1.Traditional Chinese Medicine Regulates Signaling Pathways Related to Precancerous Lesions of Gastric Cancer: A Review
Maofu ZHANG ; Xinyu LI ; Yanyun SHEN ; Yeyuan LIU ; Jialin ZHONG ; Lulu CHEN ; Haihong ZHAO ; Zhongyang SONG ; Zhiming ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):297-306
Precancerous lesions of gastric cancer (PLGC) are a group of pathological changes caused by abnormalities in the structure, morphology, and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific, PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly, the incidence of this disease is increasing year by year, which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex, involving inflammatory microenvironment, bile reflux, glycolysis, autophagy, and apoptosis. Currently, PLGC is mainly treated with anti-inflammatory and endoscopic therapies, which are difficult to curb the development of PLGC. Therefore, seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine (TCM), characterized by treatment based on syndrome differentiation and a holistic view, exerts effects via multiple pathways, mechanisms, and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), Wnt/β-catenin, Sonic Hedgehog, nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), hypoxia-inducible factor-1α (HIF-1α), neurogenic locus notch homolog protein (Notch), nuclear factor E2-related factor 2 (Nrf2) and other signaling pathways. By targeting these pathways, TCM can inhibit aerobic glycolysis, reduce oxidative stress, repair the inflammatory microenvironment, regulate cellular autophagy, and promote vascular normalization, thereby delaying or reversing PLGC. However, few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad, this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC, with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.
2.Regulatory Mechanism of Mitochondrial Apoptosis in Gastric Cancer and Intervention of Traditional Chinese Medicine: A Review
Lulu CHEN ; Yuchan CHEN ; Zhongyang SONG ; Haihong ZHAO ; Maofu ZHANG ; Zhiming ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):259-269
Gastric cancer (GC) is one of the most common cancers in the world, with hidden symptoms, complex pathogenesis, high morbidity, high mortality, and poor prognosis. As one of the classical apoptosis pathways, mitochondrial apoptosis has been widely described in the apoptosis escape by GC cells. Mitochondrial apoptosis can regulate the proliferation, invasion, and metastasis of GC cells via oxidative stress, cell cycle, mitochondrial membrane potential, mitochondrial translocation and other mechanisms, and it is one of the potential targets of traditional Chinese medicine (TCM) intervention to restore the mitochondrial function in GC. The theory of spleen-mitochondria in correlation explains that spleen deficiency and cancer toxin are the root causes of mitochondrial apoptosis. Accordingly, the TCM treatment should follow the basic principle of invigorating spleen to restore healthy Qi and removing cancer toxin to eliminate the root cause. Mitochondrial apoptosis can be promoted by inhibiting oxidative stress, promoting cell cycle arrest, and reducing mitochondrial membrane potential. This therapy can improve the energy metabolism, restore the mitochondrial structure and function, and prevent the occurrence and development of GC, with mild side effects and low drug resistance. However, the mechanism of mitochondrial apoptosis in GC and the target of TCM intervention in GC have not been systematically reviewed. Therefore, this paper systematically summarized the effects of mitochondrial apoptosis on the occurrence and development of GC and the role of TCM in the treatment of GC by intervening in mitochondrial apoptosis, aiming to provide a theoretical reference for the treatment and further research of GC.
3.Status of Outcome Index in Randomized Controlled Trials of Traditional Chinese Medicine for Treatment of Tic Disorder in Children
Yujing CHEN ; Hui LIU ; Qianfang FU ; Haihong YAN ; Ping RONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):103-110
This study analyzed the outcome index and related design elements of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) in the treatment of children with tic disorder (TD) in the past ten years, so as to provide a basis for the construction of the core index set of TCM in the treatment of children with TD. Eight databases were searched, including four English databases (PubMed, Web of Science, Embase, and Cochrane Library) and four Chinese databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and China Biology Medicine disc (CBMdisc), as well as ClinicalTrials.gov and China Clinical Trial Registry. The search time was limited to from January 1, 2013 to October 29, 2023. RCTs on the TD in children treated with TCM were collected. Two researchers independently conducted literature screening, data extraction, and literature quality evaluation and summarized clinical outcome indexes and related trial design elements through qualitative analysis. A total of 67 RCTs were included, including 63 outcome indexes, with a total frequency of 348 times. The related outcome indexes could be divided into six categories: 12 symptom/sign indexes with a frequency of 134 (38.5%), seven TCM symptom/syndrome indexes with a frequency of 31 (8.9%), 33 physical and chemical examination indexes with a frequency of 97 (27.9%), four safety indexes with a frequency of 67 (19.3%), three long-term prognostic indexes with a frequency of 14 (4.0%), and one kind of quality-of-life evaluation index (0.3%). Currently, the RCTs research design of TCM in the treatment of TD in children has not yet formed a unified standard, and there are many problems in the quality of methodology, which reduces the authenticity and reliability of clinical conclusions. There are problems with clinical outcome indexes, such as significant quantity differences, unclear primary and secondary outcome indexes, unreasonable alternative indexes, non-standard TCM syndrome types and TCM evaluation indexes, lack of economic evaluation indexes, and less attention to long-term prognostic indexes and safety indexes. It is suggested that the researchers should design a more rigorous trial scheme and reasonably design the outcome index which is in line with the clinical trial efficacy evaluation of TCM, so as to construct the core index set with the characteristics of TCM for the treatment TD in children.
4.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
5.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
6.Mechanism design and analysis of a simple leg-sliding rehabilitation equipment
Haihong PAN ; Taiwei LI ; Yuancai LIU ; Meiming LU ; Lin CHEN
Chinese Journal of Rehabilitation Theory and Practice 2023;29(4):396-401
ObjectiveTo design a simple leg-sliding rehabilitation equipment for patients with lower limb dysfunction who need to exercise their leg muscles in bed at the early stage of rehabilitation. MethodsThe mechanism scheme was designed using the crank slider transmission system. The kinematic model was established and the structural dimensions were determined according to the human joint mobility, analysis and verification were then implemented; and the strutural strength of the machanism was verified, and based on the analysis, a protype was built to verify the feasibility of proposed scheme. ResultsThe range of joint activities of the proposed mechanism was in line with the normal human joint activities, the structural strength met the requirements, the prototype operated smoothly, and the actual running speed was basically consistent with the theoretical planning speed. ConclusionThis design could meet the needs of rehabilitation training for bedridden patients with lower limb dysfunction at the early stage of rehabilitation. It has the advantages of small size and light weight, which provides reference value for promoting the development of miniaturized and lightweight lower extremity rehabilitation equipment.
7.Establishment of prediction nomogram model of type 2 diabetes mellitus complications based on laboratory indexes such as glycosylated hemoglobin
Liucheng DU ; Ying CHEN ; Jianping ZOU ; Haihong WANG ; Yan YU
Chinese Journal of Postgraduates of Medicine 2023;46(3):259-264
Objective:To study the effect of related laboratory indexes such as glycosylated hemoglobin on the occurrence of complications in patients with type 2 diabetes mellitus, and to construct a nomogram model.Methods:The clinical data of 203 patients with 2 diabetes mellitus from May 2020 to April 2022 in Quzhou Hospital, Zhejiang Medical and Health Group were retrospectively analyzed. Among them, 64 patients had no diabetic complications (control group), and 139 patients had diabetic complications (complication group). The clinical data of the two groups were recorded, and the related influencing factors of complications in patients with type 2 diabetes were analyzed; receiver operating characteristic (ROC) curve was used to analyze the predicting value of significant indexes for the complications in patients with type 2 diabetes; multivariate Logistic regression analysis was used to analyze the independent risk factors of complications in patients with type 2 diabetes; R language software 4.0 "rms" package was used to construct the nomogram model for predicting the complications in patients with type 2 diabetes, the calibration curve was internally validated, and the decision curve was used to evaluate the predictive efficacy of the nomogram model.Results:The hypertension rate, hyperlipemia rate, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin in complication group were significantly higher in those in control group: 44.60% (62/139) vs. 20.31% (13/64), 48.92% (68/139) vs. 25.00% (16/64), (5.42 ± 0.68) years vs. (4.84 ± 0.51) years, (12.60 ± 2.80) mmol/L vs. (10.20 ± 1.90) mmol/L, (16.50 ± 3.10) mmol/L vs. (12.50 ± 2.90) mmol/L and (9.62 ± 1.33)% vs. (7.96 ± 0.85)%, and there were statistical differences ( P<0.01); there were no statistical differences in gender composition, age, body mass index, smoking rate, drinking rate, albumin and creatinine between the two groups ( P>0.05). ROC curve analysis result showed that the area under the curve of the course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin for predicting the complications in patients with type 2 diabetes were 0.725, 0.752, 0.830 and 0.861, respectively; the optimal cut-off values were 5 year, 11.8 mmol/L, 15.1 mmol/L and 9.23%. Multivariate Logistic regression analysis result showed that hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin were independent risk factors of complications in patients with type 2 diabetes ( OR = 1.563, 1.692, 1.451, 1.703, 1.506 and 1.805; 95% CI 1.268 to 1.689, 1.483 to 1.824, 1.215 to 1.620, 1.402 to 1.903, 1.303 to 1.801 and 1.697 to 1.926; P<0.05). The hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin were used as predictors to construct a nomogram model for predicting the complications in patients with type 2 diabetes. Internal validation result showed that the nomogram model predicted the complications with good concordance in patients with type 2 diabetes (C-index = 0.815, 95% CI 0.796 to 0.843); the nomogram model predicted the complications in patients with type 2 diabetes at a threshold >0.18, provided a net clinical benefit, and all had higher clinical net benefits than hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin. Conclusions:The nomogram model constructed based on hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin has better clinical value in predicting the complications in patients with type 2 diabetes.
8.The safety and efficacy of radiofrequency in the treatment of overactive bladder
Yunbei YANG ; Yuda YU ; Huiping YE ; Zhiliang WENG ; Haihong JIANG ; Hang HUANG ; Haiyan LI ; Xiangxiang YE ; Gonghui LI ; Yanlan YU ; Zhenghui WANG ; Yicheng CHEN ; Dahong ZHANG ; Zhihui XU
Chinese Journal of Urology 2023;44(1):37-41
Objective:To explore the safety and efficacy of radiofrequency in the treatment of overactive bladder(OAB).Methods:A prospective, multicenter, non-randomized controlled trial was conducted. Eligible patients were divided into test group and control group in Zhejiang Provincial People’Hospital, The First Affiliated Hospital of Wenzhou Medical University, and Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from March 2019 to June 2020. Inclusion criteria: patients diagnosed with OAB, and bladder capacity>100ml. Exclusion criteria: pregnant and lactating women; patients with secondary OAB symptoms such as urinary tract obstruction; patients with uncontrolled urinary tract infection within 1 week; patients in stable stage by using other treatment methods; patients implanted with any nerve stimulator, cardiac pacemaker or implantable defibrillator; patients with malignant tumors, serious cardiovascular, cerebrovascular diseases, renal insufficiency or received BTX treatment in recent 12 months. The patients were allocated to test group and the control group in a ratio of 2∶1 according to the time sequence of the visit. The patients in the test group were treated with radiofrequency treatment. After entering the group, they were treated for 4 times at the 1st, 2nd, 7th and 8th week respectively. In the control group, the energy was turned off during the radiofrequency treatment. The patients were followed-up every week until the end of the 12th week. The treatment success rate [the average frequency of urination in 24 h was reduced more than 50% from the baseline or returned to the normal (≤8 times/day) or the average frequency of urgent urination in 24 h was reduced more than 50% from the baseline], the frequency of urination, urgent urination and nocturnal urination before and after treatment, the residual urine volume of the bladder, the quality of life (QOL) score and the occurrence of catheter related adverse events in two groups were compared.Results:114 patients were enrolled in the study, including 76 patients in the test group and 38 patients in the control group. There were no significant differences in the age [(44.2±12.8) vs. (41.7 ± 12.1) years old], male female ratio (13/63 vs. 4/34), average course of disease [2.0(1.2, 5.0) vs. 2.0 (1.0, 4.0) years], the frequency of urination[12.8 (10.6, 16.8) vs. 12.8 (10.3, 17.0) times], urgency urination [11.8(9.3, 15.8) vs. 11.8 (9.0, 17.0) times], nocturia [2.7 (1.3, 3.7) vs. 2.3(0.7, 3.3) times], residual urine volume of bladder [12.0 (3.0, 28.0) vs. 14.0 (3.7, 20.0) ml ] and the QOL score [5.0(4.0, 5.0) vs. 4.0(4.0, 5.0)]before the treatment between the two groups ( P>0.05). The treatment success rate in the test group was 76.3% (58/76), while 26.3% (10/38) in the control group, with a statistically significant difference ( P<0.01). There were significant differences between the test group and control group in the frequency of urination [9.7 (7.7, 12.0) vs. 12.9 (9.6, 15.7) times], urgent urination [7.3 (5.0, 10.0) vs. 11.7 (7.3, 15.3) times], nocturia [1.3 (0.7, 2.0) vs. 1.7 (1.0, 3.0) times] and the QOL score of the patients[3.0(1.0, 3.0) vs. 4.0(3.0, 4.5)]after the treatment(all P<0.05). The frequency of urination, urgency urination, nocturia, the residual urine volume and the QOL score in the test group were significantly improved ( P<0.05) after the treatment.The frequency of urination, nocturia, residual urine volume and the QOL score in the control group were improved ( P<0.05) after the treatment. 13 (11.4%) patients had catheter related adverse events. In the test group and the control group, there were 7 cases of macroscopic hemorrhage caused by the placement of instruments (5/76 vs. 2/38), 5 cases of acute urinary tract infection within 3 days (3/76 vs. 2/38), and 1 case of instrument breakage (catheter breakage) (0/76 vs. 1/38). There were no significant differences in the adverse events between the two groups ( P> 0.05). Conclusions:Radiofrequency treatment of OAB can effectively improve the symptoms of patients, improve the QOL of patients, and has low incidence of adverse events, with good efficacy and safety.
9.Autophagy, not apoptosis, plays a role in lumen formation of eccrine gland organoids.
Lijie DU ; Lei ZHANG ; Junhong ZHAO ; Zixiu CHEN ; Xiang LIU ; Manxiu CAO ; Lei YOU ; Yonghong ZHANG ; Xiaobing FU ; Haihong LI
Chinese Medical Journal 2022;135(3):324-332
BACKGROUND:
Sweat secreted by eccrine sweat glands is transported to the skin surface through the lumen. The eccrine sweat gland develops from the initial solid bud to the final gland structure with a lumen, but how the lumen is formed and the mechanism of lumen formation have not yet been fully elucidated. This study aimed to investigate the mechanism of lumen formation of eccrine gland organoids (EGOs).
METHODS:
Human eccrine sweat glands were isolated from the skin for tissue culture, and the primary cultured cells were collected and cultured in Matrigel for 14 days in vitro. EGOs at different development days were collected for hematoxylin and eosin (H&E) staining to observe morphological changes and for immunofluorescence staining of proliferation marker Ki67, cellular motility marker filamentous actin (F-actin), and autophagy marker LC3B. Western blotting was used to detect the expression of Ki67, F-actin, and LC3B. Moreover, apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay kit, and the expression of poly (ADP-ribose) polymerase and Caspase-3 was detected by Western blot. In addition, 3-methyladenine (3MA) was used as an autophagy inhibitor to detect whether the formation of sweat glands can be effectively inhibited.
RESULTS:
The results showed that a single gland cell proliferated rapidly and formed EGOs on day 4. The earliest lumen formation was observed on day 6. From day 8 to day 14, the rate of lumen formation in EGOs increased significantly. The immunofluorescence and Western blot analyses showed that the expression of Ki67 gradually decreased with the increase in days, while the F-actin expression level did not change. Notably, the expression of autophagy marker LC3B was detected in the interior cells of EGOs as the apoptosis signal of EGOs was negative. Compared with the control group, the autophagy inhibitor 3MA can effectively limit the formation rate of the lumen and reduce the inner diameter of EGOs.
CONCLUSION
Using our model of eccrine gland 3D-reconstruction in Matrigel, we determined that autophagy rather than apoptosis plays a role in the lumen formation of EGOs.
Apoptosis
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Autophagy
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Eccrine Glands
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Epithelial Cells
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Humans
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Organoids
10.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

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