Objective To investigate the levels of serum neuregulin-4(NRG4)and serum fatty acid binding protein 4(FABP4)in patients with diabetes retinopathy(DR)and their diagnostic value.Methods From A-pril 2020 to April 2023,a total of 84 DR patients admitted to Endocrine and Metabolic Disease Hospital Affili-ated to Shandong First Medical University were regarded as the observation group.Based on the type of retinal lesions,they were grouped into proliferative lesion group(35 cases)and non proliferative lesion group(49 ca-ses).In addition,84 patients with simple diabetes in the same period were regarded as the NDR group,and 84 healthy people who underwent physical examination in the same period were regarded as the control group.Enzyme linked immunosorbent assay was applied to detect serum levels of NRG4 and FABP4.Multivariate Logistic regression was applied to analyze the influencing factors of DR occurrence.Receiver operating charac-teristic(ROC)curve was applied to analyze the diagnostic value of serum NRG4 and FABP4 levels for DR.Results The levels of C-reactive protein(CRP),fasting plasma glucose(FPG),fasting insulin(FINS)and FABP4 in the observation group were higher than those in the NDR group and the control group(P<0.05),and the serum NRG4 level was lower than those in the NDR group and the control group(P<0.05).The ser-um NRG4 level in the proliferative lesion group was lower than that in the non proliferative lesion group(P<0.05),and the FABP4 level was higher than that in the non proliferative lesion group(P<0.05).NRG4 was a protective factor for the occurrence of DR(P<0.05),while FABP4 was a risk factor for the occurrence of DR(P<0.05).The area under the curve(AUC)of serum NRG4 and FABP4 for diagnosing DR was 0.850 and 0.866,and the AUC of combined diagnosis was 0.930.The efficacy of the combination of the two was su-perior to that of the individual diagnosis of serum NRG4 and FABP4(Zcombination-NRG4=3.467,Zcombination-FABP4=2.987,P=0.001,0.002).Conclusion The serum FABP4 level in DR patients is greatly increased,while the NRG4 level is greatly decreased.The combination of the two has high diagnostic value for DR.

Objective:To discuss the infection status and clinical outcomes in the patients with bullous pemphigoid(BP),and to analyze the risk factors for infection in hospitalized BP patients,as well as to construct and evaluate the risk prediction model.Methods:A total of 126 patients first diagnosed with BP were selected.According to the occurrence of infection,the patients were divided into infection group(52 cases)and non-infection group(74 cases).The infection status and outcomes of the patients in two groups were recorded;statistical analysis was performed on the general data,laboratory examination results,FRAIL scale scores for frailty screening,NRS2002 scores,and skin lesion severity of the patients in two groups;multivariate Logistic regression model was used to identify the risk factors for infection in the patients;the goodness-of-fit test was used to evaluate the model;receiver operating characteristic(ROC)curve was used to evaluate the predictive value of the model for infection.Results:Among the 126 hospitalized BP patients,52 cases had infection,with an infection rate of 41.27％.The mortality rate of the patients in infection group was higher than that in non-infection group(P＜0.05),and the remission rate of the patients in non-infection group was higher than that in infection group(P＜0.05).The FRAIL scale score for frailty screening,NRS2002 score,serum albumin level,prealbumin level,number of hospitalization,skin lesion severity,and time of hospital stay of the patients in infection group were significantly higher than those in non-infection group(P＜0.05).The multivariate Logistic regression analysis results derived the regression equation:Logistic(P)=-7.63+0.922× skin lesion severity+2.565×FRAIL scale score for frailty screening+1.214×NRS2002 score.The area under the curve of the Logistic regression model was 0.916.Conclusion:The FRAIL scale score for frailty screening,NRS2002 score,and skin lesion severity are the risk factors for infection in the hospitalized BP patients.The constructed infection risk prediction model based on these factors has good predictive value and may provide new ideas for the prevention and control of infection in the hospitalized BP patients.

Objective To investigate the correlations of serum levels of endothelial cell-specific molecule-1(ESM-1,also known as endocan),interleukin(IL)-1α,and human chondroglycan pro-tein-39(also known as YKL-40)with disease severity and prognosis in children with recurrent respira-tory infections(RRI).Methods A total of 86 children with RRI were prospectively enrolled as case group and divided into mild(37 cases),moderate(31 cases),and severe(18 cases)groups based on disease severity,and divided into good prognosis(64 cases)and poor prognosis(22 cases)groups based on prognosis.Additionally,94 healthy children who underwent physical examinations during the same period were selected as control group.Serum levels of endocan,IL-1α,and YKL-40 were measured using enzyme-linked immunosorbent assay(ELISA)in all children.Spearman's correla-tion analysis was used to assess the correlation between serum levels of endocan,IL-1α,and YKL-40 and disease severity in children with RRI.Multivariate Logistic regression analysis was conducted to explore the factors influencing the prognosis of children with RRI.Receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum endocan,IL-1α,and YKL-40 for the prognosis of children with RRI.Results The serum levels of endocan,IL-1α,and YKL-40 in the case group were higher than those in the control group(P＜0.05).The serum levels of en-docan,IL-1α,and YKL-40 in the moderate and severe groups were higher than those in the mild group,and the levels in the severe group were higher than those in the moderate group(P＜0.05).The serum levels of endocan,IL-1α,and YKL-40 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).Serum levels of endocan,IL-1α,and YKL-40 were significantly positively correlated with disease severity in children with RRI(r=0.407,0.493,0.452,respectively;P＜0.001).Multivariate Logistic regression analysis showed that serum en-docan(OR=1.412),IL-1α(OR=1.583),and YKL-40(OR=1.259)were independent influen-cing factors for the prognosis of children with RRI(P＜0.05).The ROC curve showed that the area under the curve for the combined prediction of poor prognosis in children with RRI by serum en-docan,IL-1α,and YKL-40 was 0.925,which was significantly larger than that for endocan,IL-1α,and YKL-40 alone.Conclusion Serum levels of endocan,IL-1α,and YKL-40 are closely related to disease severity and prognosis in children with RRI,and their combined detection has high predictive value for the prognosis of children with RRI.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To explore the current status of back patting and sputum drainage nursing performed by nurses in the Neurological Intensive Care Unit (NICU) and their design requirements for a nursing robot, providing a reference for the design of nursing robots for back patting and sputum drainage.Methods:This descriptive qualitative study employed a purposive sampling method. From January to February 2024, semi-structured interviews were conducted with 15 nurses from the NICU of Xuanwu Hospital, Capital Medical University. Data were analyzed using Colaizzi 7-step analysis method.Results:A total of three major issues were identified regarding the current practice of back patting and sputum drainage nursing by NICU nurses: heavy workload and time-consuming; difficulties in patient positioning and maintenance; deficiencies in nursing care. The design requirements for a back patting and sputum drainage nursing robot were categorized into two main themes with 10 sub-themes: functional requirements (turning function, supporting function, intelligent recognition function, abnormality detection with alarm or pause feature, and evaluation of post-percussion effectiveness) ; design requirements (basic functional design, support component design, percussion component design, coordination between support and percussion functions, and overall structural design) .Conclusions:Understanding the design requirements of NICU nurses for a back patting and sputum drainage nursing robot provides valuable insights for developing a safe, scientific, reasonable, and effective robotic system.

Objective:To explore the current status of back patting and sputum drainage nursing performed by nurses in the Neurological Intensive Care Unit (NICU) and their design requirements for a nursing robot, providing a reference for the design of nursing robots for back patting and sputum drainage.Methods:This descriptive qualitative study employed a purposive sampling method. From January to February 2024, semi-structured interviews were conducted with 15 nurses from the NICU of Xuanwu Hospital, Capital Medical University. Data were analyzed using Colaizzi 7-step analysis method.Results:A total of three major issues were identified regarding the current practice of back patting and sputum drainage nursing by NICU nurses: heavy workload and time-consuming; difficulties in patient positioning and maintenance; deficiencies in nursing care. The design requirements for a back patting and sputum drainage nursing robot were categorized into two main themes with 10 sub-themes: functional requirements (turning function, supporting function, intelligent recognition function, abnormality detection with alarm or pause feature, and evaluation of post-percussion effectiveness) ; design requirements (basic functional design, support component design, percussion component design, coordination between support and percussion functions, and overall structural design) .Conclusions:Understanding the design requirements of NICU nurses for a back patting and sputum drainage nursing robot provides valuable insights for developing a safe, scientific, reasonable, and effective robotic system.

Objective:Studying the effect of PRDX4 on esophageal squamous cell carcinoma cells(esophageal carcinoma,ESCC)proliferation and apoptosis as well as its potential mechanism.Methods:The University of Alabama at Birmingham cancer data analysis portal(UALCAN),gene expression profiling interactive analysis(GEPIA)and the Cancer Genome Atlas(TCGA)databases were used to predict PRDX4 expres-sion in ESCC and its relationship with pathological features and prognosis.The cancer and adjacent tissues of 60 patients with ESCC who un-derwent radical resection in the Affiliated Hospital of Weifang Medical College from August 2010 to August 2023 were selected as research samples.The expression level of PRDX4 in the patients was detected by immunohistochemistry(IHC).The extracted cancer and adjacent tis-sues were homogenized to analyze its mRNA expression.The expression levels of PRDX4 mRNA and related signaling proteins in ESCC cells were analyzed by real-time quantitative PCR and Western blot.Cell Counting Kit-8(CCK-8)assay and flow cytometry were used to analyze the effect of PRDX4 on cell proliferation and apoptosis.Finally,a subcutaneous tumor model in nude mice was constructed to validate the in vitro experimental results.Results:The data from the GEPIA and UALCAN showed that PRDX4 expression was abnormally increased and re-lated to the pathology stage,grade,and survival rate of patients.After knockdown and overexpression of PRDX4 in an ESCC cell line,the ex-pression of PRDX4,phos-phosphatidylinositol 3-kinase(p-PI3K),phos-protein kinase B(p-AKT),cyclinD1,and survivin protein decreased and increased,respectively;cell proliferation and apoptosis were positively regulated.Compared with the sh-NC group,tumor volume and weight in the sh-PRDX4 group were decreased.Conclusions:PRDX4 regulates the proliferation and apoptosis of ESCC cells by activating the PI3K/AKT signaling pathway.