1.Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism.
Jifeng LI ; Haolin GUO ; Ying DONG ; Shuo YUAN ; Xiaotong WEI ; Yuxin ZHANG ; Lu DONG ; Fei WANG ; Ting BAI ; Yong YANG
Chinese Journal of Natural Medicines (English Ed.) 2024;22(1):4-14
Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans
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Drugs, Chinese Herbal/pharmacology*
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Liver Diseases/drug therapy*
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Antioxidants
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Polysaccharides/therapeutic use*
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Medicine, Chinese Traditional
2.The Characteristics of Auditory Brainstem Response Waveform in Autistic Children with Normal Hearing
Zhihan LIN ; Xin ZHOU ; Xuetong WANG ; Ying LI ; Xueyao WANG ; Xin JIN ; Zhipeng ZHENG ; Yi ZHOU ; Jifeng SHI ; Haihong LIU
Journal of Audiology and Speech Pathology 2024;32(2):118-123
Objective To investigate the effect of auditory brainstem response(ABR)in clinical detection and severity assessment of autism spectrum disorder(ASD)in children with normal hearing.Methods ① A total of 55 autistic children(110 ears)with normal hearing and 55 children(110 ears)with typical development(TD)who did not differ in sex composition ratio and average monthly age were divided into four sub-groups according to age:≤24 months group(22 ears),25~36 months group(40 ears),37~48 months group(28 ears)and>48 months group(20 ears).The ABR latencies and interpeak latencies were compared between ASD children and age-matched TD children.② ASD children were graded by severity according to the Diagnostic and Statistical Manual of Mental Dis-orders(DSM-V),and the correlations between the ABR latencies and interpeak latencies in autistic children with normal hearing and the severity grading were studied.Results ① No statistically significant differences in ABR wave latencies and interpeak latencies were found in autistic children with normal hearing under 24 months of age compared to age-matched TD children(P>0.05).② Compared with children with TD,autistic children with nor-mal hearing at 25~36 months of age had significantly longer wave Ⅲ latencies and the interpeak latencies of Ⅰ-Ⅲ andⅠ-Ⅴ;the significantly longer wave Ⅲ,Ⅴ latencies,the interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ and Ⅰ-Ⅴ in autistic chil-dren with normal hearing at 37~48 months of age.Autistic children with normal hearing in the>48 months group had significantly longer wave Ⅴ latencies and interpeak latencies of Ⅲ-Ⅴ,Ⅰ-Ⅴ than age-matched TD children(P<0.05).③ The higher the ASD severity grading the longer the wave Ⅲ and V latencies and the longer interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ,and Ⅰ-Ⅴ(P<0.05).Conclusion Differences in the level of auditory brainstem pathway de-velopment emerged at 25 months of age,and autistic children with normal hearing had significantly lower levels of auditory brainstem development than age-matched TD children.There were correlations between the latencies and interpeak latencies of ABR in autistic children with normal hearing and the severity grading.
3.Recognition of unilateral auditory neuropathy in children
Ying LI ; Zhihan LIN ; Xueyao WANG ; Yang YANG ; Xiao ZHANG ; Yi ZHOU ; Xin JIN ; Zhipeng ZHENG ; Jifeng SHI ; Xuetong WANG ; Jie BAI ; Lining GUO ; Haihong LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(5):447-454
Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.
4.Meta-analysis of the correlation between ocular and neurological manifestations in 43 Chinese children with sialidosis type I
Huaxin ZUO ; Xiaofang ZHOU ; Xiaotun REN ; Wei SHI ; Li LI ; Jifeng YU ; Chunxia PENG
Chinese Journal of Ocular Fundus Diseases 2024;40(1):52-57
Objective:To investigate the correlation between macular cherry red spot (CS) and severity of neurological manifestations in Chinese children with sialidosis (SD) type I.Methods:A evidence-based medical study. "China", "Sialidosis" and "Sialidoses" were used as Chinese and English search terms. The literature was searched in CNKI, Wanfang and PubMed. The cases were all from China and matched the diagnostic criteria. According to the presence or absence of CS in the fundus, the SD children were divided into a group with CS (+) and a group without CS (-), and the correlation between the occurrence of ocular CS and neurological manifestations was compared with meta-analysis by RevMan 5.3 software.Results:Sixty-eight studies were initially retrieved according to the search strategy, and 17 studies were finally included, and 5 studies with CS+ and CS- were meta-analyzed. Among the 43 patients, 28 were male and 15 were female, with a median age of 12 years. Visual impairment was observed in 37 cases (90.2%, 37/41, 2 cases not recorded), and CS was present in 24 cases (55.8%, 24/43). The most common neurological manifestation was myoclonus (97.7%, 42/43), followed by cerebellar ataxia (95.1%, 39/41, 2 cases not recorded) and seizures (91.4%, 32/35, 8 cases not recorded). Pathogenic NEU1 gene mutations were detected in 42 cases and one case was undocumented. The incidence of seizure in group CS+ (100%, 20/20) was higher than that in group CS- (80%, 12/15). Meta-analysis showed that there was no statistically significant difference between the incidence of myoclonus or ataxia [relative risk ( RR)=1.13, 95% confidence interval ( CI) 0.79-1.63, P=0.49] and seizure ( RR=1.13, 95% CI 0.84-2.06, P=0.24) among the children in the CS+ and CS- groups. Conclusions:The incidence of ocular CS in Chinese children with type I SD was 55.8%. There was no correlation with neurological manifestations, however the incidence of seizure was significantly higher in patients with CS than in others without CS.
5.Health inequity analysis in global burn incidence from 1990 to 2019
Shaobin GUO ; Yanran XU ; Jie CHEN ; Jialong DING ; Zeshan CHEN ; Guina GUO ; Jifeng LI
Chinese Journal of Plastic Surgery 2024;40(11):1206-1214
Objective:To study the regional distribution, temporal trend, and health inequity of burn incidence in the world from 1990 to 2019.Methods:The data related to burns worldwide from 1990 to 2019 were collected from the database of Global Burden of Disease (GBD). Based on the number of burn cases and age-standardized incidence rates, the incidence of burn was observed by age, region, socio-demographic index (SDI) area (divided into 5 categories of SDI areas: high, medium-high, medium, medium-low and low, the higher the area, the higher the degree of social development) and country, all of which were expressed as estimated values. Joinpoint regression analysis of the age-standardized incidence of burns from 1990 to 2019 was performed using Joinpoint 4.8.0.1 software to observe the average annual percentage change (AAPC). Rstudio software was used to analyze the Spearman correlation between the age-standardized incidence of burns and SDI from 1990 to 2019. The global inequities of burn incidence were evaluated using the slope index and concentration index from the health equity assessment toolkit, where the slope index reflected the absolute difference in burn incidence between countries with the lowest and highest SDI, and the concentration index indicated the degree to which burn incidence was concentrated in countries with low or high SDI.Results:From 1990 to 2019, the number of global burncases increased from 8 378 121.71 to 8 955 227.68, with an increase of 6.89%. However, the age-standardized incidence rate of burns showed an overall downward trend, from 149.86/100 000 in 1990 to 117.51/100 000 in 2019, with an AAPC of -0.80%. The incidence of burns in the population aged 10-19 years ranked the first in all age groups during the 30 years. Among the six regions of the world, the number of burn cases and the age-standardized incidence rate of burn in the Americas were the highest in 2019, but these two indexes were lower than those in 1999. In 2019, the number of burn patients in medium SDI areas was the highest, and the number of burn patients in low SDI areas was the lowest. The age-standardized incidence of burns was the highest in high SDI areas, and the lowest in medium-low SDI areas. From 1990 to 2019, the number of patients in high and medium-high SDI areas decreased, and the number of patients in other SDI areas increased. Compared with 1990, the age-standardized incidence rates of burns decreased in all SDI regions in 2019, with the greatest decline seen in high SDI and medium-high SDI regions. Cuba had the highest standardized incidence of burns, while Pakistan had the lowest. Spearman correlation analysis showed that from 1990 to 2019, the age-standardized incidence rates of burns in 204 countries and regions were positively correlated with SDI (all P<0.05), and the correlation coefficient decreased from 0.49 in 1990 to 0.37 in 2019. The health inequality slope index decreased from 212.90/100 000 in 1990 to 59.12/100 000 in 2019, and the concentration index decreased from 21.77% in 1990 to 8.38% in 2019. Conclusion:From 1990 to 2019, the global burn incidence rates are disproportionately concentrated in countries and regions with better development status. A significant reduction in the global burn incidence has been accompanied by a significant reduction in these inequities.
6.Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease
Yuwen ZHAO ; Lixia QIN ; Hongxu PAN ; Tingwei SONG ; Yige WANG ; Xiaoxia ZHOU ; Yaqin XIANG ; Jinchen LI ; Zhenhua LIU ; Qiying SUN ; Jifeng GUO ; Xinxiang YAN ; Beisha TANG ; Qian XU
Chinese Medical Journal 2024;137(4):450-456
Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.
7.Health inequity analysis in global burn incidence from 1990 to 2019
Shaobin GUO ; Yanran XU ; Jie CHEN ; Jialong DING ; Zeshan CHEN ; Guina GUO ; Jifeng LI
Chinese Journal of Plastic Surgery 2024;40(11):1206-1214
Objective:To study the regional distribution, temporal trend, and health inequity of burn incidence in the world from 1990 to 2019.Methods:The data related to burns worldwide from 1990 to 2019 were collected from the database of Global Burden of Disease (GBD). Based on the number of burn cases and age-standardized incidence rates, the incidence of burn was observed by age, region, socio-demographic index (SDI) area (divided into 5 categories of SDI areas: high, medium-high, medium, medium-low and low, the higher the area, the higher the degree of social development) and country, all of which were expressed as estimated values. Joinpoint regression analysis of the age-standardized incidence of burns from 1990 to 2019 was performed using Joinpoint 4.8.0.1 software to observe the average annual percentage change (AAPC). Rstudio software was used to analyze the Spearman correlation between the age-standardized incidence of burns and SDI from 1990 to 2019. The global inequities of burn incidence were evaluated using the slope index and concentration index from the health equity assessment toolkit, where the slope index reflected the absolute difference in burn incidence between countries with the lowest and highest SDI, and the concentration index indicated the degree to which burn incidence was concentrated in countries with low or high SDI.Results:From 1990 to 2019, the number of global burncases increased from 8 378 121.71 to 8 955 227.68, with an increase of 6.89%. However, the age-standardized incidence rate of burns showed an overall downward trend, from 149.86/100 000 in 1990 to 117.51/100 000 in 2019, with an AAPC of -0.80%. The incidence of burns in the population aged 10-19 years ranked the first in all age groups during the 30 years. Among the six regions of the world, the number of burn cases and the age-standardized incidence rate of burn in the Americas were the highest in 2019, but these two indexes were lower than those in 1999. In 2019, the number of burn patients in medium SDI areas was the highest, and the number of burn patients in low SDI areas was the lowest. The age-standardized incidence of burns was the highest in high SDI areas, and the lowest in medium-low SDI areas. From 1990 to 2019, the number of patients in high and medium-high SDI areas decreased, and the number of patients in other SDI areas increased. Compared with 1990, the age-standardized incidence rates of burns decreased in all SDI regions in 2019, with the greatest decline seen in high SDI and medium-high SDI regions. Cuba had the highest standardized incidence of burns, while Pakistan had the lowest. Spearman correlation analysis showed that from 1990 to 2019, the age-standardized incidence rates of burns in 204 countries and regions were positively correlated with SDI (all P<0.05), and the correlation coefficient decreased from 0.49 in 1990 to 0.37 in 2019. The health inequality slope index decreased from 212.90/100 000 in 1990 to 59.12/100 000 in 2019, and the concentration index decreased from 21.77% in 1990 to 8.38% in 2019. Conclusion:From 1990 to 2019, the global burn incidence rates are disproportionately concentrated in countries and regions with better development status. A significant reduction in the global burn incidence has been accompanied by a significant reduction in these inequities.
8.Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.
Binghe XU ; Qingyuan ZHANG ; Xichun HU ; Qing LI ; Tao SUN ; Wei LI ; Quchang OUYANG ; Jingfen WANG ; Zhongsheng TONG ; Min YAN ; Huiping LI ; Xiaohua ZENG ; Changping SHAN ; Xian WANG ; Xi YAN ; Jian ZHANG ; Yue ZHANG ; Jiani WANG ; Liang ZHANG ; Ying LIN ; Jifeng FENG ; Qianjun CHEN ; Jian HUANG ; Lu ZHANG ; Lisong YANG ; Ying TIAN ; Hongyan SHANG
Acta Pharmaceutica Sinica B 2023;13(5):2250-2258
Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).
9.Analysis of risk factors of sarcopenia in maintenance hemodialysis patients
Hong LI ; Ruman CHEN ; Xin ZENG ; Yafei BAI ; Mingzhi XU ; Jifeng LI ; Gongxiong WEN ; Chaoqun WANG
Chinese Journal of Nephrology 2023;39(11):815-821
Objective:To explore the prevalence and risk factors of sarcopenia in patients with maintenance dialysis (MHD).Methods:It was a cross-sectional study. Patients who received MHD treatment in the Blood Purification Center of Hainan Provincial People's Hospital in October 2019 were included as study subjects. The patients were divided into sarcopenia group and non-sarcopenia group according to whether they had sarcopenia or not. Chest CT imaging and laboratory examination data were collected. Dual-energy X-ray absorptiometry was used to measure the skeletal muscle mass. Chi-square test or Mantel-Haenszel trend chi-square test was used to compare the clinical data of patients with and without sarcopenia. Multivariate logistic regression equation was used to analyze the risk factors of sarcopenia.Results:A total of 182 MHD patients were enrolled in the study, and the prevalence of sarcopenia was 33.5% (61/182). The proportions of age ≥60 years old, diabetic nephropathy, tunneled-cuffed catheter, body mass index <18 kg/m 2, serum albumin <40 g/L, low density lipoprotein cholesterol ≥3.37 mmol/L, left ventricular ejection fraction <50%, chest CT-suspected pulmonary tuberculosis (PTB) and PTB in sarcopenia group were higher than those in non-sarcopenia group (all P<0.05). Multivariate logistic regression analysis results showed that left ventricular ejection fraction <50% (≥50% as a reference, OR=3.250, 95% CI 1.035-10.206, P=0.044), low-density lipoprotein cholesterol ≥3.37 mmol/L (<3.37 mmol/L as a reference, OR=6.354 ,95% CI 1.675-24.108, P=0.007), chest CT-suspected PTB (normal as a reference, OR=7.433, 95% CI 1.531-36.083, P=0.013), and PTB (normal as a reference, OR=28.871, 95% CI 3.208-259.872, P=0.030) were independent influencing factors of sarcopenia in MHD patients. Conclusions:The prevalence of sarcopenia is higher in MHD patients. Blood low-density lipoprotein cholesterol ≥3.37 mmol/L, ejection fraction <50%, chest CT-PTB and suspected PTB are independent risk factors of sarcopenia in MHD patients. Correcting left ventricular systolic function, regulating blood lipids and preventing PTB as early as possible can reduce the prevalence of sarcopenia in MHD patients.
10.PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis.
Weili YANG ; Xiangyu GUO ; Zhuchi TU ; Xiusheng CHEN ; Rui HAN ; Yanting LIU ; Sen YAN ; Qi WANG ; Zhifu WANG ; Xianxian ZHAO ; Yunpeng ZHANG ; Xin XIONG ; Huiming YANG ; Peng YIN ; Huida WAN ; Xingxing CHEN ; Jifeng GUO ; Xiao-Xin YAN ; Lujian LIAO ; Shihua LI ; Xiao-Jiang LI
Protein & Cell 2022;13(1):26-46
In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

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