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 investigate the main causes of failed endoscopic retrograde cholangiopancreatography (ERCP) in children and the remedial treatment strategies.Methods:This retrospective cohort study analyzed the clinical data of 21 children who experienced failed ERCP at Beijing Children′s Hospital, Capital Medical University between January 2021 and December 2024. Data was collected included demographic information, clinical diagnoses, and ERCP outcomes. The annually trend in the ERCP failure rate was analyzed. Patients were categorized by etiology into the following groups: chronic pancreatitis, post-surgical status, pancreatic trauma, pancreas divisum, non-neoplastic pancreatic lesions, and ulcerative colitis. The relationship between etiologies and ERCP failure was analyzed by Fisher exact test.Results:A total of 175 ERCP procedures were included, of which 21 procedures failed (12.0%). The failure rate decreased annually from 2021 to 2024: 18.2% (4/22), 13.2% (5/38), 11.4% (5/44), and 9.9% (7/71), respectively. The etiological distribution among the 21 failed cases was as follows: chronic pancreatitis 28.6% (6/21), pancreatic duct stenosis following pancreatic trauma 23.8% (5/21), post-surgical status 14.3% (3/21), pancreas divisum 9.5% (2/21), acute pancreatitis 9.5% (2/21), non-neoplastic pancreatic lesions 9.5% (2/21), and pancreatic duct stenosis associated with ulcerative colitis 4.8% (1/21). Remedial treatments included surgical intervention (2 cases), ultrasound-guided percutaneous drainage (3 cases), and repeat ERCP (2 cases). For post-surgical and pancreatic trauma patients, failure was primarily due to bile duct stenosis, pancreatic duct stenosis, or pancreaticobiliary duct disruption. Active surgical interventions such as cholangiojejunostomy and pancreaticojejunostomy, and ultrasound-guided drainage following ERCP failure led to significant clinical improvement.Conclusions:A stratified management approach guided by etiology is essential following failed ERCP in children. Early and active remedial treatment, particularly surgical interventions, is recommended for post-surgical and pancreatic trauma cases.

Breast cancer has become the malignant tumor with the highest incidence rate among women， seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia， and from pre-cancerous lesions to cancerous lesions， is a long-term progressive process. Therefore， early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer， which is mainly based on surgery and systemic treatment， whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer， surgery is also the mainstay of treatment. In recent years， traditional Chinese medicine （TCM） has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions， TCM compound prescriptions， single herbs or herb pairs， and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion， promote the apoptosis and autophagy of tumor cells， and regulate the cell cycle and the immune microenvironment， thus exerting anti-tumor effects. At the same time， they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However， the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， and Notch， which still need to be verified by a large number of clinical and experimental studies. Therefore， this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years， aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.

Objective:To investigate the main causes of failed endoscopic retrograde cholangiopancreatography (ERCP) in children and the remedial treatment strategies.Methods:This retrospective cohort study analyzed the clinical data of 21 children who experienced failed ERCP at Beijing Children′s Hospital, Capital Medical University between January 2021 and December 2024. Data was collected included demographic information, clinical diagnoses, and ERCP outcomes. The annually trend in the ERCP failure rate was analyzed. Patients were categorized by etiology into the following groups: chronic pancreatitis, post-surgical status, pancreatic trauma, pancreas divisum, non-neoplastic pancreatic lesions, and ulcerative colitis. The relationship between etiologies and ERCP failure was analyzed by Fisher exact test.Results:A total of 175 ERCP procedures were included, of which 21 procedures failed (12.0%). The failure rate decreased annually from 2021 to 2024: 18.2% (4/22), 13.2% (5/38), 11.4% (5/44), and 9.9% (7/71), respectively. The etiological distribution among the 21 failed cases was as follows: chronic pancreatitis 28.6% (6/21), pancreatic duct stenosis following pancreatic trauma 23.8% (5/21), post-surgical status 14.3% (3/21), pancreas divisum 9.5% (2/21), acute pancreatitis 9.5% (2/21), non-neoplastic pancreatic lesions 9.5% (2/21), and pancreatic duct stenosis associated with ulcerative colitis 4.8% (1/21). Remedial treatments included surgical intervention (2 cases), ultrasound-guided percutaneous drainage (3 cases), and repeat ERCP (2 cases). For post-surgical and pancreatic trauma patients, failure was primarily due to bile duct stenosis, pancreatic duct stenosis, or pancreaticobiliary duct disruption. Active surgical interventions such as cholangiojejunostomy and pancreaticojejunostomy, and ultrasound-guided drainage following ERCP failure led to significant clinical improvement.Conclusions:A stratified management approach guided by etiology is essential following failed ERCP in children. Early and active remedial treatment, particularly surgical interventions, is recommended for post-surgical and pancreatic trauma cases.

Objective:To investigate the therapeutic effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and stent implantation in the treatment of pancreaticobiliary injuries in children.Methods:A retrospective analysis was conducted on the clinical data of children diagnosed with pancreaticobiliary injury and undergoing ERCP and stent implantation at Beijing Children′s Hospital, Capital Medical University from January 2021 to December 2022. Demographic information, clinical data, endoscopic treatment methods, postoperative complications and clinical prognosis of the children were collected. The etiology, location of pancreaticobiliary injury, occurrence of complications after endoscopic treatment, and the time for improvement and recovery after endoscopic treatment were analyzed. The patients were divided into five groups according to the etiologies of pancreaticobiliary duct injuries: post-surgical, pancreatic trauma, acute pancreatitis, chronic pancreatitis, and systemic lupus erythematosus groups. They were also classified into four groups according to the sites of pancreaticobiliary duct injuries: common bile duct, pancreatic head, pancreatic body, and pancreatic tail groups. Multi-factor analysis of variance was used for comparing the time of improvement and recovery among different groups.Results:Among 22 patients, there were 8 males and 14 females, and the age was 7.5 (3.3,10.8) years. There were 19 cases of pancreatic or bile duct fistula, and 3 cases of pancreatic or bile duct stenosis. A total of 33 endoscopic procedures were performed on the 22 patients, out of which, 3 duct stenosis were failed to insert the stent because the catheter failed to pass through the stenosis site. The success rate was 91% (30/33). The pancreatic duct or bile duct stent was inserted, with the stent located at pancreatic or bile duct fistula. Postoperative complications included pancreatitis in 3 cases (9%, 3/33), hyperamylasemia in 5 cases (15%, 5/33), and postoperative infection in 4 cases (12%, 4/33). All patients were followed up for more than 1 year. Significant improvement was observed in external drainage and imaging monitoring among patients with successfully placed stents. There was no significant difference in the improvement time of ERCP in the treatment of pancreaticobile duct injury caused by different etiology ( F=0.65, P=0.637). However, there were significant differences in healing time ( F=6.46, P=0.004), among which the healing time of injuries caused by systemic lupus erythematosus was significantly different from that after surgery, trauma, acute pancreatitis and chronic pancreatitis (all P<0.05). There was no significant difference in the improvement and healing time among different injury sites (all P>0.05). Conclusions:ERCP and stent implantation can safely and effectively improve the clinical symptoms of children with pancreaticobiliary injury. Early intervention can improve long-term prognosis.

Objective:To study the relationship between urinary arsenic methylation metabolism patterns and skin keratinization and pigmentation abnormalities in population exposed to arsenic through drinking water.Methods:Using a cross-sectional study method, a survey on endemic arsenic poisoning was conducted among permanent residents of drinking water endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region in 2004 (before water improvement). In 2017 (after water improvement), 71 arsenic exposed individuals were followed up as survey subjects. According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the clinical grading of skin injuries (skin keratinization, pigmentation abnormalities) in the survey subjects was evaluated. Urine samples were collected for detection of arsenic methylation metabolite levels by high-performance liquid chromatography inductively coupled plasma mass spectrometry and calibrated with urinary creatinine. The changes and amplitudes of urinary arsenic methylation indicators before and after water improvement were calculated and analyzed according to the outcome of skin keratinization and pigmentation abnormalities which were divided into reduced, unchanged, and added groups.Results:(1) The changes in urinary total arsenic (TAs), inorganic arsenic (iAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) levels in different outcome groups of skin keratinization were compared, and the differences were statistically significant ( H = 9.08, 8.77, 9.28, 8.57, P < 0.05). The changes in urinary TAs, iAs, MMA, DMA levels, iAs percentage (iAs%), DMA percentage (DMA%), and primary methylation index (PMI) in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 8.04, 10.67, 8.29, 9.14, 6.30, 9.10, 7.20, P < 0.05). (2) The comparison of amplitudes in urinary TAs, iAs, MMA, and DMA levels in different outcome groups of skin keratinization showed statistically significant differences ( H = 6.92, 7.34, 6.66, 6.16, P < 0.05). The amplitudes in urinary iAs level, iAs%, DMA%, and PMI in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 7.94, 7.61, 9.95, 7.22, P < 0.05). Conclusion:The changes pattern of urinary TAs, iAs, MMA, DMA, iAs%, DMA%, and PMI in population exposed to arsenic through drinking water is related to the transformation of skin keratinization and pigmentation abnormalities.

Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.

Objective:To study the application value of biomimetic model combined with scenario simulation in the training of otolaryngology skills.Methods:This study included 21 residents who underwent standardized residency training in the Department of Otolaryngology of the Second Hospital of Dalian Medical University from March to October 2023. The application of a teaching method combining biomimetic model and scenario simulation was evaluated by comparing pre- and post-training performance in terms of operation time, pass rate, and success rate. SPSS 23.0 was used for the paired sample t test and paired chi-square test. Results:Significant improvements were observed in several key indicators after training, including foreign body detection rate [(11/21) vs. (19/21)], number of assistance requests during using forceps [(1.62±0.92) vs. (0.90±0.94)], the number of touching the lateral pharyngeal wall [(4.62±0.92) vs. (1.90±1.34)], residual body incidence [(12/21) vs. (2/21)], operation time [(26.52±3.61) vs. (22.76±4.55)], and suture time [(19.10±2.98) vs. (15.24±1.18)]. Number of requests for tonsillectomy [(2.90 ± 1.04) vs. (0.86 ± 0.48)]( P<0.05). Conclusions:The combination of 3D biomimetic model with scenario simulation not only compensates for the limited practical training in otolaryngology and meets the requirements of clinical teaching, but also provides new ideas and methods for the reform of teaching otolaryngology. This approach is feasible for implementation in other training centers of similar scale.

BACKGROUND:Dexamethasone and hindlimb suspension are commonly used methods for modeling sarcopenia in animal experiments due to their short modeling time,ease of operation,and low cost.OBJECTIVE:To compare the differences in muscle mass,strength and functional phenotypes and molecular mechanisms between two mouse sarcopenia models induced by dexamethasone and hindlimb suspension.METHODS:Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group).The normal control group received no intervention.The dexamethasone group received daily intraperitoneal injections of 1 mg/kg/d dexamethasone sodium phosphate solution for 6 continuous days to establish sarcopenia models in mice,while mice in the hindlimb suspension group were suspended by tail harness for 16 hours,once per day,to establish sarcopenia models.Within 6 weeks after modeling,changes in body mass were monitored.After 6 weeks of modeling,mice were tested for limb grip strength,mobility(swimming test),skeletal muscle wet mass,and skeletal muscle pathological morphology.Expressions of skeletal muscle protein synthesis and catabolism indexes as well as the AMPK/FoXO3α signaling pathway were detected by RT-PCR and western blot.RESULTS AND CONCLUSION:(1)Two weeks after modeling,both dexamethasone and hindlimb suspension groups showed a significant decrease in body mass compared with the normal control group(P<0.001).After 6 weeks of modeling,grip strength of mice in both dexamethasone and hindlimb suspension groups was lower than that in the normal control group(P<0.001).The wet mass of gastrocnemius and extensor digitorum longus muscles and the cross-sectional area of gastrocnemius and soleus muscles in the dexamethasone group were lower than those in the normal control group(P<0.05).Compared with the hindlimb suspension group,the cross-sectional area of gastrocnemius muscle was significantly smaller in the dexamethasone group(P<0.05),while the cross-sectional area of soleus muscle was larger in the dexamethasone group(P<0.05).Mice in the dexamethasone group had reduced mobility when compared with those in the normal control group and the hindlimb suspension group(P<0.05).(3)Compared with the normal control group,PI3K,mTOR,AMPK,and PGC-1α mRNA expression and P-AMPK/AMPK protein were decreased in the two modeling groups(P<0.05),and FoXO3α mRNA expression and PGC-1α and FoXO3 protein expression were elevated(P<0.05);in the dexamethasone group,Akt1 mRNA expression was decreased(P<0.05),while Atrogin-1 and MuRF-1 mRNA expression was elevated(P<0.05);in the hindlimb suspension group,Akt1 mRNA expression was elevated(P<0.05).(4)Compared with the dexamethasone group,mTOR,Akt1,and FoXO3α mRNA expression was elevated in the hindlimb suspension group(P<0.05),while Atrogin-1 and MuRF-1 mRNA expression was decreased(P<0.05).To conclude,both modeling methods could decrease the levels of mitochondrial energy metabolism in skeletal muscle,with the dexamethasone group mediating atrophy of skeletal muscle through the dual action of ubiquitin proteasome and energy metabolism pathways,and the hindlimb suspension group inducing atrophy of skeletal muscle by mediating the energy metabolism pathway through the AMPK/FoXO3α signaling pathway,subsequently causing a reduction in mass,strength,and function of skeletal muscle.

Objective:To analyze the evolution and diffusion characteristics of policies related to life expectancy(LE)and healthy life expectancy(HLE)in China from 1982 to 2024 using a biometric approach to policy analysis,revealing the patterns of policy diffusion.Methods:By retrieving databases such as PKULAW.com,We comprehensively collected 701 policy documents closely related to LE and HLE during the period(including 62 central policies and 639 local policies),the policy diffusion process was quantified in four dimensions:diffusion intensity,diffusion breadth,diffusion speed and diffusion direction by using the policy—reference network analysis method.Results:Related policy has gone through the germination period(1982-2001),the development period(2002-2010),the rapid rise period(2011-2015)and the four stages of innovation and pioneering period(2016—present).Policy diffusion is influenced by the hierarchical level of the issuing institution,policy type,and regional economic development level.Policies promulgated by central institutions exhibit stronger and broader diffusion,with guideline—type policies diffusing most widely.The diffusion rate follows a trend of"initial growth,followed by deceleration,and then a slight increase."The primary diffusion directions are vertical diffusion from central to local levels and horizontal diffusion among peers.Conclusion:The diffusion of policies related to LE and HLE is characterized by significant stages,regions and levels.