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:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective This study aims to establish a hidden curriculum-based medical humanities teaching pathway within surgical internship education and evaluate its effectiveness in enhancing students' humanistic care competence.Methods A single-group pre-test and post-test design was adopted.A total of 76 interns from a tertiary teaching hospital in 2024 were in-cluded.A five-dimensional hidden curriculum framework—material,spiritual,behavioral,faculty,and institutional—was con-structed.Humanistic competence was assessed before and after the intervention using the Humanistic Professional Awareness Scale for Healthcare Students and Providers(HPAS-HSP).Results Post-intervention scores significantly improved compared to pre-intervention across the total scale in the three dimensions:personal integrity and responsibility,sensitivity to others,and pro-fessional competence(P＜0.05),with the greatest improvement observed in sensitivity to others.Conclusion The structured hidden curriculum is effective in enhancing medical students' humanistic qualities,especially in fostering emotional resonance and professional identity.Future work should focus on verifying behavioral transformation and developing multi-source evaluation sys-tems to improve effectiveness and applicability.

Objective This study aims to establish a hidden curriculum-based medical humanities teaching pathway within surgical internship education and evaluate its effectiveness in enhancing students' humanistic care competence.Methods A single-group pre-test and post-test design was adopted.A total of 76 interns from a tertiary teaching hospital in 2024 were in-cluded.A five-dimensional hidden curriculum framework—material,spiritual,behavioral,faculty,and institutional—was con-structed.Humanistic competence was assessed before and after the intervention using the Humanistic Professional Awareness Scale for Healthcare Students and Providers(HPAS-HSP).Results Post-intervention scores significantly improved compared to pre-intervention across the total scale in the three dimensions:personal integrity and responsibility,sensitivity to others,and pro-fessional competence(P＜0.05),with the greatest improvement observed in sensitivity to others.Conclusion The structured hidden curriculum is effective in enhancing medical students' humanistic qualities,especially in fostering emotional resonance and professional identity.Future work should focus on verifying behavioral transformation and developing multi-source evaluation sys-tems to improve effectiveness and applicability.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Bovine coronavirus(BCoV)can cause diarrhea in calves,as well as respiratory diseases,and lead to the death of calves in severe cases,resulting in great economic losses to the cattle pro-duction.BCoV is highly prevalent and widely spread.So far in China there is no independently de-veloped vaccine against BCoV on the market.In this study,the most conserved N gene of BCoV was first selected to construct a prokaryotic expression vector,and the N protein was expressed and purified;subsequently,BALB/c mice were immunized with BCoV N protein combined with Freund's adjuvant,and the antibody potency,the proportion of splenic T-lymphocyte subpopulation and the cytokine release of the immunized mice were detected by ELISA and flow cytometry.The results showed that a soluble BCoV N protein about 55 kDa in size was successfully obtained.The ELISA test showed that the antibody potency of serum IgG and IgA was 1∶51 200 and 1∶3 200,respectively,in mice immunized with BCoV N protein combined with Freund's adjuvant.The flow cytometry test showed that the percentage of CD4+/CD8+T-lymphocytc subsets was extremely higher in the immunized mice(P＜0.01),and the release of TNF-α was significantly higher(P＜0.05),producing a cellular immune response biased towards the Th1 type in comparison with that in control mice.It is indicated that the soluble expression of BCoV N protein can be successfully a-chieved by the prokaryotic expression system,and the obtained BCoV N protein presents good im-munogenicity which induces strong humoral,mucosal and cellular immune responses in the immu-nized mice.Our study provides an important technical support for the development of a safe and ef-fective BCoV subunit vaccine.

Bovine coronavirus(BCoV)can cause diarrhea in calves,as well as respiratory diseases,and lead to the death of calves in severe cases,resulting in great economic losses to the cattle pro-duction.BCoV is highly prevalent and widely spread.So far in China there is no independently de-veloped vaccine against BCoV on the market.In this study,the most conserved N gene of BCoV was first selected to construct a prokaryotic expression vector,and the N protein was expressed and purified;subsequently,BALB/c mice were immunized with BCoV N protein combined with Freund's adjuvant,and the antibody potency,the proportion of splenic T-lymphocyte subpopulation and the cytokine release of the immunized mice were detected by ELISA and flow cytometry.The results showed that a soluble BCoV N protein about 55 kDa in size was successfully obtained.The ELISA test showed that the antibody potency of serum IgG and IgA was 1∶51 200 and 1∶3 200,respectively,in mice immunized with BCoV N protein combined with Freund's adjuvant.The flow cytometry test showed that the percentage of CD4+/CD8+T-lymphocytc subsets was extremely higher in the immunized mice(P＜0.01),and the release of TNF-α was significantly higher(P＜0.05),producing a cellular immune response biased towards the Th1 type in comparison with that in control mice.It is indicated that the soluble expression of BCoV N protein can be successfully a-chieved by the prokaryotic expression system,and the obtained BCoV N protein presents good im-munogenicity which induces strong humoral,mucosal and cellular immune responses in the immu-nized mice.Our study provides an important technical support for the development of a safe and ef-fective BCoV subunit vaccine.

Objective To study the stability of plate-assisted intramedullary nailing for fixing proximal third tibiafractures, compare and observe biomechanical characteristics of anterolateral or posteromedial plate-assisted intramedullary nailing after fixation of proximal third tibia fractures. Methods Eight artificial tibia of 4th-generation sawbones were divided into two groups based on location of the assisted plate, namely, anterolateral plate group and posteromedial plate group, with 4 specimens in each group. Each two locking bolts were fixed to theintramedullary nail proximally and distally, and each three bicortical screws were fixed to the plate proximally and distally. The specimens were osteotomized with a 10-mm defect which located 0. 5 cm to the proximal locking bolt of intramedullary nail or 5-6 cm distally to the knee joint line, in order to simulate an AO/ OTA 41-A2 type proximal third tibia fracture after fixation of intramedullary nail. After osteotomy was finished, axial compression test, three point bending test, cyclic loading and overstress test were conducted by mechanical testing machine. The results of axial stiffness and three-point stiffness between two groups were compared and analyzed. Results Axial compression test showed that the average axial stiffness in posteromedial plate group was lower than that in anterolateral plate group, but no significantly statistical differences were found between the two groups. Three point bending test showed that the average bending stiffness in posteromedial plate group was significantly higher than that in anterolateral plate group when stimulating either varus stress (plate located at pressure side of the fracture, t = 3. 679, P<0. 05) or valgus stress (plate located at tension side of the fracture, t = 8. 975, P<0. 05). Conclusions Plate-assisted intramedullary nailing for fixation of proximal third tibia fractures can minimize the angulation malalignment, improve the stability of nailed proximal tibial fragment and allow the early weight bearing. Both anterolateral and posteromedial plate-assisted intramedullary nail can provide satisfactory axial stability for proximal third tibia fractures, while posteromedial plate-assisted intramedullary nail shows better bending stability than anterolateral plate in countering varus or valgus stress deformity. This study provides an essential basis for clinical decision making about plate-assisted intramedullary nailing for fixing proximal third tibia fractures.

Objective To evaluate the effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022, so as to provide insights into formulation of future control interventions. Methods Data pertaining to comprehensive echinococcosis control measures with emphasis on management of infectious source and echinococcosis surveillance in Sichuan Province from 2010 to 2022 were collected. The effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source was evaluated with prevalence of human echinococcosis, detection of newly diagnosed echinococcosis patients, prevalence of Echinococcus infection in domestic dogs, prevalence of cystic echinococcosis in livestock, prevalence of alveolar echinococcosis in small mammals and awareness of echinococcosis control knowledge, and Spearman’s rank correlation analysis. Results The prevalence of human echinococcosis reduced from 1.08% in 2010 to 0.40% in 2022 in Sichuan Province (χ² = 1 482.97, P < 0.05), with a reduction from 0.30% to 0.02% in the detection of newly diagnosed echinococcosis cases (χ² = 2 776.41, P < 0.05), a reduction from 15.87% to 0.46% in the prevalence of Echinococcus infection in domestic dogs (χ² = 20 823.96, P < 0.05), a reduction from 8.05% to 1.07% in the prevalence of cystic echinococcosis in livestock (χ² = 1 296.02, P < 0.05), and the awareness of echinococcosis control knowledge increased from 50.65% to 95.24% (χ² = 34 938.63, P < 0.05); in addition, there was a year-specific prevalence rate of alveolar echinococcosis in small mammals (χ² = 164.07, P < 0.05). Spearman’s rank correlation analysis revealed that the detection of newly diagnosed echinococcosis cases correlated positively with the prevalence of Echinococcus infections in domestic dogs (r_s = 0.823, P < 0.05) and the prevalence of cystic echinococcosis in livestock (r_s = 0.795, P < 0.05), and correlated negatively with the awareness of echinococcosis control knowledge (r_s = − 0.918, P < 0.05), and the prevalence of Echinococcus infection in domestic dogs correlated positively with the prevalence of cystic echinococcosis in livestock (r_s = 0.753, P < 0.05) and negatively with the awareness of echinococcosis control knowledge (r_s = −0.747, P < 0.05); however, there was no correlation between the prevalence of Echinococcus infections in domestic dogs and the prevalence of alveolar echinococcosis in small mammals (r_s = −0.750, P > 0.05). Conclusions The comprehensive echinococcosis control measures with emphasis on management of infectious source had achieved remarkable effectiveness in Sichuan Province; however, the transmission chain of echinococcosis has not been interrupted. Reinforced comprehensive echinococcosis control measures with emphasis on management of infectious source and sustained tracking evaluation of the effectiveness are recommended in Sichuan Province.

Objective:To analyze the therapeutic effect of 3D printing technology combined with locking plate fixation on femoral shaft fracture in patients with femoral deformity.Methods:The clinical data of 33 patients with femoral shaft fracture with femoral deformity who met the inclusion criteria and underwent locking plate fixation in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from June 2014 to December 2020 were retrospectively analyzed. The patients were divided into 3D printing group ( n=18) and control group ( n=15) according to whether 3D printing was performed before operation. The 3D printing group including 11 males and 7 females with an age of (46.78±13.76) years.The control group including 9 males and 6 females with an age of (48.20±14.27) years.The operation time, intraoperative blood loss, fracture healing time and complications of the two groups were recorded. Visual analogue scale (VAS) scores of pain were evaluated before and 6, 12, 24, 48 and 72 h after operation. According to the Harris hip score, the Hospital for Special Surgery (HSS) knee score and The MOS 36-item short-from Health Survey (SF-36), the hip and knee function and quality of life of the patients before and 12 months after injury were evaluated. The measurement data were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data between groups was conducted by Chi-square test or Fisher exact probability. Results:The operation time, intraoperative blood loss, and incidence of complications in the 3D printing group were (91.50±9.07) min, (191.11±16.01) mL, and 0(0/18), respectively, and those in the control group were (118.07±14.19) min, (270.27±17.59) mL, and 26.7% (4/15), the differences between the two groups were statistically significant ( P <0.05). The pain VAS scores of the 3D printing group were significantly better than those of the control group at 6, 12, 24, 48, and 72 h after operation ( P<0.05). There were no differences in fracture healing time and preoperative pain VAS between the two groups( P>0.05). There were no significant differences in hip function, knee function and quality of life scores between the two groups before injury and 12 months after injury( P>0.05). Conclusion:In the treatment of femoral shaft fractures in patients with femoral deformity with locking plate fixation, the application of 3D printing technology can be used for preoperative design and plate preshaping, which can shorten the operation time, reduce the amount of intraoperative blood loss, reduce the VAS of pain and the incidence of complications, improve the satisfaction of surgery, and provide a new option for the treatment of femoral shaft fractures in patients with femoral deformity.