1.Relationship of dyslipidemia, hypertension and diabetes comorbidities and lifestyle among adults in Hebei Province
Yajing CAO ; Jingjing ZHAO ; Mei LI ; Tiantian GUO ; Fujuan YUE ; Xiuli NIU ; Xiaoli LIU
Journal of Public Health and Preventive Medicine 2026;37(3):56-61
Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.
2.Prevalence of hyperuricemia and its influencing factors in comorbidities with hypertension, diabetes, and dyslipidemia among adults in Hebei Province
Jingjing ZHAO ; Yajing CAO ; Dongsheng JIANG ; Tiantian GUO ; Yuhuan LIU ; Fujuan YUE ; Xiaoli LIU
Journal of Public Health and Preventive Medicine 2026;37(4):31-35
Objective To analyze the prevalence of hyperuricemia (HUA) among adults in Hebei Province and its influencing factors related to comorbidities with “three highs”, and to provide a theoretical basis for the prevention and control of HUA and multi-disease co-management. Methods Data were derived from the 2018 China Chronic Disease and Risk Factors Surveillance program conducted in Hebei Province. A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. All statistical analyses were adjusted for complex weighting. Design-based logistic regression was employed to analyze factors influencing HUA prevalence, and ordinal logistic regression was used to analyze the influencing factors of HUA patients and their comorbidity with “three highs”. Results The prevalence of HUA among adults in Hebei Province was 10.42%, with males showing higher rates than females (P<0.05). The highest prevalence of HUA was observed in the 18-39 age group, followed by a declining trend, and a resurgence in those aged ≥70 (P<0.05). Among HUA patients with comorbidities, isolated HUA, 1 comorbidity, 2 comorbidities, and 3 comorbidities accounted for 13.94%, 33.33%, 39.17%, and 13.56%, respectively. HUA combined with hypertension and dyslipidemia represented the highest proportion (31.07%). Analysis of the influencing factors of HUA revealed that higher education levels, obesity, central obesity, and dyslipidemia increased the risk of HUA (P<0.05). Ordinal logistic regression analysis of HUA combined with three highs showed that HUA patients aged ≥50 years, overweight individuals, and those with chronic kidney disease had a higher number of patients with three highs (P<0.05). Conclusion HUA exhibits insidious onset, and it is recommended to include uric acid testing in routine physical examinations. Targeted prevention measures, such as early uric acid testing and health education, should be implemented by Hebei authorities for populations with higher education levels, obesity, central obesity, and dyslipidemia to reduce HUA incidence. Additionally, health education and regular medical check-ups are recommended for overweight HUA patients and those with chronic kidney disease to prevent comorbidities and alleviate disease burden.
3.Pharmacokinetic interactions between empagliflozin and donafenib/lenvatinib in rats
Ying LI ; Zihan LIU ; Wenyu DU ; Jing AN ; Congyang DING ; Yue ZHAO ; Bingnan REN ; Zefang YU ; Yajing LI ; Zhanjun DONG
Journal of Clinical Hepatology 2025;41(9):1853-1860
ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug, and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups: empagliflozin group 1 and 2, donafenib group, lenvatinib group, donafenib pretreatment+empagliflozin group, lenvatinib pretreatment + empagliflozin group, empagliflozin pretreatment+donafenib group, and empagliflozin pretreatment+lenvatinib group, with 6 rats in each group. The doses of empagliflozin, donafenib, and lenvatinib were 2.5 mg/kg, 40 mg/kg, and 1.2 mg/kg, respectively. The rats in the empagliflozin group, donafenib group, and lenvatinib group were given a blank solvent by gavage for 7 consecutive days, followed by a single dose of empagliflozin, donafenib, or lenvatinib on day 7 after the administration of the blank solvent; the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days, followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points, and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib, lenvatinib, and empagliflozin, and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug (area under the plasma concentration-time curve [AUC], time to peak [Tmax], peak concentration [Cmax], and half-life time [t1/2]). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group, the donafenib pretreatment+empagliflozin group had significant increases in the AUC0-t and AUC0-∞ of empagliflozin (P=0.011 and 0.008), while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin, with a slightly shorter Tmax (P=0.019). Compared with the donafenib group, the empagliflozin pretreatment+donafenib group had significant increases in the AUC0-t and AUC0-∞ of donafenib (P=0.027 and 0.025), as well as a significant increase in Cmax (P=0.015) and significant reductions in CLz/F and Vz/F (P=0.005 and 0.004); compared with the lenvatinib group, the empagliflozin pretreatment+lenvatinib group had a reduction in the t1/2 of lenvatinib by approximately 5 hours (P=0.002), with a trend of reduction in AUC0-t (P0.05). ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs, leading to a significant increase in the exposure levels of both drugs, and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.
4.The Effects of Physical Activity Duration,Sleep Quality,and Weight Control on Patient-Reported Outcomes in Hypertensive Patients
Ru ZHANG ; Yajing ZHAO ; Wen ZHANG ; Shunding TANG ; Han WANG ; Xiaoqing ZHANG
Journal of Kunming Medical University 2025;46(2):80-87
Objective To investigate the correlation between physical activity duration,sleep quality,weight control,and PRO(patient-reported outcomes)in individuals with hypertension,providing effective information for enhancing patient-reported outcomes in this population.Methods A total of 625 hypertensive patients were randomly selected from four counties in Yunnan Province from April to June 2020 to participate in a field survey.The questionnaire included patients'basic information,lifestyle,health status and the PRO Scale for Hypertension-PROISCD-HY(V1.0).Statistical analyses including t-tests,one-way ANOVA,and multivariate linear regression were conducted to investigate the relationships between physical activity duration,sleep quality,weight control,and PRO,with the Bootstrap method used to examine potential mediating effects.Results After adjusting for potential covariates,the multiple linear regression model indicated a significant association between a physical activity duration of≥2 hours with PRO[B=6.551,95%CI(2.611,10.491)].Stratified analysis showed that this association was only present among males,females,and younger adults,but not in older adults.Additionally,a positive correlation was found between good sleep quality and PRO[B=1.870,95%CI(0.449,3.291)],with this association being consistent across all populations after stratification.Patients who managed their condition through exercise and diet had higher PRO scores[B=1.904,95%CI(0.383,3.424)],while those controlling weight through diet and other methods exhibited a decrease in PRO scores[B=-4.873,95%CI(-7.860,-1.887);B=-7.105,95%CI(-12.211,-1.999)],with variations among different groups.The bootstrap method revealed that physical activity duration had both direct and indirect effects on PRO,with sleep quality acting as a partial mediator between physical activity duration and PRO.Conclusion A Physical activity duration of at least 2 hours,good sleep quality,and weight control have been shown to improve PRO in individuals with hypertension.
5.Impact of muscle strength decline and exercise intervention on multimorbidity of chronic diseases in older adults.
Journal of Central South University(Medical Sciences) 2025;50(5):897-906
Multimorbidity of chronic diseases is one of the most common health issues among older adults, and the resulting demand for long-term medical care and management imposes a considerable burden on healthcare systems. Muscle strength, a core indicator of overall health status, is closely associated with the risk of developing multimorbidity of chronic diseases in older adults. Decline in muscle strength not only increases the risk of multimorbidity of chronic diseases but also interacts with it to exacerbate disease burden. In older adults with existing multimorbidity of chronic diseases, muscle strength decline can impair physical function and quality of life, leading to a vicious cycle of disease progression and physical disability. Strength training can help prevent multimorbidity, with potential mechanisms including the promotion of anti-inflammatory effects and enhancement of mitochondrial energy metabolism. This review summarizes the impact of muscle strength decline on multimorbidity of chronic diseases in older adults and the effectiveness and potential mechanisms of exercise interventions, providing evidence to delay muscle strength decline, prevent the occurrence and progression of multimorbidity of chronic diseases, and improve quality of life in older adults.
Humans
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Aged
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Chronic Disease/prevention & control*
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Muscle Strength/physiology*
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Multimorbidity
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Quality of Life
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Resistance Training
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Exercise Therapy
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Exercise
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Sarcopenia
6.Clinical Evidence Profile of Eleven Expensive Chinese Patent Medicines: A Scoping Analysis
Yajing LI ; Miaomiao LI ; Le ZHANG ; Wenya WANG ; Hui ZHAO ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):227-238
ObjectiveThis study employed the scoping review method to systematically retrieve and analyze the basic information and clinical research evidence of expensive Chinese patent medicines (CPMs), aiming to provide a basis for future related research and clinical applications. MethodsEight Chinese and English databases were systematically searched for the clinical research evidence on expensive CPMs. ResultsEleven expensive CPMs (Angong Niuhuang Wan, Jufang Zhibao Wan, Suhexiang Wan, Pien Tze Huang, Niuhuang Qingxin Wan, Qinggong Shoutao Wan, Compound Realgar Natural Indigo Tablets, Xihuang Wan, Dingkun Wan, Babao Wan, and Guilingji Capsules) were selected. A total of 365 related studies were included in this review, comprising 331 clinical studies (of which 291 were randomized controlled trials), 30 systematic reviews and Meta-analyses, 3 expert consensus, and 1 rapid health technology assessment. Among the 11 CPMs, 2(Angong Niuhuang Wan and Jufang Zhibao Wan) had a daily price over 500 yuan. The famous and precious Chinese medicinal materials involved included Moschus (frequency of 7), Bovisc Alculus (7), and Borneol (5). The dosage forms included pills, capsules, oral liquid, tablets, and lozenges. The diseases treated by these CPMs mainly included malignant tumors, cerebrovascular diseases, gynecological diseases, and hepatobiliary system diseases. The sample sizes of the clinical studies were mainly concentrated within the range of 51-100 cases, and the main control form was CPM + basic Western medicine treatment vs. basic Western medicine treatment. The 331 clinical studies reported a total of 44 adverse events occurred, of which 36 were determined to be adverse reactions. ConclusionThe scarcity of raw materials leads to the high prices of expensive CPMs. The difficulty of conducting clinical research and the critical and severe cases treated lead to a lack of clinical research evidence with large sample sizes. The uneven distribution of existing studies, incomplete information on medicine package, and non-standard clinical research designs remain to be addressed in the future.
7.Central nervous system-targeted reactivator HI-6 lipid nanoparti-cles for salvage of organophosphorus-induced brain injury mice
Ruizhi LIN ; Jianyu WANG ; Yajing WEI ; Xinran ZHAO ; Lin WANG ; Jun YANG ; Yongan WANG ; Cuiyun YU
Chinese Journal of Pharmacology and Toxicology 2025;39(9):641-650
OBJECTIVE To construct novel central nervous system(CNS)-targeted lipid nanoparti-cles for the treatment of organophosphorus-induced brain injury in mice.METHODS(1)Preparation,screening,and characterization of lipid nanoparticles.① Lipid nanoreactivators were prepared using the thin-film hydration method,with asoxime(HI-6)as the therapeutic drug and lipid carriers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS),1,2-dipalmitoyl-sn-glycero-3-phospho-choline(DPPC),and cholesterol(CHOL)(PDC)at varying molar ratios(1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3)(HI-6@PDC 1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3).② FLU-labeled lipid nanocarriers(FLU@PDC 1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)were prepared and physically mixed with phospholipase A2(PLA2)solution(at the final PLA2 concentration of 10 kU·L-1)to obtain FLU@PDC+PLA2.Male KM mice were randomly divided into normal control(PBS),FLU,and FLU@PDC+PLA2(1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)groups(n=7 per group).After intravenous(iv)administration(FLU dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 1 h,homogenized,centrifuged,and analyzed via fluorescence spectrophotom-etry to screen the optimal CNS-targeted lipid carrier composition.③ The morphology of HI-6@PDC 5∶2∶3 was characterized by transmission electron microscope(TEM).The particle size,polydispersity index(PDI),and zeta potential of HI-6@PDC 5∶2∶3 were measured using a Zeta potential and particle size analyzer.Encapsulation efficiency and loading efficiency of HI-6@PDC 5∶2∶3 were determined using an ultrafiltration centrifugation method combined with high-performance liquid chromatography(HPLC).In vitro release kinetics of HI-6@PDC 5∶2∶3 and HI-6@PDC+PLA2 5∶2∶3 were assessed using a dialysis bag diffusion method combined with fluorescence spectrophotometry.(2)Validation of CNS targeting.① Cyanine7(Cy7)-labeled PDC 5∶2∶3(Cy7@PDC)was prepared and mixed with PLA2 solution(Cy7@PDC+PLA2 5∶2∶3).Mice were divided into normal control,Cy7,Cy7@PDC 5∶2∶3 and Cy7@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy7 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain fluorescence was visualized at 3 h using a small animal in vivo imaging(IVIS)system.② Cyanine 3(Cy3)-labeled PDC 5∶2∶3(Cy3@PDC 5∶2∶3)was prepared and mixed with PLA2 solution(Cy3@PDC+PLA2 5∶2∶3).Mice were divided into Cy3@PDC 5∶2∶3 and Cy3@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy3 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 2 h for fluorescent staining and Cy3 fluorescence observation.(3)Therapeutic efficacy eval-uation.① Male KM mice were randomly divided into normal control,brain injury,HI-6 treatment,and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=6 per group).Except for the normal control,all the mice were subcutaneously(sc)injected with soman(120 μg·kg-1),followed by immediate iv treatment(HI-6 dose:22 mg·kg-1,carrier dose:80 mg·kg-1).At 10 min,orbital blood and brain tissues were collected before brain weight was recorded.Acetylcholinesterase(AChE)reactivation in blood and brain was measured using the Ellman method.② Grouping and treatment were identical to ①(n=3 per group).At 24 h,brain tissues were collected for HE staining to assess histopathological damage.③ Mice were divided into brain injury and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=10 per group)and treated as in ①(soman dose:220 ug·kg-1).Survival rates,neurotoxic symptoms(tremors,salivation),and seizure latency were recorded,and survival curves were plotted.RESULTS(1)PDC 5∶2∶3 exhibited the highest brain fluorescence,indicating optimal CNS targeting.HI-6@PDC 5∶2∶3 appeared in regular spherical shapes,and were negatively charged,with a size of(219.4±3.1)nm,PDI of 0.4±0.02,entrapment effi-ciency of 72.9%and loading efficiency of 49.7%.HI-6@PDC+PLA2 5∶2∶3 showed a cumulative release of 43.5%at 60 min,which was lower than that of rhodamine B(RB)but sufficient for CNS therapeutic timelines.(2)In vivo fluorescence and pathological fluorescence confirmed PLA2-mediated CNS delivery.(3)HI-6@PDC+PLA2 5∶2∶3 significantly enhanced AChE reactivation in the blood and brain compared to HI-6.Histopathology revealed mitigated brain injury in treated mice.HI-6@PDC+PLA2 5∶2∶3 prolonged survival,reduced convulsions,alleviated neurotoxicity,and extended seizure latency.CONCLUSION HI-6@PDC 5∶2∶3 can effectively cross the blood-brain barrier via PLA2 mediation,demonstrating strong CNS targeting.It can significantly improve AChE reactivation in peripheral and central tissues and offers potent therapeutic efficacy against organophosphate-induced brain injury.
8.Prevalence of chronic kidney disease and influencing factors in adults in Hebei Province
Tiantian GUO ; Xiaoli LIU ; Jingjing ZHAO ; Mei LI ; Lijuan TANG ; Fujuan YUE ; Yajing CAO
Chinese Journal of Epidemiology 2025;46(1):107-117
Objective:To analyze the prevalence of chronic kidney disease (CKD) and influencing factors of adults in Hebei Province, and provide scientific evidence for the development of comprehensive CKD prevention and control strategies.Methods:In China Adult Chronic Disease and Nutrition Surveillance in Hebei in 2018, a total of 7 562 permanent residents aged ≥18 years were selected by multi-stage stratified cluster random sampling from 13 surveillance points in Hebei for questionnaire survey, medical examination and laboratory test.Results:A total of 1 067 CKD patients were detected in the adults aged ≥18 years in this survey, with a weighted prevalence rate of 12.10%. The results of multivariate analysis showed that the daily total static behavior time ( OR=1.07, 95% CI: 1.04-1.09), living in rural area ( OR=1.50, 95% CI: 1.14-1.97), coal use ( OR=1.37, 95% CI: 1.16-1.61), coal gas/liquefied gas/natural gas/biogas use ( OR=2.92, 95% CI: 2.40-3.54) and solar energy/electricity use ( OR=1.75, 95% CI: 1.36-2.25), insufficient fruit intake ( OR=1.39, 95% CI: 1.06-1.83), insufficient physical activity ( OR=1.35, 95% CI: 1.11-1.64), suffering from hypertension ( OR=1.80, 95% CI: 1.44-2.24) and suffering from diabetes ( OR=1.77, 95% CI: 1.27-2.45) were risk factors for CKD in adults in Hebei. High education level ( OR=0.41, 95% CI: 0.19-0.91), excessive drinking ( OR=0.53, 95% CI: 0.28-0.99), central obesity ( OR=0.75, 95% CI: 0.58-0.97), history of allergic diseases ( OR=0.44, 95% CI: 0.27-0.72) were protective factors for CKD. Conclusions:The prevalence of CKD in adults in Hebei was relatively high, especially in those who had too long average daily static behavior, lived in rural area, used coal, gas/liquefied gas/natural gas/biogas, solar energy/electricity, had inadequate intake of fruits, lacked physical activity and suffered from hypertension and diabetes. It is necessary to pay attention to the early prevention and treatment of CKD, strengthen the health education about healthy lifestyle and improve the management of patients with chronic disease, such as hypertension and diabetes, to further reduce the risk for CKD.
9.Central nervous system-targeted reactivator HI-6 lipid nanoparti-cles for salvage of organophosphorus-induced brain injury mice
Ruizhi LIN ; Jianyu WANG ; Yajing WEI ; Xinran ZHAO ; Lin WANG ; Jun YANG ; Yongan WANG ; Cuiyun YU
Chinese Journal of Pharmacology and Toxicology 2025;39(9):641-650
OBJECTIVE To construct novel central nervous system(CNS)-targeted lipid nanoparti-cles for the treatment of organophosphorus-induced brain injury in mice.METHODS(1)Preparation,screening,and characterization of lipid nanoparticles.① Lipid nanoreactivators were prepared using the thin-film hydration method,with asoxime(HI-6)as the therapeutic drug and lipid carriers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS),1,2-dipalmitoyl-sn-glycero-3-phospho-choline(DPPC),and cholesterol(CHOL)(PDC)at varying molar ratios(1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3)(HI-6@PDC 1∶6∶3,3∶4∶3,5∶2∶3 and 7∶0∶3).② FLU-labeled lipid nanocarriers(FLU@PDC 1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)were prepared and physically mixed with phospholipase A2(PLA2)solution(at the final PLA2 concentration of 10 kU·L-1)to obtain FLU@PDC+PLA2.Male KM mice were randomly divided into normal control(PBS),FLU,and FLU@PDC+PLA2(1∶6∶3,3∶4∶3,5∶2∶3,and 7∶0∶3)groups(n=7 per group).After intravenous(iv)administration(FLU dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 1 h,homogenized,centrifuged,and analyzed via fluorescence spectrophotom-etry to screen the optimal CNS-targeted lipid carrier composition.③ The morphology of HI-6@PDC 5∶2∶3 was characterized by transmission electron microscope(TEM).The particle size,polydispersity index(PDI),and zeta potential of HI-6@PDC 5∶2∶3 were measured using a Zeta potential and particle size analyzer.Encapsulation efficiency and loading efficiency of HI-6@PDC 5∶2∶3 were determined using an ultrafiltration centrifugation method combined with high-performance liquid chromatography(HPLC).In vitro release kinetics of HI-6@PDC 5∶2∶3 and HI-6@PDC+PLA2 5∶2∶3 were assessed using a dialysis bag diffusion method combined with fluorescence spectrophotometry.(2)Validation of CNS targeting.① Cyanine7(Cy7)-labeled PDC 5∶2∶3(Cy7@PDC)was prepared and mixed with PLA2 solution(Cy7@PDC+PLA2 5∶2∶3).Mice were divided into normal control,Cy7,Cy7@PDC 5∶2∶3 and Cy7@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy7 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain fluorescence was visualized at 3 h using a small animal in vivo imaging(IVIS)system.② Cyanine 3(Cy3)-labeled PDC 5∶2∶3(Cy3@PDC 5∶2∶3)was prepared and mixed with PLA2 solution(Cy3@PDC+PLA2 5∶2∶3).Mice were divided into Cy3@PDC 5∶2∶3 and Cy3@PDC+PLA2 5∶2∶3 groups(n=3 per group).After iv injection(Cy3 dose:1 mg·kg-1,carrier dose:80 mg·kg-1),brain tissues were collected at 2 h for fluorescent staining and Cy3 fluorescence observation.(3)Therapeutic efficacy eval-uation.① Male KM mice were randomly divided into normal control,brain injury,HI-6 treatment,and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=6 per group).Except for the normal control,all the mice were subcutaneously(sc)injected with soman(120 μg·kg-1),followed by immediate iv treatment(HI-6 dose:22 mg·kg-1,carrier dose:80 mg·kg-1).At 10 min,orbital blood and brain tissues were collected before brain weight was recorded.Acetylcholinesterase(AChE)reactivation in blood and brain was measured using the Ellman method.② Grouping and treatment were identical to ①(n=3 per group).At 24 h,brain tissues were collected for HE staining to assess histopathological damage.③ Mice were divided into brain injury and HI-6@PDC+PLA2 5∶2∶3 treatment groups(n=10 per group)and treated as in ①(soman dose:220 ug·kg-1).Survival rates,neurotoxic symptoms(tremors,salivation),and seizure latency were recorded,and survival curves were plotted.RESULTS(1)PDC 5∶2∶3 exhibited the highest brain fluorescence,indicating optimal CNS targeting.HI-6@PDC 5∶2∶3 appeared in regular spherical shapes,and were negatively charged,with a size of(219.4±3.1)nm,PDI of 0.4±0.02,entrapment effi-ciency of 72.9%and loading efficiency of 49.7%.HI-6@PDC+PLA2 5∶2∶3 showed a cumulative release of 43.5%at 60 min,which was lower than that of rhodamine B(RB)but sufficient for CNS therapeutic timelines.(2)In vivo fluorescence and pathological fluorescence confirmed PLA2-mediated CNS delivery.(3)HI-6@PDC+PLA2 5∶2∶3 significantly enhanced AChE reactivation in the blood and brain compared to HI-6.Histopathology revealed mitigated brain injury in treated mice.HI-6@PDC+PLA2 5∶2∶3 prolonged survival,reduced convulsions,alleviated neurotoxicity,and extended seizure latency.CONCLUSION HI-6@PDC 5∶2∶3 can effectively cross the blood-brain barrier via PLA2 mediation,demonstrating strong CNS targeting.It can significantly improve AChE reactivation in peripheral and central tissues and offers potent therapeutic efficacy against organophosphate-induced brain injury.
10.Prognoses of patients with medial or lateral medullary infarction and their influencing factors
Na ZHAO ; Ran LIU ; Yajing ZHANG ; Ling LING ; Lei XIANG ; Wei YUE
Chinese Journal of Neuromedicine 2025;24(4):370-377
Objective:To investigate the prognoses of patients with medial medullary infarction (MMI) or lateral medullary infarction (LMI) and their influencing factors.Methods:A retrospective analysis was performed; 489 patients with acute medullary infarction admitted to Department of Neurology, Tianjin Huanhu Hospital from January 2017 to January 2024 were enrolled. Among them, 186 patients had MMI, which was divided into isolated MMI group ( n=126) and group of MMI with other infarcts ( n=60); 303 patients had LMI, which was divided into isolated LMI group ( n=176) and group of LMI with other infarcts ( n=127). Prognosis 90 days after onset was assessed by modified Rankin Scale (mRS, scores of 3-6 as poor prognosis). Clinical data, prognosis and mortality 90 days after onset, early neurological deterioration, respiratory failure, and complications were compared between isolated MMI group and group of MMI with other infarcts and between isolated LMI group and group of LMI with other infarcts. Univariate and multivariate Logistic regression analyses were used to identify the independent influencing factors for poor prognosis 90 days after onset in patients with MMI or LMI. Results:(1) Compared with isolated MMI group, group of MMI with other infarcts had significantly lower rates of alcohol history and sensory symptoms but higher rates of Horner's syndrome, dysphagia, dysarthria, and facial palsy ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly lower rates of sensory symptoms but higher rates of dizzy and dysarthria, and statistically different Trial of ORG 10172 in Acute Stroke Treatment types ( P<0.05). (2) The poor prognosis rate 90 days after onset in patients with MMI was significantly higher than that in patients with LMI (31.8% vs. 18.8%, P<0.05). Compared with isolated MMI group, group of MMI with other infarcts had significantly higher rates of respiratory failure, urinary retention, and pulmonary infection ( P<0.05). Compared with isolated LMI group, group of LMI with other infarcts had significantly higher rates of poor prognosis 90 days after onset, mortality 90 days after onset, early neurological deterioration, respiratory failure, stress ulcers, and pulmonary infection ( P<0.05). (3) Multivariate Logistic regression analysis revealed that dyskinesia ( OR=10.522, 95% CI: 1.246-88.853, P=0.031) and vertical multi-level involvement ( OR=4.585, 95% CI: 1.405-14.962, P=0.012) were independent influencing factors for poor prognosis in isolated MMI patients 90 days after onset; age ( OR=1.089, 95% CI: 1.017-1.166, P=0.015), vertical multi-level involvement ( OR=9.429, 95% CI: 1.625-54.502, P=0.012) were independent influencing factors for poor prognosis in MMI patients with other infarcts 90 days after onset; age ( OR=1.069, 95% CI: 1.006-1.136, P=0.031) and vertical multi-level involvement ( OR=7.125, 95% CI: 2.243-22.636, P<0.001) were independent influencing factors for poor prognosis in isolated LMI patients 90 days after onset; diabetes ( OR=2.807, 95% CI: 1.056-7.461, P=0.038), dysphagia ( OR=6.821, 95% CI: 1.978-23.518, P=0.002), and temporal-occipital infarcts ( OR=3.419, 95% CI: 1.133-10.302, P=0.029) were independent influencing factors for poor prognosis in LMI patients with other infarcts. Conclusion:Patients with LMI had better prognosis compared with patients with MMI; however, LMI patients with other infarcts had poorer prognosis compared with LMI patients; LMI patients with diabetes mellitus, dysphagia or temporal-occipital infarcts are prone to have poor prognosis.


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