1.The relationship between abnormal expression of SIRT1 and chondrocyte apoptosis in patients with Kashin-Beck disease
Xiaoli YANG ; Jingmin CHE ; Di ZHANG ; Cuixiang XU ; Zhankui JIN ; Yongmin XIONG
Chinese Journal of Endemiology 2024;43(8):622-628
Objective:To analyze the expression of silent information regulator 2-related enzyme 1 (SIRT1) and its relationship with chondrocyte apoptosis in patients with Kashin-Beck disease (KBD).Methods:Twenty patients with KBD were selected as the KBD group from Guide County, Qinghai Province, and 40 healthy subjects matched by age and sex were selected as the control group. Fasting elbow venous blood of the study subjects was collected, and peripheral blood mRNA levels of SIRT1 and selenoprotein genes [glutathione peroxidase (GPX) 2, GPX3, thioredoxin reductase (TXNRD) 1, TXNRD3, iodothyronine deiodinase Ⅰ (DIO1), and selenophosphate synthetase 2 (SPS2)] were detected by real-time PCR. The correlation between SIRT1 expression and selenoprotein genes in peripheral blood of KBD patients was analyzed by curve fitting method. Meanwhile, normal human chondrocytes cultured in vitro were divided into control group (without any treatment), resveratrol (RES) group (to verify the activation effect of RES on SIRT1), tert-butyl hydroperoxide (tBHP) injury group (oxidative injury model of chondrocyte), and RES protection group (tBHP injury after RES pre protection). The mRNA levels of SIRT1, selenoprotein genes, and apoptosis-related genes [B lymphoblastoma-2 gene (BCL2), BCL2-associated X protein (BAX), nuclear transcription factor κB (NF-κB) p65, and tumor suppressor gene P53] in each group of cells were detected by real-time PCR. Results:In the population study, the peripheral blood SIRT1 mRNA level in the KBD group (1.12 ± 0.38) was lower than that of control group (1.87 ± 0.97), and the difference was statistically significant ( t = 3.31, P = 0.002). According to curve fitting analysis, the mRNA levels of GPX3, TXNRD1, and TXNRD3 in peripheral blood of KBD group increased with the increase of SIRT1 mRNA level ( R2 = 0.48, 0.66, 0.95, P < 0.001). The level of DIO1 mRNA showed a trend of decreased first and then increased with the increase of SIRT1 mRNA level ( R2 = 0.51, P = 0.024). The mRNA levels of GPX2 and SPS2 showed no significant change trend with the increase of SIRT1 mRNA level ( R2 = 0.16, 0.12, P = 0.064, 0.114). In cell studies, compared with the control group (1.00 ± 0.10), the SIRT1 mRNA level in the RES group (1.79 ± 0.07) was higher ( P < 0.05). Compared with tBHP injury group, the RES protection group had higher mRNA levels of selenoprotein genes GPX3, TXNRD1, TXNRD3, and DIO1 ( P < 0.05); the mRNA levels of apoptosis-related genes BAX, P53 and the ratio of BAX/BCL2 were lower, while the mRNA levels of BCL2 and NF-κB p65 were higher ( P < 0.05). Conclusions:KBD patients have low expression of SIRT1. And RES activation of SIRT1 may enhance the antioxidant capacity of chondrocyte by up-regulating the expression of selenoprotein genes, thus inhibiting chondrocyte apoptosis.
2.Assessment of oxidative stress levels in patients with Kashin-Beck disease and its relationship with SIRT1 expression
Xiaoli YANG ; Qiang LI ; Di ZHANG ; Cuixiang XU ; Zhankui JIN ; Yongmin XIONG
Chinese Journal of Endemiology 2024;43(10):783-789
Objective:To investigate the role of oxidative stress and silent information regulator 2 homolog 1 (SIRT1) in cartilage injury in Kashin-Beck disease (KBD) by evaluating the level of oxidative stress and the effect of oxidative injury on SIRT1 expression in patients with KBD.Methods:In May 2017, Twenty patients with KBD were selected from Guide County of Qinghai Province as the KBD group, and 40 healthy subjects were selected as the control group, 5 ml elbow venous blood was collected, centrifuged, and the upper plasma was retained. The glutathione peroxidase (GPX) activity and reactive oxygen species (ROS) level were determined by enzyme linked immunosorbent assay (ELISA), and SIRT1 mRNA level was determined by real-time fluorescence quantitative PCR (RT-qPCR). Meanwhile, 150 μmol/L tert-butyl hydroperoxide (tBHP) was selected to damage chondrocytes; and different concentrations of sodium selenite (Na 2SeO 3) were used to intervene in chondrocytes to detect cell viability, and appropriate concentration of Na 2SeO 3 was selected for pre protection. Total RNA and DNA of chondrocytes were extracted. The mRNA levels of SIRT1, DNA methyltransferase 1 (DNMT1), and the DNA methylation level in the SIRT1 promoter region were determined by RT-qPCR. At the same time, Hoechst 33342 staining was used to detect chondrocyte apoptosis. Results:The plasma GPX activity [(35.48 ± 8.82) U/g·Hb] in KBD group was lower than that in control group [(40.43 ± 6.68) U/g·Hb, t = - 2.43, P = 0.018], and the ROS level [(577.10 ± 96.92) U/ml] was higher than that in control group [(526.44 ± 62.63) U/ml, t = 2.13, P = 0.043]. GPX activity was positively correlated with SIRT1 mRNA level ( r s = 0.44, P = 0.005), while ROS level was negatively correlated with SIRT1 mRNA level ( r s = - 0.39, P = 0.006). After 48 hours of treatment with 150 μmol/L tBHP (tBHP injury group), the survival rate of chondrocytes decreased to (55.27 ± 2.96)%; and the survival rate of chondrocytes pre-protected with 0.10 μg/ml Na 2SeO 3 (selenium protection group) was significantly higher than that of tBHP injury group ( P < 0.05). Compared with control group, the SIRT1 mRNA level of chondrocytes in tBHP injury group was significantly decreased; while the DNA methylation level in the SIRT1 promoter region, DNMT1 mRNA level and cell apoptosis rate were significantly increased ( P < 0.05). Compared with tBHP injury group, the selenium protection group had higher levels of SIRT1 mRNA in chondrocytes, lower levels of DNA methylation in the SIRT1 promoter region, DNMT1 mRNA, and cell apoptosis rate ( P < 0.05). The apoptosis rate was negatively correlated with SIRT1 mRNA level ( r s = - 0.78, P = 0.004), and positively correlated with the DNA methylation level in the SIRT1 promoter region ( r s = 0.76, P = 0.006). Conclusions:KBD patients have increased levels of oxidative stress, which may be associated with low expression of SIRT1. Oxidative injury may down-regulate SIRT1 expression and promote chondrocytes apoptosis by catalyzing DNA methylation in the SIRT1 promoter region.
3.Prevalence and radiographic morphology of atlantoaxial dislocation in Kashin-Beck disease
Xueyuan WU ; Zhi YI ; Ming LING ; Hongwei MA ; Zhankui JIN ; Yanhai CHANG ; Zhengming SUN ; Shizhang LIU
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(5):726-731
【Objective】 Until now, most clinical and basic studies on Kashin-Beck disease (KBD) have focused on the visible deformed extremities, and there is a lack of reports concerning their spinal features, especially for the atlantoaxial joint. The purpose of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in KBD in adult patients. 【Methods】 The prevalence and radiographic features of AAD were determined by the basic information collected, clinical symptoms, and lateral and dynamic plain radiography in 111 KBD patient and 120 non-KBD participants. In the KBD group, AAD and non-AAD patients were compared in age, gender, height, weight, BMI, smoking history, chronic history, disease duration and grade of disease so as to identify the related factors of the occurrence of AAD. 【Results】 Symptoms at the neck or neurological manifestations were present in 17.5% (21/120) in the non-KBD population and 39.6% (44/111) patients with KBD. AAD case was not detected in the non-KBD population, while in 16.2% (18/111) of KBD patients in the endemic area. The prevalence was higher in the KBD patients than in the non-KBD population, and there was a significant difference in the detection rate of AAD between the two groups (χ2=21.10, P<0.001). Plain radiography demonstrated that there were 10 (55.6%) cases with separation of the odontoid process and the other 8 (44.4%) cases with hypoplasia of odontoid process. Anterior AAD was noted in 12 (66.7%) patients and posterior AAD in 6 (33.3%) cases based on the displacement direction, while 16 (88.9%) cases were reducible and 2 (11.1%) cases were irreducible on the basis of the reducibility. Comparing the 93 patients with non-AAD KBD patients and 18 patients with AAD patients, there was no significant difference in age, sex, BMI, history of medical disease or smoking (all P>0.05). There were significant differences in height, weight, disease duration and grade of disease between AAD and non-AAD patients (all P<0.05). 【Conclusion】 KBD can cause the occurrence of atlantoaxial dislocation by inducing separation or hypoplasia of the odontoid process. This research may provide clinical evidence for screening, earlier prevention and treatment of atlantoaxial dislocation in adult KBD patients.
4.The value of intravesical instillation of Nocardiarubra cell wall skeleton in preventing recurrent after transurethral resection for the treatment of non-muscle invasive bladder cancer
Shunli YU ; Chaohui GU ; Binjie LUO ; Yiping KOU ; Tianyuan ZHAI ; Zhibo JIN ; Zhankui JIA ; Jinjian YANG
Chinese Journal of Urology 2019;40(7):521-525
Objective To investigate the efficacy and safety of Nocardiarubra cell wall skeleton (N-CWS) bladder irrigation in prevention of recurrence after transurethral resection for the treatment of non-muscle invasive bladder cancer (NMIBC).Methods The clinical data of patients with NMIBC treated by N-CWS and epirubicin collected between October 2013 and November 2018 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.All patients underwent TURBT.Among the 118 NMIBC patients,the average age was (65.1 ± 1 1.9) years,and the sex ratio (male/female) was 1.9∶1 (77/41).Patients were divided into two group:N-CWS group (n =55) and epirubicin group (n =63) according to different instillation regimens.N-CWS was given as an instillation of 800 μg in 50 ml of saline and maintained in the bladder for 2 h in the N-CWS group.Epirubicin was given as an instillation of 50 mg in 50 ml of saline and maintained in the bladder for 1 h in the epirubicin group.In the N-CWS group,mean agewas (64.9 ± 12.1) years and 37 (67.3%) were male.Multiple tumors were present in 17 (69.1%) patients.Tumor size was ≤3 cm in 49(89.1%) and 7(12.7%) had a history of NMIBC.Stage was Ta and T1 in 36(65.5%) and 19(34.5%),respectively.Grade 1,Grade 2 and Grade 3 were the primary grades in 38(69.1%),13(23.6%) and 4(7.3%),respectively.Low risk,intermediate risk and high risk were present in 14 patients(25.5%),16 (29.1%) and 25 (45.5%),respectively.In the epirubicin group,mean age was (65.3 ± 11.2) years and 40(63.5%)were male.Multiple tumors were present in 19(30.2%) patients.Tumor size was ≤3 cm in 56(88.9%) and 11 (17.5%) had a history of NMIBC.Stage was Ta and T1 in 37(58.7%) and 26 (41.3%),respectively.Grade 1,Grade 2 and Grade 3 were the primary grades in 44(69.8%),12(19.0%)and 7(11.1%),respectively.Low risk,intermediate risk and high risk were present in 13 (20.6%),19 (30.2%) and 31 (49.2%),respectively.The tumor recurrence,progression and adverse reactions after Intravesical Instillation in both groups were followed up and recorded.No significant differences were found between the two groups.Results A total of 118 patients were followed up.Mean follow-up time was (33.7 ± 5.4) months.25.5% (14/55) in the N-CWS group vs.42.8% (27/63) in the epirubicin group had recurrence after 5 years (x2 =3.922,P =0.048).The five-year RFS was higher in the N-CWS group than in the epirubicin group (74.2% vs.56.5%,P =0.044).No significant difference was found in the progression rate between the two groups(5.5% vs.7.9%,P =0.867).The incidences of adverse events in the two groups were 16.4% (9/55) and 19.0% (12/63),respectively.The N-CWS group had significantly fewer cases with urinary frequency and dysuria than the epirubicin group.No significant differences were found in other side effects.Conclusions Intravesical instillation of N-CWS after NMIBC TURBT was found to be a promising procedure to prevent recurrence and prolong the recurrence-free survival with less side effects.
5.Primary melanoma of the urinary system: a report of 5 cases and review of the literature
Zhibo JIN ; Yan SHI ; Tao WANG ; Yihe GENG ; Zhankui JIA ; Yinghui DING ; Zhenlin HUANG ; Jinjian YANG
Chinese Journal of Urology 2018;39(4):271-274
Objective To discuss the clinical diagnosis,treatment and prognosis of malignant melanoma of urinary system.Methods The clinical data of 5 patients with primary malignant melanoma of urinary system were retrospectively analyzed.There were 2 cases of primary melanona of the urethra,3 cases of primary malignant melanoma of the bladder.The diameter of the tumor ranged from 0.9 to 5.1 cm with an average of 3.1 cm.Results Two cases of urethral patients underwent radical resection of urethra.Among 3 cases of bladder,1 cases were in poor condition,and underwent laparoscopic partial cystectomy.In 1 young men,radical resection was refused and only transurethral resection of the bladder tumor was performed.Radical resection of bladder was done in 1 cases.Postoperative pathology showed that the tumor cells of 4 cases were fusiform under microscope,1 case was polygonal.5 cases showed melanin in the cytoplasm and diffuse proliferation of tumor cells,with obvious heterogeneity,cell proliferation index Ki-67 10%-30%.During the follow-up period of 7-30 months (median 19 months),3 patients died of metastasis.Conclusions Malignant melanona of urinary system is rare,with high malignancy and poor prognosis.Targeted therapy and immune therapy has become a new treatment option,which could improve the prognosis of patients.
6.Assessment of quality of life after total knee arthroplasty in patients with severe knee osteoarthritis of Kashin-Beck disease
Zhankui JIN ; Cuixiang XU ; Xiong GUO ; Zhengming SUN ; Xianghui DONG ; Xueyuan WU ; Yanhai CHANG
Chinese Journal of Endemiology 2018;37(10):818-821
Objective To evaluate the quality of life of patients with Kaschin-Beck disease (KBD)receiving total knee arthroplasty (TKA) before and after the operation.Methods Clinical efficacy of 25 patients with KBD who underwent TKA in Department of Orthopaedics,Shaanxi Provincial People's Hospital from January 2015 to January 2017 was prospectively analyzed.A questionnaire survey on KBD quality of life (KBDQOL)was carried out to evaluate the quality of life of the patients before,6 months and 1 year after the surgery.Results The scores of physical function,activity limit,social support,mental status and total health scores of KBDQOL in 6 months after the surgery (30.60 ± 3.73,23.24 ± 2.03,15.16 ± 1.62,18.92 ± 2.89,12.80 ± 2.57) and 1 year after the surgery (32.00 ± 3.19,23.76 ± 1.59,15.60 ± 1.29,20.16 ± 2.67,17.28 ± 3.88) were significantly higher than those of before the surgery (18.84 ± 4.94,21.04 ± 2.72,12.80 ± 2.06,13.68 ± 3.42,7.92 ± 1.93,P < 0.05).However,there was no significant difference in economic scores before,6 months and 1 year after the surgery (10.68 ± 2.98,10.60 ± 2.78,10.48 ± 2.80,P > 0.05).Conclusions The quality of life after TKA in patients with KBD severe knee osteoarthritis is significantly better than that before the surgery.The KBDQOL questionnaire is an appropriate tool for evaluating the quality of life in KBD patients.
7.Therapeutic effects of arthroscopic debridement combined with sodium hyaluronate injection in treatment of Kashin-Beck disease with ankle arthritis
Zhengming SUN ; Xianghui DONG ; Yanhai CHANG ; Xueyuan WU ; Zhankui JIN ; Zhi YI ; Ming LING ; Xiong GUO
Chinese Journal of Endemiology 2018;37(11):900-903
Objective To study the therapeutic effects of arthroscopic debridement combined with sodium hyaluronate injection in treatment of Kashin-Beck disease with ankle arthritis.Methods Using prospective study,Kashin-Beck disease patients with ankle arthritis,who had underwent arthroscopic debridement combined with sodium hyaluronate injection,were selected as study subjects.X-ray stratification was performed based on Kellgren-Lawrence grading method,grade 1,2,3 were studied,if there were fewer patients at grade 1,then merge with grade 2.Visual analogue scale (VAS),anterior and posterior ankle activity and ankle hindfoot score were used to evaluate the effects before and 3,6,12 months after the treatment.Results Totally 33 patients were collected,VAS scores (6.9 ± 0.2,2.9 ± 0.2,2.1 ± 0.1,1.9 ± 0.1),anterior and posterior ankle activities (20.9 ± 0.6,31.5 ± 0.6,32.1 ± 0.6,34.1 ± 0.4),and ankle hindfoot scores (51.3 ± 0.5,70.8 ± 1.1,76.0 ± 0.9,77.0 ± 0.9) before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =267.47,703.09,756.49,P < 0.01).VAS scores (7.0 ± 0.2,2.8 ± 0.2,1.7 ± 0.1,1.7 ± 0.1;7.0 ± 0.3,3.2 ± 0.3,2.8 ± 0.2,2.2 ± 0.2),anterior and posterior ankle activities (22.4 ± 0.7,32.5 ± 0.6,33.1 ± 0.6,51.3 ± 0.5;18.1 ± 0.9,29.6 ± 1.0,30.2 ± 1.0,31.4 ± 0.9),and ankle hindfoot scores (51.6 ± 0.9,70.9 ± 0.5,77.7 ± 0.9,79.1 ± 1.0;50.6 ± 0.5,65.5 ± 1.8,72.8 ± 1.4,72.9 ± 1.4) in grade 1 + grade 2,and grade 3 patients before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =244.80,64.04;379.94,498.83;1 393.07,159.70,P < 0.01).Compared with those before the treatment,VAS scores of all,grade 1 + grade 2,and grade 3 patients in 3,6,12 months after the treatment significantly decreased,anterior and posterior ankle activities and ankle hindfoot scores significantly increased (P < 0.05).Conclusion Arthroscopic debridement combined with sodium hyaluronate injection is effective in the treatment of Kashin-Beck with disease ankle arthritis.
8. Impact of hypertensive disorder complicating pregnancy on neonatal mortality and major complications in preterm infants
Meiyu WANG ; Xiangyong KONG ; Zhichun FENG ; Fengdan XU ; Hongyan LYU ; Lihong YANG ; Sujing WU ; Rong JU ; Jin WANG ; Li PENG ; Zhankui LI ; Xiaolin ZHAO ; Shujuan ZENG ; Huixian QIU ; Weixi WEN ; Hui WU ; Ying LI ; Nan LI ; Xuefeng ZHANG ; Wenzheng JIA ; Guo GUO ; Weipeng LIU ; Feng WANG ; Gaimei LI ; Fang LIU ; Wei LI ; Xiao-ying ZHAO ; Hongbin CHENG ; Yunbo XU ; Wenchao CHEN ; Huan YIN ; Yanjie DING ; Xiaoliang WANG ; Ruiyan SHAN ; Ping XU ; Meiying HAN ; Chunyan YANG ; Tieqiang CHEN ; Xiaomei TONG ; Shaojun LIU ; Ziyuan LIU
Chinese Journal of Applied Clinical Pediatrics 2018;33(14):1065-1070
Objective:
To investigate the effect of hypertensive disorder complicating pregnancy (HDCP) on the mortality and early complications of premature infants.
Methods:
The general clinical data of preterm infants with gestational age 24-36+ 6 weeks were collected from the cooperative units in the task group from January 1, 2013 to December 31, 2014.According to the severity of HDCP, the infants were divided into 4 groups: HDCP group, preeclampsia group, eclampsia group and non HDCP group, the mortality and major complications of preterm infants were compared, and the influencing factors were analyzed.
Results:
The mortality rate of preterm in the HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (
9.Retrospective Study of Detection of Serum IL-17 for Predicting Early Acute Renal Allograft Rejection by Luminex Technique
Cuixiang XU ; Zhankui JIN ; Xi WANG ; Le YANG ; Feng HAN ; Wanli DUAN ; Puxun TIAN
Journal of Modern Laboratory Medicine 2017;32(4):87-90
Objective To detect the expression of IL-17 in renal transplant recipients by Luminex and evaluate the relationship between the level of serum IL 17 and early acute renal allograft rejection.Methods 38 kidney transplant recipients and healthy controls (HC,healthy volunteers,n =20) were selected in this study from January 2009 to October 2011.All patients were divided into two groups according to their allograft outcome as acute rejection group (ARG,n-18) and non-rejection group (NRG,n=20).The expression of serum IL-17 was detected by Luminex technique in two groups of kidney transplant recipients and HC.To evaluate the correlation between the level of serum IL-17 and early acute renal allograft rejection.Results The mean level of IL-17 in all renal transplant recipients 1.3 ± 1.9 pg/ml at the pre-transplantation was significantly lower than that in HC (6.9± 8.5 pg/ml,t=3.968,P<0.001).The results highlighted that the level of serum IL-17 in ARG 3.4±5.8 pg/ml was significantly higher than that in NRG (0.5±0.4 pg/ml) on the 7th days post Kidney transplantation (post KTx,t=2.242,P =0.031).Kaplan-Meier survival analysis showed that the probability of rejectionfree survival in the higher levels group of IL-17 on the 7th days post-KTx was significant lower than that in the lower levels group (P<0.001).The results of receiver operating characteristic curve showed that the sensitivity and specificity of the combined IL-17 to predict acute rejection were 66.67% and 100%,respectively.Conclusion The serum IL-17 levels in renal transplant recipients on the 4th and 7th post-KTx days can predict early renal transplant rejection.
10.Effects of Percutaneous Kyphoplasty on Osteoporosis Vertebral Compression Fractures in Elderly
Xiaoqing WANG ; Xueyuan WU ; Zhankui JIN ; Yanhai CHANG
Chinese Journal of Rehabilitation Theory and Practice 2016;22(8):977-980
Objective To observe the clinical effect and safety of percutaneous kyphoplasty (PKP) on osteoporosis vertebral compres-sion fractures (OVCF) in elderly. Methods From January, 2014 to May, 2015, 88 patients with OVCF treated with PKP were retrospective studied. Visual Analogue Scale (VAS) and Oswestry Dysfunction Index (ODI) were used to evaluate the pain and quality of life, and the ky-photic angle (Cobb's angle) and anterior vertebral body height were recorded before operation, one week after operation and the last fol-low-up. The cement leakage and its effect on nerve function were recorded. Results Bone cement leakage was found in eleven patients, in which two in pedicle, three in venous leakage, three in intervertebral disc and three in vertebral posterior. Nerve root symptoms appeared in one patient, who was treated with decompression. The scores of VAS and ODI, and the Cobb's angel were significantly lower (t>29.518, P<0.001), and the vertebral body height was significantly higher (t>35.173, P<0.001) one week after operation and the last follow-up than be-fore operation. Conclusion PKP is safe and effective for OVCF in elderly. It can efficiently reduce the pain, correct kyphotic deformity and improve the quality of life.

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