements,and presence of concurrent pulmonary infection among the infected infants.Based on wheezing severity,the infection group was further divided into a severe wheezing group and a mild wheezing group.Clinical characteristics and biological indicators were analyzed and compared between these two groups to identify potential independent risk factors.Pearson correlation analysis was performed to evaluate the association between peripheral blood levels of IL-6,NLRP3,and MMP-9 and the severity of acute wheezing exacerbation in children.Results A one-way ANOVA indicated statistically significant differences in WBC count,neutrophil count,CRP,IL-1β,IL-6,TLR4,NLRP3,and MMP-9 levels across the study groups(all P<0.001).Both the RSV and co-infection groups demonstrated significantly higher rates of severe wheezing,oxygen requirement,and prolonged wheezing duration compared to the HRV group(all P<0.05).Among these,the co-infection group exhibited the highest oxygen requirement rate,although the duration of wheezing was shorter than that observed in the RSV group(P<0.05).The incidence of concurrent pulmonary infection was significantly greater in the RSV group compared to the HRV group(P<0.05).Additionally,the proportion of infants with a prior history of wheez-ing was significantly higher in the RSV group than in both the HRV and co-infection groups(P<0.05).Both the RSV and co-infection groups showed a significantly higher prevalence of eczema history among infants compared to the HRV group(P<0.05).Moreover,the co-infection group had a significantly higher proportion of parental allergic history compared with both the RSV and HRV groups(P<0.05).Clinical data analysis stratified by wheezing severity revealed that RSV was the most commonly detected virus among the enrolled infants,particularly in those presenting with severe wheezing(χ2=3.940,P=0.002).The severe wheezing group exhibited significantly higher rates of prior wheezing,history of eczema,parental allergy,need for oxygen supplementation,and concurrent pulmonary infections compared to the mild wheezing group(P<0.001).Furthermore,the duration of wheezing was significantly prolonged in the severe group relative to the mild group(t=2.058,P=0.040).Levels of IL-6,NLRP3,and MMP-9 were also significantly elevated in the severe wheezing group(P<0.05).Multivariate logistic regression analysis revealed that RSV infection,along with elevated levels of IL-6,NLRP3,and MMP-9,were independent risk factors associated with severe wheezing(OR=3.217,1.023,1.022,and 1.056,respectively;all P<0.05).In children with RSV/HRV infection,the severity of acute wheezing demonstrated a positive correlation with NLRP3 and MMP-9 levels(P<0.05).The Pearson correlation coefficient between NLRP3 and MMP-9 was r=0.238(P<0.001),indicating a weak yet statistically significant positive relationship.Conclusions RSV may provoke more severe respiratory inflammatory responses and clinical manifestations compared to HRV.Individuals with a genetic predisposition to allergies or a pre-existing history of respiratory conditions may experience height-ened severity of wheezing following viral infection.The NLRP3 inflammasome may further intensify airway inflam-mation and remodeling through the promotion of MMP-9 release.These mechanisms may collectively contribute to the pathogenesis of acute wheezing episodes and subsequently influence the progression of respiratory diseases.

Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective To explore the application of standardized teaching mode in clinical teaching for B-type ultrasound-guided peripherally inserted central catheters(PICC),and to discuss its influence on the teaching quality,comprehensive skills and student satisfaction.Methods A total of 74 nurses,who learned B-type ultrasound-guided PICC operation at the Department of Emergency of a certain grade Ⅲ-A hospital in Guangzhou City of China from September 2021 to September 2023,were randomly divided into the study group and the control group with 37 nurses in each group.The teaching content of both groups was B-type ultrasound-guided PICC operation.The conventional teaching method was adopted for the control group,while on the basis of the conventional teaching method,additional standardized teaching mode was carried out for the study group.Teaching and training lasted for 3 months.The management indicators,teaching quality,comprehensive skills and student satisfaction with teaching were compared between the two groups.Results Compared with the control group,in the study group the catheterization time was shorter,the pain score was lower,and the success rate of single puncturing was higher(all P＜0.05).The results of final theory examination,case analysis ability,and clinical actual operation score(including the indications,puncturing method,and puncturing technique of B-type ultrasound-guided PICC)in the study group were significantly better than those in the control group(all P＜0.05).The comprehensive skills were remarkably improved in both groups.The scores of doctor-patient communication,physical examination,medical ethics,operation process in the study group were obviously higher than those in the control group(all P＜0.05).Moreover,the expression ability,the sense of team cooperation,the ability to search and read literature,the ability of clinical practice,the degree of knowledge mastery,the ability to analyze and solve problems,and the learning initiative in the study group were prominently better than those in the control group(all P＜0.05).Conclusion In clinical teaching for B-type ultrasound-guided PICC operation,the implement of standardized teaching mode can help to improve the quality of teaching and improve the nurse s comprehensive skills of PICC operation with higher degree of satisfaction with teaching,therefore,this kind of teaching mode is worth popularizing and applying.