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.

Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

To investigate the phenotype and genomic characterization of a mucoid-type Salmonella Saintpaul ST50 isolate from a urinary tract infection patient,promoting clinical diagnosis and treatment for urinary tract infections caused by Salmo-nella spp.Culture-based quantitative counts of midstream urine sample from the patient were conducted,and further biochemi-cal identification,mass spectrometry detection,serum agglutination test and antimicrobial susceptibility test(AST)were con-ducted on Salmonella isolate(2024JD5).Whole-genome sequencing(WGS)was performed on isolate 2024JD5 to predict sero-type,multilocus sequence type(MLST),resistance genes,and virulence genes.Two smooth-type of Salmonella Saintpaul ST50 were selected as comparative genomic reference strains from the Chinese local Salmonella genome database.The literature reviews of global Salmonella serotype of urinary tract infection were summarized.Specific serum agglutination confir-mation of isolate 2024JD5 failed due to characterization of the mucus type.The strain 2024JD5 was predicted as Salmonella Saintpaul(4,5,12:e,h:1,2)ST50 using WGS,and was resistant to ciprofloxacin,nalidixic acid,chloramphenicol and tetracy-cline with carrying aminoglycoside resistance genes aac(6')-Ⅰaa and aph(3)-Ⅱa,chloramphenicol resistance gene floR,tetra-cycline resistance gene tet,quinolone resistance gene qnrS1,and S83Y substitution in the gyrA gene was found in the quinolo-ne resistance determination region(QRDR).In addition,the strain 2024JD4 carried six types of non-plasmid-based mobile ge-netic elements and 144 virulence genes,including 71 secretion transporter genes and 58 fimbriae adhesion genes,respectively.Four types of fimbriae regulatory genes(csgB,csgC,fimW,fimY)were absent in comparison with smooth-type Salmonella Saintpaul.The literature reviews showed Salmonella Saintpaul was currently a rare Salmonella serotype in cases of urinary tract infections worldwide.Salmonella Saintpaul ST50 with mucoid-type is the pathogen of urinary tract infection with multi-drug resistant phenotypic and genotypic characteristics,and the high mucoid expression may be related to the compensatory mechanism of fimbriae regulatory genes absence in urinary tract colonization and adaptation.WGS combined with the Chinese local Salmonella genome database can effectively solve the diagnosis and biosafety assessments of rare Salmonella phenotypes.

The patent data in the key technology field of capsule endoscopy industry was retrieved in IncoPat Global Patent Database from January 1,2003 to December 31,2022,and the development trend of key technologies and patent competition in the global capsule endoscopy industry were analyzed in terms of the applicant,concentration of China's patent applications and regional layout.It's pointed out Japan's Olympus company gained advantages in the key technology field,the enterprise played a main role in the innovation of the key technology field,the main exporters and target markets included the United States,South Korea,Japan and China and China became more and more important for the innovation of the key technology field.References were provided for the technology development of capsule endoscopy industry in China.[Chinese Medical Equipment Journal,2025,46(5):60-65]

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective To investigate the effect of Tan Ⅰ on SA-AKI in rats by mediating Wnt/β-catenin signaling pathway.Methods Sprague-Dawley rats were randomly divided into the following groups(n=8 per group,including 2 reserve animals per group):Sham,SA-AKI,SA-AKI+5 mg/kg Tan I,SA-AKI+10 mg/kg Tan I,SA-AKI+15 mg/kg Tan I(SA-AKI+Tan I),SA-AKI+salinomycin sodium(SS,Wnt signal inhibitor,SA-AKI+SS),SA-AKI+SS+Tan I,SA-AKI+laduviglusib(LG,Wnt signal activator,SA-AKI+LG),and SA-AKI+LG+Tan I.Rat SA-AKI model was induced by cecal ligation and puncture(CLP),with Tan I,SS,and LG administered via intraperitoneal injection.Hematoxylin-eosin and TUNEL staining were used to observe renal tissue pathological damage.Enzyme-linked immunosorbent assay was used to detect serum concentrations of neutrophil gelatinase-associated lipocalin(NGAL),IL-1β,IL-8,IL-6,and TNF-α.Creatinine(Cre)and blood urea nitrogen(BUN)kit were used to detect serum Cre and BUN concentrations.Western blot and immunofluorescence staining were used to detect the expression and fluorescence intensity of Wnt1,GSK3β,and β-catenin.Results Administration of Tan I at doses of 10 mg/kg and 15 mg/kg significantly attenuated renal injury in rats with SA-AKI(P<0.05),suppressed the levels of SA-AKI biomarkers NGAL,Cre,and BUN and pro-inflammatory cytokines(P<0.05),reduced apoptosis,and downregulated Wnt1 and GSK3β while upregulating β-catenin expression(P<0.05).Although Tan I at 5 mg/kg exhibited a modest protective effect against SA-AKI in rats,no statistically significant difference was observed compared to the sham group(P>0.05).SS weakened CLP-induced kidney injury and the production of inflammatory cytokines in rats(P<0.05),and LG further aggravated CLP-induced kidney injury in rats(P<0.05).Tan Ⅰ reversed the promoting effect of LG on kidney injury in SA-AKI rats(P<0.05).Conclusion Tan Ⅰ provides a protective effect on CLP-induced SA-AKI rat by inhibiting Wnt/β-catenin signaling pathway.