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Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by pain, oppressing sensation, or discomfort associated with the bladder, accompanied by lower urinary tract symptoms, lasting for more than 6 weeks (or 6 months). Since IC/BPS was first reported, its diagnosis and treatment have been a challenge to clinicians. This article will review its classification and phenotype, fundamental research, imaging, symptom score, cystoscopy, treatment and potential therapeutic targets.
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Objective To acknowledge the NALP3 inflammasome expression and significance in the interstitial cystitis/bladder pain syndrome (IC/PBS).Methods The urine of 16 IC/BPS patients and 16 normal persons was collected to measure the IL-1β content by ELISA.Bladder tissue of 16 IC/BPS patients and para-carcinoma tissue of 16 bladder cancer patients were collected.And the levels of NALP3,caspase1 and IL-1β were detected by Western Blot.60 female rats were randomly divided into control group(bladder was infused with 0.5 ml saline),hyaluronidase group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml)],NALP3 antagonist group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml) and Glyburide(10 mg/kg)] and mucosal protectant group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml) and sodium hyaluronate(0.8 mg/ml)] to carried out the animal experiment,and 15 rats in each group.The models were created by long-term (1 month) intermittent intravesical hyaluronidase infusion.Voiding patterns were investigated by cystometry.Toluidine blue staining was used to detected mast cell’s changes.The levels of NALP3,caspase-1 and IL-1β were determined by Western Blot,HE staining was to detect tissue inflammation of the bladder,and the severity of pain was examined by Von-frey brush by using the strength of 0.07、0.4、1.0 g.The comparison between the chemotaxis of 200 ng,400 ng IL-1β and 200ng SCF IL-1β to mast cells was checked by Transwell experiment.Results The expressions of IL-1β in IC/PBS patients was increased in IC/PBS group than normal control group [(381 ± 112) μg/L vs.(98 ± 40) μg/L,P ＜0.01].The expressions of NALP3,Caspase-1 and IL-lβ had increased in the IC/PBS group than normal group(0.22 ±0.08 vs.0.11 ±0.02,0.25 ±0.03 vs.0.10 ±0.01,0.19 ±0.04 vs.0.11 ± 0.02,P ＜ 0.05)by Western Blot.In the IC/PBS rats,compared with the control group,the intercontraction intervals [(120.0 ± 15.6) s vs.(447.3 ± 24.6) s] and bladder capacity [(0.34 ± 0.02) ml vs.(1.33 ± 0.04) ml] of the model group were significantly decreased (both P ＜ 0.05).In mucosal protectant group and NALP3 antagonist group,the intercontraction intervals [(323 ± 16.3)s,(280 ± 12.5)s] and bladder capacity [(1.14 ± 0.05) ml,(0.84 ± 0.04) ml] were increased compared with control group (P ＜ 0.05).The amount of mast cell in model group were significantly increased than control group (3.4 ±0.8 vs.0.4 ± 0.2,P ＜ 0.05) while in mucosal protectant group (1.8 ± 0.5) and NALP3 antagonist group (1.5 ± 0.7) were decreased compared with control group (P ＜ 0.05).The protein levels in modle group of NALP3 (5.91 ±0.33 vs.1.00 ±0.12),caspase-1 (6.75 ±0.42 vs.1.00 ±0.22) and IL-1β(7.12 ±0.45 vs.1.00 ± 0.18)were increased than control group.In mucosal protectant group and NALP3 antagonist group,theNALP3 (2.921 ±0.21,2.07±0.18),caspase-1 (3.28 ±0.31,2.25 ±0.19) and IL-1β(3.33± 0.41,1.98 ±0.21) were decreased compared with control group.VonFrey pain score in model group were significantly increased than control group(0.07 g:7.5 ± 1.8 vs.2.1 ± 0.5,0.4 g:9.2 ± 1.9 vs.5.2 ± 1.1,1.0g:15.4±3.8 vs.6.8±1.5,P＜0.05) and VonFrey pain score(0.07 g:2.4±0.3,2.8± 0.7;0.4 g:5.2 ±0.4,6.5 ±1.3;1.0 g:6.4 ±0.8,7.3 ±1.1;P＜0.05) in NALP3 antagonist group were significantly decreased.In vitro,Transwell experimental results showed that 400 ng IL-1β of mast cell chemotaxis is similar with that of the 200 ng SCF (3 800 ±400 vs.4 800 ±500,P ＞0.05).Conclusions The levels of NALP3/Caspase-1/IL-1β in the urine of patients with IC/PBS were significantly higher than those in normal control group.NALP3 is activated in chronic cystitis rat model,and related to pain and frequent urination.This may be related to the down-regulation of expression of NALP3,caspase-1,IL-1β,and other inflammatory mediators,and blocking the chemotactic effects of IL-1 β on mast cells.
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Objective To investigate the significance of mast cells activation,and IL-6,IL-10,sialic acid-binding immunoglobulin-like lectins 8 (Siglec-8) expression in interstitial cystitis/bladder pain syndrome.Methods Bladder mucosal biopsy tissues of 21 patients with IC/BPS admitted to our hospital from March 2016 to October 2017 were taken as the IC/BPS group,and normal bladder mucosa biopsy tissues of 9 patients who underwent ureteroscopy were taken as the control group.In the IC/BPS group,there were 3 males and 18 females aged (56.2 ± 3.4) years,and the patients'pain symptom score (PUF) was (24.6 ± 3.6).Four males and five females in the control group were aged (63 ± 5.1) years.The infiltration of bladder mucosa mast cells and plasma cells in IC/BPS group and control group was observed by transmission electron microscopy.The expression of IL-6,IL-10 and Siglec-8 were detected by immunohistochemical staining.The relationship between the expression level of the immune index and the PUF score was analyzed.Results In the IC/BPS group,mast cells and plasma cells was observed in 18 of the 21 cases,but no mast cells or plasma cells were observed in the control group.Expression of IL-6 in IC/BPS group 1 case (-),11 cases(+) and 9 cases (+ +).IL-6 expression in the control group 9 cases were all (-).The difference of IL-6 expression between the IC/BPS group and the control group was statistically significant (P =0.001).Expression of IL-10 were 3 cases (-),7 cases (+ +),11 cases (+ +) in IC/BPS group,while 7 cases (-),2 cases (+ +),and 0 cases (+ +)in the control group,and there was significant difference between the two group (P =0.001).In the IC/BPS group,expression of Siglee-8 were 12 cases (-),5 (+),4 (+ +),while in control group 7 cases (-),2 (+),and 0 (+ +),no statistically significant difference was found between the two group (P =0.214).The PUF score of the patients with IL-10 expression (-) was 19.7 ± 2.1,lower than those with IL-10 (+ +) (27.1 + 2.5,P ＜ 0.001).PUF of patients with IL-10 (+) was 22.7 ± 1.8,lower than those with (+ +) (P =0.001).The PUF score of IL-6 expression (-) was 21.The PUF score of IL-6 expression (+) was (23.2 + 3.2),lower than (+ +) (26.7 + 3.1,P =0.025).The PUF score of (+ +) IC/BPS patients was (26.6 ± 2.4),higher than that of (+) IC/BPS patients (21.5 ± 2.1,P ＜ 0.0 l).The PUF score of Siglec-8 expression (+ +) and (+) in IC/BPS group was (21.3 ± 2.0),lower than that of Siglec-8 (-) (27.0 ± 2.3,P ＜ 0.0l).Conclusions Mast cells and plasma cells were expressed in IC/BPS tissues.The expression of IL-6 and IL-10 was positively correlated with clinical symptoms,while the expression of Siglec-8 was negatively correlated with clinical symptoms.
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Objective To evaluate the efficacy of the intravesical injection of botulinum toxin A (BTX-A) and bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).Methods We retrospectively reviewed 153 women with IC/BPS from January 2003 to December 2015.Of the 153 patients,77 were treated with BTX-A(group A),the average age was (56.0 ± 4.1) years old.76 underwent bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation (group B),the average age was (58.0 ± 3.3) years old.The patients were evaluated using the O'Leafy-Saint score,visual analog scale pain score,urinary frequency record and quality of life questionnaire before treatment and 1 week,1,3,6 and 12 months after treatment.Results In group A,only 2 had acute urinary retention,27 received a repeat injection,and 28 were lost to follow-up.In group B,3 had urinary tract infection,15 switched to BTX-A injection at 6 months because the treatment of hydrodistention plus Cystistat instillation is not good.31 were lost to follow-up.BTX-A was shown to remain effective for up to 6 months after treatment.After repeated Chinese BTX-A injections,symptoms improved significantly.Hydrodistention plus Cystistat remained effective for up to 3 months after treatment.Conclusions Intravesical injection of BTX-A is a effective therapeutic option for patients with IC/BPS.The average duration of the effect of one dose of Chinese BTX-A was 6 months.Repeated injection of BTX-A is effective.
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Objective To evaluate the effectiveness and security of Botulinum toxin type A (BTX-A) in treating interstitial cystitis /bladder pain syndrome,and also the effect of different site injection.Methods Sixty-nine consecutive BPS/IC patients from October 2011 to February 2016 were divided into three groups randomly,including control group (group A) and treatment group (group B and group C).There were 5 males and 64 females,with age from 23 to 66 years old (average 44.5 years old).Twentythree patients (1 male and 22 females,aged from 23 to 69 years old,with mean age of 44.6 years old) in control group (group A) underwent hydrodistention.Twenty-four patients (2 males and 22 females,aged from 27 to 65 years old,with mean age of 42.8 years old) in group B underwent BTX-A detrusor combined triangle injection plus hydrodistention.Twenty-two patients (2 males and 20 females,aged from 30 to 68 years old,with mean age of 44.3 years old) in group C underwent BTX-A triangle injection alone plus hydrodistention.The parameters such as daytime frequency,nocturia,visual analogue scale/score (VAS),functional cystemetric volume (FCV),post-void residual volume (PVR),QOL score,maximal bladder capacity (MBC),interstitial cystitis symtom index (ICSI),interstitial cystitisproblem index (ICPI),Qmax,and Hamilton anxiey scale (HAMA) score between pre-treatment and 1,3,6 and 9 months after therapy in the three groups were compared.Results There were no serious complications observed in the three groups.All parameters 1 month after therapy were obviously superior to that of pretreatment.The efficacy in control group decreased significantly 3 months after treatment except nocturia (3.0 vs.5.0),daytime frequency(7.0 vs.14.0)and Q (14.0 ml/s vs.13.0 ml/s).However,all parameters in research groups except PVR were still obviously superior to pretherapy.The parameters except Q and nocturia in group B had statistically significant difference from contemporaneous group A (all P ＜ 0.05).However,the parameters except Q nocturia and somatic anxiety score in group C had statistically significant difference from contemporaneous group A (all P ＜ 0.05).VAS (2.0 vs.3.0) and somatic anxiety score (6.0 vs.10.0) in group B were superior to group C (all P ＜ 0.05).When it came to 6 months after therapy,urinary frequence and urgency and pain symptoms were the same to pretherapy and all parameters had no statistically significant difference between pretherapy and after therapy in group A(all P ＞ 0.05).But all parameters except PVR in research group was still superior to pretherapy.the parameters except PVR,Q and QOL in group B had statistically significant difference from contemporaneous group A (all P ＜ 0.05).However,The parameters except PVR,Q MBC,ICSI and QOL in group C had statistically significant difference from contemporaneous group A (all P ＜ 0.05).Meanwhile,efficacy in group B was better than group C in term of ICPI (6.0 vs.8.0) and somatic anxiety score (7.0 vs.10.0) (all P ＜ 0.05).The efficacy decreased significantly 9 months after treatment in both group B and C,with no statistically significant difference compared with that of pretreatment.ICSI(10.0 vs.13.0),ICPI(9.0 vs.13.0),QOL(5.0 vs.6.0)in group B,and QOL(5.0 vs.6.0)in group C had statistically significant difference compared with the contemporary parameters in group A.ICSI(10.0 vs.12.0),MBC(285.0 ml vs.237.5 ml) in group B was better than that in group C (P ＜ 0.05).Conclusions Symptoms in IC/BPS patients can be alleviated significantly by detrusor BTX-A injection plus hydrodistention.Quality of life can be improved remarkably and HAMA scores can be reduced significantly after treatment.Thus,it's an effective therapeutic mnethod for IC/BPS,and detrusor combined triangle injection can provide a better effect than single triangle injection.