1.Dipsacus asper Treats Alzheimer's Disease in Caenorhabditis elegans by Regulating PPARα/TFEB Pathway
Mengmeng WANG ; Jianping ZHAO ; Limin WU ; Shuang CHU ; Yanli HUANG ; Zhenghao CUI ; Yiran SUN ; Pan WANG ; Hui WANG ; Zhenqiang ZHANG ; Zhishen XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):104-114
ObjectiveTo investigate the anti-Alzheimer's disease (AD) effect of Dipsacus asper(DA) in the Caenorhabditis elegans model, and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α (PPARα)/transcription factor EB (TFEB) pathway. MethodsFirst, transgenic AD C. elegans individuals were assigned into the blank control, model, positive control (WY14643, 20 µmol·L-1), and low-, medium-, and high-dose (100, 200, and 400 mg·L-1, respectively) DA groups. The amyloid β-42 (Aβ42) formation in the muscle cells, the paralysis time, and the deposition of amyloid β-protein (Aβ) in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ, LC3I, LAMP2, and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα, and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain (LBD). ResultsCompared with the model group, the positive control group and 200 and 400 mg·L-1 DA groups showed prolonged paralysis time (P<0.05), and all the treatment groups showed decreased Aβ deposition in the head (P<0.01). DA within the concentration range of 50-500 mg·L-1 did not affect the viability of BV2 cells. In addition, DA enhanced the autophagy flux (P<0.05), up-regulated the mRNA levels of beclin1, Atg5, LAMP2, and CLN2 (P<0.05, P<0.01), promoted the nuclear translocation of TFEB (P<0.05), increased LAMP2 expression and autophagy flux (P<0.05, P<0.01), and enhanced the transcriptional activities of PPARα and TFEB (P<0.01). The positive control group and 200 and 400 mg·L-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus (P<0.01). UPLC-MS detected nine known compounds of DA, from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.
2.Application of comfort nursing model intervention in home-based peaceful care for advanced cancer patients
Chunyan PAN ; Yingying WU ; Hongmei JI ; Lixiu LIU ; Yan WANG ; Limin ZHANG
Chinese Journal of Practical Nursing 2024;40(8):575-582
Objective:To explore the effect of comfort nursing intervention in hospice care for advanced cancer patients at home, and to provide reference for hospice care for advanced cancer patients at home.Methods:A randomized controlled trial was conducted. A total of 105 patients with advanced cancer who were treated in the Cancer Hospital Affiliated to Harbin Medical University from January to February 2023 were selected as the research objects. According to the random number table, they were divided into control group of 53 cases and intervention group of 52 cases. The control group received routine nursing methods, while the intervention group received comfort nursing interventions on this basis. The intervention lasted for 4 weeks. The changes in palliative care outcomes, quality of life and death anxiety were compared between the two groups before and after intervention.Results:Totally 105 cases were included, 53 cases in the control group and 52 cases in the intervention group. In the control group, there were 25 males, 28 females, aged (58.96 ± 10.71) years old; in the intervention group, there were 22 males, 30 females, aged (59.82 ± 10.53) years old. Before intervention, there was no statistically significant difference in palliative care outcomes, quality of life and cancer death anxiety scores between the two groups of patients (all P>0.05). After intervention, the total score of palliative care outcomes in the intervention group was (13.34 ± 5.88) points, significantly lower than (16.15 ± 5.72) points in the control group, with a statistically significant difference ( t = 2.48, P<0.05). The overall health status score of quality of life was (68.55 ± 9.34) points in the intervention group, higher than (63.01 ± 9.28) points in the control group ( t = 3.05, P<0.05). The total score of cancer death anxiety was (8.85 ± 2.72) points, significantly lower than (10.59 ± 3.14) points of the control group, with a statistically significant difference ( t = 3.04, P<0.05). Conclusions:The application of comfort nursing mode in home based hospice care can improve the quality of hospice care for advanced cancer patients, reduce their level of death anxiety, and is of great significance for improving the quality of life of advanced cancer patients.
3.Study on the Characteristics of Supramolecular"Imprinting Template"of Curcuma kwangsiensis and Curcuma phaeocaulis
Weilong ZHANG ; Yuchai WANG ; Ru QIAO ; Peng HE ; Shanshan LIANG ; Sheng LIU ; Yingyang TAN ; Yu TANG ; Limin GONG ; Fuyuan HE ; Xue PAN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(6):123-129
Objective The characteristics of supramolecular"imprinting template"of volatile oil of Curcuma kwangsiensis and Curcuma phaeocaulis were analyzed and studied based on the supramolecular"qixi"theory of Chinese materia medica combined with chemometrics.Methods The volatile oil of C.kwangsiensis and C.phaeocaulis were extracted by steam distillation,and the fingerprint and composition information of each batch were obtained by GC-MS.Total statistical moment method was used to compare the imprinting characteristics of the"imprinting template"of C.kwangsiensis and C.phaeocaulis.The core index(CI)of each batch of essential oil of C.kwangsiensis and C.phaeocaulis was calculated,and the topological characteristics of types of"imprinting template"of C.kwangsiensis and C.phaeocaulis were compared by chemometrics.Results There was no significant difference in the extraction rate of volatile oil between C.kwangsiensis and C.phaeocaulis.The average values of total zero order moment(AUCT)were(1.907±0.177)×108,(1.979±0.413)×108 μV·s,respectively,showing that there was no significant difference in the total content of volatile oil between the two groups.The mean values of the total first order moment(MCRTT)were(30.969±0.962)and(33.198±0.409)min.The average value of total second order moment(VCRTT)was(56.176±11.368)and(43.891±4.113)min2,respectively,indicating that there were significant differences in the content ratio and species of volatile oils between the two groups.The similarity of total statistical moments of C.kwangsiensis and C.phaeocaulis was mostly lower than the defined value,indicating that the chemical composition and composition ratio of the volatile oil were different.Principal component analysis and orthogonal partial least squares discriminant analysis could obviously divide C.kwangsiensis and C.phaeocaulis into two categories.Through the analysis of P value and VIP value,the CI values of Xvp 4th order,Xvpc 5th order,Xvpc 6th order,Xvpc 7th order,Xvc 3rd order,Xvpc 4th order were the main difference values of C.kwangsiensis and C.phaeocaulis.Conclusion Through the characterization of"imprinting property"and"topological characteristics"of the supramolecular"imprinting template"and combining with chemometric analysis,it is possible to successfully distinguish C.kwangsiensis and C.phaeocaulis,and find the different CI values between two"imprinting templates".
4.Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway
Shuang CHU ; Yanrao WU ; Limin WU ; Zhenghao CUI ; Pan WANG ; Yiran SUN ; Zhishen XIE ; Zhenqiang ZHANG
China Pharmacy 2023;34(1):12-17
OBJECTIVE To explore the effect mechanism of ethanol extract from Atractylodes macrocephala (EEAM) on microglial phagocytosis and degradation of amyloid β (Aβ) based on peroxisome proliferator-activated receptor γ (PPAR- γ) signaling pathway. METHODS Taking neuromicroglial cell BV2 as subjects, confocal microscopy was used to observe the effects of EEAM (0.3, 0.4, 0.5 mg/mL, similarly hereinafter) on phagocytosis and degradation of Aβ in microglia. Human embryonic kidney cell HEK293 was used to investigate the effects of EEAM on luciferase transcriptional activity of PPAR-γ. The effect of EEAM on nuclear translocation of PPAR-γ was investigated by immunofluorescence. Alzheimer’s disease BV2 cell model was induced by Aβ1-42, and quantitative polymerase chain reaction was used to investigate the effects of EEAM on mRNA expressions of PPAR-γ downstream target genes (Lxra, Lxrb, Abca1, Abcg1, Cd36, Sra and Apoe). RESULTS The results of Aβ uptake experiment showed that after the intervention of medium and high doses of EEAM, fluorescence intensity of Aβ in BV2 cells increased significantly (P<0.05). The degradation experiment of Aβ showed that after the intervention of medium and high doses of EEAM, fluorescence intensity of Aβ in BV2 cells decreased significantly (P<0.05). After the intervention of different doses of EEAM, luciferase transcriptional activity of PPAR-γ in HEK293 cells increased significantly (P<0.05); fluorescence intensity of PPAR-γ in BV2 cells and nuclei (except for low-dose group) increased significantly (P<0.05). mRNA expressions of Lxra, Lxrb, Abca1, Abcg1, Cd36, Sra and Apoe in BV2 cells were increased significantly (P<0.05). CONCLUSIONS EEAM can promote the uptake and degradation of Aβ in microglia by activating PPAR-γ signaling pathway, thus improving Alzheimer’s disease.
5.Surgical approaches and clinical outcomes of endoscopic endonasal resection for trigeminal schwannomas
Laisheng PAN ; Xiao WU ; Bin TANG ; Shenhao XIE ; Limin XIAO ; Bowen WU ; Yuxing CHEN ; Tao HONG
Chinese Journal of Microsurgery 2023;46(5):563-569
Objective:To investigate the surgical approaches and clinical outcomes of endoscopic endonasal approaches (EEA) for trigeminal schwannomas(TSs).Methods:Clinical data, surgical videos and outpatient follow-up notes of 41 patients with TSs and underwent EEA between January 2013 to October 2022 in the Department of Neurosurgery of the First Affiliated Hospital of Nanchang University were retrospectively studied. The patients were 19 males and 22 females, with an average age of 45.3 (22-63) years old. Twenty-four patients had TSs on the left and 17 on the right. According to Jeong's classification, for 6 TSs with type MP, 2 tumours were resected by trans-Meckel's cave approach (TMCA) alone, and the remaining 4 TSs were resected by combined transclival approach (TCA). For the 4 tumours that involved infratemporal fossa(2 of type E3, 1 of type mE3 and 1 of type Mpe3), the surgery were performed via a trans-prelacrimal recess approach(TPRA), of which the operation for type Mpe3 was combined with a TMCA. The trans-laminal papyracea approach (TLPA) was applied to remove 2 tumours of type E1. The rest of 29 patients received the surgery by TMCA alone to remove tumours including 15 of types M, 10 of type Mp, 1 of type ME2, 2 of type E2 and 1 of type MpE2. Gross total tumour resection was achieved in 40 patients(97.6%), with only 1 patient (2.4%) had a subtotal tumour resection.Results:A total of 40 patients had completed the long-term follow-up, with 1 patient lost in follow-up. The average follow-up period was 34(3-101) months; No tumour recurrence or progression was observed over follow-up. After the surgery, preoperative symptoms were improved in 34 patients(89.5%). The main improved symptoms were: facial numbness(78.9%), facial pain(70.0%), headache(88.2%), mastication weakness (50.0%), poor vision (60.0%), diplopia (83.3%), and abducens nerve palsy (100%). Transient and permanent neurological deficits occurred in 8 (19.5%) and 9 (22.0%) patients, respectively. Cerebrospinal fluid leakage and internal carotid artery injury occurred in 1 patient each.Conclusion:According to the location of a tumour, an appropriate EEA should be selected and satisfactory results can be achieved for all types of tumours, except the TSs that has the main body of the tumour located in the posterior cranial fossa.
6.Reference values for urinary flow rate in elderly women: based on a national multicenter study
Xiaodong LIU ; Lingfeng MENG ; Jiawen WANG ; Tianming MA ; Jingchao LIU ; Hai HUANG ; Qingwei WANG ; Min CHEN ; Limin LIAO ; Hong SHEN ; Zhongqing WEI ; Yuansong XIAO ; Tiejun PAN ; Jian REN ; Peng ZHANG ; Xiaojun TIAN ; Benkang SHI ; Yaoguang ZHANG
Chinese Journal of Geriatrics 2023;42(12):1406-1410
Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.
7.Lipopolysaccharide induced intestinal epithelial injury: a novel organoids-based model for sepsis in vitro.
Sisi HUANG ; Sheng ZHANG ; Limin CHEN ; Xiaojun PAN ; Zhenliang WEN ; Yizhu CHEN ; Lidi ZHANG ; Jiao LIU ; Dechang CHEN
Chinese Medical Journal 2022;135(18):2232-2239
BACKGROUND:
Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.
METHODS:
Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer Operetta™ was used to obtain high-resolution images of three-dimensional organoids.
RESULTS:
An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.
CONCLUSIONS
This study provides the primary intestinal in vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.
Mice
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Animals
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Lipopolysaccharides/toxicity*
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Sepsis
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Intestinal Diseases
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Tumor Necrosis Factor-alpha
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Disease Models, Animal
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Organoids
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RNA
8.Two year follow up of myopia cohort in central Jiangsu Province
Chinese Journal of School Health 2022;43(9):1298-1300
Objective:
Based on observational, longitudinal and intervention study of common diseases among students in Jiangsu Province, this paper presents the current progress of two year follow up of myopia cohort regarding the association between growth parameters with progression of myopia among children and adolescents in areas with rapid economic growth.
Methods:
This survey adopted the stratified cluster sampling method for school selection. The full automatic computer optometry (TOPCON RM800) was used to track myopia related parameters for all participants from 2019 to 2020 under the condition of mydriasis (compound topicamide eye drops). Relationship between growth parameters of children and adolescents and the incidence and progression of myopia was analyzed by using Cox regression multiple statistical model.
Results:
The myopia rates of students from grade 1 to grade 3 in 2019 were 5.4%, 21.5% and 37.3% respectively. After one year, the myopia rates of all school stages increased to 25.3%, 43.3% and 58.1% respectively( χ 2=53.59, 49.63, 32.52, P <0.01). The mean diopter of right eye and left eye after mydriasis were ( 0.30± 1.24/0.39±1.26)D in 2019 and (-0.33±1.54/-0.19±1.55)D in 2020, respectively based on Cox multiple regression results, age ( HR =1.21, 95% CI =1.09-1.34), naked eye vision ( HR =0.08, 95% CI =0.07-0.11), height ( HR =0.98, 95% CI =0.97-0.99) showed a strong correlation with the incidence and progression of myopia( P <0.05).
Conclusion
Myopia is growing rapidly in the central region of Jiangsu Province. It is suggested that diopter, axial length, naked eye vision, age, height and other indicators should be included in the refractive archives of children and adolescents in the region.
9.Efficacy of plasma exchange in the treatment of autoimmune hemolytic anemia in children
Yi MENG ; Yubin WU ; Yefei LEI ; Qiang QU ; Zhihong HAO ; Li YU ; Yao ZHANG ; Ping ZHOU ; Sijia ZHANG ; Xuemei LIU ; Hongxia ZHANG ; Yanyan PAN ; Liqun DONG ; Yuhong TAO ; Lijuan ZHANG ; Jianjiang ZHANG ; Limin JIA ; Junmei LIU ; Cuihua LIU ; Hongjiang LI ; Guangbo LI
Chinese Pediatric Emergency Medicine 2022;29(9):691-695
Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.
10.Investigation on status quo and needs of pharmaceutical training among general practice faculty
Zhiyan LIU ; Tianhao WANG ; Limin LAO ; Xiaoyu LI ; Wei WU ; Qing XU ; Qianzhou LYU ; Zhigang PAN
Chinese Journal of General Practitioners 2022;21(6):526-532
Objective:To investigate the current situation and needs of pharmaceutical training for general practice faculty.Methods:A self-designed questionnaire survey was conducted in April 2019. The participants were general practice faculty attending the national training course in Zhongshan Hospital and selected by convenience sampling method.Results:A total of 219 general practice teachers participated in the survey, 51.14% (112/219) of the participants thought that the current pharmaceutical knowledge did not meet the needs of pharmaceutical services in daily work, and 67.58% (148/219) attended pharmacy related training every year, and the frequency was mainly 1—2 times per year (56.62%, 124/219). The main reasons for attending the training were working needs (68.24%, 101/148) and willingness (55.41%, 82/148); 63.51% (94/148) of the participants thought that the training was moderate or less effective, mainly because of the weak strength of trainers (40.54%, 60/148), insufficient attention paid by trainers (37.16%, 55/148) and lack of depth (37.16%, 55/148). The survey showed that 76.26% (167/219) of general practice teachers had pharmaceutical training needs; and gender, working years and working experience in secondary and/or tertiary hospitals were influencing factors for pharmaceutical training needs. And female faculty, those working less than 10 years and with working experience in secondary hospitals had higher demand for pharmaceutical training. The expected pharmaceutical training focused primarily on the selection and optimization of medication schemes (72.60%, 159/219), interaction/incompatibility between medicines (62.10%, 136/219) and pharmaceutical care in medical treatment (57.08%, 125/219). The expected training methods were mainly interactive case analysis and discussion (69.41%, 152/219) through the internet or APP (such as WeChat) (54.34%, 119/219); the expected training frequency was no more than once in two months (36.07%, 79/219), better in working time (48.86%, 107/219) and each session was 30—45 minutes (38.36%, 84/219).Conclusion:General practice faculty has a high demand for pharmaceutical training. Targeted, individualized and systematic pharmaceutical training courses should be developed according to the pharmaceutical training needs of participants.


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