ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

End-stage dilated cardiomyopathy belongs to the irreversible cardiac decompensation stage,and neither drugs nor cardiac resynchronization therapy can improve the symptoms of heart failure in patients.Orthotopic heart transplantation is a surgical procedure that involves removing the diseased heart of the recipient and implanting the donor heart in its original position.With the advancements in surgical transplantation techniques and immunosuppressive therapy,it has become an effective treatment for end-stage heart disease.Coronary artery disease after heart transplantation is one of the issues that need attention after heart transplantation.This article reports a 68-year-old male who suffered from recurrent heart failure and ventricular tachycardia due to"dilated cardiomyopathy"and underwent allogeneic orthotopic heart transplantation 5 years ago.The patient underwent coronary angiography and intravascular ultrasound examination under local anesthesia.This case has certain guiding significance for studying the progression of coronary artery disease in heart transplant patients.

OBJECTIVE To explore the epidemiological characteristics of common allergens among children with al-lergic rhinitis(AR)in a children's specialized hospital of Beijing.METHODS A total of 2120 children who met the diagnostic criteria of AR and were treated in otolaryngology department of Beijing Jingdu Children's Hospital from 2021 to 2023 were recruited as the research subjects.The specific immunoglobulin E(sIgE)of allergens was de-tected by western blot quantitative assay.The positive rates of the allergens were statistically analyzed according to the age,sex and years.The epidemiological characteristics and changing trends were observed.RESULTS The pos-itive rate of allergens was 47.78％among the 2120 children,in whom multiple allergies polysensitization were pre-dominant;the positive rate of allergens and polysensitization rate were the highest among the population aged be-tween 1 and 7 years old.The inhalational allergens were dominant,and the positive rate of the Candida group was highest.The positive rates of inhalant allergens and ingested allergens reached the peak at the age of 1-7 and then declined with age;milk and egg white were the two types of predominant ingested allergens in childhood.Among the 2120 children,there were significant differences in the positive rates of allergens between the male and the fe-male,and the positive rates of the male were higher than those of the female(P＜0.001).The positive rates of al-lergens generally showed upward trends during the 3 years,the positive rates of the inhalant allergens such as mugwort,cat hair and dog dandruff ascended by a large margin,and the positive rates of the ingested allergens such as milk,egg white and egg yolk showed remarkable rising trends.CONCLUSIONS The causes of AR are complicated.There are a variety of factors affecting the allergen test.The epidemiological characteristics of the al-lergens among the AR children are observed from multiple perspectives,which may provide references for preven-tion and treatment of the children with AR.

OBJECTIVE To stimulate the debridement and dressing process under the approximately real clinical scene by fluorescence labeling and understand the contamination status of the operators' bodies and their surround-ings so as to improve the strategies.METHODS A total of 41 trainees were recruited from Enterostomal Therapist Nursing Education Program of Peking University School of Medicine and International School of Wound Thera-pists of Peking University First Hospital in 2023.The examination was designed by stimulating the debridement and dressing operations with fluorescence labeling,the orange was used to simulate the wound of the patients,and the pad towel was placed under the orange to represent the contaminated surroundings of the wound.A round le-sion area with diameter of 2 cm was uniformly marked on the surface of the orange peel by the operators,the trai-nees were asked to remove the lesion tissues and take dressings.The fluorescent powders were smeared evenly on the orange and pad towel before the examination,and no fluorescence labeling for the surroundings was guaranteed.The trainees were required to wear hats,masks,isolation gowns and gloves during the operations,and take off the gloves and trace the scope of fluorescent contamination with ultraviolet radiator after the examina-tion.RESULTS The contamination rate was 92.68％for the trainees' bodies,100.00％for their surroundings.The hands and forearms were the most severe contaminated body sites,and the contamination rates were 85.37％(35/41)and 34.15％(14/41),respectively.The downside of the pad towel was the most frequently contaminated area of the surroundings,with the proportion of 90.24％(37/41);the right side of the pad towel was the area with the contamination disseminated farthest,with the median distance of dissemination 13.50 cm.In addition,the dressing change carts of 75.61％(31/41)of the trainees were contaminated.CONCLUSIONS The operations of de-bridement and dressing change may lead to varying degrees of contamination of their bodies and surroundings.It is necessary to strengthen the hand hygiene and protective isolation during the process of dressing change and pay attention to the disinfection of the dressing change carts so as to minimize the risk of hospital-associated infec-tions.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To investigate the association of spleen volume with the risk of non-alcoholic fatty liver disease(NAFLD)as well as their causal relationship.Methods We included 90 NAFLD cases and 47 healthy controls who had received contrast-enhanced computed tomography(CT)scan of the abdomen at the Second Affiliated Hospital of Xi'an Jiaotong University from November 2022 to November 2023.We conducted three-dimensional reconstruction of the spleen through a deep learning network model using a two-stage coarse-to-fine segmentation approach.We compared the two groups using the two-sample t test or Mann-Whitney U test for continuous data and using the chi-square test for categorical data;evaluated the correlation between spleen volume and liver function indicators through Pearson correlation or Spearman rank correlation analyses;determined the factors influencing the development of NAFLD through multivariable Logistic regression analysis;and further assessed the casual relationship between spleen volume and NAFLD using the inverse variance-weighted two-sample Mendelian randomization(IVW-MR)method.Results Spleen volume was significantly larger in NAFLD cases than in controls(272.93±104.16 vs 204.37±81.20 cm3,P<0.001).The Spearman rank correlation analysis showed that spleen volume was positively correlated with the hepatic steatosis index(rs=0.422,P<0.001)and gamma-glutamyl transferase levels(rs=0.211,P=0.047)in patients with NAFLD.The multivariable Logistic regression analysis indicated that spleen volume was an independent risk factor for the development of NAFLD(odds ratio[OR]=1.01,95%confidence interval[CI]:1.00-1.02,P=0.049).The IVW-MR analysis detected a causal relationship between spleen volume and NAFLD(OR=1.16,95%CI:1.05-1.28,P=0.005).Conclusion Increased spleen volume may be a risk factor for the development and progression of NAFLD.Further studies are still needed to investigate the specific mechanism.

Objective To evaluate the impact of healthcare-associated infection(HAI)control culture construction on the hand hygiene(HH)compliance of health care workers(HCWs),and provide a basis for strengthening HAI management.Methods HCWs in a hospital in Xi'an City were selected as the research objects.On the occasion of World HH Day,a series of publicity activities on HH as well as HAI prevention and control were held.Pre-activi-ties period was April 1-30,2024.During May 1-31,2024,a series of publicity activities on HH as well as HAI prevention and control were carried out.The post-activities investigation period was June 1-30,2024.During De-cember 1-31,2024,HH compliance survey was carried out in batches in the whole hospital(including key depart-ments).HH compliance at different stages was compared.Results After a series of publicity activities on HH as well as HAI prevention and control,HCWs'HH compliance rate was improved.HH compliance rate of nursing staff increased from 70.15％to 85.11％;HH compliance rate of HCWs before contacting with patients increased from 47.83％to 78.38％;both with statistically significant difference(both P＜0.05).During December 1-31,2024,a batch survey on HH compliance of the whole hospital(including key departments)showed that the HH compliance rates of medical and nursing staff in key departments were higher than those of the whole hospital,and the differences were statistically significant(all P＜0.05).HH compliance rates before aseptic operation and after contacting with patients in key departments were both higher than those of the whole hospital,and the differences were statistically significant(all P＜0.05).Conclusion Publicity activities on HH as well as HAI prevention con-trol can improve HH compliance rate of HCWs.HAI managers should pay more attention to the general depart-ments and improve HH compliance rate of HCWs.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.