Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Neuro-inspired optical sensor array for high-accuracy static image recognition and dynamic trace extraction.

Neuro-inspired vision systems hold great promise to address the growing demands of mass data processing for edge computing, a distributed framework that brings computation and data storage closer to the sources of data. In addition to the capability of static image sensing and processing, the hardware implementation of a neuro-inspired vision system also requires the fulfilment of detecting and recognizing moving targets. Here, we demonstrated a neuro-inspired optical sensor based on two-dimensional NbS2/MoS2 hybrid films, which featured remarkable photo-induced conductance plasticity and low electrical energy consumption. A neuro-inspired optical sensor array with 10 × 10 NbS2/MoS2 phototransistors enabled highly integrated functions of sensing, memory, and contrast enhancement capabilities for static images, which benefits convolutional neural network (CNN) with a high image recognition accuracy. More importantly, in-sensor trajectory registration of moving light spots was experimentally implemented such that the post-processing could yield a high restoration accuracy. Our neuro-inspired optical sensor array could provide a fascinating platform for the implementation of high-performance artificial vision systems.

Immediate implant placement with and without provisionalization: A comparison of a one-year longitudinal study.

Background/purpose: Immediate implant placement (IIP) with and without immediate provisionalization (Ipro) may yield satisfactory results in appropriate indications and treatment, especially in the esthetic zone. The aim of this study was to compare implant stability, marginal bone loss (MBL), survival rates, and patient satisfaction between IIP with Ipro and IIP without Ipro. Materials and methods: Seventy patients, each with a failed maxillary anterior tooth, were randomly assigned to IIP with Ipro (Group A: n = 35) or IIP without Ipro (Group B: n = 35). Implant stability quotient (ISQ) and standardized periapical radiographs were performed at surgery and at 3, 6, 9, and 12 months postoperatively to investigate implant stability and MBL, respectively. Survival was assessed 1 year after surgery. Patient satisfaction was evaluated with a visual analogue scale (VAS). Results: Primary ISQ and MBL were not significantly different between groups A and B immediately after surgery (P ＞ 0.05). Implant survival was 100% in both groups, and only one mechanical complication was observed. Patient satisfaction was good at definitive crown delivery and postoperatively 1-year in both groups. However, the immediate postoperative VAS score in Group A was significantly higher than that in Group B (P < 0.05). Conclusion: Group A revealed significantly higher secondary ISQ than Group B at postoperatively 3, 6, 9, and 12 months. There were no significant differences between groups A and B in terms of MBL and survival. Notably, patient satisfaction in Group A was significantly higher than in Group B immediately after surgery.

Laparoscopic management of second trimester ruptured cornual heterotopic pregnancy with subsequent live birth delivery: A case report and literature review.

OBJECTIVE: Heterotopic pregnancy (HP) is the coexistence of extra- and intrauterine gestation implantation sites. A rare case of a second-trimester ruptured cornual HP (CHP) treated with laparoscopic cornual resection with the primary repair is presented. Risk factors, clinical presentations, treatments, and outcomes of CHPs are also reviewed. CASE REPORT: A 35-year-old pregnant woman with CHP presented with lower abdominal pain with hemoperitoneum and her hemoglobin level dropped. Laparoscopic management of a ruptured HP was performed, leaving the surplus intrauterine fetus intact. She delivered a 2360 g male infant via cesarean section at 34 weeks' gestation due to preterm premature rupture of membranes. We found a well-healed wound over the left uterine cornua during the cesarean section. CONCLUSION: Ruptured CHP is a rare but life-threatening complication of an obstetric emergency. Although the pregnant uterus becomes congested and fragile, using reliable laparoscopic energy devices and barbed sutures, successful treatment is feasible.

Melatonin-Assisted Cisplatin Suppresses Urinary Bladder Cancer Cell Proliferation and Growth through Inhibiting PrPC-Regulated Cell Stress and Cell Proliferation Signaling.

This study investigated whether melatonin (Mel) would promote cisplatin to suppress the proliferation and growth of bladder cancer (BC) cells by inhibiting cellular prion protein (PrPC)-mediated cell stress and cell proliferation signaling. An immunohistochemical staining of tissue arrays from BC patients demonstrated that the PrPC expression was significantly upregulated from stage I to III BC (p < 0.0001). The BC cellline of T24 was categorized into G1 (T24), G2 (T24 + Mel/100 µM), G3 (T24+cisplatin/6 µM), G4 (PrPC overexpression in T24 (i.e., PrPC-OE-T24)), G5 (PrPC-OE-T24+Mel), and G6 (PrPC-OE-T24+cisplatin). When compared with a human uroepithelial cell line (SV-HUC-1), the cellular viability/wound healing ability/migration rate were significantly increased in T24 cells (G1) and further significantly increased in PrPC-OE-T24 cells (G4); and they were suppressed in Mel (G2/G5) or cisplatin (G3/G6) treatment (all p < 0.0001). Additionally, the protein expressions of cell proliferation (PI3K/p-Akt/p-m-TOR/MMP-9/PrPC), cell cycle/mitochondrial functional integrity (cyclin-D1/clyclin-E1/ckd2/ckd4/mitochondrial-cytochrome-C/PINK1), and cell stress (RAS/c-RAF/p-MEK1/2, p-ERK1/2) markers showed a similar pattern of cell viability among the groups (all p < 0.001). After the BC cell line of UMUC3 was implanted into nude mouse backs, by day 28 mthe BC weight/volume and the cellular levels of PrPC/MMP-2/MMP-9 were significantly, gradually reduced from groups one to four (all p < 0.0001). The protein expressions of cell proliferation (PI3K/p-Akt/p-m-TOR/MMP-9/PrPC), cell cycle/mitophagy (cyclin-D1/clyclin-E1/ckd2/ckd4/PINK1), and cell stress (RAS/c-RAF/p-MEK1,2/p-ERK1,2) signaling were significantly, progressively reduced from groups one to four, whereas the protein expressions of apoptotic (Mit-Bax/cleaved-caspase-3/cleaved-PARP) and oxidative stress/mitochondrial damaged (NOX-1/NOX-2/cytosolic-cytochrome-C/p-DRP1) markers expressed an opposite pattern of cell proliferation signaling among the groups (all p < 0.0001). Mel-cisplatin suppressed BC cell growth/proliferation via inhibiting the PrPC in upregulating the cell proliferation/cell stress/cell cycle signaling.

Effectiveness of Tai Chi for Health Promotion of Older Adults: A Scoping Review of Meta-Analyses.

Background. Tai Chi is a form of exercise that is accessible to people from different socioeconomic backgrounds, making it a potentially valuable activity for health promotion of older adults. Purpose. The objective of this scoping review was to summarize the current knowledge about the effectiveness of Tai Chi for older adults across a range of general health outcomes from published, peer reviewed, unique meta-analyses. Methods. Meta-analyses were retrieved from Medline, Embase, AMED, CINAHL, SPORTDiscus, PsychINFO, Web of Science, PubMed Health, and the Cochrane Library from database inception to late August 2019. Multistage deduplication and screening processes identified eligible full-length meta-analyses. Two people independently appraised 27 meta-analyses based on the GRADE system and organized results into 3 appendices subsequently collated into heterogeneous, statistically significant, and statistically insignificant tables. Results. "High" and "moderate" quality evidence extracted from these meta-analyses demonstrated that practicing Tai Chi can significantly improve balance, cardiorespiratory fitness, cognition, mobility, proprioception, sleep, and strength; reduce the incidence of falls and nonfatal stroke; and decrease stroke risk factors. Conclusions. Health care providers can now recommend Tai Chi with high level of certainty for health promotion of older adults across a range of general health outcomes for improvement of overall well-being.

Pelvic Floor Myofascial Pain Might Influence Treatment Outcome of Interstitial Cystitis/Bladder Pain Syndrome: A Prospective Study.

BACKGROUND: In patients with interstitial cystitis or bladder pain syndrome (IC/BPS), 85% were found to have pelvic floor myofascial pain (PFMP) and hypertonicity (PFH). However, they physicians are not typically trained to consider or assess PFMP as a contributing factor to patients' IC/BPS symptoms. OBJECTIVE: This study aimed to explore the relationship between PFMP and treatment outcomes in women with IC/BPS. STUDY DESIGN: A prospective study. SETTING: Department of Urology, Medical Center, Hualien, Taiwan. METHODS: Patients with IC/BPS who received any type of treatment were prospectively enrolled. They underwent vaginal digital examination at baseline. PFMP severity was quantified on the visual analog scale (VAS). Subject assessment items included O'Leary-Sant symptom score (OSS), Global Response Assessment (GRA), and Beck's anxiety inventory. Object assessment items included bladder computed tomography (CT), urodynamic parameters, maximum bladder capacity, and grade of glomerulation. RESULTS: A total of 65 women with IC/BPS (mean age, 57.1 ± 11.3 years) were enrolled in the study. Patients with more severe PFMP had significantly higher rate of dyspareunia (P = 0.031); more comorbidities (P = 0.010); higher number of PFMP sites (P < 0.001); and higher OSS (P = 0.012). PFMP severity was not significantly correlated with bladder conditions, whether subjective or objective. Moreover, PFMP severity (VAS) was significantly negatively associated with the GRA score. LIMITATIONS: There was a small sample size and short follow-up duration, the patients in this study are all women, and the applicability to other populations is uncertain. CONCLUSION: PFMP might affect the subjective results of IC/BPS treatment but not the bladder condition. Therefore, in the future treatment of patients with IC/BPS, digital vaginal examinations of pelvic floor muscles should be performed and focused more on the PFM-related conditions, and necessary PFM treatments, such as the vaginal pelvic floor muscle message, should be scheduled.

Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance.

Inflammation is closely linked to the abnormal phospholipid metabolism chain of cyclooxygenase-2/microsomal prostaglandin E2 synthase-1/prostaglandin E2 (COX-2/mPGES-1/PGE2). In clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) as upstream COX-2 enzyme activity inhibitors are widely used to block COX-2 cascade to relieve inflammatory response. However, NSAIDs could also cause cardiovascular and gastrointestinal side effects due to its inhibition on other prostaglandins generation. To avoid this, targeting downstream mPGES-1 instead of upstream COX is preferable to selectively block overexpressed PGE2 in inflammatory diseases. Some mPGES-1 inhibitor candidates including synthetic compounds, natural products and existing anti-inflammatory drugs have been proved to be effective in in vitro experiments. After 20 years of in-depth research on mPGES-1 and its inhibitors, ISC 27864 have completed phase II clinical trial. In this review, we intend to summarize mPGES-1 inhibitors focused on their inhibitory specificity with perspectives for future drug development.

Comparison of Prolift, Perigee-Apogee, Prosima, and Elevate transvaginal mesh systems in pelvic organ prolapse surgery: Clinical outcomes of a long-term observational study.

OBJECTIVES: To evaluate and compare the long-term clinical outcomes of four different transvaginal mesh systems. METHODS: This retrospective study included 695 patients classified into four groups (Prolift, n = 132; Perigee-Apogee, n = 186; Prosima, n = 60; Elevate; n = 317), with a median follow-up time of 5.8 years (range 0.5-12.2 years). The outcomes were objective anatomic success (Pelvic Organ Prolapse [POP] Quantification system stage ≤1), mesh exposure, and urologic functional assessments. RESULTS: For anatomic outcomes, we stepwise analyzed the short-term (within 3 years) and long-term (after 3 years) results. Prolift had the highest long-term success rate (9 years: 82.1%, P = .007). Elevate had a comparable short-term success rate (3 years: 87.5%), but its long-term success rate significantly decreased over time (5 years: 78.6%, 9 years: 66.8%, P = .007). Prosima had the lowest short-term success rate (P = .027). For the long-term mesh exposure rate (9-year cumulative), Elevate had the lowest with 11.1%; next were Perigee-Apogee (18.8%) and Prolift (24.6%); and Prosima had the highest with 39.4%, with a significant difference. In terms of urinary functional results, we observed no significant differences in voiding dysfunction, de novo stress urinary incontinence, or de novo overactive bladder symptoms among the four mesh groups, whether combined with midurethral sling surgery or not. CONCLUSION: Different vaginal mesh designs have various advantages and features. Prolift provided the best long-term anatomic success but had a high mesh exposure rate. Elevate gave comparable short-term success but had a decreased long-term success rate. However, Elevate is superior with the lowest long-term mesh exposure rate. Prosima had the worst anatomic correction and highest mesh exposure rates. This study provides a comprehensive long-term comparative result for POP patients and surgeons.

Laparoscopic pectopexy: the learning curve and comparison with laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: In addition to laparoscopic sacrocolpopexy (LS), laparoscopic pectopexy (LP) is a novel surgical method for correcting apical prolapse. The descended cervix or vaginal vault is suspended with a synthetic mesh by fixing the bilateral mesh ends to the pectineal ligaments. This study was aimed at developing a learning curve for LP and to compare it with results with LS. METHODS: We started laparoscopic/robotic pectopexy in our department in August 2019. This retrospective study included the initial 18 consecutive women with apical prolapse receiving LP and another group undergoing LS (21 cases) performed by the same surgeon. The medical and video records were reviewed. RESULTS: The age was older in the LP group than in the LS group (65.2 vs 53.1 years). The operation time of LP group was significantly shorter than that of the LS group (182.9 ± 27.2 vs 256.2 ± 45.5 min, p < 0.001). The turning point of the LP learning curve was observed at the 12th case. No major complications such as bladder, ureteral, bowel injury or uncontrolled bleeding occurred in either group. Postoperative low back pain and defecation symptoms occurred exclusively in the LS group. During the follow-up period (mean 7.2 months in LP, 16.2 months in LS), none of the cases had recurrent apical prolapse. CONCLUSIONS: Laparoscopic pectopexy is a feasible surgical method for apical prolapse, with a shorter operation time and less postoperative discomfort than LS. LP may overcome the steep learning curve of LS because the surgical field of LP is limited to the anterior pelvis and avoids encountering the critical organs.

Two different techniques combined with MIS-TLIF in the treatment of degenerative lumbar spondylolisthesis:a case-control study / 中国骨伤

OBJECTIVE@#To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis.@*METHODS@#A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation.@*RESULTS@#①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(P<0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation (P<0.05), but there was no significant difference between the three group(P>0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation (P<0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation(P<0.05), and the intervertebral heigh was increased compared with that before operation(P<0.05), however, there was no significant difference among three groups at 12 months afrer operation(P>0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation(P>0.05).@*CONCLUSION@#The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.

Extracorporeal Shock Wave Therapy Protected the Functional and Architectural Integrity of Rodent Urinary Bladder against Ketamine-Induced Damage.

This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + ECSW) and G4 (RBdSMCs + menadione + ECSW). The results showed protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), inflammatory markers (MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-6/IL-1ß/MMP-9/iNOS), and cell-stress response signalings (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38/p-53) were significantly increased in G2 than in G1 and G3, and those were significantly reversed in G4 (all p < 0.0001). Adult-male SD rats (n = 24) were equally categorized into group 1 (sham-control), group 2 (ketamine/30 mg/kg/daily i.p. injection for four weeks), group 3 [ketamine/30 mg/kg + ECSW/optimal energy (0.12 mJ/mm2/120 impulses/at 3 h and days 3/7/14/21/28 after ketamine administration)] and group 4 [(ketamine/30 mg/kg + ECSW/higher energy (0.16 mJ/mm2/120 impulses)] and animals were euthanized by day 42. The results showed the urine levels of pro-inflammatory cytokines (TNF-α/IL-6) were lowest in group 1, highest in group 2 and significantly higher in group 3 than in group 4 at days 1/7/14/28 (all p < 0.0001). The duration of urinary bladder contraction was lowest in group 2, highest in group 1 and significantly higher in group 4 than in group 3, whereas the maximal pressure of urinary bladder exhibited an opposite pattern of bladder contraction among the groups (all p < 0.0001). The histopathological findings of fibrosis/inflammation/keratinization and protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), and inflammatory (TLR-2/TLR-4/MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-1ß/MMP-9/iNOS) and cell-stress response (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38) signalings and apoptotic/fibrotic biomarkers (cleaved-caspas3/cleaved-PARB/Smad3/TFG-ß) exhibited an identical pattern of urine proinflammatory cytokine among the groups (all p < 0.0001). ECSW effectively attenuated ketamine-induced bladder damage and dysfunction.

The surgical effect on overactive bladder symptoms in women with pelvic organ prolapse.

This study aimed to explore the effect of pelvic reconstruction surgery on the relation of pelvic organ prolapse (POP) and overactive bladder (OAB) and the impact of preoperative vaginal oestrogen supplement on vaginal tissue. A total of 100 postmenopausal women with symptomatic POP who underwent pelvic reconstruction surgery (laparoscopic sacrocolpopexy or transvaginal mesh) were enrolled in this study. Preoperative vaginal oestrogen was prescribed in 28 cases. The evaluation tools consisted of POP-Q, urodynamic study, Overactive Bladder Symptom Score (OABSS), and urinary NGF. Vaginal maturation index and vaginal specimens for hormone receptors study were investigated during operation to evaluate the effect of topical oestrogen. Follow-up assessments were performed at 1, 3, and 6 months after surgery. Preoperatively, 58 (58%) were POP with OAB. After reconstruction surgery, the OABSS decreased significantly (6.87 ± 0.85 vs 3.77 ± 0.61, p < 0.001) at postoperative 6 months in the group. Remarkable increasing trends of urinary NGF levels are noted till 3 months postoperatively, then decreasing to the baseline level at 6 months postoperative follow-up. Remarkable decrease of mRNA of the androgen receptor and significant higher expression of progesterone receptor (PR) were noted after use of the vaginal oestrogen cream. The severity of OAB in the POP women shows moderate degree according to OABSS. Pelvic reconstruction surgery can significantly improve the OAB symptoms. The surgery induced inflammation effect lasts for about 6 months. Short-term preoperative supplement of topical oestrogen brings alterations of the vaginal epithelium.

Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury.

BACKGROUND: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. METHODS AND RESULTS: Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001). CONCLUSION: Mel-ADMSCs effectively protected the testis against TTIR injury.

Factors associated with treatment outcomes after intravesical hyaluronic acid therapy in women with refractory interstitial cystitis: A prospective, multicenter study.

BACKGROUND: Bladder instillation of hyaluronic acid (HA) is an acceptable treatment for bladder pain syndrome/interstitial cystitis (BPS/IC). The treatment is limited by a high proportion of non-responders (~30%-40%). Here, we aimed to evaluate predisposing factors associated with treatment outcomes. METHODS: This is a prospective multicenter study. We enrolled a total of 137 (out of 140) women with refractory IC. They all underwent a standard protocol of 6-month intravesical HA therapy (initial 4 weeks, once weekly, followed by once monthly). To assess the outcomes, we used the pain Visual Analog Scale (Pain-VAS), Interstitial Cystitis Symptom and Problem Index (ICSI & ICPI), and a scaled Global Response Assessment (GRA). RESULTS: The age of patients was 47.6 ± 27.5 (range 24-77) years. We found statistically significant improvement (p < 0.001) in the Pain-VAS and the ICSI & ICPI scores both after the initial 4-weekly instillations and at the end of 6-month treatment. Those who reported moderate/marked improvement on GRA at the 2 follow-up visits were considered responders: 39.4% (n = 54) at the first follow-up, and 59.9% (n = 82) at the second follow-up. No remarkable side effect was noted. After statistical analyses, treatment outcomes on GRA were positively associated with baseline functional bladder capacity and with Pain-VAS scores. The initial treatment responses optimally (p < 0.001) predicted final treatment outcomes (McNemar). CONCLUSION: Intravesical HA therapy is safe and effective for most (~60%) of our patients with refractory IC. Functional bladder capacity and Pain-VAS scores before treatment, and the early treatment responses are helpful predictors of treatment outcomes.

Short-term results of stress urinary incontinence in women undergoing laparoscopic sacrocolpopexy with and without midurethral sling.

OBJECTIVES: This study aimed to assess the short-term results of stress urinary incontinence (SUI) in women undergoing laparoscopic sacrocolpopexy (LSC) with and without midurethral sling (MUS). METHODS: This retrospective study was conducted from July 2012 to December 2017. Women with stage 3 or 4 in the Pelvic Organ Prolapse Quantification (POP-Q) who underwent LSC were recruited. Multichannel urodynamic studies were performed in all women. Assessment included pre- and postoperative POP-Q stages, urodynamic parameters, peri- and postoperative complications, and symptoms. RESULTS: One hundred and eighteen patients met the inclusion criteria in total. A total of 19.5% (23/118) of them had concomitant MUS. The mean follow-up duration was 16.9 ±  16.0 (range 3-69) months. Meanwhile, 33.9% (40/118) of the patients were diagnosed with overt SUI, and 50% (20/40) underwent MUS. In the concomitant MUS group, the rate of having postoperative SUI was only 5% (1/20). Patients diagnosed with SUI and without concomitant MUS had a 45% rate (9/20), and 25% of them (5/20) received MUS later. Preoperatively, 16.1% (19/118) of the patients were diagnosed with occult SUI. Among the patients without anti-incontinence sling during prolapse surgery, 25% (4/16) of them complained about having SUI during the follow-up. However, none of the women required subsequent anti-incontinence surgery. Postoperative de novo SUI occurred to 13.6% (16/118) of them. None of the patients received further operation. Based on the preoperative and postoperative urodynamic studies in the combination surgery group, a significant improvement was observed in the pad test. CONCLUSIONS: The combination of LSC with MUS procedure is likely to be beneficial in selected patients.

Botulinum toxin A injection in the treatment of chronic pelvic pain with hypertonic pelvic floor in women: Treatment techniques and results.

Chronic pelvic pain (CPP) is an extremely bothersome condition which leads to major effects in women's everyday life. In addition to visceral sources of pain, pelvic floor dysfunction including myofascial pain and spasm on the pelvic floor muscles causing hypertonicity are causes often overlooked. Injecting botulinum toxin type A (BoNT-A) into hypertonic pelvic floor muscles may aid the relaxation of pelvic floor musculature. The muscles that are injected in CPP treatment include the obturator internus, levator ani (pubococcygeus, iliococcygeus, and puborectalis), and coccygeus. Generally, injections can be performed tolerably with safety under conscious sedation combined with local anesthesia. Most practitioners perform BoNT-A injection of pelvic floor muscles using anatomical landmarks identified by manual palpation only. For the precise location of injection sites, some needle guidance techniques were proposed, including electromyography, electrical stimulation, ultrasound, fluoroscopy, and/or computed tomography. Side effects of BoNT-A injection in CPP are rare and self-limiting. Because of the reversible nature of BoNT-A, reinjection appears to be necessary. Increasing proof points out that BoNT-A is a promising treatment option for CPP in women. We conducted a review of published literature in Pubmed, using chronic pelvic pain in women, hypertonic pelvic floor, and botulinum toxin as the keywords. This article aims to summarize the treatment techniques and results of BoNT-A injection for hypertonic pelvic floor in women with chronic pelvic pain.

Sacrospinous ligament fixation with uterine preservation reduces the risk of anatomical recurrence in pelvic organ prolapse.

OBJECTIVES: This study investigated the effectiveness of sacrospinous ligament fixation (SSLF) and whether uterine preservation reduces the anatomical recurrence rate. METHODS: The medical records of 82 patients who received SSLF in a single medical center were reviewed retrospectively. Anatomical recurrence was defined as Pelvic Organ Prolapse-Quantification stage 2 or higher in any compartment. The primary outcome was intergroup analysis for uterine preservation and concomitant hysterectomy patients. The secondary outcomes were anatomical recurrence risk factors and the incidence of adverse events. Propensity score matching (PSM) was used to adjust for demographic differences between groups. RESULTS: The anatomical recurrence rate was 19.5%, and the retreatment rate was 11.0% (mean follow-up duration: 22.9 months). Cystocele was the most common recurrent compartment (17.1%). The uterine preservation group (n = 66) was younger, had lower parity, and had fewer stage 3 to 4 cystoceles and uterine prolapses than the concomitant hysterectomy group (n = 16). Shorter operation times (99.4 minutes vs 153.7 minutes, P = .002) and lower anatomical recurrence rates (11.5% vs 45.5%, P = .039) were found in the uterine preservation group before and after PSM. Previous pelvic organ prolapse surgery (hazard ratio 3.14) and concomitant hysterectomy (hazard ratio 4.08) were identified as risk factors for anatomical recurrence. The most common adverse event was buttock pain (14.6%), which resolved spontaneously within 4 weeks. CONCLUSIONS: SSLF is an effective surgical method using native tissue for pelvic reconstruction. Compared with concomitant hysterectomy, SSLF with uterine preservation reduces the anatomical recurrence rate.

Long-term effect of extracorporeal shock wave therapy on attenuating radiation-induced chronic cystitis in rat.

BACKGROUND: This study tested the long-term effect of extracorporeal shock wave (ECSW) therapy on ameliorating radiotherapy-induced chronic cystitis (CC) in rat. METHODS AND RESULTS: Adult-female SD rats (n = 24) were equally categorized into group 1 (normal control), group 2 (CC induced by radiotherapy with 450 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.1 mJ/mm2/120 impulses once every 3 days after radiotherapy)]. Bladder specimens were harvested by day 60 after radiotherapy. By day 60, the degree of detrusor contraction was significantly reduced in group 2 than groups 1 and 3, and significantly reduced in group 3 than in group 1 (P < 0.0001). Number of WBC, occulted blood and bacteria were significantly higher in group 2 than in groups 1 and 3 (P < 0.01), but they showed no difference between the latter two groups (P > 0.3). The protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (cleaved-caspase-3/cleaved-PARP), DNA-damaged marker (γ-H2AX), fibrosis (TGF-ß/Smad3) and inflammatory signaling (TLR-4/MYD88/Mal/TRAF6/p-IκBα/p-NFκB/TNF-α/MMP-9/COX-2) were significantly higher in group 2 than in group 1, and were significantly reduced in group 3 (all P < 0.001). The cellular expressions of inflammatory (CD14+/CD68+/MIF+/MMP-9), immunoreactive (CD4+/CD8+) and cytokeratin (CK17/CK18) biomarkers, and collagen-deposition/fibrotic areas as well as bladder-damaged score/disruption of the bladder mucosa displayed an identical pattern compared to that of oxidative stress among the three groups (all P < 0.0001). CONCLUSION: The long-term effect of ECSW treatment was reliable on protecting the urinary bladder from radiation-induced CC.