Changes in bowel symptoms after different pelvic organ prolapse surgeries among elderly women at the 1-year follow up.

OBJECTIVE: To investigate the prevalence of bowel symptoms in patients with pelvic organ prolapse (POP), to evaluate the changes in bowel symptoms after different POP surgeries, and to identify risk factors for unrelieved bowel symptoms. METHODS: This was an observational prospective cohort study conducted at Peking University First Hospital from 2020 to 2021. Demographic, clinical, and therapeutic data were collected. Participants underwent POP Quantification examination and completed the Pelvic Floor Distress Inventory-20 questionnaire at baseline and 1 year postoperatively. RESULTS: The prevalence of bowel symptoms and bothersome bowel symptoms in women with POP was 46.38% and 24.40%, respectively. Surgical correction of prolapse was associated with significant relief in bowel symptoms (P < 0.05). Colpocleisis may relieve bowel symptoms better than reconstructive surgeries (41% vs. 31%, P = 0.048). However, 35% of women had at least one bowel symptom at the 1-year follow up. A long perineal body (Pb) and levator ani muscle injury were found to be predictors of unrelieved bowel symptoms in patients undergoing colpocleisis and those undergoing reconstructive surgery, respectively (odds ratio [OR] 2.306, 95% confidence interval [CI] 1.112-4.783, P = 0.025 and OR 3.245, 95% CI 1.266-8.317, P = 0.014, respectively), and perineoplasty was a protective factor for women who underwent colpocleisis (OR 0.102, 95% CI 0.025-0.417, P = 0.001) CONCLUSION: Women with POP have a high prevalence of bowel symptoms. Although bowel symptoms can be relieved after POP surgeries, one-third of women still experience bowel symptoms. A long Pb and levator ani muscle injury were associated with unrelieved bowel symptoms, while perineoplasty was a protective factor.

Comparison of long-term bowel symptoms after laparoscopic radical hysterectomy versus abdominal radical hysterectomy in patients with cervical cancer.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the long-term bowel symptoms between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in patients with cervical cancer. METHODS: A total of 207 patients who underwent radical hysterectomy (79 underwent LRH and 128 underwent ARH) at Peking University First Hospital from January 2010 to August 2020 were enrolled and their bowel symptoms were investigated using the Colorectal Anal Distress Inventory-8 (CRADI-8) of the Pelvic Floor Distress Inventory-20. The prevalence and severity of bowel symptoms were compared in the LRH and ARH groups, and multivariate analysis was performed to determine the factors associated with bowel symptoms. RESULTS: There was no difference in the CRADI-8 scores between the two groups. However, the prevalence of straining at stool was significantly higher in the ARH group than in the LRH group (19.5% versus 1.3%, p<0.001), and the score was significantly higher in the ARH group than in the LRH group too (0.4 versus 0, p<0.001). The prevalence of incomplete defecation was significantly higher in the ARH group than in the LRH group (13.3% versus 3.8%, p=0.029), and the ARH group also had a significantly higher score than the LRH group (0.3 versus 0.1, p=0.028). Multivariate analysis showed that ARH and postoperative interval were independent risk factors for the development of straining at stool. CONCLUSIONS: Patients with cervical cancer who underwent ARH may be more likely to develop symptoms related to constipation than those who underwent LRH. This finding has to be interpreted with caution owing to the study design.

Assessment of long-term sexual function of cervical cancer survivors after treatment: A cross-sectional study.

OBJECTIVES: This study aimed to investigate the long-term sexual function of patients with cervical cancer who underwent treatment and to explore influential factors. METHODS: This retrospective cross-sectional study was conducted at Peking University First Hospital in (Beijing, China). A total of 207 patients, who were diagnosed with Stage IA-IIA cervical cancer and had undergone surgical treatment (some patients had also been treated with adjuvant radiotherapy and chemotherapy) between January 2010 and August 2020, completed questionnaires via telephone. The median time since diagnosis was 54 (range, 13-138) months. Sexual function was assessed using the validated short form of Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). The multivariate logistic regression analysis was performed to determine factors influencing sexual function after treatment. RESULTS: The mean preoperative PISQ-12 score was 39.42 ± 3.922, and the mean postoperative PISQ-12 score was 32.60 ± 6.592, indicating a significant decrease in postoperative PISQ-12 score compared with preoperation (p < 0.001). In total, 49.8% of the patients had sexual dysfunction after treatment. According to the results of the multivariate logistic regression analysis, longer follow-up (months), ovariectomy, lack of hormone replacement therapy after ovariectomy and adjuvant radiotherapy were significantly associated with sexual dysfunction after treatment (p < 0.05). There was no significant correlation among surgical method, tumor stage, adjuvant chemotherapy, and sexual dysfunction after treatment. CONCLUSIONS: The sexual function of cervical cancer survivors significantly decreased after treatment, which was related to the length of follow-up, ovariectomy, and adjuvant radiotherapy. Hormone replacement therapy after ovariectomy can help patients to improve their sexual function.

Disulfide-stapled design of α-helical bundles to target the trimer-of-hairpins motif of human respiratory syncytial virus fusion protein.

Human respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infections worldwide in infants and young children. The RSV F glycoprotein is a class I fusion protein that mediates viral entry into host cells and is a major target of neutralizing antibodies. Targeting F glycoprotein has been recognized as a promising antiviral therapeutic strategy against RSV infection. Here, we reported the disulfide-stapled design of α-helical bundle to target the trimer-of-hairpins (TOH) motif of RSV F glycoprotein, which is the central regulatory module that triggers viral membrane fusion event. In TOH motif, three N-terminal heptad repeat (NtHR) helices form a trimeric coiled-coil core and other three C-terminal heptad repeat (CtHR) helices add to the core in an antiparallel manner. Interaction analysis between NtHR and CtHR revealed that the C-terminal tail of CtHR packs tightly against NtHR as compared to the N-terminal and middle regions of CtHR. A core binding site in CtHR C-terminus was identified, which represents a 13-mer chp peptide and can effectively interact with NtHR helix in native ordered conformation but would become largely disordered when splitting from the protein context of CtHR helix. Two chp helices were stapled together in a parallel manner with single, double or triple disulfide bridges, thus systematically resulting in seven disulfide-stapled α-helical bundles. Molecular simulations revealed that the double and triple stapling can effectively stabilize the structured conformation of α-helical bundles, whereas the free conformation of single-stapled bundles still remain intrinsically disordered in solvent. The double-stapled bundle chp-ds[508,516] and the triple-stapled bundle chp-ts[508,512,516] were rationally designed to have high potency; they can form a tight three-helix bundle with NtHR helix, thus potently targeting NtHR-CtHR interactions involved in RSV-F TOH motif through a competitive disruption mechanism.

[A retrospective analysis of clinic-pathological characteristics and prognostic factor for 137 cases of breast cancer brain metastasis].

OBJECTIVE: To investigate the clinicopathological characteristics and prognosis in breast cancer with brain metastasis (BCBM). METHODS: The clinical data of 137 BCBM from June 2002 to June 2008 was reviewed and analyzed. Their molecular subtypes were categorized based on detection of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression. The focal area included 35 cases of triple-negative breast cancer (TNBC), 38 cases of HR (ER and PR) (-)/HER-2(+), 40 cases of HR(+)/HER-2(-), 24 cases of HR(+)/HER-2(+). The clinical characteristics and the outcome in patients with influence were analyzed. RESULTS: In 137 BCBM, the median overal survival after brain metastasis was 6.5 month. The median survivals of TNBC, HR(-)/HER-2(+), HR(+)/HER-2(-) and HR(+)/HER-2(+) were 5.0, 5.5, 10.0 and 9.5 months, respectively. The median survivals after brain metastasis of the breast cancer patients who received the combination therapy of whole brain radiation therapy (WBRT) and neurosurgery and/or stereotactic radiosurgery, received WBRT but not combination therapy and didn't receive WBRT were 15.0, 9.5 and 4.0 months, respectively. In univariate survival analysis, substyle, number of brain metastasis, brain metastasis as initial recurrence or not, brain-only metastases or not, the combination therapy status after brain metastasis were obviously correlated with the prognosis (χ(2) = 6.891 to 29.414, P < 0.05). Substyle (RR = 1.234, 95%CI: 1.057 to 1.440) and the combination therapy status after brain metastasis (RR = 1.838, 95%CI: 1.389 to 2.431) were independent prognostic factor in multivariable analysis (P < 0.05). CONCLUSIONS: TNBC confers a high risk of death after brain metastases. Systemic treatment via combined modalities are helpful for breast cancer patients, even after the detection of brain metastases.