1.Development and clinical advancement of small molecules for ex vivo expansion of hematopoietic stem cell.
Jiaxing LI ; Xiao WANG ; Jiayu DING ; Yasheng ZHU ; Wenjian MIN ; Wenbing KUANG ; Kai YUAN ; Chengliang SUN ; Peng YANG
Acta Pharmaceutica Sinica B 2022;12(6):2808-2831
Hematopoietic stem cell (HSC) transplantation is the only curative therapy for many diseases. HSCs from umbilical cord blood (UCB) source have many advantages over from bone marrow. However, limited HSC dose in a single CB unit restrict its widespread use. Over the past two decades, ex vivo HSC expansion with small molecules has been an effective approach for obtaining adequate HSCs. Till now, several small-molecule compounds have entered the phase I/II trials, showing safe and favorable pharmacological profiles. As HSC expansion has become a hot topic over recent years, many newly identified small molecules along with novel biological mechanisms for HSC expansion would help solve this challenging issue. Here, we will give an overview of HSC biology, discovery and medicinal chemistry development of small molecules, natural products targeting for HSC expansion, and their recent clinical progresses, as well as potential protein targets for HSC expansion.
2.Effect comparison of lateral-rectus approach and ilioinguinal approach in the treatment of toddlers with Torode-Zieg type IV pelvic fracture
Yujin TANG ; Chengliang YANG ; Cheng GU ; Xiaodong YANG ; Qiguang MAI ; Tao LI ; Yuhui CHEN ; Zhenhua ZHU ; Jianwen LIAO ; Shicai FAN
Chinese Journal of Trauma 2022;38(1):40-46
Objective:To compare the clinical efficacy of lateral-rectus approach and ilioinguinal approach in the treatment of Torode-Zieg type IV pelvic fracture in toddlers.Methods:A retrospective cohort study was used to analyze the clinical data of 12 toddlers with Torode-Zieg type IV pelvic fracture admitted to Affiliated Hospital of Youjiang Medical College for Nationalities and Third Affiliated Hospital of Southern Medical University from June 2012 to June 2019. There were 6 males and 6 females, aged 13-36 months [(23.9±7.4)months]. Treatment via ilioinguinal approach was performed for 5 patients (ilioinguinal group), and via lateral-rectus approach for 7 patients (lateral-rectus group). Operation duration, intraoperative blood loss and postoperative complications were compared between the two groups. At the last follow-up, pelvic function was evaluated by Majeed function score, and fracture reduction was evaluated according to Mears-Velyvis radiological evaluation criterion.Results:All patients were followed for 24-72 months [(46.0±18.5)months]. In ilioinguinal group and lateral-rectus group, the operation time was (295.0±95.3)minutes and (165.1±52.2)minutes, respectively ( P<0.05), and the intraoperative blood loss was (190.0±65.2)ml and (225.7±92.0)ml, respectively ( P>0.05). In ilioinguinal group, the development of bilateral iliac wings was asymmetric in 3 patients. In lateral-rectus group, fracture-dislocation of epiphyseal plate together with abnormal development of iliac wing occurred in 1 patient, but had no effects on the function of lower limbs. According to Majeed function score at the last follow-up, the pelvic function in ilioinguinal approach group was rated as excellent in 1 patient, good in 2, fair in 1 and poor in 1, with the excellent and good rate of 60%, while the pelvic function in lateral-rectus group was excellent in 4 patients, good in 1, fair in 2 and poor in none, with the excellent and good rate of 71% ( P>0.05). According to Mears-Velyvis radiological evaluation criterion at the last follow-up, the fracture reduction in ilioinguinal group was rated as satisfied in 3 patients and dissatisfied in 2 patients, with the satisfaction rate of 60%, while the fracture reduction in lateral-rectus group was satisfied in 7 patients and dissatisfied in none, with the satisfaction rate of 100% ( P>0.05). Conclusions:For Torode-Zieg type IV pelvic fracture in toddles, both surgical approaches can complete the reduction and fixation. However, the lateral-rectus approach has shorter operation time and less damage to the epiphyseal structure around the pelvis than the ilioinguinal approach.
3.Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy.
Kailin LI ; Jieqiong YOU ; Qian WU ; Wen MENG ; Qiaojun HE ; Bo YANG ; Chengliang ZHU ; Ji CAO
Acta Pharmaceutica Sinica B 2021;11(9):2738-2748
Synthetic lethality is a proven effective antitumor strategy that has attracted great attention. Large-scale screening has revealed many synthetic lethal genetic phenotypes, and relevant small-molecule drugs have also been implemented in clinical practice. Increasing evidence suggests that CDKs, constituting a kinase family predominantly involved in cell cycle control, are synthetic lethal factors when combined with certain oncogenes, such as
4.Association of Apolipoprotein E Polymorphisms with White Matter Lesions and Brain Atrophy
ZhiLi NIU ; PingAn ZHANG ; Dong LI ; ChengLiang ZHU ; LiNa FENG ; Ge XIONG ; NaNa SONG ; Pei TANG ; Feng LIU
Psychiatry Investigation 2020;17(2):96-105
Objective:
Apolipoprotein E (ApoE) is mainly synthesized in the liver. So far, it is unknown the relationship among APOE gene polymorphisms and WML, brain atrophy. Therefore, the aim of the study was to assess the associations of APOE gene polymorphisms in patients with WML and brain atrophy.
Methods:
A total of 58 patients with WML, 128 patients with brain atrophy, 112 patients with co-occurrence of WML and brain atrophy and 95 healthy elderly volunteers were recruited from Renmin Hospital of WuHan University.
Results:
Allele E3 was the most common allele. The alleles E2 had significantly higher levels of ApoB and lower age in WML group. The alleles E2 was associated with the lower level of ApoB, LDL-Ch, TCh, and sdLDL in co-occurrence group. The E3/E3 genotype has higher level of sdLDL, but lower age and female frequency in WML. The E3/E4 genotype had higher level of TG, but lower age in WML. Gender, Age, E2, Hyperhomocysteinemia and UA were also significantly associated with disease progression.
Conclusion
This study found that clinical data, lipids and metabolic complications were closely related to ApoE genotypes and alleles, and also disease progression and type.
5.Risk factors for fatal outcome in patients with severe COVID-19: an analysis of 107 cases in Wuhan
Kai DAI ; Anyu BAO ; Peng YE ; Ming XU ; Qinran ZHANG ; Yu ZHOU ; Wanli JIANG ; Wubian JIANG ; Huimin WANG ; Mengfei ZHU ; Lingling TANG ; Chengliang ZHU ; Yuchen XIA ; Ying’an JIANG ; Xiufen ZOU ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(4):257-263
Objective:To analyze the risk factors of fatal outcome in patients with severe COVID-19.Methods:The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression.Results:Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators ( P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient’s clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion:COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.
6.Exploration of Learning Mode of "College in Hospital" in Nursing Specialty
Meijian REN ; Aihong XING ; Chengliang ZHU
Chinese Medical Ethics 2018;31(2):198-201,240
Objective:To understand the implementation of learning mode of "College in Hospital", and ex-plore the new ideas of vocational education, in order to provide reference basis for enriching talent training mode. Method:Since the fourth semester of February 2016 , nursing specialty of Shandong Medical College sent nursing students to cooperation hospital for the study of nursing professional courses, including hospital classroom learning and beside study of clinical department. It adopted the way of classroom learning in the morning and clinical clerk-ship in the afternoon, and achieved that theoretical learning and clinical operation were seamlessly linked, the two sides jointly constructed a teaching plan, the teaching process was interconnected timely, evaluation methods was innovated and process evaluation and summative assessment modes were adopted. Result: The"College in Hospi-tal" learning mode was conducive to the improvement of nursing students' learning efficiency, and really achieved professional and industry, occupation post docking, professional courses and professional standard docking, the teaching process and the production process docking, academic certificate and occupation qualification certificate docking and vocational education and lifelong learning docking. Conclusion:The learning mode has achieved re-markable results, with demonstration and promotion value.
7.Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome.
Qiaohong LAI ; Wenpei XIANG ; Qing LI ; Hanwang ZHANG ; Yufeng LI ; Guijin ZHU ; Chengliang XIONG ; Lei JIN
Frontiers of Medicine 2018;12(5):518-524
The increased levels of intracellular reactive oxygen species (ROS) in granulosa cells (GCs) may affect the pregnancy results in women with polycystic ovary syndrome (PCOS). In this study, we compared the in vitro fertilization and embryo transfer (IVF-ET) results of 22 patients with PCOS and 25 patients with tubal factor infertility and detected the ROS levels in the GCs of these two groups. Results showed that the PCOS group had significantly larger follicles on the administration day for human chorionic gonadotropin than the tubal factor group (P < 0.05); however, the number of retrieved oocytes was not significantly different between the two groups (P > 0.05). PCOS group had slightly lower fertilization, cleavage, grade I/II embryo, clinical pregnancy, and implantation rates and higher miscarriage rate than the tubal factor group (P > 0.05). We further found a significantly higher ROS level of GCs in the PCOS group than in the tubal factor group (P < 0.05). The increased ROS levels in GCs caused GC apoptosis, whereas NADPH oxidase 2 (NOX2) specific inhibitors (diphenyleneiodonium and apocynin) significantly reduced the ROS production in the PCOS group. In conclusion, the increased ROS expression levels in PCOS GCs greatly induced cell apoptosis, which further affected the oocyte quality and reduced the positive IVF-ET pregnancy results of women with PCOS. NADPH oxidase pathway may be involved in the mechanism of ROS production in GCs of women with PCOS.
Abortion, Spontaneous
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epidemiology
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Acetophenones
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therapeutic use
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Adult
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Apoptosis
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drug effects
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Embryo Transfer
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Female
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Fertilization in Vitro
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Granulosa Cells
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metabolism
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Humans
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NADPH Oxidases
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antagonists & inhibitors
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Onium Compounds
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therapeutic use
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Oocyte Retrieval
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Oxidative Stress
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Polycystic Ovary Syndrome
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drug therapy
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Pregnancy
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Pregnancy Rate
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Reactive Oxygen Species
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metabolism
8.The Clinical Value of Ultrasound-Guided Percutaneous Lauromacrogol Injection Sclerotherapy for Simple Renal Cyst
Chengwei LIU ; Chengliang YANG ; Changyu ZHU ; Zhendong ZHANG
Chinese Journal of Biochemical Pharmaceutics 2017;37(8):414-415
Objective To analyze the clinical value of ultrasound-guided percutaneous Lauromacrogol Injection sclerotherapy in the treatment of simple renal cyst. Methods A total of eighty patients with simple renal cyst, who were divided into 40 groups according to the random number table, were divided into two groups from February 2016 to April 2017. The traditional group used traditional open renal cyst unroofing decompression. Ultrasound guided ultrasound guided percutaneous Lauromacrogol Injection sclerotherapy was performed in the ultrasound guided group. The therapeutic effect, operation time and the rate of successful puncture were compared between two groups of simple renal cysts. It needs to compare the volume of the cyst and the quality of life before and after the intervention. Results Ultrasound guided group simple renal cyst treatment effect was higher than the traditional group (P<0.05). The operation time of the ultrasound guided group was shorter than that of the traditional group, and the success rate of the one shot puncture was higher than that of the traditional group(P<0.05). Before the intervention, the volume and quality of life of the two groups were similar. In the ultrasound guided group, the volume and quality of life in the ultrasound guided group were better than those in the traditional group(P<0.05). Conclusion Ultrasound guided percutaneous Lauromacrogol Injection sclerotherapy is of high clinical value in the treatment of simple renal cysts. The utility model can improve the success rate of one puncture, shorten the operation time, and the exact effect can speed up the regression of symptoms and reduce the volume of the cyst. Therefore, this method can improve the quality of life of patients.
9.Risk factors for early death after abdominal damage control operation
Chengliang ZHU ; Bo TONG ; Peijun YAN
Chinese Journal of Trauma 2016;32(1):74-77
Objective To report the early mortality and associated risk factors after damage control operation (DCO) in patients with severe abdominal trauma.Methods A total of 146 patients hospitalized from January to March in 2015 were retrospectively analyzed.Early death was defined as death occurring within 72 h of first surgery and before the definitive surgery.Based on the death definition, the subjects were divided into death group and survival group.The two groups were compared for gender, age, injury time, injury classification, vital signs, need for cardiopulmonary resuscitation, Glasgow coma score (GCS), injury severity score (ISS), hemoglobin, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), blood pH, base excess, operative time, and postoperative acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ).Logistic regression analysis was applied to examine the predicators of early postoperative mortality.Results There were 118 patients (80.8%) in survival group and 28 patients (19.2%) in death group.Survival and death groups differed significantly with regard to the percent of elderly (6.8% vs.21.4%), percent of patients with multiple injury (62.7% vs.85.7%), body temperature [(36.1 ± 0.4) vs.(35.2 ± 0.8) ℃], percent of patients with greater ISS (31.4% vs.64.3%), PT [(12.1±1.5) vs.(13.9±1.2)s], bloodpH (7.25±0.04vs.7.08±0.11), base excess [(-8.9±2.8) vs.(-10.6±3.3)mmol/L], postoperative APACHE Ⅱ[(12.8 ± 1.8) vs.(17.5 ± 2.0) points] (P < 0.05).Logistic regression analysis identified the age (OR=1.512, 95% CI 1.112-4.157,P<0.05), ISS (OR =1.313,95% CI 1.134-5.442, P < 0.05), APACHE Ⅱ (OR =1.361,95 % CI 1.182-5.222, P < 0.05) as the independent risk factors for early mortality.Conclusion The patients underwent DCO for severe abdominal trauma has a high early mortality, which is closely associated with the age, injury severity and postoperative medical status.
10.Follow-up Study on Long-term Prognosis of Gastric Cancer Patients with Acute Disease
Chengliang ZHU ; Bo TONG ; Jindao WANG
Chinese Journal of Gastroenterology 2016;21(8):484-487
Background:Gastric cancer is a common gastrointestinal malignancy. The detection rate of early gastric cancer is still low in China,and some gastric cancer patients visit the hospital due to acute disease,such as gastric perforation. Aims:To investigate the influence of acute disease on long-term prognosis in gastric cancer patients. Methods:A total of 318 patients with gastric cancer from Jan. 2009 to Jan. 2015 at Shaoxing People’s Hospital were enrolled,and were divided into acute disease group and non-acute disease group. Clinicopathological characteristics were analyzed. Patients were followed up,and survival rate was compared between the two groups. Results:Fifty-three(16. 7% )patients had acute disease,and the remaining 265(83. 3% )patients were without acute disease. Compared with non-acute disease group, percentage of TNM Ⅳ stage was significantly increased(P < 0. 05),and percentage of radical surgery was significantly decreased in acute disease group(P < 0. 05). Kaplan-Meier assay showed that survival rate in acute disease group was significantly decreased when compared with non-acute disease group( P < 0. 05). After adjusting the TNM stage and surgical treatment,no significant difference in survival rate was found between the two groups. Conclusions:Gastric cancer patients with acute disease have lower survival rate. Acute disease may be not an independent prognostic factor, higher TNM stage and lower proportion of radical surgery are the main reasons for poor prognosis in gastric cancer patients with acute disease.

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