What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation.

Objective: At present, Alzheimer's disease (AD) lacks effective treatment means, and early diagnosis and intervention are the keys to treatment. Therefore, for mild cognitive impairment (MCI) and AD patients, blood sample analysis using the 4D nonstandard (label-free) proteomic in-depth quantitative analysis, looking for specific protein marker expression differences, is important. These marker levels change as AD progresses, and the analysis of these biomarkers changes with this method, which has the potential to show the degree of disease progression and can be used for the diagnosis and preventive treatment of MCI and AD. Materials and Methods: Patients were recruited according to the inclusion and exclusion criteria and divided into three groups according to scale scores. Elderly patients diagnosed with AD were selected as the AD group (n = 9). Patients diagnosed with MCI were classified into the MCI group (n = 10). Cognitively healthy elderly patients were included in the normal cognition control group (n = 10). Patients' blood samples were used for 4D label-free proteomic in-depth quantitative analysis to identify potential blood biomarkers. The sample size of each group was expanded (n = 30), and the selected biomarkers were verified by enzyme-linked immunosorbent assay (ELISA) to verify the accuracy of the proteomic prediction. Results: Six specific blood markers, namely, APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8, were detected by 4D label-free proteomic quantitative analysis. These markers showed a statistically significant upregulation trend in the MCI and AD groups compared with the normal cognition control group (P < 0.05). ELISA results showed that the levels of these six proteins in the MCI group were significantly higher than those in the normal cognition control group, and the levels of these six proteins in the AD group were significantly higher than those in the MCI group (P < 0.05). Conclusion: The plasma levels of APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8 in cognitively healthy elderly patients and patients with MCI and AD were significantly different and, more importantly, showed a trend of increasing expression. These results indicate that these six human plasma markers have important diagnostic and therapeutic potential in the identification of cognitive impairment and have value for in-depth research and clinical application.

BODIPY Cored A-D-A'-D-A Type Nonfused-Ring Electron Acceptor for Efficient Polymer Solar Cells.

In this work, boron dipyrromethene (BODIPY) is for the first time employed as electron-deficient core (A') to construct an A-D-A'-D-A type nonfused-ring electron acceptor (NFREA) for polymer solar cells (PSCs). Among, cyclopentadithiophene (CPDT) and fluorinated dicyanoindanone (DFIC) are involved as electron-donating (D) bridges and terminal A groups, respectively. Bearing with the steric BODIPY core, tMBCIC exhibits twisted configuration with dihedral angles >45°  between BODIPY and CPDT bridges. Thus, compared with the BODIPY-free planar A-D-D-A structured bCIC, reduced aggregation, weakened intramolecular D-A interactions with up-shifted lowest unoccupied molecular orbital by 0.4 eV as well as blueshifted absorption by up to 150 nm is observed in tMBCIC. Moreover, owing to the intrinsic large molar extinction coefficient from BODIPY, promoted light-harvest ability is achieved for tMBCIC, particularly in its blend films. Therefore, PSCs by using PBDB-T as donor, tMBCIC as NFREA afford superior power conversion efficiency (PCE) of 9.22% and higher open-circuit voltage (Voc ) of 0.954 V compared to 4.47% and 0.739 V from bCIC-devices. Moreover, compared to other BODIPY-flanked electron acceptors (<5%) reported so far, BODIPY-cored tMBCIC realizes a remarkable progress in PCE.

Tension-free vaginal tape-obturator for the treatment of stress urinary incontinence: a 12-year prospective follow-up.

OBJECTIVE: To evaluate the long-term safety and effectiveness of inside-out transobturator tape (tension-free vaginal tape-obturator, TVT-O) for the treatment of stress urinary incontinence (SUI). PATIENTS AND METHODS: Between August 2004 and August 2006, 87 consecutive patients with SUI who underwent TVT-O were enrolled in this prospective cohort study. Patients with mixed UI, or pelvic organ prolapse requiring surgery, were excluded. Data relating to long-term postoperative complications, subjective satisfaction rate (Patient Global Impression of Improvement), objective cure rate (stress test), quality of life (QoL), and sexual function, were collected during follow-up. The Incontinence Impact Questionnaire (IIQ-7) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were used to assess QoL and sexual function, respectively. Statistical analyses were performed using paired-sample t-tests. RESULTS: At the 12-year follow-up, 73 patients (84%) were available for evaluation. Overall, the long-term complication rate was 45.2%. De novo overactive bladder was observed in 12.3% of patients. None of the patients reported severe voiding dysfunction that required treatment by tape removal or catheterisation. However, 16 patients (16/73, 21.9%) had voiding changes compared with their preoperative status. Persistent groin pain was reported in 1.4% of the patients, and tape exposure occurred in 5.5%. The subjective satisfaction rate and objective cure rate were 80.8% and 82.2%, respectively. Compared with preoperative scores, the IIQ-7 score decreased significantly (P < 0.05), whilst there was no significant difference in the PISQ-12 score (P = 0.893). CONCLUSIONS: This 12-year follow-up study showed that TVT-O is a highly effective procedure for the treatment of SUI. The long-term complication rate appears to be slightly high, which should raise concern.

Tension-Free Vaginal Tape for the Treatment of Stress Urinary Incontinence: A 13-Year Prospective Follow-Up.

STUDY OBJECTIVE: To evaluate the long-term safety and efficacy of tension-free vaginal tape (TVT). DESIGN: Prospective observational study (Canadian Task Force classification II-2). SETTING: Tertiary referral center in China. PATIENTS: Between January 2004 and December 2005, 85 consecutive patients who underwent the TVT procedure were included. Patients with mixed incontinence or pelvic organ prolapse requiring surgery were excluded. INTERVENTIONS: TVT procedure. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were long-term postoperative complications. The secondary outcomes included long-term subjective satisfaction (Patient Global Impression of Improvement), objective cure rate (stress test), quality of life, and sexual function. At the 13-year follow-up, 70 patients (82%) were available for evaluation. De novo overactive bladder was observed in 15.7% of patients, and voiding symptoms were found in 17.1% of patients. None of the patients reported voiding dysfunction that needed treatment with tape removal or catheterization. Tape exposure occurred in 2.9% of patients. The subjective satisfaction rate and objective cure rate were 78.6% and 81.4%, respectively. CONCLUSION: TVT is a safe and effective treatment for stress urinary incontinence, even at the 13-year follow-up. The prevalence rates of overactive bladder and voiding symptoms are increased with advancing age and should not be considered long-term postoperative complications.

Induction of human umbilical cord mesenchymal stem cells into tissue-forming cells in a murine model: implications for pelvic floor reconstruction.

HUMSCs were isolated, differentiated and characterized in vitro. Both HUMSCs and smooth muscle cells differentiated from HUMSCs were used to fabricate tissue-engineered fascia equivalents. Forty-eight mature female Sprague Dawley rats were randomly assigned to four groups: group A (GynemeshTMPS, n = 12), group B (GynemeshTMPS + HUMSCs; n = 12), group C (GynemeshTMPS + smooth muscle cells differentiated from HUMSCs; n = 12) and group D (GynemeshTMPS + HUMSCs + smooth muscle cells differentiated from HUMSCs; n = 12). The posterior vaginal wall was incised from the introitus and the mesh was then implanted. Three implants of each type were tested at 1, 4, 8 and 12 weeks. Fibrotic remodeling, inflammation, vascularization and tissue regeneration were histologically assessed. The levels of type I and type III collagen were determined. There was no difference in fibrotic remodeling between cell-seeded and unseeded meshes at any time (p > 0.05). At 12 weeks, there did not appear to be fewer inflammatory cells around the filament bundles in the mesh with cells compared with the mesh alone (P > 0.05). Group D showed a trend toward better vascularization at 12 weeks compared with group A (P < 0.05). Twelve weeks after implantation, a thin layer of new tissue growth covered the unseeded scaffold and a thicker layer covered the cell-seeded scaffold (P < 0.05). No significant difference in the ratio of collagen type I/III could be detected among the different groups after 12 weeks (P > 0.05). HUMSCs with differentiated smooth muscle cells might have a potential role in fascia tissue engineering to repair POP in the future.

Edge defect switched dual spin filter in zigzag hexagonal boron nitride nanoribbons.

Unlike graphene nanoribbons, zigzag monolayer hexagonal boron nitride nanoribbons (ZBNNRs) possess two distinct edges (B and N edges). Using first-principles calculations, we investigate the spin-dependent electronic transport of ZBNNRs with edge defects. It is found that the defects could make the system operate as a dual spin filter, where the direction of spin polarization is switched by the defect. Further analysis shows that the transmission eigenchannels for the opposite spins reside spatially separated on opposite edges. The defect on one edge could suppress the transmission for only one spin component, but preserve that for the other spin, resulting in a dual spin filter effect. This effect is found to be unaffected by the width of the ribbon and the length of the defect. Moreover, by constructing defects on both edges, the system exhibits two transmission peaks with opposite spins residing discretely on both sides of the Fermi level, suggesting that an electrically controlled dual spin filter based on ZBNNRs is also realizable. As controllable defects have been experimentally fabricated on monolayer boron nitride [T. Pham, A. L. Gibb, Z. Li, S. M. Gilbert, C. Song, S. G. Louie and A. Zettl, Nano Lett., 2016, 16, 7142-7147], our results may shed light on the development of B/N-based spintronic devices.

Changes in voiding function after laparoscopic sacrocolpopexy for advanced pelvic organ prolapse: a cohort study of 76 cases.

INTRODUCTION AND HYPOTHESIS: We evaluated changes in voiding function at 3 months after laparoscopic sacrocolpopexy (LSC) for advanced pelvic organ prolapse (POP) patients and identified risk predictors for postoperative voiding dysfunction. METHODS: Seventy-six patients with advanced POP who underwent LSC were enrolled in this retrospective cohort study. Pre- and postoperative objective voiding function was assessed by uroflowmetry plus postvoid residual (PVR) volumes. Voiding dysfunction was defined as a maximum flow rate (Qmax) < 15 ml/s, average flow rate (Qave) < 10 ml/s, or PVR > 50 ml. Statistical analyses were performed using paired-sample t tests, McNemar's tests, and multivariate regression analyses. RESULTS: Thirty patients (39%) showed evidence of voiding dysfunction preoperatively, but two thirds of these patients were asymptomatic. Voiding dysfunction decreased significantly from baseline to 3 months after surgery (39% vs. 21%, p = 0.009), including a decrease among patients with Qave < 10 ml/s (32% vs. 17%, p = 0.043) and PVR > 50 ml (24% vs. 9%, p = 0.019). Voiding difficulty decreased significantly from baseline to 3 months after surgery (32% vs. 9%, p < 0.001); urgency and urinary incontinence symptoms did not exhibit significant improvement (p > 0.05). Multivariate analysis identified Qave < 10 ml/s as the independent predictor of postoperative voiding dysfunction [p = 0.014, odds ratio (OR) = 4.77, 95% confidence interval (CI) 1.37-16.54]. CONCLUSIONS: Preoperative voiding dysfunction is common among patients with POP and significantly improves at 3 months following LSC. A preoperative Qave < 10 ml/s was an independent risk factor for postoperative voiding dysfunction.

The value of the preoperative 1-h pad test with pessary insertion for predicting the need for a mid-urethral sling following pelvic prolapse surgery: a cohort study.

PURPOSE: Part of the patients with pelvic organ prolapse but without symptoms of stress urinary incontinence (SUI) may demonstrate SUI after prolapse surgery (occult SUI), and no optimal preoperative screening method is currently available for it. The aim of this study was to estimate the value of the preoperative 1-h pad test with pessary insertion for predicting the need for a mid-urethral sling (MUS) following prolapse surgery. METHODS: Two hundred and six patients were enrolled for advanced prolapse without complaining of urinary incontinence (UI) in this prospective cohort study. Exclusion criteria included prior or concomitant anti-incontinence surgery. Preoperatively, a stress test, the 1-h pad test and uroflowmetry were performed with prolapse reduction. Primary outcome was postoperative de novo UI. Median follow-up was 31 months (range 12-48 months). RESULTS: Of the 206 patients, 45 (21.8 %) had evidence of occult SUI preoperatively, 62 (30.1 %) exhibited de novo UI postoperatively, and only 13 (6.3 %) opted MUSs. Patients with occult SUI experienced higher de novo UI rate (53.3 vs. 23.6 %; P = 0.000). The OSUI and concomitant hysterectomy were identified as independent risk factors related to de novo UI (P = 0.000, P = 0.044). We performed receiver operating characteristic (ROC) curve analysis to evaluate the value of preoperative 1-h pad test. The area under ROC curve was 0.816 ± 0.085 (95 % CI 0.649-0.983); the cutoff value was 1.9 g (sensitivity 80.0 %, specificity 83.9 %). CONCLUSIONS: The preoperative 1-h pad test with prolapse reduction is feasible for screening occult SUI, and more than 1.9 g may be a practical indicator of a postoperative subsequent MUS.

Which factors should be considered in choosing pessary type and size for pelvic organ prolapse patients in a fitting trial?

INTRODUCTION AND HYPOTHESIS: This study explored whether the optimal pessary type and size can be predicted using the specific pelvic organ prolapse quantification system (POP-Q) measurements in women with pelvic organ prolapse in a fitting trial. METHODS: We conducted a prospective study in women who had undergone pessary fitting. A total of 78 patients with stage II, III or IV symptomatic pelvic organ prolapse completed a detailed history. Data were analysed using nonparametric tests, continuity correction chi-squared tests and multivariate logistic regression. RESULTS: Differences in total vaginal length (TVL; p < 0.01) and vaginal introitus width/TVL ratio (p = 0.012) were observed between patients with and without a history of hysterectomy. Patients with a history of hysterectomy and patients with a larger vaginal introitus had more success with the Gellhorn pessary than with the ring pessary with support (p = 0.005 and p = 0.01, respectively). Factors determining the size of the ring pessary with support were the genital hiatus (GH) width (p = 0.044), TVL (p = 0.011), vaginal introitus width (p < 0.001), and vaginal introitus width/TVL ratio (p = 0.025). Factors determining the size of the Gellhorn pessary were the GH width (p = 0.025), GH width/TVL ratio (p = 0.013), vaginal introitus width (p = 0.003), vaginal introitus width/TVL ratio (p = 0.001), stage of apical prolapse (p = 0.006) and stage of posterior prolapse (p = 0.003). CONCLUSIONS: Patients with a history of hysterectomy or with a larger vaginal introitus were more likely to achieve success with the Gellhorn pessary. The GH width and the vaginal introitus width influenced the size of both pessaries chosen. The TVL was predictive of the optimal size of the ring pessary with support but was not predictive of the optimal size of the Gellhorn pessary. Finally, the size of the Gellhorn pessary was associated with POP stage.

Successful use of ring pessary with support for advanced pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Support pessaries are not recommended for patients with advanced prolapse. This study aimed to explore the efficacy of the ring pessary with support for the treatment of advanced pelvic organ prolapse (POP). METHODS: We conducted this prospective study on pessary fittings performed between November 2013 and September 2014 at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Beijing. A total of 109 patients with stage III or IV POP completed a detailed history. A successful fitting was defined as the continued use of the device for over 3 months from the initial fitting. Data were analyzed with the Wilcoxon rank-sum test, independent sample t tests, continuity correction χ(2) tests, and Fisher's exact test. RESULTS: A total of 74.3 % (81/109) of the patients were successfully fitted with the ring pessary with support at the initial visit. Among those women with a successful initial fitting, the failure rate was less than 10 % (8/81) at 3 months. Furthermore, 82.7 % (67/81) of the patients were able to manage the pessary by themselves. Seven patients experienced vaginal erosion. There was no association of prolapse stage and the predominant prolapse compartment with pessary trial outcome. The average vaginal length of the patients with successful pessary use was 7.58 cm. CONCLUSIONS: The ring pessary with support was successfully fitted in patients with advanced POP with a high success rate and few complications. Older patients were more likely to prefer the ring pessary with support due to its convenient use.

The protective effect of Lonicera japonica Thunb. against lipopolysaccharide-induced acute lung injury in mice: Modulation of inflammation, oxidative stress, and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Various components of Lonicera japonica Thunb. (LJT) exhibit pharmacological activities, including anti-inflammatory and antioxidant effects. Nevertheless, the relationship between LJT and ferroptosis remains largely unexplored. AIM OF THE STUDY: The purpose of this research was to look into the role of LJT in regulating LPS-induced ferroptosis in ALI and to compare the effects of different parts of LJT. MATERIALS AND METHODS: We established a mice ALI model by treating with LPS. Administered mice with different doses of Lonicerae Japonicae Flos (LJF), Lonicera Japonica Leaves (LJL) and Lonicerae Caulis (LRC) extracts, respectively. The levels of IL-6, IL-1ß, TNF-α, IL-4, IL-10, and PGE2 in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay. Furthermore, the concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and total ferrous ions (Fe2+) in lung tissues were evaluated. Hematoxylin and eosin staining was conducted to examine the morphological structure of lung tissues. Transmission electron microscopy was used to investigate the ultrastructural morphology of mitochondria. Furthermore, the effects of LJT were evaluated via immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction analyses. Finally, employing molecular docking and molecular dynamics research techniques, we aimed to identify crucial components in LJT that might inhibit ferroptosis by targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). RESULTS: We observed that pretreatment with LJT significantly mitigated LPS-induced lung injury and suppressed ferroptosis. This was supported by reduced accumulation of pro-inflammatory cytokines, ROS, MDA, and Fe2+, along with increased levels of anti-inflammatory cytokines, SOD, GSH, Nrf2, and GPX4 in the lung tissues of ALI mice. Luteolin-7-O-rutinoside, apigenin-7-O-rutinoside, and amentoflavone in LJT exhibit excellent docking effects with key targets of ferroptosis, Nrf2 and GPX4. CONCLUSIONS: Pretreatment with LJT may alleviate LPS-induced ALI, possibly by suppressing ferroptosis. Our initial results indicate that LJT activates the Nrf2/GPX4 axis, providing protection against ferroptosis in ALI. This finding offers a promising therapeutic candidate for ALI treatment.

Long-term outcome and fertility results of intraplacental choriocarcinoma: a retrospective study of 14 patients and literature review.

BACKGROUNDS: Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. RESULTS: Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of "fear and worry about choriocarcinoma recurrence". We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. CONCLUSIONS: IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. CLINICAL TRIAL REGISTRATION: N/A.

De novo urinary incontinence and lower urinary tract symptoms after colpocleisis: A single-center prospective study.

Background: Colpocleisis is one of traditional surgical procedures for elderly and frail women with advanced pelvic organ prolapse. The occurrence of de novo urinary incontinence following colpocleisis was considered to impair the postoperative quality of life. The incidence of de novo urinary incontinence after colpocleisis has been reported to be ranging from 6.6 % to 27 %. There was an absence of prospective large-sample study to investigate the accurate incidence of de novo urinary incontinence following colpocleisis and the impact on the quality of life till now. Purpose: s The primary objective was to report the incidence of de novo urinary incontinence after colpocleisis. The second objectives were to evaluate the long-term quality of life in patients with de novo urinary incontinence, and to conduct detailed pre- and post-operative evaluations of lower urinary tract symptoms. Methods: This prospective study included 253 patients with symptomatic pelvic organ prolapse who underwent colpocleisis between 2009 and 2021. De novo urinary incontinence was defined as the occurrence of urinary incontinence 3 months postoperatively. All patients were required to complete the Urinary Distress Inventory questionnaire and the Urinary Impact Questionnaire for the evaluation of patients' quality of life, and the Patient Global Impression of Improvement questionnaire for the evaluation of patients' satisfaction. Results: 245 patients (245/253, 96·8 %) completed the 3-month follow-up, and were included in the final analysis. The incidence of de novo urinary incontinence was 5.4 % (10/185). There was no significant difference in the Urinary Distress Inventory -6 scores (22.50 vs. 10.30, P = 0.276) or the subjective satisfaction rate (100 % vs. 98.9 %, P = 0.250) between the patients with or without de novo urinary incontinence at the long-term follow-up. The incidence of voiding difficulty was significantly reduced after colpocleisis (27.8 % vs. 0.0 %, P < 0.001). The patients' quality of life indicated by Urinary Distress Inventory-6 and Urinary Impact Questionnaire-7 scores were significantly improved postoperatively (26.27 vs. 13.39, and 19.13 vs. 6.05, P < 0.05). Conclusion: The incidence of de novo urinary incontinence after colpocleisis was very low. Patients' quality of life, and low urinary tract symptoms were significantly improved after colpocleisis.

Case Report: Management of Recurrent Ovarian Squamous Cell Carcinoma With PD-1 Inhibitor.

Malignant transformations, such as ovarian squamous cell carcinoma (SCC) in ovarian mature cystic teratoma (OMCT), are rare tumors. The management of recurrent disease is still a challenge, and the gene mutations involved remain unclear. We herein report a recurrent case of ovarian SCC with a PIK3CA gene variation and immunohistochemical staining of programmed death-ligand 1 (PD-L1) >10%. This patient achieved clinical remission after platinum-based effective chemotherapy and programmed death 1 (PD-1) immunotherapy.

Multiple CAR-T cell therapy for acute B-cell lymphoblastic leukemia after hematopoietic stem cell transplantation: A case report.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. The cure rate has reached 90% after conventional chemotherapy and hematopoietic stem cell transplantation (HSCT), but the prognosis of patients with relapsed and refractory (R/R) leukemia is still poor after conventional treatment. Since FDA approved CD19 CAR-T cell (Kymriah) for the treatment of R/R B-ALL, increasing studies have been conducted on CAR-T cells for R/R ALL. Herein, we report the treatment of a patient with ALL who relapsed after allogeneic HSCT, had a complete remission (CR) to murine scFv CD19 CAR-T but relapsed 15 months later. Partial response was achieved after humanized CD19 CAR-T treatment, and the patient finally achieved disease-free survival after sequential CD22 CAR-T treatment. By comparing the treatment results of different CAR-T cells in the same patient, this case suggests that multiple CAR-T therapies are effective and safe in intramedullary and extramedullary recurrence in the same patient, and the expansion of CAR-T cells and the release of inflammatory cytokines are positively correlated with their efficacy. However, further clinical studies with large sample sizes are still needed for further clarification.

Burch colposuspension for stress urinary incontinence: a 14-year prospective follow-up.

We aimed to evaluate the long-term effectiveness and safety of Burch colposuspension (BC) for stress urinary incontinence (SUI). In this prospective cohort study, 84 patients with SUI undergoing BC were enrolled from February 2004 to January 2010. Data on long-term subjective success and postoperative complications were collected at clinic visits and by telephone follow-up. During a mean follow-up period of 14.2 years, 68% (57/84) patients completed the follow-up. A total of 68.4% of patients (39/57) reported absence of SUI symptoms, 73.6% (42/57) were subjectively satisfied according to the Patient Global Impression of Improvement, and 68.4% (39/57) reported subjective success regarding urinary symptoms via the Urinary Distress Inventory Short Form. However, 28.1% (16/57) suffered at least one long-term postoperative complication and incident. Specifically, 1 in 25 (4.0%) sexually active patients reported dyspareunia, 3 patients (5.3%) had de novo overactive bladder, and 6 patients (10.5%) reported voiding dysfunction. Four patients (7.0%) reported new onset prolapse symptoms, and 3 patients (5.3%) underwent secondary urinary incontinence surgery. Our study indicated that Burch colposuspension is an effective procedure for SUI, and the cure effect was largely maintained for the 14-year follow-up period, with relatively low complication rates. BC should be considered a surgical option for SUI.

Antimicrobial therapy and the potential mechanisms in Alzheimer's disease.

Alzheimer's disease treatments have been a heavily investigated research area, however, new drugs have failed one after another. Some scientists have begun to reposition drugs, including antimicrobial agents. Here, the treatment effects of nine antimicrobial agents on Alzheimer's disease and their possible therapeutic mechanisms are described to clarify their efficacy. In vivo and in vitro studies are quite encouraging and tend to demonstrate that antimicrobial therapy is effective in Alzheimer's disease. Nevertheless, unsatisfactory clinical efficacy, side effects, and insufficient knowledge have yet to be overcome. Further laboratory and clinical studies are required to recommend antimicrobial treatment regimens.

Adjuvant therapy in conservative surgery for adenomyosis.

OBJECTIVE: To investigate the significance of perioperative levonorgestrel-releasing intrauterine system (LNG-IUS) and/or gonadotropin-releasing hormone agonists (GnRHa) as adjuvant therapy in preventing recurrences or progression of diseases. METHODS: Medical records were collected from patients diagnosed with adenomyosis who underwent uterus-sparing surgeries from March 1, 2012 to December 31, 2018. The associations of perioperative adjuvant therapy with recurrence of disease and symptoms were analyzed with the Kaplan-Meier method and proportional hazards models with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 322 eligible patients were included, of whom 173 (58.1%) received perioperative adjuvant therapy. Perioperative adjuvant therapy (HR 0.44, 95% CI 0.22-0.91, P = 0.022) and perioperative GnRHa therapy (HR 0.48, 95% CI 0.24-0.99, P = 0.042) significantly reduced disease recurrence. No patient using perioperative LNG-IUS therapy experienced recurrence. In the multivariate analysis, increased age (>35 years at surgery) was the only risk factor for disease recurrence (HR 2.35, 95% CI 1.01-5.45, P = 0.047). CONCLUSION: Perioperative adjuvant therapy with GnRHa and/or the LNG-IUS can significantly reduce disease recurrence or progression for adenomyosis patients undergoing uterus-sparing surgery. Older patients are more likely to experience disease recurrence.

Selection of Treatment Regimens for Recurrent Cervical Cancer.

OBJECTIVE: The selection of individualized treatment for recurrent cervical cancer is challenging. This study aimed to investigate the impact of various therapies on survival outcomes after recurrence. METHODS: Eligible patients were diagnosed with recurrent cervical cancer between March 2012 and April 2018. Postrecurrence progression-free survival (PFS) and overall survival (OS) were investigated in the whole cohort and in subgroups, categorized by recurrence site and prior radiotherapy history, using a multivariate model that incorporated treatment for primary and recurrent tumors, histological pathology, and FIGO staging. RESULTS: Two hundred and sixty recurrent cervical cancer patients were included. As of March 1, 2020, the median postrecurrence PFS and OS were 7.0 (range 0-94) and 24.0 (1.8-149.1) months, respectively. In a multivariate model measured by PFS, radiotherapy was superior to other therapies for the whole cohort (p=0.029) and recurrence only within the pelvic cavity (p=0.005), but the advantages of radiotherapy disappeared in patients with a history of radiotherapy (p values >0.05). For recurrence only beyond the pelvic cavity, combination therapy resulted in improved PFS (p=0.028). For recurrence both within and beyond the pelvic cavity, no therapy regimen provided additional PFS benefits (p values >0.05). Radiotherapy and combination therapy were also associated with improved postrecurrence OS for recurrence within the pelvic cavity (p=0.034) and only beyond the pelvic cavity (p=0.017), respectively. CONCLUSIONS: In cervical cancer patients, postrecurrence radiotherapy can improve PFS and OS for patients with recurrence within the pelvic cavity and without prior radiotherapy. For recurrence beyond the pelvic cavity or cases with a history of radiotherapy, combination or individualized therapy may provide potential survival benefits.

Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas.

The association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV- groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV- group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV- group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.