Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

OBJECTIVE To study the pharmacokinetic characteristics of ciprofol in pregnant and fetal rats， and provide reference for the application of ciprofol in cesarean section. METHODS Eight pregnant rats were selected. A single dose of 2.4 mg/kg of ciprofol was administered via the tail vein. One fetal rat was selected at 2， 4， 8， 12， 16， 25， 35， 45， 60， and 90 minutes respectively after ciprofol administration. Subsequently， whole blood samples were collected simultaneously from both the pregnant rats and fetal rats. HPLC-MS/MS method was used to determine the concentration of ciprofol in the bodies of pregnant and fetal rats. The ratios of fetal-to-maternal blood concentrations （F/M ratios） at each time point were calculated， and the F/M-time curves were plotted. Subsequently， non-compartmental pharmacokinetic parameters were computed using DAS 2.0 software. RESULTS Compared with pregnant rats， cmax， AUC0-90 min and AUC0-∞ of ciprofol in fetal rats were decreased significantly， while MRT was increased significantly （P＜0.05）. The F/M curve of ciprofol initially increased and then decreased， and between 0.16- 0.84， reaching a maximum value of 0.84 at 45 minutes. CONCLUSIONS Ciprofol can penetrate the placental barrier， and there are significant differences in pharmacokinetic parameters between pregnant and fetal rats. Moreover， the exposure level of ciprofol in fetal rats is much lower than that in pregnant rats. Therefore， ciprofol shows promise as an ideal anesthetic agent for cesarean section delivery.

Objective:This study aims to evaluate the application of learning cycle theory(LCT)in a university"Clinical Nutrition"general education elective course,and to compare students'knowledge,attitudes,and behaviors related to clinical nutrition before and after the course.The goal is to explore more efficient teaching models and approaches for clinical nutrition education in universities.Methods:A cluster sampling method was used to select all students enrolled in the Clinical Nutrition elective course at Nanjing University in 2024 as study participants.Based on LCT,a"Clinical Nutrition"general education elective course was designed,consisting of four modules:theoretical teaching,skills training,clinical thinking instruction,and comprehensive simulation.The course lasted 16 weeks,totaling 32 class hours.Before and after the course,a survey was administered using a self-designed questionnaire based on the Knowledge-Attitude-Practice(KAP)model to assess the effectiveness of the LCT-based course.Results:A total of 76 students completed the survey.The students'scores on clinical nutrition knowledge increased significantly,from(6.74±1.60)before the course to(7.91±1.62)after the course.Attitude scores increased from(20.87±2.39)to(22.75±1.99),and behavior scores improved from(16.99±3.59)to(18.54±3.58),with all differences being statistically significant(P<0.05).Additionally,96.05%of students reported being very satisfied or satisfied with the course.Conclusion:The LCT-based clinical nutrition general education elective course was effective in significantly improving students'knowledge,attitudes,and behaviors regarding clinical nutrition.This teaching approach could be further expanded in the future to enhance the nutrition and health levels of university students.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:To explore the effects of neutrophil extracellular traps (NET) on the proliferation and migration of breast cancer cells and the related mechanisms.Methods:The peripheral blood neutrophils were separated using density gradient centrifugation, 100 nmol/L phorbol 12-myristate 13-acetate (PMA) was used to stimulate the formation of NET. Breast cancer cell line MDA-MB-231 was selected and treated with NET (NET group) or deoxyribonucleaseⅠ (DNase Ⅰ) digested NET (NET+DNase Ⅰ group),normal cultured MDA-MB-231 cells were used as the control group. In MDA-MB-231 cells of each group; cell proliferation ability was detected using CCK-8 assay; cell migration was detected by cell scratch assay and Transwell assay; real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expressions of frizzled homolog 10 (FZD10), cyclin D1, E-cadherin and Vimentin immunofluorescence assay was performed to detect the formation of NET and the expressions of E-cadherin and Vimentin; Western blotting was used to detected the expression of FZD10-Wnt-β-catenin signaling pathway-related proteins.Results:Neutrophils were stimulated with PMA for 4 hours, and immunofluorescence assay results showed that NET exhibited fibrous reticular structure with high expression of citrullinated histone (citH3) and myeloperoxidase (MPO). The CCK-8 assay results showed that the absorbance values of cells in the control group, NET group and NET+DNase Ⅰ group were 1.25±0.06, 2.14±0.15 and 1.47±0.11, respectively, and the difference was statistically significant ( F = 80.60, P < 0.001). The results of scratch assay displayed that the percentage of wound closure in the control group, NET group and NET+DNase Ⅰ group were (36.2±1.3)%, (67.2±2.0)% and (46.3±3.2)%, respectively, and the difference was statistically significant ( F = 140.50, P < 0.001). Transwell assay indicated that the number of migrating cells in the control group, NET group and NET+DNase Ⅰ group were 317±18, 512±23 and 356±23, respectively, and the difference was statistically significant ( F = 75.39, P < 0.001). qRT-PCR assay revealed that the relative expressions of FZD10, cyclin D1 and Vimentin mRNA in the NET group were higher than those in the control group, while the relative expression of E-cadherin mRNA was lower than that in the control group, and the differences were statistically significant (all P < 0.001); the relative expressions of FZD10, cyclin D1 and Vimentin mRNA in the NET+DNase Ⅰ group were lower than those in the NET group, while the relative expression of E-cadherin mRNA was higher than that in the NET group, and the differences were statistically significant (all P < 0.001). Immunofluorescence assay indicated that the number of cells expressing Vimentin in the control group, NET group and NET+DNase Ⅰ group were 35±6, 86±13 and 51±6, respectively, and the difference was statistically significant ( F = 24.65, P = 0.001); the number of cells expressing E-cadherin were 31±4, 11±3 and 24±2, respectively, and the difference was statistically significant ( F = 38.36, P < 0.001). Western blotting results demonstrated that the relative expressions of FZD10, β-catenin and Vimentin proteins in the NET group were higher than those in the control group, while the relative expression of E-cadherin protein was lower than that in the control group; the relative expressions of FZD10, β-catenin and Vimentin proteins in the NET+DNase Ⅰ group were lower than those in the NET group, while the relative expression of E-cadherin protein was higher than that in the NET group. Conclusions:NET may promote the proliferation and migration of breast cancer cells by upregulating the expression of FZD10 and subsequently activating the Wnt-β-catenin signal pathway.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.