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.

BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis＜10°),compensated group(10°＜pelvic incidence-lumbar lordosis＜20°),and decompensated group(pelvic incidence-lumbar lordosis＞20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P＜0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P＜0.01),and decreases in hip-knee-angle,and knee flexion angle(P＜0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P＜0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P＜0.05)and a significant increase in pelvic incidence-lumbar lordosis(P＜0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P＜0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.

BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis＜10°),compensated group(10°＜pelvic incidence-lumbar lordosis＜20°),and decompensated group(pelvic incidence-lumbar lordosis＞20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P＜0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P＜0.01),and decreases in hip-knee-angle,and knee flexion angle(P＜0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P＜0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P＜0.05)and a significant increase in pelvic incidence-lumbar lordosis(P＜0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P＜0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.

ObjectiveTo investigate the correlation between sleep patterns and myopia progression among younger school-age children at a primary school in Changning District of Shanghai, based on the data from the Shanghai Students’ Common Diseases and Health Influencing Factors Monitoring System and a sleep-specific survey, so as to provide data support for myopia prevention and control in this age group. MethodsOne primary school was selected from the common diseases and health influencing factors monitoring system for students in Changning District, Shanghai. A total of 230 first-grade students were included in the study. Myopia and refractive parameters were examined, and sleep patterns were investigated. General demographic characteristics and myopia-related behavior data of the students were also collected. Sleep patterns were evaluated in terms of sleep duration, sleep efficiency, and sleep quality, with the latter assessed using the Chinese version of the Children’s Sleep Habits Questionnaire (CSHQ). Multiple linear regression and binary logistic regression models were used to analyze the association between sleep patterns and myopia progression among these students. ResultsThe results of the regression analyses revealed that the total CSHQ score of the students at baseline survey was (48.85±7.15) points. Their sleep efficiency was (94.49±8.48)%, sleep duration was (9.58±0.93) hours, and the proportion of those with insufficient sleep (<10 hours) was 78.26%. At baseline survey, students’ higher daytime sleepiness scores were associated with lower spherical equivalent (SE) ( β=-0.18, 95%CI: -0.31 to -0.04) and an increased risk of axial length (AL) / corneal radius (CR) ratio >3 (OR=1.52, 95%CI: 1.00 to 2.29), whereas longer sleep duration and higher sleep efficiency were associated with higher SE (β=0.18, 95%CI: 0.05 to 0.32; β=0.17, 95%CI: 0.04 to 0.31, respectively), shorter (AL) (β=-0.15, 95%CI: -0.27 to -0.03; β=-0.13, 95%CI: -0.25 to 0, respectively) and a reduced risk of AL /CR>3 (OR=0.70, 95%CI: 0.51 to 0.96; OR=0.73, 95%CI: 0.53 to 0.99, respectively). At baseline survey, children’s higher propensity for sleep problems (OR=1.70, 95%CI: 1.04 to 2.78), sleep resistance (OR=2.26, 95%CI: 1.36 to 3.75), and sleep anxiety scores (OR=2.15, 95%CI: 1.33 to 3.48) were all associated with an increased risk of AL/CR >3 at follow-up (all P<0.05). Furthermore, higher sleep anxiety scores predicted prolonged AL at follow-up (β=0.03, 95%CI: 0 to 0.05). According to the mixed-effects model, higher daytime sleepiness scores and prolonged sleep duration were independently linked to reduced right-eye SE (β=-0.05, 95%CI: -0.10 to 0, P<0.05) and shorter right-eye AL (β=-0.05, 95%CI: -0.10 to 0, P<0.05). ConclusionIn this school in Shanghai, there are problems of insufficient and poor-quality sleep among young children. Sleep problems such as sleep resistance, delayed sleep onset, sleep anxiety, and daytime sleepiness among children may accelerate the risk of myopia progression, while longer sleep duration and higher sleep efficiency may serve as protective factors against the occurrence and development of myopia.

ObjectiveTo analyze the association between sleep chronotypes and myopia among junior high school students in Changning District of Shanghai, and to provide scientific basis for myopia intervention in this population. MethodsThis study was conducted as a cross-sectional survey using stratified cluster sampling. Four junior high schools in Changning District were selected as the research sites. Two methods were used to assess chronotypes, including the sleep-wake pattern calculated based on sleep duration and the sleep chronotype evaluated by the Morningness-Eveningness Questionnaire-5 items (MEQ-5). Myopia status of students was determined through distant visual acuity examination combined with non-cycloplegic computerized refraction. The χ2 test or t test was used to compare the distribution differences of sleep chronotypes between the myopic and non-myopic groups. Furthermore, a multivariate logistic regression model was used to analyze the association between sleep chronotypes and myopia. Statistical analyses were performed using SPSS 27.0 software. ResultsA total of 801 middle school students participated in this survey, with a screening-based prevalence of myopia of 81.77%. Univariate analyses showed that both the sleep chronotype calculated based on the sleep-wake pattern (χ²=4.54, P=0.033) and the sleep chronotype assessed by the MEQ-5 (χ²=12.75, P=0.013) were statistically associated with myopia. After adjusting for grade, maternal age at birth, parental myopia, frequency of weekend outdoor activities, and sleep duration, multivariate analyses indicated that a higher grade (e.g., grade 9: OR=3.63, 95%CI=1.92‒6.87) and myopia in both parents (OR=2.73, 95%CI=1.23‒6.06) were associated with a higher risk of myopia. In contrast, older maternal age at birth (OR=0.64, 95%CI=0.49‒0.85) and more frequent weekend outdoor activities (e.g., 1‒2 times per week: OR=0.21, 95%CI=0.05‒0.88; ≥5 times per week: OR=0.16, 95%CI=0.04‒0.71) were associated with a lower risk of myopia. The association between MEQ-5 chronotype and myopia was not statistically significant after multivariate adjustment (P=0.124). However, compared with the “absolute evening type”, the odds ratios (ORs) for myopia risk across sleep chronotypes decreased from 3.22 (moderate evening type) to 0.57 (absolute morning type), with fluctuations in between (0.95 for the “intermediate type” and 0.98 for the “moderate morning type”). ConclusionA sleep chronotype tending toward the “evening type” in junior high school students may be associated with an increased risk of myopia, and this association requires further prospective studies to validate.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

Pregnancy complicated by aortic root aneurysm in patients with Marfan syndrome is one of the main causes of termination of pregnancy or even death in pregnant women. A very small number of pregnant women require cardiac surgery to preserve pregnancy under extracorporeal circulation, and all surgeries use aortic root replacement. We reported a 30-year-old patient with severe aortic regurgitation combined with giant aortic root aneurysm and Marfan syndrome in mid-pregnancy. Valve-sparing root replacement using reimplantation technology was performed via a multidisciplinary cooperation model. This not only achieved the patient’s desire to continue pregnancy but also avoided the anticoagulation and bleeding complications brought by mechanical valve replacement, reduced pregnancy risks and improved long-term quality of life. Postoperative echocardiography showed a small amount of aortic valve regurgitation, aortic valve coaptation height of 0.6 cm, effective height of 1.1 cm, maximum aortic flow velocity of 1.4 m/s, mean transvalvular pressure gradient of 4.4 mm Hg, and satisfactory clinical results.

In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Objective: To explore the relationship between visual acuity and physical fitness of university freshmen, so as to provide reference for myopia prevention and control for freshmen. Methods: From October to November 2022, 2 160 college freshman without majoring in public safety administration, selected from Guangxi Police College in 2022 by using the stratified cluster random sampling method, were reviewed for the results of visual acuity test and physical fitness scores. The physical fitness indices were evaluated by using the Z scores of physical fitness test scores, and the strength of association between the level of physical fitness index and myopia was analyzed by using Logistic regression model. Results: Among 2 160 college freshman without majoring in public safety administration, 917 (42.5%) students were diagnosed screening myopia, including 66 (3.1%) cases of high myopia, 383 (17.7%) cases of moderate myopia and 468 (21.7%) cases of mild myopia. The differences in the distribution of visual acuity tests among students with different physical fitness indices, body mass index, and gender were statistically significant ( Z/H=54.50, 49.53, 15.51, P <0.01). Low level and low middle level physical fitness indices were associated with screening myopia among freshmen[ OR (95% CI )=2.81(1.93-4.08),1.87(1.38-2.54)], and low level physical fitness indexes were associated with high myopia [ OR (95% CI )=7.22(2.33-22.32)] ( P <0.01). Conclusions Screening myopia among college freshman without majoring in public safety administration is related to physical fitness, and low level and low middle level physical fitness index are risk factors for myopia. Improving the level of physical fitness might be effective in preventing myopia.