A predictive model for therapy failure in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy.

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

Pre- vs Post-Operative Levator Ani Subtended Volume in Patients Undergoing Hysterectomy: A Comparative Imaging Study.

INTRODUCTION AND HYPOTHESIS: The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM. METHODS: This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV. RESULTS: High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm3 and 18.87 cm3 respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact. CONCLUSIONS: Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

Comparing carbon nanoparticles and indocyanine green for sentinel lymph node mapping in endometrial cancer: A randomized-controlled single-center trial.

BACKGROUND AND OBJECTIVES: To compare the feasibility and diagnostic value of sentinel lymph node (SLN) mapping with carbon nanoparticles (CNPs) and indocyanine green (ICG) in endometrial cancer (EC). METHODS: This was a single-center, open-label, randomized controlled trial. Between August 1, 2020 and April 30, 2022, patients with early-stage EC were assessed for enrollment. All patients underwent SLN mapping with ICG or CNPs ± pelvic and/or para-aortic lymphadenectomy. The detection rate (DR), its impact factors, the sensitivity and the negative predictive value (NPV) of SLN mapping were analyzed. RESULTS: In total, 206 patients, with 103 per group, were included. The overall and bilateral DRs of the two groups were comparable without significant differences. There was no difference regarding the distribution of mapped SLNs. The sensitivity was 66.7% for both groups, and the NPVs were not significantly different. Furthermore, the sensitivity and NPV reached 100% when calculated either per hemipelvis or only in patients with bilateral SLN detection. CONCLUSIONS: SLN mapping by CNPs in EC is feasible with high DRs and diagnostic accuracy compared with ICG. CNPs might be an alternative to ICG for SLN mapping when near-infrared imaging equipment is lacking, especially in stage IA patients.

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma.

BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

Gestational diabetes mellitus and pelvic floor function 6 weeks postpartum in Chinese women.

INTRODUCTION AND HYPOTHESIS: With the significant increase in its incidence, gestational diabetes mellitus (GDM) has received growing attention for its effect on pelvic floor function. This study was aimed at investigating the association of GDM with pelvic floor function and diastasis recti abdominis (DRA) in postpartum women. METHODS: This is a retrospective cohort study. At 6 weeks postpartum, 1,133 postpartum women with vaginal delivery underwent routine examinations including measurement of the pelvic floor muscle (PFM) strength and endurance, determination of the stress urinary incontinence (SUI) by questionnaire, quantification of pelvic organ prolapse (POP) and assessment of DRA. Statistical analysis was performed using binary logistic regression and multiple linear regression analysis. RESULTS: One hundred and seventy-six (176) of the 1,133 women were confirmed to be suffering from GDM, with a rate of 15.53% (176 out of 1,133). The age and pre-pregnancy body mass index of the GDM group were significantly higher than those without GDM (p < 0.05). The GDM group was more likely to have smaller gestational age and a higher chance of having to undergo a lateral episiotomy. No statistically significant differences are found in PFM endurance (B: -0.025, p = 0.462) or PFM strength (B: -0.001, p = 0.979) between women with and without GDM. And these two groups are not significantly different in terms of the prevalence of SUI (19.3% vs 20.4%), POP (35.8% vs 37.5%) and DRA (29.0% vs 25.8%; p > 0.05). CONCLUSIONS: Pelvic floor muscle function and SUI/POP/DRA prevalence of women at 6 weeks postpartum are not significantly affected by GDM.

Help-seeking behavior for nonsevere stress urinary incontinence among elderly women in communities, Beijing, China.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is a common health problem and influences women's quality of life significantly. In order to enhance health education according to a specific situation, it is essential to identify barriers to seeking help among elderly women with nonsevere SUI. The objectives were to investigate reasons for (not) seeking help for nonsevere SUI among women aged ≥60 years, and to analyze factors affecting help-seeking behavior. METHODS: We enrolled 368 women aged ≥60 years with nonsevere SUI from communities. They were asked to filled out sociodemographic information, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Incontinence Quality of Life (I-QOL), and self-constructed questiones on help-seeking behavior. Mann-Whitney U tests were used to analyze the different factors between seeking group and nonseeking group. RESULTS: Only 28 women (7.61%) had ever sought help from health professionals for SUI. The most frequent reason for seeking help was urine-soaked clothes (67.86%, 19 out of 28). The most frequent reason for not seeking help was that women thought it was normal (67.35%, 229 out of 340). Compared with the nonseeking group, the seeking group had higher total ICIQ-SF scores and lower total I-QOL scores. CONCLUSION: Among elderly women with nonsevere SUI, the rate of seeking help was low. Lack of correct perception about the SUI kept women from doctor visits. Women who were bothered by more severe SUI and lower quality of life were more likely to seek help.

Eclampsia as the First Manifestation of Primary Hyperparathyroidism: a Case Report.

BACKGROUND: This study aimed to explore the diagnosis and treatment strategies of eclampsia during pregnancy and postpartum acute pancreatitis caused by primary hyperparathyroidism. METHODS: This study reported a 26-year-old patient who had maternal eclampsia as her first symptom and was admitted to the hospital. The pregnancy was terminated by cesarean section immediately. Postpartum life-threatening complications, such as severe hypercalcemia and acute pancreatitis, occurred afterward. Following completion of the relevant examination, primary hyperparathyroidism was initially considered to be the cause. Symptomatic treatment is ongoing and will be improved, and the patient will be admitted again for parathyroidectomy. RESULTS: The patient gave birth to a premature neonate via cesarean section. The postpartum diagnosis was primary hyperparathyroidism, for which post-surgical pathology showed a parathyroid adenoma. CONCLUSIONS: The clinical manifestations of pregnancy with primary hyperparathyroidism are atypical but may cause serious maternal and fetal complications. Early diagnosis and appropriate treatment can prevent serious prenatal and postnatal complications and foster better pregnancy outcomes.

A rapid and highly sensitive multiple detection of human adenovirus type 3, type 7 and respiratory syncytial virus by recombinase-aided reverse transcription PCR.

BACKGROUND: Polymerase chain reaction (PCR) has been widely used for many pathogen detection. However, PCR technology still suffers from long detection time and insufficient sensitivity. Recombinase-aided amplification (RAA) is a powerful nucleic acid detection tool with high sensitivity and amplification efficiency, but its complex probes and inability of multiplex detection hinder the further application of this technology. METHODS: In this study, we developed and validated the multiplex reverse transcription recombinase-aided PCR (multiplex RT-RAP) assay for human adenovirus 3 (HADV3), human adenovirus 7 (HADV7), and human respiratory syncytial virus (HRSV) within 1 h with Human RNaseP protein as a reference gene to monitor the whole process. RESULTS: Using recombinant plasmids, the sensitivity of multiplex RT-RAP for the detection of HADV3, HADV7, and HRSV was 18, 3, and 18 copies per reaction, respectively. The multiplex RT-RAP showed no cross-reactivity with other respiratory viruses, demonstrating its good specificity. A total of 252 clinical specimens were tested by multiplex RT-RAP and the results were found to be consistent with those of corresponding RT-qPCR assays. After testing serial dilutions of selected positive specimens, the detection sensitivity of multiplex RT-RAP was two to eightfold higher than that of corresponding RT-qPCR. CONCLUSION: We conclude the multiplex RT-RAP is a robust, rapid, highly sensitive, and specific assay with the potential to be used in the screening of clinical samples with low viral load.

Comparison of sentinel lymph node distribution and lymphatic drainage pathway between high- and low-risk endometrial cancers.

PURPOSE: This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. METHODS: In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. RESULTS: The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. CONCLUSION: The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping.

Acceleration of pelvic tissue generation by overexpression of basic fibroblast growth factor in stem cells.

BACKGROUND: Pelvic organ prolapse (POP) is a common debilitating condition affecting approximately 30-40% of women. The FDA issued a warning about polypropylene mesh used for pelvic floor repair due to erosion, exposure and other complications and banned it in 2019. The application of stem cell therapy and growth factors has strongly promoted the development of pelvic tissue engineering. PURPOSE: we intend to address the issues of direct application of growth factors, the side effects of long-term exogenous treatment, and the directional differentiation of stem cells. Methods: we evaluated the paracrine effects and directional differentiation of adipose mesenchymal stem cells through stable overexpression of basic fibroblast growth factor (bFGF). RESULTS: we found that the modified stem cells could continuously and stably release bFGF in the initial stage and could spontaneously differentiate into fibroblasts with a high differentiation efficiency in the later stage. CONCLUSION: following ADSCs are designed to continuously release controllable levels of growth factors during the control period of repair, taking advantage of the paracrine function of stem cells to accelerate cell growth and extracellular matrix (ECM) reconstruction during the early stage of stem cell implantation, and then stem cells are differentiated into target tissues-fibroblasts to accelerate the reconstruction of pelvic floor tissues, this study demonstrated the strong therapeutic potential of this approach for pelvic tissue engineering. ABBREVIATIONS: POP: Pelvic organ prolapse; ADSCs: Adipose-derived stem cells; bFGF: Basic fibroblast growth factor; BMSCs: Bone marrow-derived mesenchymal stem cells; HUVECs: Human umbilical vein endothelial cells; EMSCs: Endometrial mesenchymal stem cells; VEGF: Vascular endothelial growth factor; PDGF: Platelet-derived growth factor ECM: Extracellular matrix; IGF: Insulin-like growth factor; HGF: Hepatocyte growth factor; EGF: Epidermal growth factor; BMP-2: Bone morphogenetic protein 2; FBR: Foreign body reaction.

Discovery of EGFR-Targeted Environment-Sensitive fluorescent probes for cell imaging and efficient tumor detection.

Overexpression of human epidermal growth factor receptor (EGFR) plays an important role in several signaling pathways inside and outside the cell, especially in the processes of cell proliferation, differentiation, and death in various cancers. Due to the complexity of the structure and function of EGFR, research on the fluorescence visualization of EGFR protein visualization has proved challenging. One possible strategy for designing a receptor-targeting fluorescent probe with a switching mechanism is to introduce an environment-sensitive fluorophore into the drug ligand. Based on this strategic molecular design, we introduced two environment-sensitive small molecular fluorophores, dansyl chloride (DNS) and nitrobenzoxadiazole (NBD), to replace the morpholine group of gefitinib, achieving a series of fluorescent molecular probes bearing a switching mechanism. The GN probes exhibited prominent environment sensitivity, suggesting good performance as turn-on EGFR-targeting fluorescent ligands. The representative probe GN3 specifically responded to tumor cells overexpressing EGFR, which was validated with live-cell fluorescence imaging and in vivo xenograft tumor imaging. Ligand-induced EGFR phosphorylation in A431 cells was considerably inhibited by probe GN3, demonstrating that this probe still functions as an EGFR inhibitor. Owing to the turn-on response of GN3 to EGFR in tumor cells, and the competitive replacement behavior to the EGFR inhibitor gefitinib, these probes have the potential to be used for fluorescence imaging of cells overexpressing EGFR.

The association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy in primary school students.

PURPOSE: To study the association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy (ß-PPA) in 8-11 years old primary school students. METHODS: This study was a prospective, school-based investigation. This study included 610 children (1008 eyes) who were continuously observed and had data available from 2016 to 2017 in the Sanhe Cohort Study of the Risk Factors for Myopia (SCSRFM). The children underwent a comprehensive eye examination including measurement of visual acuity, autorefractometry, and posterior segment of the eye. ß-PPA regions and optic disc ovality index were identified and measured on the fundus photographs. RESULTS: The prevalence of myopia was 72.62% (732/1008) in 2016. In myopic children, the prevalence of the vertical ß-PPA, the horizontal ß-PPA, and the oval optic disc were 75.68% (554/732), 75.96% (556/732) and, 11.61% (85/732) respectively. From 2016 to 2017, with the progression of vertical ß-PPA, horizontal ß-PPA, area of ß-PPA, and optic disc ovality index, the myopic diopter and the axial length (AL) were increased. The progression of horizontal ß-PPA was significantly correlated with the progression of myopic diopter and AL (all p < 0.05). The analysis on the distribution of progression rate of parameters in different groups found that the progression rate of horizontal ß-PPA, area of ß-PPA, and optic disc ovality index increased with the increase of the progression of diopter and AL. The progression of horizontal ß-PPA, area of ß-PPA, optic disc ovality index, and diopter in girls were greater than that in boys, and the progression of optic disc ovality index and diopter had a statistical significance (all p < 0.05). CONCLUSIONS: The 1-year follow-up study of the third-grade primary school students showed that with the progression of myopia and the growth of AL, ß-PPA and optic disc ovality index also changed. There was a positive correlation between the change of ß-PPA and optic disc ovality index and the progression of myopia diopter and AL.

Evaluation of pelvic floor muscle function (PFMF) in cervical cancer patients with Querleu-Morrow type C hysterectomy: a multicenter study.

INTRODUCTION: To evaluate the pelvic floor muscle function (PFMF) of cervical cancer patients after type QM-C hysterectomy and to explore the relationship between decreased PFMF and related factors. METHODS: This was a multi-centered retrospective cohort study. 181 cervical cancer patients who underwent type QM-C hysterectomy were enrolled from 9 tertiary hospitals. Strength of PFMF were measured using neuromuscular apparatus (Phenix U8, French). Risk factors contributing to decreased PFMF were analyzed by univariate and multivariate ordinal polytomous logistic regression. RESULTS: Totally 181 patients were investigated in this study. 0-3 level of type I muscle fibre strength (MFSI) was 52.6% (95/181), 0-3 level of type IIA muscle fibre strength (MFSIIA) was 50% (91/181). Subjective stress urinary incontinence was 46% (84/181), urinary retention was 27.3% (50/181), dyschezia was 41.5% (75/181), fecal incontinence was 9% (18/181). ① MFSI: Multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05), chemotherapy and radiotherapy (p = 0.038) are independent risk factors of MFSI's reduction after type QM-C hysterectomy. ② MFSIIA: multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05) are independent risk factors of MFSIIA's reduction after type QM-C hysterectomy. The pelvic floor muscle strength (PFMS) increased after 9 months than in 9 months after operation, which showed that the PFMS could be recovered after operation. CONCLUSIONS: We advocate for more attention and emphasis on the PFMF of Chinese female patients with cervical cancer postoperation. PEKING UNIVERSITY PEOPLE'S HOSPITAL: PFMF after QM-C hysterectomy has not been analyzed by current study. The contribution is that patients with radical hysterectomy should do pelvic floor rehabilitation exercises in 3 months after operation. Clinical Trails NCT number of this study is 02492542.

Carbon nanoparticles combined with indocyanine green for sentinel lymph node detection in endometrial carcinoma.

OBJECTIVE: To evaluate the feasibility and clinical value of the combination of carbon nanoparticles (CNPs) and indocyanine green (ICG) for identifying sentinel lymph nodes (SLNs) in endometrial cancer. MATERIALS AND METHODS: About 153 patients with endometrial cancer were recruited from July 2015 to May 2019. All patients underwent SLN biopsy according to the SLN algorithm for surgical staging with ICG and/or CNPs. The detection rate, factors associated with the detection rate, sensitivity, and negative predictive value (NPV) of SLNs were analyzed. RESULTS: The detection rates of SLNs with the combined method were the highest among the different methods. As calculated per hemipelvis, the sensitivity and NPV with ICG alone or with ICG plus CNPs were 100%. With CNP, tumor Grade 3 and laparoscopy were related to unsuccessful overall SLN mapping while tumor diameter greater than 2 cm and laparoscopy were statistically associated with failed bilateral mapping. With ICG, a higher body mass index was significantly associated with unsuccessful bilateral detection of SLN. CONCLUSION: SLN assessment in endometrial cancer is feasible and safe with high sensitivity and high NPV when ICG and CNPs are combined and in low-risk patients. It is a superior option to use CNPs in laparotomy for patients with endometrial cancer.

Association of pelvic floor function with postoperative urinary incontinence in cervical cancer patients after the radical hysterectomy.

AIMS: To assess the pelvic floor function in cervical cancer patients after radical hysterectomy and its relationship with urinary incontinence (UI). METHODS: Cervical cancer patients who underwent radical hysterectomy were recruited from 18 hospitals in China from January 2012 to March 2015. Pelvic floor examinations were conducted by measuring the pelvic floor muscle strength, fatigue of pelvic floor muscle fatigue, dynamic pressure of vaginal, nerve injury, A3 feedback, muscle potential, static tension, and dynamic tension. Postoperative urinary incontinence (UI) was identified using the International Consultation on Incontinence Questionnaire. Multivariable logistic regression analysis was used to assess the association of pelvic floor function examination results with postoperative UI. RESULTS: Totally 169 patients were included in this study. The prevalence of UI was 39.6% (67/169). The proportion of abnormal fatigue of Type I muscle (64% vs. 36%, p = .04) and abnormal A3 feedback (53.9% vs. 46.1%, p = .03) were higher among patients with postoperative UI compared to those without UI. In the multivariable analysis, abnormal fatigue of Type I muscle (odds ratio [OR] = 3.73, 95% confidence interval [CI]: 1.42-9.84), abnormal A3 feedback (OR = 2.40, 95% CI: 1.04-5.51), and length of resected vagina > 3 cm (OR = 3.44, 95% CI: 1.27-9.31) were associated with postoperative UI. Compared to laparoscopy, laparotomy was less likely to cause postoperative UI (OR = 0.12, 95% CI:0.04-0.33). CONCLUSIONS: The abnormal function of the pelvic floor muscle is related to postoperative UI. Early assessment among these patients is needed to prevent the development of pelvic floor disorder postoperatively.

Synthesis and biological activity of imidazole group-substituted arylaminopyrimidines (IAAPs) as potent BTK inhibitors against B-cell lymphoma and AML.

Bruton's tyrosine kinase (BTK) is a member of the Tec kinase family and plays a key role in the modulation of the B-cell receptor (BCR)-mediated signaling pathway. Inhibition of BTK has been proven to be an effective therapeutic approach for various hematological malignancies, such as chronic lymphocytic leukemia (CLL), mantle cell leukemia (MCL), diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML). Here, a new series of imidazole group-substituted arylaminopyrimidines (IAAPs) were designed and synthesized as potent inhibitors of the enzymatic activity of BTK with a half maximal inhibitory concentration (IC50) ranging from 13.10 to 42.40 nM. In particular, 11a and 11b exhibited stronger antiproliferative activity against AML and B lymphomas cell lines compared with BTK inhibitor ibrutinib and showed low cytotoxicity against normal peripheral blood mononuclear cells (PBMCs). In addition, analysis of the mechanism of action of these compounds revealed that 11a and 11b induced significant apoptosis in AML and B lymphoma cells by arresting the cell cycle at the G1/G0 or G2/M stage and blocked BTK autophosphorylation as well as the ensuing abrogation of pro-survival AKT and ERK signaling. Taken together, these results suggest that 11a and 11b might serve as valuable preclinical candidates for the treatment of AML and B-cell lymphoma.

Demethyleneberberine promotes apoptosis and suppresses TGF-ß/Smads induced EMT in the colon cancer cells HCT-116.

Colorectal cancer (CRC) is one of the most common malignant tumours in the world. Recent reports have revealed natural products displayed inhibition on colon cancer potential by suppressing transforming growth factor-ß/Smads induced epidermal-mesenchymal transition (EMT). In this article, 12 kinds of natural berberine analogues were screened for their effects on the inhibition of the colon cancer cells, the results showed that demethyleneberberine (DM-BBR) exhibited an interesting and potential effect on inducing the apoptosis of HCT-116 cells with drug concentrations of 6, 12 and 18 µM. Particularly, DM-BBR reversed the EMT process by inhibiting the expression of p-Smad2 and p-Smad3 in the transforming growth factor-ß/Smads signal pathway, up-regulated pro-apoptotic protein cleaved caspase-9, and blocked cell cycle at the S phase and increasing the expression of cyclin proteins P27 and P21. Taken together, these findings suggested that DM-BBR could promote apoptosis and suppress TGF-ß/Smads induced EMT in the colon cancer cells HCT-116.

Vault changes and pupillary responses to light in myopic and toric implantable collamer lens.

BACKGROUND: Achieving an appropriate vault is the main concern after the implantation of Implantable Collamer Lens (ICLs) for surgical correction of high myopia. The vault will vary with time and optical parameters, such as accommodation and pupil size. This research is to evaluate the vault change in Myopic and Toric ICLs under different lighting conditions; and to analyze the relationship between vault changes and pupillary responses to light. METHODS: We enrolled and analyzed 68 eyes from 68 patients who were implanted with Myopic EVO ICLs; we also included 60 eyes from 60 patients who were implanted with Toric EVO ICLs. The anterior chamber depth, pupil size and the post-operative vault were evaluated, 1 week after the operation, using a Visante Optical Coherence Tomography (OCT) under different lighting conditions. For each eye that was assessed, we calculated the vault change, which is defined as the difference between vault under mesopic condition and photopic condition; and the rate of vault change, which is defined as the vault change divided by mesopic vault. RESULTS: No significant difference was noted with the anterior chamber depth between mesopic and photopic conditions in either group. A significant decrease in vault and pupil size was detected under photopic condition in both groups. We found no difference in vault change between Myopic and Toric EVO ICLs under different lighting conditions. Moreover, the rate of vault change had a significant decrease with increased mesopic vault (baseline value). CONCLUSIONS: Too low a mesopic vault has a big rate of vault change, which may cause the contact of ICL with crystalline lens in photopic state; Too high a mesopic vault would constrict the posterior movement of pupil. The findings of the study suggest that, for patients with high or low vault, we should be more careful and must perform checks in different lighting conditions.

The Fractional CO2 Laser for the Treatment of Genitourinary Syndrome of Menopause: A Prospective Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Genitourinary syndrome of menopause (GSM) is a common condition affecting of most postmenopausal women, which greatly impacks the quality of life,and need to treat. This prospective multicenter cohort study aimed to compare the efficacy and safety of the fractional carbon dioxide (CO2 ) laser with that of topical estrogen for vaginal treatment and relieving symptoms of genitourinary syndrome of menopause (GSM). STUDY DESIGN/MATERIALS AND METHODS: This study included 162 postmenopausal patients who received vaginal laser or topical Estriol cream therapy between January 2017 and May 2019 at eight study centers in China. The degree of GSM-related symptoms (vaginal burning, dryness, and dyspareunia) was evaluated using the Vaginal Health Index score (VHIS) and Visual Analog Scale (VAS) at baseline, 1, 3, 6, and 12 months posttreatment. The primary endpoint was the improvement in vaginal burning, dryness, and dyspareunia at 6 months after treatment. Multivariate logistic regression was used to compare the rate of improvement in the two groups. RESULTS: At baseline, the laser and control groups showed no significant difference in the mean age, time after menopause, and the VHIS (all P > 0.05). In the laser group, compared with baseline, significant differences were seen in the VHIS after the first or second treatment session and at 1, 3, 6, and 12 months posttreatment (P < 0.01). In the control group, compared with baseline, the VHIS showed significant differences after 1, 3, and 6 months of treatment (P < 0.05). However, there was no significant difference after 3 and 6 months of follow-up between the two groups (P > 0.05). The VHIS scores were significantly higher after 1 month (16.63 ± 2.79 vs. 15.57 ± 2.43) and 12 months (15.72 ± 2.59 vs. 12.12 ± 4.08) of treatment in both the groups (P < 0.05). At 6 months after treatment, both groups showed improvement in vaginal burning, vaginal dryness, and dyspareunia (P > 0.05). The VAS findings at 6 months posttreatment were significantly different when compared with the pretreatment findings (P < 0.001). There were no significant adverse effects in the two groups. CONCLUSIONS: Fractional CO2 laser vaginal treatment could be a safe and effective option for treating symptoms of GSM, including vaginal burning, dryness, and dyspareunia. The improvement in symptoms was comparable with that seen with topical estrogen therapy and lasted for at least 6-12 months posttreatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.