1.Dosiomics-based prediction of the occurrence of bone marrow suppression in patients with pelvic tumors
Yanchun TANG ; Jingyi TANG ; Jinkai LI ; Qin QIN ; Hualing LI ; Zhigang CHANG ; Tianyu ZHANG ; Yaru PANG ; Xinchen SUN
Chinese Journal of Radiation Oncology 2024;33(7):620-626
Objective:To assess the predictive value of dosiomics in predicting the occurrence of bone marrow suppression (BMS) in patients with pelvic tumors during radiotherapy.Methods:A retrospective analysis was conducted on the clinical data and radiotherapy planning documents of 129 patients with pelvic region tumors who underwent radiotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2019 to January 2023. The region of interest (ROI) was outlined for bone marrow in the pelvic region by Accu Contour software in planning CT, and the ROI was exported together with the dose distribution file. According to a stratified randomization grouping method, the patients were divided into the training set and test set in an 8 vs. 2 ratio. The dosiomic features were extracted from the ROI, and the two independent samples t-test and the least absolute shrinkage and selection operator (LASSO) algorithm was employed to identify the best predictive characteristics. Subsequently, the dosiomic scores were calculated. Clinical predictors were identified through both univariant and multivariate logistic regression analyses. Predictive models were constructed by using clinical predictors alone and combining clinical predictors and dosiomic scores. The efficacy of predictive model was assessed by plotting the receiver operating characteristic (ROC) curve and evaluating its performance through the area under the ROC curve (AUC), the calibration curve, and decision curve analysis (DCA). Results:Fourteen dosiomic features that showed a strong correlation with the occurrence of BMS were screened and utilized to calculate the dosiomic scores. Based on both univariant and multivariate logistic regression analyses, chemotherapy, planning target volume (PTV) and V 5 Gy were identified as clinical predictors. According to the combined model, the AUC values for the training set and test set were 0.911 and 0.868, surpassing those of the clinical model (AUC=0.878 and 0.824). Furthermore, the analysis of both the calibration curve and DCA suggested that the combined model had higher calibration and net clinical benefit. Conclusion:The combined model has a high diagnostic value for predicting BMS in patients with pelvic tumors during radiotherapy.
2.Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets.
Bo JIN ; Xuechao PANG ; Qingce ZANG ; Man GA ; Jing XU ; Zhigang LUO ; Ruiping ZHANG ; Jiangong SHI ; Jiuming HE ; Zeper ABLIZ
Acta Pharmaceutica Sinica B 2023;13(4):1699-1710
Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.
3.Comparative analysis of single kidney transplantation for children between low weight and high weight pediatric donor
Hongchang XIE ; Ming YI ; Yonghua FENG ; Xianlei YANG ; Zhigang WANG ; Junxiang WANG ; Lei LIU ; Jinfeng LI ; Xinlu PANG ; Wenjun SHANG ; Guiwen FENG
Chinese Journal of Urology 2021;42(5):370-374
Objective:To compare the efficacy of single kidney transplantation for children from pediatric donors between body weight ≤15 kg and >15 kg.Methods:A retrospective review in 156 children with single donor kidney transplantation from August 2010 to December 2019 in the Kidney Transplantation Department of the First Affiliated Hospital of Zhengzhou University was conducted. The patients were classified into the small kidney group (pediatric donor body weight ≤15 kg) and the big kidney group (pediatric donor body weight >15 kg). In this study, 89 cases were concluded in the small kidney group and 67 cases were concluded in the big kidney group. The donor kidneys were obtained from 46 cases of small weight (≤15 kg) pediatric donors and 48 cases of large weight (>15 kg) pediatric donors. There were significant differences in age [1.00 (0.02 - 4.00) years vs. 10.00 (3.00-18.00) years], body weight [10.0 (3.4 - 15.0) kg vs. 35.0 (16.2- 35.0) kg], height [76 (50- 113) cm vs. 144 (67-172) cm], GFR [(31.50±7.46)ml/min vs. (36.79±7.00) ml/min], and renal length to diameter [(5.91±0.48) cm vs. (8.71±1.88) cm] between the small kidney group and the big kidney group ( P < 0.01). There was no significant difference between the two groups of donors in gender, cold/warm ischemia time and cause of death ( P>0.05). There were significant differences in age [(11.28±3.89) years vs. (13.86±3.56) years], body weight [(31.83±10.45)kg vs. (35.13±9.15) kg], and height [(130.02±28.56) cm vs. (143.97±16.59) cm] between recipients of the small kidney group and big kidney group ( P < 0.05). While there were no significant differences in preoperative serum creatinine level [(822.65 ± 135.04) μmol/L vs. (777.31 ± 165.40) μmol/L], HLA mismatch [(3.4 ± 1.4) site vs. (3.2±1.3) site], and primary disease between the two groups ( P > 0.05). The recovery of renal function, postoperative adverse events, postoperative children, and graft survival were compared between the two groups. Results:The renal function of the two groups of recipients returned to normal 3 months after operation. The perioperative complications in the small kidney group and the big kidney group mainly included renal delayed recovery [5.6% (5/89) vs. 7.5% (5/67), P=0.89], renal vascular embolization [3.4% (3/89) vs. 0, P=0.35], and acute rejection [2.2% (2/89) vs. 4.3% (3/67) , P=0.75]. The main cause of recipient death during the follow-up period was pulmonary infection [4.5% (4/89) vs. 6.0% (4/67) , P=0.68]. The postoperative small kidney group was followed up for an average of 30 (3-74) months. The survival rates of children in the small kidney group at the 1, 3 and 5 years after surgery were 96.6% (86/89), 91.0% (81/89) and 91.0%(81/89), while the transplanted renal survival rates were 92.1% (82/89), 86.5% (77/89) and 84.2% (75/89), respectively. The postoperative big kidney group was followed up for an average of 32 (4-89 ) months. The survival rates of children in the big kidney group were 95.5% (64/67), 94.0% (63/67) and 91.0%(61/67) in the first 1, 3 and 5 years postoperatively, while the graft survival rates were 92.5% (62/67), 83.6% (56/67) and 83.6% (56/67), respectively. The postoperative kidneys of two groups were fast-growing, and there was no significant difference between the small kidney group and the big kidney group in graft length to diameter [(9.63±0.31) cm vs. (9.75±0.71) cm] after 1 year ( P>0.05). Conclusions:The effect of single pediatric kidney transplantation for pediatric donor with body weight ≤15 kg is equivalent to that for pediatric donor with body weight >15 kg , which can be carried out clinically.
4.Complications and efficacy of kidney transplantation in children and adolescents with infant donors
Hongchang XIE ; Ming YI ; Yonghua FENG ; Zhigang WANG ; Junxiang WANG ; Lei LIU ; Jinfeng LI ; Jianguo WEN ; Xinlu PANG ; Wenjun SHANG ; Guiwen FENG
Chinese Journal of Applied Clinical Pediatrics 2021;36(21):1614-1617
Objective:To retrospectively analyze clinical data of infant donors with body weight ≤15 kg into children recipients, and to investigate the efficacy and complications under the strategy of pediatric donor to pediatric recipient (PTP) of pediatric kidney transplantation allocation.Methods:Clinical data of kidney transplantation for children with infant donors performed in the First Affiliated Hospital of Zhengzhou University from August 2010 to December 2019 were collected.Clinical data of donors and recipients, postoperative adverse events, postoperative renal recovery, and human and renal survival were analyzed.Results:A total of 50 infant donors and 93 pediatric recipients were enrolled in this study.Recipients included 89 patients with single kidney transplantation (SKT) and 4 with en-bloc kidney transplantation (EBKT). The major perioperative complications were delayed graft function (DGF) (5 cases, 5.4%) and vascular thrombosis (VT) (3 cases, 3.2%), followed by recurrence of primary nephropathy (3 cases, 3.2%), respiratory tract infection (3 cases, 3.2%), and acute rejection (AR) (2 cases, 2.2%). During the follow-up period, the main cause of death was respiratory tract infection (4 cases, 4.3%). Except for the cause of death, the main causes of graft loss were rejection (2 cases, 2.2%) and recurrence of primary kidney disease (2 cases, 2.2%). Serum creatinine decreased progressively from (824.77±150.24) μmol/L preoperatively to (90.73±47.24) μmol/L 1 month postoperatively.In SKT group, the median follow-up time was 31 months (3-74 months), and the survival rates of recipients and transplanted kidneys at 1, 3 and 5 years postoperatively were 97.5%/94.2%, 96%/88.8% and 93.1%/86.1%, respectively.In EBKT group, the median follow-up time was 50 months (13-65 months), and the survival rates of recipients and transplanted kidneys at 1, 3 and 5 years postoperatively were all 100.0%.During the fo-llow-up period, there was no significant difference in the human/kidney survival rate between groups (all P>0.05), and well acceptable transplantation outcomes were obtained. Conclusions:Single/double kidney transplantation for children and adolescent recipients from infant donors in the First Affiliated Hospital of Zhengzhou University has achieved acceptable outcomes.Adopted by the PTP strategy, the incidence of complications after kidney transplantation does not increase, indicating its safety and reliability.
5.Evaluation with time-zero biopsy in donors with acute kidney function injury and clinical effect after transplantation
Kunlun ZHU ; Lei LIU ; Wenjun SHANG ; Xinlu PANG ; Zhigang WANG ; Yonghua FENG ; Junxiang WANG ; Jinfeng LI ; Xianlei YANG ; Guiwen FENG
Chinese Journal of Organ Transplantation 2021;42(12):717-722
Objective:To evaluate the time-zero biopsy of donor kidney with acute kidney injury(AKI)in organ donation donors and examine the clinical effect after transplantation.Methods:From May 2019 to May 2020, clinical data were retrospectively reviewed for 104 donors assessed by time-zero biopsy at First Affiliated Hospital, Zhengzhou University.According to the definition of AKI and Banff2016 criteria, the kidneys of 104 donors were grouped and evaluated for transplantation.And the post-transplantation effects of donor kidneys with different degrees of pathological changes were analyzed.Results:AKI occurred in 32/104 donors.Compared with non-AKI donors, statistically significant differences existed in degrees of renal interstitial fibrosis and acute renal tubular injury ( P<0.05). However, there were no significant differences in other pathological manifestations ( P>0.05). In AKI group, kidneys of 2 donors with Banff score>3 were abandoned; in non-AKI group, among 12 donors with Banff score>3, 1 donor kidney was abandoned due to a high degree of chronic diseases.No significant inter-group difference existed in creatinine value or estimated glomerular filtration rate(eGFR)( P>0.05). AKI group had a higher incidence of postoperative delayed graft function(DGF)and longer duration.There was no statistical significance in other complications ( P>0.05). Conclusions:AKI donor kidneys with pathological manifestations below moderate renal tubular injury and Banff score<3 are feasible for transplantation.Although renal function recovery is slow after transplantation, safe outcomes may be obtained.
6.Clinical features of frequent acute exacerbations of chronic obstructive pulmonary disease in elderly patients
Zhigang PANG ; Yufeng DU ; Xia WANG ; Jianying XU
Chinese Journal of Geriatrics 2020;39(9):1029-1033
Objective:To investigate the clinical features of frequent acute exacerbations of chronic obstructive pulmonary disease(COPD)in the elderly.Methods:A total of 93 elderly patients with stable COPD who were followed up in Bethune Hospital Affiliated to Shanxi Medical University from August 2015 to September 2016 were retrospectively analyzed.They were divided into the frequent acute exacerbation group(n=45)and the non-frequent acute exacerbation group(n=48). Data on the body mass index(BMI), lung function, the smoking index(package year), the respiratory status questionnaire and serum creatinine levels were collected.Logistic regression analysis was used to analyze the influencing factors for the frequency of acute exacerbations of COPD in elderly patients.Results:The BMI was lower [19.59(18.08-23.50)kg/m 2vs. 23.36(21.14-25.46)kg/m 2, Z=8.898, P=0.003], while scores of the modified Medical Research Council(mMRC)dyspnea scale, COPD Assessment Test(CAT)and smoking index were higher [3.00(1.00-3.00) vs. 1.00(0.00-1.00), 15.00(8.50-17.50) vs.10.00(6.00-13.75), 60.00(30.00-80.00)package years vs.37.50(3.75-60.00)package years, Z=17.671, 7.318 and 6.589, P<0.001, 0.007 and 0.010]in the frequent acute exacerbation group than in the non-frequent acute exacerbation group.The glomerular filtration rate(GFR)and percentage of predicted forced expiratory volume in the first second were lower in the frequent acute exacerbation group than in the non-frequent acute exacerbation group [105.13(89.84-114.69)ml·min -1·1.73m -2vs.121.74(93.89-142.02)ml·min -1·1.73m -2, 40.10(31.40-56.00)% vs.70.65(47.36-85.36)%, Z=6.071 and 17.814, P=0.014 and<0.001]. Logistic regression analysis showed that the odds ratios( OR)with 95% confidence interval(95% CI)of the smoking index and GFR were 1.025(1.006-1.044)and 0.957(0.927-0.995)( P=0.009 and 0.025), respectively, indicating that with the increase of smoking index and the decrease of GFR, the risk of frequent exacerbations of COPD was increased. Conclusions:There are phenotypic differences between elderly COPD patients with frequent acute exacerbations and without frequent acute exacerbations.Elderly COPD patients with frequent acute exacerbations have a lower BMI index, a higher smoking index, more clinical symptoms, worse pulmonary function, and are prone to early kidney injury.
7.Cognitive impairment in patients with recurrent major depression disorder
Zhigang LIU ; Xiaofeng ZHAO ; Huijie ZHANG ; Tingting FENG ; Jing YAO ; Jianyue PANG ; Hengfen LI
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(7):636-641
Objective To explore the psychological process of cognitive impairment in patients with recurrent major depression disorder (MDD). Methods Patients with first-episode (n=30) and recurrent MDD (n=68) in the outpatient department of the First Affiliated Hospital of Zhengzhou University from Sep-tember 2016 to December 2017 were collected and healthy controls(n=30) were collected at the same time. According to HAMD-24 score,the group with recurrent attacks was further divided into recurrent attacks-on-set period (n=35) and recurrent attacks-remission period (n=33). All subjects were tested for cognitive function by MATRICS Consensus Cognitive Battery( MCCB). Results (1) In terms of cognitive function assessment,the scores of information processing speed ( 41. 27 ± 8. 44, 37. 00 ± 11. 68), working memory (40. 53±10. 33,41. 26±9. 37),attention/alertness ( 40. 50± 7. 25,39. 58± 8. 23),word learning ( 38. 83± 8. 39,38. 84±9. 57),visual memory(39. 30±14. 03,37. 57±10. 42),reasoning and problem solving(37. 80± 9. 55,38. 78±8. 66),and social cognition (34. 63± 9. 66) in the first-episode group and the recurrent group were lower than those in the control group ( information processing speed ( 48. 23±7. 63),working memory (50. 57±7. 84),attention/alertness (51. 63±7. 41),word learning (45. 57±9. 55),visual memory (50. 57± 8. 42),reasoning and problem solving (50. 03±9. 87) and social cognition (47. 90±19. 01)) (F=12. 818, 12. 173,26. 166,6. 004,15. 085,18. 331,10. 218,P<0. 05); (2) In working memory and social cognition, the difference was statistically significant in the first-episode group,repeated attacks-episodes(working mem-ory:37. 89±9. 15,social cognition:28. 48± 8. 35) and recurrent group-remission( working memory:44. 85± 8. 32,social cognition:40. 44 ± 11. 36, P=0. 010,0. 001). Further comparisons revealed that the score of working memory in repeated attacks-episodes was lower than that in recurrent group-remission (P=0. 003). the score of social cognition in the first-episode group was higher than that in the recurrent-attack period group (P=0. 038). The score of social cognition in the recurrent group-remission was higher than that in re-current-attack period group (P<0. 01). Conclusion There is cognitive impairment in the first episode and the recurrence MDD. The impairment in the recurrent episode is more serious than that in the first episode of depression. The impairment of social cognitive in the recurrent attacks-episodes is more serious than that in the first-episode of depression.
8.The mechanism of bone marrow-derived endothelial progenitor cells in the treatment of peripheral neuropathy of diabetic rats
Rongrong YUAN ; Yu ZHANG ; Dandan LI ; Liping ZHU ; Wei GAO ; Lei XUE ; Wuyan PANG ; Zhigang ZHAO
Chinese Journal of Endocrinology and Metabolism 2018;34(4):312-317
Objective To explore the mechanism of bone marrow-derived endothelial progenitor cells (EPCs)in the treatment of peripheral neuropathy of diabetic rats. Methods Rats with diabetic peripheral neuropathy (DPN)were induced by streptozotocin(60 mg/kg). Male SD rats were divided into normal control group(NC group),DPN group, DPN+saline group(DPN+S group), and DPN+ EPCs group. Sciatic nerve motor nerve conduction velocity(MNCV)was measured. The expressions of NF-κB and myelin basic protein(MBP)in sciatic nerve were detected by immunohistochemistry. Results Compared with DPN group,the expression of NF-κB was reduced in the sciatic nerve of DPN+EPCs group,while the expression of NF-κB was increased in the sciatic nerve of DPN+ S group. There was no statistical difference in the expression of MBP between DPN and DPN+ EPCs groups. Compared with DPN+S group, the expression of MBP was higher in DPN+EPCs group. Conclusion Transplantation of EPCs inhibits the expression of NF-κB and increases the expression of MBP, which might be conducive to the repairs of nerve injury.
9.Long-term effects of kidney transplantation in children
Wenjun SHANG ; Jingjun SUO ; Fei XU ; Zhigang WANG ; Xinlu PANG ; Jinfeng LI ; Hongchang XIE ; Lei LIU ; Yonghua FENG ; Junxiang WANG ; Guiwen FENG
Chinese Journal of Organ Transplantation 2018;39(2):71-75
Objective To explore the long-term clinical effect of kidney transplantation in children.Methods The clinical data of 53 children with kidney transplantation from March 2008 to September 2014 were retrospectively analyzed.The influence of the dependent factors on the estimated glomerular filtration rate (eGFR) (greater than 90 mL/min/1.73 m2 or <90 mL/min/1.73 m2) was estimated in the three years after the operation,and the influencing factors were analyzed by the dual logistic regression equation.Results There were 19 cases of living donors,17 cases of organ donors after death,and 6 others.The 53 patients were followed up for 3-9 years.The level of blood creatinine was decreased from the preoperative (820.1 ± 323.1) μmol/L to (51.6 ± 24.9) μmol/L 3 years after the operation (P<0.05).eGFR was increased to (103.5 ± 11.4) mL/min/1.73 m2at 3rd year after the operation from the preoperative (17.1 ± 7.8) mL/min/1.73 m2 (P<0.05).The age of recipients,preoperative dialysis time,number of HLA mismatching and postoperative delayed graft function healing (DGF),rejection and infection were the influencing factors of eGFR at 3rd year postoperation (P<0.05).The multi-factor binary logistic regression equation analysis showed that only rejection was the risk factor for eGFR at 3rd year p0ostoperation.Eight cases of DGF (8/53,15.1%) recovered rapidly.There were 6 cases of acute rejection (6/47,12.8 %) and 1 case of chronic rejection (1/47,2.1%).There were 9 cases of infection (9/47,19.1%).There were 6 cases of recurrence after surgery.The 3-year recipient and kidney survival rate was 94.3% (50/53) and 88.7% (47/53) respectively.The average height of the patients in the first,second and third year after the surgery was increased by (4.6 ± 1.9) cm (0.5-19.1 cm),(3.7 ± 1.8) cm (0.7-14.3 cm) and (2.8± 1.2) cm (0.3-8.7 cm) respectively.Conclusion The long-term effect of children kidney transplantation is satisfactory.
10.Association of programmed cell death 1 (PDCD1) gene polymorphisms with colorectal cancer among Han Chinese population.
Yuancun ZHAO ; ; Zhangj@scu.edu.cn. ; Zhigang MAO ; Hua PANG ; Xiaohong ZHAO ; Shu ZHANG ; Zehua GAO ; Yiwen YANG ; Ting FANG ; Qizhao MA ; Xiaodan MA ; Yufang WANG ; Ji ZHANG
Chinese Journal of Medical Genetics 2018;35(2):219-223
OBJECTIVETo assess the association of programmed cell death 1 (PDCD1) gene polymorphisms with the susceptibility and/or progression of colorectal cancer.
METHODSA hospital-based case-control study was carried out, which recruited 426 colorectal cancer patients and 500 healthy individuals. Five single nucleotide polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and rs10204525, were selected for the study and genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
RESULTSThe G allele of rs36084323 under a dominant model was associated with increased risk of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02-2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525 were negatively associated with the occurrence of colorectal cancer.
CONCLUSIONThe G allele of rs36084323 is associated with increased risk of advanced TNM staging of colorectal cancer. Conversely, the incidence of colorectal cancer is negatively associated with the haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525.
Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; ethnology ; Colorectal Neoplasms ; genetics ; pathology ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Programmed Cell Death 1 Receptor ; genetics

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