1.Effects of sodium hydrosulfide on HK2-NLRP3-GSDMD pathway and pyroptosis induced by lung ischemia/reperfusion in rats
Lu SHI ; Xiaoting WANG ; Zhenzhen LUO ; Jun CHENG ; Sian CHEN ; Jun-Peng XU ; Qihao ZHANG ; Wenjie CAO ; Man HUANG ; Yunna TIAN ; Xuguang JIA ; Wantie WANG
Chinese Journal of Pathophysiology 2024;40(6):1105-1113
AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.
2.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
3.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
4.Effect of self-made Yiqi Yangyin Decoction on immune function, tumor markers and toxic and side effects of chemotherapy in patients with advanced gastric cancer chemotherapy
Guangwei SHI ; Wendong JING ; Xingyu JIN ; Xiaoting ZHENG ; Shengbao WU
International Journal of Traditional Chinese Medicine 2022;44(2):154-158
Objective:To explore the effect of self-made Yiqi Yangyin Decoction on immune function, serum tumor markers and toxic and side effects of chemotherapy in patients with advanced gastric cancer chemotherapy.Methods:A total of 88 patients with advanced gastric cancer who met the inclusion criteria in the hospital between December 2018 and December 2020 were divided into two groups according to the random number table method, with 44 in each group. The control group was treated with chemotherapy, and the observation group was given self-made Yiqi Yangyin Decoction on the basis of the control group. The two groups were treated for 4 consecutive cycles with 3 weeks as 1 cycle. The Traditional Chinese Medicine (TCM) symptoms were scored before and after treatment, and the levels of IgG, IgA and IgM were detected by immunoturbidimetry. The levels of carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) were detected by ELISA. The gastrointestinal reactions, thrombocytopenia, anemia, leukopenia and neurotoxicity were recorded and evaluated during treatment, and the clinical efficacy was assessed.Results:The total effective rate was 81.8% (36/44) in observation group and 61.4% (27/44) in control group (χ 2=4.53, P<0.05). After treatment, the scores of stomachache and gastric distension, poor appetite, shortness of breath, and drooping spirit in observation group were significantly lower than those in the control group ( t=17.28, 11.91, 5.02, 5.65, all Ps<0.001) while the levels of serum IgG [(9.39±0.46)g/L vs. (8.54±0.23) g/L, t=10.96], IgA [(1.35±0.42) g/L vs. (1.07±0.15) g/L, t=6.90] and IgM [(0.92±0.09) g/L vs. (0.78±0.10) g/L, t=4.17] were significantly higher than those in the control group ( P<0.01). The levels of serum CEA [(9.07±1.01) μg/L vs. (14.89±2.13) μg/L, t=16.38] and CA125 [(24.87± 4.68) kU/L vs. (30.75±5.33) kU/L, t=5.50] were significantly lower than those in the control group ( P<0.01). During treatment, the toxic and side effects of gastrointestinal reactions, thrombocytopenia, anemia, leukopenia and neurotoxicity were significantly lower in the observation group than those in the control group ( Z=18.52, 2.54, 3.12, 3.84, 2.34, P<0.05). Conclusion:Self-made Yiqi Yangyin Decoction can improve the TCM symptoms, enhance the immunity, reduce the levels of serum tumor markers, and relieve the toxic and side effects of chemotherapy of patients undergoing chemotherapy for advanced gastric cancer.
5.Development and Application of the First Carbon Ion Therapy System in China.
Rong LIU ; Qian MIAO ; Guoxiu SHI ; Yuqin LIU ; Xiaoyue DU ; Xiaoting QIANG ; Yinxia MA ; Lihong XUAN ; Shan ZHENG
Chinese Journal of Medical Instrumentation 2022;46(5):517-522
At present, heavy ion is an ideal radiation for cancer treatment, and carbon ion is used in the treatment of many kinds of cancer due to its higher relative biological effect value. In 2019, Wuwei heavy ion center built the first medical heavy ion accelerator-carbon ion radiotherapy system in China, and obtained the registration license from the National Medical Products Administration, and officially received cancer patients in March 2020. This study introduced the development and application of the first carbon ion radiotherapy system in China.
Carbon
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China
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Heavy Ion Radiotherapy
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Heavy Ions
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Humans
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Neoplasms/radiotherapy*
6.Normoalbuminuric diabetic kidney disease and hyperuricaemia in elderly type 2 diabetic patients
Wenxia CUI ; Mingrui ZHANG ; Lei GAO ; Xiaoting SHI ; Man LI ; Yun HU
Chinese Journal of Endocrinology and Metabolism 2022;38(10):854-858
Objective:To assess the correlation between hyperuricaemia and normoalbuminuric diabetic kidney disease(NADKD) in elderly type 2 diabetic patients.Methods:This retrospective case-control study enrolled 910 patients with type 2 diabetes mellitus who were hospitalized in the Geriatric Department of Nanjing Drum Tower Hospital from 2015 to 2020. The patients were divided into NADKD group [urinary albumin/creatinine(UACR)<30 mg/g and estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, n=169)], albuminuria DKD group [UACR ≥30 mg/g and eGFR <60 mL·min -1·(1.73 m 2) -1, n=234], and control group [UACR <30 mg/g and eGFR≥60 mL·min -1·(1.73 m 2) -1, n=507]. Medical history, physical examination, and laboratory tests were collected. Results:The proportion of women in the NADKD group was significantly higher than that in the albuminuric DKD group(50.89% vs 40.60%, P<0.05). Duration of diabetes, HbA 1C, fasting plasma glucose(FPG), the prevalences of hypertension and hyperuricaemia, blood urea nitrogen, blood creatinine, and blood uric acid were significantly lower in the NADKD group than those in the albuminuric DKD group(all P<0.05). Blood urea nitrogen, serum creatinine, triglycerides, serum uric acid and the prevalence of hyperuricemia were significantly higher in the NADKD group compared the control group(all P<0.001) while the proportion of hypertension, systolic blood pressure, LDL-C, HbA 1C, and FPG were lower(all P<0.05). Multivariate linear regression analysis showed that eGFR was negatively associated with urea nitrogen and serum uric acid while positively associated with HbA 1C in normoalbuminuric elderly type 2 diabetic patients(all P<0.001). Logistic regression analysis revealed that hyperuricaemia was a risk factor for NADKD in elderly type 2 diabetic patients after adjusting for BMI, blood pressure, lipids, and glucose( OR=1.963, 95% CI 1.157-3.332, P=0.012). Conclusion:Hyperuricaemia is significantly associated with NADKD in elderly patients with type 2 diabetes.
7.Dose level of pediatric CT scanning in a hospital
Yuenan WANG ; Yan WANG ; Xiaohong DU ; Xiaoting SHI ; Lantao LIU
Chinese Journal of Radiological Health 2022;31(2):153-156
Objective To investigate the dose level of pediatric CT scan in one hospital, and to provide recommendations for optimized scanning. Methods The CT scan data of children were collected from this hospital to analyze the differences in typical dose values and typical scanning parameters between different age groups and different scanning parts. Results The sample size was >10 for routine cranial scan, routine maxillary sinus scan, and routine chest scan in each age group, and the 1-year-old group and the 5-year-old group had the same kV, mA, and CTDIvol values of routine cranial scan and maxillary sinus scan, but with relatively great differences in the parameters of chest scan. Conclusion Scanning parameters in this hospital can be further optimized, and optimization measures should be adopted continuously.
8.The expression and clinical significance of promyelocytic leukemia zinc finger in human peripheral blood with asthma
Xiaoting REN ; Tianyun SHI ; Na LI ; Yanchao HE ; Ling QIAN ; Jingjing FENG ; Zhoufang MEI ; Zhijun JIE
Chinese Journal of Emergency Medicine 2022;31(10):1389-1395
Objective:To investigate the expression of promyelocytic leukemia zinc finger (PLZF) in human peripheral blood with asthma and its clinical significance.Methods:Forty patients with stable asthma from May 2021 to October 2021 in the Department of Respiratory Medicine of the Shanghai Fifth People's Hospital were enrolled, and forty healthy controls were recruited in the study. The levels of cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (qPCR) was used to detect the expression of PLZF mRNA in plasma. The level and distribution of PLZF+ cells in PBMCs were detected by flow cytometry after isolating peripheral blood mononuclear cells (PBMCs). Independent sample t test, Mann-Whitney U test, χ 2 test, ROC curve and Logistic regression were used to analyze the results with SPSS 26.0 and Graphpad Prism 7.0. A P<0.05 was considered statistically significant. Results:The levels of cytokines IFN-γ, IL-2, IL-4, TNF-α and IL-17 in human peripheral blood from the asthma group were obviously higher than those in the control group ( P<0.05), whereas there was no significant difference in the level of cytokine IL-10 between the two groups. The level of PLZF mRNA in PBMCs from the asthma group was significantly up-regulated compared to that in the control group [(3.40%±2.52%) vs. (1.23%±0.78%), P<0.05]. CD8+PLZF+ and Vβ11+PLZF+T cells in the asthma group were significantly outnumbered than those in the control group ( P<0.05). Logistic regression and ROC curve analysis showed that PLZF expression in PBMC was a risk factor for the development of asthma ( OR =3.67, AUC=0.87, P<0.05). Conclusions:The high expression of PLZF in peripheral blood may play an important role in the development of asthma, which needs to be further confirmed by large sample studies.
9.Research advances on pharmacological interventions for hypertrophic scar
Liangliang SHI ; Mingzhuo LIU ; Zhengying JIANG ; Xiaoting YU ; Jiaqi LI ; Guanghua GUO
Chinese Journal of Burns 2022;38(12):1179-1184
Hypertrophic scar is an abnormal fibrous proliferative disease that occurs after deep cutaneous injury, which not only affects aesthetics and function but also has negative psychological effects on the patients. However, the mechanism of hypertrophic scar formation has not been fully elucidated, and its clinical treatment is complex with a high rate of recurrence and no radicle cure. Intervention based on molecular targets will likely be the future direction for the prevention and treatment of hypertrophic scar. In this article, we review the specific roles and mechanisms of drug-targeted interventions in hypertrophic scar formation, including general drugs, cytokines, immunomodulators, herbal extracts, exosomes, and nanomaterials, in the context of advances in both basic and clinical research at home and abroad.
10.Integrative Analysis of Genome,3D Genome,and Transcriptome Alterations of Clinical Lung Cancer Samples
Li TINGTING ; Li RUIFENG ; Dong XUAN ; Shi LIN ; Lin MIAO ; Peng TING ; Wu PENGZE ; Liu YUTING ; Li XIAOTING ; He XUHENG ; Han XU ; Kang BIN ; Wang YINAN ; Liu ZHIHENG ; Chen QING ; Shen YUE ; Feng MINGXIANG ; Wang XIANGDONG ; Wu DUOJIAO ; Wang JIAN ; Li CHENG
Genomics, Proteomics & Bioinformatics 2021;19(5):741-753
Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.


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