1.Protective Effect of Liuwei Dihuangwan on Mitochondrial Damage in AD Model of Caenorhabditis Elegans
Jinfeng ZHANG ; Yuliang TONG ; Jiapeng WANG ; Ting SU ; Deping ZHAO ; Hao YU ; Kun ZUO ; Ziyue ZHU ; Meiling JIN ; Ning ZHANG ; Xia LEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):18-25
ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan (LW) on mitochondrial damage in the Alzheimer's disease (AD) model of Caenorhabditis elegans (C. elegans). MethodC. elegans transfected with human β-amyloid protein (Aβ) 1-42 gene was used as an AD model. The rats were divided into blank group, model group, metformin group (50 mmol·L-1), and low, medium, and high dose (1.04, 2.08, 4.16 g·kg-1) LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine (5-HT) in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate (ATP) kit, and mitochondrial membrane potential was detected by the JC-1 method. In addition, the mRNA expression of Aβ expression gene (Amy-1), superoxide dismutase-1 (SOD-1), mitochondrial transcription factor A homologous gene-5 (HMG-5), mitochondrial power-associated protein 1 (DRP1), and mitochondrial mitoprotein 1 (FIS1) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT (P<0.05) and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group, in the model group, the mRNA expression of Aβ protein and Amy-1 increased (P<0.01), and the mRNA expression of SOD-1 and HMG-5 decreased (P<0.01). The mRNA expression of DRP1 and FIS1 increased (P<0.01), and the level of mitochondrial membrane potential decreased (P<0.05). The content of ATP decreased (P<0.01). Compared with the model group, in the positive medicine group and medium and high dose LW groups, the mRNA expression of Aβ protein and Amy-1 decreased (P<0.05,P<0.01), and the mRNA expression of SOD-1 and HMG-5 increased (P<0.01). The mRNA expression of DRP1 decreased (P<0.05,P<0.01), and that of FIS1 decreased (P<0.01). The level of mitochondrial membrane potential increased (P<0.01), and the content of ATP increased (P<0.05,P<0.01). ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria, protect mitochondrial DNA, reduce the fragmentation of mitochondrial division, repair the damaged mitochondria, adjust the mitochondrial membrane potential, restore the level of neuronal ATP, and reduce the neuronal damage caused by Aβ deposition.
2.Application of optical coherence tomography in orthokeratology fitting
Jing HAO ; Gaixin WANG ; Yunfei LI ; Jin LI ; Yuxia ZUO ; Yu BAI ; Yingying QIAO ; Jin WANG
International Eye Science 2024;24(8):1345-1348
AIM: To assess the gap between the peak of the base curve to the surface of the cornea, as well as examines the correlation between the thickness of the tear film and the fitting of the orthokeratology lens through optical coherence tomography(OCT), providing an intuitive and quantitative clinical evaluation method for the fitting of the orthokeratology lens.METHODS: Myopia patients who fitted orthokeratology at our hospital from January to December 2023 were included. Examinations, including naked vision, slit lamp, non-contact intraocular pressure, ocular fundus, eye position, corneal diameter, corneal topography, tear film rupture time, optometry, etc., were performed on all patients before fitting. The trial lens parameter was selected according to the examination results, and fluorescein staining was performed to evaluate lens fitting state after patients adapted to wearing glasses. According to the performance of fluorescein staining, the inspected eyes are divided into three groups: lens loose group, lens fitting group, and lens tight group. In addition, the tear film thickness of three groups of subjects was measured by OCT, and the differences between the three groups of data were evaluated.RESULTS: A total of 49 myopic patients(77 eyes)were included. The average sphere degree was -3.10±1.25 D, the average cylinder degree was -0.43(-0.75, 0)D, the average horizontal keratometry(HK)was 42.48±0.81 D, and vertical keratometry(VK)was 42.98(42.25, 43.50)D. There were 21 cases(34 eyes)in the lens fitting group, with 13 cases of bilateral eyes, 8 cases of one eye, 14 cases(22 eyes)in the lens loose group, with 8 cases of bilateral eyes, 6 cases of one eye, and 14 cases(21 eyes)in the lens tight group, with 7 cases of bilateral eyes, 7 cases of one eye. There was no statistical difference in the main basic data of the subjects in the three groups(all P>0.05). OCT showed that the tear film thickness of the lens fitting group, the lens loose group, and the lens tight group was 231.18(219.0, 243.0), 220.41(214.0, 224.3), and 249.00(241.5, 258.0)μm, respectively, and there was statistical significance in the thickness among the three groups(P<0.05).CONCLUSION: OCT can serve as a safe and reliable method for measuring the tear film thickness, which can help evaluate the suitability of orthokeratology and provide a non-invasive, more intuitive, and quantitative evaluation method for the fitting and evaluation of orthokeratology.
3.Research status of traditional Chinese medicine monomer,drug-to-drug groups and compound formula in the treatment of endometriosis
Bin YUE ; Yuan-Huan CHEN ; Quan-Sheng WU ; Xiao-Hua ZHANG ; Yuan CHENG ; Hao MEI ; Can-Can HUANG ; Zuo-Liang ZHANG ; Xiu-Jia JI
The Chinese Journal of Clinical Pharmacology 2024;40(15):2283-2287
Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.
4.Therapeutic results of three-dimensional aortic valve anatomic repair for regurgitant bicuspid aortic valve
Jun LI ; Chunsheng WANG ; Zheng ZUO ; Hao LAI ; Lili DONG ; Kai ZHU ; Junyu ZHAI ; Yongxin SUN ; Wenjun DING ; Tao HONG
Chinese Journal of Surgery 2024;62(11):1024-1031
Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.
5.Genetic and clinical characteristics of single and compound types of patients with long QT syndrome type 3
Zhonghe ZHANG ; Jing ZUO ; Yan HUANG ; Hongyi DUAN ; Hao XIA ; Hong JIANG ; Dan HU
Chinese Journal of Cardiology 2024;52(7):777-783
Objective:To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3).Methods:This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands.Results:A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion:Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.
6.Nanozyme-based Spinal Cord Injury Treatment
Shi-Qun CHEN ; Yi-Li WANG ; Zuo-Hong CHEN ; Hao WANG ; Xiao-Dong ZHANG
Progress in Biochemistry and Biophysics 2024;51(11):2905-2920
Traumatic spinal cord injury (SCI) refers to damage to the structure and function of spinal cord caused by external trauma. This damage results in the loss of sensation, movement, or autonomous functions, which can lead to partial or complete paralysis and impact the patients’ independence and quality of life. Studying drugs related to spinal cord injuries and their mechanisms of action will help enhance patients’ quality of life and alleviate social and economic burdens. Traumatic spinal cord injury can be categorized into primary and secondary injuries. It leads to ongoing neurodegeneration, inflammation, and scarring, necessitating continuous intervention to reduce the cascading effects of secondary injuries. Regenerative repair of SCI has been one of the most challenging problems in medicine. It is characterized by the involvement of microglia, phagocytes (including neutrophils and monocytes), and antigen-presenting cells of the central nervous system, such as dendritic cells. These inflammatory mediators contribute to axonal demyelination and degeneration, leading to severe nerve damage. Currently, there has been little progress in the clinical treatment of SCI. Current clinical modalities, such as surgical interventions and hormone shock therapies, have not yielded specific pharmacotherapeutic options, hindering significant functional recovery. The current treatment methods are ineffective in alleviating oxidative stress and neuroinflammatory responses caused by spinal cord injury. They also do not offer neural protection, resulting in ongoing neurofunctional degradation. Intravenous injection of methylprednisolone through the arm has been used as a treatment option for spinal cord injury. Recent studies have shown that the potential side effects of the drug, such as blood clots and pneumonia, outweigh its benefits. Methylprednisolone is no longer recommended for the routine treatment of spinal cord injury. In recent years, significant progress has been made in spinal cord injury intervention through the use of nanotechnology and biomaterials. Nanozymes can enhance the therapeutic efficacy of spinal cord injury by catalyzing the clearance of free radicals similar to enzymes and suppressing inflammatory responses. Nanozymes can reduce the degree of fibrosis, promote neuron survival and angiogenesis, and provide favorable conditions for tissue regeneration. Through in vitro and in vivo toxicology experiments, it was found that the nanozyme demonstrates good biocompatibility and safety. It did not cause any significant changes in body weight, hematological indicators, or histopathology. These findings indicate the potential for its clinical applications. Based on current research results and discoveries, nanozymes have broad application prospects in the biomedical field. There are numerous potential research directions and application areas that are worthy of further exploration and development. Although there have been preliminary studies on the catalytic performance of nanozymes, further research is needed to thoroughly investigate their catalytic mechanisms. Further exploration of the interaction between nanozymes and substrates, reaction kinetics, and factors affecting catalytic activity will help to better understand their mechanism of action in the field of biocatalysis.
7.Therapeutic results of three-dimensional aortic valve anatomic repair for regurgitant bicuspid aortic valve
Jun LI ; Chunsheng WANG ; Zheng ZUO ; Hao LAI ; Lili DONG ; Kai ZHU ; Junyu ZHAI ; Yongxin SUN ; Wenjun DING ; Tao HONG
Chinese Journal of Surgery 2024;62(11):1024-1031
Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.
8.Clinical Analysis of Reversible Posterior Encephalopathy Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation in Children
Zuo-Feng LI ; Hao XIONG ; Zhi CHEN ; Li YANG ; Ming SUN ; Wen-Jie LU ; Shan-Shan QI ; Fang TAO ; Lin-Lin LUO ; Yu-Qing JIAO
Journal of Experimental Hematology 2024;32(5):1560-1565
Objective:To summarize the clinical features of reversible posterior encephalopathy syndrome(PRES)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed,and their clinical characteristics,imaging examination,laboratory examination,and treatment regression were summarized.Results:Among 281 children underwent allo-HSCT,6 cases(2.14%)developed PRES,with a median age of 5.1(1.5-9.7)years old.4 cases underwent related haploidentical donor transplantation,and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation,respectively.All six children had an acute onset of illness,with clinical manifestations of nausea and vomiting,seizures,psychiatric disorders,visual disturbances.The five cases elevated blood pressure.All children with PRES were treated with oral immunosuppressive drugs during seizures,and 3 cases were combined with different degrees of graft-versus-host disease.Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications(cyclosporine,etc.)and symptomatic supportive treatments(oral antihypertensive,diazepam for antispasmodic,mannitol to lower cranial blood pressure),and one of them relapsed more than 8 months after the first seizure.Conclusion:PRES is rare after hematopoietic stem cell transplantation in children,and its onset may be related to hypertension,cytotoxic drugs,graft-versus-host disease,etc.Most of them can be recovered after active treatment,but not completely reversible,and the prognosis of those who combined with TMA is poor.
9.Effects of gastrodin on astrocyte phenotype and the receptor of advanced glycation endproducts expression after hypoxic-ischemic brain damage in neonatal rats
Peng-Xiang WANG ; Xue-Qi REN ; Han-Jun ZUO ; Cheng WAN ; Jin-Sha SHI ; Hao-Long SHI ; Min ZHAO ; Juan-Juan LI
Acta Anatomica Sinica 2024;55(6):677-684
Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P<0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P<0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P<0.05),and the protein expression levels of BDNF and IGF-1 further increased(P<0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P<0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P<0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P<0.05),the expressions of BDNF and IGF-1 increased significantly(P<0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.
10.Intestinal tissue injury and gut microbiome changes in mice treated with whole body irradiation by gamma rays
Min DUAN ; Zhe YANG ; Ying LIU ; Yongyi WANG ; Yumeng YE ; Yanhui HAO ; Hongyan ZUO ; Yang LI
Military Medical Sciences 2024;48(9):641-649
Objective To investigate the effects of 0.5 Gy 60Co γ-ray irradiation on intestinal tissue injury and intestinal microflora in mice.Methods C57BL/6N mice were irradiated with 0.5 Gy 60Co γ-ray at 1 d,3 d,7 d and 14 d after irradiation.Jejunum tissues were fixed and frozen,and feces were frozen.Hematoxylin-eosin staining was used to observe the pathological injury to jejunum after irradiation,ki67 immunohistochemical staining was adopted to detect the proliferation of jejunum crypt cells,and TdT-mediated dUTP nick end labeling was employed to detect the apoptosis of jejunum crypt cells.The expressions of TNF-α,IL-1β,IL-6 and IL-10 cytokines in small intestines were detected via radioimmunoassay.The changes of intestinal flora in mice after irradiation were analyzed by metagenomic sequencing,and LEfSe analysis and ROC analysis were used to screen the bacteria with significant differences.Results After 0.5 Gy 60Co γ-ray irradiation,the proliferative cells of the jejunal crypt were significantly decreased at 1 d after irradiation(P<0.05),while the apoptotic cells were significantly increased at 1 and 3 d after irradiation(P<0.01).The expression of TNF-α at 7 and 14 d after irradiation,that of IL-1 β at 1,3,7 and 14 d after irradiation and that of IL-6 at 3,7 and 14 d after irradiation were significantly increased(P<0.05),while the expression of IL-10 at 7 and 14 d after irradiation was significantly decreased(P<0.05).After 0.5 Gy 60Co γ-ray irradiation,intestinal flora composition changed significantly at phylum,genus and species levels,and Lactobacillus murinus,Lactobacillus johnsonii,Alistipes-unclassified,Mucispirillum schaedleri underwent the most significant changes and had higher LDA scores.Conclusion The whole body irradiation of 0.5 Gy 60Co γ-ray can cause intestinal tissue damage and change the composition of intestinal flora in mice.

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