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.Short-term efficacy of non-intubation anesthesia in thoracoscopic lobectomy for lung cancer: A systematic review and meta-analysis
Xiaofan YANG ; Qingchao SUN ; Desheng LI ; Liwei ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1181-1188
Objective To compare the postoperative enhanced recovery outcomes of lobectomy performed under non-intubated video-assisted thoracic surgery (NIVATS) versus intubated video-assisted thoracic surgery (IVATS). Methods Computerized searches were performed in the following databases: China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Information, China Biomedical Literature Database (CBMdisc), Web of Science, Clinicaltrials.gov, The Cochrane Library, EMbase, and PubMed. We collected randomized controlled trials (RCTs) and observational studies comparing NIVATS and IVATS. The search period extended from the inception of each database to April 1, 2023. Two independent researchers screened the literature and assessed study quality. Results A total of 14 studies were included, comprising 4 RCTs, 7 retrospective cohort studies, and 3 propensity score matching studies, involving 1 840 patients. Meta-analysis results indicated that, compared to IVATS, NIVATS was associated with significantly shorter operative time [MD=–13.39, 95%CI (–20.16, –6.62), P<0.001], shorter length of hospital stay [MD=–0.81, 95%CI (–1.39, –0.22), P=0.005], shorter chest tube duration [MD=–0.73, 95%CI (–1.36, –0.10), P=0.02], shorter postoperative anesthesia recovery time [MD=–20.34, 95%CI (–26.83, –13.84), P<0.001], and shorter time to oral intake after surgery [MD=–5.68, 95%CI (–7.63, –3.73), P<0.001]. Furthermore, NIVATS showed a lower incidence of postoperative airway complications [OR=0.49, 95%CI (0.34, 0.71), P<0.001] and less total chest tube drainage volume [MD=–251.11, 95%CI (–398.25, –103.98), P<0.001], all contributing to significantly accelerated postoperative enhanced recovery for patients. Conclusion NIVATS is a safe and technically feasible anesthesia method in thoracoscopic lobectomy, which can to some extent replace IVATS.
3.Identification of Lipid Metabolism Genes in Cerebral Infarction and Intervention Effect of Huoxue Rongluo Prescription
Siyang YAN ; Renyi YANG ; Feiya LI ; Menghao HE ; Lijuan LIU ; Desheng ZHOU ; Xiaofeng GAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):33-40
Objective To identify lipid metabolism genes in cerebral infarction;To explore the intervention effect of Huoxue Rongluo Prescription.Methods Multi-chip combined differential analysis(GSE61616,GSE30655)was used to identify lipid metabolism genes in cerebral infarction in combination with Reactome database,and the expression differences of lipid metabolism genes in cerebral infarction were identified and verified in GSE97537 chip;Pearson correlation analysis was used to analyze the correlation of 51 cerebral infarction samples in GSE61616,GSE30655,GSE97537,GSE137595,GSE22255,GSE163614,and GSE78731 datasets;PPI,GO and KEGG analysis of lipid metabolism genes in cerebral infarction were performed through STRING database and R clusterProfiler package.SD rats were made to the model of cerebral infarction,and was administered with Huoxue Rongluo Prescription extract 11.7 g/kg by intragastric administration for 7 days.The symptoms of neurological deficit,the changes of Nissl bodies and the mRNA expressions of PLA2G4A,SPHK1,and PTGES key genes in lipid metabolism in cerebral infarction were observed.Results TSPO,CYP1B1,PLIN2,CH25H,PLA2G4A,ANGPTL4,PTGS1,SPHK1,and PTGES were identified as lipid metabolism genes in cerebral infarction,and were significantly highly expressed and positively correlated in cerebral infarction.Among them,PTGS1,PLA2G4A,and SPHK1 interacted with each other,which were the key genes of lipid metabolism in cerebral infarction;the lipid metabolism gene in cerebral infarction mainly exerted molecular functions such as oxidoreductase activity,iron ion binding,heme binding,etc.,mediating arachidonic acid metabolism,phospholipase D signaling pathway,VEGF signaling pathway,involved in regulation of lipid metabolism process,fatty acid metabolism process,fatty acid derivative metabolism process.The symptoms of neurological deficit in the model rats with cerebral infarction were severe(P<0.001),and Huoxue Rongluo Prescription could effectively improve the neurological deficit of model rats(P<0.001).The Nissl staining indicated that the neuronal structure was abnormal and the number was significantly reduced after cerebral infarction(P<0.001).Huoxue Rongluo Prescription could increase the number of neurons(P<0.001)and repair the neuronal structure.RT-qPCR showed that the key genes of lipid metabolism in cerebral infarction were significantly higher in cerebral infarction(P<0.001),corroborated with the bioinformatics results,and Huoxue Rongluo Prescription could reduce the expression of key lipid metabolism genes of PTGS1,PLA2G4A,and SPHK1(P<0.001,P<0.01,P<0.05).Conclusion Huoxue Rongluo Prescription can down-regulate the expressions of PTGS1,PLA2G4A,SPHK1,exert molecular functions such as oxidoreductase activity,iron ion binding,heme binding,and mediate arachidonic acid metabolism,phospholipase D signaling pathway,and VEGF signaling pathway.It participates in the process of lipid metabolism regulation,fatty acid metabolism,and fatty acid derivative metabolism,increases the number of Nissl bodies,improves the symptoms of neurological deficits,and exerts neuroprotective effects.
4.Establishment and performance evaluation of nanobody-based cat dander specific IgE antibody hypersensitivity assay
Yanyan SUN ; Desheng QI ; Furao SHEN ; Caiyue YANG ; Xiangmei SUN ; Guoning CHEN ; Jianwei WU
Chinese Journal of Immunology 2024;40(4):818-823
Objective:To prepare anti-human IgE nanobody by phage display technology,and to establish a method for hyper-sensitivity detection of cat dander specific IgE antibody.Methods:Allergen bio-information of cat was searched in WHO/IUIS Allergen Database.After synthesizing sequence,recombinant cat dander allergenic protein Fel d 1 was expressed and purified in prokaryotic ex-pression system.Human IgE was used to immunize Bactrian camel and RNA were extracted from lymphocyte to construct phage dis-play library.Library capacity,diversity and insertion rate were analyzed,anti-human IgE nanobody were obtained by screening and identification.A magnetic particle chemical method for cat dander specific IgE antibody detection was established using recombinant allergen-coupled magnetic particles and acridine ester-labeled nanobodies.Results:Capacity of phage display library was 1.88×108 cfu/ml,insertion rate was 93.6%,and purity of nanobody was>95%.Linear range of the method based on nanobody was 0.1~100 U/ml,who was consistent with ImmunoCAP detection system by clinical data.Conclusion:Nanobody-based cat dander specific IgE antibody hypersensitivity assay is successfully prepared,providing a technical basis for auxiliary diagnosis of cat allergic diseases.
5.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.
6.Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial
Pengfei MA ; Sen LI ; Gengze WANG ; Xiaosong JING ; Dayong LIU ; Hao ZHENG ; Chaohui LI ; Yunshuai WANG ; Yinzhong WANG ; Yue WU ; Pengyuan ZHAN ; Wenfei DUAN ; Qingquan LIU ; Tao YANG ; Zuomin LIU ; Qiongyou JING ; Zhanwei DING ; Guangfei CUI ; Zhiqiang LIU ; Ganshu XIA ; Guoxing WANG ; Panpan WANG ; Lei GAO ; Desheng HU ; Junli ZHANG ; Yanghui CAO ; Chenyu LIU ; Zhenyu LI ; Jiachen ZHANG ; Changzheng LI ; Zhi LI ; Yuzhou ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(10):977-985
Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.
7.Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial
Pengfei MA ; Sen LI ; Gengze WANG ; Xiaosong JING ; Dayong LIU ; Hao ZHENG ; Chaohui LI ; Yunshuai WANG ; Yinzhong WANG ; Yue WU ; Pengyuan ZHAN ; Wenfei DUAN ; Qingquan LIU ; Tao YANG ; Zuomin LIU ; Qiongyou JING ; Zhanwei DING ; Guangfei CUI ; Zhiqiang LIU ; Ganshu XIA ; Guoxing WANG ; Panpan WANG ; Lei GAO ; Desheng HU ; Junli ZHANG ; Yanghui CAO ; Chenyu LIU ; Zhenyu LI ; Jiachen ZHANG ; Changzheng LI ; Zhi LI ; Yuzhou ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(10):977-985
Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.
8.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*
9.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.
10.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.

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