Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

Objective To explore the influence of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with brain-computer interface rehabilitation robot in patients with upper limb motor dysfunction after stroke.Methods A total of 126 patients with upper limb motor dysfunction after stroke were divided into the combined group(61 cases,low-frequency rTMS combined with brain-computer interface rehabilitation robot on the basis of routine rehabilitation treatment)and the magnetic stimulation group(65 cases,low-frequency rTMS on the basis of routine rehabilitation treatment)according to different treatment methods,and both groups were continuously treated for 3 weeks.The upper limb motor function[upper-extremity Fugl-Meyer scale(UFMA),action research arm test(ARAT)],hand Brunnstrom staging,upper limb surface electromyography indicators[root mean square(RMS)and integrated electromyography(iEMG)of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle],cerebral artery hemodynamics[systolic blood flow velocity(Vs),resistance index(RI),mean blood flow velocity(Vm)]and ratio of fractional anisotropy(FA)of central region of brain lesion and FA of mirror-image region of healthy cerebral hemisphere(rFA)were observed before and after treatment in the two groups.Results Compared with the magnetic stimulation group,the UFMA score,ARAT score,hand Brunnstrom staging,Vs,Vm and rFA were higher after treatment in the combined group(P＜0.05).The RMS and iEMG of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle were higher in the combined group compared with those of the magnetic stimulation group(P＜0.05),while the RI was lower(P＜0.05).Conclusion Combined treatment can more effectively improve the upper limb motor function of patients,enhance hand activity ability,promote the recovery of upper limb muscle and nerve function,and regulate the hemodynamics of cerebral arteries.

OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

Objective To evaluate the effect of programmed nursing on dry eye after the phacoemulsification for cataract.Methods A total of 100 cases undergoing the phacoemulsification for cataract in our hospital from January 2022 to January 2024 were divided randomly into the control group and the observation group based on nursing differences with 50 cases in each group.The control group received the routine nursing,while the observation group was given the programmed nursing.The incidence of postoperative dry eye,nursing satisfaction,and dry eye-related complications were compared between the two groups.Results The results showed that the corneal fluorescence staining,tear secretion test,and tear film rupture time in the observation group were(1.46±1.13)points,(17.18±1.45)mm,and(6.86±0.92)s,respectively,which were superior to the control group's(2.96±0.09)points,(11.04±2.79)mm,and(5.98±1.26)s(all P<0.05);The incidence of dry eye complications in the observation group at 45 days and 90 days after the surgery was 8.0%and 6.0%,respectively,lower than that in the control group at 18.0%and 16.0%(both P<0.05);The satisfaction rate of the observation group with nursing care was 98.0%,which was higher than the control group's 84.0%(P<0.05).The differences between the groups were statistically significant.Conclusion Programmed nursing for patients undergoing the phacoemulsification for cataract can reduce the incidence of dry eye,improve the eye condition of patients and increase the patient satisfaction.

Objective:To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia.Methods:Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc. Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results:A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR=2.65, 95% CI: 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P<0.05). Conclusions:Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.

Based on the Global Burden of Disease (GBD) 2019, this study characterized the burden of dietary iron deficiency across 154 countries participating in the Belt and Road Initiative (BRI). A joinpoint regression model was employed to assess temporal trends in disease burden. Pearson correlation analysis and locally weighted regression were utilized to investigate the relationship between burden and the socio-demographic index (SDI). Slope indices and concentration indices were calculated to evaluate health inequalities, while frontier analysis explored disease burden benchmarks. Key metrics included prevalence and disability-adjusted life years (DALYs). Results revealed downward trends in age-standardized prevalence rates and age-standardized DALYs rates of dietary iron deficiency among children under 10 years old in 117 and 125 BRI countries, respectively, from 1990 to 2019. A significant negative correlation was observed between disease burden and SDI in 2019 ( R=-0.80, P<0.001). The slope indices decreased from -936 (95% CI:-1 006, -806) in 1990 to -1 128 (95% CI:-1 256, -999) in 2019, while the concentration indices declined from -0.24 (95% CI:-0.28, -0.20) to -0.35 (95% CI:-0.39, -0.30) during the same period. Frontier analysis further identified substantial gaps between observed outcomes and optimal performance thresholds in several countries.

Based on the Global Burden of Disease (GBD) 2019, this study characterized the burden of dietary iron deficiency across 154 countries participating in the Belt and Road Initiative (BRI). A joinpoint regression model was employed to assess temporal trends in disease burden. Pearson correlation analysis and locally weighted regression were utilized to investigate the relationship between burden and the socio-demographic index (SDI). Slope indices and concentration indices were calculated to evaluate health inequalities, while frontier analysis explored disease burden benchmarks. Key metrics included prevalence and disability-adjusted life years (DALYs). Results revealed downward trends in age-standardized prevalence rates and age-standardized DALYs rates of dietary iron deficiency among children under 10 years old in 117 and 125 BRI countries, respectively, from 1990 to 2019. A significant negative correlation was observed between disease burden and SDI in 2019 ( R=-0.80, P<0.001). The slope indices decreased from -936 (95% CI:-1 006, -806) in 1990 to -1 128 (95% CI:-1 256, -999) in 2019, while the concentration indices declined from -0.24 (95% CI:-0.28, -0.20) to -0.35 (95% CI:-0.39, -0.30) during the same period. Frontier analysis further identified substantial gaps between observed outcomes and optimal performance thresholds in several countries.

Objective To explore the influence of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with brain-computer interface rehabilitation robot in patients with upper limb motor dysfunction after stroke.Methods A total of 126 patients with upper limb motor dysfunction after stroke were divided into the combined group(61 cases,low-frequency rTMS combined with brain-computer interface rehabilitation robot on the basis of routine rehabilitation treatment)and the magnetic stimulation group(65 cases,low-frequency rTMS on the basis of routine rehabilitation treatment)according to different treatment methods,and both groups were continuously treated for 3 weeks.The upper limb motor function[upper-extremity Fugl-Meyer scale(UFMA),action research arm test(ARAT)],hand Brunnstrom staging,upper limb surface electromyography indicators[root mean square(RMS)and integrated electromyography(iEMG)of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle],cerebral artery hemodynamics[systolic blood flow velocity(Vs),resistance index(RI),mean blood flow velocity(Vm)]and ratio of fractional anisotropy(FA)of central region of brain lesion and FA of mirror-image region of healthy cerebral hemisphere(rFA)were observed before and after treatment in the two groups.Results Compared with the magnetic stimulation group,the UFMA score,ARAT score,hand Brunnstrom staging,Vs,Vm and rFA were higher after treatment in the combined group(P＜0.05).The RMS and iEMG of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle were higher in the combined group compared with those of the magnetic stimulation group(P＜0.05),while the RI was lower(P＜0.05).Conclusion Combined treatment can more effectively improve the upper limb motor function of patients,enhance hand activity ability,promote the recovery of upper limb muscle and nerve function,and regulate the hemodynamics of cerebral arteries.

Objective:To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia.Methods:Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc. Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results:A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR=2.65, 95% CI: 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P<0.05). Conclusions:Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.