1.Annual review of liver transplantation basic research of China in 2024
Desheng CHEN ; Linsen YE ; Wei LIU ; Yang YANG
Organ Transplantation 2025;16(3):338-349
Liver transplantation has currently become an important treatment for patients with end-stage liver disease or hepatocellular carcinoma (HCC), significantly improving patients’ prognosis. However, liver transplantation still facing many challenges, such as donor sources, liver preservation technology, transplant rejection, biliary complications and postoperative tumor recurrence after HCC liver transplantation, which urgently need to be solved and optimized. With the development of new technologies, liver transplantation in our country is facing new opportunities and challenges. Domestic research teams actively respond to the needs of the times and continuously promote innovation and breakthroughs in the basic research of liver transplantation. This article reviews the cutting-edge progress in the field of basic liver transplantation research in 2024 and evaluates the important research achievements obtained by Chinese research teams in this field. The systematic sorting out of these research advances not only helps to promote the integration of Chinese characteristic liver transplantation research into the international academic system and the docking of Chinese liver transplantation research with the global forefront, but also helps researchers and clinical surgeons to fully understand the current status of basic liver transplantation research in China, provides a clear direction for future basic research, and thus promotes the vigorous development of Chinese liver transplantation cause.
2.Construction of Nomogram prediction model of myopia risk and lifestyle among primary school students in Tianjin City
LIU Shengxin, DU Bei, JIN Nan, TANG Chunyu, SONG Desheng, ZHANG Xin, WEI Ruihua
Chinese Journal of School Health 2024;45(1):21-24
Objective:
To explore the relationship between lifestyle and myopia and construct Nomogram model to predict myopia risk among primary school students in Tianjin, so as to provide a scientific basis for precision myopia prevention and control.
Methods:
From April to July of 2022, a census method was used to conduct vision testing and lifestyle related questionnaires among 373 180 primary school students in 15 districts of Tianjin. The relationship between lifestyle and myopia was analyzed by the multivariate Logistic regression, and a nomogram prediction model was constructed to predict myopia risk.
Results:
The detection rate of myopia among primary school students in Tianjin was 37.6%. The results of the multivariate Logistic regression showed that daily outdoor activity time of 1-2 h ( OR =0.94) and >2 h ( OR =0.84), time of using daily electronic devices of >2 h ( OR =1.03), daily paper materials reading and writing time of 1-2 h ( OR =1.02) and >2 h ( OR =1.09), weekly fresh vegetable intake of 2-6 times ( OR =0.93) and ≥7 times ( OR =0.88) were statistically correlated with myopia ( P <0.01). The Nomogram prediction model showed that the factors associated with myopia were grade, family history of myopia, gender, daily outdoor activity time, weekly frequency of fresh vegetable intake, daily paper materials reading and writing time, and time of using daily electronic devices time.
Conclusions
The lifestyle of primary school students in Tianjin is associated with myopia. The constructed nomogram model could provide a scientific basis for identifying key intervention populations for myopia prevention and taking targeted prevention and control measures.
3.A survey of common eye behaviors and influencing factors of myopia in pri-mary and secondary school students in Tianjin
Nan JIN ; Bei DU ; Desheng SONG ; Jing LI ; Ruihua WEI
Recent Advances in Ophthalmology 2024;44(4):302-305,310
Objective To explore the eye behaviors and myopia-related risk factors among primary and secondary school students in Tianjin,in order to carry out targeted eye health education and guidance.Methods A cross-sectional study was conducted.In December 2021,an eye health questionnaire was distributed to primary and secondary school students in Tianjin to investigate their eye habits;combined with the campus vision screening data in the second half of 2021,a multivariate logistic regression analysis model was constructed to explore the risk factors related to myopia.Re-sults A total of 821 459 questionnaires were collected,including 701 104 valid questionnaires.The usage time of electron-ic learning products and electronic entertainment products for primary school students was mostly less than 1 hour(ac-counting for 57.74%and 40.98%,respectively).The population of junior high school students who spend more than 2 hours using electronic learning products and electronic entertainment products(accounting for 26.61%and 35.05%,re-spectively)significantly increased compared to primary school students(accounting for 11.21%and 20.93%,respective-ly).Most senior high school students spend more than 2 hours daily using electronic devices for learning and entertainment purposes,as well as reading paper materials.51.59%of primary school students do not meet the standard for sleep dura-tion,while the rate of reaching the standard sleep duration of junior high and senior high school students was 60.09%and 64.99%,respectively.Most(55.74%)primary and secondary school students have an average outdoor activity duration of 1-2 hours daily.The results of multivariate logistic regression analysis showed that the risk of myopia in primary school students was correlated with the time spent using electronic products(including learning and entertainment),the time spent reading paper materials at a close range,outdoor activities,time to fall asleep,and sleep duration(all P<0.05);the risk of myopia among junior high school students was related to the time spent using electronic entertainment products,reading paper materials at a close range,outdoor activities,and sleep duration(all P<0.05);the risk of myopia among senior high school students was only related to the time spent reading paper materials at a close range and the duration of outdoor activities(both P<0.05).Conclusion The proportion of primary school students,junior high school students and senior high school students in Tianjin who use electronic products for more than 2 hours is gradually increasing,and the rate of reaching the standard sleep duration is gradually increasing.The risk of myopia among these students is related to the time spent reading paper materials at a close range and outdoor activities.Science popularization should be carried out and management of eye behaviors should be strengthened in the whole society to reduce myopia rates in children and adolescents in China.
4.Inhibition of EMT in colorectal cancer by rosemarinic acid explored based on the Wnt/β-catenin pathway
Feng ZHOU ; Desheng SHA ; Yuanyuan LU ; Wei CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):726-733
Objective To investigate the role and action mechanism of rosemarinic acid(RA)on the malignant behavior of colorectal cancer(CRC)SW480 cells.Methods We collected tumor tissues from patients with primary untreated CRC who underwent surgery in People's Hospital of Rugao from January 2019 to December 2020,as well as colon tissues from normal individuals.The expression of β-catenin was detected by immunohistochemistry and Western blotting to analyze its relationship with the clinical stage,prognosis,and immune infiltration.CCK-8 was used to detect the effects of 10,15 and 20 μmol/L of RA on the proliferation of SW480 cells;flow cytometry detected apoptosis;Transwell and scratch assay detected changes in the invasion and migration ability of the cells,respectively.Western blotting detected the expressions of proteins related to apoptosis,epithelial-mesenchymal transition(EMT),and Wnt/β-catenin pathway.A mouse model of CRC transplant tumor was established,and the effect of RA on the growth of transplant tumor was investigated by gavage administration.The levels of inflammatory factors were detected by ELISA.Results The expression of β-catenin was low in normal colon tissues and significantly higher in CRC tissues.In the CRC patients with high expression of β-catenin,the number of patients with tumors larger than 5 cm was significantly higher than that in the low expression group,whereas the overall survival of the patients was significantly smaller than that in the low expression group(P<0.05).Cell proliferation was significantly inhibited and decreased in a concentration-dependent manner in the RA group at all concentrations(P<0.05).In animal experiments,the expression of apoptotic proteins Bax and Bad was significantly increased and the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the RA-treated group compared with the control group(P<0.05).It was also found that the invasive and migratory ability of SW480 cells was significantly inhibited(P<0.05),the expression of E-cadherin protein was significantly increased,the expression of Snail,N-cadherin and Vimentin was significantly reduced(P<0.05),the expression of Axin and GSK-3β was increased,and the expression of β-catenin was reduced(P<0.05).Conclusion RA may inhibit the biological activity of SW480 by interfering with Wnt/β-catenin pathway-mediated EMT.
5.Quercetin increases the sensitivity of human colon cancer cells SW480 and SW620 to cisplatin
Feng ZHOU ; Desheng SHA ; Yuanyuan LU ; Wei CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):902-908
[Objective] To investigate the inhibitory effect of quercetin on cisplatin-resistant human colorectal cancer (CRC) cells SW480 and SW620 and its possible mechanism. [Methods] Cisplatin-resistant subtypes of SW480 and SW620 cells were first cultured and the effects of quercetin on cell proliferation and chemosensitivity were determined by MTT assay. Flow cytometry was used to detect apoptosis and protein blotting was used to detect the expressions of relevant proteins. [Results] MTT assay showed that quercetin at the concentrations of 80 μmol/L and 160 μmol/L significantly inhibited the proliferation of SW480 and SW620 cells. Flow cytometry results showed that the apoptosis rate was significantly higher in the cisplatin combined with quercetin group than in the other three groups. Protein blotting showed that cleaved-caspase-3 and caspase-9 expressions were significantly increased in the cisplatin combined with quercetin group. The chemotherapeutic drug sensitivity assay showed that the elevated IC
6.A Phase Ⅲ Clinical Observation of Yishen Yangxin Anshen Tablets in Treatment of Insomnia with Deficiency of Heart Blood and Insufficiency of Kidney Essence
Wei WANG ; Junxia REN ; Yongzheng WANG ; Jianke HAN ; Limin YANG ; Weidong WANG ; Fengmei LIAN ; Changshan AI ; Xiaoli YIN ; Baoliang WANG ; Yi MENG ; Shuguang YUAN ; Desheng ZHOU ; Xuedong GAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):110-116
ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia (heart-blood deficiency and kidney-essence insufficiency syndrome). MethodA randomized block, double-blind, placebo-controlled, multi-center clinical trial design method was adopted, and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence (treatment group-control group 3∶1) from seven hospitals (Guang'anmen Hospital, China Academy of Chinese Medical Sciences, The First Clinical Hospital, Jilin Province Academy of Traditional Chinese Medicine(TCM), The Second Affiliated Hospital of Liaoning University of TCM, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan Province Hospital of TCM, Hebei General Hospital, The First Hospital of Hunan University of Chinese Medicine) were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets (4 tablets/time, 3 times/day, 4 weeks of administration, 4 weeks of follow-up after drug withdrawal). The sleep dysfunction rating scale (SDRS) score, pittsburgh sleep quality index (PSQI) score, TCM, polysomnography (PSG) indicators from four hospital (Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Henan Province Hospital of TCM, Hebei General Hospital, The First Hospital of Hunan University of Chinese Medicine), and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination, laboratory examination, and observation of adverse events, the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment, the total score of SDRS in the treatment group was lower than that in the control group (P<0.01). After drug withdrawal for 4 weeks, the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment, indicating that the rebound change of curative effect was not obvious. After treatment, the total score of PSQI in the treatment group decreased as compared with that in the control group (P<0.01), and the change of total score of PSQI in the treatment group was statistically significant (P<0.05) after drug withdrawal for 4 weeks but small, indicating that the rebound change of curative effect was not obvious. After treatment, the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group (χ2=137.521,P<0.01). After treatment, the disappearance rates of single indexes in the treatment group, such as difficulty in falling asleep, easily waking up after sleeping, early awakening, short sleep time, dreamfulness, palpitation, forgetfulness, dizziness, mental fatigue, and weakness of waist and knee, increased compared with those in the control group (P<0.01). After treatment, the treatment group demonstrated fewer awaking times (AT), longer total sleep time (TST), lower ATA/TST ratio, and higher sleep efficiency (%) than the control group (P<0.05). No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.
7.Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome.
Chaojuan YANG ; Yonglu TIAN ; Feng SU ; Yangzhen WANG ; Mengna LIU ; Hongyi WANG ; Yaxuan CUI ; Peijiang YUAN ; Xiangning LI ; Anan LI ; Hui GONG ; Qingming LUO ; Desheng ZHU ; Peng CAO ; Yunbo LIU ; Xunli WANG ; Min-Hua LUO ; Fuqiang XU ; Wei XIONG ; Liecheng WANG ; Xiang-Yao LI ; Chen ZHANG
Protein & Cell 2022;13(3):203-219
Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals
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Disease Models, Animal
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Fragile X Mental Retardation Protein/metabolism*
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Fragile X Syndrome/metabolism*
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Humans
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Mice
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Mice, Knockout
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Neurons/metabolism*
8.Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.
Chenxue MAO ; Juan CHEN ; Ting ZOU ; Yuankang ZHOU ; Junyan LIU ; Xi LI ; Xiangping LI ; Min LI ; Pinhua PAN ; Wei ZHUO ; Yang GAO ; Shuo HU ; Desheng XIAO ; Lin WU ; Zhan WANG ; Heng XU ; Wen YANG ; Yingjie XU ; Haihua XIAO ; Kazuhiko HANADA ; Wei ZHANG ; Honghao ZHOU ; Jiye YIN ; Zhaoqian LIU
Acta Pharmaceutica Sinica B 2022;12(3):1514-1522
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
9.Expression of METTL14 in epithelial ovarian cancer and the effect on cell proliferation, invasion and migration of A2780 and SKOV3 cells
Yousheng WEI ; Desheng YAO ; Li LI ; Yan LU ; Xinmei YANG ; Wenge ZHANG
Chinese Journal of Obstetrics and Gynecology 2022;57(1):46-56
Objective:To study the expression of methyltransferase-like protein 14 (METTL14) in epithelial ovarian cancer and its clinical significance, and to explore the effect of METTL14 expression on the proliferation, invasion and migration of ovarian cancer cells.Methods:Immunohistochemistry (IHC) was used to detect METTL14 expression in tumor tissue samples, and analyze the relationships among METTL14 expression, clinicopathological factors, and prognosis in ovarian cancer. Lentiviral vectors and small interfering RNA (siRNA) were used to up-regulate and down-regulate the METTL14 expression in ovarian cancer cell lines A2780 and SKOV3, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to detect the N6-methyladenosine (m6A) content in ovarian cancer cells. Cell counting kit-8 (CCK-8), wound healing assay, and transwell assay were used to examine the function of METTL14 expression in the cells.Results:(1) The IHC score of METTL14 protein was 6.2±3.7 in 20 samples of ovarian cancer tissues and 3.3±2.5 in 15 samples of normal ovarian tissues, and the difference was statistically significant ( t=-2.64, P=0.012). Among the patients who suffered from ovarian cancer, there were 69 cases with high expression of METTL14 protein (IHC score≥6), accounting for 57.0% (69/121), and the cases with low expression of METTL14 protein (IHC score<6) accounting for 43.0% (52/121). Compared with the patients with low expression of METTL14, the patients with high expression of METTL14 had later stages, higher rates of lymph node metastasis, abdominal metastasis, and more ascite amount. The differences were statistically significant (all P<0.05). The overall survival rate was significantly lower in patients with high METTL14 expression than the low expression ( P=0.009). (2) LC-MS/MS data showed that the relative expression of m6A in A2780 and SKOV3 cells in the lentivirus (LV)-METTL14 group were 0.213±0.024 and 0.181±0.018, which were significantly higher than those in the LV-normal control (NC) group (0.109±0.022 and 0.128±0.020; all P<0.05). While the relative expression of m6A in A2780 and SKOV3 cells in the si-METTL14 group were 0.063±0.012 and 0.069±0.015, which were significantly lower than the expression in si-NC group of 0.108±0.014 and 0.121±0.014 (all P<0.05). CCK-8 assay showed that the absorbance values were significantly lower in the si-METTL14 group compared with the si-NC group at 36, 48, 60 hours (all P<0.05); while were significantly increased in the LV-METTL14 group compared with the LV-NC group at 48, 60 hours (all P<0.01). Scratch wound assays showed that the migration rate of the si-METTL14 group was lower than those of the si-NC group, while the LV-METTL14 group were higher than the LV-NC group by 24 hours, the differences were statistically significant (all P<0.01). Cell migration and invasion were detected by transwell migration and invasion assays. After cultivated for 24 hours, the invasion cell number and the migration cell number in the si-METTL14 group were less than those in the si-NC group. While the invasion cell number and the migration cell number in the LV-METTL14 group were more than those in the LV-NC group, respectively. The differences were statistically significant (all P<0.01). Conclusion:Patients with high METTL14 expression have a worse prognosis in ovarian cancer, which may increase the m6A modification of ovarian cancer cells and promote cells proliferation, invasion and migration.
10.Factors affecting phenotypes in the patients with MMACHC gene c. 609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria
Ruxuan HE ; Ruo MO ; Yao ZHANG ; Ming SHEN ; Lulu KANG ; Zhehui CHEN ; Yi LIU ; Jinqing SONG ; Hongwu ZHANG ; Hongxin YAO ; Yupeng LIU ; Hui DONG ; Ying JIN ; Mengqiu LI ; Jiong QIN ; Hong ZHENG ; Yongxing CHEN ; Haiyan WEI ; Dongxiao LI ; Xiyuan LI ; Rongxiu ZHENG ; Huifeng ZHANG ; Min HUANG ; Chunyan ZHANG ; Yuwu JIANG ; Desheng LIANG ; Yaping TIAN ; Yanling YANG
Chinese Journal of Medical Genetics 2022;39(6):565-570
Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.


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