1.Correlation between the mutation spectrum of the UGT1A1 gene and clinical phenotype in patients with inherited hyperunconjugated bilirubinemia
Qingfang XIONG ; Yujia LU ; Lei ZOU ; Hui ZHOU ; Hao REN ; Xiaoning FENG ; Yongfeng YANG
Chinese Journal of Hepatology 2024;32(4):340-345
Objective:To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia.Methods:Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ2 testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results:112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups ( F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 ( n=10) and TA7/TA7 ( n=14) mutations were statistically significant in TBil ( t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous ( n=9) and isolated ( n=15) mutation had no statistical significance in TBil ( t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups ( F=270.992, P<0.001). There was no statistically significant difference ( χ2=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion:The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.
2.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.
3.Rac1 promotes the formation of heterotypic cell-in-cell structure.
Tao HU ; Pengfei FENG ; Haoyuan LI ; Lulin ZHOU ; Zubiao NIU ; Yinuo HUANG ; Xiaoning WANG ; Chenxi WANG ; Hui LIU ; Chengjun WU
Chinese Journal of Biotechnology 2023;39(10):4123-4134
Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.
4.A case of death in children with hypereosinophilia complicated with Loffler endocarditis
Xinhua WU ; Lin FENG ; Xiaoning WANG ; Juan HE
Clinical Medicine of China 2023;39(1):50-53
Objective:To investigate the clinical features of hypereosinophilia (HE) complicated with Loffler endocarditis in children, in order to analyze the etiology, clinical stage and prognosis of HE complicated with Loffler endocarditis.Methods:A case of childhood hypereosinophilia complicated with Loffler endocarditis diagnosed and treated in the Second Hospital of Hebei Medical University was analyzed retrospectively, and its clinical characteristics, causes and clinical stages were analyzed.Results:In this study, the patient was a young male. He had diarrhea for more than 40 days due to intermittent abdominal pain, dyspnea for 10 days, and poor food intake for 3 days. The blood routine showed that he was HE. The ultrasound showed Loffler endocarditis. The child had severe heart failure and multiple organ functions were involved. After active treatment, he still had multiple organ failure, and finally died of multiple organ failure and ventricular fibrillation.Conclusion:Loffler endocarditis is a serious complication of HE, with low morbidity and rare clinical manifestations. Early intervention can reduce mortality.
5.High mobility group box-1 inhibition reduces expression of matrix metalloproteinase-9 in astrocytes in rats after spinal cord injury
Lin SUN ; Chen DENG ; Jun MEI ; Xiaoning FENG ; Liping WANG ; Jinming LIU ; Junqiao LYU
Chinese Journal of Orthopaedic Trauma 2023;25(8):711-717
Objective:To investigate the role and underlying mechanisms of inhibiting high mobility group box-1 (HMGB1) in the expression of matrix metalloproteinase-9 (MMP-9) in spinal cord astrocytes (AS) in rats after spinal cord injury (SCI).Methods:After an SCI model was established in Sprague-Dawley (SD) rats using a modified Allen's Weight-Dropping method and ethyl pyruvate (EP) or glycyrrhizin (GL) was used to inhibit the effect of HMGB1, the rats were divided into a sham group, an SCI group, an SCI+EP (50 mg/kg) group, and an SCI+GL (100 mg/kg) group. The expression levels of glial fibrillary acid protein (GFAP) and MMP-9 in spinal cord AS were observed. After the spinal cord AS in SD rats was cultured and incubated by the oxygen-glucose deprivation/reoxygenation (OGD/R) procedure, the expression of MMP-9 protein was detected at 6 h/R 6 h, 12 h, 24 h, and 48 h after OGD. The time point with the highest expression was chosen in the subsequent experiments as an OGD/R group. HMGB1 was inhibited by HMGB1 shRNA or EP to observe the effect of HMGB1 on the expression of MMP-9 protein in AS treated with OGD/R. Then, toll-like receptor 4 (TLR4) inhibitor, TIR-domain-containing adaptor inducing interferon- β (TRIF) inhibitor, and nuclear factor-kappa B (NF- κB) inhibitor were used to investigate the effects of TLR4/TRIF/NF- κB signaling pathway during the regulation of HMGB1 on MMP-9 in vitro. Results:Western blot showed that the expression of MMP-9 protein in the spinal cord was significantly increased in rats at 1 d after SCI, and the expression of MMP-9 protein in the SCI+EP group and the SCI+GL group was significantly lower than that in the SCI group ( P<0.001). Immunofluorescence showed that GFAP and MMP-9 proteins were co-localized in the spinal cord after SCI, and the expression of GFAP and MMP-9 proteins in the SCI+EP and SCI+GL groups was significantly lower than that in the SCI group ( P<0.05). Since the expression of MMP-9 protein in the spinal cord AS cultured in vitro was significantly higher in the OGD 6h/R 12h group than that in the normal group and the OGD 6h/R 6h, 24, and 48 h groups, the OGD 6h/R 12h was taken as the OGD/R group. The MMP-9 protein expression in AS in the OGD/R+HMGB1 shRNA group and the OGD/R+EP group was significantly lower than that in the OGD/R group ( P<0.001). In the cultured AS, moreover, inhibiting TLR4, TRIF, and NF- κB reduced MMP-9 protein expression after OGD 6 h/R 12 h when compared with that in the OGD/R group ( P<0.001). Conclusions:HMGB1 inhibition may result in a reduction in MMP-9 expression both in the spinal cord AS in SCI rats and in AS after OGD/R treatment in vitro. HMGB1 may regulate MMP-9 protein expression in AS after OGD/R treatment via the TLR4/TRIF/NF- κB signal pathway.
6.Research on the Resource Allocation Level and Equity Measurement of China's Health and Pension Industry
Zhen XUE ; Xingyue LIU ; Zhiqiang FENG ; Xiaoning HAO
Chinese Health Economics 2023;42(12):66-70
Objective:To construct an indicator system to comprehensively evaluate the resource allocation level of the health and pension industry in 31 provinces of China from 2016 to 2021,calculate the fairness of resource allocation,clarify the problems in resource allocation of the health and pension industry in China,and promote high-quality development of the health and pension industry.Methods:The entropy method is used to comprehensively evaluate the level of resource allocation in the health care industry,and the Gini coefficient and Theil index are used to analyze the fairness of resource allocation in the health care industry.Results:The level of resource allocation in the health and pension industry is generally not high,with significant inter provincial differences;the unequal allocation of resources in the health industry is on the rise;regional differences are the leading force that causes differences in the fairness of resource allocation in the health and pension industry.Conclusion:It is suggested to improve the infrastructure and stimulate the endogenous impetus of the development of the health and pension industry;deeply cultivate market demand and improve the level of resource allocation in the health and pension industry;optimize financial investment and bridge the gap in regional health resource allocation.
7.Characteristics of gut microbiota in hyperuricemia population based on full-length 16S rRNA sequencing
Haiying JIA ; Feng HU ; Li YANG ; Xiaoning ZOU ; Zhen WANG ; Lingjun MENG ; Yerong LI
Chinese Journal of Microbiology and Immunology 2022;42(4):265-274
Objective:To analyze the differences in gut microbiota between patients with hyperuricemia (HUA) and healthy population for better understanding the correlation between gut microflora and high uric acid.Methods:This study recruited 63 adult volunteers, including 25 HUA patients (HUA group) and 38 healthy people (control group), who underwent physical examination in the PLA Strategic Support Force Characteristic Medical Center in 2021. Their fecal samples were collected and analyzed by 16S rRNA high-throughput full-length gene sequencing to analyze the composition of gut microbiota.Results:The overall composition of gut microbiota was different between HUA group and control group. The α diversity index decreased significantly in HUA group and β diversity analysis showed that there were significant differences between the two groups. HUA group showed increased Bacteroidetes and decreased Firmicutes. LEfSe analysis indicated a unique microbiota structure in HUA group, characterized by significantly decreased short-chain fatty acid (SCFA)-producing bacteria represented by Faecalibacterium prausnitzii and significantly increased Streptococcus salivarius, Bacteroides fragilis, Fusobacterium hwasookii, Flavonifractor plautii, Mycobacterium mucogenicum B and Blautia sp003287895. In addition, functional prediction through PICRUSt2 showed that the metabolism related to gut microbiota SCFA pathway in HUA group was decreased, which was consistent to the unique microbiota structure. Conclusions:Compared with healthy population, patients with hyperuricemia had different composition of gut microbiota and metabolic feature.
8.Characterization of gut microbiota based on full-length 16S rRNA gene sequencing in high diamine oxidase population
Yerong LI ; Feng HU ; Li YANG ; Xiaoning ZOU ; Zhen WANG ; Lingjun MENG ; Haiying JIA
Chinese Journal of Microbiology and Immunology 2022;42(5):383-389
Objective:To investigate the correlation between gut microbiota and serum diamine oxidase (DAO) level and to analyze the differences in gut microbiota between high DAO (DAO-H) and normal DAO populations.Methods:This study recruited 62 adult volunteers (31 in DAO-H group and 31 in normal control group) taking health examination in the Strategic Support Forces Special Medical Center in 2021. Their stool samples were collected to analyze the composition of gut microbiota in the two populations by full-length 16S rRNA gene sequencing.Results:No significant difference in the alpha diversity of gut microbiota was found between the DAO-H group and the normal control group, but the structure and function of gut microbiota varied. In the DAO-H group, commensal bacteria decreased, such as Phocaeicola and Bacteroidetes, while potential pathogenic bacteria increased, such as Klebsiella pneumoniae. There were changes in the metabolism of gut microbiota in the DAO-H group, including inhibited sphingolipid metabolism and enhanced biosynthesis of vancomycin group antibiotics, one carbon pool by folate pathway, terpenoid backbone biosynthesis, cell cycle-Caulobacter, protein export, base excision repair and nitrogen metabolism.Conclusions:Compared with the people with normal DAO, the population with high DAO had unique characteristics in gut microbiota composition and metabolism.
10.Pathological significance of p-STAT3 and Survivin expression in gastric cancer and establishment of preoperative prognostic model
Wen Yue ; Xiaojun Wang ; Miaomiao Ma ; Dandan Zhang ; Feng Pan ; Jiaqi Nie ; Xiaoning Li ; Haikang Cui ; Lan Yang ; Wenjie Zhang
Acta Universitatis Medicinalis Anhui 2022;57(5):816-822
Objective:
To investigate the relationship between the expression of p-Stat3 and Survivin in gastric cancer and the clinical characteristics and prognosis of patients, and to establish the prediction model of postoperative survival of patients combined with alanine aminotransferase(ALT) and aspartate aminotransferase(AST).
Methods:
Data of 133 patients undergoing gastric tumor resection were collected and followed up. The expression of p-STAT3 and Survivin in gastric cancer and precancerous tissues were detected by immunohistochemical method. Kaplan-Meier method was used to draw the survival curve. Logistic regression model combined with receiver operating characteristic curve(ROC) curve was used to describe the predictive value of multi-index combined detection on postoperative survival status of patients. The prediction model of the histogram was established using Survival and RMS packages in R Studio software.
Results:
The expressions of p-Stat3 and Survivin in gastric cancer tissues were higher than those in precancerous tissues. The expression of p-Stat3 in gastric cancer tissues was positively correlated with the depth of invasion and TNM stage, while the expression of Survivin in gastric cancer tissues was positively correlated with the degree of differentiation and the depth of invasion. The higher the expression levels of p-Stat3 and Survivin, the worse the prognosis. The lower the ALT level, the worse the prognosis. Survivin, ALT and AST were the optimal combination for predicting postoperative survival in patients with gastric cancer.
Conclusion
The expression of p-Stat3 and Survivin plays an auxiliary role in the diagnosis of gastric cancer. P-Stat3, Survivin and ALT are correlated with the prognosis of patients with gastric cancer and have predictive value. Survivin, ALT and AST combined model has a big value to predict the postoperative survival prognosis of gastric cancer patients, which can provide a reference for clinical practice.


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