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OBJECTIVE To provide reference for safe drug use in the clinic by mining the adverse drug event （ADE） signals of 4 kinds of biological agents for the treatment of inflammatory bowel disease （IBD）. METHODS ADE data of infliximab， adalimumab， ustekinumab and vedolizumab were collected from the FDA adverse event reporting system between the first quarter in 2004 and the fourth quarter in 2022， and were mined by using reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method. The system organ class （SOC） was used for the classification and statistics of drug ADE terminology. RESULTS & CONCLUSIONS A total of 65 173， 247 894， 37 596 and 6 134 ADE reports were retrieved for the above 4 biologic agents， involving 1 664， 1 731， 588， 303 ADE signals and 27， 27， 24， 26 SOC， respectively. The largest number of ADE reported of infliximab were various musculoskeletal and connective tissue diseases， and the signal intensity of disseminated tuberculosis was stronger. The largest number of ADE reported of adalimumab were systemic disease and various reactions at the administration site， and the signal intensity of papular at the injection site was stronger. The largest number of ADE reported of ustekinumab were various injuries， poisoning and operation complications， and the signal intensity of latent tuberculosis was slightly stronger. The largest number of ADE reported of vedolizumab were systemic diseases and various reactions at the administration site， and the signal intensity of shorter treatment response time was stronger. When clinically administering the four drugs， it is crucial to pay close attention to common ADEs and other ADE not mentioned in the drug label. For infliximab， clinicians should exercise caution due to the potential risk of synovitis and basal cell carcinoma； when prescribing adalimumab， caution should be exercised due to ADEs related to synovitis and hernia； for ustekinumab， the ADE associated with hepatobiliary diseases should be vigilant； for vedolizumab， clinicians should be vigilant for blood in the stool， increasing frequency of defecation. Except for ustekinumab， the other 3 biological agents also require attention for ADE associated with pregnancy.
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【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E2) levels in the HYPO group were higher than those in the SCO group (P<0.05). NOA patients were grouped according to the results of Micro-TESE surgical treatment. There was a statistically significant difference in AMH and INHB levels between the Micro-TESE positive and negative groups (P<0.05). The binary logistic regression analysis of factors affecting the Micro-TESE outcomes of NOA patients showed AMH was negatively correlated with the Micro-TESE outcome (OR=0.904,95%CI:0.91-1.08,P<0.05). 【Conclusion】 Age,FSH,LH,AMH,and INHB are correlated with sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm. The INHB level was the lowest in the SCO group. The results of Micro-TESE in patients with NOA can be predicted by serum AMH level.
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Objective:To explore the role of an exosomal long non-coding RNA zinc finger E-box-bingding homeobox 1 antisense 1(ZEB1-AS1) from adipose-derived MSC(adMSC) and its action mechanism in DN.Methods:DN rat model and high glucose(HG)-induced glomerular mesangial cell(GMCs) model treated with exosomal ZEB1-AS1 from adMSC were used for biochemical analysis and inflammation/oxidative stress assessment. The binding relationships among ZEB1-AS1, microRNA(miR)-142-5p, and phosphatase and tensin homolog deleted on chromosome 10(PTEN) were confirmed by dual luciferase reporter assay. Western blotting was used for the measurement of PTEN protein level.Results:adMSC-secreted exosomal ZEB1-AS1 reduced the levels of blood glucose, serum creatinine, 24 h urinary protein, kidney weight, fibrosis, and inflammatory cell infiltrations in DN rats. Meanwhile, both in DN rats and HG-induced GMCs, the levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β were inhibited, but glutathione peroxidase(GPx), superoxide dismutase(SOD), catalase(CAT), and glutathione(GSH) were promoted by exosomal ZEB1-AS1 treatment. Additionally, miR-142-5p was identified to bind to ZEB1-AS1, while miR-142-5p further targeted PTEN. miR-142-5p overexpression or PTEN silencing reversed the inhibiting effects of exosomal ZEB1-AS1 on inflammatory cytokine levels and the promoting effects on the concentrations of antioxidant enzymes.Conclusion:Exosomal ZEB1-AS1 from adMSC prevents DN progression by controlling inflammation and oxidative stress via the miR-142-5p/PTEN pathway, suggesting that ZEB1-AS1 may serve as a potential and effective therapeutic target for treating DN.
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Objective To analyze the factors which may affect postoperative patency of microsurgical vasoepididymostomy (VE).Methods Ninety-four patients underwent VEs from September 2014 to June 2016 in the Department of Urology,Peking University Third Hospital,with average age of (30.7 ± 4.8) years,and body mass index (BMI) of (25.1 ± 3.0) kg/m2.Semen analyses were performed 1 month,3 months and 5 to 6 months after the operation.The following semen analyses were performed every 3-6 months thereafter.Patency was defined by finding sperms in twice or more analyses during the followup until August 2017.Patients were followed up by face-to-face or telephone interview.Seven factors (age,BMI,bilateral or unilateral anastomosis,anastomosis sites,the adjustment of anastomosis sites,motility and quantity of sperms found in epididymal fluid) were analyzed by Chi-square analysis and multifactor logistic regression analysis.Results Eighty-two patients were followed up (87.2％,82/94) while 12 patients were lost of follow-up.The mean follow-up time was 19 months.Sperms were found in the ejaculate in 59 patients postoperatively.The overall patency rate was 72.0％ (59/82),and natural paternity rate was 32.8％ (19/58).Patients ≤28 years old and those ＞28 years old had patency rates of 89.3％ (25/28) and 63.0％ (34/54,P =0.012),respectively.Patients with BMI ＜26.0 kg/m2 and BMI≥26.0 kg/m2 had patency rates of 80.4％ (41/51) and 58.1％ (18/31,P =0.029),respectively.Patency rate of bilateral surgery was 72.1％ (44/61) and of unilateral surgery was 71.4％ (44/62,P =0.727).Patency rate of caput anastomosis achieved 75.0％ (15/20) and of corpus/caudal anastomosis was 71.0％ (44/62,P =0.727).Patency rates of patients with and without adjustment of anastomosis sites were 77.8％ (7/9) and 71.2％ (52/73,P =0.680),respectively.Patency rates of a lot,a few,motile and seldom-motile sperms in epididymal fluid were 74.3％ (55/74) vs.50.0％ (4/8,P =0.146) and 70.0％ (28/40) vs.73.8％ (31/42,P =0.701),respectively.Multifactor logistic regression analysis showed that age was well associated with patency rate (OR=4.705,95％CI 1.181-18.742,P=0.028).Conclusions Age ≤28 years is an independent factor leading to higher patency rates.Patients with lower BMIs and younger could have higher patency rates.Factors of anastomosis sides,anastomosis sites,the adjustment of anastomosis sites,motility and quantity of sperms found in epididymal fluid showed no statistical difference in patency rates.
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To explore the best measurement of waist circumference related with intra-abdominal fat area evaluated by magnetic resonance imaging ( MRI). Totally 207 participants aged 20-60 years were enrolled. Waist circumference were measured at the levels of navel ( WC1) and the midpoint between costal brim and iliac cest (WC2). Intra-abdominal fat area was evaluated by MRI scan. Intra-abdominal fat area was significantly higher in men than in women [(132. 17 ± 59. 49 vs 70. 56 ± 35. 33)cm2 , P<0. 01]. Pearson correlation analysis showed that WC1 and WC2 were positively correlated with intra-abdominal fat area (r = 0. 779, r = 0. 809, both P<0. 01). Multiple linear stepwise regression analysis demonstrated that WC1 and WC2 were independently associated with intra-abdominal fat area(β=0. 553, R2 =0. 714, P<0. 01; β = 0. 603, R2 = 0. 735, P<0. 01). All of the two different measurements of waist circumference parameters may reflect intra-abdominal fat area, while WC1 seems to be the simpler one.
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To explore the best measurement of waist circumference related with intra-abdominal fat area evaluated by magnetic resonance imaging ( MRI). Totally 207 participants aged 20-60 years were enrolled. Waist circumference were measured at the levels of navel ( WC1) and the midpoint between costal brim and iliac cest (WC2). Intra-abdominal fat area was evaluated by MRI scan. Intra-abdominal fat area was significantly higher in men than in women [(132. 17 ± 59. 49 vs 70. 56 ± 35. 33)cm2 , P<0. 01]. Pearson correlation analysis showed that WC1 and WC2 were positively correlated with intra-abdominal fat area (r = 0. 779, r = 0. 809, both P<0. 01). Multiple linear stepwise regression analysis demonstrated that WC1 and WC2 were independently associated with intra-abdominal fat area(β=0. 553, R2 =0. 714, P<0. 01; β = 0. 603, R2 = 0. 735, P<0. 01). All of the two different measurements of waist circumference parameters may reflect intra-abdominal fat area, while WC1 seems to be the simpler one.
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Objective:To discuss the treatment options for patients with azoospermia factor (AZF)c microdeletion on Y chromosome.Methods:One hundred and eighty three patients,who were diagnosed as AZFc microdeletion on Y chromosome in Peking University Third Hospital,were recruited in our stu-dy.In order to get better treatment option for this kind of patients,we retrospectively analyzed their clinic data including the treatment process and pregnancy outcome and found out the characteristics of their se-men.Results:Among the 183 patients,sperms can be found in ejaculated semen in 105 patients (57.4%,105 /183).One hundred and three patients (98.1%,103 /105)were diagnosed as severe or extremely severe oligospermia.Regular medication was given to 98 patients,6 patients (6.1%,6 /98) of which got natural pregnancy.The other 99 patients who have sperms in their semen received intracyto-plasmic sperm injection (ICSI),68 patients (68.7%,68 /99)of which got pregnancy.Seventy eight patients were diagnosed as azoospermia among all the 183 patients.Forty nine patients received testicular sperm aspiration (TESA),and 21 patients choose to receive micro-TESE directly.Among the 49 patients with TESA,sperms were retrieved in 17 patients (34.7%,17 /49),and sperms were not retrieved in 32 patients (65.3%,32 /49),of which 12 patients (37.5%,12 /32)gave up treatment and 20 patients (62.5%,20 /32)choose micro-TESE.Among the 41 patients who choose to receive micro-TESE,ope-ration has been done on 19 patients,of which 11 patients (57.9%,11 /19)got sperms.Among the 11 patients,TESA has been done on 6 patients before micro-TESE,of which 4 patients (66.6%,4 /6)got sperms.ICSI has already been done on 7 azoospermia AZFc microdeletion patients who underwent micro-TESE,of which 4 patients (57.1%,4 /7)get pregnancy.Conclusion:AZFc microdeletion patients who had sperms were always diagnosed as severe or extremely severe oligospermia.ICSI was their first choice instead of drug therapy.For AZFc microdeletion patients who were diagnosed as azoospermia, TESA was one of their choices,however,the success rate is not high.Micro-TESE is still possible to get sperms even after the failure of TESA.Therefore,we may choose micro-TESE instead of TESA in some azoospermia patients in order to reduce surgical trauma on patients.
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Objective To investigate the relationship between intra-abdominal fat area(IAFA)in male with abdominal obesity and glycometabolism related indicators. Methods Ninety-four obesity males,aged from 21 to 62 years old,were selected as our subjects. They were divided into abdominal obesity group(n = 70)and non-abdominal obesity group( n = 24). The general information of all subjects was recorded. The indexes of height,weight,waist circumference,hip circumference,body mass index(BMI)were measured. The fasting oral glucose tolerance test was performed. The levels of blood glucose(0,1,2 h)and insulin(0,1,2 h)were measured,and insulin resistance index was calculated. MRI measurement was applied to calculate the IAFA. Compared the difference between the two groups in term of the level of blood glucose,insulin and insulin resistance index,and analyzed the correlation between glycometabolism related indicators and IAFA. Results BMI,waist circumference,hip circumference,insulin resistance index and IAFA in abdominal obesity group were (28. 67 ± 4. 20)kg/ m2 ,(99. 75 ± 4. 07)cm,(104. 42 ± 7. 62)cm,2. 60 ± 1. 80,(153. 06 ± 53. 23)cm2 respectively,higher than those in non-abdominal obesity group((21. 80 ± 1. 97)kg/ m2 ,(79. 50 ± 10. 05)cm, (91. 86 ± 4. 49)cm,1. 52 ± 0. 73,(71. 78 ± 25. 48)cm2 ),and the differences were statistically significant(t= - 7. 704,- 9. 583,- 7. 618,- 2. 877,- 7. 184,P < 0. 05). The level of blood glucose at 0,1,2 h of patient in abdominal obesity group were(5. 89 ± 1. 36)mmol/ L,(10. 55 ± 3. 07)mmol/ L,and(8. 41 ± 3. 63) mmol/ L,higher than that in non-abdominal obesity group((5. 29 ± 0. 53)mmol/ L,(8. 76 ± 1. 96)mmol/ L, (6. 54 ± 1. 50)mmol/ L). Meanwhile,The insulin at 0,1,2 h of man in abdominal obesity group were(9. 71 ± 5. 05)mU/ L,(83. 29 ± 64. 51)mU/ L,(63. 56 ± 21. 09)mU/ L),significantly higher than those in non-abdominal obesity group((6. 42 ± 2. 96)mU/ L,(33. 00 ± 19. 82)mU/ L,(63. 56 ± 21. 09)mU/ L),and the differences were significant( t = - 2. 098,- 2. 671;- 2. 447,- 3. 010;- 3. 784,- 3. 089;P < 0. 05). The IAFA in abdominal obesity was positively correlated with age,BMI,waist circumference,hip circumference,blood glucose(0,1,2 h)insulin(0,2 h)and insulin resistance index(r = 0. 254,0. 533,0. 521,0. 615,0. 245,0. 315, 0. 294,0273,0. 249,0. 225,P < 0. 05 ). After adjustment for confounding factors,age( x1 ),abdominal circumference(x2)and insulin resistance index(x3)were related to IAFA(y = 1. 369x1 + 4. 472x2 + 25. 072x3- 333. 626). Conclusion Compared with patients with non-abdominal obesity,the IAFA of patient with abdominal obesity with abdominal fat area size is associated with insulin resistance.