1.Neuroprotective effect of ethanol extract of Corni Fructus on Aβ25-35- induced Alzheimer's disease mice by regulating LSD1/PSD95
Jige YANG ; Lixin LI ; Zhonghua LI ; Yunfang SU ; Zijuan ZHANG ; Junying SONG ; Huahui ZENG ; Zhenqiang ZHANG ; Jinlian MA
Journal of Beijing University of Traditional Chinese Medicine 2024;47(3):352-363
Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.
2.Currentstatus and effect of"communication with intractable high-risk patients"in a tertiary hospital in Guangzhou
Zhongqi LIU ; Cheng QIU ; Zhonghua ZENG ; Ting WU ; Hongzhong HUANG ; Qiusheng LIU ; Dayue LIU
Modern Hospital 2024;24(5):726-728,732
This paper aims to focus on and implement strategies for preventing and resolving medical complaints and dis-putes at their emergence.The hospital promptly compiled a summary of the main problems and concerns reported from patients o-ver the past few years.It combined medical practices with the characteristics of admitted patients with severe diseases,complex treatment plans,and high risks.Since 2020,this hospital has been actively engaging with intractable high-risk patients and de-veloped a scheme that engaging clinical departments,medical management,and dispute management departments together to con-duct preoperative/pre-treatment communication.With a focus on patient management,this hospital upholds the concept of the pa-tient-centered humanistic philosophy in the process of doctor-patient communication to enhance the quality of communication.Consequently,the hospital has benefited from the communication scheme,achieving satisfactory effect in ensuring a solid medical safety and reducing the incidence of medical disputes.
3.Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.
Chengyuan GU ; Zengjun WANG ; Tianxin LIN ; Zhiyu LIU ; Weiqing HAN ; Xuhui ZHANG ; Chao LIANG ; Hao LIU ; Yang YU ; Zhenzhou XU ; Shuang LIU ; Jingen WANG ; Linghua JIA ; Xin YAO ; Wenfeng LIAO ; Cheng FU ; Zhaohui TAN ; Guohua HE ; Guoxi ZHU ; Rui FAN ; Wenzeng YANG ; Xin CHEN ; Zhizhong LIU ; Liqiang ZHONG ; Benkang SHI ; Degang DING ; Shubo CHEN ; Junli WEI ; Xudong YAO ; Ming CHEN ; Zhanpeng LU ; Qun XIE ; Zhiquan HU ; Yinhuai WANG ; Hongqian GUO ; Tiwu FAN ; Zhaozhao LIANG ; Peng CHEN ; Wei WANG ; Tao XU ; Chunsheng LI ; Jinchun XING ; Hong LIAO ; Dalin HE ; Zhibin WU ; Jiandi YU ; Zhongwen FENG ; Mengxiang YANG ; Qifeng DOU ; Quan ZENG ; Yuanwei LI ; Xin GOU ; Guangchen ZHOU ; Xiaofeng WANG ; Rujian ZHU ; Zhonghua ZHANG ; Bo ZHANG ; Wanlong TAN ; Xueling QU ; Hongliang SUN ; Tianyi GAN ; Dingwei YE
Chinese Medical Journal 2023;136(10):1207-1215
BACKGROUND:
LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.
METHODS:
We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.
RESULTS:
On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).
CONCLUSION:
LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04563936.
Humans
;
Male
;
Antineoplastic Agents, Hormonal/therapeutic use*
;
East Asian People
;
Gonadotropin-Releasing Hormone/agonists*
;
Goserelin/therapeutic use*
;
Prostate-Specific Antigen
;
Prostatic Neoplasms/drug therapy*
;
Testosterone
4.A public attitude survey on organ xenotransplantation
Zhendi WANG ; Qiuxiang XIA ; Xianpeng ZENG ; Heng LI ; Zhonghua CHEN
Chinese Journal of Organ Transplantation 2022;43(9):536-543
Objective:To survey the public attitude towards xenotransplantation and examine its influencing factors.Methods:A survey form with 46 multiple-choice questions is offered. It is composed of general profiles of respondent and scale. The questionnaire is distributed online through the platform of Wenjuanxing(https: //www.wjx.cn). All adult respondents filled in anonymously online. Statistical processing included descriptive analysis, reliability and validity testing and variance and correlation analysis.Results:A total of 4 414 valid questionnaires are obtained between December 1, 2021 and January 31, 2022. Cronbach's alpha coefficient is 0.912 and the scale has decent reliability. Based upon the results of exploratory factor analysis, the items are grouped into five main factors, namely organ source, decision, psychosocial change, infection risk and other risks. If pig organs are proven feasible, the risks and prognosis are basically the same as human organs, 65.4% of the respondents definitely supported xenotransplantation. Among the respondents, individuals aged 31~50 years, male, born or resident in Chinese western region, higher education, non-medical institution practitioners, self/family members/friends have done or awaiting organ transplantation, self/partners supporting organ donation, future needs for organ transplantation, previous discussion of organ donation or organ transplantation with family/friends, blood donation, volunteer social worker, atheist or Buddhist/Christianc and hearing about xenotransplantation are more inclined to support xenotransplantation.Correlation analysis showed significant correlations among five main factors.Conclusions:Despite differences in attitudes towards xenotransplantation among different populations, overall attitude is favorable. Respondents are more concerned about their associated risks, especially psychosocial changes. The related researches should be stressed. And for different groups of people, corresponding stratified tutoring should be carried out. Strengthening clinical trials, heightening public attention and training medical staff are expected to further popularize this new technology.
5.Role of 14-3-3σgene in the regulation of endotoxin/lipopolysaccharide-induced inflammatory responses in human pulmonary epithelial cells
Chunxia GAN ; Mingzhuo LIU ; Xincheng LIAO ; Zhonghua FU ; Xiaoping ZENG ; Hongmei WANG ; Guanghua GUO
Chinese Journal of Burns 2020;36(4):260-266
Objective:To explore the mechanism of 14-3-3σgene in regulating inflammatory response of human pulmonary epithelial cells induced by endotoxin/lipopolysaccharide (LPS).Methods:(1) Cells of human normal pulmonary epithelial cell line BEAS-2B cultured in logarithmic growth period were collected and divided into control group and PCMV6-14-3-3σgroup using the random number table, with 3 wells in each group. Cells in control group were transfected with empty plasmid, and cells in PCMV6-14-3-3σgroup were transfected with PCMV6-14-3-3σplasmid. The protein expression of 14-3-3σin cell was detected by Western blotting at 48 hours after transfection. (2) Cells of human normal pulmonary epithelial cell line BEAS-2B cultured in logarithmic growth period were collected and divided into control group, PCMV6-14-3-3σgroup, PCMV6-14-3-3σ+ LPS group, and LPS group using the random number table, with 3 wells in each group. Cells in control group were transfected with empty plasmid for 42 hours. Cells in PCMV6-14-3-3σgroup were transfected with PCMV6-14-3-3σplasmid for 42 hours. Cells in PCMV6-14-3-3σ+ LPS group were stimulated with 1 μg/mL LPS (the same final mass concentration below) for 6 hours after being transfected with PCMV6-14-3-3σplasmid for 42 hours. Cells in LPS group were stimulated by LPS for 6 hours. The protein expressions of Bax and B-cell lymphoma-2 (Bcl-2) were detected by Western blotting, and the ratio of Bax to Bcl-2 was calculated. Apoptotic rate was detected by flow cytometry. The mRNA expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1beta (IL-1β) in cells were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction technique. Content of TNF-α and IL-1β in cell culture supernatant was detected by enzyme-linked immunosorbent assay. Data were statistically analyzed with t test, one-way analysis of variance, and least significant difference test. Results:(1) At 48 hours after transfection, the protein expression of 14-3-3σin cells of PCMV6-14-3-3σgroup (1.05±0.03) was significantly higher than that in control group (0.78±0.04, t=5.41, P<0.01). (2) Compared with those in control group, the ratio of Bax to Bcl-2, apoptotic rate, mRNA expressions of TNF-α and IL-1β, and content of TNF-α and IL-1β in cell supernatant in PCMV6-14-3-3σgroup showed no significant difference ( P>0.05); the above-mentioned indexes of cells in LPS group were significantly higher or increased ( P<0.01). Compared with those in LPS group, the above-mentioned indexes of cells in PCMV6-14-3-3σ+ LPS group were significantly lower or decreased ( P<0.01). Conclusions:14-3-3σis a key factor in regulating apoptosis. It can alleviate the LPS-induced inflammatory responses by regulating the ratio of apoptotic regulators Bax to Bcl-2 and inhibiting apoptosis of human pulmonary epithelial cells.
6.A case report of transplanted pancreas survival longer than 18 years after simultaneous pancreas-kidney transplantation and literature review
Xia LU ; Nianqiao GONG ; Fanjun ZENG ; Zhonghua CHEN ; Zhishui CHEN ; Changsheng MING
Chinese Journal of Organ Transplantation 2019;40(5):277-279
Objective To explore the influencing factors and treatment strategies of long-term survival after simultaneous pancreas and kidney transplantation (SPK ) .Methods One case of long-term post-SPK survival was reviewed and its influencing factors were analyzed along with the relevant literature .Results At 10 years post-SPK ,the patient lost transplanted kidney due to rejection and underwent secondary kidney transplantation . The transplanted pancreas functioned well and has survived for more than 18 years .Conclusions Strict preoperative screening ,adopting mature surgical approaches ,aggressive managements of various perioperative complications ,strengthening of health education of recipients ,improving of compliance and long-term regular follow-ups are conducive for enhancing long-term survival of recipients and grafts of SPK .
7.Risk factors of continuous blood purification extracorporeal circulation apparatus plugging without anticoagulation
Zhonghua ZHANG ; Tieying ZENG ; Rong XU ; Jianjun YAN ; Hui TONG ; Gang XU
Chinese Journal of Modern Nursing 2019;25(34):4405-4411
Objective To explore the risk factors of continuous blood purification (CBP) extracorporeal circulation apparatus plugging without anticoagulation. Methods From May 2014 to May 2018, data from 257 patients with CBP without anticoagulation for the first time in Blood Purification Center at Tongji Hospital were retrospectively collected. The data included patients' general demographic data, apparatus types, areas and materials of membrane, types of blood access, treatment models, apparatus use time, whether infusing concentrated red cell, whether washing with 0.9% sodium chloride solution periodically, frequencies of nursing intervention when poor blood flow, laboratory data 24 hours before treatment, immediate transmembrane pressure gradient and venous pressure when apparatus plugging. The simple correlation and multivariate Cox proportional hazard regression model were used to analyze the risk factors of CBP extracorporeal circulation apparatus plugging without anticoagulation. Results Among those 257 patients, the use time of extracorporeal circulation apparatus was (248.51±87.56) min with 48.64% for the incidence of plugging. Multivariate Cox proportional hazard regression model showed that the risk factors of CBP extracorporeal circulation apparatus plugging included the high volume ratio of blood coagulation in the vein pot (HR: 1.024, 95%CI: 1.016-1.032), high frequency of nursing intervention when poor blood flow (HR: 1.600, 95%CI: 1.381-1.852) and high hematocrit (HR: 1.047, 95%CI: 1.003-1.094) with statistical differences (P<0.05). Conclusions CBP extracorporeal circulation apparatus plugging without anticoagulation has correlations with the volume ratio of blood coagulation in the vein pot, frequency of nursing intervention when poor blood flow and patients' hematocrit.
8.Treatment analysisin early postoperative inflammatory small bowel obstruction after abdominal surgery
Lu LU ; Wu TANG ; Wei LAI ; Yujie ZENG ; Zhonghua CHU
The Journal of Practical Medicine 2017;33(15):2511-2513
Objective To discusses the clinical features of early inflammatory bowel obstruction (EPIS-BO) after abdominal surgery,and analyze diagnosis and treatment. Methods The clinical data of 48 patients with early inflammatory bowel obstruction after abdominal surgery were analyzed retrospectively from July 2005 to July 2015. Results 45 patients were recovered after non-operative treatment including gastrointestinal decompression , total parenteral nutrition (TPN),antibiotics,glucocorticoid and somatostatin. The average time of treatment was 17.45 days. The other 3 patients underwent laparotomy respectively on 16,19 and 20 days after conservative treat-ment.Two cases were turned to intestinal fistula after operation ,and one of them died after reoperation because of severe abdominal infection 9 days later. Conclusion Conservative treatment should be regarded as the first choice for EPISBO in clinical practice due to less complications and better effect than operative treatment.
9.Clinicopathological characteristics and prognostic factors of rectal neuroendocrine neoplasms
Gengzhou WEI ; Wei WANG ; Xingyu FENG ; Yu ZHANG ; Yujie ZENG ; Zhonghua CHU ; Ye CHEN ; Jie CHEN ; Zhiwei ZHOU ; Yong LI
Chinese Journal of General Surgery 2017;32(10):828-831
Objective To analyze the clinicopathological characteristics and the related factors influencing the prognosis of rectal neuroendocrine neoplasms.Methods The clinical and follow-up data of 442 patients with rectal neuroendocrine neoplasms admitted between Sep 1993 and Dec 2015 in 5 hospitals in southern China were analyzed retrospectively.The univariate and multivariate analysis of survival prognosis were analyzed statistically.Results Of the 442 patients,the median age was 50 years and 64.7% were males.The average tumor size was (1.4 ± 0.7) cm.NENs < 1 cm accounted for 66.1% cases,1-2 cm accounted for 17.2% and >2 cm accounted for 16.7% of the tumors.Stage Ⅰ,Ⅱ,Ⅲ and Ⅳ accounted for 73.5%,8.6%,7.2%,10.6% of the tumors;G1,G2,G3 accounted for 76.5%,14.7%,8.8% of the tumors;The median survival time for all 442 patients was 35 months (range,1-224 months).The overall 5-year survival rate was 85%.The 5-year survival rates for patients in stage Ⅰ-Ⅳ were 95%,94%,52%,36% respectively.The 5-year survival rates for patients with G1-3 were 94%,80%,19%respectively.Univariate analysis showed that G grade,T stage,N stage,M stage,TNM stage,functional,gender,medication,surgical therapy,age,tumor sizes were statistically significant (all P < 0.05).Multivariate analysis revealed that G grade (P =0.001),tumor sizes (P =0.012) and TNM stage (P =0.008) were the independent factors affecting the prognosis.Conclusion Patients with rectal neuroendocrine neoplasms have no specific clinical characteristics.G grade,tumor sizes and TNM stage were the independent factors affecting the prognosis.
10.Identification and in vitro antifungal susceptibility of Penicillium marneffei in yeast phase
Juan WANG ; Hao LI ; Shujuan ZHENG ; Ling ZENG ; Zhonghua DENG
Chinese Journal of Infection Control 2016;15(12):934-938
[Abstract ] Objective To understand the identification and in vitro antifungal susceptibility of Penicillium marneffei(PM)in yeast phase,and guide clinic antifungal application.Methods Strains isolated from blood and bone marrow of 23 patients infected with PM in a hospital between 2009 and 2016 were collected,colony morpholo-gy of PM in yeast phase was observed,susceptibility to itraconazole,voriconazole,amphotericin B,and fluconazole were detected with E-test method.Results Colony morphology of PM were as follows:direct microscopic examina-tion of Wright’s staining of tissue specimens found visible oval or round spore with apparent septum,and mainly lo-cated in macrophage;Gram staining of blood culture specimens found that strains were with bulbous and slightly curved ends,occasionally branched and with septum. PM was dimorphic fungi,presented mycelium at 28° C,pro-duced red pigment and diffused into medium;PM presented yeast form at 35° C,there were typical colony morpholo-gy. Minimum inhibitory concentrations (MICs)of itraconazole,voriconazole,amphotericin B,and fluconazole to PM in yeast phase were 0.002-0.016,0.012-0.125,0.002-0.500,and 0.500-16.000μg/mL respectively. Conclusion Typical colony morphology and fungal spore of PM in bone marrow and peripheral blood are important features for identification. PM is most susceptible to itraconazole,followed by voriconazole and amphotericin B, while fluconazole is less susceptible.

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