1.Basic and Clinical Research of Fecal Microbiota Transplantation in The Treatment of Central Nervous System Diseases
Hong-Ru LI ; Cai-Hong LEI ; Shu-Wen LIU ; Yuan YANG ; Hai-Xia CHEN ; Run ZHANG ; Yin-Jie CUI ; Zhong-Zheng LI
Progress in Biochemistry and Biophysics 2024;51(11):2921-2935
As a microbial therapy method, fecal microbiota transplantation (FMT) has attracted the attention of researchers in recent years. As one of the most direct and effective methods to improve gut microbiota, FMT achieves therapeutic benefits by transplanting functional gut microbiota from healthy human feces into the intestines of patients to reconstruct new gut microbiota. FMT has been proven to be an effective treatment for gastrointestinal diseases such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel disease. In addition, the clinical and basic research of FMT outside the gastrointestinal system is also emerging. It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system (CNS) through the gut-brain axis. Some gut bacteria can synthesize and release neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and dopamine. Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters, thereby affecting brain function. Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function. FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves, immunity, and metabolites. This article introduces the development of FMT and the research status of FMT in China, and reviews the basic and clinical research of FMT in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neurotraumatic diseases (spinal cord injury, traumatic brain injury) and stroke from the characteristics of three types of nervous system diseases, the characteristics of intestinal flora, and the therapeutic effect and mechanism of fecal microbiota transplantation, summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets. We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis. (1) Gut microbiota metabolites, such as SCFAs, TMAO and LPS. (2) Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB. (3) Neurotransmitter 5-HT. In the process of reviewing the studies, we found the following problems. (1) In basic researches on the relationship between FMT and CNS diseases, there are relatively few studies involving the autonomic nervous system pathway. (2) Clinical trial studies have shown that FMT improves the severity of patients’ symptoms and may be a promising treatment for a variety of neurological diseases. (3) The improvement of clinical efficacy is closely related to the choice of donor, especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases. However, there are common challenges in current research on FMT, such as the scientific and rigorous design of FMT clinical trials, including whether antibiotics are used before transplantation or different antibiotics are used, as well as different FMT processes, different donors, different functional analysis methods of gut microbiota, and the duration of FMT effect. Besides, the safety of FMT should be better elucidated, especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully. It is worth mentioning that the clinical development of FMT even exceeds its basic research. Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013. FMT therapy has great potential in the treatment of nervous system diseases, is expected to open up a new situation in the medical field, and may become an innovative weapon in the medical field.
2.Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum.
Jia XUE ; Hai-Jie CHEN ; Yong-Yi ZHOU ; Jia-Huan YUAN ; Zhi-Chen CAI ; Nan WU ; Cui-Hua CHEN ; Xun-Hong LIU ; Li-Si ZOU ; Sheng-Xin YIN ; Wei YANG ; Jian-Ming CHENG
China Journal of Chinese Materia Medica 2023;48(13):3448-3461
A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid
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Epimedium
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Tandem Mass Spectrometry
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Chromatography, Liquid
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Multivariate Analysis
3.Clinicopathological features of spinal solitary fibrous tumor.
Hai Jing GE ; Jing Jing YAO ; Li LI ; Bo Wen LI ; Cui GE ; Hao LIU ; Yong LI ; Hong Fang YIN
Chinese Journal of Pathology 2022;51(9):875-880
Objective: To investigate the clinicopathological, molecular genetic, immunohistochemical and prognostic features of spinal solitary fibrous tumor (SFT). Methods: The clinical data of 12 cases of spinal SFT in Beijing Tsinghua Changgung Hospital, Affiliated to Tsinghua University, diagnosed from January 2015 to December 2021 were collected and reclassified. The clinical data, histopathology, immunohistochemistry and molecular genetics were analyzed. Follow-up and related literature reviews were conducted. Results: Among the 12 patients, there were 5 males and 7 females; the age ranged from 31 to 73 years, with a median age of 50.5 years. All 12 cases were primary tumors, including 4 cases diagnosed at the first time and 8 recurrent cases. Among the 12 cases, 8 were WHO grade 1, 3 were WHO grade 2, and 1 was WHO grade 3. Microscopically, the spinal SFT appeared as a spindle cell tumor, the stroma was rich in many thin-walled blood vessels with various histological features such as cell morphology and necrosis according to the different tumor grade. All (12/12) of the cases expressed vimentin and STAT6 (diffuse and strong nuclear stain), 11 cases (11/12) expressed both CD34 and bcl-2, and 7 cases (7/12) expressed CD99. Next-generation sequencing showed that 12 (12/12) of the patients had NAB2-STAT6 gene fusion. The 12 patients were followed up for 6 to 80 months. There were no recurrences or metastases in the 4 first cases after operation. Among the 8 recurrent cases, 2 of the patients relapsed and 2 died. Conclusions: Spinal SFT is rare and has a high recurrence tendency. Many aspects need to be considered in the diagnosis process. STAT6 is a relatively specific marker for the diagnosis of this tumor. Complete surgical resection is the preferred treatment while postoperative radiotherapy is recommended to reduce tumor recurrence.
Adult
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Aged
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Female
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Humans
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Immunohistochemistry
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Male
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Middle Aged
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Prognosis
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Solitary Fibrous Tumors/surgery*
4.Protection of Addition and Subtraction Therapy of Ditantang Combined with Taohong Siwutang to Brain Nerve of Patients with Cerebral Infarction and (Syndrome of Phlegm and Blood Stasis Blocking Collaterals) During Early Recovery
Yong-xia CHANG ; Jiao LI ; Wen-li HOU ; Lei GE ; Yin WANG ; Teng WANG ; Qiu-yun MA ; Hai-chao MENG ; Xiao-hong ZUO ; Wan-seng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(1):135-140
Objective:To discuss clinical effect of addition and subtraction therapy of Ditantang combined with Taohong Siwutang to cerebral infarction and syndrome of phlegm and blood stasis blocking collaterals during early recovery, and to study protection to brain nerve. Method:One hundred and fifty-two patients were randomly divided into control group (76 cases) and observation group (76 cases) by random number table, 71 patients in control group completed the therapy (5 patients were falling off, missing visit or eliminated), and 70 patients in observation group completed the therapy. Both groups' patients got comprehensive rehabilitation measures. Patients in control group got Zhongfeng Huichun pills, 1.5 g/time, 3 times/day. Patients in observation group got addition and subtraction therapy of Ditantang combined with Taohong Siwutang in the morning and at night, 1 dose/day. The treatment was continued for 12 weeks. Before and after treatment, scores of degree of neurological deficit, Barthel (BI) index, Fugl-Meyer scale (FMA), modified Rankin scale (MRS) and syndrome of phlegm and blood stasis blocking collaterals were graded. And levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and neuron specific enolase (NSE). And cerebral hemodynamics were detected, and peak flow velocity (VS), vascular resistance index (RI), pulsatility index (PI) and cerebrovascular reserve function (CVR) were recorded. Safety was evaluated. Result:After the 6th week and 12th week of treatment, scores of degree of neurological deficit, BI, FMA, MRS, syndrome of phlegm and blood stasis blocking collaterals, AOPP, MDA, NSE, RI and PI were lower than those in control group (
5.Primary Study of Henan Cerebral Palsy Register and Rehabilitation Management System
Jun-ying YUAN ; Yi-wen WANG ; Jun WANG ; Jie LIU ; Bo CUI ; Zhi-jun CAI ; Hai CHEN ; Yong-qiang GAO ; Feng-wei LIU ; Guo-hui NIU ; Chun-ya SU ; Jun-hui WANG ; Liang WANG ; Hua-chun XIONG ; Hong-yin ZHAI ; Deng-na ZHU
Chinese Journal of Rehabilitation Theory and Practice 2020;26(8):885-891
Objective:To introduce the construction of Henan Cerebral Palsy Register and Rehabilitation Management System (HCPRRMS) and to explore the construction project of regional register and surveillance of cerebral palsy. Methods:The construction process, registration content and preliminary results of HCPRRMS were systematically introduced. Results:HCPRRMS was independent developed in 2014. Since March, 2015, the system has been used to register information of patients with cerebral palsy in the Third Affiliated Hospital of Zhengzhou University. Until September, 2019, a total of 23 child rehabilitation institutions had used the registration management system. There were 1357 patients with cerebral palsy registered in this system, in which 936 cases (68.98%) were male, 501 cases (36.92%) were with gestational weeks < 37, 443 cases (32.65%) were with birth weight < 2500 g, and 430 cases (31.69%) were born with hypoxic-ischemic encephalopathy. Among them, the spastic cerebral palsy patients (1117 cases, 86.74%) accounted for the highest proportion. There was significant difference among types of cerebral palsy and the classification of GMFCS. A total of 1117 patients with cerebral palsy showed MRI-identified brain abnormalities, in which, periventricular leukomalacia accounted for the most (480 cases). For the complications, epilepsy accounted for 14.44% (196 cases), vision impairment accounted for 8.03% (109 cases), hearing impairment accounted for 11.64% (158 cases). Among 769 cases aged more than two years, language-speech dysfunction accounted for 52.66% (424 cases); and among 216 cases aged more than four years, mental retardation accounted for 37.96% (82 cases). Conclusion:HCPRRMS could help to understand the risk factors, clinical characteristics, and complications of cerebral palsy.
6.A clinical study of allogeneic hematopoietic stem cell transplantation in 23 patients with early T-cell precursor acute lymphoblastic leukemia.
Yuan Xin ZHU ; Ming Qing ZHU ; Hai Ping DAI ; Si Ning LIU ; Jia YIN ; Zheng LI ; Qing Ya CUI ; Xia Ming ZHU ; De Pei WU ; Xiao Wen TANG
Chinese Journal of Hematology 2019;40(12):1021-1025
Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions: Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.
Adult
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Hematopoietic Stem Cell Transplantation
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Humans
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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Precursor Cells, T-Lymphoid
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Remission Induction
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Retrospective Studies
7.Risk of venous thromboembolism in Chinese pregnant women: Hong Kong venous thromboembolism study
Duo HUANG ; Emmanuel WONG ; Ming Liang ZUO ; Pak Hei CHAN ; Wen Sheng YUE ; Hou Xiang HU ; Ling CHEN ; Li Xue YIN ; Xin Wu CUI ; Ming Xiang WU ; Xi SU ; Chung Wah SIU ; Jo Jo HAI
Blood Research 2019;54(3):175-180
BACKGROUND: Previous Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum period in the Chinese population. We investigated the risk of venous thromboembolism in a “real-world” cohort of pregnant Chinese women with no prior history of venous thromboembolism. METHODS: In this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed. RESULTS: The mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29–36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pulmonary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester. CONCLUSION: Chinese women had a substantially lower risk of venous thromboembolism during pregnancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early pregnancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.
Asian Continental Ancestry Group
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Cesarean Section
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Cohort Studies
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Diabetes Mellitus
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Early Ambulation
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Female
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Heart Diseases
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Hong Kong
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Humans
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Hypertension
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Incidence
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Observational Study
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Postpartum Period
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Pregnancy
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Pregnancy Trimester, First
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Pregnant Women
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Pulmonary Embolism
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Venous Thromboembolism
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Venous Thrombosis
8.Three-dimensional reconstruction of pelvic CT in guiding iliac nail implantation
Chun-Guang LI ; Ning TIAN ; Pi-Bao LI ; En-Dong SHI ; Hai-Yin CUI ; Zu-Dong YIN ; Lin CHENG
Chinese Journal of Tissue Engineering Research 2018;22(3):444-449
BACKGROUND: Iliac screw implantation has no unified standard. Because of the large individual differences, preoperative pelvic three-dimensional (3D) CT reconstruction can measure the diameter, depth and angle of the screws, which increases the placement accuracy. OBJECTIVE: To measure the screw placement-related data by pelvic 3D CT reconstruction, so as to guide the screw placement and improve its accuracy. METHODS: Fifty patients with pelvic lesions or fractures admitted in Shandong Provincial Third Hospital from January 2013 to December 2016 were selected, and the pelvis was scanned with CT and then was reconstructed. The point A (the intersection of S1posterior sacral posterior wall and posterior superior iliac spine) was as the screw placement point, and three paths were measured on the point: posterior superior iliac spine path (AD path); anterior inferior iliac spine path (AC path); top of greater sciatic notch to the acetabular roof (AB path). On the plane of these three pathes, the section was made on the iliac bone, respectively; in each section, the channel for iliac nail was designed. RESULTS AND CONCLUSION: (1) In the same path, there was no significant difference in the path length of the screw between male and female patients (P > 0.05). Paired t test showed that the diameter and length depth and angle of the screws were significantly different between AD and AC paths, AC and AD (P < 0.05). (2) There was no significant difference in the inclination angle of the spiral channel between male and female patients (P > 0.05). The inclination angle of the spiral channel and lateral angle at different paths showed significant difference between male and female patients (P < 0.05). (3) To conclude, 3D reconstruction of pelvis CT can be used to measure the length, diameter and angle of the iliac screw, and to guide the surgical treatment.
9.3D Computed Tomography Assist in Making the Protocol for Primary TKA Using PSI
Feng-Jin CUI ; Ming-Xin WU ; Yin-Wei BAI ; Kang CAI ; Yun FU ; Hai-Qing XIE
Journal of Sun Yat-sen University(Medical Sciences) 2018;39(2):245-251
[Objective]To investigate the feasibility of making the protocol with computed tomography data for total knee arthroplasty using patient-specific femoral and tibial cutting blocks.[Methods]54 consecutive patients diagnosed with osteoarthritis were divided randomly into two groups. Every patients accepted 3-dimentional computed tomography scan for bilateral legs before operation,the protocol were made for every patients before operation.When making the pre-operative protocol,we accepted the prothesis surpass the osteotomy edge finitely,tibia prothesis rotational orientation according to the outline of the tibial osteotomy. The thickness of the posterior condyle of femur resected was as the same with the prothesis posterior condyle as possible. The patients in trial group undergone total knee arthroplasty(TKA) using patient-specific instruments(PSI)according to the preoperative protocol,while the patients in the control group undergone TKA using custom instruments(CI).The operation time,the times that the scale of the prosthesis were altered intraoperation,the mean thickness of the posterior condyle of femur resected in the operation,AKS score 3 months and 1 year after the operation were recorded and compared between the two groups. Plain film radiography after the operation were analyzed.[Results]No significant differences were found between two groups with respect to the operation time. 8 patients altered to a lesser prosthesis in the CI group during the operation,all in bibia contrast to no one need alteration in the PSI group.The thickness of the osteotomy on the posterior condyle of femur in the PSI group is bigger than that of CI group as a result.The AKS score of the patients in the PSI group is higher than that of CI group 3 months after the opera-tion,whereas no significant difference was found 1 year after the operation.[Conclusion]The reconstructed image by thin layer CT can be used for preoperation protocol for TKA,which might be helpful in deciding the size of femour prosthesis;the implants can surpass the edge of the osteotomy finitely in TKA,which is not necessarily cause any complain.We can orient the tibia prosthesis rotation according to the outline of the osteotomy of the patients'tibia.
10.Hyperoside Suppresses Lipopolysaccharide-induced Inflammation and Apoptosis in Human Umbilical Vein Endothelial Cells
Yan-Qiang ZHOU ; Yin-Tao ZHAO ; Xiao-Yan ZHAO ; Cui LIANG ; Ya-Wei XU ; Ling LI ; Yuan LIU ; Hai-Bo YANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2018;38(2):222-228
Finding the novel drug from the effective components of traditional Chinese herbal medicine is a hotspot of the modern pharmacological research.Hyperoside (HYP) belongs to flavonoid glycosides,and it has various properties,such as anti-inflammation,anti-spasm,anti-diuretic,antitussive,lowering blood pressure,and lowering cholesterol effects as well as protective effects for the cardiac and cerebral blood vessels.The purpose of this study was to investigate the effects of HYP on inflammatory and apoptotic responses in vascular endothelial cells stimulated by lipopolysaccharide (LPS) and further to identify the possible mechanisms underlying these effects.In our study,human umbilical vein endothelial cells (HUVECs) were stimulated with 1 μg/mL LPS in the presence or absence of HYP (10,20 and 50 μrnol/L).Our results indicated that HYP alone exerted no cytotoxicity on HUVECs,while it had an up-regulatory effect on the viability of HUVECs induced by LPS in a dose-dependent manner;increased mRNA expression of IL-1β,IL-6,TNFα and iNOS induced by LPS was attenuated after treatment with HYP both in a dose-and time-dependent manner;LPS-induced HUVECs apoptosis and cleaved-caspase 8,9,3 were all significantly reduced by HYP.Furthermore,the possible pathway involved in apoptosis and inflammation by HYP was detected,and the results showed that when treated with HYP,LPS-induced mitochondrial membrane instability was significantly inhibited through up-regulation of Bcl-2 and down-regulation of Bax.Furthermore,the expression of TLR4 and the phosphorylation of Iκ Bα and p65 in LPS-treated cells were blocked by HYP.Our results suggested that HYP treatment prevented HUVECs from LPS-induced inflammation and apoptosis responses,which might be mediated by inhibiting TLR4/NFκB pathway.

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