Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

OBJECTIVE To establish an ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of dexmedetomidine(DEX)in plasma of beagle dogs and evaluate the pharmacokinetics and sedation after nasal,buccal and sublingual mucosal admin-istration.METHODS A UPLC-MS/MS method was established and validated for dertermination of DEX in plasma of beagle dogs.DEX was administered to the nasal cavity,buccal and sublingual mucous membranes of beagle dogs,respectively.Blood samples were collected at different time points.The plasma concentration of DEX was measured by the established UPLC-MS/MS method.Pharmacokinetic parameters were fitted by Phoenix software and the sedative effect at different mucous membrane sites was evaluated in conjunction with behavioral and Ramsay scores.RESULTS The linearity of DEX was fine within the range of 0.05-100 μg·L-1(r>0.999),which was validated methodologically to meet the requirements of quantitative detection.The plasma concentration of the drug peaked the fastest with nasal administration.Tmax was 0.25 h,Cmax(4.43±1.19)μg·L-1,and the AUC0-6h was(8.92±2.07)μg·h·L-1,compared with 0.92 and 1 h,(2.87±0.69),(2.70±0.41)μg·L-1,and(7.99±1.77),(7.01±2.09)μg·h·L-1 with buccal and sublingual administration.Nasal administration had the fastest onset at 7 min,with a Ramsay score of 4,and sedation lasted for 36 min,compared with 33 and 35 min,and 38 and 37 min for buccal and sublingual administration.CONCLUSION The proposed method is sensitive,reliable and applicable to quantitative analysis of DEX in plasma of beagle dogs.Administration of DEX to the nasal cavity mucosa has a faster onset and a better sedative effect than to the buccal and sublingual mucosa.

Objective:To explore the application indications, clinical characteristics and influencing factors of extracorporeal membrane oxygenation (ECMO) in the treatment of critically ill pregnant and postpartum women in Bao′an district, Shenzhen, and summarize regional experience.Methods:A retrospective analysis was conducted on 5 cases of pregnant and postpartum women who received ECMO treatment at the CUHK Women′s and Children′s Medical Centre (Shenzhen) and the Shenzhen Bao′an People′s Hospital from 2020 to 2024. Baseline characteristics, ECMO parameters, complications and maternal-infant outcomes of the patients were collected.Results:The patients′ age was 29(24, 36) years old, gestational age was 39(31, 39) weeks, and ECMO maintenance time was 8(4, 8) days. ECMO indications included 2 cases of cardiac arrest, 1 case of respiratory and circulatory failure, 1 case of cardiogenic shock, and 1 case of acute respiratory distress syndrome. There were 4 cases of veno-arterial (VA)-ECMO and 1 case of veno-venous (VV)-ECMO. Complications included 3 cases of bleeding, 4 cases of acute renal failure, 2 cases of thrombosis, and 2 cases of infection. Both maternal and infant survival were 3 cases. Successful cases benefited from the multidisciplinary rapid response team and regional transportation cooperation, while failed cases were mostly accompanied by severe bleeding and disseminated intravascular coagulation.Conclusions:ECMO improves the success rate of treating critically ill pregnant and postpartum women in Bao′an District. Amniotic fluid embolism and severe pulmonary hypertension are the main indications. Regional multidisciplinary cooperation, accurate initiation timing and individualized anticoagulation management are the keys. It is recommended to establish a national ECMO registration system for pregnant and postpartum women to optimize treatment strategies and improve maternal and infant prognosis.

OBJECTIVE To establish an ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of dexmedetomidine(DEX)in plasma of beagle dogs and evaluate the pharmacokinetics and sedation after nasal,buccal and sublingual mucosal admin-istration.METHODS A UPLC-MS/MS method was established and validated for dertermination of DEX in plasma of beagle dogs.DEX was administered to the nasal cavity,buccal and sublingual mucous membranes of beagle dogs,respectively.Blood samples were collected at different time points.The plasma concentration of DEX was measured by the established UPLC-MS/MS method.Pharmacokinetic parameters were fitted by Phoenix software and the sedative effect at different mucous membrane sites was evaluated in conjunction with behavioral and Ramsay scores.RESULTS The linearity of DEX was fine within the range of 0.05-100 μg·L-1(r>0.999),which was validated methodologically to meet the requirements of quantitative detection.The plasma concentration of the drug peaked the fastest with nasal administration.Tmax was 0.25 h,Cmax(4.43±1.19)μg·L-1,and the AUC0-6h was(8.92±2.07)μg·h·L-1,compared with 0.92 and 1 h,(2.87±0.69),(2.70±0.41)μg·L-1,and(7.99±1.77),(7.01±2.09)μg·h·L-1 with buccal and sublingual administration.Nasal administration had the fastest onset at 7 min,with a Ramsay score of 4,and sedation lasted for 36 min,compared with 33 and 35 min,and 38 and 37 min for buccal and sublingual administration.CONCLUSION The proposed method is sensitive,reliable and applicable to quantitative analysis of DEX in plasma of beagle dogs.Administration of DEX to the nasal cavity mucosa has a faster onset and a better sedative effect than to the buccal and sublingual mucosa.

Objective:To explore the application indications, clinical characteristics and influencing factors of extracorporeal membrane oxygenation (ECMO) in the treatment of critically ill pregnant and postpartum women in Bao′an district, Shenzhen, and summarize regional experience.Methods:A retrospective analysis was conducted on 5 cases of pregnant and postpartum women who received ECMO treatment at the CUHK Women′s and Children′s Medical Centre (Shenzhen) and the Shenzhen Bao′an People′s Hospital from 2020 to 2024. Baseline characteristics, ECMO parameters, complications and maternal-infant outcomes of the patients were collected.Results:The patients′ age was 29(24, 36) years old, gestational age was 39(31, 39) weeks, and ECMO maintenance time was 8(4, 8) days. ECMO indications included 2 cases of cardiac arrest, 1 case of respiratory and circulatory failure, 1 case of cardiogenic shock, and 1 case of acute respiratory distress syndrome. There were 4 cases of veno-arterial (VA)-ECMO and 1 case of veno-venous (VV)-ECMO. Complications included 3 cases of bleeding, 4 cases of acute renal failure, 2 cases of thrombosis, and 2 cases of infection. Both maternal and infant survival were 3 cases. Successful cases benefited from the multidisciplinary rapid response team and regional transportation cooperation, while failed cases were mostly accompanied by severe bleeding and disseminated intravascular coagulation.Conclusions:ECMO improves the success rate of treating critically ill pregnant and postpartum women in Bao′an District. Amniotic fluid embolism and severe pulmonary hypertension are the main indications. Regional multidisciplinary cooperation, accurate initiation timing and individualized anticoagulation management are the keys. It is recommended to establish a national ECMO registration system for pregnant and postpartum women to optimize treatment strategies and improve maternal and infant prognosis.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

BACKGROUND:At present,there are some limitations in evaluating the severity of acute spinal cord injury,and a rapid and accurate evaluation method is urgently needed. OBJECTIVE:To analyze the correlation between the expression levels of serum oxidative stress and nerve injury indexes and the severity of the disease in patients with acute spinal cord injury. METHODS:A total of 65 patients were included in the study from August 2020 to May 2022,including 32 patients in the experimental group(acute spinal cord injury)and 33 patients in the control group(simple spinal fracture).American Spinal Injury Association(ASIA)Impairment Scale and neurological function score were evaluated within 8 hours of admission.Meanwhile,serum levels of superoxide dismutase,malondialdehyde,glutathione,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase were detected and compared between the two groups.The correlation between the expression levels of the above serological indicators in serum and ASIA impairment grade and AISA neural function score was analyzed. RESULTS AND CONCLUSION:The average serum levels of superoxide dismutase and glutathione in the experimental group were significantly lower than those of the control group(P<0.001),while the average serum levels of malondialdehyde,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase in the experimental group were higher than those of the control group(P<0.01).The serum levels of superoxide dismutase and glutathione in the experimental group were positively correlated with the damage grade of AISA(r=0.862 4,0.849 3,P<0.01),while the serum levels of malondialdehyde,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase were negatively correlated with the damage grade of AISA(r=-0.866 1,-0.638 1,-0.746 6,P<0.001),and the serum level of nitric oxide was not significantly correlated with the damage grade of AISA(r=-0.177 5,P>0.05).The serum level of glutathione in the experimental group was positively correlated with AISA sensory function scores(r=0.569 9,P<0.001),while the serum levels of malondialdehyde,glial fibrillary acidic protein and neuron-specific enolase were negatively correlated with AISA sensory function scores(r=-0.574 1,-0.099 2,-0.708 6,P<0.05),and the serum levels of superoxide dismutase and nitric oxide were not significantly correlated with AISA sensory function scores(r=0.230 8,-0.376 2,P>0.05).The serum levels of superoxide dismutase and glutathione in the experimental group were positively correlated with ASIA motor function scores(r=0.380,0.524 7,P<0.05);the serum levels of malondialdehyde,glial fibrillary acidic protein and neuron-specific enolase were negatively correlated with AISA motor function scores(r=-0.577 9,-0.452 2,-0.662 8,P<0.05);and the level of nitric oxide had no significant correlation with AISA motor function scores(r=-0.049 7,P>0.05).To conclude,the serum levels of superoxide dismutase,malondialdehyde,glutathione,nitric oxide,glial fibrillary acidic protein and neuron-specific enolase in serum of patients with acute spinal cord injury are significantly correlated with ASIA impairment grade and ASIA neural function score,which could be used as biomarkers for early clinical assessment of disease severity.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Keloids are often accompanied by clinical manifestations such as itching, pain, and discomfort. Their biological characteristics bear similar to those of tumors, making keloids difficult to cure and prone to relapse. Recent research has identified a crucial role for alterations in cellular glucose metabolism in the pathogenesis of keloids. This paper summarized the research progress on cell glucose metabolism in keloids, explaining the tumor-like proliferation of keloid fibroblasts through aerobic glycolytic metabolism. Furthermore, it explored the influence of the relationship between endothelial cell and immune cell metabolism and inflammatory response on keloids. The roles of glucose transporter, lactate dehydrogenase, and pyruvate kinase in keloid were summarized here, providing more insights for the prevention and treatment of keloids.

Keloids are often accompanied by clinical manifestations such as itching, pain, and discomfort. Their biological characteristics bear similar to those of tumors, making keloids difficult to cure and prone to relapse. Recent research has identified a crucial role for alterations in cellular glucose metabolism in the pathogenesis of keloids. This paper summarized the research progress on cell glucose metabolism in keloids, explaining the tumor-like proliferation of keloid fibroblasts through aerobic glycolytic metabolism. Furthermore, it explored the influence of the relationship between endothelial cell and immune cell metabolism and inflammatory response on keloids. The roles of glucose transporter, lactate dehydrogenase, and pyruvate kinase in keloid were summarized here, providing more insights for the prevention and treatment of keloids.