1.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.
2.Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms
Yi FENG ; Yonghua FENG ; Mingyao HU ; Hongen XU ; Zhigang WANG ; Shicheng XU ; Yongchuang YAN ; Chenghao FENG ; Zhou LI ; Guiwen FENG ; Wenjun SHANG
Chinese Medical Journal 2024;137(10):1199-1206
Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.
3.Comparisons of the efficacy of drug injections for the treatment of keloid: a network meta-analysis
Hongfan DING ; Xiao XU ; Shiyi LI ; Yichen WANG ; Qian WU ; Ruiqi BAI ; Guiwen ZHOU ; Qiang FU ; Yue LIU ; Minliang CHEN
Chinese Journal of Plastic Surgery 2023;39(12):1311-1323
Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.
4.Comparisons of the efficacy of drug injections for the treatment of keloid: a network meta-analysis
Hongfan DING ; Xiao XU ; Shiyi LI ; Yichen WANG ; Qian WU ; Ruiqi BAI ; Guiwen ZHOU ; Qiang FU ; Yue LIU ; Minliang CHEN
Chinese Journal of Plastic Surgery 2023;39(12):1311-1323
Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.
5.Vascular complications caused by hyaluronic acid injection: a clinical analysis
Kang CHEN ; Guiwen ZHOU ; Xiao XU ; Qiang FU ; Yi YANG ; Minliang CHEN
Chinese Journal of Medical Aesthetics and Cosmetology 2022;28(3):218-222
Objective:To analyze the epidemiological characteristics of vascular complications induced by hyaluronic acid facial injection.Methods:Patients with vascular complication induced by facial hyaluronic acid facial injection were collected in the Fourth Medical Center of the General Hospital of the Chinese People's Liberation Army from January 1, 2016 to October 1, 2021, including 5 males and 37 females. The age ranged from 16 to 70 (34±10) years. The clinical data, injection site, clinical symptoms and previous facial surgery history of the patients were analyzed and investigated.Results:Vascular complications occurred in 12 cases (28.6%). Nasolabial fold in 8 (19.0%) cases; Glabella in 6 (14.3%) cases; frontal part in 6 (14.3%) cases. There were 27 patients (64.3%) with a history of facial surgery. Furthermore, history of facial surgery had no effect on the clinical manifestations of vascular complications ( P>0.05). Among the 18 patients with visual impairment, 12 patients reported that the symptoms of ptosis, bulbar conjunctival congestion, and eye movement dysfunction had diminished after thrombolytic treatment, while 4 patients showed recovery to some extent in visual acuity. Likewise, 24 patients with blood circulation disorders were healed after treatment, with residual pigmentation and a slight scar left. Conclusions:Women aged 30 to 39 years old are the main target population of cosmetic surgery, as well as the most common population of vascular complications. Particular care should be taken in the nose, nasolabial fold, glabella and forehead areas of the operation. Patients with previous surgical history should be adequately informed before surgery, and postoperative observation time should be appropriately prolonged.
6.Study on the incidence of adult herpes zoster in Yichang city and its association with early-life famine exposure
Xiong DING ; Wei JIANG ; Yuehua HU ; Jing JIANG ; Ying WU ; Chengzhong XU ; Zhouzhi WU ; Yunfang YU ; Xiaojun LIU ; Guiwen LI ; Dapeng YIN
Chinese Journal of Preventive Medicine 2021;55(11):1328-1331
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ ( OR=1.21; 95% CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females ( OR=1.28, 95% CI:1.02-1.61, P=0.034).
7.Study on the incidence of adult herpes zoster in Yichang city and its association with early-life famine exposure
Xiong DING ; Wei JIANG ; Yuehua HU ; Jing JIANG ; Ying WU ; Chengzhong XU ; Zhouzhi WU ; Yunfang YU ; Xiaojun LIU ; Guiwen LI ; Dapeng YIN
Chinese Journal of Preventive Medicine 2021;55(11):1328-1331
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ ( OR=1.21; 95% CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females ( OR=1.28, 95% CI:1.02-1.61, P=0.034).
8.Preliminary results of multicenter studies on ABO-incompatible kidney transplantation
Hongtao JIANG ; Tao LI ; Kun REN ; Xiaohua YU ; Yi WANG ; Shanbin ZHANG ; Desheng LI ; Huiling GAN ; Houqin LIU ; Liang XU ; Zhigang LUO ; Peigen GUI ; Xiangfang TAN ; Bingyi SHI ; Ming CAI ; Xiang LI ; Junnan XU ; Liang XU ; Tao LIN ; Xianding WANG ; Hongtao LIU ; Lexi ZHANG ; Jianyong WU ; Wenhua LEI ; Jiang QIU ; Guodong CHEN ; Jun LI ; Gang HUANG ; Chenglin WU ; Changxi WANG ; Lizhong CHEN ; Zheng CHEN ; Jiali FANG ; Xiaoming ZHANG ; Tongyi MEN ; Xianduo LI ; Chunbo MO ; Zhen WANG ; Xiaofeng SHI ; Guanghui PEI ; Jinpeng TU ; Xiaopeng HU ; Xiaodong ZHANG ; Ning LI ; Shaohua SHI ; Hua CHEN ; Zhenxing WANG ; Weiguo SUI ; Ying LI ; Qiang YAN ; Huaizhou CHEN ; Liusheng LAI ; Jinfeng LI ; Wenjun SHANG ; Guiwen FENG ; Gang CHEN ; Fanjun ZENG ; Lan ZHU ; Jun FANG ; Ruiming RONG ; Xuanchuan WANG ; Guisheng QI ; Qiang WANG ; Puxun TIAN ; Yang LI ; Xiaohui TIAN ; Heli XIANG ; Xiaoming PAN ; Xiaoming DING ; Wujun XUE ; Jiqiu WEN ; Xiaosong XU
Chinese Journal of Organ Transplantation 2020;41(5):259-264
Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
9. Evaluations and utilizations of extended criteria donor kidneys
Zhigang WANG ; Fei XU ; Lei LIU ; Jinfeng LI ; Wenjun SHANG ; Guiwen FENG
Chinese Journal of Organ Transplantation 2019;40(10):601-605
Objective:
To explore the evaluations and recipient selection methods of extended criteria donor (ECD) kidney donation in the death of citizens and analyze the transplantation outcomes.
Methods:
From January to September 2019, the clinical data of donor-recipients were retrospectively studied. The recipients of ECD donor kidneys not evaluated for kidney zero puncture assessment from January 2014 to July 2016 were group A1 and those receiving standard donor kidney (SCD) belonged to group A2. From August 2016 to March 2019, all DCD donors were routinely evaluated for kidney zero puncture and those receiving ECD recipients fell into Group B1 and those receiving SCD belonged to Group B2. Analysis was performed for ECD/SCD donor renal zero puncture pathological features and lesion degree and utilization of ECD donor kidney; donor-recipient body surface area (BSA) ratio and lesion degree of ECD donor kidney on recipient selecting and matching. Serum creatinine value, perioperative adverse events and 1-year follow-up of human/kidney survival rate in each group were compared at 1 day, 1 week, 1 month, 3 months, 6 months and 1 year.
Results:
A total of 108, 264, 306 and 416 recipients were recruited into A1, A2, B1 and B2 groups respectively. The ECD donor renal utilization rate was 88.5% vs 93.3% during two time periods. According to the 2016 Banff standard, glomerular sclerosis (GS), renal interstitial fibrosis (Ci) and intimal fibrosis thickening (Cv), small arterial intimal hyalinization (ah), tubular atrophy (ct) and acute tubular injury (ati) accounted for more than B1 group than B2 group (
10.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.

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